ORCID Profile
0000-0002-1931-1365
Current Organisations
Forestry and Forest Products Research Institute
,
University of Melbourne
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Publisher: Springer Science and Business Media LLC
Date: 1987
DOI: 10.1007/BF01785525
Publisher: Elsevier BV
Date: 05-2005
DOI: 10.1016/J.NEULET.2005.01.009
Abstract: A renin-angiotensin system, separate to that in the periphery, has been found in the brain. Angiotensin-converting enzyme (ACE) is crucial in the synthesis of angiotensin II, breakdown of bradykinin and the hydrolysis of several other neuropeptides such as enkephalin, substance P, dynorphin and neurotensin. Changes in the levels of ACE have been found in brains of schizophrenia patients, suggesting an involvement of ACE in the illness which awaits further investigation. Prepulse inhibition (PPI) has been suggested to be an operational measure of sensorimotor gating and is disrupted in patients with schizophrenia. We found that ACE knockout mice have increased startle responses but no differences in baseline PPI compared to wildtype controls. Treatment with the dopamine receptor agonist, apomorphine, or the dopamine-releasing drug, hetamine, produced significant disruption of PPI in control mice but not in ACE knockout mice. Pretreatment with the ACE inhibitor, captopril, which itself did not affect PPI, caused a reduction in the effect of apomorphine on PPI, similar to that seen in the ACE knockout mice. These data suggest an important role of ACE substrates in modulating dopaminergic mechanisms involved in PPI. Further studies are needed to ascertain if angiotensin or other neuropeptides are involved in these interactions and to investigate the neurochemical mechanism behind these effects.
Publisher: Elsevier BV
Date: 07-1979
DOI: 10.1016/0022-4731(79)90046-3
Abstract: The reference staff of the Washington University School of Medicine Library, in an attempt to consider an alternative way of providing the information contained in the printed Chemical Abstracts, designed a study to examine whether the on-line version of Chemical Abstracts could be substituted for the hard copy. For a thirteen-week period, all patrons using the printed index were offered a free computer search of Chemical Abstracts in exchange for evaluating the searches. Only 39.6% of those offered a free search chose to do so. Of these patrons, 62% still planned to refer to the abstracts later, which are only available in the printed index. The hypothesis that the on-line version could be substituted for the printed index was not confirmed.
Publisher: Proceedings of the National Academy of Sciences
Date: 05-02-2002
Abstract: Relaxin, a peptide hormone secreted by the corpus luteum during pregnancy, exerts actions on reproductive tissues such as the pubic symphysis, uterus, and cervix. It may also influence body fluid balance by actions on the brain to stimulate thirst and vasopressin secretion. We mapped the sites in the brain that are activated by i.v. infusion of a dipsogenic dose of relaxin (25 μg/h) by immunohistochemically detecting Fos expression. Relaxin administration resulted in increased Fos expression in the subfornical organ (SFO), organum vasculosum of the lamina terminalis (OVLT), median preoptic nucleus, and magnocellular neurons in the supraoptic and paraventricular nuclei. Ablation of the SFO abolished relaxin-induced water drinking, but did not prevent increased Fos expression in the OVLT, supraoptic or paraventricular nuclei. Although ablation of the OVLT did not inhibit relaxin-induced drinking, it did cause a large reduction in Fos expression in the supraoptic nucleus and posterior magnocellular sub ision of the paraventricular nucleus. In vitro single-unit recording of electrical activity of neurons in isolated slices of the SFO showed that relaxin (10 −7 M) added to the perfusion medium caused marked and prolonged increase in neuronal activity. Most of these neurons also responded to 10 −7 M angiotensin II. The data indicate that blood-borne relaxin can directly stimulate neurons in the SFO to initiate water drinking. It is likely that circulating relaxin also stimulates neurons in the OVLT that influence vasopressin secretion. These two circumventricular organs that lack a blood–brain barrier may have regulatory influences on fluid balance during pregnancy in rats.
Publisher: Elsevier BV
Date: 2011
Publisher: Springer Science and Business Media LLC
Date: 03-1968
DOI: 10.1038/217922A0
Abstract: This paper studies the formation of Japanese ventures in family planning deployed in various villages in Asia from the 1960s onward in the name of development aid. By critically examining how Asia became the priority area for Japan's international cooperation in family planning and by analyzing how the adjective "humanistic" was used to underscore the originality of Japan's family planning program overseas, the paper shows that visions of Japanese actors were directly informed by Japan's delicate position in Cold War geopolitics, between the imagined West represented by the United States and "underdeveloped" Asia, at a time when Japan was striving to (re-)establish its position in world politics and economics. Additionally, by highlighting subjectivities and intra-Asian networks centered on Japanese actors, the paper also aims to destabilize the current historiography on population control which has hitherto focused either on Western actors in the transnational population control movement or on non-Western "acceptors" subjected to the population control programs.
Publisher: Oxford University Press (OUP)
Date: 02-1960
Publisher: Informa UK Limited
Date: 1988
DOI: 10.3109/10641968809033902
Abstract: The effect of increased potassium (K) intake (800 mmol/day) was investigated in conscious sheep to elucidate the mechanism of the anti-hypertensive effect of K loading. Mean arterial pressure rose (4mm Hg, n = 13, p less than 0.001). Cardiac output (n = 5) increased from 4.4 +/- 0.1 to 6.1 +/- 0.2 1/min (p less than 0.001). Calculated total peripheral resistance fell from 17 +/- 1 to 12 +/- 1 mmHg.min/1 (p less than 0.001). There was no change in plasma volume (n = 5), but extracellular fluid volume (n = 5) increased from 221 +/- 26 to 271 +/- 27 ml/kg (p less than 0.05). Glomerular filtration rate and effective renal plasma flow (n = 5) were unchanged. Plasma K concentration, fluid intake and urine volume increased. Urinary Na excretion increased from 106 +/- 11 to a maximum of 217 +/- 28 mmol/day on day 2 (p less than 0.001), and was decreased on day 7, 44 +/- 13 mmol/day (p less than 0.05). Calculated Na deficit was -268 mmol by day 10, but there was no change in responsiveness to infused angiotensin II, noradrenaline, vasopressin or tyramine. These changes differ from those seen with Na depletion alone in sheep, and are not compatible with the hypothesis that K loading exerts its effects solely by increasing Na excretion.
Publisher: Elsevier BV
Date: 04-1974
DOI: 10.1016/0006-8993(74)90264-9
Abstract: Socioeconomic status (SES) is strongly associated with cognition and achievement. Socioeconomic disparities in language and memory skills have been reported from elementary school through adolescence. Less is known about the extent to which such disparities emerge in infancy. Here, 179 infants from socioeconomically erse families were recruited. Using a cohort-sequential design, 90 infants were followed at 9 and 15 months, and 89 were followed at 15 and 21 months. SES disparities in developmental trajectories of language and memory were present such that, at 21 months of age, children of highly educated parents scored approximately .8 standard deviations higher in both language and memory than children of less educated parents. The home language and literacy environment and parental warmth partially accounted for disparities in language, but not memory development.
Publisher: Elsevier BV
Date: 03-1985
DOI: 10.1016/0022-4731(85)90433-9
Abstract: The plasma concentrations of 17 alpha-hydroxyprogesterone (17 alpha OHP) and 17 a'20 alpha-dihydroxy-4-pregnen-3-one (17 alpha 20 alpha OHP) have been measured in sheep during 5 days of ACTH administration at 20 micrograms/kg/day a rate of infusion known to produce hypertension. Five days of ACTH administration produced a progressive increase in plasma 17OHP from 0.45 +/- 0.12 to 128.9 +/- 28.4 nmol/l and in 17 alpha 20 alpha OHP from 0.54 +/- 0.15 to 73.1 +/- 7.2 nmol/l. Calculation of the blood production rate of both steroids during ACTH treatment confirms that the rates of infusion of 17OHP (3.0 mumol/h) and 17 alpha 20 alpha OHP (1.5 mumol/h) used to produce hypertension, when infused together with the other major ovine adrenocortical steroids, produced plasma concentrations in the range as found following administration at a rate to increase blood pressure.
Publisher: Elsevier BV
Date: 07-1989
DOI: 10.1016/0006-8993(89)91006-8
Abstract: The effect of intracerebroventricular (i.c.v.) infusion of various iso- and hypertonic saccharide solutions on water intake stimulated by intracarotid (i.c.) infusion of hypertonic NaCl was studied in sheep. Without an i.c.v. infusion, water intake during a 10-min period following an i.c. infusion of 4 M NaCl (1.4 ml/min over 20 min) was 1.5-2.0 litres. I.c.v. infusion of all saccharide solutions (made up in artificial cerebrospinal fluid (CSF) with no Na) tested, 0.27 or 0.7 M D-glucose, L-glucose, 2-deoxyglucose and sucrose, decreased (35-65%) water intake. In general, there was little or no difference in antidipsogenic effectiveness between the isotonic and the hypertonic solutions or between the different saccharides used. I.c.v. infusion of artificial CSF ([Na] = 150 mM) did not alter water intake. CSF [Na] was decreased by all of the saccharide infusions. CSF osmolality was increased by the hypertonic solutions, was decreased by the artificial CSF and was unchanged by the isotonic solutions infused. The observation that the antidipsogenic effectiveness of saccharides which readily cross the blood-brain barrier (BBB D-glucose, 2-deoxyglucose) was similar to that of saccharides which do not readily cross the BBB (sucrose, L-glucose) contrasts with effects reported on sodium appetite and suggests that the Na sensors involved in the inhibition of hypertonic NaCl-stimulated water intake are located close to or on the surface of the brain ventricular system, i.e. are responsive to changes in CSF [Na].(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: No publisher found
Date: 1977
DOI: 10.1016/0091-3057(77)90195-2
Abstract: Intracarotid infusion of ouabain (1280 ng/min) over 4 1/2 hr virtually abolished water intake of sheep in response to intracarotid infusion of either angiotensin II (800 ng/min) or 4 M NaCl (1.6 ml/min for 20 min. Ouabain treatment did not affect mean arterial pressure either before or during infusion of angiotensin. Neither ouabain nor angiotensin administration affected plasma [Na] or [K] or CSF [K]. During ouabain, but not during control infusion, angiotensin administration significantly decreased CSF [Na]. Ouabain administration also decreased water intake after 23 1/2 or 48 hr water deprivation. In the 23 1/2 hr deprivation experiments, food was made available immediately prior to water presentation and the ingestion of food appeared to ameliorate the reduction in water intake. Food intake itself, was decreased in some animals, during ouabain treatment. Ouabain infused at 960 ng/min resulted in significant, but smaller, reductions in water intake induced by angiotensin, 4 M NaCl, and 48 hr water deprivation. It was concluded that ouabain treatment affected water intake by influence on Na transport either in the thirst receptors or at some other level in the neural system between receptor and effector.
Publisher: Wiley
Date: 2013
Publisher: Elsevier BV
Date: 06-1983
DOI: 10.1016/S0140-6736(83)92720-4
Abstract: Glioblastoma is the most common malignant brain cancer with a dismal prognosis. The difficulty in treating glioblastoma is largely attributed to the lack of effective therapeutic targets. In our previous work, we identified casein kinase 1 ε (CK1ε, also known as CSNK1E) as a potential survival factor in glioblastoma. However, how CK1ε controls cell survival remains elusive and whether targeting CK1ε is a possible treatment for glioblastoma requires further investigation. Here we report that CK1ε was expressed at the highest level among six CK1 isoforms in glioblastoma and enriched in high-grade glioma, but not glia cells. Depletion of CK1ε remarkably inhibited the growth of glioblastoma cells and suppressed self-renewal of glioblastoma stem cells, while having limited effect on astrocytes. CK1ε deprivation activated β-catenin and induced apoptosis, which was further counteracted by knockdown of β-catenin. The CK1ε inhibitor IC261, but not PF-4800567, activated β-catenin and blocked the growth of glioblastoma cells and glioblastoma stem cells. Congruently, IC261 elicited a robust growth inhibition of human glioblastoma xenografts in mice. Together, our results demonstrate that CK1ε regulates the survival of glioblastoma cells and glioblastoma stem cells through β-catenin signaling, underscoring the importance of targeting CK1ε as an effective treatment for glioblastoma.
Publisher: Elsevier BV
Date: 03-2000
DOI: 10.1016/S0006-8993(00)01953-3
Abstract: The effects of prolonged intracerebroventricular (i.c.v.) steroid infusions on memory performances (Y-maze arm discrimination test) and on neurosteroids brain levels were studied in young adult male mice. The Y-maze test consisted of two trials separated by a time interval. In the first trial, one arm of the maze (subsequently called novel arm) was closed, and mice were allowed to visit the two accessible arms. After a short 2-h intertrial interval (ITI), control mice explored preferentially the novel arm, whereas with a longer 6-h ITI, they did not remember the location of the novel arm and performed at random level (33% of time spent in each arm). Using a 2-h ITI, allopregnanolone (THPROG, 0.5 and 1 ng/h) decreased memory performances to random level after 3 and 6 days of infusion. Conversely, with a 6-h ITI, pregnenolone sulfate (PREG S, 10, 50, and 100 ng/h) significantly increased memory performances after 3 days, but only the smallest dose was still effective after 6 days. THPROG infusion (1 ng/h) increased the forebrain concentration of 5alpha-dihydroprogesterone (DHPROG) and tended to increase its own level. PREG S administration (10 ng/h) increased its own concentration and tended to increase those of pregnenolone (PREG) and of further metabolites. In conclusion, the memory-enhancing effects of PREG S and the inhibitory ones of THPROG have been confirmed. A persistent, however moderate, increase of PREG S brain concentration might be of interest for the treatment of amnesic deficits.
Publisher: Proceedings of the National Academy of Sciences
Date: 21-02-2006
Abstract: A significant proportion of aged humans may have impaired thirst and inadequate fluid intake after a period of fluid deprivation. We have studied the water drinking responses, relative to body weight, of Munich Wistar (MW) rats in response to osmotic, hypovolemic, dehydrational, and angiotensin (Ang)-related stimuli as they aged from 3 to 24 months. Young 3-months-old (m.o.) rats had the largest daily fluid intakes and drinking responses to hypertonic and dehydrational stimuli, suggesting that they have accentuated thirst in comparison with older age groups. There were no differences in daily fluid intake from 6–24 m.o. however, drinking responses to i.p. injection of hypertonic 0.4 mol/liter NaCl gradually declined over this period so that in 24-m.o. rats the response was only half that of 6-m.o. rats. Water intake after 24-h water deprivation also declined gradually over 24 months. Drinking responses to hypovolemia induced by s.c. injection of colloid (polyethylene glycol) were unchanged in 6- to 15-m.o. rats, then declined precipitously in 18- to 24-m.o. rats. Drinking responses to s.c. Ang II or s.c. isoproterenol were not reduced in 24-m.o. rats, nor was the drinking associated with feeding. Therefore, there are specific impairments of water intake in response to hypertonicity and hypovolemia in aged MW rats, but Ang-related drinking is not reduced. Like aged humans, aged MW rats exhibit high plasma atrial natriuretic peptide levels and impaired cardiovascular reflexes that could contribute to the impairment of thirst with age.
Publisher: Elsevier BV
Date: 05-1987
DOI: 10.1016/0006-8993(87)91437-5
Abstract: Male rats were dehydrated for 22 h and then given 4 h intracerebroventricular (i.c.v.) infusions which commenced 2 h prior to the beginning of a 2-h fluid access period. I.c.v. infusion of iso-osmotic 0.27 M mannitol-CSF more than halved the amount of water normally drunk by dehydrated rats during the fluid access period. Whilst i.c.v. infusion of 0.7 M mannitol-CSF did not alter the amount of water drunk during the fluid access period. Presumably both infusates reduce CSF [Na] but only 0.7 M mannitol elevates CSF osmolality. The evidence is consistent with the involvement of both sodium and osmoreceptors in thirst in the rat. A reduction of CSF [Na] will inhibit dehydration induced water drinking provided the osmotic pressure of the CSF is not greatly elevated. In addition evidence is provided to show that a contrived reduction of CSF [Na] alone is not a sufficient physiological trigger to initiate salt appetite in rats.
Publisher: Elsevier BV
Date: 04-1984
DOI: 10.1016/0090-6980(84)90088-1
Abstract: The haemodynamic and renin responses to prostacyclin (PGI2) infusion were examined in sheep during sodium depletion and dietary sodium restriction. The haemodynamic effects of PGI2 infusion in sodium depleted and sodium restricted sheep were similar to those obtained in the sodium replete animal. The renin proportionate response to PGI2 was not altered by sodium restriction but blunted by sodium depletion, compatible with the hypothesis that endogenous PGI2 is high in Na depletion.
Publisher: Elsevier BV
Date: 10-1996
DOI: 10.1016/0031-9384(96)00085-6
Abstract: The systemic administration of adrenocorticotrophic hormone (ACTH) stimulates the intake of sodium chloride and water in many species. In mice the daily intake of water may reach half of the total body water content. To establish whether this very high water intake was primary or secondary to the sodium chloride intake, Synacthen was infused s.c. at 2.8 micrograms/day by Alzet miniosmotic pump to mice that did not have access to sodium chloride solution. On low-sodium food, the daily water intake increased from 2.99 +/- 0.08 ml (mean +/- SEM) to 9.85 +/- 0.74 ml (p < 0.05, n = 6) by day 7 of infusion and remained significantly higher than the control value until the fourth postinfusion day. On high-sodium food, the daily water intake also increased 350% from a higher baseline, 4.55 +/- 0.14 ml, and returned to the control value by the second postinfusion day. The same ACTH treatment for 4 days increased plasma [Na] and appeared to expand plasma volume. The results show that a high water intake caused by ACTH administration in mice is not secondary to a concurrent increase in sodium chloride intake. The water intake may be induced by stimulation of the secretion of adrenal steroid hormones which increase plasma [Na].
Publisher: Elsevier BV
Date: 04-1976
DOI: 10.1016/0091-3057(76)90048-4
Abstract: The specificity of choice in drinking by sheep was examined when a cafeteria of water and of 900 mmol/1 solutions of NaCl and KCl was presented, during intracarotid infusion of angiotensin II (800-1200 ng/min) or 4M NaCl (1.6 ml/min), and following 48 hr of water deprivation or following Na depletion. Water was the fluid of predominant choice with angiotensin II, 4M NaCl infusion and water deprivation. The hypertonic NaCl was the clear choice of the Na deficient animals. With a cafeteria of 300 mmol/l solutions, there was no clear discrimination between NaCl and water with intracarotid angiotensin II infusion. A 2 choice study of taste preference for water or NaCl concentrations with free access indicated sheep elect to take more of higher NaCl concentrations than the rat, and that 300 mmol/1 NaCl is not less preferred than water in sheep. The data indicated, overall, that the dipsogenic effect of supraphysiological cerebral blood concentrations of angiotensin II is biased to water drinking when the choice is between water and 900 mM NaCl and KCl solutions. It does not induce any specific salt appetite.
Publisher: Informa UK Limited
Date: 1984
DOI: 10.3109/10641968409062573
Abstract: Epidemiological evidence supports the thesis that high salt intake is involved in the aetiology of hypertension. If sodium intake is not causal, it appears other factors do not cause high blood pressure in unacculturated societies with low sodium intake. In this context, it is potentially important that stress causing ACTH release, as well as other neurohumoral effects, causes increased salt appetite and can impair renal sodium excretion.
Publisher: Elsevier BV
Date: 10-1996
DOI: 10.1016/0167-0115(96)00052-3
Abstract: From the outset, the study of angiotensin II (Ang II) in body fluid homeostasis has been both complicated and intriguing. Since the publication of an early report of the dipsogenic action of this peptide, the pursuit of the role of Ang II in thirst and Na appetite has continued for the last 25 years. This pursuit captured the attention of all workers interested in the behavioural hysiological regulation of body fluid balance, with major contributions being made by James T. Fitzsimons and his colleagues. In spite of its powerful dipsogenic actions, delineation of its precise role in physiological thirst has been elusive and difficult to demonstrate. The influence of Ang II on Na intake took longer to show convincingly. However, in contrast to thirst, the role of Ang II in physiological Na appetite has been demonstrated clearly. The technological advances made during the recent years have greatly increased our ability to delineate the neurobiological context of Ang II-mediated responses. Thus, the future is promising in regard to illuminating the subtleties of the role of Ang II in body fluid balance.
Publisher: Proceedings of the National Academy of Sciences
Date: 25-02-2000
Abstract: Stress is a large stimulus of Na appetite in rabbits, rats, and mice. This study investigated the influence of some peptides implicated in stress, i.e., adrenocorticotropin (ACTH), corticotropin-releasing factor (CRF), and the recently discovered member of the CRF family, urocortin, on the ingestive behavior of sheep. Intracerebroventricular infusion of these peptides over 4 days decreased the need-free Na intake of Na-repleted sheep. Intracerebroventricular infusion of urocortin, however, did not alter Na intake of Na-depleted sheep. Systemic infusion of ACTH increased, whereas systemic infusion of either urocortin or CRF decreased, Na intake of Na-repleted sheep. The increase in Na intake caused by the peripheral infusion of ACTH was blocked by concurrent i.v. infusion of urocortin, substantiating the inhibitory role of this peptide on Na appetite. Central administration of all peptides and i.v. administration of urocortin or urocortin and ACTH combined decreased food intake. Water intake was not directly influenced by the peptides. Rather, decreased water intake, when observed, was secondary to decreased food intake, as determined by pair-feeding experiments. Whereas systemic infusion of ACTH mimics the increase in Na intake observed in several different stressful situations, CRF and urocortin actually inhibit Na intake, indicating a direct central action overriding any effect of these peptides on ACTH release. Indeed, the inhibition of Na intake by urocortin occurred despite its stimulation of ACTH release and the subsequent increase in peripheral level of cortisol. Thus it would appear that hormones associated with stress have both excitatory and inhibitory influences on Na intake. Presumably, other physiological processes entrained by stress also will be important in determining the quantitative outcome on Na appetite.
Publisher: Proceedings of the National Academy of Sciences
Date: 02-03-1999
Abstract: Positron emission tomography studies were conducted during genesis of moderate thirst by rapid i.v. infusion of hypertonic saline (0.51 M) and after satiation of thirst by drinking water. The correlation of regional cerebral blood flow with the change in the plasma Na concentration showed a significant group of cerebral activations in the anterior cingulate region and also a site in the middle temporal gyrus and in the periaqueductal gray. Strongest deactivations occurred in the parahippoc al and frontal gyri. The data are consistent with an important role of the anterior cingulate in the genesis of thirst.
Publisher: Elsevier BV
Date: 08-1996
Publisher: Proceedings of the National Academy of Sciences
Date: 27-04-1999
Abstract: There are defined hypothalamic functions in the genesis of thirst, but little is known of the cortical processes subserving consciousness of thirst notwithstanding the medical disorders that occur in psychiatric illness, addiction, and the attested decline of thirst with aging. In 10 adult males, positron emission tomography scans were made ( i ) during genesis of moderate thirst by infusion of i.v. hypertonic saline 0.51 M, ( ii ) after irrigation of the mouth with water to remove the sensation of dryness, and ( iii ) 3, 14, 45, and 60 minutes after drinking water to fully satiate thirst. The correlation of regional cerebral blood flow with thirst score showed the major activation to be in the posterior cingulate. Maximum thirst sensation evoked 13 highly significant activations and 9 deactivations in cingulate and parahippoc al gyri, insula, thalamus, amygdala, and mesencephalon. It is possible that cingulate sites (Brodmann’s areas 32, 24, and 31) that persisted with wet mouth but disappeared immediately after drinking to satiation may have an important role in the consciousness of thirst. Consciousness of thirst, a primal vegetative emotion, and satiation of thirst appear to be subserved by phylogenetically ancient brain regions. This is salient to current discussion on evolutionary emergence of primary consciousness.
Publisher: Springer Science and Business Media LLC
Date: 08-1979
DOI: 10.1038/280490A0
Abstract: Vasoactive intestinal peptide, one of the putative neurotransmitters of non-adrenergic inhibitory nerves in human airways, is a potent relaxant of human airways in vitro. Previous in vivo studies of infused vasoactive intestinal peptide in asthmatic subjects have shown only a small bronchodilator effect, which may have been secondary to the cardiovascular effects of the peptide. The effect on airway function of infused vasoactive intestinal peptide was studied in normal subjects, who readily develop bronchodilation in response to a beta agonist. Separate experiments were designed to assess whether there is any synergy between this peptide and the beta agonist isoprenaline. Incremental doses of 1, 3, and 6 pmol/kg/min of vasoactive intestinal peptide were infused for 15 minutes. At 6 pmol/kg/min it caused a mean fall in systolic blood pressure from 108 to 88 mm Hg and a rise in heart rate from 71 to 95 beats/min. There was no significant change in specific airways conductance (sGaw) at any dose of vasoactive intestinal peptide. No significant changes were found with placebo. Isoprenaline (400 microgram) given by inhalation at the end of the infusion produced a mean increase in sGaw of 50%. Infused peptide caused no significant change in the cumulative dose-response curve for inhaled isoprenaline. The lack of effect of vasoactive intestinal peptide on airway responses in vivo may be due to rapid enzymatic breakdown of the peptide or to the fact that dosage has to be limited by the cardiovascular effects.
Publisher: Elsevier BV
Date: 12-1984
DOI: 10.1016/0024-3205(84)90028-6
Abstract: We have previously reported that adrenocortical steroids raise blood pressure by a 'hypertensinogenic' mechanism of action which is not simply related to their classical 'mineralocorticoid' or 'glucocorticoid' actions. This study presents evidence for specific antagonism of this 'hypertensinogenic' activity. The effects of separate IV infusions of prednisolone (P) 100 mg/d and 9 alpha-fluoro-prednisolone (9 alpha F-P) 0.6 mg/d on mean arterial pressure (MAP), plasma [K], plasma [glucose] and urinary Na excretion (UNaV) after 2 days were studied in sheep. In the same group of sheep which received P alone for 2 days, 9 alpha F-P was given for a further 2 days while continuing the P infusion (P + 9 alpha F-P). P alone had no effect on MAP or plasma [K] or UNaV but increased plasma [glucose], effects which are characteristic of 'glucocorticoid' activity. 9 alpha F-P alone increased MAP by 14 mmHg (P less than 0.001) and reduced plasma [K] and UNaV but had no effect on plasma [glucose]. Thus 9 alpha F-P exhibited both 'hypertensionogenic' and 'mineralocorticoid' activity. In the sheep which received the combined P + 9 alpha F-P infusion, the increase in MAP normally produced by 9 alpha F-P was blocked. Although pretreatment with P blocked the pressor effect of 9 alpha F-P, it did not alter the 'mineralocorticoid' effects, namely hypokalaemia and urinary Na retention, produced when 9 alpha F-P was infused alone. These results provide further evidence for our concept of a 'hypertensinogenic' class of steroid activity and are the first demonstration of specific antagonism of steroid induced hypertension.
Publisher: Elsevier BV
Date: 07-2004
Publisher: Elsevier BV
Date: 02-1985
DOI: 10.1016/0031-9384(85)90103-9
Abstract: The behaviour involved in the correction of sodium deficit has been studied in wild rabbits and also laboratory bred rabbits. They were offered 0.5 M NaCl to drink. In adrenalectomized wild rabbits variable sodium deficits were produced by withdrawal of mineralocorticoid for 24-72 hr. Correction of the deficit was remarkably precise and was achieved in 9-24 hr, being slower with smaller deficits. That is, the rate of drinking was almost commensurate with the degree of body deficit. No overdrinking occurred by 24 hr. Repetition of the experiment with 24 hr deficiency and with the offer of a cafeteria of 0.5 M NaCl, 0.5 M KCl, 0.25 M CaCl2 and 0.25 M MgCl2 showed the increased appetite was specific for NaCl. Both wild and laboratory rabbits, adrenally intact, were made sodium deficient by the diuretic furosemide. Voluntary salt intake did not peak until 6-12 hr later reflecting the characteristic delay in the genesis of salt appetite. If presentation of salt were delayed 24 hr after furosemide, the highest rate of intake was seen immediately in both wild and laboratory rabbits, but the wild rabbits were much faster in fully correcting body deficit. Infusion of isotonic NaCl, adequate to correct the deficit, given during the third-sixth hour of access to NaCl under the 24 hr delay of presentation regime, halved salt appetite over this period, and by 9-12 hr it was abolished. Polyethylene glycol induced subcutaneous fluid sequestration, salt appetite and thirst but caused an obvious severe deterioration in the animals condition.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Elsevier BV
Date: 1989
DOI: 10.1016/0022-4731(89)90165-9
Abstract: Studies of the mechanism of ACTH induced hypertension in sheep have led to the hypothesis that adrenocortical steroids may raise blood pressure by a "hypertensinogenic" action which can be distinguished from effects mediated by occupancy of classical mineralocorticoid or glucocorticoid receptors. This concept is supported by recent structure-activity studies using synthetic and naturally occurring steroids. Development of steroid hypertension is rapid (4-6 h) and although associated with an increase in cardiac output, changes in total peripheral resistance are important. Many different mechanisms have been proposed to explain how steroids raise blood pressure. In sheep it has been shown that the autonomic nervous system and vasoactive prostanoids appear to buffer, rather than cause, the rise in blood pressure. The renin-angiotensin system, AVP and serotonin are also unlikely to be involved. Further, the effects of steroids on blood pressure are not simply related to effects on Na status and changes in body fluid volumes. A direct involvement of the central nervous system remains to be established. In understanding how ACTH raises blood pressure, studies in sheep have shown that it is important to try and dissociate the effects of steroids involved in development of hypertension from the many other actions of steroids.
Publisher: Elsevier BV
Date: 02-1978
Publisher: Informa UK Limited
Date: 1987
DOI: 10.3109/10641968709158972
Abstract: The study was performed to examine the hypothesis that adrenocorticotrophic hormone (ACTH) induced hypertension in sheep would be enhanced if the blood level of angiotensin II (ANG II), normally suppressed during ACTH administration, was kept at control levels by intravenous infusion of ANG II. Administration of ACTH at 1.0 microgram/kg/day for 6 days produced a half maximum rise in mean arterial pressure, delta 14 mmHg, associated with hypokalaemia and initial urinary sodium retention. A rate of ANG II infusion, (0.9 microgram/kg/day) for 6 days, was contrived to produce a small increase in peripheral resistance and mean arterial pressure, delta 10 mmHg. Pressor responses to concomitant infusion of ACTH and ANG II were additive, delta 25 mmHg. There was no potentiation of ACTH hypertension by ANG II in the sheep.
Publisher: Informa UK Limited
Date: 1984
DOI: 10.3109/10641968409062568
Abstract: ACTH dependent and independent adrenocortical steroid hypertension in experimental animals is thought to be due to the 'mineralocorticoid' and/or 'glucocorticoid' activity of the steroid/s. Studies in sheep examining ACTH and adrenocortical steroid hypertension have provided evidence for a 'hypertensinogenic' class of steroid activity. A hypothesis is proposed to explain how the 'hypertensinogenic' actions of a steroid may produce hypertension. It is suggested that effects mediated via 'mineralocorticoid' and 'glucocorticoid' receptors may modulate or lify the 'hypertensinogenic' activity. In idual steroids may express any, all or none of these three types of steroid hormone activity.
Publisher: Springer Science and Business Media LLC
Date: 06-1956
DOI: 10.1038/1771035A0
Publisher: Proceedings of the National Academy of Sciences
Date: 09-07-1996
Abstract: The progression of animal life from the paleozoic ocean to rivers and erse econiches on the planet's surface, as well as the subsequent reinvasion of the ocean, involved many different stresses on ionic pattern, osmotic pressure, and volume of the extracellular fluid bathing body cells. The relatively constant ionic pattern of vertebrates reflects a genetic "set" of many regulatory mechanisms--particularly renal regulation. Renal regulation of ionic pattern when loss of fluid from the body is disproportionate relative to the extracellular fluid composition (e.g., gastric juice with vomiting and pancreatic secretion with diarrhea) makes manifest that a mechanism to produce a biologically relatively inactive extracellular anion HCO3- exists, whereas no comparable mechanism to produce a biologically inactive cation has evolved. Life in the ocean, which has three times the sodium concentration of extracellular fluid, involves quite different osmoregulatory stress to that in freshwater. Terrestrial life involves risk of desiccation and, in large areas of the planet, salt deficiency. Mechanisms integrated in the hypothalamus (the evolutionary ancient midbrain) control water retention and facilitate excretion of sodium, and also control the secretion of renin by the kidney. Over and above the multifactorial processes of excretion, hypothalamic sensors reacting to sodium concentration, as well as circumventricular organs sensors reacting to osmotic pressure and angiotensin II, subserve genesis of sodium hunger and thirst. These behaviors spectacularly augment the adaptive capacities of animals. Instinct (genotypic memory) and learning (phenotypic memory) are melded to give specific behavior apt to the metabolic status of the animal. The sensations, compelling emotions, and intentions generated by these vegetative systems focus the issue of the phylogenetic emergence of consciousness and whether primal awareness initially came from the interoreceptors and vegetative systems rather than the distance receptors.
Publisher: The Royal Society
Date: 2006
Abstract: Sylvia Agnes Sophia Tait was born on 8 January 1917 in Tumen, Siberia, Russia. She was the daughter of James Wardropper, an agronomist and trader, working in Russia. It seems that James Wardropper worked there with his elder brother, Robert (Huntford 1997). The wife of James Wardropper, Ludmilla, was a Russian who had the rare distinction of graduating in mathematics from the University of Moscow in the time of the reign of the Tsar. James and Ludmilla Wardropper adopted a Russian girl, Pasha she became part of the family and helped to look after Sylvia. During the revolution, in 1920 the whole family, including Pasha (but not including Robert) left Russia from Vla ostok for the UK, where James Wardropper eventually became a successful civil engineer. The fate of Robert Wardropper remains a mystery. The other Wardroppers first stayed in the UK in Ealing, London, where Sylvia attended the local secondary school, the Ealing County School for Girls. In her senior years there, she mainly studied languages, particularly German but also French and Latin. The Wardroppers had relatives in Germany and, before World War II, Sylvia spent some time in Germany, including Berlin, which improved her German. In addition, of course, at that time she spoke fairly fluent Russian with her mother and step-sister, Pasha. Sylvia had considerable trouble in establishing her citizenship because of her birthplace but eventually was officially declared British. Because of the nature of the father's history as a Scottish engineer in Russia and also the effects of the revolution, Sylvia never met her maternal grandparents and knew little about them.
Publisher: Elsevier BV
Date: 03-2009
DOI: 10.1016/J.PHYSBEH.2008.12.021
Abstract: Endocrine responses to fluid deprivation/restoration and preference for ethanol solution vs. water were assessed in sheep maintained for 5 months on a 10% ethanol solution as their sole source of fluid. Blood pressure, body weight, plasma composition and hormone levels of the alcohol maintained sheep were all within a normal range, except for high plasma concentrations of ANG II and ALDO. During fluid deprivation, AVP concentration increased and fluid-deprived sheep displayed a natriuresis and then a rehydration anti-natriuresis. Sheep did not drink the 10% ethanol solution avidly upon fluid restoration, preferring to drink steadily over the following 24 h there was an associated increase in blood alcohol concentration (BAC). PRC, ANG II and ALDO all increased throughout the fluid restoration period, whereas plasma AVP and ANP gradually fell. In a separate experiment when water was also supplied to the sheep, they preferred water to 10% ethanol however, alcohol intake was not eliminated. Overall, this degree of chronic consumption of 10% ethanol solution did not appear to adversely affect physiological mechanisms concerned with body fluid homeostasis after fluid deprivation conditions.
Publisher: Proceedings of the National Academy of Sciences
Date: 24-03-2014
Abstract: Drinking water in response to thirst following fluid loss is a pleasant experience, whereas drinking water after thirst has been satiated is unpleasant. The pleasantness of drinking when thirsty is associated with activation in the anterior cingulate cortex and orbitofrontal region. The unpleasantness and aversion of overdrinking is associated with activations in the midcingulate cortex, insula, amygdala, and periaqueductal grey. Activations in the putamen and cerebellum, and also in the motor cortex, possibly reflect volitional effort to conduct compliant drinking in the face of mechanisms inhibiting intake. These regions may contribute to the termination of drinking. Overdrinking with hyponatraemia and cerebral edema can occur in schizophrenia, reflecting that this brain disorder can derange physiological mechanisms regulating water balance.
Publisher: Elsevier BV
Date: 10-1989
DOI: 10.1016/0006-8993(89)91139-6
Abstract: The effect of 4 h intracerebroventricular (i.c.v.) infusion of various solutions on the renal excretion of Na and K and urinary flow rate was examined in conscious unrestrained rats not water-loaded. I.c.v. infusion of iso- or hypo-osmotic solutions with low [Na] induced a diuresis but did not alter renal excretion of Na or K. I.c.v. infusion of hyperosmotic solutions with normal or elevated [Na] induced a natriuresis and kaliuresis. Hyperosmotic mannitol solutions caused a diuresis but hyperosmotic NaCl or sucrose solutions caused a diuresis only when the rats drank water and/or sodium solution during the infusion period. I.c.v. infusion of hyperosmotic NaCl but not hyperosmotic mannitol increased blood pressure. The results are consistent with the involvement of cerebral osmosensors in the control of urinary excretion of Na and K, and of cerebral Na sensors in the control of urinary flow rate. Increased blood pressure, as occurred during i.c.v. infusion of hyperosmotic NaCl, may also contribute to the increased excretion of Na and K.
Publisher: Proceedings of the National Academy of Sciences
Date: 05-08-1997
Abstract: Recent data have identified leptin as an afferent signal in a negative-feedback loop regulating the mass of the adipose tissue. High leptin levels are observed in obese humans and rodents, suggesting that, in some cases, obesity is the result of leptin insensitivity. This hypothesis was tested by comparing the response to peripherally and centrally administered leptin among lean and three obese strains of mice: diet-induced obese AKR/J, New Zealand Obese (NZO), and A y . Subcutaneous leptin infusion to lean mice resulted in a dose-dependent loss of body weight at physiologic plasma levels. Chronic infusions of leptin intracerebroventricularly (i.c.v.) at doses of 3 ng/hr or greater resulted in complete depletion of visible adipose tissue, which was maintained throughout 30 days of continuous i.c.v. infusion. Direct measurement of energy balance indicated that leptin treatment did not increase total energy expenditure but prevented the decrease that follows reduced food intake. Diet-induced obese mice lost weight in response to peripheral leptin but were less sensitive than lean mice. NZO mice were unresponsive to peripheral leptin but were responsive to i.c.v. leptin. A y mice did not respond to subcutaneous leptin and were 1/100 as sensitive to i.c.v. leptin. The decreased response to leptin in diet-induced obese, NZO, and A y mice suggests that obesity in these strains is the result of leptin resistance. In NZO mice, leptin resistance may be the result of decreased transport of leptin into the cerebrospinal fluid, whereas in A y mice, leptin resistance probably results from defects downstream of the leptin receptor in the hypothalamus.
Publisher: Elsevier BV
Date: 02-1985
DOI: 10.1016/0006-8993(85)91388-5
Abstract: Infusion into a lateral brain ventricle (IVT) of different hypertonic (0.7 M) saccharide solutions decreased [Na+] of cerebrospinal fluid (CSF). Increased Na appetite of moderately Na-deplete sheep was observed during infusion of mannitol, L-glucose or L-fucose, while no change was observed during infusion of D-glucose, D-fucose, D-mannose, 2-deoxy-D-glucose, 3-O-methyl-glucose or fructose. In other experiments, increased Na appetite was observed during infusion of 2.3 mM phlorizin (a relatively specific blocker of Na-coupled glucose transport into cells) or 2.3 mM phlorizin plus 0.7 M D-glucose. In addition, phlorizin eliminated the characteristic decrease in Na appetite but did not affect the increase in water intake caused by IVT infusion of hypertonic NaCl which increased [Na+] of CSF. The results suggest that: (a) there are sensors within the neuropil which respond to change of [Na+] and influence Na appetite, and that these changes of [Na+] are induced deep within the neuropil by those saccharides which do not cross the blood-brain barrier or enter cells change of CSF[Na+] alone is not sufficient to alter appetite but a change in brain extracellular fluid (ECF)[Na+] is probably necessary (b) the theory is advanced that the stimulus for altered Na intake could be altered brain ECF[Na+] producing a change in cerebral intracellular fluid (ICF)[Na+] of the sensors and (c) phlorizin, in reducing or blocking Na-coupled glucose transport, could increase Na appetite by producing a fall in ICF[Na+] of the specific neurones subserving sodium appetite or prevent a decrease in Na appetite caused by IVT infusion of hypertonic NaCl by preventing an increase in ICF[Na+] of this same neuronal system.
Publisher: Elsevier BV
Date: 05-1992
DOI: 10.1016/0006-8993(92)90749-Y
Abstract: The effect of intracerebroventricular (i.c.v.) infusion (20 micrograms/h) over 3 h) of human alpha-atrial natriuretic peptide (ANP) on Na and water intake of sheep was studied. I.c.v. infusion of ANP decreased (p less than 0.01) Na and water intakes of water-deprived sheep but did not affect significantly Na or water intakes of Na and water-replete sheep. In addition, i.c.v. infusion of ANP decreased (P less than 0.05) Na and water intakes of sheep infused i.c.v. with angiotensin II. The results suggest that ANP may act on brain mechanisms concerned with both Na appetite and thirst. These mechanisms may involve action on the angiotensin II component of sodium appetite but effects on other factors determinant of appetite cannot be excluded at present.
Publisher: Elsevier BV
Date: 05-1985
DOI: 10.1016/0262-1746(85)90026-5
Abstract: The present experiments examine the hemodynamic effects of an intravenous infusion of prostacyclin on the development of ACTH-induced hypertension in conscious sheep. Prostacyclin was infused at either 0.01 microgram/kg min-1 for 9 days or 0.25 microgram/kg min-1 for 4 days. At 0.01 microgram/kg min-1 prostacyclin had no effect on blood pressure in normotensive sheep or on the development of ACTH hypertension. Infusion at 0.25 microgram/kg min-1 increased heart rate, cardiac output and plasma renin concentration and decreased stroke volume and peripheral resistance in normotensive sheep. Despite these effects it did not prevent development of ACTH-induced hypertension. It is unlikely on the basis of these results that glucocorticoid-induced inhibition of vasodepressor prostacyclin and resulting increase in pressor responsiveness to circulating agonists is the primary cause of ACTH induced hypertension in sheep.
Publisher: Springer Science and Business Media LLC
Date: 02-1957
DOI: 10.1038/179341A0
Publisher: Elsevier BV
Date: 10-1988
DOI: 10.1016/0167-0115(88)90422-3
Abstract: The effect of atrial natriuretic peptide (ANP) on water and sodium intake was investigated in wild rabbits, a species which does not drink water following i.c.v. or i.v. administration of angiotensin II but develops sodium appetite following i.c.v. infusion of angiotensin II. ANP was given during or after depletion of extracellular fluid volume: hemorrhage, fluid deprivation and administration of furosemide. Systemically administered ANP reduced the water, but not the sodium intake of wild rabbits. I.c.v. administration of ANP inhibited both water and sodium intake. The suppression of thirst following both i.v. and i.c.v. administration of ANP indicates that inhibition of the effect of angiotensin II is not the exclusive mechanism and the circumventricular organs are probably not the exclusive sites of action for ANP. The inhibition of sodium appetite in wild rabbits was consistent with earlier proposals that ANP acts through the inhibition of the effects of angiotensin II. Reduction of food intake coincident with administration of ANP was also noted, but dose-dependent decrease was not observed.
Publisher: Elsevier BV
Date: 10-1984
DOI: 10.1016/0262-1746(84)90086-6
Abstract: The aim of this study was to determine the effect of ACTH-induced hypertension on the hemodynamic dose-response curves to intravenous infusion of prostacyclin (PGI2) in conscious sheep. PGI2 was infused for 10 minutes at doses of 0.05-0.50 micrograms/kg per min and hemodynamic dose-response curves were performed before, during and after ACTH-induced hypertension. Prior to ACTH administration prostacyclin infusions produced dose dependent decreases in mean arterial pressure (MAP), calculated total peripheral resistance (CTPR) and stroke volume (SV). These changes were accompanied by an increase in cardiac rate (CR) and cardiac output (CO). After five days of ACTH treatment MAP had risen from 72 +/- 1 to 91 +/- 2 mm Hg and infusions of PGI2 produced similar effects on MAP to those seen prior to ACTH. However the effects on CTPR, CO, SV and CR were all potentiated relative to normotensive animals. Three days after ACTH administration had ceased and basal pressure had returned to normotensive levels, the responses of CR, CO and SV to PGI2 infusions were similar to those seen prior to ACTH. However the exaggerated fall in CTPR seen during ACTH treatment was still present and this resulted in a very large decrease in MAP. These studies suggest that in this model of steroid-induced hypertension the resistance vessels are more sensitive to PGI2 and that the blood pressure response to PGI2 is regulated by different mechanisms to those seen prior to ACTH.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-10-2007
DOI: 10.1161/CIRCULATIONAHA.106.675579
Abstract: Background— Addition of up to 15.0 g/d salt to the diet of chimpanzees caused large rises in blood pressure, which reversed when the added salt was removed. Effects of more modest alterations to sodium intakes in chimpanzees, akin to current efforts to lower sodium intakes in the human population, are unknown. Methods and Results— Sodium intakes were altered among 17 chimpanzees in Franceville, Gabon, and 110 chimpanzees in Bastrop, Tex. In Gabon, chimpanzees had a biscuit diet of constant nutrient composition except that the sodium content was changed episodically over 3 years from 75 to 35 to 120 mmol/d. In Bastrop, animals were ided into 2 groups 1 group continued on the standard diet of 250 mmol/d sodium for 2 years, and sodium intake was halved for the other group. Lower sodium intake was associated with lower systolic, diastolic, and mean arterial blood pressures in Gabon (2-tailed P .001, unadjusted and adjusted for age, sex, and baseline weight) and Bastrop ( P .01, unadjusted P =0.08 to 0.10, adjusted), with no threshold down to 35 mmol/d sodium. For systolic pressure, estimates were −12.7 mm Hg (95% confidence interval, −16.9 to −8.5, adjusted) per 100 mmol/d lower sodium in Gabon and −10.9 mm Hg (95% confidence interval, −18.9 to −2.9, unadjusted) and −5.7 mm Hg (95% confidence interval, −12.2 to 0.7, adjusted) for sodium intake lower by 122 mmol/d in Bastrop. Baseline systolic pressures higher by 10 mm Hg were associated with larger falls in systolic pressure by 4.3/2.9 mm Hg in Gabon/Bastrop per 100 mmol/d lower sodium. Conclusions— These findings from an essentially single-variable experiment in the species closest to Homo sapiens with high intakes of calcium and potassium support intensified public health efforts to lower sodium intake in the human population.
Publisher: Springer Science and Business Media LLC
Date: 04-1966
DOI: 10.1038/210102A0
Abstract: The asymmetric unit of the title mol-ecular salt (systematic name: 4-amino-anilinium 5-carb-oxy-penta-noate), C
Publisher: Elsevier BV
Date: 04-1990
DOI: 10.1016/0091-3057(90)90365-O
Abstract: The present study reports the effects of ICV administered eledoisin, the most potent anti/dipsogenic member of the tachykinin family, in three species. Sheep with chronic parotid fistula lost daily 200-400 mmol sodium in 3-4 l of saliva. During ICV infusion of eledoisin, 2 to 50 ng/min, a decrease in sodium intake was observed. If water was withheld for 22 hours, sheep normally drank 5.4 l water on presentation. During ICV infusion of eledoisin, 50 ng/min, water intake increased significantly. Wild rabbits lost 5 mmol sodium in 50 ml of urine after injection of furosemide. During ICV infusion of eledoisin, 30 ng/min, a decrease in sodium intake and an increase in water drinking was observed. Cows prepared with parotid fistula had access to sodium solution every other day to replace salivary sodium loss. During ICV infusion of eledoisin, 50 and 150 ng/min, a decrease in sodium intake occurred, and water intake was unaffected. These results confirm that central administration of eledoisin specifically influences ingestive behaviour in mammals and draws attention to some species differences in the observed effects.
Publisher: Elsevier BV
Date: 03-1982
DOI: 10.1016/0006-8993(82)90048-8
Abstract: Ablation of the organum vasculosum of the lamina terminalis (OVLT) and adjacent midline tissue in the anterior wall of the optic recess of the third ventricle resulted in greatly reduced water drinking to intracarotid infusion of hypertonic NaCl in sheep. Daily food and water intake and angiotensin II drinking were not consistently reduced by these lesions. Tissue in or close to the OVLT is probably involved in osmotically induced water-drinking.
Publisher: Elsevier BV
Date: 02-1994
DOI: 10.1016/0006-8993(94)91256-4
Abstract: Thirst, the longing or compelling desire to drink, arises physiologically by two main mechanisms-extracellular and cellular dehydration. The hormone angiotensin II has been implicated in the former but not in the latter brain mechanism. To test this apparent difference, experiments in 5 mammalian species examined the effect of intracerebroventricular infusion of losartan, an angiotensin II type I receptor antagonist, on the third induced by intracerebroventricular infusion of an artificial cerebrospinal fluid made hypertonic by the inclusion of 500 mM NaCl. The losartan infusion reduced the water intake due to increased brain sodium concentration in all 5 species, cattle, sheep, rabbits, rats and mice. Thus, the thirst evoked by cellular dehydration, as well as the thirst evoked by extracellular dehydration, may be mediated by angiotensin II.
Publisher: Elsevier BV
Date: 03-1970
DOI: 10.1016/S0039-128X(70)80060-5
Abstract: A 27-year-old woman developed bilateral acute angle closure glaucoma (AACG) and transient myopia after taking oseltamivir for four days. On the fourth day, she received systemic and topical intraocular pressure (IOP)-lowering agents, and IOP decreased in both eyes. However, her visual acuity was unchanged. A myopic shift of -5.25 D OD and -5.0 D OS was estimated to have occurred in the acute phase. A-scan ultrasonography and Pentacam showed markedly shallow anterior chambers and increased lens thickness. Ultrasound biomicroscopy revealed an annular ciliochoroidal effusion with forward displacement of the lens-iris diaphragm. Ciliochoroidal effusion and transient myopia were resolved after discontinuation of oseltamivir.
Publisher: Elsevier BV
Date: 10-2000
Publisher: Elsevier
Date: 1970
DOI: 10.1016/S0079-6123(08)61528-9
Abstract: The past several years have seen dramatic leaps in our understanding of how gene expression is rewired at the translation level during tumorigenesis to support the transformed phenotype. This work has been driven by an explosion in technological advances and is revealing previously unimagined regulatory mechanisms that dictate functional expression of the cancer genome. In this Review we discuss emerging trends and exciting new discoveries that reveal how this translational circuitry contributes to specific aspects of tumorigenesis and cancer cell function, with a particular focus on recent insights into the role of translational control in the adaptive response to oncogenic stress conditions.
Publisher: Informa UK Limited
Date: 1984
DOI: 10.3109/10641968409044071
Abstract: The present study examines the blood pressure and metabolic effects of 5 day infusions of 19-nor-deoxycorticosterone (19-nor-DOC) and 19- nor-progesterone (19-nor-PROG) in the intact conscious sheep. Both these steroids raise blood pressure in the rat. 19-nor-DOC (5 mg/d) produced a significant increase in mean arterial pressure (MAP) of 17 mmHg on day 5 (p less than 0.001), associated with 'mineralocorticoid' effects hypokalaemia, hypernatraemia and an initial urinary sodium retention. In contrast 19-nor-PROG (5 mg/d and 50 mg/d) had no effect on MAP and displayed no 'mineralocorticoid' activity.
Publisher: Informa UK Limited
Date: 1984
DOI: 10.3109/10641968409044073
Abstract: This study examines the blood pressure and electrolyte response to adrenocorticotrophic hormone (ACTH) in K loaded sheep to test the hypothesis that ACTH-induced hypertension is blunted in K loaded sheep. ACTH treatment in sheep on a 'normal' Na (70-100 mmol/day) and high K intake (congruent to 800 mmol/day) increased mean arterial pressure (MAP) by upto 17 mmHg over 5 days. Cardiac rate and urinary Na excretion also increased. Plasma [Na] and [K] fell with ACTH. On a lower Na (30 mmol/day) and high K intake (congruent to 800 mmol/day) ACTH raised MAP by upto 16 mmHg over 5 days. Cardiac rate, urinary Na and K excretion also increased. Plasma [Na] fell and plasma [K] was unchanged. Thus, ACTH hypertension is not modified in chronically K loaded sheep, although electrolyte responses are different from normal.
Publisher: Informa UK Limited
Date: 1984
DOI: 10.3109/10641968409044072
Abstract: 9 alpha-Fluorocortisol (9 alpha FF) is an analogue of cortisol with 'mineralocorticoid', 'glucocorticoid' and 'hypertensinogenic' activity. 9 alpha FF was infused at 2 mg/day for 5 days to sheep receiving a normal Na intake (100 mmol/d) and a high K intake (congruent to 800 mmol/d). K loading modified the Na retaining effects of 9 alpha FF but had no effect on the development of the hypertension. These experiments suggest that the effects of K loading on the development of 9 alpha-FF hypertension are not related simply to the effects that K has on modifying the Na retaining effects of the steroid.
Publisher: Proceedings of the National Academy of Sciences
Date: 20-01-2009
Abstract: In heart failure (HF), sympathetic nerve activity is increased. Measurements in HF patients of cardiac norepinephrine spillover, reflecting cardiac sympathetic nerve activity (CSNA), indicate that it is increased earlier and to a greater extent than sympathetic activity to other organs. This has important consequences because it worsens prognosis, provoking arrhythmias and sudden death. To elucidate the mechanisms responsible for the activation of CSNA in HF, we made simultaneous direct neural recordings of CSNA and renal SNA (RSNA) in two groups of conscious sheep: normal animals and animals in HF induced by chronic, rapid ventricular pacing. In normal animals, the level of activity, measured as burst incidence (bursts of pulse related activity/100 heart beats), was significantly lower for CSNA (30 ± 5%) than for RSNA (94 ± 2%). Furthermore, the resting level of CSNA, relative to its maximum achieved while baroreceptors were unloaded by reducing arterial pressure, was set at a much lower percentage than RSNA. In HF, burst incidence of CSNA increased from 30 to 91%, whereas burst incidence of RSNA remained unaltered at 95%. The sensitivity of the control of both CSNA and RSNA by the arterial baroreflex remained unchanged in HF. These data show that, in the normal state, the resting level of CSNA is set at a lower level than RSNA, but in HF, the resting levels of SNA to both organs are close to their maxima. This finding provides an explanation for the preferential increase in cardiac norepinephrine spillover observed in HF.
Publisher: Informa UK Limited
Date: 1988
DOI: 10.3109/10641968809103528
Abstract: The anti-hypertensive effect of potassium (K) loading in human essential hypertension and several types of experimental hypertension is well established. However, the mechanism of the anti-hypertensive effect is not understood. The natriuretic effect of a high K intake has lead many to conclude that the blood pressure lowering effect of K may be mediated through enhanced sodium (Na) excretion leading to negative Na status. Review of the literature suggests that the anti-hypertensive effect of K loading, at least in sheep, can not be explained simply by changes in Na excretion.
Publisher: Elsevier BV
Date: 10-1980
Publisher: Proceedings of the National Academy of Sciences
Date: 13-02-2001
Abstract: There are defined medullary, mesencephalic, hypothalamic, and thalamic functions in regulation of respiration, but knowledge of cortical control and the elements subserving the consciousness of breathlessness and air hunger is limited. In nine young adults, air hunger was produced acutely by CO 2 inhalation. Comparisons were made with inhalation of a N 2 /O 2 gas mixture with the same apparatus, and also with paced breathing, and with eyes closed rest. A network of activations in pons, midbrain (mesencephalic tegmentum, parabrachial nucleus, and periaqueductal gray), hypothalamus, limbic and paralimbic areas (amygdala and periamygdalar region) cingulate, parahippoc al and fusiform gyrus, and anterior insula were seen along with caudate nuclei and pulvinar activations. Strong deactivations were seen in dorsal cingulate, posterior cingulate, and prefrontal cortex. The striking response of limbic and paralimbic regions points to these structures having a singular role in the affective sequelae entrained by disturbance of basic respiratory control whereby a process of which we are normally unaware becomes a salient element of consciousness. These activations and deactivations include phylogenetically ancient areas of allocortex and transitional cortex that together with the amygdalar eriamygdalar region may subserve functions of emotional representation and regulation of breathing.
Publisher: Proceedings of the National Academy of Sciences
Date: 06-05-2008
Abstract: In addition to its role in the storage of fat, adipose tissue acts as an endocrine organ, and it contains a functional renin-angiotensin system (RAS). Angiotensin-converting enzyme (ACE) plays a key role in the RAS by converting angiotensin I to the bioactive peptide angiotensin II (Ang II). In the present study, the effect of targeting the RAS in body energy homeostasis and glucose tolerance was determined in homozygous mice in which the gene for ACE had been deleted (ACE −/− ) and compared with wild-type littermates. Compared with wild-type littermates, ACE −/− mice had lower body weight and a lower proportion of body fat, especially in the abdomen. ACE −/− mice had greater fed-state total energy expenditure (TEE) and resting energy expenditure (REE) than wild-type littermates. There were pronounced increases in gene expression of enzymes related to lipolysis and fatty acid oxidation (lipoprotein lipase, carnitine palmitoyl transferase, long-chain acetyl CoA dehydrogenase) in the liver of ACE −/− mice and also lower plasma leptin. In contrast, no differences were detected in daily food intake, activity, fed-state plasma lipids, or proportion of fat excreted in fecal matter. In conclusion, the reduction in ACE activity is associated with a decreased accumulation of body fat, especially in abdominal fat depots. The decreased body fat in ACE −/− mice is independent of food intake and appears to be due to a high energy expenditure related to increased metabolism of fatty acids in the liver, with the additional effect of increased glucose tolerance.
Publisher: Elsevier BV
Date: 06-1980
DOI: 10.1016/0024-3205(80)90212-X
Abstract: Hospitals worldwide are facing an increasing incidence of hard-to-treat infections. Limiting infections and providing patients with optimal drug regimens require timely strain identification as well as virulence and drug-resistance profiling. Additionally, prophylactic interventions based on the identification of environmental sources of recurrent infections (e.g., contaminated sinks) and reconstruction of transmission chains (i.e., who infected whom) could help to reduce the incidence of nosocomial infections. WGS could hold the key to solving these issues. However, uptake in the clinic has been slow. Some major scientific and logistical challenges need to be solved before WGS fulfils its potential in clinical microbial diagnostics. In this review we identify major bottlenecks that need to be resolved for WGS to routinely inform clinical intervention and discuss possible solutions.
Publisher: Proceedings of the National Academy of Sciences
Date: 03-02-2006
Abstract: This study used positron-emission tomography to establish the patterns of brain activity involved in the isolated and concurrent experiences of thirst and pain. Ten subjects were scanned while experiencing pain evoked with noxious pressure, while experiencing thirst after the infusion of hypertonic saline, and while experiencing pain when thirsty. After the onset of thirst, noxious pressure evoked more intense sensations of pain. Noxious pressure did not change subjective ratings of thirst. Thirst caused activation in the anterior cingulate (Brodmann area 32) and the insula. Enhanced pain responses were associated with increased activity in cortical regions that are known to correlate with pain intensity, and also with unique activity in the pregenual anterior cingulate and ventral orbitofrontal cortex. These findings suggest a role for limbic and prefrontal cortices in the modulation of pain during the experience of thirst.
Publisher: Informa UK Limited
Date: 1987
DOI: 10.3109/10641968709161449
Abstract: This study investigated the effect of 5 day infusions of 6 alpha and 9 alpha-fluoro and 16 alpha, 17 alpha-acetal analogues of prednisolone on blood pressure in conscious sheep. In vivo mineralocorticoid (MC) and glucocorticoid (GC) activities of these steroids were also measured. Prednisolone (100 mg/d) produced a small increase in mean arterial pressure associated with increased fasting plasma [glucose] and polyuria, but had no MC activity. 9 alpha-fluoro substitution greatly enhanced both the pressor and MC activity of prednisolone. The effect of 9 alpha-fluoro substitution on pressor activity was not affected by beta-methylation at C-16 (betamethasone), but was attenuated by either alpha-hydroxylation or alpha-methylation at C-16 (triamcinolone and dexamethasone, respectively). The effect of 9 alpha-fluoro substitution on MC activity as determined by urinary Na excretion was not altered by a methyl group at C-16 in either alpha or beta configuration but the MC activity was attenuated by an alpha-hydroxyl group at C-16. In contrast, 6 alpha-fluoro substitution had little influence on pressor, MC and GC activities. 16 alpha, 17 alpha-acetonide and 16 alpha, 17 alpha-butylidenedioxy substitution increased the pressor activity of parent compounds, but had no influence on either GC or MC activity. This study demonstrates a dissociation between the pressor effects and the MC and GC activities associated with steroid administration and provides further evidence to support the concept of 'hypertensinogenic' class of steroid activity which can be distinguished from their MC and GC activity.
Publisher: Springer Science and Business Media LLC
Date: 10-1976
DOI: 10.1038/263608A0
Abstract: Desferrioxamine, a safe and effective iron chelator, was evaluated for its antibacterial and antifungal activity. The susceptibilities of 124 urinary tract isolates and 28 clinical isolates of Neisseria gonorrhoeae to desferrioxamine concentrations that are readily achievable in urine were determined. Of all isolates, 27% were inhibited by a concentration of less than or equal to 12.5 mM. Proteus mirabilis and N. gonorrhoeae isolates were particularly susceptible to the chelator. Desferrioxamine appears to have limited potential as an antibacterial agent.
Publisher: American Physiological Society
Date: 09-2011
DOI: 10.1152/AJPREGU.00817.2010
Abstract: The pattern of regional brain activation in humans during thirst associated with dehydration, increased blood osmolality, and decreased blood volume is not known. Furthermore, there is little information available about associations between activation in osmoreceptive brain regions such as the organum vasculosum of the lamina terminalis and the brain regions implicated in thirst and its satiation in humans. With the objective of investigating the neuroanatomical correlates of dehydration and activation in the ventral lamina terminalis, this study involved exercise-induced sweating in 15 people and measures of regional cerebral blood flow (rCBF) using a functional magnetic resonance imaging technique called pulsed arterial spin labeling. Regional brain activations during dehydration, thirst, and postdrinking were consistent with the network previously identified during systemic hypertonic infusions, thus providing further evidence that the network is involved in monitoring body fluid and the experience of thirst. rCBF measurements in the ventral lamina terminalis were correlated with whole brain rCBF measures to identify regions that correlated with the osmoreceptive region. Regions implicated in the experience of thirst were identified including cingulate cortex, prefrontal cortex, striatum, parahippoc us, and cerebellum. Furthermore, the correlation of rCBF between the ventral lamina terminalis and the cingulate cortex and insula was different for the states of thirst and recent drinking, suggesting that functional connectivity of the ventral lamina terminalis is a dynamic process influenced by hydration status and ingestive behavior.
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.CONCOG.2008.06.009
Abstract: Primordial emotions are the subjective element of the instincts which are the genetically programmed behaviour patterns which contrive homeostasis. They include thirst, hunger for air, hunger for food, pain and hunger for specific minerals etc. There are two constituents of a primordial emotion--the specific sensation which when severe may be imperious, and the compelling intention for gratification by a consummatory act. They may dominate the stream of consciousness, and can have plenipotentiary power over behaviour. It is hypothesized that early in animal evolution complex reflex mechanisms in the basal brain subserving homeostatic responses, in concert with elements of the reticular activating system subserving arousal, melded functionally with regions embodied in the progressive rostral development of the telencephalon. This included the emergent limbic and paralimbic areas, and the insula. This phylogenetically ancient organization subserved the origin of consciousness as the primordial emotion, which signalled that the organisms existence was immediately threatened. Neuroimaging confirms major activations in regions of the basal brain during primordial emotions in humans. The behaviour of decorticate humans and animals is discussed in relation to the possible existence of primitive awareness. Neuroimaging of the primordial emotions reveals that rapid gratification of intention by a consummatory act such as ingestion causes precipitate decline of both the initiating sensation and the intention. There is contemporaneous rapid disappearance of particular regions of brain activation which suggests they may be part of the jointly sufficient and severally necessary activations and deactivations which correlate with consciousness [Crick, F. & Koch, C. (2003). A framework for consciousness. NatureNeuroscience,6, 119-126].
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2018
DOI: 10.1519/JSC.0000000000001827
Abstract: Lee, NA, Fell, JW, Pitchford, NW, Hall, AH, Leveritt, MD, and Kitic, CM. Combined carbohydrate and protein ingestion during Australian rules football matches and training sessions does not reduce fatigue or accelerate recovery throughout a weeklong junior tournament. J Strength Cond Res 32(2): 344–355, 2018—Australian rules football (ARF) is a physically demanding sport that can induce high levels of fatigue. Fatigue may be intensified during periods where multiple matches are played with limited recovery time. Combined carbohydrate and protein (CHO + PRO) intake during physical activity may provide performance and recovery benefits. The aim of this study was to investigate whether CHO + PRO ingestion during ARF matches and training sessions throughout a tournament would enhance performance or recovery in comparison with CHO-only ingestion. Australian rules football players ( n = 21) competing in a 7-day national tournament participated in this randomized and double-blinded study. Beverages containing either CHO ( n = 10) or CHO + PRO ( n = 11) were provided during matches (day 1, day 4, and day 7) and training sessions (day 2 and day 3). Countermovement jumps (CMJs), ratings of muscle soreness, and autonomic function were assessed throughout the tournament. Gastrointestinal tract (GI) discomfort was measured after matches. Countermovement jump peak velocity increased in the CHO + PRO group ( p = 0.01) but not in the CHO group. There were no differences in the other CMJ variables. In both groups, muscle soreness increased from days 0 and 1 to day 2 ( p ≤ 0.05) but did not remain elevated. R-R intervals (time elapsed between successive peaks in QRS complexes) increased in both groups from day 1 to day 7 (mean difference = 59.85 ms, p 0.01). Postmatch GI discomfort was not different ( p 0.05) between groups. When daily dietary protein is adequate ( .8 g·kg −1 ·d −1 ), the ingestion of CHO + PRO during matches and training sessions throughout a tournament does not reduce muscle soreness nor have clear benefits for neuromuscular recovery or modulate autonomic function in junior ARF athletes, compared with that of CHO alone.
Publisher: Elsevier BV
Date: 08-1979
DOI: 10.1016/0009-8981(79)90064-0
Abstract: The automated (AutoAnalyzer II) determination of cholesterol in nine serum pools in the concentration range 3.465-8.871 mmol/l, gave results that were approximately 10% higher than reference values when the analyses were based on unesterified cholesterol standards containing the same amount of water as the s le extracts (1963 analyses in 12 laboratories during a 12 month period automated value = 0.032 + 1.10 X (Reference value)). A serum calibration procedure was successful ilues, and was equally effective in correcting the values observed for aliquots of 368 fresh-frozen plasma s les analyzed in each of the 12 laboratories during a 38 month period.
Publisher: Springer Science and Business Media LLC
Date: 05-1964
DOI: 10.1038/202461A0
Publisher: Elsevier BV
Date: 04-1995
DOI: 10.1016/0031-9384(94)00319-X
Abstract: Intracerebroventricular (ICV) infusion of basic fibroblast growth factor (FGF-2) at 50 ng/h for 5 days in male BALB/c mice suppressed the daily intakes of water and food (n = 4). Intakes were reduced on the second day, and were suppressed until the second day after stopping the infusion. The same infusion for 4 days had little effect on the high intakes of 0.3 M NaCl solution and water induced by prolonged ICV infusion of angiotensin II, or the daily food intake in these experiments (n = 7). However, the same infusion for 3-4 days reduced the increased intake of NaCl solution in Na-depleted mice (n = 8), reduced the increased water intake of water-restricted mice (n = 6 or n = 7), and reduced daily food intake in both experiments. Ventricular enlargement was noted in mice at the end of these experiments but, for reasons advanced, did not appear to account for the responses. The results indicate that FGF-2 may have an inhibitory role in these ingestive behaviours.
Publisher: American Physiological Society
Date: 05-2008
DOI: 10.1152/AJPREGU.00848.2007
Abstract: Water intakes in response to hypertonic, hypovolemic, and dehydrational stimuli were investigated in mice lacking angiotensin II as a result of deletion of the angiotensinogen gene (Agt−/− mice), and in C57BL6 wild-type (WT) mice. Baseline daily water intake in Agt−/− mice was approximately threefold that of WT mice because of a renal developmental disorder of the urinary concentrating mechanisms in Agt−/− mice. Intraperitoneal injection of hypertonic saline (0.4 and 0.8 mol/l NaCl) caused a similar dose-dependent increase in water intake in both Agt−/− and WT mice during the hour following injection. As well, Agt−/− mice drank appropriate volumes of water following water deprivation for 7 h. However, Agt−/− mice did not increase water or 0.3 mol/l NaCl intake in the 8 h following administration of a hypovolemic stimulus (30% polyethylene glycol sc), whereas WT mice increased intakes of both solutions during this time. Osmoregulatory regions of the brain [hypothalamic paraventricular and supraoptic nuclei, median preoptic nucleus, organum vasculosum of the lamina terminalis (OVLT), and subfornical organ] showed an increased number of neurons exhibiting Fos-immunoreactivity in response to intraperitoneal hypertonic NaCl in both Agt−/− mice and WT mice. Polyethylene glycol treatment increased Fos-immunoreactivity in the subfornical organ, OVLT, and supraoptic nuclei in WT mice but only increased Fos-immunoreactivity in the supraoptic nucleus in Agt−/− mice. These data show that brain angiotensin is not essential for the adequate functioning of neural pathways mediating osmoregulatory thirst. However, angiotensin II of either peripheral or central origin is probably necessary for thirst and salt appetite that results from hypovolemia.
Publisher: Proceedings of the National Academy of Sciences
Date: 25-02-2000
Abstract: Recent studies implicate the cerebellum, long considered strictly a motor control structure, in cognitive, sensory, and affective phenomenon. The cerebellum, a phylogenetically ancient structure, has reciprocal ancient connections to the hypothalamus, a structure important in vegetative functions. The present study investigated whether the cerebellum was involved in vegetative functions and the primal emotions engendered by them. Using positron emission tomography, we examined the effects on the cerebellum of the rise of plasma sodium concentration and the emergence of thirst in 10 healthy adults. The correlation of regional cerebral blood flow with subjects' ratings of thirst showed major activation in the vermal central lobule. During the development of thirst, the anterior and posterior quadrangular lobule, lingula, and the vermis were activated. At maximum thirst and then during irrigation of the mouth with water to alleviate dryness, the cerebellum was less activated. However, 3 min after drinking to satiation, the anterior quadrangular lobule and posterior cerebellum were highly activated. The increased cerebellar activity was not related to motor behavior as this did not occur. Instead, responses in ancient cerebellar regions (vermis, fastigal nucleus, archicerebellum) may be more directly related to vegetative and affective aspects of thirst experiences, whereas activity in neocerebellar (posterior) regions may be related to sensory and cognitive aspects. Moreover, the cerebellum is apparently not involved in the computation of thirst per se but rather is activated during changes in thirst/satiation state when the brain is “vigilant” and is monitoring its sensory systems. Some neocerebellar activity may also reflect an intentionality for gratification by drinking inherent in the consciousness of thirst.
Publisher: Elsevier BV
Date: 1987
DOI: 10.1016/0031-9384(87)90374-X
Abstract: Alteration of the sodium concentration in the cerebrospinal fluid (CSF) of sheep induces reciprocal changes in sodium appetite. Similar studies have now been performed in cattle. Heifers were prepared with a unilateral parotid fistula and guide tubes were implanted in the skull for the introduction of probes into the lateral ventricles in order to s le CSF and infuse artificial CSF solutions. The cows were Na depleted by loss of saliva for 46 hr and then given free access for 2 hr to 300 mM NaCl/NaHCO3 solution. Artificial CSF infusions at 1.9 ml/hr were begun one hour before Na access. In control experiments, the cows drank 26.4 +/- 1.2 l of Na solution in 2 hr, 1.2 +/- 0.2 l of water in the preceding hour, and 0.3 +/- 0.1 l of water during Na access. Sham or standard isotonic CSF infusions did not alter these values. CSF [Na+] rose from approximately 142 to approximately 148 mmol/l, attributable to the effects of drinking the large volume of hypertonic Na solution. Infusion of 500 mM NaCl CSF increased CSF [Na+] and reduced Na intake and increased water intake. Infusion of 700 mM mannitol: 150 mM NaCl CSF reduced CSF [Na+] and increased both Na and water intake. Infusion of a mixture of these solutions had no effect on CSF [Na+] and increased water intake only. Infusion of 270 mM mannitol CSF reduced CSF [Na+] and slightly reduced Na intake. Standard isotonic CSF containing 0.5 or 2.0 micrograms/ml of angiotensin II increased water intake only.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Elsevier BV
Date: 10-1987
DOI: 10.1016/0022-4731(87)91064-8
Abstract: 18-Oxo-cortisol (18-oxo-F) has been isolated from the urine of subjects with primary aldosteronism. This study examines the pressor, mineralocorticoid and glucocorticoid effects of 18-oxo-F in conscious sheep--a well studied species for the assessment of the pressor effect of steroid hormones. 18-oxo-F (24 mg/day i.v. for 5 days, n = 3) increased mean arterial pressure MAP (64 +/- 2 mmHg control and 75 +/- 6 mmHg on day 5 P less than 0.001). There was no change in heart rate. Plasma [K+] decreased from a control of 4.3 +/- 0.1 mmol/l control to 2.9 +/- 0.3 mmol/l on day 5 (P less than 0.001). Urinary Na+ excretion decreased on the first infusion day (233 +/- 18 mmol/day control and 124 +/- 20 mmol/day on infusion day 1 P less than 0.001). Urinary K+ excretion was reduced on days 1, 4 and 5 of the infusion. Thus in sheep, 18-oxo-F increased blood pressure associated with in vivo evidence of mineralocorticoid activity.
Publisher: Proceedings of the National Academy of Sciences
Date: 13-02-2001
Abstract: Little is known about the physiological mechanisms subserving the experience of air hunger and the affective control of breathing in humans. Acute hunger for air after inhalation of CO 2 was studied in nine healthy volunteers with positron emission tomography. Subjective breathlessness was manipulated while end-tidal CO 2 - was held constant. Subjects experienced a significantly greater sense of air hunger breathing through a face mask than through a mouthpiece. The statistical contrast between the two conditions delineated a distributed network of primarily limbic aralimbic brain regions, including multiple foci in dorsal anterior and middle cingulate gyrus, insula/claustrum, amygdala eriamygdala, lingual and middle temporal gyrus, hypothalamus, pulvinar, and midbrain. This pattern of activations was confirmed by a correlational analysis with breathlessness ratings. The commonality of regions of mesencephalon, diencephalon and limbic aralimbic areas involved in primal emotions engendered by the basic vegetative systems including hunger for air, thirst, hunger, pain, micturition, and sleep, is discussed with particular reference to the cingulate gyrus. A theory that the phylogenetic origin of consciousness came from primal emotions engendered by immediate threat to the existence of the organism is discussed along with an alternative hypothesis by Edelman that primary awareness emerged with processes of ongoing perceptual categorization giving rise to a scene [Edelman, G. M. (1992) Bright Air, Brilliant Fire (Penguin, London)].
Publisher: Elsevier BV
Date: 09-1999
DOI: 10.1016/S0031-9384(99)00085-2
Abstract: The influence of intracerebroventricular (i.c.v.) infusion of angiotensin II on intake of water and ethanol solutions was determined in C57BL/6J mice. Compared to other mice, C57 mice do not show an aversion to ethanol solutions. With both water and ethanol solutions available, the C57 mice consumed 40-60% of their total daily fluid intake as ethanol solution when the concentration of ethanol solution offered was 4-14%. When given a choice between 0.3 M KCl and either 4 or 10% ethanol solution, the mice clearly preferred the ethanol solution. With water only available, i.c.v. infusion of angiotensin II increased intake from 3-5 mL/day (baseline) to 11-12 mL/ day (Day 4 of infusion). A similar increase in intake occurred in mice with access to a nonpreferred solution of 0.3 M KCl. In comparison, when only 4% ethanol solution was available, angiotensin II increased intake to 7-8 mL/day, and when only 10% ethanol solution was available, intake was transiently increased. The results demonstrated that thirst for water caused by i.c.v. infusion of angiotensin II in C57 mice is similar to that observed in BALB/C mice. Unlike BALB/C mice, however, i.c.v. infusion of angiotensin II stimulated intake of ethanol solution. The failure of angiotensin II to cause a large increase in 4% ethanol solution or a sustained increase in 10% ethanol solution intake does not seem to be caused by an aversion to the taste of ethanol solution, but most likely due to postingestional factors.
Publisher: Elsevier BV
Date: 04-1978
DOI: 10.1016/0091-3057(78)90067-9
Abstract: Subcutaneous injections of long-acting synthetic ACTH (5 U/day) caused a large increase in the intakes of both 0.5 M NaCl and water in rats. By the fifth day of treatment the rats were turning over an amount of sodium approximating their own total body sodium. The mineral appetite was specific for NaCl. Intakes of KCl, MgCl2 and CaCl2 were unchanged. ACTH was ineffective in adrenalectomized rats suggesting that the appetite was dependent on adrenal hormones.
Publisher: Proceedings of the National Academy of Sciences
Date: 13-02-2001
Abstract: Recent neuroimaging and neurological data implicate cerebellum in nonmotor sensory, cognitive, vegetative, and affective functions. The present study assessed cerebellar responses when the urge to breathe is stimulated by inhaled CO 2 . Ventilation changes follow arterial blood partial pressure CO 2 changes sensed by the medullary ventral respiratory group (VRG) and hypothalamus, entraining changes in midbrain, pons, thalamus, limbic, paralimbic, and insular regions. Nearly all these areas are known to connect anatomically with the cerebellum. Using positron emission tomography, we measured regional brain blood flow during acute CO 2 -induced breathlessness in humans. Separable physiological and subjective effects (air hunger) were assessed by comparisons with various respiratory control conditions. The conjoint physiological effects of hypercapnia and the consequent air hunger produced strong bilateral, near-midline activations of the cerebellum in anterior quadrangular, central, and lingula lobules, and in many areas of posterior quadrangular, tonsil, biventer, declive, and inferior semilunar lobules. The primal emotion of air hunger, dissociated from hypercapnia, activated midline regions of the central lobule. The distributed activity across the cerebellum is similar to that for thirst, hunger, and their satiation. Four possible interpretations of cerebellar function(s) here are that: it subserves implicit intentions to access air it provides predictive internal models about the consequences of CO 2 inhalation it modulates emotional responses and that while some cerebellar regions monitor sensory acquisition in the VRG (CO 2 concentration), others influence VRG to adjust respiratory rate to optimize partial pressure CO 2 , and others still monitor and optimize the acquisition of other sensory data in service of air hunger aroused vigilance.
Publisher: Elsevier BV
Date: 06-1986
DOI: 10.1016/0006-8993(86)90761-4
Abstract: Binding of [125I]-(Sar1,Ile8)angiotensin II (AII) to frozen sections of sheep brain was determined by in vitro autoradiography. Greatest AII-binding occurred in the organum vasculosum of the lamina terminalis, subfornical organ, median preoptic and periventricular nuclei situated in the anterior third ventricle wall. Other binding sites included the hypothalamic supraoptic and paraventricular nuclei and the medullary nucleus tractus solitarius. These regions may be central receptor sites for AII involvement in fluid and electrolyte balance and blood pressure regulation.
Publisher: Elsevier BV
Date: 09-1987
DOI: 10.1016/0006-8993(87)90248-4
Abstract: It has been shown previously in sheep that physiological increase of cerebrospinal fluid (CSF) [Na] by infusion of 0.5 M NaCl artificial CSF causes a large reduction of sodium appetite of the sodium-deplete animal. Equivalent increase of CSF osmotic pressure caused by infusion 0.7 M mannitol artificial CSF which lowers CSF [Na] causes a doubling of sodium appetite. The results of the experiments here show that simple dilution of CSF [Na] with isotonic mannitol CSF, as distinct from use of hypertonic 0.7 M mannitol CSF, is an equally effective strong stimulus of sodium appetite. Lowering CSF [Na] concentration stimulates salt appetite in the severely sodium-deplete as well as in the mild to moderately sodium-deplete animal, and the effect of decrease of CSF [Na] on sodium appetite is sustained over 48 h. In addition, i.c.v. infusion of angiotensin II for the preceding 22 h at a rate which is an effective stimulus of both water and sodium solution intake in the sodium-replete animal, in fact, significantly decreased the sodium appetite stimulating effect of reduction of CSF [Na] in the Na-deplete animal.
Publisher: Elsevier BV
Date: 1987
DOI: 10.1016/0022-4731(87)90177-4
Abstract: Previous studies in sheep have provided evidence for a separate "hypertensinogenic" class of adrenocortical steroid activity which is not simply related to their classical mineralocorticoid (MC) and/or glucocorticoid (GC) actions. This study investigated the structure-activity relationships of the effects of structural analogues of prednisolone on mean arterial pressure (MAP), and MC and GC actions in sheep. Infusions of these synthetic GC at 0.6 and 24 mg/day produced variable pressor effects which were dissociated from their MC and GC actions. In other experiments, the minimum adrenocortical steroid requirement to reproduce the onset of ACTH-dependent hypertension was determined. Infusion of cortisol, aldosterone, 17 alpha-hydroxy progesterone and 17 alpha,20 alpha-dihydroxy-4-pregnene-3-one was found to be sufficient to reproduce the hypertensive response to ACTH administration in sheep. A subsequent experiment showed that substitution of cortisol by the more potent synthetic GC, prednisolone had no effect on MAP. Therefore, cortisol appears to exert an essential action in ACTH hypertension which is not dependent on its GC activity. Other studies have found that prednisolone (100 mg/day) antagonized 9 alpha-fluoro-prednisolone (0.6 mg/day) induced hypertension but not its MC effects. The effect of progesterone (500 mg/day) and the progesterone analogues, norethisterone, medroxy-progesterone and 16 alpha-methyl progesterone on ACTH (5 micrograms/kg per day) hypertension was investigated. Progesterone completely blocked the hypertension and MC effects of ACTH infusion, while medroxy-progesterone partially blocked the increase in MAP. These data support our concept of a "hypertensinogenic" class of steroid activity.
Publisher: Elsevier BV
Date: 1990
DOI: 10.1016/0006-8993(90)90513-B
Abstract: Sheep with guide tubes implanted over the brain lateral ventricles, in order to facilitate episodic s ling of cerebrospinal fluid (CSF), were used to determine the effects of increasing cranial blood osmolality or electroconvulsive shock (ECS) on the permeability of the blood-brain barrier (BBB) to zinc. Zinc acetate solution (1 mg Zn/ml) was infused intravenously (i.v.) at 1.0 ml/min for 30 min and then continuously at 0.125 ml/min. This infusion increased plasma total zinc concentration (pZn) approximately 10-fold without altering CSF zinc concentration (CSFZn). After 1.5-3.5 h, 4 M NaCl was infused at 5-10 ml/min for 10 min into one carotid artery with the other carotid artery occluded, or the animals were anaesthetized and given an ECS (140 V, 2 s). Paired s les of blood and CSF were collected before and after these treatments. Results were: (i) CSFZn was approximately one tenth of pZn (ii) zinc administered i.v. was almost completely excluded from the CSF (iii) increased cranial blood osmolality or ECS increased CSFZn in all experiments, but the time course and extent of the rise were variable. CSFZn reached the concentrations of zinc in normal sheep plasma in some experiments (iv) CSFZn subsequently fell towards the low values of zinc in normal CSF (v) the animals suffered no evident ill-effects from either procedure. The procedures may, therefore, be used for reversible opening of the BBB to particles such as zinc in conscious or anaesthetized sheep with no troublesome sequelae.
Publisher: American Psychological Association (APA)
Date: 1987
Publisher: Elsevier BV
Date: 10-1989
DOI: 10.1016/0006-8993(89)90331-4
Abstract: The sodium intake of sodium deplete sheep was studied during local, push-pull perfusion of different solutions within the third cerebral ventricle. Sheep were made sodium deplete by continuous loss of parotid saliva, and were allowed access to 0.6 M NaHCO3 solution for 2 h daily. Local perfusion within the third cerebral ventricle was performed before and during the access to sodium solution. Four perfusion sites were used: anterior dorsal and ventral, and posterior dorsal and ventral. Perfusion of 200 mM Na-csf caused a decrease in sodium intake at each perfusion site. Perfusion of ouabain, 10(-6) M, caused a reduction in sodium intake only during perfusions within the anterior portion of the third ventricle. The results may indicate that specific neuronal elements sensitive to changes in intracellular sodium concentration are located around the anterior portion of the third cerebral ventricle. These neurones, however, are not exclusive sites from where sodium intake of sodium deplete sheep can be influenced.
Publisher: Proceedings of the National Academy of Sciences
Date: 25-03-2005
Abstract: Thermoregulatory mechanisms are remarkably efficient, ensuring minimal temperature variation within the core of the human body under physiological conditions. Diverse afferent and efferent neural pathways contribute to the monitoring of core and skin temperature, generation of heat, and control of thermal exchange with the external environment. We have investigated the cortical, thalamic, and hypothalamic responses to cooling and warming by using positron-emission tomography activation imaging of subjects clad in a water-perfused suit, which enabled rapid change of their skin-surface temperature. Human brain regions that respond to changes in skin temperature have been identified in the somatosensory cortex, insula, anterior cingulate, thalamus, and hypothalamus, with evidence that the hypothalamic response codes for the direction of temperature change. We conclude that signals from thermosensors in the skin providing crucial afferent information to the brain are integrated with signals from central thermosensors, resulting in thermoregulatory responses that maintain core temperature within a remarkably narrow range.
Publisher: Elsevier BV
Date: 03-1976
DOI: 10.1016/0091-3057(76)90235-5
Abstract: Initially it was shown that infusion of Sar1-Ala8-angiotensin II (P113) into the third ventricle (50-100 mug/ml at 1.1 ml/hr) effectively abolished the large water intake induced 1-2 min after beginning an intracarotid infusion of angiotensin II at 800 ng/min which causes an unphysiologically high concentration of angiotensin II in cerebral arterial blood. Infusion of P113 (50-100 mug/ml at 1.1 ml/hr) into the third brain ventricle for 20 min prior to and during presentation of water to sheep after 48 hr water deprivation did not reduce water intake. Water intake associated with rapid food intake or carotid artery infusion of hypertonic NaC1 was similarly unaffected by intraventricular administration of P113. While high concentrations of angiotensin II are dipsogenic in sheep, these results cast doubt on a contributory role for angiotensin II in thirst caused by water depletion or rapid food intake in the sheep.
Publisher: Elsevier BV
Date: 02-1983
DOI: 10.1016/0022-4731(83)90084-5
Abstract: The blood clearance rate (BCR) of aldosterone, cortisol, 17 alpha-hydroxyprogesterone (17 alpha OHP) and 17 alpha, 20 alpha-dihydroxy-4-pregnen-3-one (17 alpha 20 alpha OHP) has been measured in conscious sheep prior to and after 5 or 6 days ACTH treatment. ACTH increased the BCR of cortisol but did not change the BCR of the other three steroids. 17 alpha OHP had a BCR greater than liver blood flow suggesting extra-hepatic metabolism. In vivo conversion of 17 alpha OHP to 17 alpha 20 alpha OHP by ovine red cells has been shown to be a significant site of this metabolism. It is suggested that this conversion of 17 alpha OHP to 17 alpha 20 alpha OHP may be important in the expression of the "hypertensionogenic" effect of 17 alpha OHP.
Publisher: Informa UK Limited
Date: 1984
DOI: 10.3109/10641968409044057
Abstract: Methylprednisolone has been reported to be produce hypertension in the rat but to have no effect on blood pressure in the dog. In this study, methylprednisolone infused to conscious sheep for up to 10 days at either 20 micrograms/kg/hr or 100 micrograms/kg/hr, failed to induce a hypertensive response. Metabolic effects characteristic of glucocorticoid activity, such as increased water intake and urine volume, were observed in all animals. No consistent decrease in plasma potassium concentration was observed with either rate of infusion, indicating a lack of in-vivo mineralocorticoid activity. In the conscious sheep, like the dog, methylprednisolone exhibits only glucocorticoid activity and does not increase blood pressure.
Publisher: Elsevier BV
Date: 1991
DOI: 10.1016/0361-9230(91)90197-R
Abstract: Intracerebroventricular (ICV) infusion of CRF, for 22 h, induced five- to seven-fold increase in the daily intake of sodium chloride solution in wild rabbits. The increased sodium intake persisted for 3 days after the infusion stopped and was accompanied by increased sodium excretion, water turnover and decreased food intake. ICV infusion of CRF also induced a change in the general behaviour of the animals, which lasted throughout the infusion only. Systemic, but not ICV administration of ACTH, similar to systemic administration of adrenal steroid hormones (demonstrated in earlier studies), induced gradual increases in the daily sodium intake and excretion of rabbits, as did restraint by tight jackets. The increased sodium intake was accompanied by increased sodium excretion and water turnover, and lasted as long as the administration of hormones. Together these results lead to the hypothesis that increased sodium intake might be an integral part of the stress reaction of the body and not the consequence of distortions of other regulatory functions.
Publisher: Elsevier BV
Date: 1986
DOI: 10.1016/0031-9384(86)90374-4
Abstract: Increases in cerebrospinal fluid pressure (CSFP) were measured in the lateral ventricle in barbiturate anaesthetized male Sprague Dawley rats during intracerebroventricular (IVT) infusions into the contralateral ventricle. IVT infusions of isotonic artificial CSF (art-CSF) solutions at 10 and 38 microliters/hr increased mean CSFP from control preinfusion level of 3.6 cm H2O to 4.6 cm H20 (n.s.) and 5.2 cm H2O (p less than 0.01) respectively with CSFP appearing to attain equilibrium after 30-60 min of infusion. IVT infusion of hyperosmolar art CSF solutions (saccharide and salt solutions of approximate 1000 mOsm/kg) at 38 microliters/hr resulted in a larger increase of CSFP which equilibrated at 8.5 cm H2O (p less than 0.001) after 90 min of infusion. It is suggested that on the basis of CSFP measurements in these and other experiments cited that IVT infusions be run at infusion rates of less than 40 microliters/hr to ensure minimal physiological change.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.NEUROIMAGE.2009.12.034
Abstract: This study used arterial spin labeling (ASL) fMRI to measure brain perfusion in a group of healthy men under conditions that closely resembled customary sexual behavior. Serial perfusion measures for 30 min during two self-limited periods of partnered penis stimulation, and during post-stimulatory periods, revealed novel sexual activity-related cerebral blood flow (rCBF) changes, mainly in subcortical parts of the brain. Ventral pallidum rCBF was highest during the onset of penile erection, and lowest after the termination of penis stimulation. The perceived level of sexual arousal showed the strongest positive association with rCBF in the right basal forebrain. In addition, our results demonstrate that distinct subregions of the hypothalamus and cingulate cortex subserve opposite functions during human male sexual behavior. The lateral hypothalamus and anterior part of the middle cingulate cortex showed increased rCBF correlated with penile erection. By contrast, the anteroventral hypothalamus and subgenual anterior cingulate cortex exhibited rCBF changes correlated with penile detumescence after penile stimulation. Continuous rapid and high-resolution brain perfusion imaging during normal sexual activity has provided novel insights into the central mechanisms that control male sexual arousal.
Publisher: Elsevier BV
Date: 03-1991
DOI: 10.1016/0006-8993(91)90030-Y
Abstract: The effect of intracerebroventricular (i.c.v.) infusion (50 micrograms/h over 3 h) of somatostatin (SOM) on Na and water intake of sheep was determined. In Na-deplete sheep, infusion of SOM-(28) but not SOM-(14) decreased (P less than 0.05) Na intake, while both SOM-(28) and SOM-(14) increased water intake. I.c.v. infusion of SOM-(28) did not significantly affect Na or water intake of Na-replete sheep. I.c.v. infusion of SOM-(28) decreased (P less than 0.01) Na intake but did not alter the high water intakes of water-deprived sheep or sheep infused i.c.v. with angiotensin II. The results are compatible with an inhibitory action of somatostatin on stimulated brain mechanisms subserving Na appetite but not on stimulated brain mechanisms subserving thirst. Somatostatin may antagonize the inhibition of thirst in Na-deplete sheep. The results suggest that somatostatin may have a regulatory role in ingestive behavior concerned with body fluid and Na homeostasis. The difference between SOM-(14) and SOM-(28) in decreasing the Na intake of Na-deplete sheep may be due to a difference in potency or mechanism of action.
Publisher: Elsevier BV
Date: 1987
DOI: 10.1016/0031-9384(87)90373-8
Abstract: Infusions into the lateral cerebral ventricle of hypertonic solutions of NaCl, mannitol or sucrose all induced water drinking in cattle. However, infusion of hypertonic NaCl caused a significantly greater water drinking response than did the infusions of mannitol or sucrose, despite the fact that CSF osmolality increase was similar. In contrast, hypertonic solutions of NaCl or mannitol had similar dipsogenic effects when infused intravenously. The intracerebroventricular infusions of hypertonic NaCl or mannitol did not affect the intakes of food or Na solution. The results are consistent with the hypothesis that both cerebral osmoreceptors and Na sensors are involved in regulating thirst in cows.
Publisher: Proceedings of the National Academy of Sciences
Date: 09-07-1996
Abstract: The reactions of chimpanzees to regular mirrors and the results of the standard Gallup mark test have been well documented. In addition to using the mark test to demonstrate self-recognition in a regular mirror, we exposed six female chimpanzees to mirrors that produced distorted or multiplied self-images. Their reactions to their self-images, in terms of mirror-guided self-referenced behaviors, indicated that correct assessment of the source of the mirror image was made by each subject in each of the mirrors. Recognition of a distorted self-image implies an ability for abstraction in the subjects in that the distortion must be rationalized before self-recognition occurs. The implications of these results in terms of illuminating the relative importance of feature and contingency of movement cues to self-recognition are discussed.
Publisher: The Endocrine Society
Date: 12-2004
DOI: 10.1210/EN.2004-0432
Abstract: The neuroendocrine hormones ACTH and corticotropin- releasing factor (CRF), which are involved in the stress response, have acute effects on arterial pressure. New evidence indicates that urocortin (UCN), the putative agonist for the CRF type 2 receptor, has selective cardiovascular actions. The responses to long-term infusions of these hormones, both peripherally and centrally, in conscious animals have not been studied. Knowledge of the long-term effects is important because they may differ considerably from their acute actions, and stress is frequently a chronic stimulus. The present experiments investigated the cardiovascular effects of CRF, UCN, and ACTH in conscious sheep. Infusions were made either into the lateral cerebral ventricles (icv) or iv over 4 d at 5 μg/h. UCN infused icv or iv caused a prolonged increase in heart rate (HR) (P & 0.01) and a small increase in mean arterial pressure (MAP) (P & 0.05). CRF infused icv or iv progressively increased MAP (P & 0.05) but had no effect on HR. Central administration of ACTH had no effect, whereas systemic infusion increased MAP and HR (P & 0.001). In conclusion, long-term administration of these three peptides associated with the stress response had prolonged, selective cardiovascular actions. The striking finding was the large and sustained increase in HR with icv and iv infusions of UCN. These responses are probably mediated by CRF type 2 receptors because they were not reproduced by infusions of CRF.
Publisher: Proceedings of the National Academy of Sciences
Date: 11-07-2011
Abstract: Sodium appetite is an instinct that involves avid specific intention. It is elicited by sodium deficiency, stress-evoked adrenocorticotropic hormone (ACTH), and reproduction. Genome-wide microarrays in sodium-deficient mice or after ACTH infusion showed up-regulation of hypothalamic genes, including dopamine- and cAMP-regulated neuronal phosphoprotein 32 kDa (DARPP-32), dopamine receptors-1 and -2, α-2C- adrenoceptor, and striatally enriched protein tyrosine phosphatase (STEP). Both DARPP-32 and neural plasticity regulator activity-regulated cytoskeleton associated protein (ARC) were up-regulated in lateral hypothalamic orexinergic neurons by sodium deficiency. Administration of dopamine D1 (SCH23390) and D2 receptor (raclopride) antagonists reduced gratification of sodium appetite triggered by sodium deficiency. SCH23390 was specific, having no effect on osmotic-induced water drinking, whereas raclopride also reduced water intake. D1 receptor KO mice had normal sodium appetite, indicating compensatory regulation. Appetite was insensitive to SCH23390, confirming the absence of off-target effects. Bilateral microinjection of SCH23390 (100 nM in 200 nL) into rats’ lateral hypothalamus greatly reduced sodium appetite. Gene set enrichment analysis in hypothalami of mice with sodium appetite showed significant enrichment of gene sets previously linked to addiction (opiates and cocaine). This finding of concerted gene regulation was attenuated on gratification with perplexingly rapid kinetics of only 10 min, anteceding significant absorption of salt from the gut. Salt appetite and hedonic liking of salt taste have evolved over million y (e.g., being present in Metatheria). Drugs causing pleasure and addiction are comparatively recent and likely reflect usurping of evolutionary ancient systems with high survival value by the gratification of contemporary hedonic indulgences. Our findings outline a molecular logic for instinctive behavior encoded by the brain with possible important translational–medical implications.
Publisher: Elsevier BV
Date: 05-1988
DOI: 10.1016/0196-9781(88)90182-9
Abstract: Two rabbit strains, New Zealand (laboratory) rabbits and Australian wild rabbits, both members of the Oryctolagus cuniculus genus were studied. New Zealand rabbits under control conditions consumed 2-5 times more water and 8-30 times more 0.5 M NaCl/kg body weight than wild rabbits. Single injections of angiotensin II or III administered ICV did not induce water drinking in either strain. Acute ICV infusion of angiotensin II also did not influence water intake, but after several days of administration, induced increased sodium intake. Intravenous infusion of graded doses of angiotensin II induced diuresis only at the higher doses in both strains. In New Zealand rabbits, this was accompanied by a commensurate and concurrent increase in water intake. Intravenous infusion of angiotensin II also induced urinary sodium loss that was either accompanied or followed by increased sodium intake. The development of salt appetite in both strains was preceded by sodium loss.
Publisher: Elsevier BV
Date: 03-1991
DOI: 10.1016/0006-8993(91)91570-Q
Abstract: Sodium and water intake and excretion of wild rabbits was studied during intracerebroventricular (icv) infusion of corticotropin-releasing factor (CRF). Icv infusion of 200 and 600 pmol/h for 22 h induced changes in the ingestive and general behavior of animals. Increased consumption of 0.5 M NaCl solution was observed during the day of infusion, accompanied by increased sodium excretion, and food intake was decreased. The rabbits maintained the high sodium turnover, together with a high water turnover, for 2-3 days after the icv infusion stopped. Icv infusion of CRF induced strange behaviour in wild rabbits, they appeared to react with fright to normal daily events around them. The strange behaviour started about two hours after the beginning of icv infusion and disappeared immediately after the infusion stopped. On the basis of present and earlier observations, that systemic administration of adrenocorticotropin (ACTH) and adrenal steroid hormones induce increased sodium turnover, it is proposed that changes in the sodium and water metabolism might constitute part of the general stress reaction of the body.
Publisher: Elsevier BV
Date: 05-2006
DOI: 10.1016/J.SEMNEPHROL.2006.02.001
Abstract: Thirst and resultant water drinking can arise in response to deficits in both the intracellular and extracellular fluid compartments. Inhibitory influences mediating the satiation of thirst also are necessary to prevent overhydration. The brain regions that underpin the generation or inhibition of thirst in these circumstances can be categorized as sensory, integrative, or cortical effector sites. The anterior cingulate cortex and insula are activated in thirsty human beings as shown by functional brain-imaging techniques. It is postulated that these sites may be cortical effector regions for thirst. A major sensory site for generating thirst is the lamina terminalis in the forebrain. Osmoreceptors within the organum vasculosum of the lamina terminalis and subfornical organ detect systemic hypertonicity. The subfornical organ mediates the dipsogenic actions of circulating angiotensin II and relaxin. Major integrative sites are the nucleus of the tractus solitarius, the lateral parabrachial nucleus, the midbrain raphé nuclei, the median preoptic nucleus, and the septum. Despite these advances, most of the neural pathways and neurochemical mechanisms subserving the genesis of thirst remain to be elucidated.
Publisher: Elsevier BV
Date: 02-1995
DOI: 10.1016/S0195-6663(95)80002-6
Abstract: The effects of adrenal steroid hormones on sodium appetite were determined in female Balb/c mice by the subcutaneous implantation for 7 days of slow-release pellets containing aldosterone, corticosterone, deoxycorticosterone (DOC) or 11-deoxycortisol, separately or in a "cocktail" combination. Placebo pellets were also implanted. The daily intake of 0.3 M NaCl was increased for 2 days by aldosterone (calculated 2.9 micrograms/day released) or corticosterone (240 micrograms/day) and for 7 days by DOC (4.8 micrograms/day). The combination of these steroids plus 11-deoxycortisol (95 micrograms/day) increased daily sodium intake nine-fold (days 3-7) and also increased water intake 1.5-fold. Placebo pellets had small effects on water intake on three days. Subcutaneous infusion of ACTH (Synacthen) at 2.8 micrograms/day for 7 days by mini-osmotic pump increased sodium intake five-fold and water intake three- or four-fold. Thus, several adrenal steroids evoked sodium appetite in Balb/c mice, DOC being the most potent at the doses used. The effects of in idual steroids are consistent with their contribution to the effect of ACTH on sodium appetite.
Publisher: Elsevier BV
Date: 06-1989
DOI: 10.1016/0091-3057(89)90510-8
Abstract: The effect of ACTH or dexamethasone treatment on ingestion of 10% ethanol, 0.5 M NaCl and water was studied in in idually- and pair-housed rats. Crowding or decreasing the amount of space per rat by increasing the number of rats per cage from 1 to 2, together with the associated increase in social interactions caused a large increase in ethanol intake. In pair-housed rats and in rats housed alone, ACTH treatment caused a large increase in Na intake but no change in ethanol intake. In pair-housed rats and in rats housed alone, dexamethasone treatment caused no change in either ethanol or Na intake. Thus, it would appear that the induction or maintenance of a high ethanol intake of rats during crowding, a presumed social stressor, can not be attributed entirely to either an increase in blood ACTH levels with the subsequent increase in glucocorticoid hormones or to a decrease in blood ACTH and natural glucocorticoid hormone levels. However, the possibility that ACTH and/or adrenocorticoid hormones, combined with other physiological or environmental factors, causes stressor-induced ethanol intake cannot be excluded.
Publisher: Elsevier BV
Date: 12-1983
DOI: 10.1016/0361-9230(83)90007-2
Abstract: Examination of the ventricular surface of the organum vasculosum of the lamina terminalis (OVLT) of sheep with the scanning electron microscope revealed an elongated protuberance occupying most of the frontal wall of the third ventricle below the level of the anterior commissure. This protuberance lacked ciliated ependymal cells. Examination of horizontal sections with the transmission electron microscope revealed an apparent lack of regularly apposed ependymal cells, suggesting that ependyma is either greatly modified or absent. The surface was composed of numerous intertwining cell processes with some scattered cells situated on this surface. The body of this structure was composed of many cell processes separated by a network of extracellular channels sometimes extending to the ventricular surface. Towards the base of this protuberance, a plexus of blood vessels was observed. Some of these vessels exhibited fenestrated endothelium. Neuronal processes were also apparent in this region. These unusual anatomical features suggest a specific function for this brain region in sheep.
Publisher: Elsevier BV
Date: 08-1990
DOI: 10.1016/0006-8993(90)90245-7
Abstract: The effect of subfornical organ (SFO) lesion on various models of ingestive behaviour was investigated in rats. Intake of water after 24 h water deprivation or systemic administration of hypertonic NaCl were not altered by SFO lesions. Intake of food or water after 24 h of food deprivation were not altered by SFO lesions. Intake of NaCl after furosemide-induced Na depletion was decreased by ablation of the SFO. This decrease in Na intake was ameliorated by pretreatment with a low dose of captopril. These results suggest that the SFO is involved in Na intake after Na depletion, but not in water or food intake following periods of water or food deprivation, respectively. The observation that a low dose of captopril can eliminate the decrease in Na appetite which occurred subsequent to SFO lesion suggests that other brain areas may also participate in Na-depletion-induced Na appetite.
Publisher: No publisher found
Date: 1983
Publisher: Cold Spring Harbor Laboratory
Date: 20-10-2020
DOI: 10.1101/2020.10.20.327296
Abstract: Naegleria fowleri is a pathogenic, thermophilic, free-living amoeba which causes primary amebic meningoencephalitis (PAM). Penetrating the olfactory mucosa, the brain-eating amoeba travels along the olfactory nerves, burrowing through the cribriform plate to its destination: the brain’s frontal lobes. The amoeba thrives in warm, freshwater environments, with peak infection rates in the summer months and has a mortality rate of approximately 97%. A major contributor to the pathogen’s high mortality is the lack of sensitivity of N. fowleri to current drug therapies, even in the face of combination-drug therapy. To enable rational drug discovery and design efforts we have pursued protein production and crystallography-based structure determination efforts for likely drug targets from N. fowleri. N. fowleri genes were selected if they had homology to drug targets listed in Drug Bank or were nominated by primary investigators engaged in N. fowleri research. In 2017, 178 N. fowleri protein targets were queued to the Seattle Structural Genomics Center of Infectious Disease (SSGCID) pipeline, and to date 89 soluble recombinant proteins and 19 unique target structures have been produced. Many of the new protein structures are potential drug targets and contain structural differences compared to their human homologs, which could allow for the development of pathogen-specific inhibitors. Five of the structures were analyzed in more detail, and four of five show promise that selective inhibitors of the active site could be found. The 19 solved crystal structures build a foundation for future work in combating this devastating disease by encouraging further investigation to stimulate drug discovery for this neglected pathogen.
Publisher: Informa UK Limited
Date: 1979
DOI: 10.3109/10641967909068630
Abstract: It is generally believed that adrenal steroid hypertension is due to the 'mineralocorticoid' and/or 'glucocorticoid' activities of the steroid(s). The present study examines the blood pressure and metabolic effects of steroid hormone infusion in intact conscious sheep to assess the relative contributions of 'glucocorticoid' and 'mineralocorticoid' activity. Cortisol at 5 mg/h increased mean arterial pressure (MAP) but the effect was small (MAP + 10 mm Hg on day 5). This rate of infusion produces blood cortisol levels appropriate for maximal ACTH stimulation. Cortisol at 20 mg/hr produced hypertension (MAP + 25 mm Hg on day 5, p less than 0.01) but also produced the 'mineralocorticoid' effect of severe hypokalaemia. Dexamethasone at 1 mg/hr produced small increases in MAP but a profound fall in plasma [K]. Aldosterone at 80 microgram/hr (a pharmacological rate) produced hypokalaemia, urinary Na retention but no effect on MAP over 5 days. Thus, in short term infusion experiments, 'mineralocorticoid' effects are not associated with hypertension. Pharmacological concentrations of predominantly 'gluc-corticoid' steroid hormones produced hypertension but also exhibited substantial 'mineralocorticoid' activity. At levels approximating maximal physiological secretion, the rise in blood pressure was small. These results supported the contention that ACTH induced hypertension in sheep represents a mechanism different from a simple 'mineralocorticoid' or 'glucocorticoid' action.
Publisher: Elsevier BV
Date: 1997
DOI: 10.1016/S0196-9781(97)00077-6
Abstract: The role of brain angiotensin II (ANG II) in water, Na and food intake of rats was studied. Intracerebroventricular (i.c.v.) infusion (100 micrograms/h) of the non-peptide ANG II receptor antagonist losartan (type 1), but not PD123319 (type 2), completely blocked water intake caused by i.c.v. infusion of ANG II at 50 ng/h. Following food deprivation, food intake was reduced by PD123319 and associated water intake was decreased by losartan or PD123319. Neither water intake after water deprivation nor Na intake after Na depletion was altered by losartan or PD123319. In conclusion, evidence was consistent with a role for brain ANG II in both food and water intake after food deprivation but not in thirst subsequent to water deprivation or Na intake after Na depletion alone.
Publisher: Springer Science and Business Media LLC
Date: 10-1995
DOI: 10.1038/NM1095-1009
Abstract: A colony of 26 chimpanzees given a fruit and vegetable diet of very low Na and high K intake were maintained in long-standing, socially stable small groups for three years. Half of them had salt added progressively to their diet during 20 months. This addition of salt within the human dietetic range caused a highly significant rise in systolic, mean and diastolic blood pressure. The change reversed completely by six months after cessation of salt. The effect of salt differed between chimpanzees, some having a large blood pressure rise and others small or no rise. These results in the species phylogenetically closest to humans bear directly on causation of human hypertension, particularly in relation to migration of preliterate people, with low Na diet, to a Western urban lifestyle with increased salt intake. The hedonic liking for salt and avid ingestion was apt during human prehistory involving hunter-gatherer-scavenger existence in the interior of continents with a scarcity of salt, but is maladaptive in urban technological life with salt cheap and freely available.
Publisher: American Psychological Association (APA)
Date: 1983
Publisher: Informa UK Limited
Date: 1981
DOI: 10.3109/10641968109037174
Abstract: The effect of intravenous injection of the angiotensin converting enzyme inhibitor SQ 14 225 on blood pressure, heart rate and plasma renin concentration (PRC) was investigated in 15 intact conscious ewes as follows: sodium replete during angiotensin I infusion (n = 4) sodium replete (n = 6) sodium deplete (n = 5) chronic water deprivation (n = 5) AcTH treated sodium replete (n = 6). Following SQ 14 225 mean arterial pressure fell 5 +/- 1 mmHg in sodium replete, 20 +/- 4 mmHg in acutely sodium deplete, 7 +/- 2 mmHg in chronic water deprivation and 6 +/- 2 mmHg in ACTH treated sodium replete sheep. This suggests that the renin-angiotensin system plays no significant role in maintaining the elevated blood pressure of sheep with ACTH induced hypertension. Heart rate rose in all groups except the water deprived animals following SQ 14 225. PRC rose from 5.1 +/- 2.1 pmo1AI/ml plasma/h. to 12.4 +/- 2.0 in sodium replete sheep, from 11.9 +/- 1.0 to 68 +/- 13 in acutely sodium deficient animals, and from 13.3 +/- 4.3 to 32.9 +/- 0.6 in chronically water deprived animals, but showed little change in ACTH treated sheep, falling from 2.3 +/- 0.5 to 1.7 +/- 0.2 pmo1AI/ml plasma/h.
Publisher: Elsevier BV
Date: 1985
DOI: 10.1016/0031-9384(85)90075-7
Abstract: The effect of 24 hr water deprivation on Na balance was studied in rats. Under baseline conditions, the animals had free access to food and water. During water deprivation, Na excretion was increased, Na intake (i.e., food intake) was decreased and Na deficits of 0.8-1.0 mmol were incurred. During the 24 hr period immediately following the deprivation period when water was returned, Na excretion was decreased and Na balance was restored to baseline or pre-deprivation level. In a second series of experiments, under baseline conditions, the animals had free access to food, water and 0.5 M NaCl. During water deprivation with NaCl solution withheld, Na excretion was not changed relative to baseline but Na deficits of 0.8-1.0 mmol were incurred due to decreased Na intake. During the 24 hr period immediately following deprivation when both water and NaCl solution were returned, intake of the hypertonic NaCl solution was increased and Na balance was restored. In a third series of experiments, under baseline conditions, the animals had free access to food, water, 0.5 M NaCl, 0.5 M KCl, 0.25 M of MgCl2 and 0.25 M CaCl2. During the 24 hr period following water deprivation and also the withholding of the electrolyte solutions, the appetite induced was predominantly for NaCl. The results suggest that the Na appetite observed subsequent to a period of water deprivation may be due to Na deficiency.
Publisher: Informa UK Limited
Date: 1983
DOI: 10.3109/10641968309048807
Abstract: ACTH administration in sheep produces an adrenally dependent rise in blood pressure. Cardiac output and heart rate are usually increased. The precise mechanisms involved in the genesis of the hypertension are unclear. This study examines the sensitivity of the baroreflex heart rate response to phenylephrine hydrochloride and sodium nitroprusside before, during and after ACTH administration in sheep. During ACTH administration there was a sustained rise in blood pressure within 24 hours, whereas heart rate rose gradually. There was a sustained fall in baroreflex sensitivity to sodium nitroprusside within 24 hours, whereas baroreflex sensitivity to phenylephrine fell gradually over the first three days. The different time course of the change in sensitivity suggests that two different mechanisms are influenced by ACTH administration, for instance, changes in function in both cardiac vagal efferents and sympathetic pathways.
Publisher: Elsevier BV
Date: 04-1987
DOI: 10.1016/S0195-6663(87)80002-8
Abstract: Sheep with a parotid fistula and sodium-deprived for 24 or 48 h (Na deficit = 500-700 mmol) were trained to drink their entire requirement of sodium bicarbonate solution from a cup in their cage in a single draught for up to 2 min. The cup was connected to a reservoir by an apparatus that enabled the concentration of the solution offered to be changed after the animal had drunk the first 100 or 150 ml of fluid without interrupting the flow of fluid or disturbing the drinking sheep. Under control conditions, the concentrations of solutions in the cup and reservoir were the same, either 900 mM or 300 mM NaHCO3. On experimental days, the concentration of NaHCO3 in the cup and reservoir were different so that the concentration of fluid increased from 300 mM to 900 mM or decreased from 900 mM to 300 mM NaHCO3. On those experimental days when the concentration of NaHCO3 was increased from 300 to 900 mM, the sheep drank a volume of fluid sufficient to maintain intake commensurate with loss. However, when the concentration of NaHCO3 was decreased from 900 to 300 mM, the sheep drank a volume of fluid insufficient to correct the deficit. It is proposed that the failure of sheep to react appropriately to a decrease in NaHCO3 concentration is a consequence of taste adaptation.
Publisher: Elsevier BV
Date: 03-1983
DOI: 10.1016/0006-8993(83)90326-8
Abstract: Water deprivation caused daily urinary Na output to more than double in normal sheep, but caused no increase in Na excretion in sheep (A3VL-sheep) in which the anterior third ventricle wall had been ablated. Dehydrated A3VL-sheep exhibited a much greater degree of hypernatremia than dehydrated normal sheep, although water losses were similar in both groups. We postulate that the natriuresis induced by dehydration is a cerebrally mediated homeostatic response.
Publisher: Proceedings of the National Academy of Sciences
Date: 04-10-2004
Abstract: The hypothalamus and neocortex are sub isions of the mammalian forebrain, and yet, they have vastly different evolutionary histories, cytoarchitecture, and biological functions. In an attempt to define these attributes in terms of their genetic activity, we have compared their genetic repertoires by using the Serial Analysis of Gene Expression database. From a comparison of 78,784 hypothalamus tags with 125,296 neocortical tags, we demonstrate that each structure possesses a different transcriptional profile in terms of gene ontological characteristics and expression levels. Despite its more recent evolutionary history, the neocortex has a more complex pattern of gene activity. Gene identities and levels of gene expression were mapped to their chromosomal positions by using in silico definition of GC-rich and GC-poor genome bands. This analysis shows contrasting views of gene activity on a genome scale that is unique to each brain substructure. We show that genes that are more highly expressed in one tissue tend to be clustered together on a chromosomal scale, further defining the genetic identity of either the hypothalamus or neocortex. We propose that physical proximity of coregulated genes may facilitate transcriptional access to the genetic substrates of evolutionary selection that ultimately shape the functional sub isions of the mammalian brain.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 1985
Publisher: Elsevier BV
Date: 06-1986
DOI: 10.1016/0006-8993(86)90212-X
Abstract: Ablation of tissue in the midline anterior wall of the third ventricle (AV3V) of sheep did not consistently alter baseline plasma renin concentration (PRC) in water replete animals, but caused a greatly augmented increase in PRC in response to water deprivation. PRC might increase in these sheep in order to maintain blood pressure, however it is possible that a central inhibitory influence on renal renin release, operative during dehydration, is disrupted by AV3V-lesions.
Publisher: Wiley
Date: 07-2003
DOI: 10.1046/J.1460-9568.2003.02760.X
Abstract: The influence of urocortin (UCN) on ingestive behaviours and brain neural activity, as measured immunohistochemically by the presence of Fos protein, was determined in mice. Rat UCN was administered by continuous intracerebroventricular (ICV) or subcutaneous (SC) infusion. ICV infusion of UCN (100 ng/h, 14 days) transiently reduced daily food and water intakes (days 1-4) but body weight was reduced from day 2 into the post-infusion period. Sodium intake was reduced from day 3 to the end of infusion. SC infusion of UCN caused similar but smaller reductions in food and water intakes and body weight, without change in sodium intake. In separate experiments, Fos immunoreactivity was increased in several brain nuclei known to be involved in the control of body fluid and energy homeostasis, e.g. central nucleus of the amygdala, median preoptic nucleus, bed nucleus of the stria terminalis and arcuate nucleus. Increased Fos expression was similar for ICV and SC infusions when measured on days 2-3 or 6-7 of infusion. In conclusion, increases of brain activity by UCN may be associated with stimulation of adrenocorticotrophic hormone release and sympathetic nervous activity, but increases may also indicate suppression of ingestive behaviours by stimulating central inhibitory mechanisms located in areas known to control body fluid and energy homeostasis.
Publisher: Proceedings of the National Academy of Sciences
Date: 08-01-2008
Abstract: Levels of thirst and ad libitum drinking decrease with advancing age, making older people vulnerable to dehydration. This study investigated age-related changes in brain responses to thirst and drinking in healthy men. Thirst was induced with hypertonic infusions (3.1 ml/kg 0.51M NaCl) in young (Y) and older (O) subjects. Regional cerebral blood flow (rCBF) was measured with positron emission tomography (PET). Thirst activations were identified by correlating rCBF with thirst ratings. Average rCBF was measured from regions of interest (ROI) corresponding to activation clusters in each group. The effects of drinking were examined by correlating volume of water drunk with changes in ROI rCBF from maximum thirst to postdrinking. There were increases in blood osmolality (Y, 2.8 ± 1.8% O, 2.2 ± 1.4%) and thirst ratings (Y, 3.1 ± 2.1 O, 3.7 ± 2.8) from baseline to the end of the hypertonic infusion. Older subjects drank less water (1.9 ± 1.6 ml/kg) than younger subjects (3.9 ± 1.9 ml/kg). Thirst-related activation was evident in S1/M1, prefrontal cortex, anterior midcingulate cortex (aMCC), premotor cortex, and superior temporal gyrus in both groups. Postdrinking changes of rCBF in the aMCC correlated with drinking volumes in both groups. There was a greater reduction in aMCC rCBF relative to water drunk in the older group. Aging is associated with changes in satiation that militate against adequate hydration in response to hyperosmolarity, although it is unclear whether these alterations are due to changes in primary afferent inflow or higher cortical functioning.
Publisher: Informa UK Limited
Date: 1979
DOI: 10.3109/10641967909068629
Abstract: 9 alphafluorohydrocortisone (9 alphaFF) is an analogue of hydrocortisone with both 'mineralocorticoid' and 'glucocorticoid' activity. 9 alphaFF was infused at 0.2, 0.63 and 2.0 mg/day for 5 days to intact conscious trained sheep. At high dose (0.63 and 2 mg/day) 9 alphaFF raises blood pressure in sheep, (mean arterial pressure rise 32 and 29 mm Hg respectively on the fifth day), lowers plasma [K], raises plasma [Na] and produces initial urinary sodium retention. At low dose (0.2 mg/day) blood pressure is raised (+16 mm Hg on day 5) but plasma and urinary electrolytes are unaltered. 9 alphaFF had no effect on water intake or urine output at any dose. In all animals withdrawal of 9 alphaFF was associated with a natriuresis. On the basis of its affinity for 'mineralocorticoid' and 'glucocorticoid' ovine renal receptors, 9 alphaFF at low dose may raise blood pressure by mechanisms not simply related to its 'glucocorticoid' and/or 'mineralocorticoid' action.
Publisher: Informa UK Limited
Date: 1984
DOI: 10.3109/10641968409044027
Abstract: Ganglioneuroma (GN) is a rare and benign tumor that originates from autonomic nervous system ganglion cells. The most frequently involved sites are the posterior mediastinum, the abdominal cavity, and the retroperitoneal space. It rarely occurs in the cervical area, compressing the spinal cord. Neurofibromatosis type 1 (NF-1) is an autosomal dominant inheritance disorder, whose prevalence rate approximates one per 3000. We report an extremely rare case of bilateral and symmetric dumbbell GNs of the cervical spine with NF-1. A 27-year-old man with NF-1 presented with a one-year history of gradually progressive right upper extremity weakness and numbness in both hands. Magnetic resonance imaging showed bilateral and symmetric dumbbell lesions at the C1-C2 levels compressing the spinal cord. We performed total resection of bilateral tumors, and the postoperative histopathological diagnosis of the resected mass was GN. After operation, the preoperative symptoms were gradually relieved without complications. To our knowledge, this is the sixth report of cervical bilateral dumbbell GNs. In some cases, cervical bilateral dumbbell GNs could be associated with NF-1. The exact diagnosis cannot be obtained before operation, and pathological outcome is the current gold standard. Surgical resection is the most effective option, and disease outcome is generally good after treatment.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 14-10-2016
Abstract: The relationship between bio ersity and ecosystem productivity has been explored in detail in herbaceous vegetation, but patterns in forests are far less well understood. Liang et al. have amassed a global forest data set from ,000 s le plots in 44 countries. A positive and consistent relationship can be discerned between tree ersity and ecosystem productivity at landscape, country, and ecoregion scales. On average, a 10% loss in bio ersity leads to a 3% loss in productivity. This means that the economic value of maintaining bio ersity for the sake of global forest productivity is more than fivefold greater than global conservation costs. Science , this issue p. 196
Publisher: Proceedings of the National Academy of Sciences
Date: 12-2012
Abstract: Thirst was induced by rapid i.v. infusion of hypertonic saline (0.51 M at 13.4 ml/min). Ten humans were neuroimaged by positron-emission tomography (PET) and four by functional MRI (fMRI). PET images were made 25 min after beginning infusion, when the sensation of thirst began to enter the stream of consciousness. The fMRI images were made when the maximum rate of increase of thirst occurred. The PET results showed regional cerebral blood flow changes similar to those delineated when thirst was maximal. These loci involved the phylogenetically ancient areas of the brain. fMRI showed activation in the anterior wall of the third ventricle, an area that is key in the genesis of thirst but is not an area revealed by PET imaging. Thus, this region plays as major a role in thirst for humans as for animals. Strong activations in the brain with fMRI included the anterior cingulate, parahippoc al gyrus, inferior and middle frontal gyri, insula, and cerebellum. When the subjects drank water to satiation, thirst declined immediately to baseline. A precipitate decline in intensity of activation signal occurred in the anterior cingulate area (Brodmann area 32) putatively related to consciousness of thirst. The intensity of activation in the anterior wall of the third ventricle was essentially unchanged, which is consistent with the fact that a significant time (15–20 min) would be needed before plasma Na concentration changed as a result of water absorption from the gut.
Publisher: Elsevier BV
Date: 07-1999
DOI: 10.1016/S0031-9384(99)00034-7
Abstract: The effect of sodium intake on the reproductive performance of BALB/C mice was assessed in four groups of 11 or 12 mice that received ad lib access to low or higher sodium food (LSF 4-5, HSF 120-143 mmol Na+/kg). The two groups that received HSF had (mean values) 100% matings, 83 and 91% litters, 5.9 pups/litter, pups weighing 2.05 and 2.22 g (3 days after birth) and 10.47 and 10.96 g at weaning (19 days). One of the HSF groups that also had 300 mM NaCl to drink did not show any benefit. Two groups received LSF, and one of them also received 30 mM NaCl. The group given LSF only had 83% matings, 20% litters, 1.5 pups/litter, and pups that were significantly smaller at birth and at weaning. However, the LSF group given 30 mM NaCl to drink performed almost as well as the two HSF groups. The results show that (a) the daily sodium requirement for optimal reproduction was > or = 400 (micromol/day, based on voluntary sodium intake late in gestation and lactation (b) sodium deficiency was the cause of reproductive deficiency in mice on LSF (c) severe sodium deficiency suppressed reproduction primarily at the gestation step (d) this deficiency could be prevented by the voluntary sodium intake of mothers with access to salt solution and (e) pups on the LSF showed an avid innate salt appetite when offered salt solution at 12 days of age.
Publisher: Elsevier BV
Date: 09-1986
DOI: 10.1016/0022-4731(86)90254-2
Abstract: This study investigated the effect of 5 day infusions of two structurally novel synthetic steroids, nivazol and cortivazol on blood pressure and in vivo indices of "glucocorticoid" and "mineralocorticoid" activity. Cortivazol at 24 mg/day raised mean arterial pressure (MAP) by 16 mmHg (P less than 0.001). This was associated with increased cardiac rate, and increased fasting plasma [glucose], polyuria and polydipsia a trilogy characteristic of glucocorticoid effect. Cortivazol had no consistent action on plasma [Na] or [K], but caused an initial transient urinary Na retention and raised urinary excretion of Na and K on days 3 and 4 of treatment. Nivazol at 24 mg/day raised MAP 10 mmHg (P less than 0.001), but cardiac rate was unchanged. This infusion was also associated with the glucocorticoid effects of increased fasting plasma [glucose] and increased urine volume. Plasma [K] fell from a control of 4.4 +/- 0.1 to 4.0 +/- 0.1 mmol/l (P less than 0.01) after 5 days of infusion. There was no significant effect of nivazol on urinary Na or K excretion. This study demonstrates that replacement of the 3-keto group, by a bulky phenylpyrazolo group fused to the A ring at position 2 and 3, does not diminish either pressor or glucocorticoid activity of steroids containing the typical 4-pregnene-3,20-dione nucleus and confirms that the 3 keto group is not essential for optimal glucocorticoid activity. It is the first demonstration of the pressor effect of these novel steroids.
Publisher: Elsevier BV
Date: 04-1974
DOI: 10.1016/0006-8993(74)90254-6
Abstract: In the pulmonary vasculature, the endothelial and smooth muscle cells are two key cell types that play a major role in the pathobiology of pulmonary vascular disease and pulmonary hypertension. The normal interactions between these two cell types are important for the homeostasis of the pulmonary circulation, and any aberrant interaction between them may lead to various disease states including pulmonary vascular remodeling and pulmonary hypertension. It is well recognized that the endothelial cell can regulate the function of the underlying smooth muscle cell by releasing various bioactive agents such as nitric oxide and endothelin-1. In addition to such paracrine regulation, other mechanisms exist by which there is cross-talk between these two cell types, including communication via the myoendothelial injunctions and information transfer via extracellular vesicles. Emerging evidence suggests that these nonparacrine mechanisms play an important role in the regulation of pulmonary vascular tone and the determination of cell phenotype and that they are critically involved in the pathobiology of pulmonary hypertension.
Publisher: Elsevier BV
Date: 11-1993
DOI: 10.1016/0006-8993(93)90952-J
Abstract: Brain structures located within the anterior wall of the third brain ventricle (subfornical organ, median preoptic nucleus and organum vasculosum of the lamina terminalis) are known to be involved in thirst as well as other aspects of body fluid and electrolyte balance. The present studies evaluated the role of these structures in the Na appetite of mildly or moderately Na-depleted sheep (sheep with a parotid fistula deprived of Na solution for 22 or 46 h). In addition, the role of these structures was tested in mildly Na-depleted sheep in which the Na appetite was enhanced by decreasing cerebrospinal fluid and brain extracellular fluid Na concentration (i.e., i.c.v. infusion of hypertonic saccharide solution) or was decreased by systemic infusion of hypertonic saline. The results indicated that sheep with lesions which reduced or eliminated daily water intake or water intake in response to hypertonicity of body fluids had, in all situations tested, appropriate changes in Na appetite (i.e., similar to their prelesion changes). Thus, the present experiments demonstrated that the brain areas involved in thirst as well as other aspects of body fluid and electrolyte balance are anatomically different from those involved in regulating Na appetite.
Publisher: Elsevier BV
Date: 07-1997
DOI: 10.1016/S0031-9384(97)00130-3
Abstract: Previous experiments indicated that the Na appetite of Na-deplete sheep is decreased by systemically administered captopril. The assumption that captopril does not readily cross the blood-brain barrier, lead to the conclusion that circulating ANG II acting in brain areas without a blood-brain barrier, i.e., circumventricular organs such as the subfornical organ or organum vasculosum of the lamina terminalis, contributes to Na appetite induced by Na depletion. The present experiments investigated the possibility that systemically administered captopril does, in fact, cross the blood-brain-barrier and thereby influence brain angiotensin II formation and that brain angiotensin II contributes to Na depletion-induced Na appetite of sheep. The results showed that systemically administered captopril blocked water intake caused by intracerebroventricular infusion of angiotensin I, and that Na depletion induced Na appetite was not decreased by intracerebroventricular infusion of various antagonists of the renin-angiotensin system. Thus, the results suggest that although captopril crosses the blood-brain-barrier and can influence the formation of brain angiotensin II, brain angiotensin II is not involved in the Na appetite of Na-deplete sheep.
No related grants have been discovered for Derek Denton.