ORCID Profile
0000-0001-8968-5912
Current Organisation
University of Tasmania
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Publisher: Springer Science and Business Media LLC
Date: 12-03-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2006
Publisher: Elsevier BV
Date: 07-2003
DOI: 10.1016/S0006-8993(03)02871-3
Abstract: Binding of [125I]-Bolton-Hunter substance P ([125I]-BHSP), [125I]-neurokinin A and [3H]-senktide to tachykinin NK(1), NK(2) and NK(3) receptors, respectively, was examined in caudal brainstem sections of 10-week-old rats pretreated as neonates (P2) with capsaicin (50 mg/kg, s.c.) or vehicle. [125I]-BHSP binding was localised to the nucleus of the solitary tract (NTS), hypoglossal nucleus and inferior olivary complex, whereas [125I]-neurokinin A and [3H]-senktide binding were confined to the NTS. The distribution and density of binding sites were similar in vehicle- and capsaicin-pretreated rats, suggesting that sensory neuron ablation by neonatal capsaicin does not affect tachykinin receptor numbers in the rat caudal brainstem.
Publisher: Elsevier BV
Date: 10-1998
DOI: 10.1016/S0304-3940(98)00743-5
Abstract: Prolonged or repetitive bouts of hypoxia may desensitize the brain stem respiratory centres leading to reduced stimulation of ventilation. We investigated the possible involvement of changes in the sensitivity of the commissural nucleus of the solitary tract (cNTS) to the tachykinin peptide, substance P (SP). Urethane-anaesthetised rats were allowed to breath room air (normoxic) or subjected to four, 30 s bouts of hypoxia (10% O2/90% N2) prior to the injection of SP (750 pmol) into the cNTS. In normoxic rats (n = 5), SP produced a fall in frequency (f, 88+/-4% control) after 4 min and a maximum rise in tidal volume (VT) after 6 min (138+/-10% control) leading to an overall increase in minute ventilation (VE, maximum, 127+/-12% control after 2 min). In rats (n = 5) exposed to four bouts of hypoxia and allowed to recover for 10 min, injection of SP produced a similar fall in f but a delayed and significantly (P < 0.001) reduced VT (maximum after 10 min, 110+/-1% control) and hence, VE response (104+/-3% control). Sixty min after hypoxia, the f, VT and VE responses to SP were identical to those of normoxic rats. These data suggest that hypoxia desensitizes SP receptors in the cNTS and this may partly explain why the respiratory response to hypoxia declines over time.
Publisher: Springer Science and Business Media LLC
Date: 07-02-2014
DOI: 10.1007/S40620-014-0058-Z
Abstract: Without a run-in phase, chronic kidney disease (CKD) patients enrolled in clinical trials may not be identified as having progressive disease. The aim of this analysis was to quantify the effects of a run-in phase on kidney function outcome in CKD patients enrolled in the Lipid Lowering and Onset of Renal Disease (LORD) trial. The LORD trial assessed the effects of atorvastatin on the rate of change in the estimated glomerular filtration rate (eGFR) and included patients with serum creatinine 120 μmol/l. In this post hoc analysis, we assessed eGFR change during the 12-month period prior to enrolment, the 3-month run-in phase and the first 12-month period of the trial. Eighty of the original 132 patients (where retrospective data were available) were included. The rate of eGFR change during each period was compared. Overall kidney function decreased during the 12 months prior to enrolment by (mean, SD) 0.39 ± 0.98 ml/min/1.73 m(2)/month, improved during the 3-month run-in phase by 0.48 ± 2.90 ml/min/1.73 m(2)/month and decreased during the first 12 months of the trial by 0.15 ± 0.57 ml/min/1.73 m(2)/month. However, only 39 % of patients had declining eGFR during the 12 months prior, 19 % in the 3-month run-in and 42 % during the first 12-month study phase. Most patients (>60 %) entering this clinical trial had stable or improving kidney function. Enrolment was associated with further improved kidney function, which may have been due to 'regression to the mean' or to the Hawthorne effect. Investigators should include a run-in period to establish the presence of eGFR decline to use as an inclusion criterion in clinical trials assessing this measure of CKD progression.
Publisher: Elsevier BV
Date: 03-2005
DOI: 10.1016/J.CBPB.2005.02.002
Abstract: In order to determine if elevated temperature during vitellogenesis had a detrimental effect on hepatic estrogen receptors of Atlantic salmon (Salmo salar), 3H-estradiol saturation binding analysis, using one- and two-site binding models, was carried out on extracts of hepatic cytosols from fish held at 14, 18 or 22 degrees C over the austral period of peak vitellogenesis (February to April). With one-site binding analysis, no temperature related difference in either receptor affinity (Kd) or number (Bmax) was found at each s ling point, but there was an apparent decrease in both affinity and number at each temperature over the period of the study. However, some analyses, notably at 22 degrees C during February, were best described using a two-site binding model. At this temperature and time, there was a clear separation of binding affinity into high and low components (Kd = 0.67+/-S.E. 0.05 and 20+/-S.E. 5.6 nM, respectively) (n = 4), which suggests that February was a critical time of temperature related hepatic sensitivity to estrogen. These results support those of other studies where we found that February was also a sensitive time with respect to temperature impairment of in vitro follicular estrogen synthesis, and the greatest period of in vivo temperature sensitivity.
Publisher: Elsevier BV
Date: 06-1998
DOI: 10.1016/S0006-8993(98)00270-4
Abstract: This study utilised autoradiography to examine [125I]-Bolton Hunter substance P (BHSP) binding in postmortem human visual cortex. In the primary visual area, layers I-III, IVC and VI exhibited low levels of BHSP binding, while high levels were observed in layers IVB and V. Because cells in layers IVB and V are known to be involved in processing direction-specific stimuli, it is possible that SP plays a role in modulating this visual process.
Publisher: Dustri-Verlgag Dr. Karl Feistle
Date: 11-2006
DOI: 10.5414/CPP44580
Abstract: Previous studies investigating associations between serum lipids and renal disease have generally not taken into account dietary intake or physical activity both known to influence circulating lipids. Furthermore, inclusion of patients on HMG-CoA reductase inhibitors may also have influenced findings due to the pleiotropic effect of this medication. Therefore, the aim of this study is to determine the relationships between serum lipids and renal function in a group of patients not taking lipid-lowering medication and taking into account dietary intake and physical activity. Data from 100 patients enrolled in the Lipid Lowering and Onset of Renal Disease (LORD) trial were used in this study. Patients were included with serum creatinine > 120 micromol/l, and excluded if they were taking lipid-lowering medication. Unadjusted and adjusted relationships were determined between fasting serum lipid concentrations (total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol/HDL ratio) and measures of renal function (estimated glomerular filtration rate (eGFR), creatinine clearance and serum creatinine) and urinary protein excretion. Significant (p < 0.05) negative unadjusted relationships were found between lipids (total cholesterol, LDL and HDL cholesterol) and serum creatinine. In support of these findings, logarithmically-transformed lipids (total cholesterol, LDL and HDL cholesterol) were significantly associated with eGFR and creatinine clearance although the effects were of a smaller magnitude. Adjustment for dietary saturated fat intake and physical activity did not substantially change these effects. These data do not support the premise that lipids are associated with renal dysfunction in patients with normocholesterolemia.
Publisher: Wiley
Date: 04-05-2016
Abstract: Vanilloid-like agents, including capsaicin, N-arachidonoyl-dopamine and N-oleoyldopamine inhibit platelet aggregation, however little is known about the precise mechanism(s) of action. The authors have previously shown that blocking of the capsaicin receptor, transient receptor potential vanilloid-1 (TRPV1), does not interfere with capsaicin action during adenosine diphosphate (ADP)-induced aggregation. This research is extended to investigate the effect of these vanilloid-like-agents on platelet count, and to test whether the effect of these agents is mediated through TRPV1 and/or cannabinoid (CB1 and CB2) receptors in the presence of other agonists, including collagen and arachidonic acid. Incubation of platelets with each of the in idual vanilloids, or with receptor antagonists of TRPV1 (SB452533), CB1 (AM251) and CB2 (AM630), for up to 2 h did not significantly affect the platelet count. Similarly, the effect of in idual vanilloids on the inhibition of platelet aggregation was not significantly different in the presence of receptor agonists compared to control, irrespective of the agonist used, suggesting that the inhibitory effect of vanilloids on platelet aggregation is independent of TRPV1, CB1 and CB2 receptors. Further research on the antiplatelet activity of vanilloids should focus on mechanisms other than those associated with vanilloid receptors.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2011
Publisher: Elsevier BV
Date: 06-1996
DOI: 10.1016/0024-3205(96)00267-6
Abstract: Previous studies with the vanilloid spice principle capsaicin have demonstrated a biphasic VO2 response, with vasoconstriction, in the perfused rat hindlimb that has led to suggestions of vanilloid receptor subtypes (VN1/VN2) in this preparation (1). In the present study, the known competitive vanilloid antagonist capsazepine inhibited the above capsaicin-mediated effects in a manner that was indicative of binding at specific vanilloid recognition sites. Low concentrations of capsazepine selectively inhibited the increased VO2 produced by the putative VN1 receptor at submicromolar concentrations of capsaicin, while the inhibition of VO2 produced by high concentrations of capsaicin (putative VN2) was enhanced. These observations, showing different susceptibilities to blockade by capsazepine, further support the presence of two vanilloid receptor subtypes in the rat hindlimb. Schild plots of the data yielded variable slopes that approach unity at greater responses to capsaicin (mean KB = 8.44 +/- 2.08 microM and 7.28 +/- 0.78 microM for VO2 and perfusion pressure curves, respectively). Low concentrations of the capsaicin antagonist ruthenium red selectively blocked the putative VN2 receptor-mediated effects produced by high concentrations of capsaicin. The noncompetitive nature of this inhibitor suggests an operation through separate receptor-coupled ion channel complexes at high and low concentrations of the vanilloid. Tetrodotoxin failed to attenuate any changes produced by capsaicin, suggesting that the mechanism of action of capsaicin in the rat hindlimb may differ from other tissues.
Publisher: Springer Science and Business Media LLC
Date: 2000
Publisher: Elsevier BV
Date: 07-2006
DOI: 10.1093/AJCN/84.1.63
Abstract: Animal and some human studies have indicated that the consumption of chili-containing meals increases energy expenditure and fat oxidation, which may help to reduce obesity and related disorders. Because habitual diets affect the activity and responsiveness of receptors involved in regulating and transporting nutrients, the effects of regular consumption of chili on metabolic responses to meals require investigation. The objective was to investigate the metabolic effects of a chili-containing meal after the consumption of a bland diet and a chili-blend (30 g/d 55% cayenne chili) supplemented diet. Thirty-six subjects with a mean (+/-SD) age of 46 +/- 12 y and a body mass index (in kg/m2) of 26.3 +/- 4.6 participated in a randomized, crossover, intervention study with 2 dietary periods (chili and bland) of 4 wk each. The postprandial effects of a bland meal after a bland diet (BAB), a chili meal after a bland diet (CAB), and a chili meal after a chili-containing diet (CAC) were evaluated. Serum insulin, C-peptide, and glucose concentrations and energy expenditure (EE) were measured at fasting and up to 120 min postprandially. Significant heterogeneity was observed between the meals for the maximum increase in insulin and the incremental area under the curve (iAUC) for insulin (P = 0.0002) the highest concentrations were with the BAB meal and the lowest with the CAC meal. When separated at the median BMI (26.3), the subjects with a BMI > or = 26.3 also showed heterogeneity in C-peptide, iAUC C-peptide, and net AUC EE (P < 0.02 for all) the highest values occurred after the BAB meal and the lowest after the CAC meal. Conversely, the C-peptide/insulin quotient (an indicator of hepatic insulin clearance) was highest after the CAC meal (P = 0.002). Regular consumption of chili may attenuate postprandial hyperinsulinemia.
Publisher: Elsevier BV
Date: 07-1988
Publisher: Springer Science and Business Media LLC
Date: 23-08-2006
Abstract: To investigate the effects of regular chilli ingestion on some indicators of metabolic and vascular function. A randomized cross-over dietary intervention study. Launceston, Australia. Healthy free-living in iduals. Thirty-six participants (22 women and 14 men), aged 46+/-12 (mean+/-s.d.) years BMI 26.4+/-4.8 kg/m(2), consumed 30 g/day of a chilli blend (55% cayenne chilli) with their normal diet (chilli diet), and a bland diet (chilli-free) for 4 weeks each. Metabolic and vascular parameters, including plasma glucose, serum lipids and lipoproteins, insulin, basal metabolic rate, blood pressure, heart rate, augmentation index (AIx an indicator of arterial stiffness), and subendocardial-viability ratio (SEVR a measure of myocardial perfusion), were measured at the end of each diet. In a sub-study, during week 3 of each dietary period, the vascular responses of 15 subjects to glyceryl-trinitrate (GTN) and salbutamol were also studied. For the whole group, there were no significant differences between any of the measured parameters when compared at the end of the two dietary periods. When analysed separately, men had a lower resting heart rate (P=0.02) and higher SEVR (P=0.05) at the end of the chilli diet than the bland diet. In the sub-study, baseline AIx on the chilli diet was lower (P<0.001) than on the bland diet, but there was no difference in the effects of GTN and salbutamol between the two diets. Four weeks of regular chilli consumption has no obvious beneficial or harmful effects on metabolic parameters but may reduce resting heart rate and increase effective myocardial perfusion pressure time in men.
Publisher: Bentham Science Publishers Ltd.
Date: 03-12-2018
DOI: 10.2174/1381612824666180711122753
Abstract: Initiating anti-apoptotic signaling or triggering cell death depends to a great extent on the nature or source of cellular stress and cell type. Interplay between each stress response eventually determines the fate of stressed cell. Numerous factors induce cell death by a number of pathways including apoptosis, autophagy and necrosis. Not surprisingly, some of the pathways are interrelated to each other through a mediator that could articulate the entire mechanism. The present review attempts to consolidate all the pathways included in intrinsic cellular stress such as oxidative stress and autophagy, endoplasmic reticular stress (ERS) and mitophagy and apoptosis as fate in cell stress. These stress responses are a hallmark of numerous diseases including neurodegenerative diseases, diabetes and cancer. Understanding the cross-talk between different intrinsic cell stress responses will help to develop new therapeutic targets and hence lead to the development of new therapeutics.
Publisher: Japan Atherosclerosis Society
Date: 2010
DOI: 10.5551/JAT.2683
Abstract: Central pulse pressure and measures of arterial stiffness (augmentation index (AIx) and aortic pulse wave velocity (PWV)) predict morbidity and mortality in patients with stage 2-4 chronic kidney disease (CKD). Although statin therapy may be of vascular benefit in patients with CKD, the long-term effect of statins on central pulse pressure and arterial stiffness has not been assessed in this patient population. Hence, the aim of this study was to assess the long-term effects of atorvastatin on arterial stiffness and central blood pressure in patients with CKD. We enrolled 37 patients with serum creatinine levels > 1.36 mg/dL into a randomized, double blind trial. Patients were allocated to receive 10 mg of atorvastatin per day (19) or placebo (18) for three years. Aortic PWV, AIx, estimated central and brachial blood pressures and were determined every nine months. At baseline, there were no significant differences in aortic PWV, AIx, central or brachial blood pressures between atorvastatin-treated and placebo-treated patients. During the trial, aortic PWV significantly (p=0.05) increased in placebo-treated, but not (p=0.10) in atorvastatin-treated patients (0.51+/-0.95 vs. 0.30+/-0.75 m/sec/yr p=0.48). This represented a 41% (but not statistically significant) slowing of the rate of increase in aortic stiffness. There were no significant changes between groups in the rate of change of AIx (atorvastatin -0.15+/-5.65 vs. placebo 0.39+/-5.38%/yr, p=0.53) or central pulse pressure (atorvastatin -2.32+/-7.46 vs. placebo -0.36+/-6.64 mmHg/yr p= 0.61). In patients with CKD arterial stiffness measured by aortic PWV showed a significant increase over time in placebo-treated patients but not in atorvastatin-treated patients.
Publisher: Wiley
Date: 06-1993
DOI: 10.1111/J.1471-4159.1993.TB03484.X
Abstract: The last decade has witnessed major breakthroughs in the study of tachykinin receptors. The currently described NK-1, NK-2, and NK-3 receptors have been sequenced and cloned from various mammalian sources. A far greater variety of tachykinin analogues are now available for use as selective agonists and antagonists. Importantly, potent nonpeptide antagonists highly selective for the NK-1 and NK-2 receptors have been developed recently. These improved tools for tachykinin receptor characterization have enabled us to describe at least three distinct receptor types. Furthermore, novel antagonists have yielded radioligand binding and functional data strongly favoring the existence of putative subtypes of NK-1 and especially NK-2 receptors. Whether these subtypes are species variants or true within-species subtypes awaits further evidence. As yet undiscovered mammalian tachykinins, or bioactive fragments, may have superior potency at a specific receptor class. The common C terminus of tachykinins permits varying degrees of interaction at essentially all tachykinin receptors. Although the exact physiological significance of this inherent capacity for receptor "cross talk" remains unknown, one implication is for multiple endogenous ligands at a single receptor. For ex le, NP gamma and NPK appear to be the preferred agonists and binding competitors at some NK-2 receptors, previously thought of as exclusively "NKA-preferring." Current evidence suggests that tachykinin coexistence and expression of multiple receptors may also occur with postulated NK-2 and NK-1 receptor subtypes. Other "tachykinin" receptors may recognize preprotachykinins and the N terminus of SP. In light of these recent developments, the convenient working hypothesis of three endogenous ligands (SP, NKA, and NKB) for three basic receptor types (NK-1, NK-2, and NK-3) may be too simplistic and in need of amendment as future developments occur (Burcher et al., 1991b). In retrospect, the 1980s contributed greatly to our understanding of the structure, function, and regulation of tachykinins and their various receptors. The development of improved, receptor subtype-selective antagonists and radioligands, in addition to recent advances in molecular biological techniques, may lead to a more conclusive pharmacological and biochemical characterization of tachykinin receptors. The 1990s may prove to be the decade of application, where a better understanding of the roles played by endogenous tachykinins (at various receptor subtypes) under pathophysiological conditions will no doubt hasten the realization of clinically useful therapeutic agents.
Publisher: Elsevier BV
Date: 12-2009
Publisher: Dustri-Verlgag Dr. Karl Feistle
Date: 11-2006
DOI: 10.5414/CNP66373
Abstract: Cyclosporin A (CsA)-treated renal transplant recipients (RTR) exhibit relative hyperhomocystinemia and vascular dysfunction. Folate supplementation lowers homocysteine and has been shown to improve vascular function in healthy subjects and patients with coronary artery disease. The aim of this study was to assess the effects of 3 months of folate supplementation (5 mg/day) on vascular function and structure in RTR. A double-blind, placebo-controlled crossover study was conducted in 10 CsA-treated RTR. Vascular structure was measured as carotid artery intima media thickness (IMT) and function was assessed as changes in brachial artery diameter during reactive hyperemia (RH) and in response to glyceryl trinitrate (GTN). Function data were analyzed as absolute and percent change from baseline and area under the diameter/time curve. Blood s les were collected before and after supplementation and analyzed for total plasma homocysteine, folate, vitamin B12 and asymmetric dimethyl arginine (ADMA) in addition to regular measures of hemoglobin, hematocrit, mean corpuscular volume (MCV) and serum creatinine. Folate supplementation significantly increased plasma folate by 687% (p < 0.005) and decreased homocysteine by 37% (p 0.05) in vitamin B12 or ADMA. There were no significant (p > 0.05) changes in vascular structure or function during the placebo or the folate supplementation phases IMT placebo pre mean +/- SD, 0.52 +/- 0.12, post 0.50 +/- 0.11 folate pre 0.55 +/- 0.17, post 0.49 +/- 0.20 mm, 5% change in brachial artery diameter (RH, placebo pre 10 +/- 8, post 6 +/- 5 folate pre 9 +/- 7, post 7 +/- 5 GTN, placebo pre 18 +/- 10, post 17 +/- 9, folate pre 16 +/- 9, post-supplementation 18 +/- 8). Three months of folate supplementation decreases plasma homocysteine but has no effect on endothelial function or carotid artery IMT in RTR.
Publisher: Elsevier BV
Date: 12-2014
Publisher: Elsevier BV
Date: 05-1990
DOI: 10.1016/0304-3940(90)90216-V
Abstract: Radioligand binding techniques were used to characterize the substance P (SP) binding site on membranes prepared from bovine adrenal medullae. 125I-labelled Bolton-Hunter substance P (BHSP), which recognises the C-terminally directed, SP-preferring NK1 receptor, showed no specific binding. In contrast, binding of [3H]SP was saturable (at 6 nM) and reversible, with an equilibrium dissociation constant (Kd) 1.46 +/- 0.73 nM, Bmax 0.73 +/- 0.06 pmol/g wet weight and Hill coefficient 0.98 +/- 0.01. Specific binding of [3H]SP was displaced by SP greater than neurokinin A (NKA) greater than SP(3-11) approximately SP(1-9) greater than SP(1-7) approximately SP(1-4) approximately SP(1-6), with neurokinin B (NKB) and SP(1-3) very weak competitors and SP(5-11), SP(7-11) and SP(9-11) causing negligible inhibition (up to 10 microM). This potency order is quite distinct from that seen with binding to an NK1 site, a conclusion confirmed by the lack of BHSP binding. It appears that Lys3 and/or Pro4 are critical for binding, suggesting an anionic binding site. These data suggest the existence of an unusual binding site which may represent a novel SP receptor. This site appears to require the entire sequence of the SP molecule for full recognition.
Publisher: Wiley
Date: 11-2002
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.THROMRES.2014.05.038
Abstract: Plant-derived and endogenous vanilloid-like agents exert their effects on cells through transient receptor potential vanilloid-1 (TRPV1). Little is known about the effects of these agents on platelet aggregation. We investigated the effect of various vanilloid-like agents on in-vitro platelet aggregation and tested whether this action is mediated through TRPV1. Understanding the mechanism of action of these compounds in platelets is important in that these compounds may be developed as novel anti-platelet agents. The effects of plant-derived (capsaicin dihydrocapsaicin, DHC) and endogenous vanilloid-like agents (N-oleoyldopamine, OLDA N-arachidonoyl-dopamine, NADA) on platelet aggregation were investigated using ADP (5, 10μM), collagen (4, 8μg/mL) and arachidonic acid (AA, 300, 400μg/mL) as agonists. The direct effects of these agents on platelet viability were also determined using an LDH release assay. Capsaicin, OLDA and NADA inhibited ADP-induced platelet aggregation in a concentration-dependent manner. OLDA and NADA, but not capsaicin and DHC, inhibited collagen-induced aggregation, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA, but not OLDA. Inhibition of aggregation was not due to direct toxicity of these agents towards platelets. The TRPV1 antagonist, SB-452533, did not affect inhibition of ADP-induced platelet aggregation by capsaicin and OLDA. These results demonstrate that the endovanilloids, OLDA and NADA, and plant-derived vanilloid, capsaicin, inhibit ADP-induced platelet aggregation. Collagen-induced aggregation was inhibited only by endovanilloids, whereas AA-induced aggregation was inhibited by capsaicin, DHC and NADA. This inhibition was not due to direct toxic effects of these agents, nor was inhibition of ADP-induced aggregation TRPV1 mediated.
Publisher: Portland Press Ltd.
Date: 10-10-2005
DOI: 10.1042/BJ20050900
Abstract: The recent discovery that the natriuretic peptide OvCNPb (Ornithorhynchus venom C-type natriuretic peptide B) from platypus (Ornithorynchus anatinus) venom contains a D-amino acid residue suggested that other D-amino-acid-containing peptides might be present in the venom. In the present study, we show that DLP-2 (defensin-like peptide-2), a 42-amino-acid residue polypeptide in the platypus venom, also contains a D-amino acid residue, D-methionine, at position 2, while DLP-4, which has an identical amino acid sequence, has all amino acids in the L-form. These findings were supported further by the detection of isomerase activity in the platypus gland venom extract that converts DLP-4 into DLP-2. In the light of this new information, the tertiary structure of DLP-2 was recalculated using a new structural template with D-Met2. The structure of DLP-4 was also determined in order to evaluate the effect of a D-amino acid at position 2 on the structure and possibly to explain the large retention time difference observed for the two molecules in reverse-phase HPLC. The solution structures of the DLP-2 and DLP-4 are very similar to each other and to the earlier reported structure of DLP-2, which assumed that all amino acids were in the L-form. Our results suggest that the incorporation of the D-amino acid at position 2 has minimal effect on the overall fold in solution.
Publisher: Elsevier BV
Date: 05-2013
DOI: 10.1016/J.REGPEP.2013.03.001
Abstract: Capsaicin, the pungent component of chilli pepper, stimulates TRPV1-expressing cells which are followed by desensitisation to subsequent exposure to capsaicin and other TRPV1 activators. At high systemic doses (>125 mg/kg), capsaicin produces long-term changes in both tachykinin receptor and TRPV1 expression and function in rats. However, whether desensitising (low) doses of capsaicin (~50 mg/kg) affect tachykinin receptor and TRPV1 gene expression in the short term has yet to be investigated. The aim of the present study was to compare tachykinin receptor (NK1, NK2 and NK3) and TRPV1 mRNA expression 24h after administration of capsaicin (50 mg/kgs.c.). Tachykinin receptor and TRPV1 mRNA were detected in all tissues studied with expression levels differing by up to 2500-fold between tissues. The highest expression of TRPV1 and NK1 mRNA was observed in the salivary gland, whereas NK2 mRNA expression was highest in the urinary bladder and NK3 mRNA expression in the frontal cortex. In the cervical spinal cord of rats treated with capsaicin, NK1 and NK3 mRNA expression were reduced by 56% and 80%, respectively (P<0.05), whereas NK2 and TRPV1 mRNA expression were increased 2.2- and 1.4-fold, respectively (P<0.05). NK1 and NK2 mRNA expression were decreased (P<0.05) in the urinary bladder and gastric fundus, respectively, following capsaicin treatment. There was a marked 100-fold increase in cFOS mRNA expression and 100-fold decrease in NK2 mRNA expression in the whole blood of capsaicin-treated rats. In conclusion, these studies show that tachykinin receptor and TRPV1 mRNA expression undergo significant changes within 24h of systemic low-dose capsaicin administration.
Publisher: Dustri-Verlgag Dr. Karl Feistle
Date: 08-2012
DOI: 10.5414/CN107421
Abstract: Oxidative stress is associated with the progression of chronic kidney disease (CKD). Links between antioxidant enzyme SNPs such as superoxide dismutase (SOD) Ala16Val, glutathione peroxidase (GPx) Pro197Leu and catalase C- 262T and CKD have not been investigated. This study compared antioxidant genotypes and activities of CKD patients with population controls, and determined their relationship to kidney function. CKD patients (n = 230) and controls (n = 224) were screened for the GPx, SOD and catalase SNPs. Plasma and red blood cell (RBC) GPx, RBC SOD and RBC catalase activities, and estimated glomerular filtration rate (eGFR) were measured. Significantly more CKD patients (n = 5) had the GPx Leu/Leu genotype compared to controls (n = 0), and had lower eGFR (p = 0.054). CKD patients had significantly lower plasma GPx and RBC catalase activities compared to controls, whereas RBC GPx and RBC SOD activities were significantly higher in CKD patients (p < 0.001). CKD is associated with reduced plasma GPx and catalase activities and enhanced RBC GPx and SOD activities. Although, genotype frequencies were similar for both groups, lower eGFR was associated with the GPx Leu/ Leu genotype.
Publisher: Springer Science and Business Media LLC
Date: 03-2007
Publisher: Elsevier BV
Date: 07-2007
DOI: 10.1053/J.JRN.2007.04.004
Abstract: The study objective was to determine the dietary intake of patients with chronic kidney disease before and after filtering for suspected underreporters and to investigate the impact of underreporting on the interpretation of diet data. This was a cross-sectional study. The study included outpatients from hospitals and clinics in Northern Tasmania, Australia. Data from 113 patients enrolled in the Lipid Lowering and Onset of Renal Disease trial were used in this study. Patients with serum creatinine greater than 120 mmol/L were included, and those taking lipid-lowering medication were excluded. Patients completed a 4-day self-report diet diary, and FoodWorks software was used to determine their daily intake of energy, macronutrients, and specific micronutrients. Diet diaries were assessed for likely underreporting using the Goldberg cutoff approach with a ratio of energy intake to estimated resting energy expenditure of 1.27. Nutrient intakes were compared with current National Kidney Foundation's Kidney Disease Outcomes Quality Initiative guidelines, World Health Organization recommendations, recommended daily allowances, and daily values adjusted for energy intake. Demographics of the patients were as follows: male/female, 71/42 age (mean +/- standard deviation), 60 +/- 15 years body mass index, 28.6 +/- 6.0 kg/m(2), and serum creatinine, 223.4 +/- 110.0 mmol/L. According to the criteria, 80 patients (70.8%) were underreporting their energy intake. Underreporters were more likely to be female and younger, and have a higher body mass index and elevated serum creatinine. In all patients, daily energy intake (89.6 +/- 32.4 kJ/kg) was lower than recommended (125-145 kJ/kg) however, this was not the case for valid reporters (128.3 +/- 23.7 kJ/kg). Protein intake was higher (0.9 +/- 0.3 g/kg) than recommended (0.75 g/kg) in all patients and even higher (1.2 +/- 0.3 g/kg) in valid reporters. Mean calcium, zinc, and dietary fiber intakes were all below recommendations in all patients, but these differences were not apparent in valid reporters. Interpreting self-report diet diary data from patients with chronic kidney disease without attempting to exclude underreporters will lead to erroneous conclusions, especially in respect to energy, protein, dietary fiber, calcium, and zinc intakes.
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.REGPEP.2011.02.004
Abstract: Transient receptor potential vanilloid 1 (TRPV1), neurokinin 1 (NK1) receptor and substance P (SP) immunoreactivity (-ir) and mRNA in the rat lumbosacral spinal cord and urinary bladder were measured 24h after s.c. injection of the vanilloids, capsaicin (50mg/kg) and resiniferatoxin (RTX, 100μg/kg), or vehicle (10% ethanol/10% Tween 80/saline). In the spinal cord, capsaicin significantly reduced TRPV1 and SP-ir (40-45%) in laminae I/II compared to controls, while RTX produced decreases of ~35%. NK1-ir in the spinal cord was unaffected by both vanilloid treatments. In the bladder, SP-ir was reduced in urothelial cells of some capsaicin- and RTX-treated rats, while SP-ir in the suburothelium and muscularis was significantly reduced by RTX. A significant increase in NK1-ir was observed in the urothelium and muscularis after capsaicin administration. Capsaicin significantly increased SP mRNA in the spinal cord, and TRPV1 and SP mRNA in the bladder, whereas RTX increased TRPV1, SP and NK1 mRNA in the spinal cord, and TRPV1 and SP mRNA in the bladder. These data suggest that stimulation of TRPV1 by low dose vanilloid administration can rapidly (within 24h) alter both transcription and translation of TRPV1 channels, SP and NK1 receptors in the rat urinary bladder and spinal cord.
Publisher: Springer Science and Business Media LLC
Date: 28-04-2022
DOI: 10.1007/S12032-022-01678-Z
Abstract: The ectopic overexpression of transient receptor potential vanilloid-1 (TRPV1) has been detected in numerous solid cancers, including breast, prostate, pancreatic, and tongue epithelium cancer. However, the expression of TRPV1 in hematological malignancies remains unknown. Here we show through in silico analysis that elevated TRPV1 mRNA expression occurs in a range of hematological malignancies and presents an optimized flow cytometry method to rapidly assess TRPV1 protein expression for both cell lines and primary patient s les. Three anti-TRPV1 antibodies were evaluated for intracellular TRPV1 detection using flow cytometry resulting in an optimized protocol for the evaluation of TRPV1 in hematological malignant cell lines and patients’ peripheral blood mononuclear cells (PBMC). Overexpression of TRPV1 was observed in THP-1 (acute monocytic leukemia) and U266B1 (multiple myeloma, MM), but not U937 (histiocytic lymphoma) compared to healthy PBMC. TRPV1 was also detected in all 49 patients including B-cell non-Hodgkin’s lymphoma (B-NHL), MM, and others and 20 healthy controls. TRPV1 expression was increased in 8% of patients (MM = 2, B-NHL = 2). In conclusion, we provide an optimized flow cytometry method for routine expression analysis of clinical s les and show that TRPV1 is increased in a subset of patients with hematological malignancies.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2009
Publisher: Wiley
Date: 03-02-2006
DOI: 10.1016/J.FEBSLET.2006.01.089
Abstract: The presence of d-amino-acid-containing polypeptides, defensin-like peptide (DLP)-2 and Ornithorhyncus venom C-type natriuretic peptide (OvCNP)b, in platypus venom suggested the existence of a mammalian d-amino-acid-residue isomerase(s) responsible for the modification of the all-l-amino acid precursors. We show here that this enzyme(s) is present in the venom gland extract and is responsible for the creation of DLP-2 from DLP-4 and OvCNPb from OvCNPa. The isomerisation reaction is freely reversible and under well defined laboratory conditions catalyses the interconversion of the DLPs to full equilibration. The isomerase is approximately 50-60 kDa and is inhibited by methanol and the peptidase inhibitor amastatin. This is the first known l-to-d-amino-acid-residue isomerase in a mammal.
Publisher: Dustri-Verlgag Dr. Karl Feistle
Date: 02-2014
DOI: 10.5414/CN108090
Publisher: Elsevier
Date: 2017
DOI: 10.1016/BS.APHA.2017.01.002
Abstract: Transient receptor potential vanilloid-1 (TRPV1) is a member of the TRP family of channels that are responsible for nociceptive, thermal, and mechanical sensations. Originally associated exclusively with sensory neurons, TRPV1 is now known to be present in almost all organs, including cells of the immune system, where TRPV1 has been shown to play a pivotal role in inflammation and immunity. Monocytes, macrophages, and dendritic cells express TRPV1, with both mouse and human studies suggesting that TRPV1 activation protects against endotoxin-induced inflammation. In contrast, TRPV1 (and other TRP channels) appears to be required for T-cell receptor activation by mitogens. Additionally, studies in cell lines derived from hematological and other malignancies suggest altered expression/function of TRPV1 might serve as a target for novel cytotoxic therapies.
Publisher: Elsevier BV
Date: 03-1998
DOI: 10.1016/S0006-8993(97)01463-7
Abstract: Binding of [125I]-labeled Bolton-Hunter substance P ([125I]-BHSP) to NK1 receptors was investigated in the spinal cord of young (3-4 month) and aged (14-16 month) rats. In homogenates of whole spinal cord, the affinity (equilibrium dissociation constant, approximately 210 pM) and maximum density of [125I]-BHSP binding sites ( approximately 0.25 fmol/mg wet weight) were similar for young and aged rats. Autoradiographic studies revealed a similar distribution of [125I]-BHSP sites in both young and old rats at all spinal levels. Intense binding was observed in the superficial dorsal horn (laminae I-III), grey commissure (lamina X) and thoracic intermediolateral cell column (IML) with lower levels of binding in the deeper dorsal horn (laminae IV-VI) and ventral horn (laminae VII-IX). However, the density of [125I]-BHSP sites was significantly (P<0.05) lower in lamina X of lumbar sections of aged rats compared with young controls. These studies suggest that ageing is associated with a selective loss of NK1 receptors in lamina X of the lumbar spinal cord, although the affinity of NK1 receptors in aged rats is unchanged.
Publisher: Wiley
Date: 21-10-2013
DOI: 10.1002/DDR.21102
Publisher: Elsevier BV
Date: 05-2007
Publisher: Springer Science and Business Media LLC
Date: 12-2008
Publisher: Oxford University Press (OUP)
Date: 05-07-2005
DOI: 10.1093/NDT/GFH875
Abstract: Transplant recipients have elevated oxidative stress, which has prompted suggestions that supplementary antioxidants may be beneficial. However, only a small number of clinical trials have investigated antioxidant supplementation in transplant recipients, with very few data on their effects on patients' immunosuppressive therapy. A randomized placebo-controlled single-blind crossover trial was conducted in 10 renal transplant recipients (RTRs) taking cyclosporin A (CsA) as part of their immunosuppressive therapy. Each phase of the trial lasted 6 months, with a 6 month wash-out period in between. During one of the phases, patients consumed a tablet twice per day which delivered 400 IU/day of vitamin E, 500 mg/day of vitamin C and 6 mg/day of beta-carotene. During antioxidant supplementation, there was no change in CsA dose. Antioxidant supplementation resulted in a significant decrease (P<0.05) in blood trough CsA by 24% (mean+/-SD, pre- 127.3+/-38.9, post- 97.2+/-30.7 microg/ml) compared with no change while taking the placebo (pre- 132.2+/-50.6, post- 138.6+/-56.0 microg/ml). The glomerular filtration rate was significantly (P 0.05) in markers of oxidative stress (malondialdehyde, susceptibility of plasma to oxidation) or plasma antioxidant enzymes. In CsA-treated RTRs, antioxidant supplementation decreased blood CsA, which may affect adequacy of immunosuppression.
Publisher: Wiley
Date: 5011
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.ATHEROSCLEROSIS.2010.07.053
Abstract: The effect of atorvastatin on kidney function was assessed in patients with stages 2-4 chronic kidney disease. We conducted a randomised, double-blind, placebo-controlled trial in chronic kidney disease clinics in Northern Tasmania and enrolled 132 patients with serum creatinine levels >120 μmol/l, not taking lipid-lowering therapy and at all levels of proteinuria and serum cholesterol. Patients were randomly assigned to receive either 10 mg of atorvastatin/day (64) or placebo (68) and were followed with trial visits 3-monthly for a mean of 2.5 yrs. The primary outcome was the rate of both MDRD eGFR and Cockcroft-Gault creatinine clearance (C-G CrCl) decline. Analysis was based on intention to treat and included all patients that had at least one follow-up visit. The rate of MDRD eGFR decline was 29% lower 1.04 ± 3.84 vs. 1.47 ± 3.74 ml/min/1.73 m(2)/yr (P=0.53), and the C-G CrCl was 20% lower 1.88 ± 5.07 vs. 2.36 ± 4.61 ml/min/1.73 m(2)/yr (P=0.58) in atorvastatin-treated, compared with placebo-treated patients. Although blood pressure decreased in both atorvastatin and placebo-treated groups there were no differences between groups. In addition, there was no difference in concomitant medication intake including angiotensin converting enzyme inhibitors and angiotensin receptor blockers between groups. There was a trend toward a slower eGFR decline in the atorvastatin-treated group that did not reach statistical significance. This may have been due to the lack of power of the study. However, atorvastatin may have a renoprotective effect in those patients with chronic kidney disease and cardiovascular disease. This needs to be assessed in further studies.
Publisher: CSIRO Publishing
Date: 2008
DOI: 10.1071/AH080488
Abstract: Objective: To examine if claims for general practice health assessments of older persons in Australia over the period 1 November 1999 to 30 September 2002 were equitably distributed. Design: Closed cohort study with data analysis using logistic regression. Setting: Private general practice in Australia. Participants: All Australians aged 75 or more years at 1 October 1999, who were eligible to claim for a health assessment. Measures studied: Medicare and Department of Veterans? Affairs (DVA) medical claims data, and personal characteristics of claimants: age, sex, DVA beneficiary status, rurality and socio-economic status of postcode of residence. Rurality was classified by the Rural Remote and Metropolitan Area Classification (RRMA) and socio-economic status by the Index of Relative Socio-economic Deprivation (IRSD) for the postcode. Results: The cohort initially contained 886 185 subjects. Over the 35 months, 271 939 in iduals (31%) claimed at least one health assessment. Those most likely to have claimed for a health assessment were aged 80 to 84 years, female, entitled to treatment under DVA arrangements, lived in postcodes classified as RRMA 1?4 and classified as the most disadvantaged IRSD quartile. Conclusion: Over this period, general practice health assessments appear to have been equitably distributed except for those living in postcodes classified as RRMA 5?7.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-2001
Publisher: Wiley
Date: 17-10-2002
DOI: 10.1046/J.1440-1681.2002.03781.X
Abstract: 1. Quantitative autoradiography and homogenate radioligand binding of [125I]-Bolton Hunter substance P ([125I]-BHSP) were used to compare brain NK1 receptors in young (2 months) and aged (18-20 months) rats. 2. The autoradiographic distribution and density of [125I]-BHSP binding sites was similar in all cortical regions of young and aged rats. In contrast, the density of [125I]-BHSP binding sites was significantly (P < 0.05) lower in the basal forebrain nuclei (intermediate part of the lateral septal nuclei, medial septal nucleus and horizontal and vertical nuclei of the diagonal band) of aged rats. In all other brain regions examined, binding densities were almost identical in young and aged rats. 3. Because a population of NK1 receptors ([125I]-BHSP binding sites) in the basal forebrain nuclei is associated with cholinergic neurons, the decrease in NK1 receptors in aged rats may reflect degeneration of cholinergic neurons and contribute to the motor and cognitive deficiencies that occur with ageing.
Publisher: Wiley
Date: 03-2000
Publisher: Wildlife Disease Association
Date: 07-2011
DOI: 10.7589/0090-3558-47.3.483
Abstract: The fungal disease mucormycosis has affected Tasmanian platypuses for nearly three decades. We investigated the influences of mucormycosis on the hematologic, plasma biochemical, and other indicators of health in free-living platypuses across 18 Tasmanian river catchments. Live trapping enabled s ling of 161 (apparently) healthy and six ulcerated, mucormycosis-affected platypuses in 75 rivers and streams between January 2008 and June 2009. There were no obvious differences in any hematologic or biochemical measures between healthy and mucormycosis-affected platypuses. However, multivariate analysis revealed that ulceration was associated with living at higher altitudes, low tail fat content (high tail fat index), and low trypanosome load. There was evidence of overall lymphocytosis and monocytosis in animals from areas currently affected by mucormycosis, which suggests that some level of immune response to the introduced fungus is now widespread in disease-affected catchments. Animals from currently, historically, and possibly disease-affected catchments had lower neutrophil counts, mean cell volumes, plasma alkaline phosphatase, alanine aminotransferase, and aspartate aminotransferase levels, and higher plasma gamma-glutamyl transpeptidase and platelet counts compared to animals from catchments with no evidence of infection. Reference intervals were generated for all hematologic and biochemical measurements. Since this is the most comprehensive, systematic, and large-scale assessment of the health of the Tasmanian platypus to date, these references intervals should act as the standard against which future studies of platypuses in Tasmania should be compared.
Publisher: Wiley
Date: 03-2000
Publisher: American Chemical Society (ACS)
Date: 27-07-2006
DOI: 10.1021/JF061331J
Abstract: The oxidation of low-density lipoprotein (LDL) is believed to be the initiating factor for the development and progression of atherosclerosis. The active ingredients of spices such as chili and turmeric (capsaicin and curcumin, respectively) have been shown to reduce the susceptibility of LDL to oxidation. One of the techniques used to study the oxidation of LDL is to isolate LDL and subject it to metal-induced (copper or iron) oxidation. However, whole serum may represent a closer situation to in vivo conditions than using isolated LDL. We investigated the effects of different concentrations (0.1-3 microM) of capsaicin, dihydrocapsaicin, and curcumin on copper-induced oxidation of serum lipoproteins. The lag time (before initiation of oxidation) and rate of oxidation (slope of propagation phase) were calculated. The lag time increased, and the rate of oxidation decreased with increasing concentrations of the tested antioxidants (p < 0.05). A 50% increase in lag time (from control) was observed at concentrations between 0.5 and 0.7 microM for capsaicin, dihydrocapsaicin, and curcumin. This study shows that oxidation of serum lipids is reduced by capsaicinoids and curcumin in a concentration-dependent manner.
Publisher: Elsevier BV
Date: 04-2008
Publisher: Elsevier BV
Date: 02-2017
Publisher: Elsevier BV
Date: 03-2005
DOI: 10.1016/J.IJCARD.2004.02.004
Abstract: Relationships between low-density lipoprotein cholesterol and endothelial function in hemodialysis patients have yet to be investigated. Furthermore, current reporting of endothelial function data using flow-mediated dilatation has recognised limitations. The aims of the study were to determine the relationship between low-density lipoproteins and endothelial function in hemodialysis patients and to investigate the validity of determining the area under the curve for data collected during the flow-mediated dilatation technique. Brachial artery responses to reactive hyperemia (endothelial-dependent) and glyceryl trinitrate (endothelial-independent) were assessed in 19 hemodialysis patients using high-resolution ultrasound. Lipid profiles and other factors known to effect brachial artery reactivity were also measured prior to the flow-mediated dilatation technique. There were no significant relationships between serum low-density lipoproteins and endothelial-dependent or -independent vasodilation using absolute change (mm), relative change (%), time to peak change (s) or area under the curve (mm x s). In hemodialysis patients with atherosclerosis, area under the curve analysis showed a significantly (p<0.05) decreased endothelial-dependent response (mean+/-S.D.: 19.2+/-17.4) compared to non-atherosclerotic patients (42.3+/-28.6). However, when analysing these data using absolute change, relative change or time to peak dilatation, there were no significant differences between the two groups. In summary, there was no relationship between low-density lipoproteins and endothelial function in hemodialysis patients. In addition, area under the curve analysis of flow-mediated vasodilatation data may be a useful method of determining the temporal vascular response during the procedure.
Publisher: Informa UK Limited
Date: 04-2013
DOI: 10.2147/JPR.S42526
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.TAAP.2018.09.025
Abstract: Human monocytes and dendritic cells express transient receptor potential vanilloid 1 (TRPV1) which may play a role in mediating the inflammatory, immune and cancer surveillance responses of these cells. The aim of the present study was to investigate TRPV1 expression and function in THP-1 monocytic cells. RT-PCR and Western blot were used to detect TRPV1. The metabolic activity and viability of THP-1 cells following exposure to vanilloids was assessed using resorufin production from rezazurin. Cytokine release was measured using ELISA. TRPV1 was expressed in cultured THP-1 monocytic cells and naïve monocytes. Lower concentrations ( 250 μM, all agonists decreased metabolic activity. Capsaicin-stimulated THP-1 metabolic activity was blocked by the TRPV1 antagonist, 5-iodo-resiniferatoxin (5'-IRTX), whereas the decline in resorufin production by THP-1 cells at higher capsaicin concentrations (due to cell death), was not affected by 5'-IRTX. Finally, capsaicin (≤125 μM) significantly increased lipopolysaccharide-stimulated IL-6 and TNF-α release from THP-1 cells, whereas phytohaemagglutinin-stimulated IL-1β, TNF-α, MCP-1 and IL-6 release were concentration-dependently inhibited by capsaicin. Modulation of IL-1β release was not TRPV1 mediated. Overall, these results show that functional TRPV1 channels are present in naïve monocytes and THP-1 cells, and when activated, increase cell metabolic activity. In addition, capsaicin modifies cytokine release from THP-1 cells and induces cell death, most likely by a mechanism that is independent of TRPV1 activation.
Publisher: Elsevier BV
Date: 12-2000
Publisher: Springer Science and Business Media LLC
Date: 18-03-2008
Publisher: Elsevier BV
Date: 10-1986
DOI: 10.1016/0014-2999(86)90432-2
Abstract: Female Sprague-Dawley rats were injected s.c. with ethynyloestradiol (EE2, 0.2 microgram/day) and levonorgestrel (NG, 2.0 micrograms/day) separately and in combination (EE2/NG). Binding of [3H]rauwolscine (alpha 2-adrenoceptor specific) and [3H]prazosin (alpha 1-adrenoceptor specific) was examined in crude membrane suspensions prepared from whole rat kidney after 3, 6 and 12 weeks of steroid administration. Receptor affinity was high for both ligands (KD, equilibrium dissociation constant [3H]rauwolscine, congruent to 2.0 nM [3H]prazosin, congruent to 0.2 nM) and was not altered in rats chronically treated with steroid contraceptives. The Bmax (maximum density of binding sites) for [3H]prazosin binding was not altered, indicating no change in the number of renal alpha 1-adrenoceptors. NG administered alone did not affect the numbers of alpha 1- or alpha 2-adrenoceptors. Catechol metabolites of endogenous oestrogens did not displace the binding of either radioligand, suggesting that these metabolites do not directly interact with renal alpha-adrenoceptors. However, after 12 weeks treatment, the number of [3H]rauwolscine binding sites was reduced in both EE2 (Bmax, 133 +/- 7 fmol/mg protein)- and combined EE2/NG (135 +/- 11 fmol/mg protein)-treated rats, compared to controls (162 +/- 9 fmol/mg protein). Since renal alpha 2-adrenoceptors inhibit renin release, this reduction in alpha 2-adrenoceptor number may contribute to increased renin levels associated with oestrogen-induced hypertension.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.JINORGBIO.2017.04.022
Abstract: Oxaliplatin-based chemotherapy is the mainstay for the treatment of advanced colorectal cancer. Copper transporter proteins have been implicated in the transport of platinum-based anticancer drugs, but their expression in human colorectal cancer cell lines and roles in controlling their sensitivity to oxaliplatin are not well studied or understood. The endogenous and modified expression of copper uptake transporter 1 (hCTR1) was studied in a panel of human colorectal cancer cell lines (DLD-1, SW620, HCT-15 and COLO205) with ~20-fold variation in oxaliplatin sensitivity. hCTR1 protein was expressed more abundantly than ATP7A and ATP7B proteins, but with broadly similar levels and patterns of expression across four colorectal cancer cell lines. In a colorectal cancer cell-line background (DLD-1), stable transfection of the hCtr1 gene enhanced hCTR1 protein expression and increased the sensitivity of the cells to the cytotoxicity of copper and oxaliplatin. Treatment with copper chelators (ammonium tetrathiomolybdate, bathocuproinedisulfonic acid and D-penicillamine) increased expression of hCTR1 protein in DLD-1 and SW620 cells, and potentiated the cytotoxicity of oxaliplatin in DLD-1 but not SW620 cells. Treatment with copper chloride altered neither the expression of copper transporters nor cytotoxicity of oxaliplatin in colorectal cancer lines. In conclusion, human colorectal cancer cell lines consistently express hCTR1 protein despite their variable sensitivity to oxaliplatin. Genetic or pharmacological modification of hCTR1 protein expression may potentiate oxaliplatin sensitivity in some but not all colorectal cancer cell lines.
Publisher: Wiley
Date: 12-2000
Publisher: Wiley
Date: 08-1990
DOI: 10.1111/J.1440-1681.1990.TB01357.X
Abstract: 1. Systolic blood pressure (SBP), bodyweight, organ weight, renal beta-adrenoceptor and myocardial beta- and myocardial alpha 1-adrenoceptor characteristics were investigated in female Sprague-Dawley rats after chronic subcutaneous (s.c.) administration of ethynyloestradiol (EE2, 0.2 microgram/day), levonorgestrel (NG, 2.0 micrograms/day) separately and in combination (EE2/NG). 2. EE2 caused a sustained increase in SBP from 6 weeks (maximum at 14 weeks, +22 mmHg compared to control) which was accompanied by increased kidney and ventricle weight after 12 weeks. EE2/NG-treated rats also demonstrated a gradual rise in SBP (maximum at 9 weeks, +18 mmHg compared with control) with renal and ventricular hypertrophy, but were normotensive by week 17 of treatment. In contrast, NG induced only transient SBP increases (maxima at 5 and 10 weeks, +14 mmHg compared with control), unaccompanied by organ hypertrophy. Norethisterone (2 micrograms/day) also produced transient increases (weeks 6-8, +13 mmHg) in SBP. 3. alpha 1- and beta-adrenoceptors were investigated using [3H]-prazosin and (-)-[125I]-iodocyanopindolol (ICYP), respectively. Myocardial alpha 1- and beta-adrenoceptors were unaffected by steroid contraceptive administration for up to 12 weeks. Renal beta-adrenoceptor affinity was markedly reduced in 12 week EE2-treated rats (equilibrium dissociation constant, KD, 53 +/- 7 pmol/L) compared with controls (KD, 31 +/- 4 pmol/L), an effect which was prevented by co-administration of NG (KD, 34 +/- 8 pmol/L). Renal beta-adrenoceptor number was not altered by any treatment. 4. The relatively late onset of organ hypertrophy and beta-adrenoceptor changes appear to result from, rather than cause, EE2-induced hypertension.
Publisher: Informa UK Limited
Date: 1994
DOI: 10.3109/10641969409067966
Abstract: Previous work has demonstrated contraceptive steroid-induced hypertension in rats. Here, we examined the relationship between steroid-induced hypertension and components of the renin-angiotensin system. Female Sprague-Dawley rats were injected s.c. with 0.2 micrograms ethynyloestradiol, 2.0 micrograms levonorgestrel, a combination of both or vehicle, six days per week. A second group of rats received 2.0 micrograms enalapril maleate, enalapril plus ethynyloestradiol or levonorgestrel, or vehicle. Systolic blood pressure increased with both ethynyloestradiol. (6 weeks, +17 mmHg 12 weeks, +32 mmHg) and levonorgestrel (6 weeks, +24 mmHg) treatment. This effect of levonorgestrel was attenuated by co-administration of enalapril, which also reversed the hypertension seen with ethynyloestradiol. Ethynyloestradiol, but not levonorgestrel treatment caused a significant increase in plasma renin concentration, plasma renin activity, and plasma angiotensin II at both 6 and 12 weeks. Plasma renin substrate was increased by ethynyloestradiol at 3, 6 and 12 weeks, prior to the observed increase in systolic blood pressure. Combined steroid treatment had less pronounced effects. Enalapril alone or in combination with ethynyloestradiol decreased plasma renin concentration, activity and angiotensin II, and in combination with levonorgestrel decreased plasma renin concentration, substrate and activity (6 weeks only) but not angiotensin II. The data indicate a positive relationship between hypertension and the renin-angiotensin system with ethynyloestradiol, but not levonorgestrel treatment in rats.
Publisher: Weston Medical Publishing
Date: 03-2012
Abstract: Objective: To determine whether there are differences in the personal socioeconomic costs of healthcare access between transdermal (TD) and oral opioid use in a rural population with chronic noncancer pain (CNCP).Design: An observational longitudinal study, measuring change in the selfreported personal time and expense of healthcare access by route of opioid administration over time (monthly for 1 year). Subjects were opioid treated patients with CNCP from North West Tasmania, Australia. Subjects completed monthly datasheets by recording all personal healthcare access time and expense, together with the route(s) of opioid administration. The outcome measures of mean monthly healthcare time (MHT) and expense (MHE), by route of opioid administration, were analyzed using generalized estimating equations with robust standard errors.Results: The details of 10,564 healthcare contacts from 198 subjects were obtained during the study. Total mean MHT with oral opioids was 3.76 hours (95% confidence interval [CI] = 2.21-5.32) and unchanged (p = 0.59) with TD opioids at 3.48 hours (95% CI = 2.23-4.72). Total mean MHE with oral opioids was AU$ 92.72 (95% CI = 51.21-134.24) and unchanged (p = 0.81) with TD opioids at AU$ 89.12 (95% CI = 54.53-123.71).Conclusions: The personal socioeconomic costs of healthcare access for rural patients with CNCP are similar for TD and oral opioid use. The prolonged analgesic affect of TD opioids may be advantageous for rural population.
Publisher: Springer Science and Business Media LLC
Date: 05-2003
DOI: 10.1007/S00421-003-0806-6
Abstract: The aim of this study was to compare the effects of two high-intensity, treadmill interval-training programs on 3000-m and 5000-m running performance. Maximal oxygen uptake (.VO(2max)), the running speed associated with .VO(2max) (v.VO(2max)), the time for which v.VO(2max) can be maintained (T(max)), running economy (RE), ventilatory threshold (VT) and 3000-m and 5000-m running times were determined in 27 well-trained runners. Subjects were then randomly assigned to three groups (1) 60% T(max), (2) 70% T(max) and (3) control. Subjects in the control group continued their normal training and subjects in the two T(max) groups undertook a 4-week treadmill interval-training program with the intensity set at v.VO(2max) and the interval duration at the assigned T(max). These subjects completed two interval-training sessions per week (60% T(max)=six intervals/session, 70% T(max) group=five intervals/session). Subjects were re-tested on all parameters at the completion of the training program. There was a significant improvement between pre- and post-training values in 3000-m time trial (TT) performance in the 60% T(max) group compared to the 70% T(max) and control groups [mean (SE) 60% T(max)=17.6 (3.5) s, 70% T(max) =6.3 (4.2) s, control=0.5 (7.7) s]. There was no significant effect of the training program on 5000-m TT performance [60% T(max)=25.8 (13.8) s, 70% T(max)=3.7 (11.6) s, control=9.9 (13.1) s]. Although there were no significant improvements in .VO(2max), v.VO(2max) and RE between groups, changes in .VO(2max) and RE were significantly correlated with the improvement in the 3000-m TT. Furthermore, VT and T(max) were significantly higher in the 60% T(max) group post- compared to pre-training. In conclusion, 3000-m running performance can be significantly improved in a group of well-trained runners, using a 4-week treadmill interval training program at v.VO(2max) with interval durations of 60% T(max).
Publisher: American Society for Microbiology
Date: 29-10-2015
Abstract: The complete genome sequence of 6.45 Mb is reported here for Pseudomonas trivialis strain IHBB745 (MTCC 5336), which is an efficient, stress-tolerant, and broad-spectrum plant growth-promoting rhizobacterium. The gene-coding clusters predicted the genes for phosphate solubilization, siderophore production, 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity, indole-3-acetic acid (IAA) production, and stress response.
Publisher: Wiley
Date: 2003
Publisher: Elsevier BV
Date: 06-2012
DOI: 10.1016/J.GENE.2012.04.011
Abstract: The presence and progression of numerous diseases have been linked to deficiencies in antioxidant systems. The relationships between single nucleotide polymorphisms (SNPs) arising from specific antioxidant enzymes and diseases associated with elevated oxidative stress have been studied with the rationale that they may be useful in screening for diseases. The purpose of this narrative review is to analyse evidence from these studies. The antioxidant enzyme SNPs selected for analysis are based on those most frequently investigated in relation to diseases in humans: superoxide dismutase (SOD2) Ala16Val (80 studies), glutathione peroxidise (GPx1) Pro197Leu (24 studies) and catalase C-262T (22 studies). Although the majority of evidence supports associations between the SOD2 Ala16Val SNP and diseases such as breast, prostate and lung cancers, diabetes and cardiovascular disease, the presence of the SOD2 Ala16Val SNP confers only a small, clinically insignificant reduction (if any) in the risk of these diseases. Other diseases such as bladder cancer, liver disease, nervous system pathologies and asthma have not been consistently related to this SOD SNP genotype. The GPx1 Pro197Leu and catalase C-262T SNP genotypes have been associated with breast cancer, but only in a small number of studies. Thus, currently available evidence suggests antioxidant enzyme SNP genotypes are not useful for screening for diseases in humans.
Publisher: CSIRO Publishing
Date: 2004
DOI: 10.1071/PY04058
Abstract: In other developed countries, older persons in deprived personal circumstances make increased use of primary care and nursing homes compared with those less disadvantaged. The influence of living in a more deprived area on the use of these services by older residents has not been so well studied. This study appraises if older Australians living in more disadvantaged locations have similar increased service usage. Retrospective analyses of fee-for-service data from 1 October 2001 to 30 September 2002 for all Medicare and Department of Veterans? Affairs claimants aged 77 years and over, not admitted to residential aged care, were undertaken. Data were analysed by age, gender and quartile of disadvantage of postcode of residence as categorised by the Australian Bureau of Statistics 1996 Census Index of Relative Socio-economic Disadvantage. The main outcome measures were: mean number of claims for general practitioner primary medical care (GP) services longer GP consultations specialist consultations rate of GP health assessments and, first claims for GP nursing home attendances. Mean number of claims for GP primary medical care services generally decreased as the disadvantage of postcode increased. Men aged 77-79 years were an exception, with no difference in the mean across quartiles of disadvantage. The mean number of claims for longer primary care consultations and all specialist consultations also decreased as the disadvantage of postcode increased. Claims for GP health assessments were more frequent as the disadvantage of the residential postcode increased. Claim rates for first nursing home attendance items by men did not differ across the range of disadvantage. This lack of difference was also seen for women aged 77-79 years. Claims for first nursing home attendance items by women aged 80 or more years decreased as the disadvantage of postcode increased. This study concluded that there are fewer claims for medical and nursing home services by older Australians living in more disadvantaged postcodes. Whether this represents under-provision of medical care leading to sub-optimal health outcomes needs further examination.
Publisher: Elsevier BV
Date: 08-1990
DOI: 10.1016/0014-2999(90)90670-2
Abstract: The selective tachykinin agonist [Sar9,Met(O2)11]substance P (Sar-SP) was radioiodinated with [125I]Bolton-Hunter reagent and the product [125I]Bolton-Hunter-[Sar9,Met(O)2)11]SP (BHSar-SP) purified using reverse phase HPLC. Autoradiographic studies showed dense specific binding of BHSar-SP over the rat submandibular gland and over several regions in rat brain, with very low nonspecific binding, identical with the pattern of binding sites seen in a parallel study with [125I]Bolton-Hunter SP (BHSP). In homogenate binding experiments, BHSar-SP bound with high affinity to a single site in membranes from rat brain (KD 261 pM) and rat submandibular gland (KD 105 pM). Comparative values for BHSP were 495 and 456 pM, i.e. of two and four fold lower affinity than BHSar-SP. Association of BHSar-SP to membranes from brain (k+1 3.7 x 10(9) M-1 min-1) was faster than to membranes from salivary gland (k+1 5.6 x 10(8) M-1 min-1). In competition studies, BHSar-SP was displaced from salivary gland membranes by substance P (SP) approximately physalaemin greater than or equal to Sar-SP approximately SP-(3-11) greater than SP-(5-11) much greater than neurokinin A (NKA) approximately eledoisin = kassinin = SP-methyl ester greater than or equal to neurokinin B (NKB) much greater than [Nle10]NKA-(4-10) greater than [MePhe7]NKB-(4-10). In brain membranes, the rank potency order was SP greater than Sar-SP greater than or equal to physalaemin greater than SP-(3-11) greater than SP-(5-11) greater than NKA greater than or equal to eledoisin much greater than NKB greater than kassinin greater than SP-methyl ester: however [MePhe7]NKB-(4-10) and [Nle10]NKA-(4-10) were ineffective competitors at concentrations up to 1 microM. Both binding patterns are consistent with BHSar-SP binding to an NK1 site. With the exception of SP, Sar-SP, SP-(3-11) and physalaemin, all competitors were 5 to 54 times less potent at BHSar-SP binding sites in brain than in salivary gland. These data reveal some differences in characteristics of NK1 binding sites in brain and submandibular gland. Although of higher affinity, BHSar-SP does not appear greatly more selective than BHSP in its ability to define NK1 binding sites.
Publisher: Oxford University Press (OUP)
Date: 16-02-2011
DOI: 10.1093/NDT/GFQ828
Abstract: Oxidative stress has been linked to the progression of disease, including chronic kidney disease (CKD). The aim of the present study was to determine the association between single-nucleotide polymorphisms (SNPs) of the antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase and their activities and the progression of CKD. This is a prospective cohort study of 185 CKD patients (Stages 2-4), followed for up to 12 months. All patients were genotyped for SNPs of SOD (SOD Ala16Val), GPx (GPx Pro197Leu) and catalase (C-262T). The rate of change over the study period of estimated glomerular filtration rate (eGFR), plasma and red blood cell (RBC) GPx, RBC SOD and RBC catalase activities were determined. CKD patients with the SOD Ala/Val and Val/Val genotypes had a significantly greater eGFR decline compared to those with the Ala/Ala genotype (Ala/Val compared with Ala/Ala odds ratio (OR) 0.35, 95% CI 0.19 to 0.64, P = 0.001 Val/Val compared with Ala/Ala OR 0.25, 95% CI 0.10 to 0.65, P = 0.005). The progression of CKD was not associated with SNPs of the GPx or catalase genes studied but there was a direct relationship between the rate of change of plasma GPx activity and the rate of change of eGFR over 12 months (P = 0.025). CKD patients with the SOD Ala/Val and Val/Val genotypes have a greater decline in kidney function than those with the Ala/Ala genotype.
Publisher: Hindawi Limited
Date: 28-03-2003
Publisher: Springer Science and Business Media LLC
Date: 26-05-2006
DOI: 10.1007/S00726-006-0346-6
Abstract: Platypus venom contains an isomerase that reversibly interconverts the second amino-acid residue in some peptides between the L-form and the D-form. The enzyme acts on the natriuretic peptides OvCNPa and OvCNPb, and on the defensin-like peptides DLP-2 and DLP-4, but it does not act on DLP-1. While the isomerization of DLP-2 to DLP-4 is inhibited by the amino-peptidase inhibitor amastatin, it is not affected by the leucine amino-peptidase inhibitor bestatin. The enzyme, that is only present in minute quantities in an extract of the venom gland, is thermally stable up to 55 degrees C, and it was found by anion-exchange chromatography to be acidic. Isolation of the isomerase was carried out by combined ion-exchange chromatography and reverse-phase high performance liquid chromatography (HPLC).
Publisher: Elsevier BV
Date: 04-1999
DOI: 10.1016/S0006-8993(99)01247-0
Abstract: The respiratory response to microinjection of substance P (SP) into the commissural nucleus of the solitary tract (cNTS) and binding of [125I]-Bolton-Hunter SP ([125I]-BHSP) to brain stem NK1 receptors were compared in young and aged rats. Injection of SP (750 pmol) into the cNTS of young rats (2 months) increased tidal volume (VT) but had no effect on respiratory rate (f). In aged rats (19-21 months), injection of SP had no significant effect on f or VT. The NTS of aged rats displayed significantly lower specific [125I]-BHSP binding than young rats, indicating a reduction in the number in NK1 receptors. These findings show that the respiratory response to microinjection of SP into the cNTS of aged rats is severely blunted and that this phenomenon may be due to a decrease in the number of NK1 receptors in the NTS.
Publisher: Wiley
Date: 08-1990
DOI: 10.1111/J.1440-1681.1990.TB01357.X
Abstract: 1. Systolic blood pressure (SBP), bodyweight, organ weight, renal beta-adrenoceptor and myocardial beta- and myocardial alpha 1-adrenoceptor characteristics were investigated in female Sprague-Dawley rats after chronic subcutaneous (s.c.) administration of ethynyloestradiol (EE2, 0.2 microgram/day), levonorgestrel (NG, 2.0 micrograms/day) separately and in combination (EE2/NG). 2. EE2 caused a sustained increase in SBP from 6 weeks (maximum at 14 weeks, +22 mmHg compared to control) which was accompanied by increased kidney and ventricle weight after 12 weeks. EE2/NG-treated rats also demonstrated a gradual rise in SBP (maximum at 9 weeks, +18 mmHg compared with control) with renal and ventricular hypertrophy, but were normotensive by week 17 of treatment. In contrast, NG induced only transient SBP increases (maxima at 5 and 10 weeks, +14 mmHg compared with control), unaccompanied by organ hypertrophy. Norethisterone (2 micrograms/day) also produced transient increases (weeks 6-8, +13 mmHg) in SBP. 3. alpha 1- and beta-adrenoceptors were investigated using [3H]-prazosin and (-)-[125I]-iodocyanopindolol (ICYP), respectively. Myocardial alpha 1- and beta-adrenoceptors were unaffected by steroid contraceptive administration for up to 12 weeks. Renal beta-adrenoceptor affinity was markedly reduced in 12 week EE2-treated rats (equilibrium dissociation constant, KD, 53 +/- 7 pmol/L) compared with controls (KD, 31 +/- 4 pmol/L), an effect which was prevented by co-administration of NG (KD, 34 +/- 8 pmol/L). Renal beta-adrenoceptor number was not altered by any treatment. 4. The relatively late onset of organ hypertrophy and beta-adrenoceptor changes appear to result from, rather than cause, EE2-induced hypertension.
Publisher: American Chemical Society (ACS)
Date: 03-06-2004
DOI: 10.1021/JP036834W
Publisher: S. Karger AG
Date: 2011
DOI: 10.1159/000324530
Abstract: Vanilloids including capsaicin and resiniferatoxin (RTX) have been identified as potential novel anti-inflammatory and analgesic compounds. We have previously shown that systemic capsaicin administration to neonatal rats evokes profound long-term alterations in transient receptor potential vanilloid 1 (TRPV1)- and neurokinin 1 (NK sub /sub ) receptor-mediated respiratory responses in the commissural nucleus of the solitary tract (cNTS). Whether this effect of capsaicin is unique to developmentally immature animals is unknown. Therefore, in the present study, we investigated the effects of systemic capsaicin administration to adult rats on NK sub /sub receptor binding sites, TRPV1 and NK sub /sub immunoreactivity and function in the cNTS. Microinjection of capsaicin (1 nmol) or RTX (75 pmol) into the cNTS of vehicle-pretreated rats produced a profound bradypnoea (maximum change: –45 breaths·min sup –1 /sup ) and a small increase in tidal volume (V i T /i ). Similarly, microinjection of the selective NK sub /sub receptor agonists [Sar sup /sup , Met(O sub /sub ) sup /sup ]substance P (SP 66 pmol) and septide (20 pmol) decreased respiratory frequency and increased V i T /i . Thirteen to 18 days after systemic administration of capsaicin (125 mg·kg sup –1 /sup s.c.), the bradypnoeic responses to both capsaicin and RTX were absent (p 0.05), indicative of sensory neuron ablation/desensitisation. Systemic capsaicin pretreatment significantly (p 0.05) reduced the density of both [ sup /sup I]Bolton-Hunter SP binding sites (NK sub /sub receptors) and NK sub /sub receptor immunoreactivity in the cNTS, but did not alter the respiratory responses evoked by microinjection of [Sar sup /sup , Met(O sub /sub ) sup /sup ]SP and septide into this region. These studies show that systemic capsaicin administration reduces NK sub /sub receptor density in the cNTS without adversely affecting NK sub /sub receptor function at this site. We speculate that adult rats may be more resistant than neonatal rats to the neuroplastic effects of systemic capsaicin administration.
Publisher: Oxford University Press (OUP)
Date: 04-05-2011
DOI: 10.1093/NDT/GFR193
Abstract: Neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C are biomarkers of kidney injury and function, respectively. This study assessed whether plasma NGAL and/or serum cystatin C predicted baseline estimated glomerular filtration rate (eGFR) and urinary protein excretion, rate of change of eGFR and urinary protein excretion and whether atorvastatin influenced changes in these biomarkers in patients with chronic kidney disease (CKD). This is a post hoc analysis of the Lipid Lowering and Onset of Renal Disease trial, a randomized double-blind, placebo-controlled trial where 88 patients with Stages 2-4 CKD received atorvastatin 10 mg/day (48) or placebo (40). Stored blood s les were analysed for NGAL and cystatin C at baseline and a mean of 1.5 and 2.9 years later. Serum creatinine and Modification of Diet in Renal Disease (MDRD) eGFR were obtained three monthly. There were negative associations between NGAL and cystatin C and eGFR (P = 0.025 and P < 0.001, respectively) at all time points. There were no associations between baseline NGAL and cystatin C and rate of change of eGFR (P = 0.44 and P = 0.49, respectively). Baseline NGAL but not cystatin C (P = 0.043 and P = 0.35, respectively) predicted rate of change of urinary protein excretion. In atorvastatin-treated patients, NGAL decreased (mean, -7.4 ng/mL/year SD 128.4), whereas it increased in the placebo group [mean, 4.6 ng/mL/year SD 56.6), the difference being statistically significant (P = 0.049). NGAL is a biomarker of existing CKD but did not predict CKD progression. Atorvastatin reduced plasma NGAL but the significance and mechanisms require further investigation. Atorvastatin had no significant effect on cystatin C.
Publisher: Oxford University Press (OUP)
Date: 24-08-2019
DOI: 10.1093/IBD/IZZ179
Abstract: This proteomics study reveals novel proteins and pathways that potentially underpin the survival and proliferation of goblet cells in the colon of Winnie mice, an ulcerative colitis model caused by misfolding of mucin-2 that results in endoplasmic reticulum stress.
Publisher: Elsevier BV
Date: 03-1992
DOI: 10.1016/0196-9781(92)90129-Q
Abstract: Binding sites for [125I]-Bolton-Hunter substance P (BHSP) were investigated in homogenates of rat submandibular gland, colon smooth muscle, and urinary bladder. In vehicle-treated animals, the equilibrium dissociation constant (KD) was similar for both submandibular gland (0.46 +/- 0.03 nM) and colon (0.57 +/- 0.04 nM), although the maximum density of binding sites (Bmax) was about six-fold higher in submandibular gland compared with colon. These binding parameters remained unchanged in capsaicin-pretreated animals (140 mg/kg IP). In contrast, capsaicin pretreatment reduced (p less than 0.05) the Bmax in urinary bladder by twenty-five percent (0.56 fmol/mg wet weight) when compared to vehicle-treated controls (0.73 fmol/mg wet weight), although the KD was unchanged (vehicle, 0.29 +/- 0.08 nM capsaicin, 0.24 +/- 0.04 nM). These data demonstrate that the NK1 receptors in submandibular gland and colon smooth muscle are not associated with or dependent upon intact primary afferent sensory neurons. However, a minority of NK1 receptors in the urinary bladder were lost after capsaicin, indicating that these receptors are located on sensory terminals, or may be dependent on growth factors or other chemicals released from these nerves.
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.BBADIS.2009.07.008
Abstract: Transient receptor potential vanilloid (TRPV) 1 channels function as sensors for a variety of noxious and inflammatory signals, including capsaicin, heat and protons, and are up-regulated under inflammatory conditions. As end-stage kidney disease (ESKD) is associated with chronic inflammation, impaired immunity and depressed lymphocyte numbers, we sought to determine whether altered TRPV1 (and related TRPV2) expression in immune cells might be a contributing factor. TRPV1 and TRPV2 mRNA expression in peripheral blood mononuclear cells (PBMC) was similar in controls and ESKD patients by quantitative real-time RT-PCR. However, using immunocytochemistry, TRPV1-immunoreactivity was significantly higher and TRPV2-immunoreactivity was significantly lower in PBMC from ESKD patients compared to controls. The plant-derived TRPV1 agonists, capsaicin and resiniferatoxin (RTX) and the putative endovanilloid/endocannabinoids, N-arachidonoyl-dopamine (NADA) and N-oleoyl-dopamine (OLDA), induced concentration-dependent death of PBMC from healthy donors with a rank order of potency of RTX>NADA>OLDA>>capsaicin. TRPV1 (5'-iodoresiniferatoxin) and cannabinoid (CB2 AM630) receptor antagonists blocked the cytotoxic effect of NADA. In subsequent experiments, PBMC from ESKD patients exhibited significantly increased susceptibility to NADA-induced death compared to PBMC from controls. The apparent up-regulation of TRPV1 may be a response to the inflammatory milieu in which PBMC exist in ESKD and may be responsible for the increased susceptibility of these cells to NADA-induced death, providing a possible explanation as to why ESKD patients have reduced lymphocyte counts and impaired immune function. Thus, TRPV1 (and possibly CB2) antagonists may have potential for the treatment of immune dysfunction in ESKD.
Publisher: CSIRO Publishing
Date: 2009
DOI: 10.1071/ZO09034
Abstract: While the fungal disease mucormycosis has infected Tasmanian platypuses for nearly three decades, its impacts remain largely unknown. This study documents the spatial and temporal distribution of mucormycosis in Tasmanian platypuses as a baseline for assessing its impacts. Over 1800 platypus capture and observation records were collated and mapped, and indicate that between 1982 and 2007 mucormycosis-infected platypuses were present in at least 11, and potentially 22, of Tasmania’s 48 river catchments. During 2008–09, live-trapping surveys were undertaken to determine the spread, prevalence and persistence of the disease. Surveys of 75 rivers and creeks across 18 catchments captured 167 in iduals, and an additional 12 platypuses were obtained from the public. Only seven of the 179 s led animals were ulcerated with clinical signs of mucormycosis. All infected in iduals were obtained from catchments with prior histories of disease, where platypuses have persisted despite mucormycosis being present for up to 20 years. Detection probabilities were calculated to estimate the probability that the other surveyed catchments are currently disease free. Detection probabilities were generally high ( .75) per catchment, indicating that s ling effort was adequate to reliably detect diseased animals at historically reported prevalence (which averaged 0.295 from surveys undertaken between 1994 and 2000). Mean disease prevalence in affected catchments s led during the present study declined to 0.071. This significant four-fold reduction in prevalence makes disease detection more challenging and increased s le sizes are required to confidently assert that some catchments are currently disease free. Reduced disease prevalence suggests that mucormycosis is exerting less impact on Tasmanian platypuses now than it was in the mid to late 1990s however, the in idual consequences of infection are poorly understood and require further investigation.
Publisher: Portland Press Ltd.
Date: 07-2019
DOI: 10.1042/CS20181009
Abstract: Chronic respiratory diseases are among the leading causes of mortality worldwide, with the major contributor, chronic obstructive pulmonary disease (COPD) accounting for approximately 3 million deaths annually. Frequent acute exacerbations (AEs) of COPD (AECOPD) drive clinical and functional decline in COPD and are associated with accelerated loss of lung function, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEs and consequently constitute a significant comorbidity in COPD. However, current pharmacological interventions are ineffective in preventing infectious exacerbations and their treatment is compromised by the rapid development of antibiotic resistance. Thus, alternative preventative therapies need to be considered. Pathogen adherence to the pulmonary epithelium through host receptors is the prerequisite step for invasion and subsequent infection of surrounding structures. Thus, disruption of bacterial–host cell interactions with receptor antagonists or modulation of the ensuing inflammatory profile present attractive avenues for therapeutic development. This review explores key mediators of pathogen–host interactions that may offer new therapeutic targets with the potential to prevent viral/bacterial-mediated AECOPD. There are several conceptual and methodological hurdles h ering the development of new therapies that require further research and resolution.
Publisher: Informa UK Limited
Date: 11-2002
DOI: 10.1080/00039890209602085
Abstract: Low-density lipoprotein oxidation is implicated in the development of atherosclerosis. Plasma susceptibility to oxidation may be used as a marker of low-density lipoprotein oxidation and thus predict atherosclerotic risk. In this study the authors investigated the relationship between plasma susceptibility to oxidation and exposure to automotive pollution in a group of automobile mechanics (n = 16) exposed to high levels of automotive pollution, vs. matched controls (n = 13). The authors induced plasma oxidation by a free radical initiator and they determined susceptibility to oxidation by (1) change in absorbance at 234 nm, (2) lag time to conjugated diene formation, and (3) linear slope of the oxidation curve. Mechanics had significantly higher values (mean +/- standard error) for change in absorbance (1.60 +/- 0.05 vs. 1.36 +/- 0.05 p < .002), and slope (1.6 x 10(-3) +/- 0.1 x 10(-3) vs. 1.3 x 10(-3) +/- 0.1 x 10(-3) p < .001), compared with controls. These results indicate that regular exposure to automotive pollutants increases plasma susceptibility to oxidation and may, in the long-term, increase the risk of developing atherosclerosis.
Publisher: Cold Spring Harbor Laboratory
Date: 08-08-2021
DOI: 10.1101/2021.08.04.21261521
Abstract: The ectopic overexpression of transient receptor potential vanilloid-1 (TRPV1) has been detected in numerous solid cancers including breast, prostate, pancreatic, and tongue epithelium cancer. However, the expression of TRPV1 in hematological malignancies remains unknown. Here we show through in silico analysis that elevated TRPV1 mRNA expression occurs in a range of hematological malignancies and present an optimized flow cytometry method to rapidly assess TRPV1 protein expression for both cell lines and primary patient s les. Three anti-TRPV1 antibodies were evaluated for intracellular TRPV1 detection using flow cytometry resulting in an optimized protocol for the evaluation of TRPV1 in hematological malignant cell lines and patients’ peripheral blood mononuclear cells (PBMC). Overexpression of TRPV1 was observed in THP-1 (acute monocytic leukemia) and U266B1 (multiple myeloma, MM), but not U937 (histiocytic lymphoma) compared to healthy PBMC. TRPV1 was also detected in all 49 patients (including B-cell non-Hodgkin’s lymphoma (B-NHL), MM and others, and 20 healthy controls. TRPV1 expression was increased in 8% of patients (MM=2, B-NHL=2). In conclusion, we provide an optimized flow cytometry method for routine expression analysis of clinical s les and show that TRPV1 is increased in 8% of patients with hematological malignancies.
Publisher: Wiley
Date: 09-1991
DOI: 10.1111/J.1749-6632.1991.TB33101.X
Abstract: Long term cure and maximising reintegration into society are major goals of childhood cancer treatment. Whether reintegration had occurred was assessed using geographic mobility as an objective proxy. Age, sex, and socioeconomic status were identified as being independently associated with mobility whereas diagnosis and relapse were not.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.FCT.2014.01.034
Abstract: Carpobrotus rossii (CR) was used by the Aboriginal population and early European settlers both as a food and therapeutic agent. Based on the presence of flavonoids in CR and results from our previous in vitro investigations, this study aimed to determine whether consumption of CR crude leaf extract: (a) affected lipoprotein profile, resting glucose, systolic blood pressure and vascular function, and (b) produced toxic effects (haematological measures, organ weight) in healthy rats. Male Hooded-Wistar rats (~230 g) were supplemented for 4 weeks with CR extract in their drinking water (35 mg/kg body weight daily). CR extract produced a significant decrease (18%, p=0.033) in atherogenic lipoproteins (but not high density lipoprotein). CR supplemented animals showed no signs of haematological toxicity and body and organ weight, daily fluid and food consumption and in vitro vascular responsiveness were similar for both groups. CR also increased (40%, p=0.049) the renal concentration of 3-hydroxy-3-methylglutaric acid (HMG), consistent with HMG-containing CR flavonoids being bioavailable, and therefore possessing the potential to interfere with cholesterol synthesis pathways. CR extract appears to be safe to ingest and may reduce cardiovascular risk.
Publisher: Elsevier BV
Date: 10-1986
DOI: 10.1016/0014-2999(86)90432-2
Abstract: Female Sprague-Dawley rats were injected s.c. with ethynyloestradiol (EE2, 0.2 microgram/day) and levonorgestrel (NG, 2.0 micrograms/day) separately and in combination (EE2/NG). Binding of [3H]rauwolscine (alpha 2-adrenoceptor specific) and [3H]prazosin (alpha 1-adrenoceptor specific) was examined in crude membrane suspensions prepared from whole rat kidney after 3, 6 and 12 weeks of steroid administration. Receptor affinity was high for both ligands (KD, equilibrium dissociation constant [3H]rauwolscine, congruent to 2.0 nM [3H]prazosin, congruent to 0.2 nM) and was not altered in rats chronically treated with steroid contraceptives. The Bmax (maximum density of binding sites) for [3H]prazosin binding was not altered, indicating no change in the number of renal alpha 1-adrenoceptors. NG administered alone did not affect the numbers of alpha 1- or alpha 2-adrenoceptors. Catechol metabolites of endogenous oestrogens did not displace the binding of either radioligand, suggesting that these metabolites do not directly interact with renal alpha-adrenoceptors. However, after 12 weeks treatment, the number of [3H]rauwolscine binding sites was reduced in both EE2 (Bmax, 133 +/- 7 fmol/mg protein)- and combined EE2/NG (135 +/- 11 fmol/mg protein)-treated rats, compared to controls (162 +/- 9 fmol/mg protein). Since renal alpha 2-adrenoceptors inhibit renin release, this reduction in alpha 2-adrenoceptor number may contribute to increased renin levels associated with oestrogen-induced hypertension.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2018
Publisher: Canadian Science Publishing
Date: 07-1995
DOI: 10.1139/Y95-126
Abstract: Tachykinin receptors in guinea-pig airways were examined using radioligand binding techniques in lung homogenates, and using isolated bronchial segments. Binding of the NK 1 selective radioligand 125 I-labelled Bolton–Hunter [Sar 9 ,Met(O 2 ) 11 ]substance P ([ 125 I]BHSarSP) was saturable and of high affinity (K D , 0.26 nM). The rank potency order of competitors for [ 125 I]BHSarSP binding was [Pro 9 ]SP CP 96345 [Formula: see text] septide [pGlu 6 ]SP(6–11) RP 67580 ≥ [DPro 9 , [Formula: see text],Trp 11 ]SP [DPro 9 ,[Formula: see text],Trp 11 ]physalaemin ≥ GR 82334 ≥ 127 I Bolton–Hunter neurokinin A (BHNKA). Septide had higher affinity than expected, and it was the only ligand to bind to two sites. Agonists interacting with NK 2 receptors were more potent contractile agents than NK 1 receptor agonists. Responses to BHNKA (pD 2 8.4) were antagonized by MDL 29913 and MEN 10207, with pK B values 6.42 and 6.79, and also by SR 48968 and GR 94800, although this was not dose dependent. This agonist was also weakly inhibited by CP 96345 and RP 67580. These data demonstrate that BHNKA can interact with both NK 1 and NK 2 receptors. There was no relationship between the binding affinity of NK 1 ligands in lung homogenates, with GR 82334 being notably weak, and their agonist or antagonist potency in bronchial smooth muscle.Key words: tachykinin receptor, radioligand binding, septide, guinea-pig bronchus, 127 I Bolton–Hunter neurokinin A.
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.MOLIMM.2006.04.027
Abstract: The vanilloid receptor family of cation channels includes the capsaicin-sensitive, proton- and heat-activated TRPV1 and noxious heat-activated TRPV2. The present study demonstrates both gene and protein expression of TRPV1 and TRPV2 in human peripheral blood cells (PBCs) using molecular and immunocytochemical techniques. Using reverse-transcription polymerase chain reaction (RT-PCR) and quantitative real-time RT-PCR (qRT-PCR), TRPV1 and TRPV2 mRNA was detected in mRNA isolated from human whole peripheral blood. Using qRT-PCR, TRPV2 mRNA was highly expressed in human whole blood isolates (9.33+/-1.19 x 10(4)copies per 10(6)copies of the housekeeping gene GAPDH), whereas TRPV1 message was detected at approximately 150-fold lower levels (638+/-121 copies per 10(6)copies GAPDH). At the protein level, TRPV1 and TRPV2 activity was determined immunocytochemically in a lymphocyte-enriched mononuclear cell preparation (83+/-2% lymphocytes). Cells were labelled with rabbit anti-TRPV1 or goat anti-TRPV2 (1:500) and subsequently labelled with goat Texas red- (TRPV1) or FITC-(TRPV2) conjugated secondary antibodies (1:1000). All cells demonstrated punctate TRPV1-immunoreactivity, which appeared to be on the plasma membrane and in the cytoplasm. In contrast, cells within subjects appeared to express the TRPV1 protein at varying intensities. TRPV2-immunoreactivity appeared diffuse. This is the first study to demonstrate the presence of both TRPV1 and TRPV2 in human peripheral lymphocytes. Further studies need to be undertaken in order to determine the role of TRPV channels in these cells.
Publisher: Elsevier BV
Date: 1993
DOI: 10.1016/0006-8993(93)91693-M
Abstract: The binding characteristics of [3H]substance P ([3H]SP) were investigated in membranes prepared from rat cerebral cortex. Binding of [3H]SP reached equilibrium after 50 min at 25 degrees C and was saturable at 8 nM. Saturation data could be resolved into high affinity (equilibrium dissociation constant, Kd, 0.22 nM) and low affinity sites (Kd, 2.65 nM). The low affinity sites were more numerous than the high affinity sites, with a ratio of 4:1. The non-hydrolyzable GTP analogue GppNHp had no effect on binding, indicating that the high and low affinity sites are not guanine nucleotide-regulated states of the same (NK-1) receptor. The low affinity sites are unlikely to represent NK-3 receptors since coincubation with the selective NK-3 receptor agonist senktide did not alter the biphasic nature of [3H]SP binding. The rank order of potency for inhibition of [3H]SP (2 nM) binding was SP > or = [Sar9, Met(O2)11]-SP > or = physalaemin >> SP(3-11) > NP gamma = [Ala3]-SP > or = SP(4-11) > or = NPK > or = SP(5-11) > or = NKB approximately NKA >> SP(1-9), compatible with binding to an NK-1 site. N-terminal fragments and non-amidated analogues were ineffective competitors for [3H]SP binding. However, competition data for several peptides including substance P (SP) and the NK-1 selective agonist [Sar9, Met(O2)11]-SP could be resolved into two components.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.ACVD.2011.06.005
Abstract: Haemodialysis patients often have impaired vascular function that can contribute to mortality. Endothelial-dependent and -independent vascular function can be assessed using the brachial artery reactivity (BAR) technique that measures flow-mediated dilatation (FMD) and the response to glyceryl trinitrate (GTN), respectively. The aim of this pilot study was to determine whether BAR measurements in haemodialysis patients were associated with mortality. Brachial artery responses to FMD and administration of GTN were assessed in consecutive haemodialysis patients. Patients were then followed up to 18 months after BAR measurements. Seventeen patients were included in the study. After 18 months of follow-up, patients were ided into two groups: survived (n=12) and deceased (n=5). Patients who survived had a significantly greater median percentage vasodilatation to GTN than those who died (19.1% vs 8.8% P=0.04) and a significantly greater median area under the diameter change-time curve (318 vs 146 mm/s P=0.03). However, there were no significant differences between survivors and deceased in median percentage vasodilation to FMD (6.0% vs 4.3% P=0.21), time to peak dilation (45 vs 40s P=0.66) or area under the diameter change-time curve (35.5 vs 20 mm/s P=0.29). In this pilot study in a small group of haemodialysis patients, endothelial-independent vasodilatory response to GTN was associated with mortality and was of better prognostic value than the endothelial-dependent response to FMD. This finding needs to be investigated in a larger cohort.
Publisher: Elsevier BV
Date: 05-1990
DOI: 10.1016/0304-3940(90)90216-V
Abstract: Radioligand binding techniques were used to characterize the substance P (SP) binding site on membranes prepared from bovine adrenal medullae. 125I-labelled Bolton-Hunter substance P (BHSP), which recognises the C-terminally directed, SP-preferring NK1 receptor, showed no specific binding. In contrast, binding of [3H]SP was saturable (at 6 nM) and reversible, with an equilibrium dissociation constant (Kd) 1.46 +/- 0.73 nM, Bmax 0.73 +/- 0.06 pmol/g wet weight and Hill coefficient 0.98 +/- 0.01. Specific binding of [3H]SP was displaced by SP greater than neurokinin A (NKA) greater than SP(3-11) approximately SP(1-9) greater than SP(1-7) approximately SP(1-4) approximately SP(1-6), with neurokinin B (NKB) and SP(1-3) very weak competitors and SP(5-11), SP(7-11) and SP(9-11) causing negligible inhibition (up to 10 microM). This potency order is quite distinct from that seen with binding to an NK1 site, a conclusion confirmed by the lack of BHSP binding. It appears that Lys3 and/or Pro4 are critical for binding, suggesting an anionic binding site. These data suggest the existence of an unusual binding site which may represent a novel SP receptor. This site appears to require the entire sequence of the SP molecule for full recognition.
Publisher: Wiley
Date: 11-09-2015
DOI: 10.1111/NEP.12502
Abstract: Statins have pleiotropic effects that include attenuation of oxidative stress that may be relevant for chronic kidney disease (CKD) patients. We investigated the effect of long-term atorvastatin therapy on oxidative stress biomarkers in CKD patients. This was a pre-specified secondary analysis of data from a randomized, double-blind, placebo-controlled trial (Lipid lowering and Onset of Renal Disease, LORD) in CKD patients. Participants received 10 mg/day atorvastatin (n = 47) or placebo (n = 39) for 3 years. Plasma measures (total F2-isoprostanes, malondialdehyde. protein carbonyls, uric acid, glutathione peroxidase (GPx) activity and total antioxidant capacity (TAC) ) were performed at baseline and at 3 years. Age and sex matched participants (n = 34) with normal kidney function were controls. CKD patients had significantly (P 0.05) in the group difference of the change values: (mean (95% CI), F2-isoprostanes = 5.3 (-29.2 to 39.8) pg/mL, protein carbonyls = 0.03 (-0.13 to 0.19) nmol/mg, GPx activity = -0.10 (-4.73 to 4.52) (U/L), uric acid = 8.8 (-33.9 to 51.6) μmol/L or TAC = -0.03 (-0.10 to 0.04) mmol/L. A significant difference (P = 0.04) in the change in malondialdehyde between groups, 1.52(0.09 to 2.96) μmol/L, was due to a large decrease in the placebo group. CKD patients had elevated oxidative stress that was not attenuated by atorvastatin 10 mg/day for 3 years.
Publisher: Wiley
Date: 12-11-2000
DOI: 10.1046/J.1440-1681.2000.03365.X
Abstract: 1. The characteristics, localization and regulation of tachykinin receptors in the rat nucleus tractus solitarius (NTS) involved in respiratory control were investigated using a combination of in vivo microinjection and in vitro autoradiographic techniques. 2. Microinjection of receptor-selective tachykinin agonists and antagonists into the NTS of urethane-anaesthetized rats suggests that stimulation of NK1 and NK3 receptors increases tidal volume, whereas NK2 and NK3 receptor activation produces a bradypnoea. 3. Depletion of NK1 receptors in the NTS due to either ageing or acute hypoxia correlates with a markedly reduced respiratory response to substance P. In contrast, chemical ablation of sensory neurons by neonatal capsaicin administration dramatically increases the respiratory response to a variety of NK1, NK2 and NK3 agonists. 4. These studies suggest that all three tachykinin receptors are present in the rat NTS and that these receptors are subject to both acute and chronic regulation.
Publisher: Elsevier BV
Date: 12-2014
Publisher: S. Karger AG
Date: 2016
DOI: 10.1159/000445437
Abstract: The effect of the plant-derived vanilloid, capsaicin (CAP), on the metabolic activity of THP-1, U266B1 and U937 hematological malignancy cells was determined. CAP reduced metabolic activity in a concentration-dependent manner in the three cell lines. A biphasic effect was observed on THP-1 cells (EC sub /sub : IC sub /sub (95% CI) 32.9 (19.9-54.3)/219 (144-246) µmol/l). U266B1 cells were more resistant to CAP than THP-1 and U937. Metabolic activity was significantly inhibited by CAP in U937 compared to U266B1 cells (IC sub /sub : 197 versus 431 µmol/l, respectively, p 0.008). Transient receptor potential vanilloid-1 (TRPV1) and CB1 antagonists (SB452533 and AM251, respectively) suppressed the CAP-induced increase in THP-1 cell metabolic activity (p 0.001). AM251 and SB452533 appeared to act as partial agonists and displayed a synergistic effect with CAP in U937 cells. CAP inhibits the metabolic activity of malignant hematological cells through non-TRPV1-dependent mechanisms.
Location: No location found
Location: Australia
Location: Australia
Start Date: 2013
End Date: 2014
Funder: Clifford Craig Medical Research Trust
View Funded ActivityStart Date: 2013
End Date: 2013
Funder: Fruit Growers Tasmania Inc
View Funded ActivityStart Date: 2013
End Date: 2013
Funder: Clifford Craig Medical Research Trust
View Funded ActivityStart Date: 2009
End Date: 2009
Funder: University of Tasmania
View Funded ActivityStart Date: 2007
End Date: 2008
Funder: Natural Heritage Trust
View Funded ActivityStart Date: 2006
End Date: 2006
Funder: Norske-Skog (Australasia) Pty Ltd
View Funded ActivityStart Date: 2004
End Date: 2004
Funder: University of Tasmania
View Funded ActivityStart Date: 2004
End Date: 2004
Funder: National Health & Medical Research Council
View Funded ActivityStart Date: 2001
End Date: 2001
Funder: University of Tasmania
View Funded ActivityStart Date: 2003
End Date: 2003
Funder: Australian Research Council
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