ORCID Profile
0000-0002-2236-9410
Current Organisation
Women's and Children's Hospital
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Publisher: Mary Ann Liebert Inc
Date: 06-2018
DOI: 10.1089/HUM.2017.059
Abstract: Cystic fibrosis (CF) lung disease is an ideal candidate for a genetic therapy. It has been shown previously that preconditioning with lysophosphatidylcholine (LPC) prior to lentiviral (LV) vector delivery results in long-term in vivo gene expression in the airway epithelium of CF mice. It was hypothesized that this outcome is largely due to transduction of airway basal cells that in turn pass the transgene onto their progeny. The aim of these studies was to confirm if the in vivo delivery of a human immunodeficiency virus type 1 (HIV-1) vesicular stomatitis virus envelope glycoprotein (VSV-G) pseudotyped LV vector following LPC airway conditioning results in transduction of mouse airway basal cells in situ and if the transgene is passed onto their progeny. Additionally, the study sought to determine the efficiency of in vitro transduction of human airway basal cells. First, normal mouse nasal airways were pretreated with LPC prior to delivery of a HIV-1 VSV-G pseudotyped LV vector carrying a LacZ marker gene (LV-LacZ). An epithelial ablation model utilizing polidocanol was then used to demonstrate that clonal outgrowth of linear and spotted clusters of transgene expressing ciliated, basal, and goblet cells occurs following transduction of basal cells. Second, human basal cells were cultured from primary bronchial epithelial cells, with identity confirmed by keratin 5 staining. High levels of transgene expression were found following LV-LacZ transduction. This study demonstrates the ability of the vector delivery protocol to transduce mouse airway basal cells, the LV vector to transduce human basal cells, and the likely role of these cells in maintaining long-term gene expression. These findings support and further develop the potential of LV gene transfer for persistent correction of CF airway disease.
Publisher: International Union of Crystallography (IUCr)
Date: 2020
DOI: 10.1107/S1600577519014863
Abstract: Small-animal physiology studies are typically complicated, but the level of complexity is greatly increased when performing live-animal X-ray imaging studies at synchrotron and compact light sources. This group has extensive experience in these types of studies at the SPring-8 and Australian synchrotrons, as well as the Munich Compact Light Source. These experimental settings produce unique challenges. Experiments are always performed in an isolated radiation enclosure not specifically designed for live-animal imaging. This requires equipment adapted to physiological monitoring and test-substance delivery, as well as shuttering to reduce the radiation dose. Experiment designs must also take into account the fixed location, size and orientation of the X-ray beam. This article describes the techniques developed to overcome the challenges involved in respiratory X-ray imaging of live animals at synchrotrons, now enabling increasingly sophisticated imaging protocols.
Publisher: Elsevier BV
Date: 1997
DOI: 10.1080/00313029700169105
Abstract: Many morphological, pharmacological and toxicological studies of hepatotoxicity require frequent s ling of liver over time. In the past this has been achieved by including large numbers of animals in the study and killing subgroups at different times. In this paper we describe a technique for repeated liver biopsy that procures sufficient liver tissue for histopathological assessment and for additional studies, for ex le measurement of hepatic iron concentration or vitamin A measurement. The advantages and disadvantages of this technique are discussed.
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.CBPA.2009.03.006
Abstract: We present here the first physiological data for the sandhill dunnart (Sminthopsis psammophila), the second largest (35-44 g) sminthopsine dasyurid marsupial, and report torpor for this species. Their thermoneutral body temperature (34.4 degrees C), thermolability below thermoneutrality (0.062 degrees C degrees C(-1)), and mild hyperthermia above thermoneutrality (35.5 degrees C) are typical of small dunnarts, and dasyurids. Basal metabolic rate (0.80 mL O2 g(-1) h(-1)) is as predicted from mass. Sandhill dunnarts generally conform to the Scholander-Irving model of endothermy, although metabolism increases less than expected and extrapolates to a higher than actual body temperature.Wet (0.22 mL O2 g(-1) h(-1) C(-1)) and dry (2.8 J g(-1) h(-1) degrees C(-1)) thermal conductances were as predicted. Thermoneutral evaporative water loss (1.6 mg g(-1) h(-1)) was only 54% of expected, but this is not significantly different, and more likely reflects variability in the marsupial dataset than an adaptation.Relative water economy resembles that of other small marsupials, rodents and birds, with a point of relative economy of 18 degrees C. Respiratory ventilation closely matches metabolic rate, with minute volume increased at low ambient temperatures by increased breathing rate rather than tidal volume oxygen extraction was constant at about 17%, except during hyperthermia above the thermoneutrality. Torpor conferred significant energetic and hygric benefits. We found no evidence of deviation from allometrically- and phylogenetically-based expectations despite the sandhill dunnart's arid habitat and large (for a dunnart) body mass.
Publisher: Elsevier BV
Date: 1997
DOI: 10.1080/00313029700169544
Abstract: Cirrhosis may be reliably produced in rats by exposing them intermittently to low levels of carbon tetrachloride vapour while feeding alcohol in the Lieber-DeCarli liquid diet. Providing the alcohol in drinking water that has been sweetened with sucrose is a cheaper and more convenient method but it does not yield reliable results. This study aimed to determine whether alcohol in drinking water sweetened with artificial sweeteners would give adequate alcohol intake to achieve the desired hepatic effects. Rats were fed alcohol (8% v/v) in drinking water sweetened with sucrose (5% w/v) (n = 12), or with one of the artificial sweeteners aspartame (0.025%), saccharin (0.025%) or cyclamate (0.05%) (n = 8 per agent). During the alcohol treatment the animals were exposed to carbon tetrachloride vapour, 40 ppm, six hours per night for five nights per week, over a period of 14 weeks. All groups achieved good alcohol intakes of 5-6 g/kg/day. Only one rat, in the aspartame group, became cirrhotic all the others had varying degrees of fibrosis which did not differ significantly among the treatments. Although it was not effective in reliably achieving cirrhosis, sweetening the alcohol solution with artificial sweeteners led to reasonable alcohol intakes with resultant hepatic fibrosis, and without the high carbohydrate intake which occurs when sucrose is used.
Publisher: SPIE
Date: 19-09-2019
DOI: 10.1117/12.2529276
Publisher: University of Chicago Press
Date: 09-2009
DOI: 10.1086/603654
Abstract: We examined the time course for measurement of basal metabolic rate (BMR measured as O(2) consumption and CO(2) production) and standard evaporative water loss (EWL) for six species of small marsupial to determine the minimum time required to achieve basal/standard values. There was a highly significant effect of measurement duration on measured physiological variables with values for O(2) consumption, CO(2) production, and EWL decreasing with time for all species. The time required to attain values statistically indistinguishable from minimal differed significantly between species, but in general O(2) consumption rate reached basal values after 4.3 h, CO(2) production after 4.5 h, and evaporative water loss after 5.2 h. For 16 BMR measurements of small marsupial species in the literature, with experimental duration provided, 10 were for less than 4 h, suggesting that their BMR values might be overestimates. For EWL, three of the four published values for small marsupials may be overestimates. It is clear that appropriate experimental duration is an important component of the measurement protocol for both BMR and standardized water loss, which needs to be rigorously observed in future studies.
Publisher: Springer Science and Business Media LLC
Date: 21-11-2014
Publisher: IEEE
Date: 09-2019
Publisher: The Company of Biologists
Date: 09-2008
DOI: 10.1242/JEB.019463
Abstract: To better understand the effects of ambient relative humidity (RH) on physiological variables and the implications of RH-correcting evaporative water loss (EWL) data for marsupials, we examined the effect of RH on EWL,body temperature (Tb), metabolic rate (MR) and thermal conductance (C) of the brushtail possum (Trichosurus vulpecula), a medium-sized marsupial. Correcting EWL data for 27 species of marsupial for water vapour pressure deficit (ΔWVP) in the chamber during measurement significantly increased, rather than decreased, the variability of the allometric relationship for EWL. For the brushtail possum,both ambient temperature (Ta) and RH significantly affected EWL. At Ta=25°C, EWL was independent of RH at≤63% RH, but decreased linearly at higher RH values. At Ta=30°C, EWL was significantly related to RH from 26%to 92% RH. There was a significant effect of Ta on Tb and dry thermal conductance (Cdry higher at 30°C), but no effect of RH. For MR and wet thermal conductance(Cwet) there was a significant effect of Ta (MR higher and Cwet lower at 25°C), and RH at Ta=30°C (MR higher and Cwet lower at the lowest RH) but not at 25°C. Our results indicate that brushtail possums do not necessarily show the linear relationship between ambient RH and EWL expected for an endotherm, possibly because of behavioural modification of their immediate microclimate. This may account for the failure of WVP deficit correction to improve the allometric EWL relationship for marsupials. Chamber RH is an important environmental factor to be considered when measuring standard physiological variables such as MR and Cwet.
Publisher: Elsevier BV
Date: 1995
DOI: 10.1016/0300-483X(94)02871-Q
Abstract: This study investigated behavioural effects of the toxic pethidine metabolite, norpethidine, in rats and its interactions with reserpine, apomorphine and physostigmine. Following intraperitoneal administration, brain concentrations of norpethidine reached a plateau after 20-40 min and remained elevated for 2 h. In the dose range 0.06-0.18 mmol/kg, norpethidine induced myoclonic jerks, a characteristic splayed posture, and episodes of exaggerated shivering. Forward locomotion, grooming, yawning and rearing were suppressed. Seizures and reverse locomotion occurred occasionally. Administration of reserpine 1 h prior to norpethidine, or of apomorphine or physostigmine 15 min after norpethidine, did not alter the norpethidine-induced behaviours neither did norpethidine block the effects of apomorphine or physostigmine. The characteristic profile of behaviours induced by norpethidine make this toxicant readily amenable to animal studies. Our results indicate that its mechanism of action is unlikely to involve dopaminergic or cholinergic pathways.
Publisher: Springer Science and Business Media LLC
Date: 12-06-2003
DOI: 10.1007/S00134-003-1803-2
Abstract: To evaluate the effect of intravenous cefazolin on gastric emptying measured by the C-13 octanoic acid breath test. Prospective, double-blind, cross-over, randomised, placebo-controlled trial. Mixed multidisciplinary intensive care unit in a university hospital. Fourteen critically ill, mechanically ventilated patients. After a 4-h fast patients received either 50 mg cefazolin or 20 ml saline over 20 min immediately prior to measurement of gastric emptying. The next day the study was repeated with the alternative therapy. Breath s les were analysed for the concentration of (13)CO2 by mass spectrometer, and the gastric emptying coefficient (GEC) and half-emptying time (t(50)) were calculated. Results are mean (standard deviation). Data were analysed with the paired t-test (saline vs cefazolin). Two patients were excluded for technical problems. Twelve patients remained (six male/six female), aged 57 (+/-16) years, with an APACHE II score of 20 (+/-8). Both GEC and t(50) were unchanged after administration of cefazolin compared with placebo (t(50) cefazolin, 138 (+/-54) vs saline 122 (+/-46) min, P=0.32 GEC cefazolin 3.27 (+/-0.83) vs saline 3.55 (+/-0.6), P=0.24). Two patients had abnormal t(50) after saline and five after cefazolin. There was no order effect of the study day. In mechanically ventilated patients, cefazolin had no effect on gastric emptying. These data do not support the use of low-dose cefazolin as a pro-kinetic agent in critically ill patients.
Publisher: University of Chicago Press
Date: 03-2009
DOI: 10.1086/595967
Abstract: We present the first complete study of basic laboratory-measured physiological variables (metabolism, thermoregulation, evaporative water loss, and ventilation) for a South American marsupial, the gracile mouse opossum (Gracilinanus agilis). Body temperature (T(b)) was thermolabile below thermoneutrality (T(b) = 33.5 degrees C), but a substantial gradient between T(b) and ambient temperature (T(a)) was sustained even at T(a) = 12 degrees C (T(b) = 30.6 degrees C). Basal metabolic rate of 1.00 mL O2 g(-1) h(-1) at T(a) = 30 degrees C conformed to the general allometric relationship for marsupials, as did wet thermal conductance (5.7 mL O2 g(-1) h(-1) degrees C(-1)). Respiratory rate, tidal volume, and minute volume at thermoneutrality matched metabolic demand such that O2 extraction was 12.4%, and ventilation increased in proportion to metabolic rate at low T(a). Ventilatory accommodation of increased metabolic rate at low T(a) was by an increase in respiratory rate rather than by tidal volume or O2 extraction. Evaporative water loss at the lower limit of thermoneutrality conformed to that of other marsupials. Relative water economy was negative at thermoneutrality but positive below T(a) = 12 degrees C. Interestingly, the Neotropical gracile mouse opossums have a more positive water economy at low T(a) than an Australian arid-zone marsupial, perhaps reflecting seasonal variation in water availability for the mouse opossum. Torpor occurred at low T(a), with spontaneous arousal when T(b) > 20 degrees C. Torpor resulted in absolute energy and water savings but lower relative water economy. We found no evidence that gracile mouse opossums differ physiologically from other marsupials, despite their Neotropical distribution, sympatry with placental mammals, and long period of separation from Australian marsupials.
Publisher: Springer Science and Business Media LLC
Date: 07-06-2005
DOI: 10.1007/S00134-005-2663-8
Abstract: To compare the effectiveness of 70-mg and 200-mg doses of intravenous erythromycin in improving gastric emptying in critically ill patients. Gastric emptying was measured on consecutive days day 1 (pre-treatment), day 2 (post-treatment) after an intravenous infusion of either 70 or 200 mg erythromycin or saline placebo (0.9%), in a randomized double-blind fashion. Mixed medical/surgical intensive care unit, tertiary referral. Thirty-five randomly selected, mechanically ventilated, enterally fed critically ill patients (median APACHE II score 19 on admission). On day 2 either 70 or 200 mg erythromycin or saline was administered intravenously over 20 min. Gastric emptying was measured using the [13C]octanoic acid breath test. The gastric emptying coefficient (GEC) and half-emptying time (t1/2) were calculated from the area under the 13CO2-recovery curve. Pre-treatment gastric emptying measurements were similar in all three patient groups. Treatment with both doses of erythromycin significantly reduced the gastric t1/2: 70 mg, 98 min (IQR 88-112) 200 mg, 86 min (75-104) vs. placebo, 122 min (102-190) (p<0.05). The GEC was higher with both doses of erythromycin: 70 mg, 3.8 (3.3-4.0) 200 mg, 4.0 (3.6-4.2) vs. placebo, 2.9 (2.5-3.7) (p<0.05). There was no difference in gastric emptying post-treatment between the two doses of erythromycin. The effect of erythromycin was greatest in patients with delayed gastric emptying. Treatment with 70 and 200 mg intravenous erythromycin are equally effective in accelerating gastric emptying in the critically ill.
Publisher: Informa UK Limited
Date: 26-11-2017
DOI: 10.1080/01902148.2017.1395931
Abstract: Purpose/Aim: Cystic fibrosis (CF) is the most common, fatal recessive genetic disease among the Caucasian population. Gene therapy has the potential to treat CF long term, however physiological barriers can prevent VSV-G pseudotyped lentiviral (LV) vectors from efficiently accessing the relevant receptors on the basolateral membrane of airway epithelial cells. The aims of this experiment were to use our new dose delivery techniques to determine whether conditioning the mouse lung conducting airways with lysophosphatidylcholine (LPC) improves the level of airway gene expression. Anaesthetised normal C57Bl/6 mice were intubated with an endotracheal cannula to non-invasively facilitate airway access. The airways were conditioned with 0.1% LPC, 0.3% LPC, or PBS (control) instilled via the ET tube. One hour later a VSV-G pseudotyped LV vector carrying the LacZ transgene was delivered. LacZ expression was measured by X-gal staining of the excised lungs 3 months after gene delivery. Endotracheal intubation enabled precise dose delivery to the trachea and conducting airways. The cartilaginous airways of the groups conditioned with 0.1% and 0.3% LPC contained significantly larger numbers of LacZ positive cells compared to the PBS control group. In the LPC conditioned groups the majority of cell transduction was in ciliated epithelial cells. LPC conditioning prior to LV vector delivery, substantially enhanced the level of conducting airway gene expression after a single gene vector delivery. These results extend the previously established effectiveness of this protocol for producing gene expression in the nasal airways to the lung airways, the primary site of deleterious pathophysiology in CF in iduals.
Publisher: Frontiers Media SA
Date: 18-05-2021
DOI: 10.3389/FPHAR.2021.682299
Abstract: Cystic fibrosis (CF) is a genetic disease caused by mutations in the CF transmembrane conductance regulator ( CFTR ) gene, resulting in defective ion transport in the airways. Addition of a functioning CFTR gene into affected airway cells has the potential to be an effective treatment for lung disease. The therapeutic efficacy of airway gene transfer can be quantified in animal models by assessing ion transport in the treated nasal epithelium using the nasal potential difference (PD) measurement technique. The nasal PD technique is routinely used in CF mice, however when applied to a recently developed CF rat model those animals did not tolerate the initial nasal PD assessment, therefore the procedure was firstly optimised in rats. This study evaluated the effect of lentiviral (LV)-mediated CFTR airway gene delivery on nasal PD in a CFTR knockout rat model. LV gene vector containing the CFTR gene tagged with a V5 epitope tag (LV-V5- CFTR ) was delivered to the nasal epithelium of CF rats, and one week later nasal PD was analysed. This study demonstrated for the first time that LV-V5- CFTR treatment produced a mean correction of 46% towards wild-type chloride response in treated CF rats. Transduced cells were subsequently identifiable using V5 immunohistochemical staining. These findings in the nose validate the use of airway gene therapy for future lung based experiments.
Publisher: Wiley
Date: 12-1997
DOI: 10.1111/J.1440-1746.1997.TB00381.X
Abstract: The influence of varying the level of supplemental dietary iron on the development of hepatic iron overload was examined in rats. Two days after giving birth, Porton rats were fed a diet supplemented with 0, 0.5, 1 or 2% carbonyl iron, to institute dietary iron supplementation to the young via breast milk. After weaning, the offspring continued to receive the assigned diet until 32 weeks of age. Liver biopsies were taken from some rats at 8, 16 and 24 weeks of age and from all rats at 32 weeks of age, for assessment of iron overload. For both male and female rats, hepatic iron content was increased in a dose-related manner by feeding supplemented diet. Hepatic iron content of male rats tended to reach a plateau after 8, 16 weeks of supplementation, while that of female rats continued to rise throughout the experimental period, such that the hepatic iron content of female rats was 2.8-fold that of similarly treated males at 32 weeks of age. Iron supplementation was associated with only moderate retardation of growth. By choosing an appropriate level of iron supplementation, good (grade III-IV) hepatic iron loading can be achieved with minimal adverse effects on the animals' overall health.
Publisher: Wiley
Date: 09-2014
DOI: 10.1002/JGM.2778
Abstract: Persistent reporter gene and cystic fibrosis transmembrane conductance regulator (CFTR) nasal airway gene expression can be achieved with a single lentiviral (LV) gene vector dosing when coupled with a preparatory lysophosphatidylcholine (LPC) airway pre-treatment. In the present study, we characterised the duration of gene expression in in idual cystic fibrosis (CF) knockout mice (cftr(tm1unc)) over their lifetimes. CF mouse nasal airways were treated with LV-Rx, a mixture of a therapeutic LV-CFTR gene vector and a LV-luciferase reporter gene vector, after pre-treatment with LPC. Control groups received either PBS sham pre-treatment followed by LV-Rx, or LPC prior to delivery of a LV vector containing no transgene (LV-MT). Airway reporter gene expression was monitored by bioluminescence, and functional CFTR expression was assessed via nasal transepithelial potential difference measurements at regular intervals up to 21 months. The presence of the CFTR transgene in the nasal septa, liver and spleen tissues were assessed by a quantitative polymerase chain reaction. Circulating antibodies to the vector glycoprotein envelope and to the luciferase protein were also measured. The combined use of LPC and LV gene vectors in the nasal airway produced enhanced and sustained luciferase and CFTR gene expression lasting at least 12 months. Improved survival was also observed in CF knockout mice treated with the LV vector mixture compared to all control CF mouse groups. The present study showed that our airway pre-treatment and gene delivery technique resulted in sustained functional CFTR expression and improved survival in CF mice.
Publisher: American Chemical Society (ACS)
Date: 29-07-2019
Publisher: Wiley
Date: 12-1994
DOI: 10.1111/J.1530-0277.1994.TB01457.X
Abstract: Cirrhosis may be reliably produced in rats by exposing them to low levels of carbon tetrachloride vapor while feeding alcohol in the Lieber-DeCarli liquid diet. This study aimed to determine whether alternative cheaper and more convenient ways of feeding alcohol would also allow the production of cirrhosis. Animals were fed alcohol in the Lieber-DeCarli diet, in a gel diet, or by addition of alcohol + sucrose to their drinking water, and were exposed to carbon tetrachloride vapor 6 hr/night, 5 nights/week. After 12 weeks of treatment, all animals (4 of 4) receiving alcohol in the Lieber-DeCarli diet, but only two in each of the gel and drinking water groups, were cirrhotic. The variable results with the gel diet may be due to loss of alcohol by evaporation from the gel. Alcohol intake in the group receiving alcohol in drinking water was greater than in those receiving Lieber-DeCarli diet. We suggest that the increased carbohydrate intake due to addition to sucrose to the water exerted a protective effect on the liver.
Publisher: Mary Ann Liebert Inc
Date: 08-2021
DOI: 10.1089/HUM.2021.031
Abstract: A gene addition therapy into the conducting airway epithelium is a potential cure for cystic fibrosis lung disease. Achieving sustained lung gene expression has proven difficult due to the natural barriers of the lung. The development of lentiviral (LV) vectors pseudotyped with viral envelopes that have a natural tropism to the airway has enabled persistent gene expression to be achieved
Publisher: IOP Publishing
Date: 16-07-2020
Abstract: Accurate in vivo quantification of airway mucociliary transport (MCT) in animal models is important for understanding diseases such as cystic fibrosis, as well as for developing therapies. A non-invasive method of measuring MCT behaviour, based on tracking the position of micron sized particles using synchrotron x-ray imaging, has previously been described. In previous studies, the location (and path) of each particle was tracked manually, which is a time consuming and subjective process. Here we describe particle tracking methods that were developed to reduce the need for manual particle tracking. The MCT marker particles were detected in the synchrotron x-ray images using cascade classifiers. The particle trajectories along the airway surface were generated by linking the detected locations between frames using a modified particle linking algorithm. The developed methods were compared with the manual tracking method on simulated x-ray images, as well as on in vivo images of rat airways acquired at the SPring-8 Synchrotron. The results for the simulated and in vivo images showed that the semi-automatic algorithm reduced the time required for particle tracking when compared with the manual tracking method, and was able to detect MCT marker particle locations and measure particle speeds more accurately than the manual tracking method. Future work will examine the modification of methods to improve particle detection and particle linking algorithms to allow for more accurate fully-automatic particle tracking.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-1992
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 03-1990
Publisher: Elsevier BV
Date: 05-2020
Publisher: Oxford University Press (OUP)
Date: 17-02-2010
Publisher: Oxford University Press (OUP)
Date: 02-06-2009
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-1990
Publisher: Elsevier BV
Date: 08-1991
DOI: 10.1016/0160-5402(91)90057-C
Abstract: The hot-plate (HP) and tail-flick (TF) tests are widely used to assess analgesic activity of drugs. These tests do not directly measure the intensity of the noxious stimulus perceived by the animal, but only the animal's response to it, and so may be affected by non-analgesic drugs. Sedatives and muscle relaxants, for ex le, may impair the ability to respond and hence be wrongly considered to have analgesic activity. We examined response of rats in the HP (55 degrees C, cutoff time 25 sec) and TF (cutoff time 5 sec) tests following administration of pentobarbitone, diazepam or pancuronium. These drugs all impaired motor performance as assessed by reduction in mean rotarod performance times to 6-32% of predrug values. However, HP and TF latencies were not appreciably prolonged. We also found that pancuronium did not alter effects of morphine on HP or TF latencies, despite reduction in rotarod performance to 38% of predrug values. Our results support the validity of HP and TF tests as analgesic assays even in the presence of substantial impairment of motor performance.
Publisher: Elsevier BV
Date: 09-2009
DOI: 10.1016/J.CBPA.2009.05.002
Abstract: The chuditch is a large carnivorous dasyurid marsupial. Historically it had one of the widest geographical distributions of all marsupials, encompassing much of arid Australia, but it is now restricted to the mesic south-west of Western Australia. It is therefore of interest to determine if its physiology better reflects adaptation to its historically arid or present mesic habitat. The basic physiological parameters of the chuditch conform to other marsupials. Body mass of males (1385 g) was >400% of that predicted by phylogeny and this may be related to its carnivorous diet. Body temperature was 33.9 degrees C at ambient temperatures < or = thermoneutrality, with hyperthermia occurring above thermoneutrality. Basal metabolic rate was 0.361 mL O(2) g(-1) h(-1) at an ambient temperature of 31 degrees C. Metabolic rate increased below the thermoneutral zone by 0.038 mL O(2) g(-1) h(-1) degrees C(-1), and above the thermoneutral zone to 0.444+/-0.059 mL O(2) g(-1) h(-1) at 33.3 degrees C. Standard evaporative water loss was 0.498+/-0.071 mg g(-1) h(-1) at an ambient temperature of 26.0 degrees C, and increased at higher ambient temperatures due to panting and licking. Changes in wet thermal conductance largely reflected changes in evaporative heat loss, and dry thermal conductance increased at high ambient temperature due in part to posture change. Ventilatory parameters were consistent with metabolic demands in and below thermoneutrality, and suggested augmented evaporative heat loss above the thermoneutral zone. Chuditch had a high point of relative water economy of 22.6 degrees C, indicating favourable water economy at even moderate ambient temperatures, due to its low evaporative water loss rather than high metabolic water production. Chuditch were physiologically more similar to marsupials from arid rather than mesic habitats, better reflecting their historical distribution than their current geographical range.
Publisher: Springer Science and Business Media LLC
Date: 02-11-2028
DOI: 10.1038/S41434-023-00403-3
Abstract: Lentiviral vectors are attractive delivery vehicles for cystic fibrosis gene therapy owing to their low immunogenicity and ability to integrate into the host cell genome, thereby producing long-term, stable gene expression. Nonetheless, repeat dosing may be required to increase initial expression levels, and/or boost levels when they wane. The primary aim of this study was to determine if repeat dosing of a VSV-G pseudotyped LV vector delivered into mouse lungs is more effective than a single dose. C57Bl/6 mouse lungs were conditioned with lysophosphatidylcholine, followed one-hour later by a LV vector carrying the luciferase reporter gene, using six different short-term (≤1 wk) and long-term ( wk) dosing schedules. Luciferase expression was quantified using bioluminescence imaging over 12 months. Most dosing schedules produced detectable bioluminescence over the 12-month period, but the shorter intervals (≤1 wk) produced higher levels of flux than the longest interval (five doses at least 1-month apart). Ex vivo lung analysis at 12 months showed that the estimated mean flux for the group that received two doses 1-week apart was significantly greater than the single dose group and the two groups that received doses over a period greater than 1-week. These results suggest that early consecutive multiple doses are more effective at improving gene expression in mouse lungs at 12 months, than longer repeat dosing intervals.
Publisher: Wiley
Date: 06-1994
DOI: 10.1111/J.1440-1746.1994.TB01719.X
Abstract: We have previously established a model for micronodular cirrhosis by feeding Wistar rats alcohol, in the Lieber-DeCarli liquid diet, and exposing them to 'low-dose' carbon tetrachloride (CCl4) vapour for 10 weeks. This study reports the spectrum of liver pathology seen in male Porton rats exposed to 'low-dose' CCl4 vapour 5 nights/week, 6 h/night while being fed alcohol (300 kcal/L) in the Lieber-DeCarli diet. Micronodular cirrhosis developed in all animals after 5-7 weeks of treatment. The simultaneous administration of silymarin, a putative hepatoprotective agent, in the liquid diet, did not alleviate or prevent the chronic liver injury. The histopathological features of the liver injury are described, with particular emphasis on the presence of small epithelial cells ('progenitor or stem cell'), which appear to be playing a role in liver regeneration.
Publisher: American Chemical Society (ACS)
Date: 28-08-2019
Publisher: Springer Science and Business Media LLC
Date: 06-1995
DOI: 10.1007/BF00170161
Publisher: Springer Science and Business Media LLC
Date: 13-06-2018
Publisher: Springer Science and Business Media LLC
Date: 23-06-2010
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 09-2001
DOI: 10.1097/00003246-200109000-00015
Abstract: To measure gastric emptying in ventilated critically ill patients with a new noninvasive breath test. Single-center, open study. Combined medical and surgical intensive care unit of a university hospital. Thirty unselected mechanically ventilated critically ill patients receiving gastric feeding and 22 healthy volunteers. None. After 4 hrs without feeding, intragastric infusion of 100 mL of a liquid meal (Ensure) labeled with 100 microL 13C-octanoic acid. End-expiratory breath s les were collected into evacuated tubes from the respirator circuit every 5 mins for the first hour, then every 15 mins for 3 hrs. End-expiratory breath s les were also collected from volunteers studied supine after an overnight fast following an identical infusion via a nasogastric tube. Breath 13CO2 was measured with an isotope ratio mass spectrometer. Performance of the breath test posed no difficulty or interference with patient care. The CO2 level was >1% in 1297/1300 breath s les, indicating satisfactory end-expiratory timing. Data are median and interquartile range. Gastric emptying was slower in patients compared with volunteers: gastric emptying coefficient 2.93 (2.17-3.39) vs. 3.58 (3.18-3.79), p <.001 and gastric half emptying time, derived from the area under the 13CO2 curve, 155 min (130-220) vs. 133 min (120-145), p <.008. Fourteen of the 30 patients had a gastric emptying coefficient <95% of all volunteers and 11 had a gastric half emptying time longer than 95% of all volunteers. The Acute Physiology and Chronic Health Evaluation (APACHE II) score (median 22, range 13-43) either at admission or on the day of the study did not correlate with gastric emptying coefficient. Gastric emptying of a calorie-dense liquid meal is slow in 40% to 45% of unselected mechanically ventilated patients in a combined medical and surgical intensive care unit. The 13C-octanoic acid breath test is a novel and useful bedside technique to measure gastric emptying in these patients.
Publisher: Frontiers Media SA
Date: 26-04-2021
DOI: 10.3389/FPHAR.2021.669635
Abstract: The lungs have evolved complex physical, biological and immunological defences to prevent foreign material from entering the airway epithelial cells. These mechanisms can also affect both viral and non-viral gene transfer agents, and significantly diminish the effectiveness of airway gene-addition therapies. One strategy to overcome the physical barrier properties of the airway is to transiently disturb the integrity of the epithelium prior to delivery of the gene transfer vector. In this study, chemical (lysophosphatidylcholine, LPC) and physical epithelium disruption using wire abrasion were compared for their ability to improve airway-based lentiviral (LV) vector mediated transduction and reporter gene expression in rats. When luciferase expression was assessed at 1-week post LV delivery, LPC airway conditioning significantly enhanced gene expression levels in rat lungs, while a long-term assessment in a separate cohort of rats at 12 months revealed that LPC conditioning did not improve gene expression longevity. In rats receiving physical perturbation to the trachea prior to gene delivery, significantly higher LacZ gene expression levels were found when compared to LPC-conditioned or LV-only control rats when evaluated 1-week post gene transfer. This proof-of-principle study has shown that airway epithelial disruption strategies based on physical perturbation substantially enhanced LV-mediated airway gene transfer in the trachea.
Publisher: Wiley
Date: 12-1994
DOI: 10.1111/J.1530-0277.1994.TB01460.X
Abstract: Dose-response relationships were examined for the production of hepatic fibrosis and cirrhosis by combined exposure of male Porton rats to alcohol and carbon tetrachloride. Alcohol was administered orally in Lieber-DeCarli liquid diet at levels of 75, 150, or 300 kcal/liter, giving mean daily intakes of 2.29, 4.61, and 8.16 g/kg/day, respectively. Carbon tetrachloride was administered by inhalation at concentrations of 10, 20, or 40 ppm, 6 hr/night, 5 nights/week. Liver biopsies were taken at intervals up to a maximum treatment period of 20 weeks. All four rats that received the high dose of both agents, and 1 of 4 that received the medium alcohol and high carbon tetrachloride treatments, were cirrhotic by 10 weeks. Two of the 4 rats that received the low alcohol and high carbon tetrachloride dose were cirrhotic at 20 weeks. Cirrhosis was not observed in rats that received the low or medium carbon tetrachloride dose, but some degree of hepatic fibrosis was observed in all treatment groups. Severity of fibrosis was significantly associated with both dose of alcohol and dose of carbon tetrachloride received. It is concluded that, in the alcohol-carbon tetrachloride rat model for chronic liver injury, both alcohol and carbon tetrachloride contribute to the response in a dose-related manner. Hepatic injury was observed even when relatively low doses of these agents are administered together.
Publisher: Springer Science and Business Media LLC
Date: 15-02-2013
DOI: 10.1038/SREP01287
Publisher: Wiley
Date: 10-03-2004
DOI: 10.1111/J.1440-1746.2003.03310.X
Abstract: A simple non-invasive test not requiring the use of radioactive isotopes is required to assess fat malabsorption in adult cystic fibrosis (CF) patients. Breath tests using substrates labeled with 13C meet these conditions. The 14C-triolein breath test is sensitive and specific for measuring fat malabsorption, but involves radiation exposure. The aim of this study was to examine the utility of a test using a 13C label and to determine whether pancreatic replacement therapy would return the test to the values of a normal control group. 13CO2 recovery was assessed after an overnight fast in six adult patients with CF, both with and without pancreatic enzyme replacement therapy (PERT) in the usual dose for a light snack, in a randomized order, on different days. Studies were also performed in eight healthy volunteers after oral ingestion. Subjects drank 50 mL of a liquid meal mixed with 200 microL 13C-triolein and breath s les were collected by blowing through a straw into collection tubes every 30 min for 6 h. The effect of gastric emptying was assessed by comparison of oral ingestion with intraduodenal infusion. Intra-in idual variability was assessed in nine volunteers by repeating the breath test after drinking the test meal on a separate day. Compared with healthy subjects there was virtually no recovery of 13CO2 in CF patients without PERT. The median (interquartile range) cumulative percentage dose recovery (cPDR) at 6 h was 3% (0-8) in CF patients compared with 28% (22-41) in healthy controls (P < 0.01). Fat absorption was normalized (37%) (36-43) after ingestion of PERT. Gastric emptying delayed the peak in 13CO2 recovery, but there was no difference in the cPDR at 6 h. There was no difference in recovery between days 1 and 2. The 13C-triolein breath test is a simple and reproducible method to measure fat malabsorption. The test provides a screening technique for fat malabsorption in adult CF patients and may be useful for monitoring the lowest effective dose of PERT.
Publisher: Wiley
Date: 02-1988
DOI: 10.1111/J.1600-0773.1988.TB01849.X
Abstract: Rats were exposed to halothane vapour, 50 p.p.m., or air for a period of four weeks. Within each exposure group, some animals drank plain water, some received water plus phenobarbitone, while some received water plus isoniazid. Halothane exposure resulted in increased serum bromide concentrations and liver injury evidenced by increased serum alanine aminotransferase activity, focal hepatocellular necrosis and fatty change. Administration of isoniazid reduced halothane metabolism by 33% as assessed by serum bromide concentrations, and completely blocked the injurious effects of halothane on the liver, suggesting that halothane metabolism plays a role in halothane hepatotoxicity under these conditions. Administration of phenobarbitone partially prevented the increase in serum alanine aminotransferase activity and hepatocellular necrosis due to halothane. In contrast to isoniazid, phenobarbitone led to a slight increase in halothane metabolism. However, phenobarbitone also caused an increase in liver size, such that the amount of halothane metabolised per gram of liver was reduced by phenobarbitone treatment. These results suggest that metabolism of halothane is an important factor in liver injury due to prolonged, subanaesthetic halothane exposure.
No related grants have been discovered for Patricia Cmielewski.