bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypothalamic Interactions Between Neuropeptide Y, Agouti‐Related Protein, Cocaine‐ and Amphetamine‐Regulated Transcript and Alpha‐Melanocyte‐Stimulating Hormone In Vitro in Male Rats
Authors: Dhillo W. S. , Small C. J. , Stanley S. A. , Jethwa P. H. , Seal L. J. , Murphy K. G. , Ghatei M. A. , Bloom S. R. 
Published: March 2003

AbstractA number of neuropeptides implicated in the hypothalamic regulation of appetite are synthesized in the arcuate nucleus (Arc). Neuropeptide Y (NPY) and agouti‐related protein (Agrp) are orexigenic. The pro‐opiomelanocortin (POMC) product alpha‐melanocyte‐stimulating hormone (α‐MSH) is anorectic. Intracerebroventricular administration of cocaine‐ and amphetamine‐regulated transcript (CART) decreases food intake. However, recent results show that CART is orexigenic when injected into discrete hypothalamic nuclei. There is almost complete coexpression of NPY and Agrp mRNA in Arc neurones, and the majority of CART‐containing neurones in the Arc also contain POMC mRNA. We investigated possible interactions between these neuropeptides in vitro using a rat hypothalamic explant system. Administration of 1, 10 and 100 nm of NPY to hypothalamic explants significantly increased release of Agrp(83‐132)‐immunoreactivity (IR). NPY (10 and 100 nm) significantly increased the release of CART(55‐102)‐IR and α‐MSH‐IR from hypothalamic explants. Agrp(83‐132) (10 nm) administered to hypothalamic explants significantly increased the release of NPY‐IR. Agrp(83‐132) (10 and 100 nm) significantly decreased the release of CART(55‐102)‐IR from hypothalamic explants. Administration of 1, 10 and 100 nm CART(55‐102) to hypothalamic explants resulted in a significant increase in NPY‐IR release. Administration of 10 nm CART(55‐102) to hypothalamic explants significantly increased the release of Agrp(83‐132)‐IR. NDP‐MSH (10 nm) administered to hypothalamic explants significantly increased the release of NPY‐IR. NDP‐MSH (10 and 100 nm) significantly increased the release of Agrp(83‐132)‐IR from hypothalamic explants. These data suggest that orexigenic neuropeptides in the arcuate nucleus stimulate the release of each other, perhaps reinforcing orexigenic behaviour via a positive‐feedback loop. Our results are also in keeping with the possibility that the melanocortin‐3 receptor in the arcuate nucleus may influence the release of arcuate neuropeptides.
Resistance to the Satiety Action of Leptin Following Chronic Central Leptin Infusion is Associated with the Development of Leptin Resistance in Neuropeptide Y Neurones
Authors: Sahu A. 
Published: March 2003

AbstractLeptin regulates food intake and body weight by acting primarily in the hypothalamus. In humans and rodents, obesity is associated with hyperleptinaemia, suggesting a possible state of leptin resistance. Thus, to begin to examine the mechanisms of leptin resistance, we developed a rat model in which chronic central leptin infusion results in the development of resistance to leptin's satiety action. Adult male rats were infused chronically into the lateral cerebroventricle with leptin (160 ng/h) or phosphate‐buffered saline via Alzet pumps for 28 days, followed by artificial cerebrospinal fluid infusion for 3 weeks. After the initial decrease in food intake, rats developed resistance to the satiety action of leptin, and withdrawal of the chronic leptin infusion resulted in hyperphagia. During leptin infusion, body weight was gradually decreased to reach a nadir on day 12, and thereafter, body weight was sustained at a reduced level throughout the entire 28‐day infusion, despite normalization in food intake. Body weight was mostly normalized by day 22 postleptin. Since neuropeptide Y (NPY) neurones are one of the targets of leptin signalling in the hypothalamus, we next examined whether the development of resistance to the satiety action of leptin was due to altered NPY gene expression. On day 3–4 of infusion, hypothalamic NPY mRNA levels, as determined by RNAse protection assay (RPA), were significantly decreased in leptin treated rats compared to controls. By contrast, on day 16 of infusion, NPY mRNA levels in the leptin treated group had returned to control levels. In situ hybridization study confirmed the results obtained with RPA and showed further that the effect of chronic leptin infusion on NPY mRNA levels was restricted to the rostral and middle parts of the arcuate nucleus. Overall, the finding that the action of continuous leptin exposure on NPY neurones was not sustained suggests that NPY neurones may be involved in the development of leptin resistance to the satiety action of leptin in the hypothalamus.
Evidence for the Biosynthesis of a Prolactin‐Releasing Factor From the Ovine Pars Tuberalis, Which is Distinct from Thyrotropin‐Releasing Hormone
Authors: Graham E. Scott , Webster C. A. , Hazlerigg D. G. , Morgan P. J. 
Published: March 2003

AbstractThis study demonstrates the presence of two prolactin‐releasing (PR) factors in media conditioned by primary pars tuberalis cells prepared from dispersed pars tuberalis tissue. One factor was identified as thyrotropin‐releasing hormone (TRH) on the basis of immunoreactivity and following purification by high‐performance liquid chromatography and mass spectrometry. The origin of TRH in the pars tuberalis conditioned media was investigated by measuring the expression of glutaminyl‐cyclase (QC) by in situ hybridization. QC expression was not detected in pars tuberalis‐specific cells, but was relatively abundant in cells in the pars distalis and hypothalamic paraventricular nucleus. These data suggest that TRH is not synthesized by the ovine pars tuberalis and more likely originated from the hypothalamic neuronal processes from the paraventricular nucleus that terminate in the median eminence. The second component of the conditioned media PR bioactivity was insensitive to the TRH‐antiserum, less than 1 kDa and was not retained by the C18 reverse‐phase column. The biosynthesis of the PR bioactivity by pars tuberalis cells was investigated using cycloheximide, forskolin and melatonin. Cycloheximide reduced the level of PR bioactivity produced by the pars tuberalis cells. Melatonin inhibited the increased level of PR bioactivity stimulated by forskolin. Collectively, these data demonstrate the synthesis of at least one regulator of prolactin secretion by ovine pars tuberalis‐specific cells.
Vasopressin and Oxytocin Decrease Excitatory Amino Acid Release in Adult Rat Supraoptic Nucleus
Authors: Currás‐Collazo M. C. , Gillard E. R. , Jin J. , Pandika J. 
Published: March 2003

AbstractOxytocin and vasopressin reduce the amplitude of excitatory postsynaptic responses in magnocellular neuroendocrine cells of the supraoptic nucleus (SON). To test whether synaptic glutamate release is modulated by these neuropeptides, we examined the combined effect of vasopressin and oxytocin on depolarization‐induced glutamate and aspartate release from acutely dissected rat SON or fronto‐parietal cortex punches. Glutamate release was stimulated with 60 mm K+ for 5–10 min and measured using ion exchange chromatography or high‐performance liquid chromatography. During depolarization with high K+, extracellular glutamate levels increased, on average, to 204% of control values. In the presence of vasopressin/oxytocin, K+‐stimulated glutamate and aspartate release were significantly reduced by 34% and 62%, respectively, in the SON. Treatment with the aminopeptidase inhibitor amastatin did not mimic the effects of exogenous vasopressin/oxytocin on glutamate or aspartate release, suggesting that, under the conditions tested here, amastatin treatment may produce more complex effects. The effects of exogenous neuropeptides are likely mediated by oxytocin and/or vasopressin receptors, as the oxytocin‐ and V1a‐receptor antagonist, Manning Compound (10–100 µm), partially reversed the effects of vasopressin/oxytocin on SON glutamate release. In contrast, in cortical punches, glutamate release was enhanced by high K+, but vasopressin/oxytocin did not significantly reduce glutamate/aspartate release, consistent with the relatively sparse distribution of vasopressin/oxytocin receptors in fronto‐parietal cortex. These findings suggest that locally released oxytocin and vasopressin may autoregulate SON magnocellular neuroendocrine cell activity in part by modulating the release of excitatory amino acids from afferent terminals targeting these cells and/or from other cellular sources.
Involvement of the Entorhinal Cortex in the Stress Response to Immobilization, But Not to Insulin‐Induced Hypoglycaemia
Authors: Umegaki H. , Zhu W. , Nakamura A. , Suzuki Y. , Takada M. , Endo H. , Iguchi A. 
Published: March 2003

AbstractAlthough the involvement of the limbic system in the neuroendocrine responses to some stressors has been documented, the specific role of the entorhinal cortex has not been elucidated. In this study, we investigated the involvement of the entorhinal cortex in stress responses. Fos immunoreactivity, a widely used marker for neuronal activation, was detected in the entorhinal cortex of rats subjected to immobilization stress, whereas no marked staining was observed in the entorhinal cortex of the control and insulin‐induced hypoglycaemia groups. Lesion of the entorhinal cortex produced by ibotenic acid significantly attenuated the adrenocorticotropic hormone (ACTH) release evoked by immobilization; however, no significant change in ACTH release was observed in insulin‐induced hypoglycaemia. No significant difference between entorhinal‐lesioned rats and control rats was observed in blood glucose concentrations when subjected to either immobilization or to insulin‐induced hypoglycaemia. Together, these results indicate that the entorhinal cortex is closely involved in the stress response to immobilization but not to insulin‐induced hypoglycaemia.
Evaluation of skin‐ versus teeth‐attached markers in wireless optoelectronic recordings of chewing movements in man
Authors: Häggman‐henrikson B. , Eriksson P. ‐O. , Nordh E. , Zafar H. 
Published: March 2003

SUMMARYThis study evaluated the applicability of skin‐ and teeth‐attached reflex markers fixed to the mandible and the head for optoelectronic recording of chewing movements. Markers were attached to the upper and lower incisors and to the skin on the forehead, the bridge of the nose, the tip of the nose and the chin in seven subjects. Chewing movements were recorded in three dimensions using a high‐resolution system for wireless optoelectronic recording. Skin markers were systematically displaced due to skin stretch. The largest displacement was observed for the chin marker, whereas minor displacement was found for markers located on the forehead and the bridge of the nose. In repeated recordings, the smallest intra‐individual variation in displacement was found for the marker on the bridge of the nose. In spite of relatively large displacement for the chin marker, the temporal estimates of the mandibular movement were not affected. Teeth markers were found to significantly increase the vertical mouth opening, although the duration of the chewing cycle was unaffected. This indicates an increase in chewing velocity. We suggest that markers located on the bridge of the nose are acceptable for recordings of chewing movements. Skin markers on the chin can be reliably used for temporal analysis. They are also acceptable for spatial analysis if an intra‐individual variability of 2 mm is allowed. Teeth‐attached markers may significantly influence the natural chewing behavior. Thus, both types of marker systems have advantages as well as disadvantages with regard to the accuracy of the chewing movement analysis. Selection of a marker system should be based on the aims of the study.
The relationship between 6‐sulphatoxymelatonin and polysomnographic sleep in good sleeping controls and wake maintenance insomniacs, aged 55–80 years
Authors: LUSHINGTON KURT , DAWSON DREW , KENNAWAY DAVID J. , LACK LEON 
Published: March 2003

SummaryThe pineal hormone, melatonin, is reported to possess hypnotic properties. This has led to an investigation of the relationship between the endogenous melatonin rhythm and sleep. However, this relationship has yet to be fully examined in aged insomniacs and controls. From media advertisements, 16 good sleeping controls (11F, 5 M) and 16 sleep maintenance insomniacs (11F, 5 M), aged over 55 years, were recruited to participate in a study involving four nights of polysomnographically (PSG) measured sleep followed by a 26 h constant routine. During the constant routine, 2 h urine samples were collected and analysed for the melatonin metabolite, 6‐sulphatoxymelatonin (aMT.6S). This was used to determine total melatonin excretion. As well, the following circadian melatonin parameters were calculated from fifth order polynomial curve fitting analyses, the goodness of the polynomial curve fit, peak melatonin concentration, the phase of the melatonin rhythm, and melatonin and sleep rhythm synchrony. Apart for one control, all subjects showed significant circadian melatonin rhythms. Although insomniacs showed a greater amount of wakefulness, less sleep in total, and lower sleep efficiency, no significant group differences were observed in any of the melatonin parameters. In addition, while subjects with more reliable melatonin curve fits showed shorter sleep latencies and higher sleep efficiencies, correlational analyses revealed no other significant relationships between any melatonin and PSG sleep parameters. Overall, the present results suggest that neither melatonin amplitude nor phase are related to sleep quality in the aged.
Word recall correlates with sleep cycles in elderly subjects
Authors: Mazzoni G. , Gori S. , Formicola G. , Gneri C. , Massetani R. , Murri L. , Salzarulo P. 
Published: March 2003

SummaryMorning recall of words presented before sleep was studied in relation to intervening night sleep measures in elderly subjects. Night sleep of 30 elderly subjects aged 61–75 years was recorded. Before sleep, subjects were presented with a list of paired non‐related words and cued recall was asked immediately after the morning awakening. Recall positively correlated with average duration of NREM/REM cycles, and with the proportion of time spent in cycles (TCT) over total sleep time (TST). No significant correlations were found with other sleep or wake measures. These results suggest the importance of sleep structure for sleep‐related memory processes in elderly adults.
The effects of leptin on REM sleep and slow wave deltain rats are reversed by food deprivation
Authors: Sinton Christopher M. , Fitch Thomas E. , Gershenfeld Howard K. 
Published: March 2003

SummaryLeptin (ob protein) is an adipose tissue derived circulating hormone that acts at specific receptors in the hypothalamus to reduce food intake. The protein is also critically involved in energy balance and metabolic status. Here the effect of leptin on sleep architecture in rats was evaluated because food consumption and metabolic status are known to influence sleep. Sprague‐Dawley rats were chronically implanted with electrodes for EEG and EMG recording and diurnal sleep parameters were quantified over 9‐h periods following leptin administration. Murine recombinant leptin (rMuLep) was administered systemically to rats that either had undergone 18 h of prior food deprivation or had received food ad libitum. In the normally fed rats, leptin significantly decreased the duration of rapid eye movement sleep (REMS) by about 30% and increased the duration of slow wave sleep (SWS) by about 13%, the latter effect reflecting enhanced power in the delta frequency band. These results are consistent with studies that have linked changes in metabolic rate with effects on sleep. Leptin administration has previously been shown to alter neuroendocrine parameters that could have mediated these changes in sleep architecture. Unexpectedly, prior food deprivation negated the effect of leptin on both REMS and SWS, a result that emphasizes the significance of the apparent coupling between sleep parameters and energy status.
Circadian variation of EEG power spectra in NREM and REM sleep in humans: Dissociation from body temperature
Authors: Dijk Derk‐Jan 
Published: March 2003

SummaryIn humans, EEG power spectra in REM and NREM sleep, as well as characteristics of sleep spindles such as their duration, amplitude, frequency and incidence, vary with circadian phase. Recently it has been hypothesized that circadian variations in EEG spectra in humans are caused by variations in brain or body temperature and may not represent phenomena relevant to sleep regulatory processes. To test this directly, a further analysis of EEG power spectra – collected in a forced desynchrony protocol in which sleep episodes were scheduled to a 28‐h period while the rhythms of body temperature and plasma melatonin were oscillating at their near 24‐h period – was carried out.EEG power spectra were computed for NREM and REM sleep occurring between 90–120 and 270–300 degrees of the circadian melatonin rhythm, i.e. just after the clearance of melatonin from plasma in the ‘morning’ and just after the ‘evening’ increase in melatonin secretion. Average body temperatures during scheduled sleep at these two circadian phases were identical (36.72°C). Despite identical body temperatures, the power spectra in NREM sleep were very different at these two circadian phases. EEG activity in the low frequency spindle range was significantly and markedly enhanced after the evening increase in plasma melatonin as compared to the morning phase. For REM sleep, significant differences in power spectra during these two circadian phases, in particular in the alpha range, were also observed.The results confirm that EEG power spectra in NREM and REM sleep vary with circadian phase, suggesting that the direct contribution of temperature to the circadian variation in EEG power spectra is absent or only minor, and are at variance with the hypothesis that circadian variations in EEG power spectra are caused by variations in temperature.
Pharmacokinetics of selamectin following intravenous, oral and topical administration in cats and dogs
Authors: Sarasola P. , Jernigan A. D. , Walker D. K. , Castledine J. , Smith D. G. , Rowan T. G. 
Published: March 2003

Pharmacokinetics of selamectin following intravenous, oral and topical administration in cats and dogs. J. vet. Pharmacol. Therap.24, 265–272.The pharmacokinetics of selamectin were evaluated in cats and dogs, following intravenous (0.05, 0.1 and 0.2 mg/kg), topical (24 mg/kg) and oral (24 mg/kg) administration. Following selamectin administration, serial blood samples were collected and plasma concentrations were determined by high performance liquid chromatography (HPLC). After intravenous administration of selamectin to cats and dogs, the mean maximum plasma concentrations and area under the concentration–time curve (AUC) were linearly related to the dose, and mean systemic clearance (Clb) and steady‐state volume of distribution (Vd(ss)) were independent of dose. Plasma concentrations after intravenous administration declined polyexponentially in cats and biphasically in dogs, with mean terminal phase half‐lives (t½) of approximately 69 h in cats and 14 h in dogs. In cats, overall Clb was 0.470 ± 0.039 mL/min/kg (±SD) and overall Vd(ss) was 2.19 ± 0.05 L/kg, compared with values of 1.18 ± 0.31 mL/min/kg and 1.24 ± 0.26 L/kg, respectively, in dogs. After topical administration, the mean Cmax in cats was 5513 ± 2173 ng/mL reached at a time (Tmax) of 15 ± 12 h postadministration; in dogs, Cmax was 86.5 ± 34.0 ng/mL at Tmax of 72 ± 48 h. Bioavailability was 74% in cats and 4.4% in dogs. Following oral administration to cats, mean Cmax was 11929 ± 5922 ng/mL at Tmax of 7 ± 6 h and bioavailability was 109%. In dogs, mean Cmax was 7630 ± 3140 ng/mL at Tmax of 8 ± 5 h and bioavailability was 62%. There were no selamectin‐related adverse effects and no sex differences in pharmacokinetic parameters. Linearity was established in cats and dogs for plasma concentrations up to 874 and 636 ng/mL, respectively. Pharmacokinetic evaluations for selamectin following intravenous administration indicated a slower elimination from the central compartment in cats than in dogs. This was reflected in slower clearance and longer t½ in cats, probably as a result of species‐related differences in metabolism and excretion. Inter‐species differences in pharmacokinetic profiles were also observed following topical administration where differences in transdermal flux rates may have contributed to the overall differences in systemic bioavailability.
The long‐term efficacy of plasma‐derived hepatitis B vaccine in babies born to carrier mothers
Authors: Young B. W. Y. , Lee S. S. , Lim W. L. , Yeoh E. K. 
Published: March 2003

summary. The long‐term efficacy of a childhood hepatitis B vaccination programme was evaluated. A total of 112 newborn babies of hepatitis B carrier mothers were given hepatitis B immune globulin (HBIG) and a 10‐μg three‐dose regimen of plasma‐derived vaccine administered at a conventional (0, 1, 6 months), delayed (2, 3, 8 months) or accelerated (0, 1, 2 months) schedule. The vaccinees were followed up to determine their anti‐HBs status over a 16‐year period. Upon completion of the vaccination schedules, 92.6% developed antibody against surface antigen (anti‐HBs) seroconverion, the rate of which fell to 33.3% at year 16. The three schedules were equally effective in preventing chronic infection, with a protective efficacy of 88.9% from hepatitis B surface antigen (HBsAg) carriage, compared with historical control. Vaccinees on the delayed schedule had a slightly higher seroconversion rate over years, and were better able to maintain an anti‐HBs level of ≥ 100 iu/L. Overall, a quarter demonstrated evidence of exposure to the virus, being positive for antibody against core antigen or HBsAg, or mounting a rise in anti‐HBs during the follow‐up period. We conclude that a three‐dose hepatitis B vaccination regimen is generally effective in protecting newborns of hepatitis B carrier mothers from infection and chronic carriage. Booster is not needed even after 16 years of monitoring.
Early viral kinetics on treatment with pegylated interferon‐α‐2a in chronic hepatitis C virus genotype 1 infection*
Authors: Jessner W. , Stauber R. , Hackl F. , Datz C. , Watkins‐Riedel T. , Hofer H. , Gangl A. , Kessler H. , Ferenci P. 
Published: March 2003

summary. Even with pegylated (PEG) interferons (IFN), therapy of chronic hepatitis C (genotype 1) remains unsatisfactory. The initial viral response to IFN identifies patients infected with IFN resistant viruses not responding to standard IFN/ribavirin therapy. The impact of primary IFN unresponsiveness for PEG‐IFN‐α‐2a/ribavirin therapy is unknown. Viral load was measured in 22 chronic hepatitis C (genotype 1) patients before and 24 h after 9 MU IFN‐α‐2a (days 0 and 1), and before and during weekly 180 μg PEG‐IFN‐α‐2a (days 7, 8, 11, 14 and 21) administration. Thereafter, ribavirin (800 mg/d) was added for 6 months. Virological responders continued treatment for a further 6 months. Twenty‐eight patients treated with standard IFN/ribavirin therapy in a previous study using an analogous protocol served as historic controls. After 6 months 15 (68.2%) patients were (HCV‐RNA) negative, eight of whom (36.4%) had a sustained response. The decrease in viral load 24 h after 9 MU IFN‐α‐2a was greater in virological responders (1.05 log [0.25–1.67]) than in nonresponders (NR) (0.34 [0.14–0.65]; P=0.003). In contrast, viral decline was not different between responders and NRs during the first 2 weeks on PEG‐IFN‐α‐2a. All patients with an initial decline > 1.4 log became sustained responders. Five of 12 patients with a log change < 0.8 became end of treatment responders, two had a sustained response. Antiviral response to PEG‐IFN‐α‐2a is different to that on standard IFN. In spite of a lower initial response PEG‐IFN‐α‐2a/ribavirin combination therapy may overcome predicted IFN unresponsiveness.