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To study their thermal responses to climatic stress, we implanted seven greater kudu (Tragelaphus strepsiceros) with intra-abdominal, brain, carotid, and subcutaneous temperature data loggers, as well as an activity logger. Each animal was also equipped with a collar holding a miniature black globe thermometer, which we used to assess thermoregulatory behavior. The kudu ranged freely within succulent thicket vegetation of the Eastern Cape Province, South Africa. The kudu spontaneously developed a bacterial pneumonia and consequent fever that lasted between 6 and 10 days. The fever was characterized by a significant increase in mean 24-h abdominal temperature from 38.9 [+ or -] 0.2[degrees]C to 40.2 [+ or -] 0.4[degrees] C (means [+ or -] SD, [t.sub.6] = 11.01, P < 0.0001), although the amplitude of body temperature rhythm remained unchanged ([t.sub.6] = 1.18, P = 0.28). Six of the kudu chose warmer microclimates during the fever than when afebrile (P < 0.0001). Despite the selection of a warmer environment, on the first day of fever, the abdominal-subcutaneous temperature difference was significantly higher than on afebrile days ([t.sub.5] = 3.06, P = 0.028), indicating vasoconstriction. Some kudu displayed increased frequency of selective brain cooling during the fever, which would have inhibited evaporative heat loss and increased febrile body temperatures, without increasing the metabolic maintenance costs of high body temperatures. Average daily activity during the fever decreased to 60% of afebrile activity ([t.sub.6] = 3.46, P = 0.014). We therefore have recorded quantitative evidence for autonomic and behavioral fever, as well as sickness behavior, in the form of decreased activity, in a free-living ungulate species. selective brain cooling; thermoregulation

By cooling the hypothalamus during hyperthermia, selective brain cooling reduces the drive on evaporative heat loss effectors, in so doing saving body water. To investigate whether selective brain cooling was increased in dehydrated sheep, we measured brain and carotid arterial blood temperatures at 5-min intervals in nine female Dorper sheep (41 [+ or -] 3 kg, means [+ or -] SD). The animals, housed in a climatic chamber at 23[degrees]C, were exposed for nine days to a cyclic protocol with daytime heat (40[degrees]C for 6 h). Drinking water was removed on the 3rd day and returned 5 days later. After 4 days of water deprivation, sheep had lost 16 [+ or -] 4% of body mass, and plasma osmolality had increased from 290 [+ or -] 8 to 323 [+ or -] 9 mmol/kg (P < 0.0001). Although carotid blood temperature increased during heat exposure to similar levels during euhydration and dehydration, selective brain cooling was significantly greater in dehydration (0.38 [+ or -] 0.18[degrees]C) than in euhydration (-0.05 [+ or -] 0.14[degrees]C, P = 0.0008). The threshold temperature for selective brain cooling was not significantly different during euhydration (39.27[degrees]C) and dehydration (39.14[degrees]C, P = 0.62). However, the mean slope of lines of regression of brain temperature on carotid blood temperature above the threshold was significantly lower in dehydrated animals (0.40 [+ or -] 0.31) than in euhydrated animals (0.87 [+ or -] 0.11, P = 0.003). Return of drinking water at 39[degrees]C led to rapid cessation of selective brain cooling, and brain temperature exceeded carotid blood temperature throughout heat exposure on the following day. We conclude that for any given carotid blood temperature, dehydrated sheep exposed to heat exhibit selective brain cooling up to threefold greater than that when euhydrated. thermoregulation; body temperature; evaporative heat loss doi: 10.1152/ajpregu.00074.2007

Neurophysiological studies have shown that serotonergic ligands that bind to 5-H[T.sub.1A], 5-H[T.sub.7], and 5-H[T.sub.4] serotonin receptors in brain stem have beneficial effects on respiratory neurons during opioid-induced respiratory depression. The effect of these ligands on respiratory function and pulmonary performance has not been studied. We therefore examined the effects of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), an agonist of 5-H[T.sub.1A] and 5-HT7 receptors, and zacopfide, an agonist of 5-H[T.sub.4] receptors, to establish whether these ligands would reverse opioid-induced respiratory depression and hypoxia without affecting the immobilizing properties of the opioid drug etorphine. When etorphine was used to sedate and immobilize goats, it significantly decreased respiratory rate (P = 0.013), percent hemoglobin oxygen saturation (P < 0.0001), and arterial oxygen partial pressure [Pa.sub.[O.sub.2]]; [F.sub.(10,70)] = 5.67, P < 0.05] and increased arterial carbon dioxide partial pressure [[F.sub.(10,70)] = 3.87, P < 0.05] and alveolar-arterial oxygen partial pressure gradient [A-a gradients; [F.sub.(10,70)] = 8.23, P < 0.0001]. Zacopride and 8-OH-DPAT, coadministered with etorphine, both attenuated the effects of etorphine; respiration rates did not decrease, and percent hemoglobin oxygen saturation and [Pa.sub.[O.sub.2]] remained elevated. Zacopride decreased the hypercapnia, indicating an improvement in ventilation, whereas 8-OH-DPAT did not affect the hypercapnia and, therefore, did not improve ventilation. The main beneficial effect of 8-OH-DPAT was on the pulmonary circulation; it improved oxygen diffusion, indicated by the normal A-a gradients, presumably by improving ventilation perfusion ratios. Neither zacopride nor 8-OH-DPAT reversed etorphine-induced catatonic immobilization. We conclude that serotonergic drugs that act on 5-H[T.sub.1A], 5-H[T.sub.7], and 5-H[T.sub.4] receptors reverse opioid-induced respiratory depression and hypoxia without reversing catatonic immobilization. serotonin; etorphine; ventilation; alveolar-arterial oxygen partial pressure gradients

This study aimed at elucidating an optimal synergistic polymer composite for achieving a desirable molecular bioadhesivity and Matrix Erosion of a bioactive-loaded Intravaginal Bioadhesive Polymeric Device (IBPD) employing Molecular Mechanic Simulations and Artificial Neural Networks (ANN). Fifteen lead caplet-shaped devices were formulated by direct compression with the model bioactives zidovudine and polystyrene sulfonate. The Matrix Erosion was analyzed in simulated vaginal fluid to assess the critical integrity. Blueprinting the molecular mechanics of bioadhesion between vaginal epithelial glycoprotein (EGP), mucin (MUC) and the IBPD were performed on HyperChem 8.0.8 software (MM+ and AMBER force fields) for the quantification and characterization of correlative molecular interactions during molecular bioadhesion. Results proved that the IBPD bioadhesivity was pivoted on the conformation, orientation, and poly(acrylic acid) (PAA) composition that interacted with EGP and MUC present on the vaginal epithelium due to heterogeneous surface residue distributions (free energy= −46.33 kcalmol−1). ANN sensitivity testing as a connectionist model enabled strategic polymer selection for developing an IBPD with an optimally prolonged Matrix Erosion and superior molecular bioadhesivity (ME = 1.21-7.68%; BHN = 2.687-4.981 N/mm2). Molecular modeling aptly supported the EGP-MUC-PAA molecular interaction at the vaginal epithelium confirming the role of PAA in bioadhesion of the IBPD once inserted into the posterior fornix of the vagina. [ABSTRACT FROM AUTHOR]

Context and Objective: To screen various polymers through extensive preformulation investigations to ultimately obtain a lead polymer combination for designing a desirable Intravaginal Bioadhesive Polymeric Device (IBPD). Materials and methods: Hydrophilic and hydrophobic polymers (18) at different combinations were blended and compressed into 62 caplet-shaped devices at 5 tons, one of the hydrophilic polymers being a modified synthetic product of polyamide 6,10 (mPA 6,10). Two sets of crosslinked PAA-based caplets comprising either allyl-sucrose (AS-PAA) or allyl-penta-erythritol (APE-PAA) were explored. The devices were subjected to in-process validation tests and thereafter to preformulation investigational screening {{equilibrium swelling ratio (ESR) being a screening parameter}}, using a One Variable at a Time (OVAT) approach. Molecular mechanics force field simulations in both vacuum and solvated systems were conducted to investigate the influence of addition and subsequent replacement of a polymer(s) on the spatial disposition and energetic profile of the sterically constrained and geometrically optimized multi-polymeric complex, IBPD. Results and discussion: The developed devices were sufficiently strong (longitudinal crushing force:286 ± 0.01 N; mean weight:600 ± 0.48 mg; mean friability:0.31 ± 0.04%). Through OVAT approach, 15 lead formulations with minimal swelling tendencies (ESRs ranging from 0.011 to 0.084) were obtained out of 62 formulations. F62 {{i.e. mPA 6,10, (150 mg), PLGA (400 mg), EC (200 mg), PVA (25 mg) and PAA (25 mg)}} displayed minimal swelling tendency and therefore the highest stability. The highly stabilized conformation of the final in silico IBPD polymeric assembly PLGA-mPA6,10-PVA-PAA-EC corroborated the experimental results in terms of preformulation investigational screening using the OVAT approach. Conclusion: The results obtained suggest that mPA 6,10, PLGA, EC, PVA and PAA at an appropriate weight ratio may be suitable for development of an IBPD. [ABSTRACT FROM AUTHOR]