The ability to minimise, if not prevent, large variations in deep body temperature that would otherwise result from some environmental conditions is a homeostatic function of unquestioned benefit that is demonstrated only by the more highly evolved animals. Nevertheless, body temperature is raised above normal values in many pathological conditions. This increase in temperature or fever is an active and co-ordinated response, which indicates the involvement of the CNS. Central injection and lesion studies have shown that the brain, in particular the PO/AH, is the site of action of fever-inducing agents, termed pyrogens. Electrophysiological data show that pyrogens modify the activity of central thermosensitive neurones as if to increase heat gain and decrease heat loss. The common response of fever to pyrogens of diverse origins is attributable to fever being mediated by an endogenous pyrogen released by phagocytic cells in the host. The mechanism by which central neuronal function is disturbed by pyrogens present in the periphery is not known. Tracer studies have yet to demonstrate the passage of a pyrogen across the blood-brain barrier. The possible involvement of several putative neuro- transmitters and modulators in fever has been reviewed here, but most compounds have not been studied sufficiently to allow firm conclusions to be drawn. Much of the data is limited to the effects of the putative mediators on normal thermoregulation but, even when the effect is hyperthermia, such observations do not necessarily indicate a role for the endogenous material in fever. Dose-response curves for agonists and the effects of antagonists are often undetermined. This shortfall in data is due to some extent to the nature of fever; a central response in vivo over several hours. Although fever may enhance other host reactions to combat infection and inflammation, neither this benefit nor the undesirability of antipyretic therapy has been demonstrated unequivocally in either homeothermic laboratory animals or humans. Consequently, antipyretic drugs continue to be used clinically to alleviate the fever, malaise and/or pain commonly associated with disease. The drugs in common usage are the nonsteroidal antipyretic analgesics, many of which also have an anti-flammatory effect. The primary mode of action of these drugs as antipyretics appears at present to be the inhibition of cyclo-oxygenase and a consequent reduction of prostanoid material in pyrogen-sensitive areas of the brain. PGEs in the PO/AH have received most study to date, but other mediators in other parts of the CNS, where the density of pyrogen receptors may be sparse, cannot be discounted and await further investigation. 相似文献
Neuropeptide Y (NPY) has at least three receptors (Y1, Y2 and Y3) through which it influences different mechanisms in many cell types. Previous data suggest that the Y2 receptor may be divided into prejunctional and postjunctional subgroups. We have examined the intracellular signalling pathways of the postjunctional Y2 receptor in rat renal proximal tubules. The results indicate that NPY regulates Na+,K+-ATPase through several signalling pathways: (1) In proximal tubule (PT) cells NPY increased intracellular calcium. The response was blocked by removing extracellular calcium and was also blocked by using nifedipine. This suggests that calcium was increased by influx from the extracellular space through L -type calcium channels. (2) NPY increased Na+,K+-ATPase activity in PT segments and this effect was also blocked by nifedipine. CaMKII-Ala286[281–302] a blocker of Ca2+/calmodulin-dependent protein kinase II (CaMKII) inhibited the NPY-stimulated Na+,K+-ATPase activity. This implies that increased intracellular calcium activates CaMKII which subsequently increases Na+,K+-ATPase activity. CaMKII thus appear to act similar to what has been proposed for protein phosphatase 2B. (3) Calphostin C, an inhibitor of protein kinase C (PKC), did not inhibit NPY-stimulated Na+,K+-ATPase activity. PKC is, therefore, unlikely to be involved. (4) Y2 receptors are negatively coupled to the cAMP pathway. NPY attenuated forskolin-stimulated cAMP production in renal tubules and exogenous cAMP counteracted the NPY-stimulated Na+,K+-ATPase activity. This illustrated the importance of NPY for the regulation of renal sodium handling. We also propose that the renal tubule cell is a good model for studying the function and mechanisms of postjunctional Y2 receptors. 相似文献
The neurotoxic actions of kainate were examined in incubated slices of adult and immature rat cerebellum using light- and electron-microscopy. In the adult, Purkinje cells and inhibitory interneurones became selectively necrotic at concentrations between 5 micro M and 20 micro M. At 30 micro M, granule cells also became affected. In the immature cerebellum, at an age (8 days after birth) when the parallel fibres (thought to use glutamate as transmitter) are largely yet to be developed, selective toxicity was still evident but Purkinje cells and inhibitory interneurones were about 10-fold, and granule cells about 30-fold, less sensitive to kainate than in the adult. Kainate and other excitotoxins also increased cyclic GMP levels in cerebellar slices, apparently through the activation of excitatory amino acid receptors. In the adult tissue, the dose-cyclic GMP response curve to kainate was biphasic suggesting the presence of two components. The lower concentrations of kainate eliciting the first component mirrored those inducing selective necrosis of Purkinje cells and inhibitory interneurones while the second component correlated with necrosis of granule cells. Similar correlations applied to the immature cerebellum, but here kainate neurotoxicity appeared to be associated with the activation of receptor types different from those evident in the adult. It is suggested that kainate receptors, whose activation is associated with both neurotoxic damage and elevation of cyclic GMP levels, are located on all cell types in the adult cerebellum, with Purkinje cells and inhibitory interneurones displaying a higher sensitivity to kainate than granule cells. The lower sensitivity of immature cerebellum to the neurotoxic effect of kainate is probably due to lower levels of kainate receptors. 相似文献
The hydrolytic interfacial polycondensation of bisphenol‐A‐bischloroformate was performed with four different phase‐transfer (PT) catalysts: N‐butylpyridinium bromide, triethylbenzylammonium (TEBA) chloride, tetrabutylammonium hydrogen sulfate, and tetraphenylphosphonium bromide. These polycondensations were conducted at 5 or 35 °C initial reaction temperature. The resulting polycarbonates were characterized by viscosity and SEC measurements and by MALDI‐TOF mass spectrometry. The four PT catalysts gave quite different results with respect to molecular weight and formation of cyclic polycarbonates. The highest molecular weights (number average, and weight average, ) were obtained with TEBA‐Cl. Lower temperatures and high feed ratios of TEBA‐Cl proved to be favorable for both high molecular weights and high fractions of cycles. Cyclic polycarbonates were detectable in the mass spectra up to 14 kDa (technical limit of the measurements). Low molecular weights in combination with unreacted chloroformate groups proved that the other PT‐catalysts were less efficient under the given reaction conditions.
MALDI‐TOF mass spectrum of the polycarbonate No. 3b . 相似文献