Effect of radioprotectors on cyclic AMP-dependent protein phosphorylation

The ability of radioprotectors (serotonin, aminoethylisothiouronium) in radioprotective doses to stimulate cyclic AMP-dependent phosphorylation of mouse liver cytosol and nuclear and spleen cytosol proteins in vivo was demonstrated. In experiments in vitro, the radioprotectors had no direct action on protein kinase activity or its stimulation by cyclic AMP. It is postulated on the basis of these results and those of previous investigations that activation of cyclic AMP-dependent phosphorylation is due to an increase in the intracellular cyclic AMP concentration under the influence of the radioprotectors.Laboratory of Radiation Biophysics, Department of Biophysics, Biological Faculty, Moscow State University. (Presented by Academician of the Academy of Medical Sciences of the USSR S. E. Severin.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 87, No. 3, pp. 230–232, March, 1979.     

Synaptic efficacy of inhibitory synapses in hypoglossal motoneurons after transection of the hypoglossal nerves

In cat hypoglossal motoneurons after axotomy the synaptic efficacy of inhibitory synapses made by the lingual nerve afferent fibers was studied. The amplitude of the short- and the long-lasting inhibitory postsynaptic potential produced in tongue protruder motoneurons 24 days after axotomy by stimulation of the lingual nerve was significantly reduced in size as compared with the control on the unoperated side. In most protruder motoneurons 40 days after axotomy a large excitatory postsynaptic potential and a spike was produced by stimulation of either the ipsilateral or the contralateral lingual nerve. We have demonstrated that the decline of synaptic efficacy of inhibitory synapses for the short-lasting inhibitory postsynaptic potential was more prominent than that for the long-lasting inhibitory potential in the motoneuron 24 days after axotomy. After the cut axons of protruder motoneurons were re-united to tongue muscles, we have demonstrated that the decline of synaptic efficacy of inhibitory synapses for the short-lasting inhibitory postsynaptic potential was less prominent than that in axotomized protruder motoneurons.     

内生致冷原对家兔内毒素性发热第二热相的影响

为验证内生致冷原(EC)能否影响内毒素(ET)性发热第二热相或热限水平,并确实脑脊液中cAMP水平是否与EC的降温作用有关,作者用90只新西兰兔进行实验。观察:①输注人尿或等量生理盐液对正常家免体温的影响,检测EC效应期血浆和脑脊液中cAMP的含量;②在第二热峰出现前输注人尿或生理盐液对第二热相的影响,检测EC效应期血浆及脑脊液中cAMP的含量。结果表明:①人尿明显降低正常家兔的直肠温度,而等量生理盐液则无此作用,且两者均引起血浆及脑脊液中cAMP浓度的明显下降,提示EC的降温作用与脑cAMP浓度下降可能无重要关系;②人尿(EC)抑制ET性发热第二热相的形成,从而降低热限水平,变双相热为单相热,同量生理盐水无此作用,两者都能降低血浆和脑脊液中cAMP的水平,但EC不及NS明显,表明EC抑制第二热相或降低热限水平的作用也与cAMP浓度变化无重要关系,作者推论cAMP不是ET性发热第二热相的唯一成因。     

Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons

Complement activation products are major components of the inflammatory response induced by cardiac surgery and cardiopulmonary bypass which contribute to postoperative organ dysfunction, fluid accumulation, and morbidity. Activation of the complement system occurs during extracorporeal circulation, during reperfusion of ischemic tissue, and after the formation of heparin-protamine complexes. In this study we examine the efficacy of Compstatin, a recently discovered peptide inhibitor of complement, in preventing heparin/protamine-induced complement activation in baboons. The study was performed in baboons because Compstatin binds to baboon C3 and is resistant to proteolytic cleavage in baboon blood (similar to humans); Compstatin inhibits only the activation of primates' complement system. After testing various doses and administration regimens, Compstatin produced complete inhibition at a total dose of 21 mg/kg when given as a combination of bolus injection and infusion. Compstatin completely inhibited in vivo heparin/protamine-induced complement activation without adverse effects on heart rate or systemic arterial, central venous, and pulmonary arterial pressures. This study indicates that Compstatin is a safe and effective complement inhibitor that has the potential to prevent complement activation during and after clinical cardiac surgery. Furthermore, Compstatin can serve as the prototype for designing an orally administrated drug.     

家兔葡萄球菌性发热及其热限的探讨

采用加热杀死的白色葡萄球菌菌体作激活物,给家兔耳缘静脉注射,观察剂量-发热效应,血浆EP的活性以及血浆和脑脊液中cAMP含量变化。结果表明,在一定的范围内,随剂量递增,发热效应相应加强,但达到一定浓度,可出现热限;发热时,血浆可检出循环EP;血浆致热活性,脑脊液cAMP含量随发热效应增强而升高,出现热限时,则不再升高。作者推论:cAMP可能是葡萄球菌性发热的重要中枢介质;EP的产生释放受限和体温调节中枢内cAMP的产生受限可能是构成葡萄球菌性热限的重要因素。     

The pharmacology of fever

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.