Involvement of interferon-alpha in the regulation of apoptosis of cells of the hypothalamo-hypophyseal-adrenocortical system of aged mice in oxidative stress

The aim of this study was to identify the involvement of interferon-alpha (IA) in controlling apoptosis of cells of the hypothalamo-hypophyseal-adrenocortical system (HHACS) in young and aged mice in conditions of hyperoxia. Oxidative stress led to increases in the numbers of cells synthesizing the proapoptotic protein c-fos in the paraventricular nucleus in mice of both age groups. However, the protective actions of IA in stress were more marked at the earlier stage of apoptosis in young mice. Thus, the level of involvement of IA in controlling programmed cell death of hypothalamic cells depends on the age of the animals. In the fascicular zone of the adrenals in young mice, the number of dying cells was significantly greater after administration of IA, but remained at the control level in conditions of hyperoxia alone and in combination with IA. The proportion of apoptotic cells in the adrenals of aged mice was no different from that in young mice and did not change in response to any of the treatments used.Translated from Morfologiya, Vol. 125, No. 1, pp. 23–26, January–February, 2004.     

The role of hypothalamo-hypophyseal-adrenocortical system hormones in controlling pain sensitivity

The present review addresses analysis of data demonstrating the role of the hypothalamo-hypophyseal-adrenocortical axis (HHACA) in controlling pain sensitivity. Experiments on rats have demonstrated the analgesic effects of exogenous hormones of all components of the HHACA — corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and glucocorticoids — in the same models, and have also shown that the opioid and non-opioid mechanisms contribute to the development of the analgesia induced by these hormones. Endogenous glucocorticoids are involved in the development of analgesia mediated by non-opioid mechanisms. Along with the non-opioid mechanisms associated with endogenous glucocorticoids, the analgesic effect of ACTH can be mediated by the opioid mechanism. Unlike the situation with ACTH, the analgesic effect of CRH is mediated exclusively by non-opioid mechanisms, one of which is associated with HHACA hormones, while the other, appearing only on systemic administration, is not associated with these hormones. The actions of glucocorticoids on pain are mediated by neurons in the central gray matter of the midbrain. __________ Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 93, No. 11, pp. 1252–1262, November, 2007.     

内质网应激激活P38通路诱导胃癌细胞对多柔比星产生耐药

目的:在二维及三维细胞培养模式下探讨内质网应激能否诱导胃癌细胞对多柔比星产生耐药及其可能机制。方法:本研究利用贴壁培养的胃癌细胞,采用流式细胞仪检测对照组、内质网应激诱导剂组、多柔比星组及内质网应激诱导剂加多柔比星组的细胞凋亡率;并检测P38通路受阻能否逆转内质网应激诱导胃癌细胞对多柔比星的耐药现象。利用前期建立的胃癌细胞三维培养模型,用流式细胞仪及live/dead assay进一步验证以上结果。结果:在贴壁培养模式下,与对照组相比,各药物处理组胃癌细胞的凋亡率均明显增高,多柔比星组细胞凋亡率显著高于内质网应激诱导剂加多柔比星组;且P38活化受阻可基本恢复内质网应激状态下胃癌细胞对多柔比星的敏感性。在三维培养模式下,流式细胞仪及live/dead assay检测结果与贴壁培养条件下一致。结论:在二维及三维培养模式下,内质网应激均可通过激活P38通路诱导胃癌细胞对化疗药物多柔比星产生耐药,阻断该通路可基本抑制内质网应激诱导胃癌细胞对该化疗药物的耐药现象。     

Palmitoylcarnitine, and important component of the repair system in the synaptosome membrane, in oxidative stress

Oxidative stress is accompanied by a considerable rise of palmitic acid incorporation into phosphatidylethanolamine of synaptosome membranes due to activation of lysophosphatidylethanolamine palmitoyltransferase and carnitine palmitoyltransferase. In the absence of ATP carnitine palmitoyltransferase plays an essential role in reacylation of phosphatidylethanolamine, and palmitoylcarnitine serves as a reserve pool of palmitoyl coenzyme A. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 123, No. 6, pp. 649–652, June, 1997     

Tightly controlled response to oxidative stress; an important factor in the tolerance of Bacteroides fragilis

The exposure of Bacteroides fragilis to highly oxygenated tissues induces an oxidative stress due to a shift from the reduced condition of the gastrointestinal tract to an aerobic environment of host tissues. The potent and effective responses to reactive oxygen species (ROS) make the B. fragilis tolerant to atmospheric oxygen for several days. The response to oxidative stress in B. fragilis is a complicated event that is induced and regulated by different agents. In this review, we will focus on the B. fragilis response to oxidative stress and present an overview of the regulators of responses to oxidative stress in this bacterium.     

Activation of the anticlotting system by prethrombin 2, a thrombin precursor

Prethrombin 2, the direct precursor of thrombin, was obtained by restricted proteolysis of prethrombin 1 by trypsin or by active factor X. In the absence of enzymes, prethrombin 1 is not converted into prethrombin 2. Factor V was shown not to affect the rate of thrombin generation from prethrombin 2. It was shown that prethrombin 2 has no intrinsic coagulating or esterase activity. After intravenous injection of preparations of prethrombin 2, the plasma recalcification time was lengthened and total fibrinolytic activity and nonenzymic fibrinolysis were increased. A considerable increase also was found in the activity of the fibrinogen-heparin complex. These results are evidence of excitation of the anticlotting system by intravenous injection of small doses of prethrombin 2.Laboratory of Physiology and Biochemistry of Blood Clotting, M. V. Lomonosov Moscow University. (Presented by Academician of the Academy of Medical Sciences of the USSR S. E. Severin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 89, No. 3, pp. 270–272, March, 1980.     

Problems in the use of the galvanic skin response (GSR) as an index of cerebral function: implications of the latent period

When does the GSR indicate cortical, subcortical, spinal, sympathetic, or purely peripheral function? The neural activity initiating the response necessarily precedes it during the latent period. Since the time required for nerve conduction is shown to occupy only a portion of the period from stimulus to detectable response, there is abundant opportunity for central participation. Cortical activity, as shown by familiar EEG a-blocking, follows almost any attention-getting or semantic stimulus and typically occurs during the latent period before the appearance of an observable GSR. Rapid diphasic reversal of EEG phase relations suggestive of “intersociative” interplay between cortical areas occurs during the GSR latent period and even precedes blocking, providing further indication of cortical contribution to GSRs resulting from high level associative activity.     

Three-dimensional stress analysis for the mechanics of plantar ulcers in diabetic neuropathy

In diabetic neuropathic subjects, the hardness of foot sole soft tissue increases, and its thickness reduces, in different foot sole areas. Finite element analysis (FEA) of a three-dimensional two-arch model of the foot was performed to evaluate the effect of foot sole stresses on plantar ulcer development. Three sets of foot sole soft-tissue properties, i.e. isotropic (with control hardness value), diabetic isotropic (with higher hardness value) and anisotropic diabetic conditions, were simulated in the push-off phase, with decreasing foot sole soft-tissue thicknesses in the forefoot region, and the corresponding stresses were calculated. The results of the stress analyses for diabetic subject (anisotropic) foot models showed that, with non-uniformly increased hardness and decreased foot sole soft-tissue thickness, the normal and shear stresses at the foot sole increased (compared with control values) by 52.6% and 53.4%, respectively. Stress analyses also showed high ratios of gradients of normal and shear stresses of the order of 6.6 and 3.3 times the control values on the surface of the foot sole, and high relative values of stress gradients for normal and shear stresses of 6.25 and 4.35 times control values, respectively, between the foot sole surface and the adjacent inner layer of the foot sole, around a particular region of the foot sole with anisotropic properties. These ratios of high gradients and relative gradients of stresses due to changes in softtissue properties may be responsible for the development of plantar ulcers in diabetic neuropathic feet.     

Wall shear stress as measured in vivo: consequences for the design of the arterial system

Based upon theory, wall shear stress (WSS), an important determinant of endothelial function and gene expression, has been assumed to be constant along the arterial tree and the same in a particular artery across species. In vivo measurements of WSS, however, have shown that these assumptions are far from valid. In this survey we will discuss the assessment of WSS in the arterial system in vivo and present the results obtained in large arteries and arterioles. In vivo WSS can be estimated from wall shear rate, as derived from non-invasively recorded velocity profiles, and whole blood viscosity in large arteries and plasma viscosity in arterioles, avoiding theoretical assumptions. In large arteries velocity profiles can be recorded by means of a specially designed ultrasound system and in arterioles via optical techniques using fluorescent flow velocity tracers. It is shown that in humans mean WSS is substantially higher in the carotid artery (1.1–1.3 Pa) than in the brachial (0.4–0.5 Pa) and femoral (0.3–0.5 Pa) arteries. Also in animals mean WSS varies substantially along the arterial tree. Mean WSS in arterioles varies between about 1.0 and 5.0 Pa in the various studies and is dependent on the site of measurement in these vessels. Across species mean WSS in a particular artery decreases linearly with body mass, e.g., in the infra-renal aorta from 8.8 Pa in mice to 0.5 Pa in humans. The observation that mean WSS is far from constant along the arterial tree implies that Murray’s cube law on flow-diameter relations cannot be applied to the whole arterial system. Because blood flow velocity is not constant along the arterial tree either, a square law also does not hold. The exponent in the power law likely varies along the arterial system, probably from 2 in large arteries near the heart to 3 in arterioles. The in vivo findings also imply that in in vitro studies no average shear stress value can be taken to study effects on endothelial cells derived from different vascular areas or from the same artery in different species. The cells have to be studied under the shear stress conditions they are exposed to in real life.     

Traumatic stress and the autonomic brain-gut connection in development: Polyvagal Theory as an integrative framework for psychosocial and gastrointestinal pathology

A range of psychiatric disorders such as anxiety, depression, and post-traumatic stress disorder frequently co-occur with functional gastrointestinal (GI) disorders. Risk of these pathologies is particularly high in those with a history of trauma, abuse, and chronic stress. These scientific findings and rising awareness within the healthcare profession give rise to a need for an integrative framework to understand the developmental mechanisms that give rise to these observations. In this paper, we introduce a plausible explanatory framework, based on the Polyvagal Theory (Porges, Psychophysiology, 32 , 301–318, 1995; Porges, International Journal of Psychophysiology, 42 , 123–146, 2001; Porges, Biological Psychology, 74 , 116–143, 2007), which describes how evolution impacted the structure and function of the autonomic nervous system (ANS). The Polyvagal Theory provides organizing principles for understanding the development of adaptive diversity in homeostatic, threat-response, and psychosocial functions that contribute to pathology. Using these principles, we outline possible mechanisms that promote and maintain socioemotional and GI dysfunction and review their implications for therapeutic targets.     

替米沙坦通过抑制胰岛内质网应激减少STZ致长期高脂喂养大鼠糖尿病的发生

目的:研究肾素血管紧张素Ⅱ受体阻断剂替米沙坦对长期高脂喂养大鼠链脲佐菌素(STZ)致糖尿病的发病率和胰岛β细胞功能的影响及其作用机制。方法:以高脂高热量饮食饲养Wistar大鼠,16周后以替米沙坦干预,24周后1次性给予小剂量STZ,注射STZ1周后行静脉胰岛素释放实验检测胰岛β细胞功能;采用反转录-聚合酶链反应及免疫组化法检测胰岛内质网应激因子及胰岛素的表达。结果:与高脂+STZ组相比,高脂+替米沙坦+STZ组大鼠糖尿病发病率明显下降,胰岛素最大分泌量增加了56.9%,早期胰岛素分泌指数(EISI)及急性胰岛素分泌反应(AIR)升高了1.98倍和0.88倍,β细胞内胰岛素表达量及胰岛素阳性表达细胞密度明显增加,胰岛β细胞内质网应激凋亡相关分子免疫球蛋白结合蛋白、C/EBP同源蛋白基因表达及Bax蛋白表达均显著下降。结论:肾素血管紧张素系统(RAS)阻断可以增强长期高脂喂养大鼠对STZ性糖尿病的抵抗性,减少β细胞内质网应激介导的凋亡因子的表达。减弱胰岛内质网应激可能是RAS阻断而改善β细胞功能、减少糖尿病发生的重要机制之一。