The Acoustic Startle Response in Inbred Roman High- and Low-Avoidance Rats

To investigate the emotional reactions of two rat strains selectively bred for good and poor two-way avoidance acquisition (RHA/Verh and RLA/Verh), male animals of both strains were tested in an acoustic startle response test. They received 40 acoustic stimuli followed by 10 electric foot shocks and another 30 acoustic stimuli. RLA/Verh rats showed a significantly higher startle response compared to RHA/Verh animals, indicating a stronger emotional reaction to acoustic stimuli. In addition, the former showed a stronger response to foot shocks. Combined with earlier findings, we conclude that selection for two-way avoidance learning does not result in cognitive defects in the RLA/Verh strain but, rather, in stronger emotional reactions to fearful stimuli.     

Influence of an established acute phase response on the severity of experimental nephritis.

Small doses of lipopolysaccharide (LPS) induced an acute phase response (APR), and a number of studies have also shown that this greatly enhances the severity of glomerular injury in the heterologous phase of nephrotoxic nephritis (hNTN), an experimental model of anti-glomerular basement membrane (GBM) disease. Here, we examined the influence of pre-existing subclinical infection and raised APR, assessed by plasma alpha 2-macroglobulin (alpha 2-M) concentration, on the degree of injury in this model of nephritis. Studies were initially performed to determine the normal range of alpha 2-M in rats and its modulation by IL-6 and different doses of LPS. Plasma concentration of alpha 2-M was found to be variable and dependent on the weight of the rats. Single injections of either LPS or IL-6 had a comparable effect, and continuous perfusions of LPS caused a progressive increase in alpha 2-M which peaked at 48 h and declined gradually over 1 week. Following induction of nephritis with 10 mg of anti-GBM antibody, rats with raised alpha 2-M had 14 +/- 3 mg/24 h albuminuria compared with 4 +/- 1 mg/24 h in rats with normal alpha 2-M (P < 0.001, Wilcoxon). Injection of 20 mg anti-GBM antibody caused 36 +/- 11 mg/24 h albuminuria compared with 16 +/- 4 mg/24 h (P < 0.001), respectively. However, all these rats remained active and none of them died. In contrast, injection of 0.25 microgram LPS before induction of nephritis with 10 mg anti-GBM antibody, in rats with raised alpha 2-M, caused severe albuminuria (115 +/- 23 mg/24 h) compared with rats having normal levels of alpha 2-M (72 +/- 15 mg/24 h, P < 0.05). Furthermore, rats with raised alpha 2-M also had severe systemic manifestations characterized by pulmonary haemorrhage and extensive glomerular thrombosis, and many of them died. These results demonstrate the potential effect of pre-existing subclinical infection and raised APR on severity of glomerular injury which may affect the outcome of experimental studies.     

急性丙型肝炎患者免疫状况的研究

用间接免疫荧光法、酶联免疫吸附试验（ＥＬＩＳＡ）及ＬＤＨ释法，对１６例急性输血后丙型肝炎（抗－ＨＣＶ、ＨＣＶ－ＲＮＡ均阳性）患者，分别进行外周血单个核细胞（ＰＢＭＣ）的Ｔ细胞亚群计数、Ｔ４／Ｔ８比值、Ｔａｃ受体的检测及血清可溶性白细胞介素２受体（ｓＩＬ－２Ｒ）ＮＫ细胞活性的测定。并与正常人组比较，经ｔ检验发现，急性丙型肝炎患者的Ｔ４亚群所占百分比、Ｔ４／Ｔ８比值及ＰＢＭＣＴａｃ受体表达均明显低于正常人组（Ｐ＜０．０５），而ＮＫ细胞活性、血清ｓＩＬ－２Ｒ明显高于正常人组（Ｐ＜０．０５）。患者的这些免疫状态改变，可能对其发病机理的研究有一定意义。     

High vs low anxiety-related behavior rats: an animal model of extremes in trait anxiety

In addition to their robust difference in trait anxiety, as illustrated by a variety of behavioral tests, HAB and LAB rats differ in their stress coping strategies, the former being more susceptible and vulnerable to stressor exposure and preferring more passive strategies. HAB rats of either gender show signs of a hyper-reactive hypothalamic-pituitary-adrenocortical (HPA) axis, thus resembling psychiatric patients. As shown by in situ hybridization and microdialysis in freely behaving animals, both the expression and release of vasopressin in the hypothalamic paraventricular nucleus are higher in HAB than in LAB rats, thus contributing to the HPA axis hyperdrive. Accordingly, in HAB animals, administration of a V1 receptor antagonist normalized the pathological outcome of the dexamethasone/corticotropin-releasing hormone test and triggered behavioral changes toward reduced anxiety and active stress coping. Pharmacological validation has revealed signs of depressive-like behavior, as HAB but not LAB rats have shown more active stress coping behavior and a normalized HPA axis after treatment with paroxetine. Of interest, this antidepressant reduced the hypothalamic overexpression of vasopressin; this novel mechanism of action is likely to contribute to paroxetine effects on both behavioral and neuroendocrine parameters. Cross-mating and cross-fostering paradigms showed that the divergent emotionality in HAB vs. LAB rats is determined genetically, rather than postnatally through maternal behavior. As the behavioral and neuroendocrine phenotyping pointed to the vasopressin gene as a candidate gene critically involved in anxiety, preliminary genetic approaches have been focused on this gene, revealing single nucleotide polymorphisms (SNPs) in the promotor area of the vasopressin gene in HAB, but not LAB rats. HAB/LAB rats are thus proving to be a unique animal model to identify and characterize neurobiological, neuroendocrine, and genetic correlates of trait anxiety, and perhaps depression, in humans.     

Effect of adaptation to anoxia on antioxidative enzyme activity in the liver of stressed animals

All-Union Cardiologic Scientific Center, Academy of Medical Sciences of the USSR. Research Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Grenburg Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR I. K. Shkhvatsabaya.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 106, No. 11, pp. 528–529, November, 1988.     

Quantitation of antigen-specific immune responses in human immunodeficiency virus (HIV)-infected individuals by limiting dilution analysis

The lymphocyte proliferative response to recall antigens is lost following HIV infection. We sought to devise a means by which the functional immune status of persons in the early stages of HIV infection could be monitored quantitatively. The response to tetanus toxoid was examined in 45 HIV-infected individuals and 11 controls using conventional lymphocyte proliferative assays concurrently with limiting dilution analysis utilizing the secretion of interleukin-2 as the measure of a response. Our data show that the limiting dilution analysis detects tetanus toxoid-reactive T cells in 80% of those tested, as compared to only 44% by proliferation. However, the frequency of tetanus-reactive T cells in HIV-infected individuals (median frequency = 1/59,156) is decrease five-fold as compared to seronegative controls (median frequency = 1/11,599). Longitudinal studies demonstrated a time-dependent decrease in the frequency of tetanus-specific T cell responses in the HIV-infected individuals. Thus, the limiting dilution analysis is a quantitative approach for detecting antigen-specific T cells in HIV-infected individuals, and may be used to monitor changes in T cell function in HIV infection.     

Urodilatin: a new peptide with beneficial effects in the postoperative therapy of cardiac transplant recipients

Summary Renal failure after heart transplantation (HTx) still remains a serious problem, especially when cyclosporin A is used for immunosuppression in the early postoperative therapy. To preserve good renal function without reducing immunosuppressive cyclosporin A treatment, we administered urodilatin (CDD/ANP-95-126) in a long-term, low-dose infusion in addition to the usual medication after heart transplantation. From November 1990 to June 1991, 51 patients (46 male and 5 female; mean age 48 years) were treated with a 620 ng/kg bw·min infusion for 96 h after HTx. The renal function and hemodynamic parameters of these urodilatin-treated patients were compared in this sequential study with 40 patients (33 male and 7 female; mean age 49 years) who had undergone HTx previously from May to November, 1990, as controls. In this phase IIa study, both groups did not differ significantly with respect to age, sex, indication for HTx, and preoperative renal function. In comparison with controls patients treated with urodilatin had a significantly better renal function: a reduction in the peak plasma creatinine (PC values day 4 : 1.5 ± 0.11 vs. 2.19 ± 0.19 mg/dl; P = 0.002), a lower peak serum urea (SU values day 4 : 109 ± 8 vs. 154.7 ± 8.94 mg/dl ; P = 0.0036), and a lower incidence of hemodialysis (6% vs. 10%) were observed. Adequate diuresis was maintained in spite of the reduction of furosemide by more than 60% (P = 0.005) on each day of urodilatin infusion in comparison with controls. The mean central venous pressure was significantly lower by about 50% (P = 0.02) during the administration of urodilatin in spite of reduced vasodilator medication with nitroglycerin. From this phase IIa study, we may conclude that urodilatin could be an important drug in intensive care treatment. For patients undergoing HTx, this peptide seems to be indicated for the improvement of renal function and cardiovascular status, especially in postoperative therapy using high-dose cyclosporin A treatment.Abbreviations ACE angiotensin converting enzyme - ANP atrial natriuretic polypeptide - ATG antithymocyte globulin - bpm beats per minute - bw body weight - CDD cardiodilatin - CDD/ANP-99-126 circulating form of vasorelaxant cardiac peptide - CHD coronary heart disease - CyA cyclosporin A - DCM dilated cardiomyopathy - GLM general linear model - hANP human atrial natriuretic polypeptide - HTx heart transplantation - NTG nitroglycerine - PC plasma creatinine - SU serum urea - SAS statistical analysing system     

ERK1/2信号转导途径在低切应力上调人脐静脉内皮细胞IL-8基因表达中的作用

血管内皮细胞位于血流和血管壁之间,除受化学因素的调节外还受力学因素的影响。切应力可通过刺激相应的力学感受系统来调节内皮细胞某些基因的表达,其中包括诱导内皮细胞表达IL- 8。为了阐明MAPK信号途径中的ERK1/ 2信号通路是否参与调控低切应力上调人脐静脉内皮细胞IL- 8基因表达,采用Western blot分析了低切应力(4.2 0 dyne/ cm2 )处理不同时间内皮细胞ERK1/ 2的磷酸化水平及TPK抑制剂Genistein,MEK抑制剂PD980 5 9对其磷酸化的影响;采用定量RT- PCR检测内皮细胞经低切应力刺激或给予阻断剂后再行切应力刺激等处理后IL- 8基因的表达。结果显示:(1)低切应力处理可引起内皮细胞ERK1/ 2蛋白磷酸化水平上调,其磷酸化水平与切应力作用时间有关,具有快速、双向性的特点(在刺激10 min时达到高峰,2 h左右降至未刺激水平) ,阻断剂Genistein和PD980 5 9处理后,ERK1/ 2磷酸化水平与低切应力刺激10 min比较明显降低;(2 )阻断剂Genistein,PD980 5 9可显著抑制低切应力所致的内皮细胞IL- 8m RNA上调。结果表明低切应力可通过ERK1/ 2信号途径上调人脐静脉内皮细胞IL- 8基因的表达。     

Endothelial Regulation of Vascular Repair: Role of bFGF in Paracrine Pathways

Vascular repair following injury is mediated by both endothelial and smooth muscle cells often through paracrine pathways. Basic fibroblast growth factor (bFGF) is present at sites of vascular injury. The role of bFGF in regulating reendothelialization through an effect on centrosome redistribution in cell migration is discussed. The role of bFGF in neointimal formation, especially as it relates to smooth muscle cell proliferation, is reviewed. It is concluded that bFGF appears to be an important agent regulating the early responses of the artery wall to injury. Presented in part at the Molecular Endocrine Pathology Symposium at the International Academy of Pathology XXI International Congress, Budapest, Hungary, October 20–25, 1996.     

Comparison of the effects of 2-deoxyglucose and immobilization on secretion and synthesis rate of catecholamines in the adrenal gland: a microdialysis study in conscious rats

Using microdialysis, extracellular 3,4-dihydroxyphenylalanine (DOPA), noradrenaline (NA) and adrenaline (AD) concentrations in the adrenal gland were monitored in conscious rats during and after 60 min of immobilization (IMM) as well as after injection of 500 mg kg^-1 2-deoxyglucose (2-DG). IMM produced a rapid and transient increase in secretion of AD (20-fold), NA (13-fold) and DOPA (3.6-fold). This was accompanied by an increase in blood pressure (+ 18 mmHg) and heart rate (- 146 b. p.m.). Repeated exposure to IMM (daily 60 min, for 5 days) had no influence on either catecholamine secretion of haemodynamic profiles, indicating the lack of habituation to stressful conditions. Unlike IMM, the stress of 2-DG-induced centralneuroglucopenia stimulated the release of AD without affecting NA secretion. AD levels peaked (5.1-fold increase) 4&60 min after 2-DG injection and then slowly declined. 2-DG induced no changes in blood pressure but reduced the heart rate (-48 b. p.m.). In separate experiments, steady-state dialysate DOPA levels, reached during continuous infusion of decarboxylase inhibitor NSD 1015 into adrenal gland tissue through the dialysis probe, served as an index of adrenomedullary tyrosine hydroxylase (TH) activity. IMM evoked a marked increase in TH activity (DOPA formation increased 2.7-fold), which remained elevated 60 min after the cessation of stress when AD and NA secretion had already fallen to baseline. After 2-DG, despite significant hormonal response, adrenal TH activity was unchanged. These results give clear evidence that IMM and 2-DG-induced neuroglucopenia may be considered as two different types of stressful stimuli.