Excitatory effect of dehydroepiandrosterone, its sulphate ester and pregnenolone sulphate, applied by iontophoresis and pressure, on single neurones in the septo-preoptic area of the guinea pig

When dehydroepiandrosterone (D), its ester sulphate (DS) and pregnenolone sulphate (PS) were applied iontophoretically or by pressure to neurones in the septo-preoptic area, an excitatory effect was observed. DS and PS, applied on the same neurone, always produced a similar effect. When DS and D were tested, some neurones were excited by both steroids whereas others responded to DS but were unaffected by D. DS-, PS- and D-induced responses displayed a short latency in onset and offset, suggesting an action at the membrane level as for other steroids.     

Treg-Cell Control of a CXCL5-IL-17 Inflammatory Axis Promotes Hair-Follicle-Stem-Cell Differentiation During Skin-Barrier Repair

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Interaction between the immune and central nervous systems

Much of the understanding of tolerance has focused on the requirements for antigen-specific lymphocyte activation and function. However, there is increasing evidence for anatomic regulation of effector access to self antigens. Recently, a number of studies have provided evidence for tissue-specific “addressins” in chemokine/chemokine receptor pairs. The central nervous system (CNS) provides special anatomic barriers to the movement of cells from the vascular compartment to the parenchyma. Herein I raise the possibility that antigen, perhaps through specialized antigen-presenting cells, may play a role in regulating access of activated lymphocytes into the CNS parenchyma. The results suggest that a reexamination of the widely held dogma that all activated lymphocytes have access to the CNS parenchyma is nessary to understand the relationship between the immune and central nervous systems.     

Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis

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Changes in cerebral endothelial barrier antigen, without alteration of permeability for intravenously injected leptin in diet-induced obesity in rats

Leptin, a potent anorectic, 16-kDa, adipose tissue-derived protein, predominantly acts in hypothalamic nuclei, signaling obesity and modulating ingestive behavior. To reach this brain area, leptin, probably has to cross the blood-brain barrier (BBB). In some cases of obesity, enhanced leptin levels in the blood do not result in anorectic effects, probably due to an altered leptin transport across the BBB. Therefore, we investigated the BBB in lean and diet-induced obese Lewis rats. To obtain information about the presence of microvessels with barrier dysfunction we examined three brain areas (hypothalamus, cortex, hippocampus) using a monoclonal antibody which detects intact microvessels of the BBB (anti-endothelial barrier antigen, anti-EBA). The results showed a significantly reduced EBA staining in the brain sections of the obese animals, except the hippocampus, compared to the control group. In a second step we injected I125-labeled leptin intravenously (i.v.) in permanent i.v.-cannulated, unrestrained Lewis rats (lean and obese). We measured the radioactivity in the cerebrospinal fluid after puncture of the cisterna magna, in the blood and brain tissue 90 min after injection. The leptin content in the cerebrospinal fluid and brain was not reduced in obese compared to lean rats, thus showing a similar transport capacity of the BBB in both experimental groups. Therefore, the results of the in vivo investigations do not indicate an impairment of the BBB in diet-induced obesity, despite the immunohistological findings. Further functional and morphological studies are necessary to evaluate the specific role of other organs and distinct forms of leptin (free and protein-bound) in the pathogenesis of diet-induced obesity.     

Control of established experimental allergic encephalomyelitis by inhibition of tumor necrosis factor (TNF) activity within the central nervous system using monoclonal antibodies and TNF receptor-immunoglobulin fusion proteins

Tumor necrosis factor (TNF) activity was inhibited during the development of actively-induced, chronic relapsing experimental allergic encephalomyelitis (CREAE) in Biozzi AB/H mice, using a mouse TNF-specific (TN3.19.12) antibody and bivalent human p55 and p75 TNF receptor-immunoglobulin (TNFR-Ig) fusion proteins. The development of disease could be inhibited when repeated doses of antibody were administered prior to the anticipated onset. It has now also been shown that a therapeutic effect is evident even when antibody is administered after the onset of clinical signs, further indicating an important role for TNF in pathogenic effector mechanisms in CREAE. Although biologically-active TNF was not detected in the circulation, TNF-α was detected in lesions within the central nervous system (CNS). This suggested that the CNS may be the main site for TNF-specific immunomodulation and was supported by the observation that intracranial injection was significantly more potent than that administered systemically, for both antibody and TNFR-Ig fusion proteins. The fusion proteins were as effective as antibody at doses 10—100-fold lower than that used for antibody, reflecting their higher neutralizing capacity in vitro. Although treatment was not curative and relapse inevitably occurred in this model if treatment was not sustained, the data indicate that anti-TNF immunotherapy, especially within the CNS, can inhibit CREAE and may, therefore, be useful in the control of human neuroimmunological diseases.     

Rapid steady-state analysis of blood-brain glucose transfer in rat

A new kinetic analysis of blood-brain glucose transport is described, based on a steady-state model that takes account of cerebral blood flow, mean capillary glucose concentration, and cerebral metabolic rate. The maximal rate (T_max) and half-saturation constant (K_m) of glucose transport from blood to brain were determined in rats by measuring the rate of blood-to-brain glucose transfer at different blood glucose concentrations. Each determination lasted 20 seconds. For whole-brain, T_max and K_m averaged 258±33 (S.E.) μmol (100 g)^-1 min^-1 and 5.9±1.6 (S.E.) mmol 1^-1, respectively. The regional variations were insignificant. The new approach permits kinetic parameters to be measured locally in brain in rapidly changing functional states.     

CO对局灶性缺血脑组织血脑屏障通透性的影响

目的:研究一氧化碳及其限速酶(血红素氧合酶-1)对局灶性缺血脑组织血脑屏障通透性的影响。方法:将SD大鼠随机分为3组(n=6),使用血红素氧合酶诱导剂及抑制剂腹腔注射,用等量生理盐水腹腔注射作为对照组,12h后复制MCAO模型。梗塞后24h后检测血液中一氧化碳浓度、血脑屏障通透性。结果:诱导剂组一氧化碳浓度明显高于对照组(P＜0.01),血脑屏障通透性明显低于对照组(P＜0.05),而抑制剂组一氧化碳浓度明显低于对照组(P＜0.01),血脑屏障通透性明显高于对照组(P＜0.05)。血红素氧合酶诱导剂、抑制剂对非梗塞侧的血脑屏障通透性没有影响(P＞0.05)。结论:一氧化碳作为一种信使分子,脑缺血时浓度升高具有保护血脑屏障的作用。     

Prevention of de-novo adhesion formation after laparoscopic myomectomy: a randomized trial to evaluate the effectiveness of an oxidized regenerated cellulose absorbable barrier

To evaluate the effectiveness of the oxidized regenerated celluloseabsorbable barrier (Interceed®, TC7) in the prevention ofde-novo adhesion formation after laparoscopic myomectomy, aprospective and randomized study was performed at the Departmentof Obstetrics and Gynaecology of the University of Cagliari,Cagliari, Italy. A total of 50 pre-menopausal non-pregnant women,aged 23—42 years, who submitted to laparoscopic myomectomyfrom January 1993 to June 1994, were randomized to surgery alone(control group, n = 25) or surgery and oxidized regeneratedcellulose barrier (Interceed group, n = 25). Neither group receivedany other treatment for adhesion prevention. A second-look laparoscopywas performed 12—14 weeks after laparoscopic myomectomy.The incidence of adhesion-free patients was assessed at second-looklaparoscopy by an investigator not informed of the treatment.The numbers of adhesion-free patients were three out of 25 (12%)in the control group and 15 out of 25 (60%) in the treatmentgroup (P < 0.05). In conclusion, the oxidized regeneratedcellulose absorbable barrier significantly reduced de-novo adhesionformation after laparoscopic myomectomy.