血小板活化因子在急性肝肾衰竭动物模型中对肾功能的影响

目的:了解血小板活化因子(PAF)在急性肝、肾衰竭动物模型中对肾功能的影响及可能的作用机制。方法:设4组大鼠,分别注射D-氨基半乳糖(D-GaLN)加内毒素(LPS),D-GaLN加PAF,D-GaLN加LPS加PAF受体拮抗剂及生理盐水,诱导急性肝、肾衰竭动物模型,测肝、肾功能指标并观察肝、肾组织病理改变。结果:注射D-GaLN大鼠的血清丙氨酸氨基转移酶、总胆红素比生理盐水组升高10倍以上,差异有显著性,病检有肝细胞坏死。注射PAF或LPS组与PAF受体拮抗剂组或生理盐水组比,肾功能指标差异有显著性。肾组织病检可见部分肾小管坏死。结论:PAF与急性肝、肾衰竭动物模型中的急性肾衰有关;PAF可能参与了内毒素相关的肝肾综合征(HRS)的形成;PAF受体拮抗剂对HRS可能有治疗作用。     

钙调素拮抗剂E6对大鼠脑一氧化氮合酶活性和突触体谷氨酸释放的影响

目的 探讨钙调素拮抗剂E6的抗脑缺血作用机制。方法 用[3H]-L-Glu（glutamic　acid,Glu）标记大鼠脑突触体,测定突触体的Gln释放量和用一氧化氮合酶（nitric oxide synthase,NOS）试剂盒测定成年大鼠脑匀浆上清中NOS活性。结果　E6促进Glu释放（与对照组比,10-5mol·L-1组增加81.0％）,但对KCl（50 mmol·L-1）引起的Glu释放有抑制作用,10-5mol·L-1E6的抑制率为23.2％。E6浓度依赖性地抑制NOS活性。钙调素（calmodulin,CaM）（30μg·ml-1）可逆转E6的抑制作用（10-6mol·L-1E6的抑制率为13.7％）,N-硝基-精氨酸（（N-nitro-arginine,L-NNA）（10μmol·L-1）可加强E6的抑命作用（10-6mol·L-1的抑制率为76.5％）。结论 E6是与CaM结合后发挥抑制 NOS活性效应的,E6对Glu 释放的影响可能与其对NOS活性及其对神经细胞内Ca2+影响有关。     

Influence of Agonist, Shear Rate, and Perfusion Time on Nitric Oxide Inhibition of Platelet Deposition

Nitric oxide (NO) is a physiological species involved in inhibition of platelet adhesion and aggregation. A novel NO delivery device was utilized to quantitatively assess the effects of gaseous NO on platelet deposition to agonist-coated biomaterials in the presence of a platelet suspension. Platelet deposition was evaluated as a function of agonist (collagen, fibrinogen, or IgG), shear rate (250, 500, and 750 s^–1), and perfusion time (5, 7.5, and 15 min). The minimal aqueous surface NO concentrations and fluxes necessary for significant inhibition of platelet deposition were quantified. Platelet deposition was completely inhibited at a gaseous NO exposure of 0.1 ppm, irrespective of the platelet agonist, shear rate, and perfusion time. The corresponding aqueous surface NO concentration was 0.09 nM at 250 s^–1 as predicted by a validated model. Surface fluxes ranged between 0.3 and 0.6 femtomoles cm^–2 s^–1. The results of this study are useful for establishing generalized guidelines (i.e., NO flux requirements in the presence of agonists, shear rate, and perfusion time) for the design and development of suitable biomaterials incorporating NO to reduce platelet deposition. Further studies incorporating blood, rather than platelet suspensions, are required to provide a more complete assessment of the required NO flux necessary to inhibit platelet deposition. © 2000 Biomedical Engineering Society. PAC00: 8717-d, 8719Tt     

Mouse macrophage development in the absence of the common γ chain: defining receptor complexes responsible for IL-4 and IL-13 signaling

The common γ chain (γ_c) forms a critical component of the receptors for interleukins (IL)-2, IL-4, IL-7, IL-9, and IL-15. We analyzed γ_c-deficient mice to define a role for γ_c signaling in the development and function of the macrophage lineage. No major differences in absolute cell numbers, cell surface phenotype, or in vitro function of γ^?_c compared to γ⁺_c macrophages were observed. We therefore conclude that signaling through the γ_c chain is not essential for the differentiation of mouse macrophages. Although B and T cells require γ_c for IL-4 responses, IL-4 up-regulated major histocompatibility class II molecules and inhibited nitric oxide production from γ^?_c macrophages following stimulation with lipopolysaccharide and interferon-γ. γ^?_c macrophages could also respond to IL-13, consistent with the model of a type II IL-4 receptor α/IL-13R which can function in the absence of γ_c. Both IL-4 and IL-13 responses could be completely inhibited with the mouse IL-4 antagonist QY, suggesting that all of the observed IL-13 responses pass through the type II receptor, making it the primary signaling receptor complex for IL-13 in mouse macrophages.     

Effects of ATP antagonists on purinoceptor-operated inward currents in rat phaeochromocytoma cells

The effects of suramin, reactive blue 2 (RB2) and d-tubocurarine (d-TC) were investigated electrophysiologically to elucidate the mechanisms underlying their antagonism of P₂ purinoceptor-mediated responses. All three compounds inhibited an adenosine triphosphate (ATP)-activated inward current in rat phaeochromocytoma PC12 cells in a concentration-dependent manner. The order of potency was RB2 > suramin > d-TC. The inhibition induced by suramin or RB2 was reversible, whereas that induced by d-TC was not reversed after a 5-min rinse. The inactivation of the ATP-activated current was accelerated by d-TC but not by suramin or RB2. RB2 administered simultaneously with ATP exerted much weaker inhibition compared to that induced by prior administration, suggesting that RB2 is a slowly acting antagonist. This was not observed for suramin or d-TC. Suramin and RB2 caused a parallel shift in the concentration/response curve for the ATP-activated current. With d-TC the maximal response of ATP was decreased but the concentration producing half-maximal response was unchanged. The voltage dependency of the ATP-activated current showed less inward rectification in the presence of d-TC. Suramin or RB2 did not affect the voltage dependency. These results suggest that suramin and RB2 reversibly block binding of ATP to receptors, whereas d-TC blocks ion permeability through the ATP-activated channel.     

Thyrotropin-releasing hormone (TRH) counteracts neuronal damage induced by a substance P antagonist

Summary Intrathecal administration of the substance P antagonist Spantide caused marked necrotic changes of the gray matter of the spinal cord extending several segments from the injection site. Intravenous treatment with several doses of thyrotropin releasing hormone before and after Spantide injection completely prevented the necrotic lesion.     

Antagonist moment of force during maximal knee extension in pubertal boys: effects of quadriceps fatigue

The examination of the moment exerted by the hamstrings during maximum isokinetic knee extensor tests is useful when comparing isokinetic strength and muscle activity patterns between children and adults. The purpose of this study was to examine the effect of antagonist moment of the hamstrings on the isokinetic moment of the knee extensors in pubertal children and to determine whether this effect is altered following a fatigue task. Eighteen healthy pubertal males [age 14.3 (0.5) years] performed 34 maximal isokinetic concentric efforts of the knee extensors at 60°·s⁻¹. The average moment of force and electromyographic (aEMG) signal of vastus medialis (VM), vastus lateralis (VL) and biceps femoris (BF) at 11–30°, 31–50°, 51–70° and 71–90° of knee flexion were calculated for each repetition. The hamstrings antagonist moment was determined before and after the fatigue task by fitting the aEMG–moment relationship at different levels of muscle effort using second-degree polynomials. The percentage contribution of the antagonist moment to the resultant joint moment ranged from 7.1 % to 60.4 % throughout the range of motion, with the highest percentage observed close to full knee extension (11–30°). The antagonist effect was significantly greater during concentric tests of the knee extensors compared to the corresponding eccentric tests (p<0.05). Following the fatigue test, there was an overall decline of the resultant joint moment, but no changes in the predicted hamstrings moment were observed. These results indicate that when testing maximal knee extensor isokinetic strength in pubertal boys, activity of the hamstrings implies a reduction of the net extensor moment as compared to the isolated capacity of the knee extensors. However, this antagonist effect is not altered following the performance of an isokinetic fatigue knee extension task. Electronic Publication     

Long-term follow-up of patients with tuberculosis as a complication of tumour necrosis factor (TNF)-α antagonist therapy: safe re-initiation of TNF-α blockers after appropriate anti-tuberculous treatment

This study investigated the long-term outcome of patients with tuberculosis (TB) as a complication of tumour necrosis factor (TNF)-α blocker therapy. All TB cases ( n  =   21) complicating TNF-α blocker therapy from French university hospitals were collated between January 2000 and September 2002. Outcome was assessed via a postal questionnaire during September 2005. The mortality rate after 4 years was 4.8%, and one patient had relapsed and six (29%) patients had recommenced TNF-α antagonist treatment, after appropriate anti-TB therapy, without reactivation. These data support the concept that TNF-α antagonists can be restarted in TB patients provided that adequate anti-TB treatment has been completed.     

Effects of LSD and BOL on the catecholamine synthesis and turnover in various brain regions

In the rat, lysergic acid diethylamide (LSD) 0.5 mg/kg and 2-bromo lysergic acid diethylamide (BOL) 0.5 mg/kg increased the rate of the striatal in vivo tyrosine hydroxylation as measured by the DOPA accumulation after decarboxylase inhibition. Neither LSD nor BOL significantly changed the DOPA accumulation in the olfactory tubercle, a dopamine-rich part of the limbic system. LSD but not BOL increased the DOPA accumulation in the cerebral cortex and in the brain stem. LSD and BOL appeared not to alter the rate of -MT-induced disappearance of DA or of NA in the whole brain, nor did they change the rate of the -MT-induced disappearance of DA in the striatum. It is suggested that in the striatum LSD and BOL block autoreceptors (presynaptic receptors) regulating the tyrosine hydroxylation. These receptors may be DA receptors, but may also be 5-HT- or LSD-sensitive receptors.The regional differences observed between LSD and BOL suggest that LSD in the cerebral cortex and in the brain stem increases the DOPA accumulation by mechanism other than that functioning in the striatum. One possible explanation is that LSD and BOL may differ in their effects on 5-hydroxytryptaminergic systems in the cerebral cortex and in the brain stem.