Interactions between epidermal growth factor-mediated autocrine regulation and linoleic acid-stimulated growth of a human prostate cancer cell line.

Human prostate cancer (PC) cell lines possess epidermal growth factor (EGF) receptors and secrete EGF-related polypeptides. We used an EGF receptor-blocking antibody (anti-EGF.R) to demonstrate a functional autocrine loop, as well as the interaction between this and the effects of linoleic acid (LA), an omega-6 fatty acid, on PC cell growth. The anti-EGF.R competed effectively with [125I]EGF for receptors on DU145 PC cells, and on a high-passage DU145 variant (DU145M); when added to the culture medium, it suppressed both DU145 and DU145M cell growth in a dose-dependent manner. LA, a precursor for eicosanoid synthesis, had little effect on DU145 cell growth rate but stimulated DU145M growth in a concentration-related manner over a range of 0.25-2.0 micrograms/ml. anti-EGF.R (10(-9) M) caused suppression of LA-stimulated growth of DU145M cells in serum-free medium, which was prevented by the addition of 2 nM EGF. We conclude that an EGF.R-mediated autocrine loop is involved in PC cell growth regulation and that at least one site of action may be the synthesis of eicosanoids from their LA precursor.     

风湿性心脏病二尖瓣置换术中细胞因子水平的变化

目的测定风湿性心脏病二尖瓣置换术中细胞因子水平,了解它们的变化规律。方法 11例体外循环(CPB)下二尖瓣置换术患者,分别于术前,主动脉阻断前,主动脉阻断后5min,主动脉开放后10min、1h、2h、4h、24h测定白介素6(IL-6)、白介素8(IL-8)、白介素10(IL-10)以及肿瘤坏死因子(TNF)。结果IL-6、IL-8、IL-10水平在CPB开始后逐渐升高,在主动脉开放后2h左右达到高峰(P<0.01)。之后逐渐下降,到主动脉开放后24h已显著下降。TNF水平在CPB开始后逐渐升高,在主动脉开放后24h仍维持在很高的水平(P<0.01)。结论CPB下二尖瓣置换术中既有促炎因子水平的升高,又有抗炎因子的激活。     

多发性硬化患者血清和脑脊液中sIL-2R及sIL-6R的研究

目的　探讨可溶性白细胞介素 2受体 (sIL 2R)和可溶性白细胞介素 6受体 (sIL 6R)在多发性硬化(MS)发病过程中的作用。方法　采用双体夹心ELISA法对 2 9例MS急性期患者及 2 0例炎性神经病患者、39例非炎性神经病患者、2 0例健康对照者脑脊液和血清中sIL 2R和sIL 6R的含量进行检测。结果　MS患者血清和脑脊液中sIL 2R、sIL 6R含量明显高于非炎性神经病组 (P <0 .0 5 )及健康对照组 (P <0 .0 1) ;MS组sIL 2R和血清sIL 6R含量与炎性神经病组比较 ,无显著性差异 ,但脑脊液中sIL 6R水平明显低于炎性神经病组 (P <0 .0 1)。结论　sIL 2R和sIL 6R在MS急性期患者体内明显升高 ,进一步证实了MS有关免疫学的发病机制 ,并为临床诊断MS提供了具有参考价值的实验室指标     

杀菌性通透性增强蛋白对失血性休克的保护作用及其机理

分别在失血和复苏开始即刻ｉｖ杀菌性／通透性增强蛋白（ＢＰＩ）１．５和３．５ｍｇｋｇ－１，观察ＢＰＩ对大鼠失血性休克转归的影响．结果显示，ＢＰＩ治疗能明显改善失血性休克大鼠肝肾功能，提高休克动物存活率（ＢＰＩ组８１％ｖｓ休克对照组４４％，Ｐ＜０．０５），ＢＰＩ组大鼠复苏后与休克前的血浆内毒素（０．２０±０．０４ｖｓ０．２４±０．０５ｋＵＬ－１）水平无明显变化，血浆肿瘤坏死因子α和白介素６水平较休克前明显升高，但均显著低于休克对照组．提示ＢＰＩ对失血性休克大鼠具有一定的保护作用，其机理可能与ＢＰＩ拮抗休克时内源性内毒素活性，抑制细胞因子反应有关．     

EFFECTS OF SARAFOTOXIN S6c ON RENAL HAEMODYNAMICS AND URINE FORMATION IN ANAESTHETIZED DOGS

1. The effects of sarafotoxin S6c (S6c), a selective endothelin ETB receptor agonist, on renal haemodynamics and urine formation were examined in anaesthetized dogs. 2. Intrarenal arterial infusion of S6c at a rate of 1 or 5 ng/kg per min produced a transient increase in renal blood flow (RBF), with no change in systemic blood pressure and heart rate; RBF then decreased gradually to below the basal value. There were significant and dose-dependent increases in urine flow and free water clearance and decreases in urine osmolality during S6c infusion, whereas urinary excretion of sodium and glomerular filtration rate (GFR) remained unchanged. Simultaneously, S6c administration elicited a marked increase in urinary excretion of nitric oxide (NO) metabolites, N0₂^? and N0₃^? (UNO*V). 3. In dogs simultaneously administered S6c (5 ng/kg per min) and iV^G-nitro-L-arginine (NOARG; 40 (jig/kg per min), a NO synthase inhibitor, the renal vasodilator effect of S6c was abolished and marked reductions in RBF and GFR were observed. The S6c-induced diuretic action was not affected by NOARG. In the presence of NOARG, there was a small amount of UNO_xV at the basal level and the administration of S6c did not increase UNOxV. 4. These results suggest that an intrarenal arterial infusion of S6c enhances the production of NO in the kidney and that this enhancement contributes to the peptide-induced renal vasodilation. In contrast, it is unlikely that S6c-induced water diuresis is related to NO production stimulated by this peptide.     

Combination of ABO blood group incompatibility and glucose-6-phosphate dehydrogenase deficiency: effect on hemolysis and neonatal hyperbilirubinemia

The incidence (%) of hyperbilirubinemia (serum bilirubin ≥257 μmol/l) was similar in neonates with a combination of ABO incompatibility and glucose-6-phosphate dehydrogenase (G-6-PD) deficiency (45%), with ABO incompatibility (54%) or G-6-PD deficiency (37%), alone (ns). Carboxyhemoglobin values, corrected for inspired CO, were similarly elevated in all three groups (0.87 ± 0.32%, 0.82 ± 0.29%, 0.76 ± 0.18%, respectively, ns), but correlated with bilirubin only in those with ABO incompatibility alone. ABO-incompatible/G-6-PD-deficient neonates, compared with those with either condition alone, are not at increased risk for hemolysis or hyperbilirubinemia.     

Pharmacology of KB‐R7943: A Na+–Ca2+ exchange inhibitor

The Na⁺–Ca²⁺ exchange (NCX) system plays a pivotal role in regulating intracellular Ca²⁺ concentration in cardiomyocytes, neuronal cells, kidney and a variety of other cells. It performs a particularly important function in regulating cardiac contractility and electrical activity. One of the leading NCX inhibitors is KB‐R9743 (KBR) that appears to exhibit selectivity for Ca²⁺‐influx‐mode NCX activity (reverse mode of NCX). In this article we reviewed pharmacology of KBR and provide a brief summary of studies with other NCX inhibitors, such as SEA0400 (SEA) and SN‐6 (SN). Potential clinical usefulness of KBR and other NCX inhibitors is still controversial but the reviewed findings may be helpful in designing more selective and clinically useful NCX inhibitors for the treatment of cardiac, neuronal and kidney diseases.     

大鼠坐骨神经慢性挤压性损伤后痛阈和血清IL-6的变化及相关性研究

目的:通过大鼠坐骨神经慢性挤压伤(CCI)神经性疼痛模型的热敏变化及血清中IL-6含量的变化,探讨血清IL-6在神经性疼痛形成中的作用及可能机制.方法:36只250～300g的健康雄性Wistar大鼠,在戊巴比妥钠麻醉下于大腿中部暴露坐骨神经并作结扎,取对侧大腿坐骨神经暴露作为模拟对照(B组).术后1,3,5,7,9,11,13,15 d测定大鼠(n=12)两侧后爪对热敏阈值的变化.于术后第15 d处死大鼠,取血清,ELISA法测定IL-6浓度.结果:大鼠双侧后爪(CCI和B)的收缩潜伏期在术后第3,5,7,9,11,13,15 d有显著差异;CCI组血清IL-6与对照组比较有显著差异.结论:IL-6与大鼠坐骨神经慢性挤压性损伤后出现的神经源性疼痛过敏有关.     

Cerebrospinal fluid-filtration reduces TNF alpha in bacterial meningitis-CSF

A 37 year old male was admitted with the diagnosis of bacterial meningitis. Pneumococci were seen in the Gram stain of the cerebrospinal fluid. The clinical condition did not suggest severely raised intracranial pressure, there were no localizing signs and symptoms. CSF was turpid, with 20.100/3/mm³, mainly polymorphonuclear cells. Tumor necrosis factor alpha in CSp was greatly increased with 813 pg/ml. Parallel to the application of intravenous Penicillin G a CSF filtration was carried out. Within 214 h 225 ml CSF were filtrated through a Pall-filter, using a bidirectional pump. Cell count dropped to 720/3 cells/mm³, TNF-alpha to 39 pg/ml. The clinical course was uneventful, on day 12 the patient could be discharged without sequelae. CSF filtration may be a highly effective method to reduce from the CSF pathogenetically important cytokines, such as TNF-alpha, being responsible for intrathecal/meningeal inflammatory processes and triggered by cell-wall components of bacteria, e.g. pneumococci.     

Interleukin 6 Influences Germinal Center Development and Antibody Production via a Contribution of C3 Complement Component

Mice rendered deficient for interleukin (IL) 6 by gene targeting were evaluated for their response to T cell–dependent antigens. Antigen-specific immunoglobulin (Ig)M levels were unaffected whereas all IgG isotypes showed varying degrees of alteration. Germinal center reactions occurred but remained physically smaller in comparison to those in the wild-type mice. This concurred with the observations that molecules involved in initial signaling events leading to germinal center formation were not altered (e.g., B7.2, CD40 and tumor necrosis factor R1). T cell priming was not impaired nor was a gross imbalance of T helper cell (Th) 1 versus Th2 cytokines observed. However, B7.1 molecules, absent from wild-type counterparts, were detected on germinal center B cells isolated from the deficient mice suggesting a modification of costimulatory signaling. A second alteration involved impaired de novo synthesis of C3 both in serum and germinal center cells from IL-6–deficient mice. Indeed, C3 provided an essential stimulatory signal for wild-type germinal center cells as both monoclonal antibodies that interrupted C3-CD21 interactions and sheep anti–mouse C3 antibodies caused a significant decrease in antigen-specific antibody production. In addition, germinal center cells isolated from C3–deficient mice produced a similar defect in isotype production. Low density cells with dendritic morphology were the local source of IL-6 and not the germinal center lymphocytes. Adding IL-6 in vitro to IL-6–deficient germinal center cells stimulated cell cycle progression and increased levels of antibody production. These findings reveal that the germinal center produces and uses molecules of the innate immune system, evolutionarily pirating them in order to optimally generate high affinity antibody responses.