髓鞘相关生长抑制因子Nogo-A及胰岛素样神经生长因子受体在局灶性脑缺血再灌注损伤后大鼠脑组织的表达特征

目的:观察髓鞘相关生长抑制因子Nogo-A及胰岛素样神经生长因子受体在脑缺血再灌注损伤大鼠脑组织区域的表达特点。方法:实验于2005-08/2006-04在青岛大学医学院附属医院脑血管病研究所进行。将80只成年健康雄性Wistar大鼠,采用双盲法随机分为正常对照组8只、假手术组8只、缺血再灌注组64只,缺血再灌注组分为2h、6h、12h、24h、48h、3d、7d、14d8个时间点,每个时间点8只,其中4只用于Nogo-A检测,另外4只用于胰岛素样神经生长因子受体的检测。应用线栓法制备大鼠大脑中动脉缺血再灌注动物模型,假手术组不插尼龙线,正常对照组不做任何处理。采用免疫组织化学方法检测脑组织Nogo-A与胰岛素样神经生长因子受体在神经细胞中的表达。结果:80只大鼠均进入结果分析。①Nogo-A蛋白表达:正常对照组及假手术组皮质、海马及纹状体区凋亡细胞呈基础表达。缺血再灌注6～12h皮质区及纹状体区Nogo-A表达达高峰,海马区表达明显增加。缺血再灌注24h均开始下降。缺血再灌注48h～3d皮质区及纹状体区均二次达高峰,海马区表达恒定。缺血再灌注7～14d均降至基础水平。缺血再灌注各组Nogo-A蛋白表达均高于正常对照组及假手术组(P<0.05)。②胰岛素样神经生长因子受体蛋白表达:正常对照组及假手术组在皮质、海马及纹状体区阳性细胞呈基础表达。缺血再灌注24h达高峰,48h恒定表达,3～14d仍维持高值表达。缺血再灌注各组胰岛素样神经生长因子受体蛋白表达均高于正常对照组及假手术组(P<0.05)。结论:脑缺血再灌注损伤后,大鼠脑海马、皮质、纹状体等区域Nogo-A与胰岛素样神经生长因子受体表达均增加。胰岛素样生长因子受体表达增加与损伤程度呈正相关,脑轻度损伤时胰岛素样生长因子受体表达仅限于大脑皮质区,重度损伤时弥漫整个海马及纹状体区。     

Suppression of Erythromycin-induced Early Afterdepolarizations and Torsade de Pointes Ventricular Tachycardia by Mexiletine

Erythromycin is a selective I_Kr-blocking, action potential duration (APD)-prolonging drug, which may induce early afterdepolarizations (EADs) and torsade de pointes ventricular tachycardia. The successful termination of an erythromycin-induced clinical torsades de pointes by the authors with mexiletine prompted them to investigate in vitro whether erythromycin is able to induce EADs in Purkinje fibers and, if so, whether EADs are suppressible or not by mexiletine. Electrically stimulated canine Purkinje fibers (n=9) were superfused with erythromycin (200 mg/l) and action potentials were recorded by an intracellular microelectrode technique. Erythromycin induced a pronounced prolongation of APD and the appearance of EADs in all Purkinje preparations (9/9). After the addition of mexiletine (10 mM), a marked shortening of APD and the disappearance of EADs (7/9) were observed. Mexiletine, an inhibitor of the tetrodotoxin-sensitive window Na+-current, may prevent IKr-blocking drug-induced torsade de pointes ventricular tachycardia by abolishing APD prolongation and EADs.     

Chronic hepatitis B infection in Canada

Recent developments in the treatment and prevention of hepatitis B virus (HBV) infections warrant revisiting important epidemiological questions, such as how prevalent is chronic HBV infection in Canada, in which Canadian subpopulations are HBV prevalence rates the highest, in what percentage of infected individuals is the virus actively replicating, and how many infected Canadians are candidates for antiviral therapy? Currently available data suggest the overall prevalence of HBV-infected individuals in the general population is approximately 2%, with 5% to 10% having serological evidence of previous HBV infection. In high risk groups, such as street-connected individuals, Aboriginals and immigrants from endemic areas, these rates of viral prevalence and serological evidence of previous HBV infection are approximately two to 10 and five to 10 times higher, respectively, than in the general population. Candidates for antiviral therapy range from less than 1% of infected Aboriginals to 15% to 30% of Asians with chronic HBV. From these data, it is clear that chronic HBV remains an important public health problem in this country. Hence, resources must be identified to enhance Canadians'' awareness of HBV infection, maintain, if not expand, efforts to identify and implement safe and effective antiviral therapy for HBV-infected individuals, and continue programs for universal vaccination to prevent new HBV infections.Key Words: Canada, Epidemiology, Hepatitis, Hepatitis B, Hepatitis B virus, Liver, Liver diseaseHepatitis B virus (HBV) infections are the ninth most common cause of death by disease in the world today (1). The majority of deaths due to HBV infection occur as a result of complications of cirrhosis and/or hepatocellular carcinoma (2). Recently, new developments in the treatment of chronic HBV infections (defined as serological evidence of HBV infection beyond six months duration) provide promise that the course of the disease may be favourably altered (3,4). Moreover, effective immunoprophylaxis raises the distinct possibility that HBV may eventually be eradicated from the world''s population (5). In light of these encouraging therapeutic and preventive developments, it is timely to review the prevalence of chronic HBV infections in the general population of Canada and in certain high risk Canadian populations.     

Structure and expression of genes of GM-CSF and G-CSF in blast cells from patients with acute myeloblastic leukemia

The hematopoietic growth factors granulocyte/macrophage colony- stimulating factor (GM-CSF) and G-CSF, available as recombinant products, stimulate the growth in culture of blasts from patients with acute myeloblastic leukemia (AML). We used cDNA probes for each gene to study the genomic organization in blast cells of 22 patients and expression in the blast cells of 18 patients. Alteration in the structure of G-CSF (two instances) and GM-CSF (two instances) was found. In two patients in whom it was possible to study DNA from bone marrow obtained at remission, the new bands detected in the leukemic cells were not found. Fifteen of 18 patients showed no RNA expression of either growth factor. Both patients with GM-CSF abnormalities as seen by Southern analysis expressed an abnormally large GM-CSF message but no G-CSF messages. One patient with an abnormal Southern pattern with G-CSF expressed normal-sized G-CSF and GM-CSF messages. The biologic significance of these findings remains to be determined. Nonetheless, the abnormal Southern patterns may prove to be useful clonal markers in the study of AML.     

Microalbuminuria and cardiovascular risk

The term 'microalbuminuria' has been introduced to describe a measurable increase in urine albumin excretion, which is still within normal total urine protein excretion levels. Many data suggest that microalbuminuria is of value as an index of vascular damage, especially in hypertension and diabetes, and there is increasing information on its associations with traditional cardiovascular risk factors and its prognostic value. The association between microalbuminuria and peripheral markers of endothelial damage or dysfunction, such as von Willebrand factor, suggests the possibility that microalbuminuria may be a simple, cheap and easy index of endothelial abnormalities in cardiovascular disease. Nevertheless, further information on the value of microalbuminuria in other atherosclerotic vascular complications, such as ischaemic heart disease, stroke and peripheral artery disease is still needed.      

氯胺酮和硝苯吡啶对培养神经元谷氨酸兴奋毒性的保护作用

以体外培养的大鼠胚胎皮层神经元为对象,以培养上清液中乳酸脱氢酶活性为指标,研究了谷氨酸兴奋毒性及药物的保护作用。结果表明,培养10d的皮层神经元置于含10或50μmol·L^-1谷氨酸和低糖(1g·L^-1)的DMEM培养液中后,随着作用时间的延长,LDH漏出逐渐增加。在谷氨酸处理前,于培养液中加入氯胺酮或硝苯吡啶,则LDH漏出量明显低于对照组。氯胺酮和硝苯吡啶并用,LDH漏出量比单独使用氯胺酮或硝苯吡啶下降更加明显。结果表明,谷氨酸对培养的神经元可产生严重损伤。氯胺酮和硝苯吡啶单用或并用均有明显的保护作用。     

Ligand-Specific Cross-Inhibition of Monocyte Phagocytosis

Human monocytes exposed to particles reacting with receptors of one specific type demonstrate a markedly reduced phagocytosis of particles reacting with receptors of another type. The phagocytosis of yeast particles (Saccharomyces cerevisiae) coated with C3 fragments and of uncoated ones by monocytes can inhibit the subsequent endocytosis of sheep erythrocytes sensitized with IgG antibody and vice versa. The erythrocytes were labelled with 51Cr and the yeast particles with 125I. The dependence of the receptor-ligand reaction on temperature and time of preincubation, as well as on ratio of cell and particle, suggests that this cross-inhibition may be associated with plasma membrane modulations beginning with the attachment of ligands to a receptor and followed by their endocytosis. The differences between the functions of temperature, time, and concentration in inhibition caused by different receptor-ligand reactions suggest that these membrane modulations are probably ligand-specific processes.     

A LIGHT AND ELECTRON MICROSCOPIC HISTOCHEMICAL STUDY ON THE MECHANISM OF DFP-INDUCED ACUTE AND SUBACUTE MYOPATHY

Tóth L., Karcsú S., Poberai M. & Sávay Gy. (1981) Neuropathology and Applied Neurobiology 7, 399–410
A light and electron microscopic histochemical study on the mechanism of DFP-induced acute and subacute myopathy
The histochemical changes occuring in association with the development of acute and subacute myopathy have been studied in the rat diaphragm 30 min-48 h after a single i.p. injection of 1–82 mg/kg of the irreversible cholinesterase inhibitor organophosphate, diisopropylfluorophosphate (DFP). In addition to a considerable inhibition of the AChE activity of the motor end-plates, accumulation of ionic Ca²⁺ and an increase in neutral protease activity in the subjunctional sarcoplasm have been demonstrated. A temporal and causal relationship has been established between the histochemical changes and the development of the ultrastructural signs of myopathy.     

Causes and Differentialdiagnosis of Hematospermia

The authors examined the most frequent causes of hematospermia on their clinical material. They describe - in the order of importance - the examinations needed to discover pathological diagnostics. They call the attention to the importance of differentiation of "clear" hematospermia and hemato-pyospermia and review the possible ways of therapy.
Ursachen und Differentialdiagnose der Haematospermie

Zusammenfassung

Anhand eigener Beobachtungen wird zur Problematik der Haematospermie Stellung genommen. Dieses Symptom gelangt nicht so häufig zur Beobachtung, allerdings stellt die Haematospermie ein Symptom dar, das sehr ernst genommen werden muß. Die Autoren unterscheiden zwischen einer „klaren” Haematospermie und einer Pyo-Haematospermie, wenn es sich zusätzlich um eine eitrige Entzündung handelt. Die für die Differentialdiagnose wichtigen einschlägigen Untersuchungsmethoden werden beschrieben. Die wesentlichen Grundsätze der Therapie werden erläutert.