受体介导的凝血酶对成骨细胞增殖及分化的作用

目的 通过凝血酶对成骨细胞的增殖及分化作用的研究来探讨受体介导的凝血酶的功能.方法 原代成骨细胞分别取自于蛋白酶激活受体(protease-activated receptor,PAR)-1敲除鼠和野生对照鼠的头颅骨.并利用凝血酶,人工合成的PAR-1或PAR-4特异性激活短肽对细胞进行处理,通过对5.溴-2-脱氧尿嘧啶的嵌入及细胞碱性磷酸酶活性的测定探讨PAR-1或PAR-4激活对细胞增殖和分化的影响.结果 在野生鼠成骨细胞,凝血酶及PAR-1激活肽均能促进的细胞增殖和降低碱性磷酸酶的活性,但PAR-4激活肽却无这些作用.然而在PAR-1 敲除鼠的成骨细胞无论是凝血酶还是PAR-4激活肽均不能改变细胞的增殖及碱性磷酸酶的活性.结论 本研究结果 表明凝血酶促进成骨细胞增殖及抑制其分化是通过PAR-1介导的.其他凝血酶受体并不具有此作用.     

Methanol poisoning: a review and case study of four patients from Central Australia

Methanol intoxication, a rare and potentially lethal form of poisoning, usually results from ingestion and occasionally inhalation of methanol. Initial symptoms of blurred vision, elongated anion gap and metabolic acidosis are typically delayed and may not at first be recognised as methanol-related complaints. Once diagnosed, treatment must be prompt and definitive. As well as general supportive care, ethanol infusion, dialysis and alkalinization form the mainstays of treatment.

The cases described in this paper are compared to previous reports from other countries worldwide and contrast the variance in outcome often seen in methanol poisoning. The paper describes two tragic deaths and two lucky survivors, all of whom had consumed a cocktail of methanol and other alcoholic beverages at the same party.

The ICU nurse's role in managing the methanol-intoxicated patient relies on that person's sound knowledge of the unusual biochemical reactions occurring in the body and the need to institute definitive and supportive measures to help both patient and family recover.     

Trichinella infection and clinical disease

Trichinellosis is caused by ingestion of insufficiently cooked meat contaminated with infective larvae of <it>Trichinella</it> species. The clinical course is highly variable, ranging from no apparent infection to severe and even fatal disease. We report two illustrative cases of trichinellosis. Returning to Denmark a few days after having eaten roasted pork in the Republic of Serbia, a female patient suffered from severe vomiting, epigastric pain, diarrhoea, and later myalgia, generalized oedema, and prostration. A biopsy showed heavy infestation with <it>Trichinella spiralis</it>, 2000 larvae/g of muscle. Life-threatening cardiopulmonary, renal and central nervous system complications developed. The patient recovered after several months. Her husband, who also ate the pork, did not have clinical symptoms, but an increased eosinophil count and a single larva in a muscle biopsy confirmed infection. The epidemiology, clinical manifestations, diagnosis, treatment and prevention of trichinellosis are reviewed.      

Hepatitis B Immunisation in Health Care Workers

Background

Hepatitis B virus (HBV) infection is an important occupational risk in health care workers (HCW). In spite of HBV vaccine availability in Armed Forces, the high prevalence of HBV infection in HCW continues to be a problem. The study was undertaken to study the HBV vaccine-compliance among HCW.

Methods

A cross-sectional study was conducted at a tertiary care hospital. HCW were requested to fill up the pre set questionnaire to assess the HBV vaccination coverage.

Result

Amongst 254 HCW, only 57.7% were vaccinated against HBV. The vaccine compliance was lowest among housekeeping professionals. The mean age at vaccination was high (30.5 years). Amongst the vaccine non-compliant subjects, 34.3% were above 30 years of age. 32.2% HCW completed primary vaccination after spending more than 10 years in the profession. Accessibility of HBV vaccine, knowledge and perception of HBV risk were important factors in vaccine non-compliance.

Conclusion

Due to low and delayed HBV vaccine-compliance, HCW continue to be at the risk of occupational HBV. Health education highlighting occupational risk of HBV, accessibility of vaccine and mandatory vaccination of HCW is recommended to increase HBV vaccine compliance among HCW.Key Words: Health care workers, Hepatitis B virus, Occupational risk, Hepatitis B vaccine     

Seletracetam (ucb 44212) inhibits high-voltage–activated Ca2+ currents and intracellular Ca2+ increase in rat cortical neurons in vitro

Purpose: We analyzed the effects of seletracetam (ucb 44212; SEL), a new antiepileptic drug candidate, in an in vitro model of epileptic activity. The activity of SEL was compared to the effects of levetiracetam (LEV; Keppra), in the same assays. Methods: Combined electrophysiologic and microfluorometric recordings were performed from layer V pyramidal neurons in rat cortical slices to study the effects of SEL on the paroxysmal depolarization shifts (PDSs), and the simultaneous elevations of intracellular Ca²⁺ concentration [Ca²⁺]_i. Moreover, the involvement of high‐voltage activated Ca²⁺ currents (HVACCs) was investigated by means of patch‐clamp recordings from acutely dissociated pyramidal neurons. Results: SEL significantly reduced both the duration of PDSs (IC₅₀ = 241.0 ± 21.7 nm ) as well as the number of action potentials per PDS (IC₅₀ = 82.7 ± 9.7 nm ). In addition, SEL largely decreased the [Ca²⁺]_i rise accompanying PDSs (up to 75% of control values, IC₅₀ = 345.0 ± 15.0 nm ). Furthermore, SEL significantly reduced HVACCs in pyramidal neurons. This effect was mimicked by ω‐conotoxin GVIA and, to a lesser extent, by ω‐conotoxin MVIIC, blockers of N‐ and Q‐type HVACC, respectively. The combination of these two toxins occluded the action of SEL, suggesting that N‐type Ca²⁺ channels, and partly Q‐type subtypes are preferentially targeted. Conclusions: These results demonstrate a powerful inhibitory effect of SEL on epileptiform events in vitro. SEL showed a higher potency than LEV. The effective limitation of [Ca²⁺]_i influx might be relevant for its antiepileptic efficacy and, more broadly, for pathologic processes involving neuronal [Ca²⁺]_i overload.     

4-烷硫基-4-脱氧-4′-去甲表鬼臼毒素的合成和抗肿瘤活性

对4’-去甲表鬼臼毒素的C₄位进行化学修饰,合成和筛选了10个4-烷硫基-4-脱氧-4’-去甲表鬼臼毒素衍生物以进一步研究C₄位不同的原子和取代基与活性之间的关系及寻找结构简单、活性更强的抗肿瘤新药。4’-去甲表鬼臼毒素与硫醇在三氟化硼·乙醚或三氟乙酸存在下生成相应的硫醚,也可用硫醇与4β-溴-4-脱氧-4’-去甲表鬼臼毒素反应生成相应的硫醚。在体外筛选中,化合物10和12抑制L1210白血病细胞的活性与依托泊甙相当或更强,化合物9,10,12和15抑制KB细胞的活性与依托泊甙相当或更强。     

ROLE OF NITRIC OXIDE IN THE DEVELOPMENT OF CORTICOTROPIN-INDUCED HYPERTENSION IN SHEEP

1. The possibility that altered synthesis of vascular nitric oxide (NO) plays a role in the development of corticotropin-induced hypertension in sheep was examined by determining the effect of concomitant infusion of L-arginine, a precursor of NO, on the development of the hypertension. 2. Corticotropin (5 μg/kg per h) infused over 2 days increased mean arterial pressure (MAP) from 83 ± 4 to 99 ± 4 mmHg in five conscious sheep. Concomitant infusion of L-arginine (60 mg/kg per h) did not alter this response; infusion of L-arginine alone had no effect on blood pressure. 3. The dose of L-arginine (60 mg/kg per h) used blocked the rise in MAP (+16 mmHg) in response to a 5 h infusion of N-nitro-L-arginine (1 mg/kg per h). 4. These findings suggest that disruption of NO synthesis does not play a role in the development of corticotropin hypertension in sheep.