神经生长因子对局灶性脑缺血神经干细胞巢蛋白表达及细胞类型的影响

目的:实验于2006-02/07在锦州医学院科学实验中心完成。将72只健康SD大鼠按随机数字表法分为假手术组、模型组、神经生长因子治疗组,每组24只。采用Logna等改良法复制大脑中动脉血栓模型,动物清醒2h后进行功能评价,动物神经功能达到2级的纳入实验。假手术组除不进行大脑中动脉线栓外,其余同模型组。神经生长因子治疗组于缺血后立即腹腔注射神经生长因子1000μg/kg,1次/d。于缺血后1,3,7,14d处死动物,运用免疫组化和免疫荧光双标的方法观察神经生长因子对脑缺血后神经干细胞巢蛋白的表达及其细胞类型的影响。结果:72只大鼠均进入结果分析。①神经生长因子治疗组和模型组大脑皮质均可见巢蛋白阳性细胞,细胞呈圆形或椭圆形。与模型组相比,除缺血后1d外,神经生长因子治疗组其他时间点的巢蛋白阳性细胞数均明显高于模型组,两组缺血后各时间点的巢蛋白阳性细胞数均高于假手术组[模型组:(3.47±0.51),(5.13±1.14),(13.95±3.56),(8.97±2.08)个;神经生长因子治疗组:(3.81±0.66),(9.88±2.08),(19.87±3.86),(26.17±2.90)个,假手术组:0,P<0.05,P<0.01]。②模型组和神经生长因子治疗组3d时缺血皮质巢蛋白阳性突起主要与胶质纤维酸性蛋白共存,14d时巢蛋白与神经元特异性烯醇化酶共存明显增多。结论:神经生长因子能增加局灶性脑缺血后巢蛋白的阳性细胞的数目,并促进其分化为神经元和神经胶质细胞。     

微创经皮钢板置入内固定治疗胫腓骨骨折的技术操作特点

目的:总结微创经皮钢板置入内固定治疗胫腓骨骨折的技术操作特点,并观察材料及宿主反应。方法:2004-06/2006-10在济宁医学院附属金乡医院对18例胫腓骨骨折患者在微创手术下进行了手术置入内固定材料。男13例,女5例,年龄17～73岁。术后按Johner-Wruhs方法评价测试各大关节功能,分为优、良、中、差。全部病例进行临床随访。术前、术后1周、6周、3个月、半年及1年分别摄X线片与健侧对比测量患肢外观、成角、旋转和短缩情况,并观察材料及宿主反应。结果:①本组病例切口均顺利愈合,术后3～14d出院。②全部获得随访,平均随访时间14个月;骨愈合时间3～10个月。③按Johner-Wruhs方法评价功能,优13例,良4例,中1例,差0例,以优良为满意标准,本组病例总体满意率94.4%。④术后1例出现跛行步态,中度疼痛,骨成角畸形15°,可能因为患者对不锈钢材料有排斥反应造成固定不牢所致。结论:微创经皮钢板置入内固定材料治疗胫腓骨骨折具有手术创伤小、骨折愈合快、功能恢复好的特点;内固定材料未出现特殊材料反应与宿主反应。     

The Heartsink Patient: A Preliminary Study

Eight GPs identified 78 heartsink patients; in an open-endedinterview they were asked to explain why they regarded themin this way. A GP's definition of a heartsink patient was influencedby GP sex, practice location, and time of surgery, althoughthe number of participating GPs was too low to make any definiteassertions. Practitioners' anticipations of heartsink consultationswere generally over-exaggerated, with most of the encountersgoing better than expected. GPs expressed the view that thesepatients raised serious professional issues for them, whilstthere was also a dislike for these patients' personalities andbehaviour. Two levels of the heartsink state are hypothesized:one, a state of inertia, is when the heartsink patient has beena chronic high user of the primary health care system, and aGP has exhausted all avenues. The other is an acute situationwith those heartsink patients who have been low users of thesystem in the past. Recent, new events in these patients' liveshave raised an issue that is just as much to do with patientand doctor reaction to these events, as it is about findinga diagnosis or solution to the problem. We present the results and hypotheses to provoke further discussionand research.     

VIOLENT BEHAVIOUR IN PYSCHIATRIC INPATIENTS

A study of violent behaviour among psychiatric inpatients in a large general hospital is presented. Over the study period of one year a total of 36 incidents of violence involving 26 patients were recorded. Schizophrenia was the most common diagnosis among assailants. Fellow patients were the main victims. Incidence of serious violence was low. Most incidents occurred in the night hours, from inmates of acute wards and mostly without any provocation.KEY WORDS: Violent behaviour, Psychiatric patients     

Prediction of cytochrome P450 isoform responsible for metabolizing a drug molecule

Background

ATP-binding cassette (ABC) transporters protect cells against unrelated (toxic) substances by pumping them across cell membranes. Earlier we showed that many ABC transporters are highly expressed in hematopoietic stem cells (HSCs) compared to more committed progenitor cells. The ABC transporter expression signature may guarantee lifelong protection of HSCs but may also preserve stem cell integrity by extrusion of agents that trigger their differentiation. Here we have studied whether non-hematopoietic stem cells (non-HSCs) exhibit a similar ABC transporter expression signature as HSCs.

Results

ABC transporter expression profiles were determined in non-hematopoietic stem cells (non-HSCs) from embryonic, neonatal and adult origin as well as in various mature blood cell types. Over 11,000 individual ABC transporter expression values were generated by Taqman Low Density Arrays (TLDA) to obtain a sensitivity comparable with quantitative real-time polymerase chain reactions. We found that the vast majority of transporters are significantly higher expressed in HSCs compared to non-HSCs. Furthermore, regardless their origin, non-HSCs exhibited strikingly similar ABC transporter expression profiles that were distinct from those in HSCs. Yet, sets of transporters characteristic for different stem cell types could be identified, suggesting restricted functions in stem cell physiology. Remarkably, in HSCs we could not pinpoint any single transporter expressed at an evidently elevated level when compared to all the mature blood cell types studied.

Conclusions

These findings challenge the concept that individual ABC transporters are implicated in maintaining stem cell integrity. Instead, a distinct ABC transporter expression signature may be essential for stem cell function. The high expression of specific transporters in non-HSCs and mature blood cells suggests a specialized, cell type dependent function and warrants further functional experiments to determine their exact roles in cellular (patho)physiology.     

HDAC6 Deacetylates Ku70 and Regulates Ku70-Bax Binding in Neuroblastoma

Ku70 was first characterized as a nuclear factor that binds DNA double-strand breaks in nonhomolog end-joining DNA repair. However, recent studies have shown that Ku70 is also found in the cytoplasm and binds Bax, preventing Bax-induced cell death. We have shown that, in neuroblastoma cells, the binding between Ku70 and Bax depends on the acetylation status of Ku70, such that, when Ku70 is acetylated, Bax is released from Ku70, triggering cell death. Thus, to survive, in neuroblastoma cells, cytoplasmic Ku70 acetylation status is carefully regulated such that Ku70 is maintained in a deacetylated state, keeping Bax complexed with Ku70. We have shown that overexpression of CREB-binding protein (CBP), a known acetyltransferase that acetylates Ku70, releases Bax from Ku70, triggering apoptosis. Although we have shown that blocking deacetylase activity using non-type-specific inhibitors also triggers Ku70 acetylation and Bax-dependent cell death, the targets of these deacetylase inhibitors in neuroblastoma cells remain unknown. Here, we demonstrate that, in neuroblastoma cells, histone deacetylase 6 (HDAC6) binds Ku70 and Bax in the cytoplasm and that knocking down HDAC6 or using an HDAC6-specific inhibitor triggers Bax-dependent cell death. Our results show that HDAC6 regulates the interaction between Ku70 and Bax in neuroblastoma cells and may be a therapeutic target in this pediatric solid tumor.     

INITIAL EXPERIENCE WITH SHOCK WAVE LITHOTRIPSY AT ARMY HOSPITAL (R & R) DELHI CANTT

Army Hospital (R & R) has acquired an Electrohydraulic Lithotripter (DIREX NOVA), the first of its kind in the Armed Forces for the treatment of stone diseases. The first 200 patients who underwent Extracorporeal Shock Wave Lithotripsy (ESWL) have been analysed in this study. This being a pilot study would serve as a beginning of an ongoing experience with this non-invasive procedure and its benefits for the stone population in the Armed Forces.KEY WORDS: ESWL, Lithotripsy     

TRANSFUSION REACTIONS: AFMC EXPERIENCE

Transfusions of blood and its components are useful and lifesaving. Adverse effects occur during or after transfusion, called hazards or complications of blood transfusion. Complications/hazards of various types which occurred in the patients following transfusion of blood/blood components in Armed Forces Hospitals of Pune-Kirkee complex were analysed with relevant investigations. Out of a total number of 13,039 transfusions of blood and blood components from 01 June 1995 to 31 July 1997, there were 104 (0.8%) adverse reactions. Non haemolytic febrile transfusion reaction was the commonest seen in 73 (70.2%) transfusions, followed by allergic reactions in 19 (18.3%) cases. Nonspecific reactions were seen in 11 (10.6%). One haemolytic transfusion reaction occurred due to wrong labelling of blood sample received from the ward for compatibility testing. There were no fatalities.KEY WORDS: Blood transfusion, Complication, Febrile reaction     

EARLY DIAGNOSIS IN POST RENAL TRANSPLANT OPPORTUNISTIC INFECTIONS: A FRESH LOOK

A total of 86 renal transplant patients who were transplanted with live related donor (LRD) and live unrelated donor (LURD) kidneys were studied for opportunistic infections. Immune diagnosis of Toxoplasma, Cytomegalovirus (CMV), Herpes-simplex virus type II (HSV-2), Aspergillosis and Tuberculosis was carried out in these patients along with sputum examination, CSF studies and biopsy of lymphnode and other tissues in few cases. A high degree of Toxoplasma, CMV & HSV-2 positivity was seen in transplanted patients. However sensitivity of serological diagnosis of tuberculos was found to be low with standard criteria, which increased significantly when modified criteria were used. It is concluded that regular immunological monitoring should be carried out in transplanted patients so as to reach an early diagnosis and management of opportunistic infections.KEY WORDS: Immune diagnosis, Opportunistic infections, Transplantation