Effects of brain-derived neurotrophic factor on induced differentiation of SH-SY5Y cells in vitro

BACKGROUND： Previous studies have demonstrated that brain-derived neurotrophic factor （BDNF） promotes neural differentiation. However, the mechanisms involved in cell cycle-related protein regulation, which highly correlates to neural proliferation and apoptosis, remain poorly understood. OBJECTIVE： To investigate the effects of various concentrations of BDNF on cycle-related protein mRNA expression in induce-differentiated SH-SY5Y cells in vitro prior to and following G2 phase, and to analyze the neuroprotective effects of BDNF. DESIGN, TIME AND SETTING： A comparison, observational study, based on cell biology, was performed at the Department of Biochemistry, Medical College of Tongji University, from March 2005 to October 2006. MATERIALS： SH-SY5Y cells were provided by Shanghai Institute of Cytology, Chinese Academy of Science; BDNF by Alomone Labs, Israel; all-trans retinoic acid （ATRA） by Sigma-Aldrich, USA. METHODS： SH-SY5Y cells were randomly divided into three groups： blank control [cells were treated in Insulin-Transferrin-Selenium （ITS） solution for 7 days], ATRA （cells were treated with ITS solution containing 10 μmol/L ATRA for 7 days）, and BDNF （cells were treated identical to the ATRA group for 5 days, and then respectively treated in ITS solution containing 1, 10, and 100 μg/L BDNF for 2 days）. The experiment was repeated three times for each group. MAIN OUTCOME MEASURES： mRNA expression levels of cyclin A1, B1, B2, cyclin-dependent kinase 1, and 5 were detected using quantitative real-time RT-PCR; percentage of cells in G1, S, and G2 phases were detected using fluorescence-activated cell sorting. RESULTS： mRNA expression levels of cyclin A1 in the high-dose BDNF group was significantly less than the ATRA group （P 〈 0.05）.mRNA expression levels of cyclin B1 was significantly less in the different BDNF concentration groups compared with the control and ATRA groups （P 〈 0.05 or P 〈 0.01）. mRNA expression levels of cyclin B2 and cyclin-dependent kinase 1 were significantly decreased in the high-dose BDNF group （P 〈 0.05 or P 〈 0.01）. Cyclin-dependent kinase 5 mRNA expression was significantly greater in the low-dose and moderate-dose BDNF groups compared with the ATRA group （P 〈 0.05）. The percentage of cells in G1 phase was significantly greater in the different BDNF concentration groups compared with the ATRA and control groups （P 〈 0.01）. Moreover, the percentage of cells in S phase was significantly less in the three BDNF groups compared with the ATRA group （P 〈 0.01）. However, the percentage of cells in S phase was significantly less in the low-dose and high-dose BDNF groups compared with the control group （P 〈 0.01）. CONCLUSION： BDNF enhanced the percentage of cells in G1 phase, but did not alter mRNA expression of cell cycle-related proteins prior to or following G2 phase. These results suggested that BDNF was not a risk factor for inducing apoptosis.     

视知觉学习治疗顺规和逆规散光性儿童弱视患者疗效比较研究

目的比较视知觉学习治疗顺、逆规散光性儿童弱视患者（perceptual learning）的疗效。方法将138例（274眼）8-13岁的顺、逆规散光性儿童弱视患者行视知觉学习治疗,观察2年后对其结果进行统计学分析。结果8—13岁的顺规散光造成重度弱视的比例较逆规散光造成重度弱视高,逆规散光性儿童弱视患者（62．7％）治疗的总有效率比顺规散光性（35．4％）高,组间比较差异有统计学意义（P〈0．05）。结论视知觉学习治疗逆规散光性儿童弱视患者总有效率高于顺规散光性儿童弱视患者。     

特异性抗原致敏的DC-CIK与DC-CTL细胞对黑色素瘤抑瘤作用的比较

目的：比较特异性抗原致敏的树突状细胞（DC）诱导的杀伤细胞（CIK）和细胞毒性T淋巴细胞（CTL）对B16黑色素瘤的抑瘤作用。方法：采用特异性肿瘤抗原致敏的DC与CIK和CTL细胞共同培养,分析其免疫表型,流式细胞检测癌细胞增殖周期中G0/G1期、S期、G2/M期细胞比率和细胞凋亡指数（AI）、细胞增殖指数（PI）的变化;并用MTT法检测其对肿瘤细胞的抑瘤作用。结果：DC-CIK及DC-CTL均可以影响肿瘤细胞的细胞周期,并具有诱导细胞凋亡的作用,但DC-CIK与DC-CTL之间无显著性差异;DC-CTL细胞组抑瘤作用较DC-CIK明显升高。结论：特异性抗原致敏的DC-CIK与DC-CTL细胞对B16黑色素瘤均有抑瘤作用,但DC-CTL更高效而特异。     

淋巴细胞活性染色质诱导系统性红斑狼疮样小鼠模型

目的建立活性染色质诱导系统性红斑狼疮(SLE)样小鼠模型。方法从ConA活化的BALB/c小鼠脾淋巴细胞中提取活性染色质,分别于d 0、d 14、d 21和d 28以染色质100μg在BALB/c小鼠尾根部及背部皮内注射免疫4次,诱导SLE样小鼠模型。目测半定量尿蛋白试纸法检测动物的尿蛋白变化,HE染色法检查动物的肾脏、脾脏病理改变,计算动物的胸腺和脾脏指数,MTT法检测ConA和LPS诱导的T、B淋巴细胞增殖反应,全自动生化分析仪检测血清中Crea和BUN水平,ELISA法检测小鼠血清中ANA、抗dsDNA、IgG1、IgG2a、IL-10、IFN-γ水平,流式细胞术检测脾脏T、B淋巴细胞亚群变化。结果诱导模型小鼠尿蛋白水平升高,出现肾小球肾炎、脾脏增生等病理改变;脾脏指数明显升高,LPS诱导的B淋巴细胞增殖反应增强;血清Crea、BUN、ANA、抗dsDNA、IgG1、IgG2a、IL-10和IFN-γ水平明显升高;脾脏CD19+、CD19+CD21+、CD19+CD23+、CD19+IgD+B淋巴细胞亚群百分比明显升高,CD4+CD25+T淋巴细胞百分比明显下降。结论 ConA活化淋巴细胞的染色质免疫同系BALB/c小鼠成功诱导了SLE样小鼠模型,其血清学、组织病理学及免疫学方面特征与人类SLE临床特征表现相似。     

Beneficial effect of the leaves of Murraya koenigii (Linn.) Spreng (Rutaceae) on diabetes-induced renal damage in vivo

Ethnopharmacological relevance

Murraya koenigii (Linn.) Spreng (curry leaf) is widely used as a nephroprotective agent in kidney's infirmities among diabetics by the traditional practitioners in Malaysia. However, the latter role of curry leaf has been grossly under reported and is yet to receive proper scientific evaluation.

Aim of the study

The present study was designed to investigate the beneficial effect of the leaves of Murraya koenigii (Linn.) on diabetes-induced renal damage in vivo with regard to prove its efficacy by local traditional practitioners in the treatment of kidney frailties in diabetics.

Materials and methods

Aqueous (AQ) extract of the leaves of Murraya koenigii (Linn.) was administered to both normal and streptozotocin (STZ) induced diabetic male rats (Sprague-Dawley strain). Animals were divided into six groups (n = 6) and treated with variable dose levels of AQ extract (200 and 400 mg/kg body weight/day) for 30 days. At the end of 30 days, animals were sacrificed, blood was collected, processed and stored at −70 °C for the zestimation of serum urea and creatinine, changes in plasma antioxidant capacity by FRAP assay, and glutathione peroxidase levels, in the normal and STZ-induced diabetic rats. Histological changes of the kidneys of these animals were also evaluated by light microscopy to determine the beneficial effect of the leaves.

Results

Daily oral administration of variable dose levels of the AQ extract for 30 days, produced significant dose dependant decrease in serum urea and creatinine levels (p < 0.001), and marked increase in the levels of plasma antioxidant capacity (p < 0.01) in diabetic treated rats, compared to the control (non-diabetic) subjects. However, the normal treated rats showed minimal variation in these parameters in comparison to normal controls. Histological studies of the kidneys of these animals showed comparable tissue regeneration by the AQ extract.

Conclusion

The results of our study scientifically support the traditional belief for using the leaves of Murraya koenigii (Linn.) as adjuvant, in the treatment of pain disorders related to renal impairments among diabetics.     

Antidiabetic activity of alcoholic stem extract of Nervilia plicata in streptozotocin-nicotinamide induced type 2 diabetic rats

Ethnopharmacological relevance

Nervilia plicata (Orchidaceae) has long been used in the antidiabetic medicinal preparations of traditional healers of Wayanad (Kerala), but recuperative potential of the plant was remained undefined. We demonstrated the regenerative potential of the plant extract on kidney affected by type 2 diabetes besides lowering blood glucose.

Aim of the study

The aim of the current study was to investigate the recuperative and regenerative potential of alcoholic stem extract of Nervilia plicata on streptozotocin-nicotinamide induced type 2 diabetic models.

Materials and methods

Non insulin dependent diabetes mellitus (NIDDM) was induced in overnight fasted rats by intramuscular injection (IMI) of 60 mg/kg STZ and 120 mg/kg of nicotinamide after 5 min interval. Blood glucose was assessed by a glucometer, serum urea and creatinine levels were determined by diacetylmonooxime method and Jaffe reaction respectively. Kidney sections were taken and stained with Masson's tri-dye and Periodic Acid Schiff (PAS) and examined for structural changes. Also lipid peroxidation product (LPP) levels were determined as thio barbituric acid reactive substance levels (TBARS) method.

Results

On administration of 5 mg/kg of plant extract, blood glucose levels of the NIDDM rats showed 62.00 and 76.29% decrease in the blood glucose levels on day 0 and day 30 respectively. Damages caused to the kidney tissue were negligible or not seen. Serum urea and creatinine levels showed 61.49 and 70.96% decrease on day 30. LPP levels of kidney and pancreas showed 70.58 and 77.41% decrease respectively.

Conclusion

These results demonstrate significant antidiabetic and regenerative potential of the Nervilia plicata, justifying the use of plant in the indigenous system of medicine. Isolation and characterisation of the compound(s) playing pivotal role in the cure would open new vistas in the therapy of type 2 diabetes.     

Second malignancies among elderly survivors of cancer

The U.S. population is aging, life expectancy is increasing, and cancer is a disease associated with aging. Advances in screening and therapeutics have led to a growing number of cancer survivors who are at risk for the development of secondary malignancies. Although the risks for the development of second malignancies following a first diagnosis of cancer are well described for survivors of childhood malignancies, there are fewer data for malignancies common in older adults. With the aging of the U.S. population, and with improving survival statistics in many adult malignancies, there is an increasing need to identify those second malignancies that might develop in the older adult survivor of cancer. In this paper, we describe the types and rates of second malignancies following cancers commonly seen in older adults and review the literature on these malignancies. Comparisons are made between older and younger adults with regard to the risks for developing treatment-related cancers with different modalities. Recommendations for early detection of second malignancies are summarized, though there remains an unmet need for evidence-based guidelines for screening for second malignancies in the older adult in particular.     

Update on the hyper immunoglobulin M syndromes

The Hyper‐immunoglobulin M syndromes (HIGM) are a heterogeneous group of genetic disorders resulting in defects of immunoglobulin class switch recombination (CSR), with or without defects of somatic hypermutation (SHM). They can be classified as defects of signalling through CD40 causing both a humoral immunodeficiency and a susceptibility to opportunistic infections, or intrinsic defects in B cells of the mechanism of CSR resulting in a pure humoral immunodeficiency. A HIGM picture can also be seen as part of generalized defects of DNA repair and in antibody deficiency syndromes, such as common variable immunodeficiency. CD40 signalling defects may require corrective therapy with bone marrow transplantation. Gene therapy, a potential curative approach in the future, currently remains a distant prospect. Those with a defective CSR mechanism generally do well on immunologoblulin replacement therapy. Complications may include autoimmunity, lymphoid hyperplasia and, in some cases, a predisposition to lymphoid malignancy.     

无痛人工流产的围手术期护理

目的探讨无痛人工流产的围手术期护理体会。方法对90例无痛人工流产患者围手术期给予综合护理措施。术前重点做好心理支持和护理准备,术中严密观察病情和精细配合手术,术后进行正确的健康指导。结果本组均顺利完成手术,无人工流产综合征发生。结论良好的围手术期护理是无痛人工流产术成功实施的重要保证。     

综合分析药物性肝损伤4076例

目的分析引起药物性肝损伤的原因、临床分型和预后。方法检索药物性肝损伤的相关文献并进行统计分析。结果本组资料显示药物性肝损伤以中年人居多,〉60岁者占20.4%,病死率约3.1%;引起肝损伤的前三位药物分别为中草药、抗结核药及抗生素,损伤类型以肝细胞损伤型居多,占54.2%;我国南北方未见明显地域差异。结论必须对患者加强引导,要遵照医嘱用药;对医务人员加强培训,注意鉴别诊断,及时报告,妥善处置。