Neuroprotective effects of alpha-lipoic acid in experimental spinal cord injury in rats

Background:

Oxidative stress is a mediator of secondary injury to the spinal cord following trauma.

Objective:

To investigate the putative neuroprotective effect of α-lipoic acid (LA), a powerful antioxidant, in a rat model of spinal cord injury (SCI).

Methods:

Wistar albino rats were divided as control, vehicle-treated SCI, and LA-treated SCI groups. To induce SCI, a standard weight-drop method that induced a moderately severe injury (100 g/cm force) at T10 was used. Injured animals were given either 50 mg/kg LA or saline at 30 minutes postinjury by intraperitoneal injection. At 7 days postinjury, neurologic examination was performed, and rats were decapitated. Spinal cord samples were taken for histologic examination or determination of malondialdehyde (MDA) and glutathione (GSH) levels, myeloperoxidase (MPO) activity, and DNA fragmentation. Formation of reactive oxygen species in spinal cord tissue samples was monitored by using a chemiluminescence (CL) technique.

Results:

SCI caused a significant decrease in spinal cord GSH content, which was accompanied with significant increases in luminol CL and MDA levels, MPO activity, and DNA damage. Furthermore, LA treatment reversed all these biochemical parameters as well as SCI-induced histopathologic alterations. Conversely, impairment of the neurologic function caused by SCI remained unchanged.

Conclusion:

The present study suggests that LA reduces SCI-induced oxidative stress and exerts neuroprotection by inhibiting lipid peroxidation, glutathione depletion, and DNA fragmentation.     

Analysis of superoxide dismutase activity levels in gingiva and gingival crevicular fluid in patients with chronic periodontitis and periodontally healthy controls

OBJECTIVES: Superoxide dismutase (SOD) is an antioxidant enzyme that acts against superoxide, an oxygen radical, released in inflammatory pathways and causes connective tissue breakdown. In this study, SOD activities in gingiva and gingival crevicular fluid (GCF) from patients with chronic periodontitis (CP) and periodontally healthy controls were compared. MATERIAL AND METHODS: Twenty-six CP patients and 18 controls were studied. In patients, teeth with moderate-to-severe periodontal breakdown and > or =5 mm pockets that required full-thickness flap surgery in the right or left maxillary quadrant, and in controls, teeth scheduled for extraction for orthodontic reasons were studied. After the clinical measurements (probing depth, clinical attachment level, gingival index, gingival bleeding index, plaque index), GCF samples were collected. Tissue samples were harvested from the same teeth, during flap operation in patients and immediately after tooth extraction in controls. SOD activities were spectrophotometrically assayed.The results were statistically analysed. RESULTS: Gingival SOD activity was significantly higher in the CP group than in controls (p<0.05). No significant difference was found in GCF SOD activity between the groups (p>0.05). Correlations between gingival and GCF SOD activities were not statistically significant in CP and control groups (p>0.05). CONCLUSION: In CP, SOD activity seems to increase in gingiva, probably as a result of a higher need for SOD activity and protection in gingiva in CP than in periodontal health, while not significantly changing in GCF, suggesting a weak SOD activity in GCF in periodontal disease state. The weak correlation between gingival and GCF SOD activities suggests distinct actions of these SODs.     

争光霉素A6和它在争光霉素复合物的地位

争光霉素A₅已鉴别为Bleomycin A₆,在争光霉素复合物中所占比例一般在10%左右,在某些批样中可高达15%以上。文献报告Bleomycin A₆在天然产的Bleomyein复合物中只有痕量。通过向发酵培养基中加入特定组分的末端胺可大大提高其特定组分在复合物中的含量比而其它组分的产生则不同程度地被抑制。但Bleomyein A₆例外,即使向培养基中加入其末端胺精胺(0.3mg/ml),在所产生的复合物中大大增多的组分是Bleomyein A₆,而Bleomycin A₆仍只有痕量。这表明争光霉素产生菌有和Bleomycin产生菌明显不同的特点。     

T2 estimates in healthy and diseased brain tissue: a comparison using various MR pulse sequences

Fourteen patients and five healthy individuals underwent magnetic resonance (MR) imaging to determine an effective multiple spin echo pulse sequence for estimating T2. Lesions examined included infarction, glioma, multiple sclerosis, and acute hematoma. A pulse repetition time (TR) of 1,500 msec and echo delays (TEs) of 25, 50, 75, and 100 msec were used. Computed T2 images were derived from all four echoes, the first two echoes, and the first and fourth echoes. T2 values were obtained from specific brain locales using region-of-interest analysis. Use of either the first two echoes or the first and fourth in the T2 fit provided T2 estimates which closely correlated with that of the four-echo analysis. The noise level in T2 maps constructed from the 25- and 100-msec echoes was modestly (typically 10%) higher than that from four echoes; noise level from the 25- and 50-msec echoes was markedly higher, typically 60%. This behavior is remarkably consistent with that predicted from theory. All 19 subjects displayed consistent relative T2 values for specific brain structures; in 13, the absolute T2 values fell within a limited range. Despite the high sensitivity of T2 images, their specificity in the detection of most brain disease appears limited except in acute intracerebral hematoma, which exhibited a decreased T2 relaxation time using high-field-strength MR imaging.     

浙贝母化学成分的研究——Ⅲ.浙贝酮的分离和鉴定

前文报道了从浙贝母(Fritillaria thunbergii Miq.)鳞茎中分离到浙贝甲素(peimine,Ⅰ)、浙贝乙素(peiminine,Ⅱ)、eduardine(Ⅲ)及二个新生物碱即浙贝宁(zhebeinine,Ⅳ)和浙贝丙素(zhebeirine,Ⅴ),它们均为具有C-去甲-D-高甾基本骨架的生物碱。 最近又从该植物中分得一新的微量生物碱命名为浙贝酮,本文报告该生物碱的分离和结构鉴定。 浙贝酮(Ⅵ)为无色针晶(丙酮),mp 181～183℃,高分辨质谱测得分子式C_(27)H_(43)NO_3,     

Factors influencing the outcome of idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy

Idiopathic sudden sensorineural hearing loss (ISSNHL) is an otologic emergency with an incidence of about 5–20 per 100,000 of the population per year. There is no universally accepted standard protocol for the treatment of patients with ISSNHL. Hyperbaric oxygen therapy (HBOT), was first reported to improve the outcome following acute inner ear disorders during the late 1960s by both French and German authors. The increase in perilymph oxygenation produced by HBOT provides logical basis for the use of this treatment modality in ISSNHL. We reviewed the records of 97 cases that received HBOT for SSNHL to identify the factors that may affect the treatment outcomes. The effects of age, gender, affected ear, status of the contralateral ear, symptoms associated with hearing loss, presence of a cardiovascular disease, dyslipidemia, history of diabetes mellitus, seasonal factor, smoking, degree of hearing loss, audiogram type, medical treatments provided prior to HBOT, onset time, and number of HBOT sessions were evaluated. The mean hearing gain in all cases after the HBOT was 29.5 dB. The gains were statistically significant in the following cases: early onset of HBOT (p = 0.016), higher number of HBOT sessions (p < 0.01), steroid usage (p = 0.009), low frequency-ascending and total audiogram configuration (p < 0.01) and profound hearing loss (p = 0.011). The success rate was significantly lower in cases with high frequency-descending audiogram configuration (p < 0.001). The most important factor affected the prognosis favorably was found as steroid therapy. This retrospective study and our clinical experience suggest that HBOT has beneficial effects when administered in the early phase of the disease together with steroids. HBOT is a safe practice when used properly by an experienced hyperbaric team. In the treatment of ISSNHL, 20 sessions of HBOT at 2.5 ATA can be tolerated well besides some minor side effects. HBOT should be considered for the cases especially with total or profound hearing loss.     

中华大蟾蜍皮化学成分的研究

从中华大蟾蜍(Bufo bufo gargarizans Cantor)皮水溶性部分应用制备型反相HPLC分离得到一个新蟾蜍毒素,根据光谱(UV,IR,¹HNMR,¹³CNMR,EIMS,FDMS)、氨基酸分析及化学性质,确定其结构为Ⅰ所示,命名为蟾毒它灵3-丁二酰精氨酸酯,同时还分到三个已和蟾蜍毒素;蟾毒灵3-丁二酰精氨酸酯(Ⅱ),华蟾毒精3-丁二酰精氨酸酯(Ⅲ),脂蟾毒配基3-丁二酰精氨酸酯(Ⅳ)。     

肾包膜内注射骨髓间充质干细胞在链脲佐菌素糖尿病模型大鼠体内的定位及功能测评

目的:观察骨髓间充质干细胞在体外不诱导条件下,移植于链脲佐菌素所致糖尿病大鼠后在胰腺的定位及胰岛素分泌情况。方法:实验于2004-08/2006-03在2级实验室唐山工人医院中心实验室和具有国家认证的屏障动物环境实验室华北煤炭医学院动物中心完成。①实验材料:青年清洁级SD大鼠购自华北煤炭医学院动物中心(SCXK2002-0003),4周龄,体质量180～250g,动物级别:SPF/VAF。②实验方法:体外培养雄性SD大鼠骨髓间充质干细胞,并采用流式细胞仪鉴定。选取雌性SD大鼠,按65mg/kg剂量腹腔注射链脲佐菌素建立糖尿病大鼠模型。给药后二三天,大鼠血糖升高,当血糖≥16.7mmol/L且稳定2d,认为糖尿病模型建立成功。将建模成功的40只大鼠完全随机分为对照组、实验组,每组20只。对照组大鼠右侧肾包囊注射磷酸缓冲液0.2mL,实验组大鼠右侧肾包囊下注射骨髓间充质干细胞0.2mL,细胞数为4×105L-1。于移植前及移植后第3,5,7天采大鼠尾静脉血检测血糖。③实验评估:于移植前及注射后7d采大鼠心脏血检测C-肽值,移植后7d取大鼠胰腺组织作石蜡切片,应用原位杂交技术检测Y染色体细胞。结果:40只大鼠全进入结果分析。①骨髓间充质干细胞鉴定:骨髓间充质干细胞呈梭形、放射状,形成数个细胞克隆时排列整齐,原代培养7～10d即可长满,按1∶3传代,生长四五天达融合。流式细胞术表面标志鉴定显示,培养的原代骨髓间充质干细胞表面标志CD90阳性,基质细胞表面标志CD44阳性,造血细胞表面标志CD45及内皮细胞表面标志CD31阴性。②大鼠尾静脉血血糖值、心脏血C-肽值分析:血糖结果显示,对照组治疗后第3,5,7天血糖值及C-肽值与治疗前相比,无明显变化(P>0.05);实验组治疗后第3,5,7天血糖值较治疗前明显下降,治疗后第7天C-肽值明显上升,与对照组对应时间比较,差异均显著[实验组治疗前:(21.75±2.44)mmol/L,(0.21±0.01)μg/L;实验组治疗后:(12.23±1.95)mmol/L,(14.00±2.85)mmol/L,(12.75±2.86)mmol/L,(0.26±0.01)μg/L;对照组治疗后:(21.63±1.34)mmol/L,(23.03±1.11)mmol/L,(22.48±1.92)mmol/L,(0.21±0.01)μg/L,P均<0.01]。③原位杂交技术检测Y染色体细胞:对照组大鼠胰腺组织切片中未见黄绿荧光Y染色体,实验组大鼠胰腺组织切片中可见黄绿荧光Y染色体,存在于胰腺腺泡间隙,或胰腺组织中。结论:雄性大鼠骨髓间充质干细胞在肾包囊注射下可到达雌性糖尿病大鼠胰腺组织,使糖尿病大鼠血糖下降,C-肽值升高,具有分化为胰岛素分泌细胞的可能性。     

Nodular lymphocyte predominance Hodgkin's disease: a monoclonal or polyclonal B-cell disorder?

Nodular lymphocyte predominance Hodgkin's disease (NLPHD) is characterized by the presence of atypical putatively neoplastic cells (L & H cells) with a B-cell phenotype. A proportion of patients with NLPHD develop a simultaneous or subsequent large cell B lymphoma (LCL) that is thought to evolve directly from the L & H cells of NLPHD. However, the clonal nature of L & H cells remains controversial, and the relationship between NLPHD and complicating LCL has not been fully established. In an attempt to determine the clonality of L & H cells and to clarify the link between NLPHD and complicating LCL, we used polymerase chain reaction (PCR) to analyze 33 cases of NLPHD, including 15 cases with simultaneous or subsequent LCL, for clonal immunoglobulin (lg) heavy chain variable region (VH) gene rearrangements. PCR amplifications with consensus primers covering framework 2 or framework 3 to joining region were performed on paraffin-embedded tissue sections and, in 12 cases, on microdissection-enriched L & H cells. No clonal Ig rearrangements were detected. In eight of the 15 LCL, monoclonal IgVH regions were amplified, four of which were cloned and sequenced. Clone specific primers were designed based on the unique N region sequences. These allowed detection of LCL clones at a sensitivity up to 1,000 times greater than the consensus primers, as determined by dilution assays. However, no LCL clones were detected in the preceding NLPHD, including microdissection-enriched L & H cells. Our results suggest that populations of L & H cells do not carry monoclonal Ig rearrangements and provide no evidence for a clonal link between NLPHD and complicating LCL.