Therapeutic role of low-carbohydrate ketogenic diet in diabetes

IntroductionChanges in dietary habits influence the glycemic level. Preliminary studies using the low-carbohydrate ketogenic diet (LCKD) were found to be quite promising in controlling diabetes mellitus. Therefore, the objectives of this study are to investigate the therapeutic effects of LCKD in experimental diabetic rats following the administration of streptozotocin (STZ).Materials and methodsAdult rats were divided into three groups: normal diet, LCKD, and high-carbohydrate diet. Each group was subdivided into normal, sham, and diabetic groups. Diabetes was induced by a single intraperitoneal injection of STZ (55 mg/kg). Specific diets were given to each group of animals for a period of 8 wk and then the animals were sacrificed. The rats were monitored daily for food and water intake, whereas body weight, urine output, and blood glucose levels were monitored weekly. The histology of the islets of Langerhans was studied by histochemical methods.ResultsThe results showed that LCKD was effective in bringing blood glucose level close to normal (P < 0.01). Food and water intake and urine output were increased in all groups except the LCKD group (P < 0.01). The body weight was significantly reduced in all diabetic animals except in the LCKD group (P < 0.01). Histologic studies showed significant decrease in the islet size and number of β cells in all the diabetic groups.ConclusionThis study indicates that LCKD has a significant beneficial effect in ameliorating the diabetic state and helping to stabilize hyperglycemia.     

Biochemical and genetic analysis of Leigh syndrome patients in Korea

Sixteen Korean patients with Leigh syndrome were identified at the Seoul National University Children’s Hospital in 2001–2006. Biochemical or molecular defects were identified in 14 patients (87.5%). Thirteen patients had respiratory chain enzyme defects; 9 had complex I deficiency, and 4 had combined defects of complex I + III + IV. Based on the biochemical defects, targeted genetic studies in 4 patients with complex I deficiency revealed two heteroplasmic mitochondrial DNA mutations in ND genes. One patient had the mitochondrial DNA T8993G point mutation. No mitochondrial DNA defects were identified in 11 (68.7%) of our LS patients, who probably have mutations in nuclear DNA. Although a limited study based in a single tertiary medical center, our findings suggest that isolated complex I deficiency may be the most common cause of Leigh syndrome in Korea.     

Immunohistochemical expression of hormone receptors and the histological characteristics of biochemically hormone receptor negative breast cancers

Background  Most of the discordant cases between biochemical and immunohistochemical (IHC) assays for hormone receptor (HR) status in breast cancers are due to negative findings from the biochemical assay but positive IHC findings. However determining HR status based on IHC only in biochemically HR negative breast cancers has never been studied. The aim of this study is to examine the histological characteristics in immunohistochemically HR positive but biochemically HR negative breast cancers. Methods  IHC staining for HRs in 345 biochemically HR-negative breast cancers was done. The relationship between HR status by IHC and the histological characteristics was assessed. Results  In 345 cancers, 105 (30.4%) were estrogen receptor- (ER) or progesterone receptor- (PR) positive by IHC. The enzyme-immunoassay (EIA) HR titer was higher in immunohistochemically HR-positive tumors (ER: 2.7 fmol/mg protein; PR: 0.8 fmol/mg protein) than in negative tumors (0.6 fmol/mg protein in both HRs). IHC-assessed ER positivity on histological sections was high in some tumor types, such as mucinous carcinoma (77.8%), invasive micropapillary carcinoma (66.7%), and infiltrating ductal carcinoma of no special type with abundant stroma (60.2%). Among infiltrating ductal carcinomas of no special type, low nuclear grade tumors were all ER positive and high nuclear grade tumors showed low ER positivity by IHC, even in biochemically HR negative cancers. Conclusion  The IHC-assessed HR status may reflect tumor cell behavior, such as overall and disease-free survival and endocrine response, better than HR status as assessed by the enzyme-immunoassay method. Immunohistochemically HR-positive but biochemically HR-negative breast cancers include infiltrating ductal carcinomas of no special type with low nuclear grade and some tumor types with high stromal content. We can assess the true HR status by IHC especially these tumors.     

猴株五日热巴尔通体药敏及生化特性研究

目的 了解猴株五日热巴尔通体的生化特性和药物敏感性, 为进一步研究五日热巴尔通体的耐药机制奠定基础。方法 采用E test法, 检测1株五日热ATCC参考株及10株五日热巴尔通体猴分离株的生化特性及对14种抗生素的最低抑菌浓度(MIC)。结果 H15SC对利福平高度耐药(MIC256), 其余菌株敏感;H98SC对克林霉素耐药, 其余菌株敏感;除S13外, 其余10株菌株对丁胺卡那霉素、多粘菌素MICs值较高;全部菌株对阿奇霉素、头孢他啶、环丙沙星、庆大霉素、红霉素、妥布霉素、氯霉素、强力霉素、苄星青霉素敏感。结论 首次发现巴尔通体菌株对利福平高度耐药, 需要进一步了解其耐药机制, 减少不合理用药, 预防利福平耐药在人分离株中发生。     

5-HT1A receptor agonists: recent developments and controversial issues

During the last decade, serotonin (5-HT)_1A receptors have been a major target for neurobiological research and drug development. 5-HT_1A receptors have been cloned and a variety of selective agonists, such as the aminotetraline 8-OH-DPAT and the pyrimidinylpiperazine ipsapirone, have become available. Demonstrations of apparent intrinsic activity of these ligands at 5-HT_1A receptors, however, depend highly on the particular assay system. This may be due to the possible existence of receptor subtypes and to assay (or brain region)-dependent differences in receptor reserve and the nature of receptor-effector coupling. Nevertheless, the apparent intrinsic activity of 8-OH-DPAT seems to be higher (although possibly not yet maximal) than that of the pyrimidinylpiperazines. In the brain, 5-HT_1A receptors are located presynaptically as somatodendritic receptors on 5-HT neurons and postsynaptically in particular limbic and cortical regions. Although it is generally accepted that presynaptic 5-HT_1A receptors control 5-HT neuronal activity, recent evidence suggests an additional role of postsynaptic 5-HT_1A receptors in cortex as part of a negative feedback loop. Anxiolytic and antidepressive properties of selective 5-HT_1A receptor agonists have now been confirmed by clinical studies. Although it is well established that the latter properties depend on theagonistic activity of these compounds, theoptimal level of intrinsic activity is still a matter of debate and may be dependent on the clinical indication. Such compounds may also have antiaggressive effects, and possibly anticraving effects (manifested by their alcohol intake-reducing effects in dependent animals), but the specificity of these so-called anti-impulsivity effects is still controversial and not yet tested clinically. Anticataleptic, antiemetic and neuroprotective properties have been demonstrated in different species. Behavioral studies on the mechanisms underlying the anxiolytic and antidepressive effects have examined the relative contribution of pre-and postsynaptic 5-HT_1A receptors by means of local cerebral application and lesion techniques. Most evidence points towards a critical involvement of presynaptic receptors in the anxiolytic effects of 5-HT_1A receptor agonists (although a possible contribution of postsynaptic receptors cannot be excluded). With regard to the antidepressive properties, a case can be made for the reverse; i.e., a strong involvement of postsynaptic receptors and a questionable contribution of presynaptic receptors. However, as the therapeutic effects of those 5-HT_1A receptor (partial) agonists which have been tested clinically require repeated administration, attention has been directed increasingly towards chronic studies. These studies have shown that a number of electrophysiological, biochemical, behavioral and endocrinological 5-HT_1A receptor-related events adapt differentially to repeated or sustained administration. Thus, several hypotheses accounting for the delayed onset of action have been advanced. Among these, time-dependent downregulation /desensitization of eitherpre- orpostsynaptic 5-HT_1A receptors, or cortical 5-HT₂ receptors have received much attention. However, these hypotheses have their weaknesses, and it is argued thatfunctional sensitization of particular postsynaptic 5-HT_1A receptor-mediated events remains a valuable alternate hypothesis. Basic research on the role of 5-HT_1A receptors in psychopathology and in the therapeutic effects of clinically effective therapeutics, as well as on the mechanism of action of 5-HT_1A receptor ligands, will enable rational design of ligands with particular profiles of intrinsic activity at different 5-HT_1A receptor populations, and may contribute to a more efficient treatment of a multiplicity of brain disorders.     

不同月龄SPF级SD大鼠血液学及生化指标的变化

目的探讨不同生长期SPF级SD大鼠的血液学指标及生化指标的差异。方法采用血液分析仪分别测定SPF级SD大鼠2月龄、3月龄、4月龄、7月龄、8月龄时血液白细胞(WBC),红细胞(RBC),血红蛋白(HGB),红细胞压积(HCT),平均红细胞体积(MCV),平均红细胞血红蛋白量(MCH),平均红细胞血红蛋白浓度(MCHC),血小板(PLT)等指标;运用全自动生化测定仪测定其谷丙转氨酶(ALT)、谷草转氨酶(AST)、总蛋白(TP)、白蛋白(ALB)、血糖(GLU)、尿素氮(BUN)、肌酐(CREA)、甘油三酯(TG)等指标。结果结果表明大鼠RBC数量随年龄增长逐渐增大,雄性大鼠PLT数量逐渐增大,MCV减小,雌性HGB、HCT逐渐增大,且WBC、RBC、HGB、HCT数量随年龄增长呈现雌雄差异,雌性值偏小;大鼠各血液学指标均有较大的波动,其中以WBC和PLT的波动范围最大;随年龄的增长,雄性大鼠TP值逐渐减小;雌性大鼠TG逐渐升高;TP、ALB、BUN呈现雌雄差异,且雌性偏高;大鼠各生化指标均有较大的波动,以AST的波动范围最大。结论研究结果表明:大鼠的部分血液学及生化学指标存在性别及年龄的差异。     

Studies on cyclic AMP metabolism in human epidermoid carcinoma (HEp-2) cells.

Cultured human epidermoid carcinoma (HEp-2) cells were found to contain a highly responsive, catecholamine-sensitive adenyl cyclase activity in cellfree preparations. By contrast, cyclic AMP levels in intact HEp-2 cells were at best only marginally increased by catecholamines under a variety of conditions. The lack of an intact cell response could not be accounted for by escape of cyclic AMP to the medium, excessive phosphodiesterase activity, inactivation of the catecholamine, or by unusual kinetics of the system. However, in the presence of 1-methyl,3-iso-butylxanthine (MIX), a potent phosphodiesterase inhibitor, a moderate catecholamine response was observed in the intact cells. A significant elevation of cyclic AMP levels in the presence of MIX was observed at 0.3 muM epinephrine, and maximal levels occurred at 10 muM. Norepinephrine was much less effective than either epinephrine or isopropylnorepinephrine at 10 muM concentrations. In addition, intact cells slowly but steadily released cyclic AMP into the incubation medium over the course of 60-min incubations in the presence of MIX and epinephrine; maximum intracellular levels were reached by 5 min.     

Ⅱ型糖尿病患者血栓标志物和血小板活化状态研究

目的探讨Ⅱ型糖尿病患者外周血中血栓标志物(D-二聚体D-D,血管性血友病因子(vWF),抗凝血酶活性AT:A,纤溶酶原活性PLG:A)水平变化和血小板活化状态标志物血小板α颗粒膜糖蛋白CD62P及溶酶体膜糖蛋白CD63的阳性表达率与糖尿病血管病变的关系。方法采用免疫比浊法、发色底物法和流式细胞术分别测定79例Ⅱ型糖尿病患者(其中45例合并血管病变)和39例健康对照者外周血中的D-D、vWF、AT:A、PLG:A水平和CD62P及CD63阳性表达率。结果糖尿病组D-D、vWF水平和CD62P、CD63的阳性表达率均明显高于对照组(P<0.05及0.01),AT:A、PLG:A水平均明显低于对照组(P<0.05及0.01)无血管病变者PLG:A水平与对照组比较,差异无统计学意义(P>0.05),有血管病变者各标志物与无血管病变者比较,差异有统计学意义(P<0.05及0.01)。相关分析D-D水平与vWF水平差异无统计学意义(P>0.05),而CD62P、CD63之间呈正相关(r=0.673,P<0.01)结论Ⅱ型糖尿病患者均存在血管内皮细胞损伤,并由此引起血小板活化、血液高凝和血栓前或血栓状态;D-D、vWF、AT:A、PLG:A、CD62P、CD63水平在一定程度上可反映Ⅱ型糖尿病患者血管病变情况,检测其水平对其诊断、观察病情及防止血管病变和血栓的发生发展均有意义。     

中西医结合治疗胎盘植入临床分析

目的探讨治疗胎盘植入的有效方法。方法将31例胎盘植入的患者分为两组,治疗组16例,采用肌内注射甲氨蝶呤20 mg,连续5 d,同时口服中药生化汤(加减)治疗;对照组15例采用中药生化汤(加减)治疗。结果两组治疗后血β人绒毛膜促性腺激素(β-HCG)值明显下降,而治疗组下降更明显(P<0.01),治疗组血β-HCG下降至正常的时间明显短于对照组(P<0.01),宫腔内残留组织缩小程度治疗组更明显(P<0.01)。结论中西医结合治疗是胎盘植入较理想的保守治疗方法,能最大限度地保留患者的生育功能。     

五年制医学专业生物化学PBL教学实践与初探

目的激发学生的学习兴趣与参与意识，培养高素质的医学人才。方法将学生分成若干小组，每小组10人，在1名教师指导下进行三段式PBL教学。结果学生由被动变为主动，学习的积极性提高了，综合分析问题和解决问题的能力、口头表达能力与交际能力提高了，同学之间的协作关系加强了。结论PBL教学比单纯灌输的教学效果要好。不过，进行PBL教学时要选好年级、选好班级、选好教师。