吉非罗齐对实验性糖尿病大鼠的降糖作用及其机制研究

 目的观察吉非罗齐(gemfibrozil,Gem)对实验性2型糖尿病(type 2 diabetes mellitus,T2DM)大鼠的降糖、降脂作用及其可能机制。方法采用高糖高脂膳食4周诱导大鼠胰岛素抵抗后,腹腔注射亚致病剂量链脲佐菌素(streptozotocin,STZ)的方法制备T2DM模型,并观察Gem对其血脂、血糖代谢的影响及其可能机制。结果连续灌胃给药8周后,Gem显著降低实验性糖尿病大鼠的空腹血糖(fasting blood glucose,FBG)和三酰甘油(triglyceride,TG)、总胆固醇(totalcholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)及游离脂肪酸含量(nonesterified fatty acid,NEFA)(P<0.05或P<0.01),显著增高实验性糖尿病大鼠血清SOD活力(superoxide dismutase,SOD),降低模型组大鼠MDA(maleic dialdehyde,MDA)含量(P<0.05或P<0.01)。结论Gem不仅对实验性T2DM大鼠血脂具有良好的调节作用,还能改善实验性T2DM大鼠的血糖代谢,显著降低FBG。     

补肾中药对骨质疏松症大鼠下丘脑BMP-4、Smad6 mRNA及蛋白表达的影响

目的探索肾虚骨质疏松症的病理机制,研究补肾中药对肾虚骨质疏松大鼠防治作用的机理。方法实验采用去双侧卵巢的方法,建立肾虚骨质疏松症模型。补肾中药复方（高、中、低）剂量对实验大鼠治疗12周,以骨疏康颗粒、盖天力牡蛎钙作为阳性对照药,并设正常对照组和模型空白组。用RT-PCR法、Western印迹法检测肾虚骨质疏松症大鼠下丘脑组织中BMP-4、Smad6 mRNA和蛋白表达。结果①与正常组比较,模型空白组大鼠下丘脑组织中的BMP-4 mRNA和蛋白表达水平明显增强;Smad6 mRNA和蛋白表达水平明显降低。②与模型空白组比较,补肾中药组对模型大鼠下丘脑组织中的BMP-4 mRNA和蛋白表达明显降低;而Smad6 mRNA和蛋白表达明显增强。结论肾虚骨质疏松症的病理机制为肾精不足,骨髓、脑髓失养,表现在下丘脑-垂体-靶腺轴的调控失常,包括下丘脑组织的细胞因子及其信号传导通路的异常。     

Nitric oxide expression in airway epithelial cells in response to tubercle bacilli stimulation

Abstract In order to investigate the role of airway epithelial cells in pulmonary tuberculosis, inducible nitric oxide synthetase (iNOS) expression and nitric oxide (NO) production were studied in A549 cells. Peripheral blood mononuclear cells (PBMC) from normal volunteers were separated and cultured for 24h with LPS or tubercle bacilli (H37Rv, H37Ra). Thereafter, A549 cells were stimulated for another 24h with culture supernatant fluids of PBMC. iNOS messenger RNA (mRNA) expression was measured with Northern blot analysis and NO production was measured with the Griess reaction, which can measure nitrite concentration. iNOS mRNA expression and NO production were minimal in the control cells. iNOS mRNA expression and NO production were significantly increased with LPS ( P < 0.05) or tubercle bacilli ( P < 0.01) stimulation. However, there was no difference in iNOS mRNA expression and NO production between H37Rv and H37Ra stimulations. Interestingly, iNOS mRNA expression and NO production were greater in A549 cells stimulated with tubercle bacilli-conditioned media than in the cells stimulated with LPS-conditioned media. IL-1β, tumour necrosis factor-alpha and interferon gamma concentrations were increased in culture supernatant fluids of PBMC stimulated with tubercle bacilli. These findings suggest that airway epithelial cells may play a certain role in the pathogenesis of pulmonary tuberculosis by producing NO. However, the role of airway epithelial cells, regarding the virulence of tubercle bacilli, was not clear in this study.     

Effects of a problem‐solving counseling program to facilitate intensified walking on Koreans with type 2 diabetes

Aim: This study aimed to evaluate the immediate and long‐term effects of a 12 week problem‐solving (PS) counseling program to facilitate intensified walking with machinery monitoring on persons with type 2 diabetes mellitus in Korea. Methods: The study used a quasi‐experimental design. The participants were 57 patients with diabetes from three endocrinology or internal medicine clinics in an urban city of South Korea. Moderate‐intensity walking and PS counseling were recommended to both groups. The difference between the two groups was whether the intensity of the exercise was monitored by an ambulatory heart rate monitor (experimental group) or was self‐regulated (comparison group). Those programs were evaluated in relation to BMI, glycemic control (blood glucose level, glycosylated hemoglobin [HbA1c]), a vascular complication index (total cholesterol, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, triglycerides, tissue plasminogen activator [t‐PA], plasminogen activator inhibitor‐1 [PAI‐1], Parma Cardiovascular Risk Index), and coping strategies at 3 and 6 months. Results: The experimental group members showed dramatic decreases in their glucose and HbA1c levels at 3 months. The values of t‐PA decreased significantly at baseline, compared to at 3 months. The levels of PAI‐1 continuously declined and the Parma Cardiovascular Risk Index score did not change significantly from baseline to at 3 months, but showed significant effects at 6 months. Conclusion: A combined program of intensified walking, using a heart rate monitor, with PS counseling is more helpful to prevent complications than self‐regulated exercise for persons with type 2 diabetes in Korea.     

Just How Stable Are Escape Rhythms after Atrioventricular Junction Ablation?

Background: Atrioventricular (AV) node ablation with implantation of a permanent pacemaker is an established mode of therapy in the treatment of atrial fibrillation. However, concern exists regarding subsequent dependency on an entirely paced rhythm and the possible sequela of unheralded pacemaker failure. Data regarding escape rhythm lability, an important feature of pacemaker dependency, are limited. Aims and Methods: The purpose of this study was twofold: (1) to determine the characteristics of escape rhythms at predefined serial time intervals following AV node ablation and pacemaker implantation, and (2) to identify risk factors predictive of unstable escape rhythms. Patients undergoing AV node ablation and pacemaker implantation were assessed for the presence or absence of an escape rhythm during pacemaker interrogation at five predetermined serial time points. Baseline demographics and comorbid conditions were evaluated as potential predictors of those with labile escape rhythms. Results : Seventy‐nine percent of the 96 patients studied had an underlying escape rhythm (≥30 beats per minute) immediately postablation. Although the percentage of patients with an escape rhythm increased at each follow‐up interval, the number of patients who consistently demonstrated an escape rhythm declined with each follow‐up, with 28% of patients lacking an escape rhythm at some time point, i.e., labile escape rhythm. There were no significant predictors of a labile escape rhythm. Conclusion: Among patients who have undergone AV node ablation and pacemaker implantation, 72% have a stable escape rhythm over time, but others are at risk for pacemaker dependency, as predicted by an underlying absent or labile escape rhythm. (PACE 2010; 939–944)     

Is There Any Objective Improvement of Nocturia by Combination Treatment of Zolpidem and Alpha‐Blocker Therapy for Unresponsive to Alpha‐Blocker Monotherapy in Men with Lower Urinary Tract Symptoms?

Objectives: The aim of the present study was to determine whether administration of zolpidem, a nonbenzodiazepine sedative‐hypnotic agent, at night would improve the nocturia unresponsive to alpha‐blocker monotherapy in men with lower urinary tract symptoms (LUTS). Methods: This was a prospective observational study comprised of 39 men aged 50 years and older. The study inclusion criteria were age more than 50 years, and nocturia twice or more per night after taking alpha‐blockers for more than 8 weeks. A total of 39 patients met the criteria and constituted the study cohort. Pittsburgh Sleep Quality Index (PSQI), International Prostate Symptom Score (IPSS), frequency volume chart (FVCs) and uroflowmetry were recorded. Patients were given 10 mg alfuzosin and 10 mg zolpidem once at night for the 8 weeks. Results: There were no serious side‐effects in any patient. Nocturia decreased from a baseline (3.1 ± 0.1) to 8 weeks (1.6 ± 0.2) (P = 0.001). After treatment, global PSQI scores and severe sleep disorders improved. Storage and voiding symptoms including total IPSS scores and quality of life index improved. Nocturnal urine volume and functional bladder capacity improved. Maximum flow rate, voided volume increased and residual urine volume decreased. Conclusion: Combined zolpidem and alpha‐blocker therapy resulted in a subjective and objective reduction in nocturia episodes when given to men with nocturia unresponsive to alpha‐blocker monotherapy.     

In vitro metabolism of the new insecticide flupyrazofos by rat liver microsomes

1. The in vitro metabolism of the new insecticide flupyrazofos was studied using rat liver microsomes. Two metabolites were produced and identified as O, O -diethyl O -(1- phenyl-3-trifluoromethyl-5-pyrazoyl) phosphoric acid ester (flupyrazofos oxon) and 1- phenyl-3-trifluoromethyl-5-hydroxypyrazole (PTMHP) based on UV and mass spectral analysis. 2. Cytochrome P450 oxidatively converted flupyrazofos to flupyrazofos oxon, a major metabolite and phenobarbital-induced microsomes increased this desulphuration by 8- fold. 3. Flupyrazofos oxon was converted to PTMHP with a half-life of 47 8?min by chemical hydrolysis and this conversion also proceeded non-enzymatically under our microsomal incubation conditions.     

RP-HPLC法测定紫杉醇在大鼠血浆中的含量

目的建立紫杉醇在大鼠血浆中的定量分析方法,为药物动力学研究提供分析方法。方法采用RP-HPLC法。Li Chrospher 100反相C18色谱柱(250 mm×4.6 mm,5μm),乙腈-水(体积比50∶50)为流动相,流速为1.0 mL.min-1,紫外检测波长为227 nm,血浆样品经乙酸乙酯萃取,以内标法定量。结果线性范围为0.025~100.0 mg.L-1(r=1.0,n=5),日内RSD小于5%,日间RSD小于10%,定量限25μg.L-1。在以7.5 mg.kg-1的剂量静脉注射紫杉醇到大鼠身上后,药物很快分布到体内(t1/2α=0.16 h),并且快速的消除,消除半衰期仅有1.65 h,药物的平均保留时间tMR为0.52 h。结论所用方法简便、准确、专属性好,能够满足药物动力学研究的需要。