Dose-Related Hemodynamic and Electrocardiographic Effects of the Calcium Promoter BAY y 5959 in the Presence or Absence of Congestive Heart Failure

Objectives. The aim of this study was to assess the cardiovascular effects of BAY y 5959, a calcium promoter modulating myocardial calcium channels, in the presence or absence of congestive heart failure.

Background. There is still a clinical need for short-term administration of intravenous positive inotropes. BAY y 5959 was developed as a new approach to increase myocardial performance by selectively enhancing calcium influx in the myocytes.

Methods. Forty-one patients (21 without and 20 with congestive heart failure) were studied in an open label, dose-ranging study. Hemodynamic variables (including left ventricular [LV] angiography) and plasma samples were obtained at baseline and after 20 min of intravenous infusion of BAY y 5959 at doses ranging from 0.25 to 4.5 μg/kg body weight per min.

Results. In both study groups, BAY y 5959 produced dose-dependent increases in the indexes of inotropic state, without affecting isovolumetric relaxation rate. The magnitude of the response was comparable in patients with or without heart failure (average 38% increase in maximal first derivative of LV pressure [dP/dt max] at plasma levels of 100 μg/liter). BAY y 5959 also induced mild but statistically significant bradycardia and significantly decreased end-systolic volume while producing a leftward shift of the pressure-volume loop. Mean aortic pressure was unaffected at doses up to 3.0 μg/kg per min, and cardiac index improved in patients with heart failure at doses of 2.0 μg/kg per min (+23%, p < 0.05). However, at a dose of 4.5 μg/kg per min, mean aortic pressure and LV systolic wall stress increased, suggesting systemic vasoconstriction. The QT interval was also prolonged significantly at most doses.

Conclusions. BAY y 5959 exhibits positive inotropic effects in patients with and without heart failure. The optimal response— combining bradycardia, reduced preload and improved cardiac output—appeared to be achieved at a dose of 2.0 μg/kg per min. The impact of QT prolongation with regard to potential antiarrhythmic or proarrhythmic effects is unclear at this time.     

Short-term trial of clofazimine in previously untreated lepromatous leprosy.

Forty-five previously untreated lepromatous leprosy patients were allocated randomly to three groups and treated, respectively, with Regimen A, standard dosage of clofazimine (CLO) in multidrug therapy (MDT) regimen; Regimen B, CLO 600 mg once every 4 weeks; and Regimen C, CLO 1200 mg once every 4 weeks. The duration of the trial was 24 weeks. By the end of the trial, although a few patients in each group did not improve at all clinically, the majority of patients showed clinical amelioration but the responses were slow. While the mean morphological index dropped to the baseline after 24 weeks of treatment, the mean bacterial index did not change significantly. About 80% of the patients in each group remained nasal-smear positive at the end of the trial, but the bacterial loads steadily declined. No significant difference has been detected in these parameters among the three groups. The patients tolerated the regimens very well and the side effects were mild. The results of serial mouse foot pad inoculation demonstrated that the positivity rates of multiplication of Mycobacterium leprae in mice and the proportions of viable organisms reduced gradually in all groups. Because the positivity rate at week 24 in Group C did not differ significantly from Group A, but was significantly smaller than that of Group B, we conclude that Regimen C was as active as Regimen A and could be applied for monthly supervised treatment along with rifampin; Regimen B is less effective and should not be used for the treatment of leprosy.     

GR 38032F (Ondansetron), a selective 5HT3 receptor antagonist,slows colonic transit in healthy man

The newly recognized class of 5-hydroxytryptamine receptors (5HT₃) may be involved in the induction of nausea, since their pharmacological antagonists are effective against emesis induced by chemotherapy. 5HT₃ receptors are present on enteric neurons, and 5HT₃ blockers may produce mild constipation; we thus hypothesized that 5HT₃ receptors would modulate colonic motility. To determine if GR 38032F, a selective 5HT₃ antagonist known to have antiemetic effects, influences colonic transit in health, a randomized, double-blind, placebo-controlled crossover study was performed. Using a radiopaque marker technique, colonic transit was quantified in 39 healthy volunteers (19 men, 20 nonpregnant women) 18–70 years of age. On a standard 25-g fiber diet, 16 mg of GR 38032F was given orally thrice daily. Gastrointestinal peptides (peptide YY, human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, substance P) were also measured in plasma fasting and postprandially. Mean total colonic transit time on placebo was 27.8 hr, while on GR 38032F it was 39.1 hr (P<0.0005). Transit times through the left colon (P<0.0005) and rectosigmoid (P<0.05) were prolonged by the drug, but right colonic transit was not significantly altered. Transit times did not correlate with age or gender, but subjects with shorter transit times were significantly more affected than were those with longer transit times. The peak release of peptide YY was minimally decreased following GR 38032F (P<0.01), but the peak and integrated postprandial responses of human pancreatic polypeptide, neurotensin, motilin, gastrin-cholecystokinin, and substance P were not significantly altered by the drug. We conclude that 5HT₃ receptors may be involved in the regulation of colonic transit in healthy man.Supported in part by a grant from Glaxo Group Research, Ltd., and the Mayo Digestive Disease Center (grant DK34988, National Institutes of Health, Bethesda, Maryland).Presented, in part, at the American Motility Socicty in October 1988, and published as an abstract inGastroenterology 95:891, 1988.     

Family history of diabetes and risk of atherosclerotic cardiovascular disease in Korean men and women

The importance of family history of type 2 diabetes (FHD) as a risk factor for atherosclerotic cardiovascular disease (ASCVD) remains controversial. A report of diabetes in parents and siblings was used to establish FHD in a cohort of 1,005,230 Koreans aged 30-95 years insured by the National Health Insurance Corporation who had a biennial medical evaluation during 1992-1995. ASCVD morbidity and mortality from 1993 to 2005 were examined in relation to FHD and other ASCVD risk factors. The risk of ischemic heart disease (IHD) increased significantly (19%) in men with FHD but not in women. A strong interaction was observed between FHD and personal history of diabetes for the occurrence of ASCVD; men with both diabetes and FHD were at significantly increased risk of developing IHD, cerebrovascular disease and ASCVD with hazard ratios (HR) of 2.28, 2.07, and 2.12, respectively, compared to those who had neither FHD nor type 2 diabetes. Corresponding risks were 2.64, 2.03, and 2.10 in women, respectively. This study demonstrates that risk of ASCVD is increased among those with diabetes and a family history of diabetes; suggesting that genetic factors associated with occurrence of familial diabetes may increase risk of ASCVD beyond the risk among people without FHD.     

血清IgG4水平升高患者临床和实验室指标的分析

目的研究血清免疫球蛋白G亚型4(IgG_4)升高患者的临床特点,探讨IgG_4水平检测对不同疾病诊疗的价值。方法2013年2月—2017年4月来我院就医的门诊及住院血清IgG_4水平升高(以国际推荐的血清IgG_4水平≥1.35 g/L为异常值)且诊断明确的患者共112例,根据诊断结果分为IgG_4相关性疾病组(8例)、风湿免疫病组(40例)、呼吸系统疾病组(31例)和其他疾病组(33例)。收集临床和实验室检查资料,进行比较分析。结果在4组疾病患者中,IgG_4相关性疾病患者的IgG_4水平明显高于免疫风湿疾病组、呼吸系统疾病组和其他疾病组(P0.05)。根据实验室检查资料,C反应蛋白、免疫球蛋白E和血沉这3项指标阳性率较高,分别为80.0%、80.0%和77.7%;IgG、血沉与IgG_4的水平呈正相关,而补体C3、C4、清蛋白、前清蛋白和IgG_4水平呈负相关。结论 IgG_4检测对IgG_4相关疾病有重要的诊断价值,临床上对于免疫球蛋白、血沉水平升高,补体和清蛋白、前清蛋白水平降低等异常指标的患者,可及时检测IgG_4水平,结合不同部位的受累器官早期做出诊断。     

GC-MS法分析蛇床子的脂溶性成分

〗摘 要 目的： 研究蛇床子的脂溶性成分。方法: 用索氏提取法提取蛇床子的脂溶性成分,甲酯化处理后,采用气相色谱 质谱联用技术首次对其脂溶性成分进行分析和鉴定。结果: 从蛇床子中鉴定了39个化合物,占蛇床子脂溶性成分的85.33%,蛇床子主要的脂溶性成分为植物醇(15.98%)、棕榈酸(12.73%)、9,12,15 十八碳三烯酸(11.02%)、油酸(6.33%)和9,12 十八碳二烯酸(4.77%)。结论:植物醇、棕榈酸、9,12,15 十八碳三烯酸和油酸是蛇床子的活性成分。     

山风化学成分研究

摘 要 目的： 研究中药材山风的化学成分。方法: 采用薄层色谱、硅胶及凝胶柱色谱法对山风进行分离纯化,通过理化方法和波谱数据进行结构鉴定。结果: 从山风中分离得到10个化合物,通过波谱数据及理化性质分别鉴定为油酸(1)、亚油酸(2)、槲皮素(3)、木犀草素(4)、柚皮素(5)、橙皮素(6)、没食子酸(7)、β 谷甾醇(8)、胡萝卜苷(9)和橙皮苷(10)。结论:化合物1、2、5、6、7、10为首次从山风中分离得到。     

胡椒碱胶囊自乳化释药系统的处方筛选及体外质量评价

摘 要 目的： 研究胡椒碱自乳化释药系统的处方及其体外特性。方法: 通过溶解度、处方配伍试验以及伪三元相图的绘制来筛选处方,并考察空白处方、含药处方对自乳化效率的影响以及自乳化后乳滴的粒度分布,考察了胡椒碱自乳化胶囊的溶出速率和稳定性。结果: 胡椒碱自乳化胶囊的最终处方为油酸乙酯、Tween 80、Transcutol P,三者之比为30∶55∶15（w∶w∶w）,药物为辅料总量的2.5%,粒径约为90 nm,胡椒碱自乳化胶囊60 min溶出度是自制的胶囊剂6倍;低温和常温稳定性考察药物含量无明显变化。结论:所制备的胡椒碱自乳化胶囊自乳化效率高、能力强、性质稳定,体外溶出率高。