Unaltered insulin sensitivity during calcium channel blockade with amlodipine

Summary The sensitivity of peripheral tissues to insulin is of pathophysiological, therapeutic and possibly also of prognostic relevance. Calcium channel blockers are widely used in the treatment of cardiovascular disorders that are commonly associated with decreased insulin sensitivity (S_I). To evaluate the effects of calcium channel blokkade on S_I, glucose homoeostasis and lipid profiles, studies were made of S_I (determined by the Minimal Model Method of Bergman), basal glucose and insulin levels, serum total triglyceride (Tg) and lipoprotein cholesterol (C) fractions and certain other variables in 38 healthy young men (24 y) during placebo and after 3 weeks of calcium channel blockade with amlodipine 5 mg once daily. Measurements were made after 3 days on a standard diet (2200 kcal · day^–1, 45% carbohydrates, 40% fat and 15% proteins) and after an overnight fast. Compared to placebo, amlodipine decreased supine systolic blood pressure (P<0.01). Heart rate, body weight and 24 h urinary sodium excretion were unaltered, and so were fasting plasma glucose (placebo vs amlodipine: 4.86 vs 4.83 mmol·1^–1, respectively) and insulin levels (7.7 vs 7.9 U·ml^–1), S_I (10.5 vs 9.6·10^–4 × min^–1 pro U·ml^–1), serum total Tg, C and lipoprotein C fractions.The findings demonstrate unchanged insulin sensitivity and secretion, as well as lipoprotein regulation, during maintenance administration of 5 mg amlodipine daily to healthy young men.This work was supported in part by the Swiss National Science Foundation     

Time course of the anti-oedematous effect of O-(β-hydroxyethyl)-rutosides in healthy volunteers

Summary O-(-hydroxyethyl)-rutosides (HR) is used for the treatment of disorders of the venous and microcirculatory systems. In order to evaluate the time course of its activity, the effect of HR on a provocation model of orthostatic oedema in healthy volunteers was used. After a 2 week placebo run-in period, 16 healthy volunteers were randomized to HR (2 tablets of 500 mg/day) of placebo for a further 3 weeks, in a double-blind parallel design. Oedema was provoked by standing motionless for 1 h, with measurement of leg volume before and afterwards. The procedure was undertaken at entry to the study and then weekly during the entire 5 week period.There were no significant differences in the extent of oedema produced by the orthostatic challenge during the 2 week run-in period or in the subjects who continued on placebo (90 arbitrary units i.e. 48 ml). During the 3 week treatment with HR, however, there was a progressive reduction (–1.1, –5.9, and –7.6 arbitrary units after 1, 2, and 3 weeks, respectively) in the volume of induced oedema, which was significant after 2 and 3 weeks of treatment compared to the placebo group.     

Dysregulation of the Hypothalamus-Pituitary-Adrenal Axis in Male and Female, Genetically Obese (ob/ob) Mice

The autosomal, recessive obesity of ob/ob mice is associated with hypercorticosteronemia and amelioration of most symptoms of obesity following adrenalectomy. Increased adrenocorticotropic hormone (ACTH) secretion has been hypothesized on the basis of several reports of higher pituitary ACTH content in ob/ob mice compared to lean littermates. However, the only measurement of ACTH blood concentration found lower levels in ob/ob mice than in leans suggesting that hypercorticosteronemia might result solely from an enhanced adrenal response to ACTH and also suggesting that the ob/ob's elevated pituitary ACTH content might be due to decreased ACTH secretion rather than increased ACTH synthesis. In our study, basal serum ACTH levels were higher in ob/ob males and females compared to sex-matched lean littermates. Anterior pituitary ACTH synthesis was also elevated as indicated by increased content of ACTH and proopiomelanocortin mRNA in obese mice of both sexes; however hypothalamic corticotropin-releasing factor content was not different in lean and obese mice. Basal serum ACTH and corticosterone (CS) levels showed normal circadian rhythm in both phenotypes and sexes, but the circadian increase in CS level was much greater in obese mice than in leans despite equal serum ACTH increases in the two phenotypes. Ether stress at both peak and trough of the circadian rhythm also stimulated much larger serum CS increases in obese mice even though ACTH increases were again equal in the two phenotypes. Taken together, these results strongly indicate that ob/ob mice have increased synthesis and secretion of pituitary ACTH despite the presence of chronically elevated serum CS. This hyperactivity of the hypothalamo-pituitary-adrenal axis appears to be most pronounced in ob/ob females since pituitary ACTH content was equal in obese males and females despite much higher circulating CS levels in the females. Furthermore, the results also indicate an enhanced response to ACTH by the adrenal cortex of the obese mouse. Thus, ob/ob mice exhibit abnormal hypothalamo-pituitary-adrenal axis function with hyperactivity occurring at the level of pituitary ACTH synthesis/secretion as well as at the level of adrenocortical response to ACTH.     

Exercise responses of healthy subjects in the evaluation of cardioselectivity ofβ-blockers

Summary The effects of intravenous propranolol, metoprolol, acebutolol and placebo on exercise-induced changes in heart rate and peak flow rate (PFR) have been studied in a group of healthy subjects. The three -blockers produced significant and comparable reductions in exercise-induced tachycardia and the magnitude of the reduction was related to the log plasma concentration of each drug. Significant cardiac -blockade was detectable for three hours after giving propranolol and for four hours after metoprolol and acebutolol. The exercise-induced changes in PFR were small and variable and were not significantly affected by any of the drugs. We conclude that, contrary to published reports, exercise-induced changes in heart rate and PFR in healthy subjects do not provide a satisfactory test system for assessing the selectivity of -blockers.     

Pharmacokinetics of methyldopa in healthy man

Summary The pharmacokinetics of 2-¹⁴C-L--methyldopa have been investigated in five healthy volunteers following intravenous and oral administration. In the intravenous study a bi-phasic plasma concentration curve was found both for chemically determined -methyldopa and for radioactivity. The plasma level of radioactivity differed significantly from chemically determined drug, a pattern which was also found in urine. This suggests the presence of unidentified metabolite(s). The difference between plasma disappearance and urine recovery of -methyldopa and radioactivity during the first 4 h after injection suggests distribution to an extravascular compartment. Plasma half-lives of total radioactivity and of unchanged drug were calculated. In three subjects, pharmacokinetic parameters for a two-compartment open body model were calculated from urine and plasma data. Urinary recovery of radioactivity was almost complete within 48 h after intravenous administration. After oral administration, however, only about 40 per cent of the radioactive dose was recovered in the urine, and it contained approximately equal amounts of unconjugated methyldopa, acid-labile conjugated methyldopa and unidentified metabolite(s). The acid-labile conjugate was found only after oral administration, which supports the theory of a mucosal conjugation process. The lack of acid-labile conjugated drug either in the plasma or urine after intravenous injection indicates that there is no enterohepatic circulation of this drug.     

利拉鲁肽治疗超重的2型糖尿病24例临床观察

目的观察胰高糖素样激动剂1（GLP-1）的类似物利拉鲁肽治疗超重或肥胖的2型糖尿病的有效性及安全性。方法选择于2011—01—12～2013—01—20在本院接受治疗的超重2型糖尿病患者24例,所有患者在二甲双胍及吡咯列酮治疗的基础上加用利拉鲁肽,最初1周给予患者利拉鲁肽0．6mg晚上睡前皮下注射,第2周加量至1．6mg。观察患者的临床疗效,每2周随访1次,观察治疗12周后患者的FPG、2h-PPG、HbAlc、体重、收缩压及舒张压水平变化和不良反应情况。结果治疗12周后患者的FPG、2h-PPG、HbAIc、体重、收缩压及舒张压与治疗前比较,均有明显的改善,差异有统计学意义（P〈0．05）。无严重的不良反应。结论利拉鲁肽治疗超重或肥胖的2型糖尿病疗效肯定,安全,不增加体重,无明显不良反应的另一类糖尿病合适选择的治疗方法。     

基于肿瘤能量代谢失衡探讨扶正解毒法在慢性结肠炎“炎癌转化”分期干预中的应用

慢性结肠炎在一定情况下可发生癌转化。慢性结肠炎“炎癌转化”是在线粒体能量代谢损伤、有氧糖酵解代谢上调的机制下,肠道上皮细胞代谢失衡,促使炎症微环境向肿瘤微环境转化的过程。认为由正气虚损而致太阴经、阳明经的寒热分离是结肠炎癌转化的触发机制,由邪毒鸱张诱发的气机升降失调是打破促瘤抑瘤平衡,进而邪聚成瘤的关键。临床治疗上应在中医恒动观理论指导下分清慢性结肠炎炎癌转化的不同阶段,灵活把握扶正与解毒的主次,改善肠道炎性环境,调节异常能量代谢,以延缓恶化时间,截断炎癌转化的进程。     

陈红风治疗乳腺癌中的扶正观

介绍陈红风教授治疗乳腺癌的临床经验。认为乳腺癌的发病与气血亏虚,肝、脾、肾及冲任二脉功能失调有关;治疗时重视通过调摄冲任以扶正、调理脏腑以祛邪。并附病例1则。     

Functional Fiber Reduces Mice Obesity by Regulating Intestinal Microbiota

Obesity may cause metabolic syndrome and has become a global public health problem, and dietary fibers (DF) could alleviate obesity and metabolic syndrome by regulating intestinal microbiota. We developed a functional fiber (FF) with a synthetic mixture of polysaccharides, high viscosity, water-binding capacity, swelling capacity, and fermentability. This study aimed to investigate the effect of FF on obesity and to determine its prevention of obesity by modulating the gut microbiota. Physiological, histological, and biochemical parameters, and gut microbiota composition were investigated in the following six groups: control group (Con), high-fat diet group (HFD), low-fat diet group (LFD, conversion of HFD to LFD), high-fat +8% FF group (8% FF), high-fat +12% FF group (12% FF), and high-fat +12% FF + antibiotic group (12% FF + AB). The results demonstrated that 12% FF could promote a reduction in body weight and epididymal adipocyte area, augment insulin sensitivity, and stimulate heat production from brown adipose tissue (BAT) (p < 0.05). Compared with the HFD, 12% FF could also significantly improve the intestinal morphological integrity, attenuate systemic inflammation, promote intestinal microbiota homeostasis, and stabilize the production of short-chain fatty acids (SCFAs) (p < 0.05). Consistent with the results of 12% FF, the LFD could significantly reduce the body weight and epididymal adipocyte area relative to the HFD (p < 0.05), but the LFD and HFD showed no significant difference (p > 0.05) in the level of inflammation and SCFAs. Meanwhile, 12% FF supplementation showed an increase (p < 0.05) in the abundance of the Bifidobacterium, Lactococcus, and Coprococcus genus in the intestine, which had a negative correlation with obesity and insulin resistance. Additionally, the treatment with antibiotics (12% FF + AB) could inhibit the effect of FF in the HFD. The Kyoto Encyclopedia of Genes and Genomes (KEGG) function prediction revealed that 12% FF could significantly inhibit the cyanogenic amino acid metabolic pathway and decrease the serum succinate concentration relative to the HFD group. The overall results indicate that 12% FF has the potential to reduce obesity through the beneficial regulation of the gut microbiota and metabolites.     

Adolescent Knowledge,Attitudes and Practices of Healthy Eating: Findings of Qualitative Interviews among Hong Kong Families

To tackle unhealthy eating among adolescents, it is crucial to understand the dietary knowledge, attitudes, and practices (KAP) on which adolescent eating habits are based. This qualitative study identifies the gaps in KAP by exploring what Chinese adolescents know, perceive, and practice regarding healthy eating to better inform targeted interventions for this important health problem. Parent–adolescent dyads were purposively sampled based on, for example, the dietary intake, age, and gender of the adolescent and household income, and each completed a 30 to 60 min interview. Twelve themes were synthesized: knowledge: (1) dietary recommendations, (2) health outcomes of healthy eating, (3) nutrition content in food, and (4) access to healthy meals; attitudes: (5) outcome expectation for healthy eating, (6) food preferences, and (7) self-efficacy regarding adopting healthy eating; and practices: (8) going grocery shopping for healthy food, (9) eating home-prepared meals. (10) eating out in restaurants or consuming takeaway food, (11) fruit and vegetable consumption, and (12) snacking, perceived unhealthy eating to be low risk, made unhealthy choices regarding snacking and eating out, and had insufficient fruit and vegetable intake. Programs should emphasize the positive short-term health outcomes of healthy eating and empower adolescents to acquire food preparation skills to sustain healthy eating habits.