Effect of antihypertensive treatment on kidney function in diabetic nephropathy.

The effect of long term, aggressive antihypertensive treatment on kidney function in diabetic nephropathy was studied prospectively in 11 insulin dependent diabetics (mean age 30). During the mean pretreatment period of 32 (range 23-66) months the glomerular filtration rate decreased significantly and albuminuria and the arterial blood pressure increased significantly. During the 72 (range 32-91) month period of antihypertensive treatment the average arterial blood pressure fell from 143/96 mm Hg to 129/84 mm Hg and albuminuria decreased from 1038 micrograms/min to 504 micrograms/min. The rate of decline in the glomerular filtration rate decreased from 0.89 (range 0.44-1.46) ml/min/month before treatment to 0.22 (range 0.01-0.40) ml/min/month during treatment. The rate of decline in the glomerular filtration rate was significantly smaller during the second three years compared with the first three years in patients who received long term antihypertensive treatment (greater than or equal to 6 years). One patient died from acute myocardial infarction (glomerular filtration rate 46 ml/min/1.74 m2). Effective antihypertensive treatment postpones renal insufficiency in diabetic nephropathy.     

Recent advances in the pharmacological management of pain

Pain is an unpleasant sensation that originates from ongoing or impending tissue damage. Management of different types of pain (acute, postoperative, inflammatory, neuropathic or cancer) is the most frequent issue encountered by clinicians and pharmacological therapy is the first line of approach for the treatment of pain. This review presents and discusses recent clinical advances regarding both the improvements in delivery of analgesic drugs and improvements in the design of analgesic molecules. The new modalities of administration of analgesics used in the clinic are reviewed, including skin patches, oral and mucosal sprays, transdermal delivery systems and intranasal administration. New insights are then presented on standard drugs used to relieve pain, such as opioids (including tramadol), NSAIDs including selective cyclo-oxygenase-2 inhibitors, paracetamol (acetaminophen), local anaesthetics and adjuvant analgesics such as antidepressants, anticonvulsants (gabapentin and pregabalin), cannabinoids, ketamine and others (e.g. nefopam). Although the understanding of pain mechanisms has improved significantly recently, much more is yet to be discovered and awaited. Broadening of our knowledge is needed to improve basic and clinical research in this field in order to better alleviate pain in millions of people.     

Recent advances in hypertension research and management

At the 17th Scientific Meeting of the International Society of Hypertension (Amsterdam, June 7-11, 1998), clinicians and scientists from all over the world exchanged the results of latest research on the pathophysiology, prevention and management of hypertension. Progress in two key areas of basic research was presented at the meeting: ion channels and experimental genetics. In the clinical arena, a number of large, long-term studies were presented on topics that included risk factors of cardiovascular events in male hypertensives; antihypertensive therapy and the risk of cancer; and antihypertensive therapy in dementia. A population-wide approach was stressed as essential in a session on diet intervention and hypertension in the 21st century.     

二甲双胍联用抗高血压药物长期治疗对高血压患者胰岛素抵抗和代谢的影响

目的研究二甲双胍联合尼群地平和阿替洛尔长期治疗对高血压患者胰岛素抵抗(IR)和代谢的影响.方法111例轻中度高血压病人,随机分为2组,分别用尼群地平和阿替洛尔联合治疗(A组,n=51)和二甲双胍联合尼群地平和阿替洛尔治疗(B组,n=60),疗程14个月.结果降压总有效率,A组较B组低,但无显著性差异(P＞0.05).A组病人治疗后较治疗前体重增加(P＜0.05),胰岛素敏感指数(ISI)无显著变化(P＞0.05),空腹血糖显著升高(P＜0.001),低密度脂蛋白显著升高,高密度脂蛋白/低密度脂蛋白比显著下降.B组病人治疗后较治疗前,体重无显著变化,ISI显著升高(P＜0.05),血糖、高密度脂蛋白/低密度脂蛋白比和血肌酐显著下降(P＜0.05).二甲双胍联合尼群地平和阿替洛尔治疗能更有效地控制血压,预防体重增加,降低IR,改善血糖代谢和肾功能.结论二甲双胍和抗高血压药物联合应用可能是一组好的药物配伍.     

Effects of antihypertensive drugs on endocrine function

Pharmacological treatment of hypertension can cause clinically significant alterations in endocrine function through effects on glucose homeostasis, thyroid and parathyroid hormones, adrenal steroid metabolism and reproductive/pituitary physiology. Long term use of thiazide diuretics causes deterioration in glucose tolerance, probably secondary to potassium depletion. Hypoglycaemic complications of beta-blockers (mainly the non-selective compounds) can be dramatic, especially in type I diabetics. Clonidine, diazoxide and calcium antagonists have all been associated with deterioration in glucose tolerance and their long term use should be avoided in type II diabetics if possible. Propranolol lowers T3 levels by decreasing the conversion of T4 to T3. Prazosin causes elevations in T4 and thyroid-stimulating hormone, while sodium nitroprusside use may result in hypothyroidism. Numerous agents are associated with sexual dysfunction, including methyldopa, reserpine, clonidine and spironolactone. Thiazide diuretics may cause hypercalcaemia, particularly in patients with hyperparathyroidism, by decreasing urinary calcium as well as directly influencing bone and gut calcium handling. Conversely, propranolol may decrease circulating parathyroid hormone levels and correct the hypercalcaemia seen in hyperparathyroidism. Awareness of drug-induced changes in endocrine function will facilitate the rational management of the hypertensive patient.     

住院高血压患者的药物利用研究

目的探讨住院高血压患者降压药物利用情况,为提高降压药物的合理利用提供参考依据。方法方便抽样选择辽宁大连三级甲等医院2所,自2011年1月1日-2016年1月1日住院高血压患者信息中分层随机抽取4000例,根据病历资料收集患者抗高血压药物使用情况,分析降压药物利用状况。结果大连地区高血压住院患者抗高血压药物利用例次最多的为氨氯地平9.05%(1011/11 176),用药频度最高的为缬沙坦(12 163.45),DUI值最大的为非洛地平(4.38),DUI值最小的为氨氯地平(0.41),DUI值接近1.0的为尼群地平(0.96)、拉西地平(1.01)、缬沙坦氨氯地平(1.02)、厄贝沙坦(1.04)、艾司洛尔(1.05)。结论大连地区高血压住院患者降压药物利用较合理。     

不同胰岛素敏感状态对高血压病人降压药治疗后代谢变化的影响

目的：研究不同胰岛素敏感状态对高血压病人降压药治疗后血糖和血脂变化的影响。方法：138例轻、中度高血压病人被随机分为3组，分别用复方降压片治疗(n=39)．福辛普利和吲达帕胺联合治疗(n=48)以及尼群地平和阿替洛尔联合治疗(n=51)，平均疗程14个月(12～16个月)。根据Cederholm公式计算的胰岛素敏感指数(ISI)为胰岛素抵抗(IR)指标，以ISI50％位点，作为判断胰岛素抵抗的切割点，把高血压病病人分为IR亚组与胰岛素敏感(IS)亚组，观察血压、血糖、血脂的变化。结果：(1)3组间降压总有效率无显差异，组内两亚组降压幅度无显差异。(2)复方降压片治疗后两亚组IsI提高和血糖下降的幅度无显差异，IR亚组三酰甘油显下降，IS亚组血脂无显变化。(3)福辛普利和吲达帕胺治疗后两亚组血糖升高，高密度脂蛋白／低密度脂蛋白比下降，ISI下降幅度IS亚组显大于IR亚组。(4)尼群地平和阿替洛尔治疗后IS亚组血糖显升高，高密度脂蛋白／低密度脂蛋白比和ISI显下降；IR亚组无显变化。结论：高血压病人用复方降压片治疗对胰岛素敏感性、血糖和血脂代谢有改善作用，胰岛素抵抗较胰岛素敏感可能更加明显；而用福辛普利和吲达帕胺联合治疗及尼群地平和阿替洛尔联合治疗对ISI、血糖和血脂代谢可产生不利影响，胰岛素敏感较胰岛素抵抗可能更加严重。     

Effects of various antihypertensive drugs on the function of osteoblast.

Several studies have suggested that high blood pressure is associated with the risk of bone loss. Since various antihypertensive drugs are in wide use for the treatment of hypertension, it is important to investigate the influences of these drugs on bone metabolism. Osteoblasts play a pivotal role in the regulation of bone formation. During differentiation, they sequentially express type I collagen, alkaline phosphatase (ALP), other bone matrix proteins, and finally undergo mineral deposition. In this study, we examined the effects of various antihypertensive drugs on the function of osteoblast using clonal MC3T3-E1 cells. Drugs examined include dihydropyridine-type calcium channel blockers (benidipine, amlodipine, and nifedipine), angiotensin-converting enzyme (ACE) inhibitors (captopril, lisinopril, and enalapril), and angiotensin II receptor type1 (AT1) antagonists (TCV-116 and KW-3433). None of the ACE inhibitors or AT1 antagonists affected ALP activity or cellular DNA content significantly. In contrast, benidipine, amlodipine, and nifedipine increased ALP activity when used in amounts 1 pM, 100 nM, and 100 nM, respectively. Benidipine blocked calcium influx through the L-type voltage dependent calcium channel of MC3T3-E1 more potently than amlodipine or nifedipine. These calcium channel blockers did not change collagen accumulation. Benidipine significantly increased in vitro mineralization at a concentration of 1 nM and higher, while amlodipine did so at 1 microM and nifedipine did not. Comparison of the effective concentration of each calcium channel blocker in our study with the reported maximum serum concentration of each drug suggests that benidipine, but not amlodipine or nifedipine, promotes mineral deposition in human.     

红花黄色素联合二甲双胍对早期糖尿病肾病患者氧化应激、胰岛素抵抗及肾功能的影响

目的 观察红花黄色素联合二甲双胍对早期糖尿病肾病(DN)患者氧化应激、胰岛素抵抗及肾功能的影响.方法 选取2015年10月至2016年10月诊治的DN患者80例,随机分为对照组和观察组,每组40例.2组均接受常规治疗,对照组在常规治疗基础上口服盐酸二甲双胍治疗,观察组在对照组基础上静脉滴注红花黄色素,疗程均为2周.观察2组血清空腹血糖(FBG)、餐后2 h血糖(2 hPG)、胰岛素(FINS)、谷胱甘肽过氧化物酶(GSH-Px)、丙二醛(MDA)、超氧化物歧化酶(SOD)、8异前列腺素F2α(8-iso-PGF2α)、胱抑素C(Cys C)、同型半胱氨酸(Hcy)、24 h尿蛋白量、尿白蛋白排泄率(UAER)变化,计算胰岛素抵抗指数(HOMA-IR).结果 与治疗前比较,2组治疗后FBG、2 hPG、FINS、HOMA-IR、MDA、Cys C、Hcy水平均较治疗前显著降低(P<0.05),GSH-Px、SOD水平均较治疗前显著升高(P<0.05),且观察组上述指标改善程度优于对照组(P<0.05).结论 红花黄色素联合二甲双胍治疗早期糖尿病肾病能够显著降低氧化应激水平,改善胰岛素抵抗,从而发挥肾脏保护作用.     

Recent advances in pharmacological research on the management of irritable bowel syndrome

Irritable bowel syndrome (IBS), a common gastrointestinal (GI) disorder, is associated with various factors, including lifestyle, infection, stress, intestinal flora, and related diseases. The pharmacotherapeutic stimulation of receptors and downstream signaling pathways is effective in reducing IBS symptoms; however, it is still associated with adverse effects. Various receptors related to GI motility and visceral hypersensitivity should be considered to enhance the benefit/risk ratio of IBS treatments. This review discusses recent pharmacological advances in IBS management. Several receptors related to GI motility and abdominal pain are investigated in various angles. 5-Hydroxytryptamine (5-HT) is an important neurotransmitter that activates the colonic mucosal 5-HT₄ receptor without causing severe cardiovascular adverse effects. The clinical potential of ramosetron for diarrhea-predominant IBS has been suggested because of a lower risk of ischemic colitis than conventional 5-HT₃ receptor antagonists. Toll-like receptors (TLRs), especially TLR2 and TLR4, show a significant effect on the post-infection symptoms and lipopolysaccharide-mediated regulation of GI motility. Histamine is a well-known nitrogenous compound that regulates inflammatory responses and visceral hypersensitivity. Histamine 1 receptor-mediated sensitization of the transient receptor potential vanilloid 1 is associated with IBS. Pharmacological approaches based on these signaling pathways could be useful in the development of novel IBS treatments.     

西红康对实验性糖尿病肾病大鼠肾脏结构和功能的影响

目的：考察西红康对实验性糖尿病肾病大鼠肾脏结构和功能的影响。方法32只 Wistar 大鼠（雄性）随机分为模型组、西红康组、糖适平阳性组和正常对照组,每组8只,建立糖尿病肾病大鼠模型,对大鼠进行8周的治疗,检测记录治疗前后大鼠的血糖、体重和尿微量白蛋白,分别采用光学显微镜及透射电镜观察大鼠肾脏的结构变化。结果给药前,各组动物的血糖、体重和尿微量白蛋白中均无统计学差异（P ＞0．05）。给药8周后,血糖水平、体重和尿微量白蛋白指标,阳性组和西红康组相对于模型组均有统计学差异（P ＜0．05）。正常组大鼠肾脏肾小球结构完整,肾脏系膜细胞、滤过膜内皮细胞和足细胞均结构正常,模型组大鼠肾小球体积增大,系膜细胞发生中度增生,毛细血管基底膜结构模糊,内皮细胞胞质局部融合,阳性组和西红康组均能不同程度降低肾小球大小,缓解系膜细胞增生,毛细血管基底膜结构更为清晰,内皮细胞胞质融合程度下降。结论西红康可减轻实验性糖尿病肾病大鼠肾脏病理损害,改善肾脏功能。     

西格列汀联合螺内酯对糖尿病肾病患者肾功能和血脂水平的影响

目的 研究西格列汀联合螺内酯对糖尿病肾病患者肾功能和血脂水平的影响。方法 选择2015年1月-2017年12月宿州市立医院收治的60例糖尿病肾病患者,随机分为两组。对照组口服螺内酯,每次20 mg,每天1次;观察组联合口服西格列汀,每次100 mg,每天1次。两组均治疗6个月。比较两组治疗前后的肾功能和血脂水平。结果 观察组的有效率（80.00%）明显高于对照组（56.67%）,差异有统计学意义（P<0.05）。治疗后,两组24 h尿蛋白定量和尿白蛋白排泄率均较治疗前显著减少,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组减少更为明显,组间差异有统计学意义（P<0.05）;但两组血肌酐和血尿素氮比较,差异无统计学意义。治疗后,两组的三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）和总胆固醇（TC）水平均明显降低,高密度脂蛋白胆固醇（HDL-C）水平明显升高,同组治疗前后比较差异有统计学意义（P<0.05）;且观察组的改善幅度更为明显,组间差异有统计学意义（P<0.05）。结论 螺内酯以及西格列汀联合使用有助于提高糖尿病肾病患者的治疗效果,有效改善肾功能和控制血脂水平,值得应用推广。     

Effects of different antihypertensive drugs on plasma fibrinogen in hypertensive patients.

1. In order to evaluate whether treatment with different antihypertensive drugs would affect plasma fibrinogen levels, 118 mild to moderate essential hypertensive subjects, all males, aged 18 to 65 years, were randomly treated with amlodipine 10 mg, atenolol 100 mg, hydrochlorothiazide 25 mg or lisinopril 20 mg, all given once daily for 8 weeks. 2. Before and after 8 weeks' treatment, blood pressure (BP), heart rate (HR), fibrinogen, total cholesterol (TC), HDL-C, LDL-C, triglycerides (TG), plasma glucose, plasma uric acid, serum creatinine and serum potassium were evaluated. 3. All four medications significantly reduced BP values, although the BP lowering effect of lisinopril, amlodipine and atenolol was significantly greater compared with that of hydrochlorothiazide. 4. Plasma fibrinogen levels were unaffected by atenolol, hydrochlorothiazide and amlodipine, whereas they were significantly decreased by lisinopril (-11.2%, P = 0.002). This fibrinogen lowering effect was more evident in smokers (-17.7%) than in non smokers (-7.4%). 5. Atenolol and amlodipine did not significantly affect plasma lipids, hydrochlorothiazide increased TC, LDL-C and TG and reduced HDL-C; lisinopril increased HDL-C and decreased TC and LDL-C. 6. Hydrochlorothiazide increased plasma glucose and uric acid concentrations, which were unaffected by the other drugs. The diuretic also reduced serum potassium. 7. The results of this study indicate that lisinopril reduces levels of plasma fibrinogen and confirm that different antihypertensive drugs may elicit different metabolic effects, which may variously influence the overall risk profile of the hypertensive patients.     

Sexual dysfunction in male patients with hypertension: influence of antihypertensive drugs

Evidence suggests that arterial hypertension, in addition to being a cardiovascular and renal risk factor, may also be associated with an impairment of male sexual function. Since other cardiovascular risk factors, especially diabetes mellitus, have also been shown to correlate with impaired sexual function it has been proposed that sexual and especially erectile dysfunction may, at least in part, represent just another manifestation of atherosclerotic vascular disease. In addition to hypertension itself, sexual function in male hypertensive patients may also be affected by antihypertensive drug treatment. Available evidence suggests that centrally acting sympatholytic agents, beta-adrenoceptor antagonists (beta-blockers) and diuretics may have the potential to further impair sexual function. Calcium channel antagonists and ACE inhibitors may be neutral with respect to this endpoint. Preliminary data from several randomised and open studies have suggested that angiotensin II (AT)(1)-receptor antagonists may even be associated with an improvement of sexual function. However, many aspects of the interaction between hypertension, antihypertensive drug treatment and male sexual function remain unclear. Among other factors, the relative contribution of disease labelling both to the higher incidence of sexual dysfunction in hypertensive versus normotensive males and to the negative impact of treatment remains an open question. Furthermore, dose dependence of the observed effects of antihypertensive agents on sexual function, the role of combination therapy and the anticipation of proposed adverse effects of treatment are unresolved issues. Thus, more data from studies of high quality using standardised definitions and procedures are urgently needed to at least partially resolve some of the many open questions.     

非诺贝特对高甘油三酯血症患者胰岛素敏感性和血管内皮功能的影响

目的 观察非诺贝特对高血脂症患者代谢参数、胰岛素敏感性和血管内皮功能的影响。方法 原发高甘油三酯血症患者60例，每天予非诺贝特0．2g治疗，共12周。治疗前后分别测定甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白（HDL-C）、低密度脂蛋白（LDL-C）、游离脂肪酸（FFA）、空腹血糖和胰岛素、尿酸（UA）以及血流介导的血管舒张（FMD）。结果 ①非诺贝特可显著降低TG、TC、FFA和UA，升高HDL-C（所有P〈0．01）；②非诺贝特改善胰岛素的敏感性，使胰岛素抵抗减轻6％（P〈0．05）；③非诺贝特可明显改善血流介导的血管扩张（FMD）（P〈0．01）。结论 非诺贝特不但具有调节血脂作用．还具有胰岛素增敏作用和改善内皮功能作用。胰岛素敏感性的增加与HDL水平的升高、FFA水平的降低以及内皮功能的改善有关。     

胰岛素强化治疗早期糖尿病肾病疗效观察

目的观察胰岛素强化治疗早期糖尿病肾病的临床疗效。方法59例早期糖尿病肾病患者按数字表法随机分为两组,观察组（30例）予胰岛素强化治疗,对照组（29例）口服降糖药,比较两组治疗效果、糖化血糖蛋白、肾功能指标等变化。结果观察组mAlb、BUN、Ser改善比对照组明显（t=12．035、13．163、15．027,均P〈0．05）。观察组血糖达理想水平时间短于对照组,差异有统计学意义（t=11．57,P〈0．05）。观察组治疗后HbAle低于对照组,差异有统计学意义（t=3．09,P〈0．05）。结论胰岛素强化治疗用于早期糖尿病肾病患者,可明显缩短达理想血糖时间,延缓肾功能损害,改善患者预后。     

卡托普利增加高血压病患者胰岛素敏感性的作用

对２６例高血压病（ＥＨ）病人进行的口服葡萄糖耐量试验（ＯＧＴＴ）和胰岛素释放试验（ＩＲＴ）表明，与对照组相比，至少在部分ＥＨ病人中存在着胰岛素抵抗（ＩＳＲ）和高胰岛素血症（ＨＩＳ），且短期服用（４－６ＷＫ）卡托普利即通用性改善ＥＨ和冠心病（ＣＨＤ）患者的ＩＳＲ和ＨＩＳ，增加机体对胰岛素（ＩＮＳ）的敏感性。     

福多司坦联合常规降压药治疗阻塞性睡眠呼吸暂停综合征伴高血压的临床疗效

目的：观察福多司坦对阻塞性呼吸暂停综合征（OSAS）合并高血压患者患者的临床效果。方法：选取55名正常人群以及120名OSAS合并高血压患者,患者随机均分为治疗组和对照组,治疗组患者除接受常规降压药物治疗处理外,同时给予福多司坦治疗2个月,对照组患者给予安慰剂及常规降压药物处理,观察两组治疗前后的通气指数（AHI）,血氧饱和度（miniSpO₂）,炎性因子ICAM-1、VCAM-1、P选择素、E选择素、IL-8、TNF-α、HS-CRP变化情况,并将患者的以上指标与正常人群组比较。结果：OSAS合并高血压患者MT、PMV均高于正常人,以及ICAM-1、VCAM-1、P选择素、IL-8、TNF-α、HS-CRP等炎症因子均明显高于常人。联合治疗后,治疗组血压得到改善,AHI下降、miniSpO₂升高,ICAM-1、VCAM-1、P选择素、IL-8、TNF-α均显著降低（P<0.05）。结论：福多司坦联合常规降压药治疗OSAS合并高血压具有较好的临床效果。     

前列地尔联合替米沙坦对早期糖尿病肾病患者的超敏C反应蛋白及胱抑素的作用研究

目的研究前列地尔（前列腺素E1脂微球制剂）联合替米沙坦在治疗早期糖尿病肾病（DN）中对超敏C反应蛋白（hsCRP）及胱抑素（CysC）水平的影响。方法收集本院门诊和住院病人71例早期DN患者,随机分为单纯前列地尔组24例,单纯替米沙坦组23例,联合用药组24例,进行12周临床观察治疗,分别比较三组血压、血糖、糖化血红蛋白（HbA1 c）、尿微量白蛋白排泄率（UAER）、hsCRP及CysC水平的变化。结果三组在治疗前各项指标无明显差异（P〉0．05）;各组治疗12周后,UAER、hsCRP及CysC指标都较治疗前均有明显好转（P〈0．01）;而联合组的UAER、hsCRP及CysC较另两组改善更明显（P〈0．05）。结论前列地尔联合替米沙坦治疗早期DN,能有效改善hsCRP、CysC及减少UAER,并长期维持尿蛋白于低水平,有利于延缓甚至防止糖尿病肾病的发生和发展。