Role of the liver in the disposition of intravenous nitroglycerin in the rat

Previous studies have indicated that the liver is the main site of nitroglycerin (NTG) elimination when the drug is systematically infused. To examine this hypothesis, we measured the apparent systemic clearance (Cls) of nitroglycerin in anesthesized rats receiving a constant intravenous infusion at a dose of 100 micrograms per kg per min. Animals were divided into shunt and sham groups; the former had undergone a portal vein ligation 10 days prior to the study, while the latter was subjected to a sham operation. On the study day, half of the animals of each group also received probenecid at 200 mg/kg, i.v., a drug previously reported to inhibit organic nitrate ester reductase (ONER) activity in rat liver. Arterial NTG samples were obtained at 41, 43 and 45 min of infusion in all four experimental groups; Cls was 439 +/- 32 ml per kg per min (mean +/- S.E.) in sham, 460 +/- 44 in sham and probenecid, 477 +/- 39 in shunt, and 461 +/- 34 in shunt and probenecid animals. During NTG infusion, hepatic blood flow (measured with a constant infusion of indocyanine green) was decreased markedly in shunted rats as was liver/body weight, indicating hepatic atrophy. The specific activity of hepatic ONER was similar in all four groups. In spite of marked differences in hepatic blood flow and hepatic mass, the Cls was similar in all four groups. The liver does not appear to be a major site for the elimination of systemic nitroglycerin as hitherto assumed.     

HACCP在学校集体食堂卫生管理中的应用研究

目的 通过HACCP在学校集体食堂管理中的应用,提高食品卫生水平,保障学生的身体健康。方法 HACCP原则。结果 食品卫生达到较高水平,极大地减少了食物中毒的发生。结论 提示HACCP原则可在学校集体食堂的卫生管理中发挥有效作用。     

半导体激光治疗老年人压疮疗效观察

目的探讨半导体激光局部照射治疗老年人压疮疗效.方法:收集2012年1月-2015年6月48例压疮患者,分为半导体组和常规组各24例.常规组采用常规治疗,半导体组采用半导体激光加常规治疗,10 d为1个疗程,不超过3个疗程.疗程结束后比较两组疗效.结果:半导体组压疮愈显率为83.33％,创面愈合时间为(12.75±5.51)d,常规组分别为54.17％和(19.63±8.65)d,组间差异有统计学意义(P＜0.05),两组均未见不良反应.结论:半导体激光加常规治疗压疮效果肯定,无明显不良反应,且操作简便.     

脑卒中恢复期患者社区综合康复的疗效观察

目的：探讨社区开展康复活动对于脑卒中患者肢体功能康复的影响。方法：选取2014年4至10月参与社区“陈睿健康工作室”康复活动的脑卒中恢复期患者50例作为观察组,选取同期延吉社区卫生服务中心门诊的50例脑卒中恢复期患者作为对照组（进行门诊随访、服药、自我康复）。采用知识、信念、行为（KAP）量表对观察组患者进行问卷调查。采用简化Fugl-Meyer肢体运动功能评分表（Fugl-Meyer assessment of motor function,FAM）比较两组患者入组时和入组6个月时的肢体功能恢复情况及对家庭医生（门诊医师）的满意度。结果：入组6个月时,两组患者的FAM均有所改善,观察组FAM得分[上肢（50.92±7.05）分,下肢（33.01±1.37）分]较对照组[上肢（34.85±6.55）分,下肢（25.20±4.88）分]更高,差异有统计学意义（t上肢=11.8215,t下肢=10.8595,P均＜0.01）。观察组患者的满意率为92%（46/50）,明显高于对照组的30%（15/50,P＜0.05）。结论：在社区开展康复活动可以促进脑卒中患者肢体功能的康复,提高患者的满意度。     

Evaluation of the safety of enalapril in the treatment of heart failure in the very old

Summary We have introduced enalapril, in doses equal to or less than the 2.5 mg currently recommended, as an adjuvant to digoxin and diuretics in 17 patients of mean (SD) age 83 (5) years with severe heart failure. Only eleven patients tolerated its introduction. Unlike those reported in younger patients, all but one of the adverse drug reactions occurred 8 h or more after the first dose. Aged patients started on ACE inhibitors should be observed in hospital until stabilized on a maintenance dose. Three patients had an adverse reaction which differed in nature from those previously reported: acute confusional state, ataxia and mesenteric ischaemia.Ten patients were discharged on 5 mg or 10 mg maintenance doses of enalapril. In nine of them improvement on triple therapy was sustained for a minimum of three months. ACE inhibition was lost in the other patient when her compliance with enalapril therapy fell to around 75%: monitoring compliance is essential when ACE inhibitors are used in low dosages.Enalapril was withdrawn during follow up in three patients because of symptoms of mesenteric ischaemia and in four because of dramatic deterioration of renal function. One of the latter was found subsequently to have severe bilateral atheromatous renal artery stenosis. When isosorbide dinitrate was substituted for enalapril, symptoms of mesenteric ischaemia resolved and renal function returned to baseline. Continuing surveillance for adverse effects is essential in patients of this age group with severe heart failure, and the risk of occult renal artery stenosis requires regular biochemical screening during follow up.The benefit to cost ratio of ACE inhibitors might be improved in aged patients by their use at an earlier stage in the natural history of heart failure, when perfusion of essential organs is not grossly impaired, but carefully monitored trials would be necessary to establish this.     

Effect of the Immunomodulator Tilorone on the in Vivo Acetylation of Procainamide in the Rat

Interferon and interferon inducers have been found to inhibit cytochrome P-450-dependent metabolism in animals and man. The effect of these agents on the acetylation of drugs has not been previously reported. Since these agents stimulate the reticuloendothelial system, together with the abundance of N-acetyltransferase in the reticuloendothelial system, it was hypothesized that these immunomodulators may affect drug acetylation. To test this hypothesis, the effect of tilorone (a synthetic interferon inducer) on the in vivo acetylation of procainamide was examined in the rat. Pretreatment with tilorone hydrochloride (50 mg/kg) 48 hr prior to the administration of procainamide hydrochloride (50 mg/kg) resulted in a 32% increase in the urinary recovery of N-acetylprocainamide and a 35% increase in the metabolic clearance of procainamide to N-acetylprocainamide. These data indicate that interferon inducers increase the N-acetylation of drugs in vivo.     

药物经济学成本-效果分析应用的相关问题探讨

目的探讨药物经济学成本-效果分析(CEA)应用的相关问题。方法运用文献计量学方法、数学证明方法等。结果与结论在运用CEA进行药品的经济性评价时,尤其需要重视临床治疗指标的选择、成本的确定、增量分析的使用和与最小成本分析的比较。     

替普瑞酮治疗老年慢性浅表性胃炎的疗效分析

目的分析替普瑞酮治疗老年慢性浅表性胃炎的疗效。方法100例老年慢性浅表性胃炎患者,通过计算机随机表数字法分为对照组和实验组,每组50例。对照组患者选择西咪替丁作为本次治疗药物,实验组患者选择替普瑞酮作为本次治疗药物。比较两组患者临床疗效、不良反应发生情况以及生活质量。结果实验组治疗总有效率92.00%高于对照组的76.00%,差异具有统计学意义(P<0.05)。实验组不良反应发生率6.00%低于对照组的20.00%,差异具有统计学意义(χ^2=4.332,P=0.037<0.05)。实验组患者治疗后的生活质量评分(68.68±4.11)分高于对照组的(57.73±3.48)分,差异具有统计学意义(t=14.377,P=0.000<0.05)。结论对于老年慢性浅表性胃炎疾病患者,选择替普瑞酮进行治疗不仅疗效更为理想,而且还不易增加患者的用药不良反应,有利于提高患者的生活质量,建议进一步推广。     

Adenosine mechanisms in the regulation of breathing in the rat

The central respiratory effects of various adenosine (A) analogues were studied in halothane-anesthetized rats. Intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) injections of the A analogues (2-Cla, L-PIA, CHA and NECA) reduced minute ventilation (VE) due to decreases in respiratory frequency (f) as well as tidal volume (VT). Dose-dependent effects were seen after i.c.v. L-PIA in both normal and vagotomized rats. Analysis of the A-induced changes using the occluded breath technique revealed an increase in expiratory time (TE) as well as a decrease in inspiratory drive. NECA, a relatively specific A2 agonist seemed to be somewhat more potent in eliciting respiratory depression than a relatively specific A1 agonist like L-PIA. Pretreatment with the methylxanthine theophylline completely antagonized the respiratory depression induced by L-PIA. It is concluded that central A receptors are involved in the central regulation of breathing and that A interacts with the respiratory control system mainly by decreasing inspiratory neural drive and prolonging expiratory time.     

Nifedipine in the treatment of hypertension in the elderly

The effect of nifedipine monotherapy, retard tablets, 20 mg bid, was evaluated in 23 hypertensive patients, mean age, 79 +/- 2 years. Twenty-one patients completed an eight-week study. Blood pressure (BP) decreased to 160/90 mm Hg in 15 patients; in four additional patients diastolic BP dropped by 15% to 28%. In a subset of five patients with isolated systolic hypertension, a significant reduction in systolic BP was noted. Side effects were relatively mild and only two patients discontinued the study. The results suggest that nifedipine monotherapy offers an alternative, logic, therapeutic approach to hypertension in the elderly.     

Piracetam in the treatment of cognitive impairment in the elderly

Reisberg, B., S.H. Ferris, M.K. Schneck, J. Corwin, P. Mir, E. Friedman, K.A. Sherman, M. McCarthy, and R.T. Bartus : Piracetam in the treatment of cognitive impairment in the elderly. Drug Dev. Res. 2: 475–480, 1982. Piracetam (Nootropil, 2-oxopyrrolidone acetamide) has been extensively investigated for the treatment of cognitive impairment. Initial studies on normal subjects and patients with mild or moderate cognitive decline have been somewhat encoruaging. Accordingly, we conducted a further evaluation of the effects of piracetam in the treatment of elderly outpatients 60 to 85 years of age with mild to moderate memory impairment consistent with a diagnosis of Primary Degenerative Dementia (PDD). In our first study, we examined the effects of piracetam in 20 patients. All patients received 7.2 g of piracetam and placebo for 4 weeks in accordance with a double-blind, randomized treatment order, crossover design with 1-week washout periods prior to each crossover period. Hence, the total study period for each patient was 10 weeks (1-4-1-4). An analysis of 43 psychometric measures revealed significant improvement (P < 0.05) in only three measures, all favoring the treatment condition. Recent findings support a rationale for examining the effects of piracetam in conjunction with cholinergic precursors in patients with cognitive decline. In our second study we conducted a 1-week open trial of 1.6 g of piracetam t.i.d. in conjunction with 3 g of choline cholride t.i.d. in 15 patients. Four patients were rated as clinically improved. These “responders” were all subjects with moderate cognitive impairment. The responders showed much higher RBC choline levels than the nonresponders, both at baseline and during treatment. We conclude that the present evidence indicates that the effects of piracetam treatment alone in elderly outpatients with mild to moderate congnitive decline are subtle and not of proven clinical significance. However, studies of longer duration and of piracetam in combination with other agents may eventually show genuine clinical utility.     

Serotonin in the control of the sleep-like states in frogs

It has been established that brain serotonin (5-HT) is involved in the control of behavioral phenomena in amphibians. The transition of frogs from active wakefulness to sleep-like states was accompanied by alteration of brain 5-HT metabolism, i.e., in sleep-like state with plastic muscle tone 5-hydroxyindoleacetic acid (5-HIAA) level was reduced and in sleep-like state with rigid muscle tone both brain 5-HIAA and 5-HT were decreased. An experimental decrease of brain 5-HT level by inhibition of its biosynthesis by p-chlorophenylalanine (200 mg/kg) induced the sleep-like state of catatonic type, i.e., the state which was characterized by lowered brain 5-HT.     

Variation in the use of biologics in the management of rheumatoid arthritis across the UK

Abstract

Objectives:

Treatment options for rheumatoid arthritis (RA) include conventional synthetic disease-modifying antirheumatic drugs (sDMARDs) and newer biologic DMARDs (biologics). This study describes treatment patterns, adherence to guidance and outcomes at hospital/regional level in the UK.     

经阴道三维超声造影在输卵管源不孕症诊断中的应用

目的探讨经阴道三维超声造影在输卵管源不孕症诊断中的应用。方法选取2012年10月-2013年12月本院生殖中心就诊疑患不孕症患者135例,采用经阴道三维超声造影诊断并治疗输卵管源不孕。结果超声造影通畅情况显示：92条输卵管通畅,107条输卵管通而不畅,59条输卵管阻塞。36例72条输卵管经3D-Hy Co Sy与腹腔镜通染液联合检查,结果显示两种方法具有较强的吻合度（κ=2.135,P〈0.05）。以腹腔镜下输卵管通液检查结果为标准,经阴道3D-Hy Co Sy诊断输卵管通畅的阳性预测值为89.74%、阴性预测值为86.67%。结论经阴道子宫输卵管三维超声造影能真实地反映输卵管的空间走行、形态结构,是一种评价输卵管通畅性安全有效的检查方法。     

The role of the gut flora in the reduction of sulphinpyrazone in the rat

Sulphinpyrazone underwent both reduction to a sulphide and oxidation to a sulphone after parenteral administration to normal Wistar rats. Oral administration was associated with a bioavailability of about 75% and with a 3-fold greater formation of the sulphide. However, no sulphide was detected in the plasma after oral administration of sulphinpyrazone to germ-free (BD/X) rats or normal rats treated with oral antibiotics. In vitro studies showed that the major site of reduction of sulphinpyrazone was the contents of the hind gut with little activity detected in the liver or other tissues. The sulphide was oxidised in vivo to sulphinpyrazone and small amounts of sulphone, while the latter underwent only slight reduction to sulphinpyrazone, but did not give detectable levels of the sulphide. These data suggest that the gut microflora are the main site of reduction of sulphinpyrazone in the rat in vivo.     

Interactions among the cannabinoids in the antagonism of the abdominal constriction response in the mouse

The ability of ⁹-tetrahydrocannabinol (THC), cannabinol (CBN), cannabidiol (CBD), 11-OH THC and 8,11-diOH THC to antagonise the abdominal constriction response in the mouse induced by formic acid, phenylquinone, 5-hydroxytryptamine, prostaglandin E₁ (PGE₁) and bradykinin was tested. THC was an effective antagonist against all nociceptive agents with an ED₅₀ in all cases between 1.0 and 2.6 mg/kg. CBN, while also effective against all nociceptive agents, was less potent than THC, with an ED₅₀ range between 46.2 and 112.5 mg/kg. CBD in doses as high as 200 mg/kg was without effect. Using PGE₁ as the nociceptive agent, 11-OH THC was equipotent to THC while 8,11-diOH THC was inactive. Naloxone, while able to antagonise the antinociceptive effect of morphine against formic acid-induced writhing, did not reverse the antinociceptive effects of THC. There were no pharmacological interactions between THC, CBD and CBN.     

高血压药费减免在农村高血压管理中的效果分析

目的：观察高血压药费减免在农村高血压管理中的效果。方法：对上海金泽镇4个自然村35岁以上人群进行血压普查，1907名高血压患者为研究对象。随机抽取1个自然村为对照组，其余3村为实验组。两组均开展高血压知识健康讲座、建立健康档案，定期随访血压、行心血管风险评估、指导健康的生活方式和合理用药等；实验组的降压药物费用，在新型农村合作医疗报销比例的基础上再减免20%，对照组不减免。比较1年后两组高血压患者的血压变化情况。结果：1年后，实验组的收缩压、舒张压均低于对照组，差异有统计学意义（P<0.05）。实验组患者的控盐率、运动锻炼率、规范服药率、定期测量血压率均高于对照组，差异有统计学意义（P<0.05）。结论：对农村高血压患者开展高血压药费减免是提高高血压管理效果的有效途径之一。