大黄对烧伤模型小鼠疗效及其机理的探讨

本文旨在研究大黄对烧伤的疗效及其作用机理。 2 6只Balb/c小鼠 ,制成烧伤模型 ,随机分成大黄汤剂治疗组和对照组。专人盲法测定肠道灌洗液中总蛋白和球蛋白 (G) ,同时送小肠病理学检查。结果发现 :①治疗组小鼠存活率较对照组有所提高 ;②病理显示对照组 ,小肠绒毛变平 ,有破损现象 ,而用了大黄的小鼠肠粘膜也有破损 ,但可见更多的完整的肠绒毛存在 ,且肠绒毛较对照组高 ;③治疗组小鼠肠道灌洗液中 ,总蛋白和球蛋白的含量均明显高于对照组 ,其均数分别为 3 72g/L和 1 5 7g/L (P <0 0 5 )及 4 12g/L和 2 13g/L (P <0 0 5 )。提示严重烧伤可导致肠粘膜屏障损害。而大黄有促肠道球蛋白分泌作用 ,及减轻肠道形态学改变的作用 ,从而降低烧伤的死亡率     

三苯氧胺对人结肠癌细胞增殖的影响及其机理的探讨

目的：探讨三苯氧胺（ＴＡＭ）对人结肠癌细胞增殖的影响及其机理。方法：采用钙离子荧光指示剂ｆｌｏｕｒ－３／Ａｍ,流式细胞仪动态检测ＴＡＭ作用后人肠癌细胞内游离钙离子（［Ｃａ＾２＋］ｉ）水平的变化,同时用ＭＴＴ比色法测定细胞增殖情况。结果：（１）ＡＴＭ使细胞内［Ｃａ＾２＋］ｉ水平在１分钟内上升,以后维持在一个较高水平（３４９．９７ｎＭ）,与静息状态细胞内［Ｃａ＾２＋］ｉ水平（１０７．８８ｎＭ）相比有显     

Assessment of Fiorinal with Codeine in the treatment of tension headache

A randomized, double-blind, placebo-controlled, multicenter study was conducted to ascertain the contribution of Fiorinal and codeine phosphate to the efficacy of Fiorinal with Codeine in relieving the pain, tension, and muscle stiffness associated with tension headache. Patients were given Fiorinal with Codeine, Fiorinal alone, codeine alone, or placebo for use during two separate headache attacks at least 24 hours apart and were asked to rate the effectiveness of the assigned medication on each occasion. The various symptoms of tension headache were evaluated by the patient 0.5, 1, 2, 3, and 4 hours after ingestion of the study medication. At the final patient visit, the investigator assessed the effect of treatment on the three chief components of tension headache, head pain, psychic tension, and muscle contraction. Fiorinal with Codeine was generally significantly more effective than placebo or Fiorinal alone in improving all patient-evaluated items between the second and the fourth hours after administration. The combination was also generally significantly better than codeine alone with respect to pain severity, pain relief, the ability to perform daily activities, and average pathology. The three variables rated by the physician also were generally reduced significantly more with the combination than with placebo or Fiorinal alone. Side effects occurred in only one patient treated with Fiorinal with Codeine.     

Antidiarrheal activity of alpha-2 adrenoceptor agonist SK&F 35886

Alpha-2 adrenoceptor agonists exhibit antidiarrheal activity in animal models and in humans. However, hypotensive and sedative side effects seriously limit the use of these agents to treat diarrhea. SK&F 35886 (2,6-dimethyl phenylamino imidazoline) is an alpha-2 adrenoceptor agonist with little central nervous system activity. In Ussing chamber preparations of rabbit ileum, SK&F 35886 produces a concentration-dependent decrease in basal short-circuit current (Isc) (EC50 0.2 microM) that is dependent on the presence of mucosal HCO3. This concentration-response curve is shifted to the right of rauwolscine, increasing the EC50 to 30 microM. Prazosin had no effect on this response. Flux studies indicate that SK&F 35886 increases net Cl absorption and enhances HCO3 absorption without altering net Na flux. After PGE2 stimulation of Isc, SK&F 35886, applied either serosally or mucosally, immediately returns the Isc to base line. This effect is due to a reversal of the PGE2-induced inhibition of Na and Cl absorption. In vivo SK&F 35886 dose-dependently inhibits PGE2-induced enteropooling when given orally (ED50 approximately 31 micrograms/kg). This effect is attenuated significantly by rauwolscine (1.0 micrograms/kg s.c.). In cecectomized rats, SK&F 35886 abolishes PGE2-induced diarrhea within 1 hr after oral administration of the drug. SK&F 35886 (500 micrograms/kg p.o.) did not alter hexobarbital sleep time or elicit piloerection or lethargy, whereas clonidine (37.3 micrograms/kg p.o.) significantly enhanced hexobarbital sleep time. These results illustrate the ability of a peripheral acting alpha-2 agonist to promote absorption and inhibit secretion and diarrhea in the mammalian intestine.     

Further Studies on the Mechanism of the Effect of Enzymes on Erythrocyte Serology with Special Reference to Pronase

The mechanism by which pronase treatment of red cells leads to agglutination with "incomplete" antibodies has been investigated. Like other serologically active enzymes, pronase hydrolyzes arginine and lysine derivatives (the former about 100 times as readily as the latter) and releases NANA from erythrocytes in a manner which correlates with development of serologic titer. In attempting to define the minimum quantity of NANA liberation consistent with appearance of agglutination, the following quantities (μmole NANA/10¹⁰RBC) were sufficient and insufficient, respectively: for pronase, 0.28 and 0.16; for papain, 0.21 and 0.19; and for trypsin, 0.16 and 0.09. These differences may reflect differences among the enzymes with regard to producing new ionogenic groups on erythrocytes. Pronase further differed from papain and trypsin in that a minimal amount of enzyme gave no progressive NANA liberation over a six-hour period, all of its effect being exerted by the end of 15 minutes. The utility of pronase in detection of "incomplete" Rh antibodies is excellent.     

Studies on the Mechanism of Action of Nalidixic Acid

With three independent techniques (absorption spectrophotometry, measurement of the deoxyribonucleic acid [DNA] melting temperature, and equilibrium dialysis), no evidence has been found for the binding of nalidixic acid to purified DNA. Also, no evidence has been found to support the hypothesis that nalidixic acid is permanently modified to a new, active compound by the bacterial cell. By using an in vitro DNA replication system developed by Bonhoeffer and colleagues, soluble extracts from nalidixic acid-sensitive cells have been shown to confer nalidixic acid sensitivity on the DNA synthesis of lysates from nalidixic acid-resistant cells. The activity in the extracts is only present in sensitive cells and is nondialyzable and heat sensitive. Finally, two known nalidixic acid-resistant mutants of Escherichia coli, mapping at nal A and nal B, respectively, have been tested to determine whether either of them is a transport mutant. It has been shown that nal B(r) is a transport mutant whereas nal A(r) is not.     

复方儿茶水提液的抗腹泻和抗炎效应

目的:观察以单味使用具有较弱的收敛、敛疮、抗菌、消炎等多种功能的中药组方的复方儿茶水提液抗腹泻和抗炎作用,寻找高效低毒的抗腹泻药。方法:实验于2005-07/12在大连大学药理实验室完成,选择清洁级昆明种小鼠280只,体质量18～22g,雌雄不拘。随机数字表法分为复方儿茶水提液2,4g/kg剂量组、阳性药对照组、生理盐水组4组,每组70只。分别灌胃复方儿茶水提液2,4g/kg,阳性药(黄连素0.03g/kg,硫酸阿托品10mg/kg,阿司匹林0.3g/kg,以等容积生理盐水制成药液),同容积生理盐水。每组再均分为7个亚组,分别施加番泻叶(2g/kg)、蓖麻油(7.5g/kg)、大黄(20g/kg)、硫酸钠(20g/kg)和二甲苯(0.05mL/只)、乙酸(0.7g/kg)7个因素致小鼠腹泻或炎症模型,观察复方儿茶水提液的抗腹泻和抗炎作用。结果:纳入280只小鼠,均进入结果分析。①复方儿茶水提液2,4g/kg剂量组给药后1,2,3,4h番泻叶、蓖麻油、大黄、硫酸钠所致腹泻次数显著低于生理盐水组(P<0.05～0.001),复方儿茶水提液4g/kg剂量组作用优于2g/kg剂量组。②复方儿茶水提液2,4g/kg组胃肠推进率与生理盐水组比较差异有非常显著性意义(P<0.01～0.001),与阳性药(硫酸阿托品10mg/kg)对照组比较差异没有显著性意义(P>0.05)。复方儿茶水提液2,4g/kg组、阳性药对照组抑制率分别为40.0%、78.6%和34.4%。③复方儿茶水提液2,4g/kg组、阳性药(阿司匹林)对照组左右耳片质量差均显著低于生理盐水组(P<0.05～0.01)。④复方儿茶水提液2,4g/kg组和阿司匹林组对乙酸提高的小鼠腹腔毛细血管通透性抑制率分别为42.5%,64.9%和66.7%(P<0.05～0.01)。结论:复方儿茶水提液抗腹泻作用机制广泛,具有抗渗透性泻下和刺激性泻下作用,可以通过抗炎对抗炎症介质的泻下作用,产生抗腹泻作用。这些抗炎作用可能是复方儿茶水提液抗腹泻作用的重要机制。     

复方儿茶水提液的抗腹泻和抗炎效应

目的：观察以单味使用具有较弱的收敛、敛疮、抗菌、消炎等多种功能的中药组方的复方儿茶水提液抗腹泻和抗炎作用，寻找高效低毒的抗腹泻药。方法：实验于2005-07／12在大连大学药理实验室完成，选择清洁级昆明种小鼠280只，体质量18-22g，雌雄不拘、随机数字表法分为复方儿茶水提液2，4g／kg剂量组、阳性药对照组、生理盐水组4组，每组70只。分别灌胃复方儿茶水提液2，4g／kg。阳性药（黄连素0．03g／kg，硫酸阿托品10mg／kg，阿司匹林0.3g/kg，以等容积生理盐水制成药液），同容积生理盐水。每组再均分为7个亚组，分别施加番泻叶（2g／kg）、蓖麻油（7．5g／kg）、大黄（20g／kg）、硫酸钠（20g／kg）和二甲苯（0．05mL／只）、乙酸（0．7g／kg）7个因素致小鼠腹泻或炎症模型，观察复方儿茶水提液的抗腹泻和抗炎作用。结果：纳入280只小鼠，均进入结果分析。①复方儿茶水提液2，4g／kg剂量组给药后1，2，3，4h番泻叶、蓖麻油、大黄，硫酸钠所致腹泻次数显著低于生理盐水组（P〈0．05-0．001），复方儿茶水提液4g／kg剂量组作用优于2g／kg剂量组。②复方儿茶水提液2，4g／kg组胃肠推进率与生理盐水组比较差异有非常显著性意义（P〈0．01-0．001），与阳性药（硫酸阿托品10mg／kg）对照组比较差异没有显著性意义（P〉0．05）。复方儿茶水提液2，4g／kg组、阳性药对照组抑制率分别为40．0％、78．6％和34．4％。③复方儿茶水提液2.4g/kg组、阳性药（阿司匹林）对照组左右耳片质量差均显著低于生理盐水组（P〈0．05-0．01）。④复方儿茶水提液2，4g／kg组和阿司匹林组对乙酸提高的小鼠腹腔毛细血管通透性抑制率分别为42．5％，64．9％和66．7％（P〈0．05-0．01）。结论：复方儿茶水提液抗腹泻作用机制广泛，具有抗渗透性泻下和刺激性泻下作用，可以通过抗炎对抗炎症介质的泻下作用，产生抗腹泻作用。这些抗炎作用可能是复方儿茶水提液抗腹泻作用的重要机制。     

Fiorinal with Codeine in the management of tension headache: impact of placebo response

The well-known difficulty in distinguishing the response to a combination headache medication and its individual components in the presence of a high placebo response was again demonstrated in a randomized, double-blind, placebo-controlled, multi-center trial comparing Fiorinal with Codeine and its Fiorinal and codeine phosphate components in relieving the pain, tension, and muscle contraction associated with tension headache. In the original analysis of the study data, no distinction was apparent between patient response to Fiorinal with Codeine and the response to the individual components, a finding that appeared to conflict with the results of a similar earlier study. This apparent discrepancy was attributable to a high placebo response in the later study. Separation of study subjects according to their baseline level of anxiety and pain identified a subset of less anxious patients with mild to moderate pain severity who were least likely to respond to placebo. Analysis of data from these patients showed that Fiorinal with Codeine was significantly better than placebo in improving patients' self-ratings of various symptoms of tension headache at 0.5, 1, 2, 3, and 4 hours after ingestion of the study medication. The combination drug was also consistently superior to Fiorinal alone and codeine alone in improving the patients' self-evaluation items, and differences between the combination and its components were generally of statistical or borderline significance during the last half of the study. The investigators' assessments of the effect of treatment on the three principal variables in tension headache (namely, headache pain, psychic tension, and muscle contraction of the head, neck, and shoulders) at the final patient visit also showed Fiorinal with Codeine to be not only significantly superior to placebo but also consistently superior to either component. The superiority of the combination over Fiorinal alone achieved borderline significance for headache pain and psychic tension.     

回输的血小板在体内清除机制研究进展

生理学，病理学方面的研究发现血小板在体内清除主要发生在肝脏和脾脏，但衰老和损伤的血小板被体内清除系统识别和清除的机制还并不清楚。这一机制研究的深入将有助于解决血小板低温保存后体内存活期短．不能较长期发挥作用的难题，为血小板保存提出新的策略。本文就血小扳回输体内后的清除机制，包括P-选择蛋白，GPIbα及其受体Mac-1和内源性金属蛋白酶在血小板清除进程中的作用等的研究进展作一综述。     

Studies on the Mechanism of Sodium Excretion during Drug-induced Vasodilatation in the Dog

The administration of vasodilating agents such as bradykinin and acetylcholine cause an increase in urinary sodium excretion. Yet the mechanisms involved in this natriuretic effect are not clear. Recent studies with another renal vasodilator, secretin have shown this drug also causes a profound increase in renal blood flow but without major changes in sodium excretion. To attempt to delineate the basis of this difference in sodium excretion with these drugs, the renal functional effects of secretin and bradykinin were compared at an equivalent vasodilating dose. Bradykinin increased renal blood flow from 222 to 342 ml/min, urine volume from 0.2 to 1.2 ml/min, and urine sodium excretion from 28 to 115 μeq/min. Urine osmolality fell from 1,230 to 401 mosmol/kg. Secretin caused a comparable increase in renal blood flow (216 to 325 ml/min) while changes in urine flow, sodium excretion, and urine osmolality were significantly less.     

Lower Esophageal Sphincter Relaxation: Studies on the Neurogenic Inhibitory Mechanism

The purpose of this study was to determine the physiological mechanism of lower esophageal sphincter (LES) relaxation. Circular muscle of the esophagus, LES, and stomach were evaluated for their inhibitory response to electrical stimulation during a maintained tonic contraction produced by a superfusion of acetylcholine and physostigmine. Only the circular muscle of the distal esophagus showed an inhibitory response to electrical stimulation. The maximal inhibition of LES muscle was 63.9+/-5.9 (mean+/-SE)% of the acetylcholine produced tension and occurred at 80 V. Upper esophageal and gastric muscle were not inhibited. The inhibitory response of the LES muscle was antagonized by tetrodotoxin and hexamethonium but not by other specific antagonists. Adrenergic nerve destruction following 6-hydroxydopamine also did not abolish the LES inhibition. These data indicate that the distal esophagus, at the zone of the manometrically determined LES, is characterized by a nonadrenergic neural inhibitory system. We suggest that these nerves may mediate LES relaxation.     

Studies on the Mechanism of Reduced Urinary Osmolality after Exposure of the Renal Papilla

Studies were performed in Munich-Wistar rats to determine whether changes in papillary plasma flow might be responsible for the concentrating defect which occurs after exposure of the extrarenal papilla. Papillary plasma flow was measured by (125)I-albumin accumulation. Initial studies in hydropenic animals revealed that papillary plasma flow was 40% higher in the kidney with the exposured papilla, 41 vs. 29 ml/min per 100 g of papilla (P < 0.001). This increase in papillary plasma flow was detectable 15 or 45 min after removing the ureter. Because it was unclear whether the rise in papillary plasma flow was a cause or the result of the fall in urine osmolality, similar studies were performed in animals undergoing a water diuresis. In this setting, papillary plasma flow still increased on the exposed side compared to the control side, 81 vs. 60 ml/min per 100 g, despite similarly low urine osmolalities of 155 and 174 mosmol/kg, respectively. This finding is compatible with the possibility that papillary exposure per se causes an increase in papillary plasma flow and that this hemodynamic alteration may lead to a reduction in urinary osmolality secondary to washout of the medullary interstitium. A final group of hydropenic rats was given either indomethacin or meclofenamate before removing the ureter. In these studies, there was no difference in either the papillary plasma flow or the urine osmolality between control and exposed kidneys. It is therefore suggested that opening the ureter induces an increase in papillary plasma flow by some mechanism which may involve an alteration in prostaglandin synthesis.     

复方磷酸可待因溶液治疗感染后咳嗽的临床观察

目的:观察复方磷酸可待因溶液治疗感染后咳嗽的临床疗效.方法:感染后咳嗽患者120例,给予复方磷酸可待因溶液治疗,每日3次,每次10～15 mL,连用3～7天后症状评分及判断疗效.结果:治疗前后比较患者咳嗽等各种症状均明显缓解,睡眠质量明显改善,副作用少而小.结论:复方磷酸可待因溶液用于治疗感染后咳嗽安全有效.     

Mechanism of the Hypolipemic Effect of Clofibrate in Postabsorptive Man

Splanchnic metabolism of triglycerides and other major substrates was studied in the postabsorptive state in normotriglyceridemic and hypertriglyceridemic human subjects who received (1/2) g of clofibrate four times daily for 3 wk. Transport in blood plasma of triglycerides produced in the splanchnic region was quantified by three methods: (a) measurement of the transsplanchnic gradient of (14)C-labeled triglycerides during constant intravenous infusion of [1- (14)C] palmitate (b) chemical measurement of the transplanchnic gradient in concentration of triglycerides of very low density lipoproteins; and (c) determination of clearance of (14)C-labeled triglycerides in extrasplanchnic tissues. The first method measures only triglycerides derived from free fatty acids and the last two measure total splanchnic production. In hypertriglyceridemic subjects treated with clofibrate, average rates of total splanchnic production of triglycerides and production from free fatty acids were the same as those of comparable untreated subjects despite a consistent fall in plasma triglyceride levels. The hypotriglyceridemic effect of the drug was therefore accompanied by improved disposal of triglycerides in extrasplanchnic tissues. In treated normotriglyceridemic subjects, unlike their untreated counterparts, total splanchnic production was significantly higher than production from free fatty acids. Failure of clofibrate to reduce triglyceride levels in normotriglyceridemic subjects may have been related to increased total splanchnic production, coupled with improved extrasplanchnic disposal.Systemic transport and net splanchnic uptake of free fatty acids were similar in treated and control subjects but the fraction of [1-(14)C]palmitate converted to acetoacetate in splanchnic tissues was significantly higher in treated subjects. Net splanchnic extraction of plasma amino acids that enter the glucogenic pathway via pyruvate was increased in treated subjects and their arterial concentrations were reduced.     

Studies on the Mechanism of Oliguria in a Model of Unilateral Acute Renal Failure

To further evaluate the mechanism of the oliguria of acute renal failure, a model was utilized in which intense and prolonged vasoconstriction produced the unilateral cessation of urine flow. The radioactive microsphere method was used to measure total and regional blood flow before and after the intrarenal infusion of norepinephrine, 0.75 mug/kg/min, for 2 h in the dog. In the control kidney, renal blood flow increased 32% 48 h after norepinephrine in association with a fall in the fractional distribution of flow to the outer cortex. In the experimental kidney, total renal blood flow fell from 190 ml/min before norepinephrine to 116 ml/min at 48 h (P < 0.025) with a uniform reduction in cortical blood flow. After the administration of 10% body wt Ringer's solution, there was a marked redistribution of flow to inner cortical nephrons in both the control and experimental kidney. In addition, there was a marked increase in total blood flow in both kidneys. On the experimental side, flow rose to 235 ml/min, a value greater than in either the control period (P < 0.05) or at 48 h after norepinephrine (P < 0.001). However, in spite of this marked increase in blood flow, there was essentially no urine flow from the experimental kidney. In separate studies, the animals were prepared for micropuncture. In all studies, the surface tubules were collapsed, and there was no evidence of tubular obstruction or leakage of filtrate. Over 99% of the 15-muM spheres were extracted in one pass through the experimental kidney. An analysis of the forces affecting filtration suggested that an alteration in the ultrafiltration coefficient may be responsible, at least in part, for the anuria in this model. In this regard, transmission and scanning electron microscopy revealed a marked abnormality in the epithelial structure of the glomerulus. It is suggested that a decrease in glomerular capillary permeability may be present in this model of acute renal failure.