EFFECTS OF PROGESTOGENS ON LIPEMIA AND LIPOLYSIS IN RAT: EFFECTS OF PROGESTERONE, MEGESTROL ACETATE, NORETHINDRONE ACETATE, AND NOMEGESTROL ACETATE

Effects of 4 progestogens at equal dosages (5 mg/kg/day) on lipid metabolism and plasma glucose levels of adult female rats were compared. The 4 progestogens studied were progesterone (P) by SC injection, and megestrol acetate (MEG), norethindrone acetate (NOR), and nomegestrol acetate (NOM) PO. MEG, a 17 alpha-hydroxyprogesterone derivative, induced significant increases in glucose, total and high-density lipid (HDL) cholesterol, triglyceride, and phospholipid plasma levels. Treatment with NOR, a 19-nortestosterone derivative, resulted in a reduced gain in body wt and in a marked decrease in all plasma lipid parameters. The 19-norprogesterone derivative NOM, like P, did not alter lipid or glucose metabolism, despite a significant increase in body wt gain. In particular, no reduction in the HDL cholesterol level occurred. Plasma and tissue lipolytic activities remained unchanged. The results of this study confirm interest in the therapeutic class of 19-norprogesterone-derived progestogens, exemplified by NOM, with respect to their lack of metabolic side effects.     

鞘内注入醋酸泼尼松龙对大鼠镇痛作用及脊髓c-fos表达的影响

目的 :探讨鞘内注入泼尼松龙镇痛作用及其对脊髓c fos表达的影响与神经毒性作用。方法 :慢性鞘内置管的SD大鼠 2 4只 ,随机分为实验组 2 0只 ,对照组 4只。实验组又分成两个亚组 ,用药组 (EP组 ,n =10 ) ,生理盐水组 (EN组 ,n =10 ) ;对照组分为二个亚组 ,用药组 (CP组 ,n =2 ) ,空白对照组 (CE组 ,n =2 )。EP组经导管鞘内注入泼尼松龙 2mg/kg ,1小时后行福尔马林试验 ,进行行为学评分并计算痛级均数 ;2小时后灌注、固定 ,取脊髓腰膨大用ABC法行c fos免疫组化反应及病理检验 ,记数脊髓背角c fos阳性神经元数 ,并与鞘内注入等量生理盐水组 (EN )相比较。结果 :实验各组痛级均数比较有显著差异 (P <0 .0 5 ) ;脊髓腰膨大背角Ⅰ、Ⅱ层c fos阳性神经元数EP组有减少趋势 ,但无显著差异 ;腰膨大病理检验未示异常。结论 :鞘内注入泼尼松龙有镇痛作用 ,无神经毒性作用。     

血清丙酮酸激酶在血液病的诊断和治疗中的应用

目的探讨血清丙酮酸激酶(Pyruvate kinase,PK)活性变化在血液系统疾病的诊断和疗效观察中的作用.方法用速率法测定血清PK活性.结果非白血病组和慢性粒细胞白血病组血清PK活性正常,与对照组比较无差异(P＞0.05);急性淋巴细胞白血病组、急性单核细胞白血病组、急性粒细胞白血病组酶活性分别呈轻度升高(140±11 IU/L)、中度升高(241±32 IU/L)、高度升高(495±151 IU/L),与对照组(63±18 IU/L)比较有显著差异(P＜0.05或P＜0.01).酶活性随治疗好转而逐渐降低,病情完全缓解时,酶活性稳定在正常范围内.结论检测血清PK活性可作为血液系统疾病诊断和疗效的动态观察的重要指标.     

醋酸氯己定与替硝唑联合药敏试验观察

目的研究醋酸氯己定与替硝唑协同抗菌效果。方法采用棋盘方阵稀释法,对醋酸氯己定与替硝唑联合应用体外抗菌作用进行了观察。结果测定替硝唑和醋酸氯己定对金黄色葡萄球菌、铜绿假单胞菌、产气荚膜梭菌和脆弱拟杆菌的MIC值,替硝唑分别为200、200、1、1μg/ml,醋酸氯己定分别为0.06、4、1、4μg/ml。替硝唑与醋酸氯己定联合应用对上述4种试验菌的MIC值与各自的单方相比较无变化,两药相加无相关作用,但相互也不干扰对方的抗菌作用。结论应用于创伤涂膜剂中的醋酸氯己定和替硝唑两种主要抗菌成分既无协同作用或相加作用,但也不互相干扰。     

中西医结合治疗高粘血症对血液流变性的影响

目的：为寻找治疗高粘血症有效的药物。方法：将１７６例高粘血症患 者随机分成丹参组、蝮蛇抗栓酶组和中西医结合组。中西医结合组联用丹参和蝮 蛇抗栓酶。 结果：丹参能明显降低全血高切还原粘度、全血低切还原粘度、红细胞 聚集指数（Ｐ＜０.０５）;蝮蛇抗栓酶对血沉、血沉方程Ｋ值、纤维蛋白原有明显降低 作用（Ｐ＜０．０５）;中西医结合治疗组血液流变各参数均有明显下降（Ｐ＜０．０５）。结 论：丹参和蝮蛇抗栓酶联合应用较单一用药更有效。     

CARDIOVASCULAR AND METABOLIC EFFECTS OF TERBUTALINE

Terbutaline is a selective beta 2 agonist used predominantly in the treatment of asthma. Since beta-mediated responses increase heart rate, dilate peripheral arteries, modify carbohydrate metabolism and the uptake of electrolytes into cells, the administration of terbutaline might be expected to produce widespread effects. In this study the intravenous administration of 0.5 mg terbutaline over 60 min has been shown to produce marked changes without upsetting the volunteers. Heart rate, systolic blood pressure and plasma glucose all increase; diastolic pressure and serum potassium decrease. The data suggests that the terbutaline infusion may be a useful tool for the investigator. The results also quantitate some of the side effects which may result from the intravenous administration of a therapeutic dose of terbutaline given to asthmatics or to pregnant women to reduce uterine activity and delay childbirth.     

钙拮抗剂、β1受体阻滞剂对高血压病患者血小板功能的影响

目的研究抗高血压药钙拮抗剂、β1受体阻滞剂对高血压病患者血小板功能的影响.方法53例高血压病Ⅰ级、Ⅱ级患者,随机接受尼群地平或倍他乐克治疗12周,治疗前后分别经流式细胞仪测定血小板GPⅡb/Ⅲa受体表达率并比较治疗前后变化.结果尼群地平组治疗后GPⅡb/Ⅲa受体表达率显著降低,而倍他乐克组治疗前后血小板GPⅡb/Ⅲa受体表达率无显著变化.结论尼群地平有拮抗血小板功能作用,倍他乐克则无影响.     

优乐散对真菌和细菌的抑制作用

对21株真菌与27株细菌试管抑菌试验表明,优乐散为一较好的抗菌药物。其对真菌的抑制作用强于克霉唑,但逊于益康唑;对细菌的抑制作用,优于磺胺甲基(口异)(口恶)唑,不及氟哌酸。     

INDUCTIVE EFFECTS OF FENOFIBRATE AND METABOLISM OF PHENOBARBITAL

The inductive effects of fenofibrate (FF) and phenobarbital (PB) were investigated in male Wistar rats. FF treatment produced an inductive effect on liver weight, cytochrome P450 content, and aniline hydroxylase (AH) and bilirubin UDP-glucuronosyltransferase (UDP-GT) activities in liver microsome fraction. PB and FF inductive effects were additive on liver weight but were not additive on P450 microsomal concentrations. On the contrary, FF administration decreased the inductive effect of PB on bilirubin UDP-GT activity. When FF and PB treatment were coupled, plasma and liver PB concentrations were not affected, whereas OHPB concentrations, especially in liver homogenate, were greatly decreased. Thus it can be concluded that the production of OHPB from PB was probably not accelerated, but the elimination of OHPB, the main metabolite of PB, was considerably enhanced. These results are to be compared with recent reports of structure-dependent induction of bilirubin glucuronidation by arylcarboxylic acids chemically related to clofibrate.     

COMPARISON OF THE EFFECTS OF PAPAIN AND VITAMIN A ON CARTILAGE : I. THE EFFECTS IN RABBITS

The administration of large amounts of vitamin A to rabbits has been shown to result in depletion of cartilage matrix. The normal basophilic, metachromatic, and Alcian blue staining properties of the matrix are lost, especially in articular and epiphyseal cartilage. The cartilage cells remain intact, but are reduced in size. These changes sometimes appeared as early as 48 hours after the initiation of daily injection of 1 million units of vitamin A, and were usually well established by 5 days. Some rabbits failed to show changes in cartilage, even after 5 daily injections. Increased amounts of material presumed to be chondroitin sulfate were present in the sera of vitamin A-treated rabbits, usually by 72 hours after the first injection. This was demonstrated by a turbidimetric procedure using hexamminecobaltic chloride. In rabbits given sulfur-35 (Na₂S³⁵O₄) 5 days before the initiation of vitamin A treatment, it was shown that sulfur-35 was lost from articular and epiphyseal cartilage. This was associated with an increase in the non-dialyzable sulfur-35 in both serum and in the cobalt-precipitable material. These rabbits also excreted more sulfur-35 than rabbits not given vitamin A. There was a reduction in sulfur-35 activity in chondromucoprotein extracted from the ear cartilage of vitamin A-treated rabbits. The changes are interpreted as indicating that the administration of large amounts of vitamin A to rabbits results in removal of chondroitin sulfate from cartilage matrix. The administration of small amounts of crude papain causes histologic changes in cartilage that are remarkably similar to those seen in vitamin A-treated rabbits. The possibility is suggested that the changes in cartilage produced by administration of vitamin A to rabbits may be the result of activation of a proteolytic enzyme or enzymes, with properties similar to those of papain.     

EFFECTS OF PURINES AND FORSKOLIN ON HAEMOLYSIS

Effects of adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenosine on the antihaemolytic action of procaine, and the effect of ATP on the antihaemolytic actions of lidocaine, dibucaine, tetracaine, pentobarbitone, and chlorpromazine were investigated in rat erythrocytes. The effects of adenosine and its analogues D-N6-phenylisopropyladenosine (D-PIA), L-N6-phenylisopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA), 2-chloroadenosine, and N6-methyladenosine, as well as the effects of cyclic-AMP (cAMP), dibutyryl cAMP, and forskolin on haemolysis were also investigated in rat erythrocytes. ATP, ADP, and AMP, but not adenosine, antagonized in a concentration-dependent manner the antihaemolytic action of procaine, and ATP was ineffective against the antihaemolytic actions of lidocaine, dibucaine, tetracaine, pentobarbitone, and chlorpromazine. Adenosine and its analogues, but not N6-methyladenosine, protected erythrocytes against hypotonic haemolysis in a concentration-dependent manner. The order of potencies was: D-PIA greater than CHA greater than L-PIA greater than adenosine greater than 2-chloroadenosine. The effect of adenosine on haemolysis was not prevented by theophylline, 8-phenyltheophylline, or 8-sulfophenyltheophylline. Dibutyryl cAMP, a stable analogue of cAMP, and forskolin, a specific activator of adenylate cyclase, mimicked the antihaemolytic action of adenosine. cAMP was less efficient than adenosine. Adenine nucleotides antagonized the antihaemolytic action of procaine, probably due to calcium-chelating properties. In contrast, adenine nucleosides have antihaemolytic properties. The possibility that the antihaemolytic effects of these substances relate to cAMP and/or to lipophilicity is discussed.     

EFFECTS OF MECHANICAL AGITATION AND OF TEMPERATURE UPON COMPLEMENT

1. Under certain conditions, mechanical agitation destroys the complementary activity of guinea pig serum. It is most injurious when carried out constantly at a temperature of 37° C., but it is extremely insignificant at 10° C. After the first few hours at 37° C., the destruction of complement proceeded much more rapidly, and after six hours it was almost complete. On the other hand, within one hour shaking had almost no destructive effect on complement, even at 37° C. From this we may conclude that the several shakings which are necessary for fixation experiments during incubation do not modify perceptibly the outcome of the reactions. 2. The rate of destruction of the complement of guinea pig serum at temperatures above 45° C. is progressively greater as it approaches 55° C., at which temperature the activity is reduced in thirty minutes to one-thirtieth to one-fortieth of the original strength of the unheated serum; but it is not completely destroyed, as is commonly assumed. The velocity of destruction of guinea pig complement when exposed to 55° C. for various lengths of time is found to be quite irregular, and not proportional to the length of time. This irregularity, however, presents a certain rhythm, a period of greater destruction alternating with one of less destruction.     

FATHERHOOD AND DEPRESSION: A REVIEW OF RISKS,EFFECTS, AND CLINICAL APPLICATION

This literature review attempted to compile a complete evaluation of the presentation, risks, and subsequent effects upon a family in relation to paternal depression. Clinical applications are reviewed as well. As with women, fathers will present with a dysphoric mood, but unlike their female counterparts, depressed men often experience a change in social behavior. Withdrawal from social situations, indecisiveness, cynicism, and an irritable mood are often found as hallmark signs of depression in the adult male. Life stress, or family stress and low social support, are risk factors associated with depression among fathers. Marital difficulties may be the most common trigger for first-time depression in husbands just as divorce amplifies depressive episodes, especially when children are involved. A variety of treatments have proven effective for depressed fathers including traditional psycho-dynamic, CBT, and group therapy. Therapy is effective when it can be initiated and continued but research repeatedly showed that men seek it out far less than women. Effective outreach programs to encourage treatment among depressed fathers are recommended.     

环胞霉素A、亲合素和钙调磷酸酶复合物的结构特性与免疫抑制及其毒理作用机理

钙调磷酸酶（calcineurin，CN）是亲免素（immunophilin）-免疫抑制药物（immunosuppressant）复合物-环胞霉素A（cyclosporin A，CsA）、环胞霉素A亲合素（cyclophilin，CyP）和FK506结合蛋白（FK506-bindingprotein，FK BP-506）、FK506的共同靶目标。这些药物蛋白的复合物都能特异地抑制CN的生物活性，但是两种结构完全不同的亲免素-免疫抑制药物复合物为何能够作用同一靶目标目前仍不清楚。     

Studies on the Mechanism of Ristocetin-Induced Platelet Agglutination: EFFECTS OF STRUCTURAL MODIFICATION OF RISTOCETIN AND VANCOMYCIN

The mechanism by which ristocetin induces platelet agglutination in the presence of the von Willebrand factor was studied by chemically altering ristocetin and a similar antibiotic, vancomycin, by reaction with a water-soluble carbodiimide in the presence of glycine methyl ester at pH 4.75. Altering ristocetin's phenolic groups (which are thought to be important in its peptide-binding properties) resulted in a loss of both platelet-agglutinating and antibiotic activities. Restoring the phenolic groups with hydroxylamine restored both activities.Vancomycin has antibiotic and peptide-binding properties similar to ristocetin's, but differs structurally in having a free carboxyl group and thus a less positive charge at neutral pH. It does not induce platelet agglutination and actually inhibits ristocetin-induced agglutination. Reacting vancomycin with the water-soluble carbodiimide resulted in alteration of phenolic groups and permanent conversion of the carboxyl to a neutral derivative. Restoring the phenolic groups with hydroxylamine (but leaving the carboxyl neutralized) produced a compound with charge properties similar to ristocetin's which induced platelet agglutination as ristocetin does.These data suggest both a binding requirement (mediated through phenolic groups) and a strong positive charge requirement for ristocetin-induced agglutination. The data are consistent with a model wherein positively charged ristocetin binds, via its phenolic groups, to sites on the platelet surface and reduces the platelet's negative charge. This could reduce the electrostatic repulsion between platelets and/or between platelets and the negatively charged von Willebrand factor, and permit the macromolecular von Willebrand factor to cause agglutination by bridging between platelets.