Effect of gomisin A (TJN-101) on the arachidonic acid cascade in macrophages

It has been reported that leukotrienes (LTs) may play a role in inflammatory liver diseases, and several inhibitors of LTs show an inhibitory effect on experimental liver injuries. In this study, the effect of Gomisin A (TJN-101), which is a lignan component of schisandra fruits, on the arachidonic acid cascade in macrophages was examined to explain the mechanisms of the inhibitory effect of TJN-101 on liver injuries. The production of leukotriene B4 was suppressed by treatment with TJN-101, while the activity of 5-lipoxygenase was not affected. The release of arachidonic acid from macrophages stimulated with fMet-Leu-Phe or the Ca++ ionophore A23187 was suppressed by treatment with TJN-101. The activity of phospholipase A2 was not affected by treatment with TJN-101. These results suggested that TJN-101 produces an inhibitory effect on the biosynthesis of LTs by preventing the release of arachidonic acid, and it was thought that the preventive effect on the arachidonic acid cascade may be partially associated with the inhibitory effect of TJN-101 on liver injuries.     

食物对两种桂利嗪胶囊人体生物利用度的影响(英文)

目的比较食物对两种桂利嗪胶囊(A和B)人体生物利用度的影响。方法用HPLC紫外检测法测定健康受试者分别在禁食及餐后一次口服50mg桂利嗪胶囊A或B后血清药物浓度。结果胶囊A的Cmax 及AUC不受食物影响 ,胶囊B的吸收受食物影响 ,禁食后的Cmax 和AUC显著低于餐后的Cmax 和AUC。结论胶囊A的制剂优于胶囊B的制剂 ,其人体生物利用度不受食物影响     

Probable involvement of vascular angiotensin II formation in the β2-adrenoceptor-mediated facilitation of the neurogenic vasopressor response in the pithed rat

Rats were pithed, vagotomized and adrenalectomized and the effect of procaterol on the pressor response to electrical stimulation of the thoracolumbar preganglionic sympathetic outflow from the spinal cord or to exogenous noradrenaline was studied in the absence and presence of beta-adrenoceptor antagonists and drugs interfering with the renin-angiotensin system. 1. Basal diastolic blood pressure was decreased by captopril, ramiprilate (angiotensin converting enzyme inhibitors), saralasin (an angiotensin II receptor antagonist), pepstatin A (a protease inhibitor with renin antagonistic properties) and by functional nephrectomy (ligation of both renal hili), but was not affected by procaterol (a beta 2-adrenoceptor agonist), nebivolol (a beta 1-adrenoceptor antagonist) and ICI 118,551 (erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobut an-2-ol; a beta 2-adrenoceptor antagonist). 2. The vasopressor response induced by electrical stimulation of the preganglionic sympathetic nerve fibres was increased by procaterol, whereas the increase in blood pressure evoked by exogenous noradrenaline was not affected. The pressor response to both electrical stimulation and exogenous noradrenaline was decreased by captopril, ramiprilate, saralasin and nephrectomy but was not affected by nebivolol and ICI 118,551. 3. The facilitatory effect of procaterol on the neurogenic, electrically induced pressor response, which was also obtained when basal blood pressure was decreased by nephrectomy and increased by Lys8-vasopressin, was abolished by ICI 118,551 but not affected by nebivolol. Under none of these experimental conditions did procaterol alter the vasopressor response to exogenous noradrenaline. 4. The facilitatory effect of procaterol on the neurogenic, electrically induced rise in blood pressure was abolished by captopril, ramiprilate, saralasin and pepstatin A.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of sulfur mustard on murine lymphocytes

The effect on spleen cells of a single in vivo treatment with sulfur mustard was analyzed in mice 1 week after intoxication. A marked decrease in the number of total spleen cells was observed in mice receiving high doses of sulfur mustard. Flow cytometric analysis indicated that B-lymphocytes were relatively more affected than T-lymphocytes by this toxic compound. However, the function of remaining B-cells, measured by thymidine incorporation and immunoglobulin secretion in the presence of lipopolysaccharide, was not significantly impaired. In addition, sulfur mustard did not depress T-lymphocyte function since their proliferation in response to concanavalin A or to an anti-CD3 antibody was not affected by the treatment. These results suggest that whereas some observations reported in patients can be found in a murine model, additional in vitro studies with human lymphocytes could more adequately provide further information on sulfur-mustard-induced alterations of the immune system.     

Club foot in the Maori: a genetic study of 50 kindreds.

A genetic study of 50 Maori kindreds suggests club foot to be inherited as a polygenic trait as in Caucasians. A higher incidence of right foot involvement was present in the Maori. Empiric risk data indicated that if the index patient was female, the chance of subsequent children being affected was four percent. If the index patient was male, the chance of subsequent children being affected was nine percent, and if parent and child were affected, the chance of subsequent children being affected was 30 percent. These risks are much higher than found in Caucasians.     

Blood beta-glucuronidase as a suitable biomarker at acute exposure of severe organophosphorus poisoning in human

Organophosphorus compounds are known to cause the selective release of liver microsomal beta-glucuronidase into plasma. Organophophoruses may induce nitrosative stress leading to the generation of nitrogen free radicals and alterations in scavengers of free radicals in many biological systems. In this study, we investigate how acute human organophosphorus intoxication is associated with changes of blood nitric oxide, total thiol molecules, and activities of the acetylcholinesterase and beta-glucuronidase. A total of 21 acute organophosphorus-poisoned patients were recruited into study and were divided into two groups of mildly (13) and severely affected (9); 26 age-matched healthy volunteers were recruited as control group. Results indicated that both mildly and severely affected patients had lower acetylcholinesterase activities as compared to controls. The extent of acetylcholinesterase reduction in the severely affected patients was higher than that of mildly affected patients. A significant increase in serum beta-glucuronidase was observed only in severely affected patients as compared to controls. Both mildly and severely affected patients had lower plasma total thiol molecules as compared to controls. The extent of reduction of total thiol molecules in the severely affected patients was higher than that of mildly affected patients. No significant difference was observed in plasma total nitric oxide of controls and patients. It is concluded that nitrosative stress has a minor role in toxicity of organophosphorus, whereas blood beta-glucuronidase is very sensitive biomarker at high exposure of severe organophosphorus poisoning.     

Validated HPLC method for determination of sennosides A and B in senna tablets

This study developed an efficient and reliable ion-pair liquid chromatographic method for quantitation of sennosides A and B in commercial senna tablets. Separation was conducted on a Hypersil C 18 column (250 x 4.6 mm, 5 microm) at a temperature of 40 degrees C, using a mixture of 0.1 M acetate buffer (pH 6.0) and acetonitrile (70:30, v/v) containing 5 mM tetrahexylammonium bromide as mobile phase. Sennosides A and B were completely separated from other constituents within 14 min. The developed method was validated. Both run-to-run repeatability (n=10) and day-to-day reproducibility (n=3) of peak area were below 0.4% RSD. Linearity of peak area was tested in the range 30-70 microg/ml (r>0.9997). Accuracy was assessed with recovery and the recoveries for sennosides A and B were 101.73+/-1.30% and 101.81+/-2.18% (n=3 x 6), respectively. Robustness of the analytical method was tested using a three-leveled Plackett-Burman design in which 11 factors were assessed with 23 experiments. Eight factors (column, concentration of ion pair reagent, % of organic modifier (acetonitrile), buffer pH, column temperature, flow rate, time constant and detection wavelength) were investigated in a specified range above and below the nominal method conditions. It was found that: (1) column and % acetonitrile affected significantly resolution and retention time, (2) column, % acetonitrile, column temperature, flow rate and time constant affected significantly the plate number of sennoside A, and (3) column and time constant affected significantly the tailing factor.     

Toxocariasis: a neglected entity

Toxocara canis infects many dogs yet has been seldom implicated as a cause of human disease in New Zealand. Nine patients with diagnostic titres for Toxocara canis who were seen in Christchurch Hospital over a five-year period are described. Ophthalmoscopic signs of toxocaral infection were visible at the optic disc or posterior pole of all ten affected eyes. A localised disciform detachment of the macula or a focal granuloma on the disc or retina were the commonest lesions. Vision was reduced to 6/60 or less in five affected eyes while the remaining five eyes lost 2-4 lines of vision on the test chart.     

Acarbose is an effective adjunct to dietary therapy in the treatment of hypertriglyceridaemias

AIMS: In diabetics, acarbose causes a reduction of blood glucose and triglyceride levels. The aim of this study was to assess the effect of this drug in non diabetic subjects with hypertriglyceridaemia. METHODS: Thirty non diabetic patients with hypertriglyceridaemia type IIb or IV (24 males, six females; mean age 51.1+/-10.2 years) were studied. They were stratified into two groups depending on their basal triglyceride concentration (group A: triglyceride values 4.5 mmol l-1 ). Treatment consisted of 4 week courses of diet plus acarbose (50 mg twice daily) alternating with 4 weeks of diet alone for a total period of 16 weeks. RESULTS: Mean triglyceride values decreased significantly during the first and third cycles of therapy, i.e. diet plus acarbose treatment cycles in both patient groups. Group A also had significant reductions in total cholesterol and HDL cholesterol concentrations after completion of the acarbose treatment. Reduction of triglyceride levels was observed after both acarbose courses in patients affected by hypertriglyceridaemia type IIb. A marked reduction of triglyceride concentrations was achieved by patients affected by hypertriglyceridaemia type IV after the second acarbose course only. CONCLUSIONS: Diet alone did not reduce triglyceride concentrations to normal values in our patients. The data suggest that acarbose is a useful adjunct to dietary control in non-diabetic patients affected by severe hypertriglyceridaemia.     

Interaction between structural,statistical, and covariate models in population pharmacokinetic analysis

The influence of the choice of pharmacokinetic model on subsequent determination of covariate relationships in population pharmacokinetic analysis was studied using both simulated and real data sets. Simulations and data analysis were both performed with the program NONMEM. Data were simulated using a two-compartment model, but at late sample times, so that preferential selection of the two-compartment model should have been impossible. A simple categorical covariate acting on clearance was included. Initially, on the basis of a difference in the objective function values, the two-compartment model was selected over the one-compartment model. Only when the complexity of the one-compartment model was increased in terms of the covariate and statistical models was the difference in objective function values of the two structural models negligible. For two real data sets, with which the two-compartment model was not selected preferentially, more complex covariate relationships were supported with the one-compartment model than with the two-compartment model. Thus, the choice of structural model can be affected as much by the covariate model as can the choice of covariate model be affected by the structural model; the two choices are interestingly intertwined. A suggestion on how to proceed when building population pharmacokinetic models is given. Supported by National Institutes of Health grants GM 26691 and GM 26676     

深静脉途径尿激酶溶栓治疗下肢深静脉血栓形成的疗效观察

目的观察不同给药途径治疗下肢深静脉血栓形成的效果。方法 40例下肢深静脉血栓形成患者分为两组,A组20例,给予尿激酶50万IU,通过患肢深静脉途径给药;B组20例,给予尿激酶50万IU,通过上肢静脉途径给药。结果 A组有效率为95%,B组有效率为55%,两组比较P<0.05,有统计学意义。结论经患肢深静脉途径给药治疗下肢深静脉血栓形成可取得良好疗效,方法简单、安全。     

Activity and tolerability of domifen bromide in patients affected by acute infectious dental diseases: a double-blind placebo-controlled trial

Thirty-one patients (21 M and 10 F), affected by acute infectious dental disease, were treated with domifen bromide (A) or placebo (Pl). It was found that A had a beneficial effect on the results of clinical controls and reduced the need for the concomitant use of an antibiotic (p = 0.001 and p = .008 respectively). Furthermore, after two days of treatment with A, there was a significant decrease in pain and inflammation (p less than 0.01). A alone or in combination with an antibiotic elicits a good response, improves the prognosis and reduces the number of days of illness.     

Effect of concanavalin A on 5'-nucleotidase activity of rabbit blood platelets

Ecto-5'-nucleotidase (ecto-5'-NU) of platelets was enhanced by concanavalin A (Con A). This effect of Con A was antagonized by alpha-methyl-D-mannose, a specific antagonist of Con A binding to glycoprotein. Coformycin, an adenosine deaminase inhibitor, did not change the effect of Con A on the ecto-5'-NU. Uptake of adenosine by platelets was not affected by Con A. It was suggested that the ecto-5'-NU of platelet might be a direct and primary site of action of Con A.     

Time course of ethylcholine aziridinium ion (AF64A)-induced cholinotoxicity in vivo

The time course of the cholinotoxicity of ethylcholine aziridinium ion (AF64A) has been investigated. Rats were injected with AF64A (3 nmols/3 microliters/side, bilateral, i.c.v.) or with vehicle. One day to one year after treatment, the hippocampus, cortex and striatum were analyzed for the activity of choline acetyltransferase (ChAT) and acetylcholinesterase (AchE) and high-affinity transport of choline (HAChT). In addition, the release of K+-stimulated acetylcholine (ACh) from superfused slices of hippocampus was determined. The first parameter affected was high affinity transport of choline. One day after treatment with AF64A, the high affinity transport of choline in the hippocampus was reduced by 23%. This reduction was maximal one week after treatment (-67%) and persisted for at least 6 months. The high affinity transport of choline in the striatum and cortex was not altered by treatment with AF64A. The activity of ChAT and AChE in the hippocampus was reduced by 2 days after treatment with AF64A. These deficits persisted for at least 6 months (AChE) to 1 year (ChAT). The activity of ChAT and AChE in the cortex and striatum was minimally affected up to 1 year after treatment with AF64A, at which time significant reductions were noted. The release of ACh was affected 3 days after treatment with AF64A, and remained attenuated 6 months later. These data indicate that the cholinergic deficit caused by in vivo treatment with AF64A was first apparent at the level of high affinity uptake of choline in the hippocampus HAChT. Subsequently, the activity of ChAT and AChE and release of ACh in the hippocampus were affected.(ABSTRACT TRUNCATED AT 250 WORDS)     

Determining the ecotoxicological mode of action of chemicals from measurements made on individuals: results from instar-based tests with Daphnia magna Straus

A short-term Daphnia toxicity test design was used to assess the ecotoxicological mode of action of pollutants. It was demonstrated that by exposing Daphnia females over a single instar to three toxic substances (3,4-dichloroaniline, cadmium and fluoranthene) it was possible to successfully measure both lethal effects on egg and adult stages and nonlethal effects on food acquisition and production rates. Dichloroaniline exposure reduced egg survival during development at concentrations below those which affected adult survival or production rates. For cadmium, however, concentration effects on production were almost an order of magnitude lower than those which affected adult survival, and no reductions in egg survival were observed. Responses to fluoranthene showed a different pattern again, with egg survival during development and production equally affected at concentrations which affected adult survival. Thus the three pollutants chosen showed contrasting dominant ecotoxicological modes of action, in terms of the relative importance of production and mortality effects, and this could be easily assessed using a novel toxicity test design. These results have important implications for risk assessment since with a relatively short, and thus cost-effective test, the functional relationship between effects on lethality and production rates and concentration can be determined.     

Inhalation toxicity studies on cigarette smoke III. Tobacco smoke inhalation dosimetry study on rats

Smoke inhalation dosimetry studies have been carried out on rats, using a new exposure system. A range of cigarettes, tobacco types and smoke concentrations was used.Penetration of smoke into the lungs was clearly demonstrated, and loads of total particulate matter (TPM) of up 1 mg were detected in the lower respiratory system of rats. The mass of TPM diposited was affected by the smoke concentration during exposure.Deposition of TPM in the head of the rat was low in relation to total respiratory system deposition. A pattern of predominantly lung deposition was achieved under the conditions used for this series of experiments. This pattern was not affected by changes in smoke dilution level, cigarette or tobacco type.     

母亲个性特征对婴儿气质和智能的影响

目的 了解母亲个性特征因素对婴儿气质和智能的影响。方法 2014年2月至2014年6月在合肥市妇幼保健所及新站区妇幼保健所健康体检门诊体检的4~12月龄正常汉族婴儿244例,采用卡特尔16项个性因素（16PF）问卷评估母亲的个性特点,采用标准化的CDCC智能测评量表,4~11月龄婴儿气质问卷修订版和12~36月龄气质问卷分别进行婴儿智能测评和气质问卷调查。结果 母亲个性因子与婴儿气质各维度均相关,母亲个性某些因子与婴儿智力发育指数、精神运动发育指数均相关。聪慧性与注意分散呈负相关;稳定性与活动水平、节律性、心境负相关;恃强性与活动水平、节律性、适应性、心境负相关;兴奋性与适应性、反应强度、注意分散负相关;敢为性与节律性、持久性负相关,与反应阈正相关;怀疑性与活动水平、持久性正相关;幻想性与适应性负相关;忧虑性与持久性正相关;自律性与活动水平、节律性、适应性、持久性负相关;紧张性与节律性、适应性、持久性、注意分散、趋避性正相关（P均<0.05）。稳定性与智力发育指数（MDI）、精神运动发育指数（PDI）正相关,敢为性与PDI正相关,忧虑性与MDI负相关,实验性与PDI正相关,紧张性与MDI、PDI负相关（P均<0.05）。结论 要重视母亲心理卫生保健工作,从而促进儿童智能发育,促进儿童早期发展。     

Effects of various tricyclic antidepressants on amine uptake

A comparative study of the ability to block the amine pump was carried out on tricyclic antidepressants including dothiepin and northiaden in vivo. Dothiepin was found to prevent the 6-OHDA-induced depletion of cardiac noradrenaline but not the PCA-induced depletion of intracerebral serotonin. Northiaden, an active metabolite of dothiepin, also possessed the same ability with a greater potency than the parent drug. Neither compound affected the biosynthesis of catecholamines and indoleamine. However, neither dothiepin nor northiaden affected 5-HT uptake, as was also observed with imipramine and amitriptyline. These results suggest that the clinical efficacy of dothiepin may be due to inhibition of the amine pump, especially of the catecholamine uptake mechanism, which is qualitatively the same as for imipramine and amitriptyline.     

Are the anti-inflammatory effects of dexamethasone responsible for inhibition of the induction of enzymes involved in prostanoid formation in rat carrageenin-induced pleurisy?

Since anti-inflammatory steroids modulate multiple gene expression, including the expression of prostaglandin H synthase-2 and phospholipase A(2), at the molecular level, we studied the effects of dexamethasone on rat carrageenin-induced pleurisy to elucidate whether regulation of phospholipase A(2) and prostaglandin H synthase-2 expression is the primary mechanism of its anti-inflammatory action. Suppression of plasma exudation by a lower dose of dexamethasone (0.3 mg/kg) was almost equal to that by aspirin (100 mg/kg), but that by higher dexamethasone doses (3 and 30 mg/kg) was considerably stronger, suggesting the involvement of effects other than that on prostanoid formation. The lower dose of dexamethasone also significantly reduced the pleural exudate neutrophil count and prostanoid levels. However, this dose affected neither the prostaglandin H synthase-2 level nor the phospholipase A(2) activity in the exudate cells. The prostaglandin H synthase-2 level was affected only at the higher doses, while phospholipase A(2) activity was not. These results suggest that the anti-inflammatory effects of dexamethasone in acute inflammation cannot be ascribed to direct interference with prostanoid formation via suppression of phospholipase A(2) and prostaglandin H synthase-2 expression.     

The effect of suboptimal concentrations of mitogens on the immunosuppressive action of azathioprine and prednisolone on human lymphocytes in vitro

The interaction of two commonly used immunosuppressive agents, azathioprine (AZA) and prednisolone sodium succinate (PSS), with three mitogens, Concanavalin A (Con A), phytohemagglutinin (PHA), and pokeweed mitogen (PWM) was studied. Using the endpoint of 50% inhibition of 3H-thymidine incorporation (ID50) as an indicator of cellular replication, the affect of suboptimal and optimal concentrations of mitogen on the immunosuppressive action of AZA or PSS on human lymphocyte replication in vitro was determined by isobolic analysis. The AZA ID50 for optimal concentrations of Con A (60 mcm/cc) was 242 +/- 21 ngm/cc (mean +/- SEM, n = 8), and at a suboptimal concentration of Con A (20 mcg/cc) it was 233 +/- 42, i.e., the AZA ID50 was independent of the concentration of Con A. This same independent interaction was found for PHA and PWM. However, at the optimal concentration of Con A (60 mcg/cc) the PSS ID50 of 523 +/- 55 ngm/cc was significantly higher (p less than 0.001) than the PSS ID at the suboptimal concentration of Con A (20 mcg/cc) which was 234 +/- 24 ngm/cc. A similar antagonistic interaction was found between PSS and either PHA or PWM. These findings emphasize the importance of accurately defining the testing parameters when assessing a drug's effect on lymphocyte proliferation. The data, along with other studies, support the hypothesis that drugs which directly interfere with DNA synthesis will not be affected by the strength of the signal for cellular replication, whereas those that modulate cellular replication are affected by the strength for lymphocyte replication.