Pharmacokinetics of a valpromide isomer,valnoctamide, in healthy subjects

Summary The pharmacokinetics of a single 400 mg oral dose of valnoctamide (VCD) has been investigated in seven healthy, adult, male volunteers. VCD was not biotransformed rapidly to its corresponding acid valnoctic acid (VCA), unlike its isomer valpromide (VPD). It had a mean residence time of 13.2 h and a terminal half-life of 9.3 h. Throughout the study, only low plasma levels of VCA could be detected. Thus, unlike VPD, which is a prodrug of the corresponding acid, (valproic acid, VPA). VCD appears to act as a drug in its own right, and it does not undergo similar hydrolysis. The pharmacokinetic difference may account for the different pharmacological activities of the two isomers.     

Combination of flavone acetic acid (FAA) with adriamycin,cis-platinum and difluoromethylornithine (DFMO) in vitro against human colon cancer cells

Summary Unresectable solid tumors in the metastatic stage are quite resistant to current chemotherapy and radiation therapy regimens. Flavone acetic acid (FAA) is a novel antitumor agent which appears to work through a different mechanism than the conventional chemotherapeutic agents. In preclinical studies it has shown effectiveness against a variety of transplantable murine and human tumors and appears to be solid tumor selective. It also has non-overlapping toxicities as compared to conventional agents. We therefore investigated FAA in vitro against human colon cancer cells and explored whether its effectiveness could be enhanced in combination with other agents such as adriamycin (ADR), cis-platinum (CP) and difluoromethyornithine (DFMO) — an inhibitor of polyamine biosynthesis. Addition of FAA for 24 hours in liquid media produced dose dependent growth inhibition. Using soft agar colony assay, growth was inhibited by 58% by 3mM FAA and only 1.4% by 0.375mM FAA. The combination of FAA and cis-platinum produced synergism at the lower doses tested. The combination of FAA and adriamycin produced antagonism at all doses tested and the combination of FAA with DFMO did not produce results significantly different from DFMO alone. We conclude that enhancement of FAA activity can be achieved in combination with conventional antitumor agents, but may be drug and dose specific.     

Effects of smoking and drinking on excretion of hippuric acid among toluene-exposed workers

Summary In order to investigate possible effects of smoking and drinking on the metabolism of toluence in occupational settings, 206 toluene-exposed men (mean age: 31.4 years) in shoemaking, painting, or surface-coating workshops together with 246 nonexposed control men (36.8 years) were studied for the time-weighted average intensities of exposure to toluene, hippuric acid concentration in shift-end urine samples, and the two social habits of smoking and drinking. The mean daily consumptions of cigarettes and ethanol were about 20 pieces and 10 g among smokers and drinkers, respectively. The geometric mean toluene concentration among the exposed subjects was about 20 ppm, with a maximum of 521 ppm. Regression analysis after classification of the subjects by smoking and drinking clearly demonstrated that the two social habits, when combined, markedly reduce the hippuric acid level in the urine of workers exposed to was a significant association between smoking and drinking habits, which hindered separate evaluation of the effects of the two habits on toluene metabolism. Comparison of the present results with the findings reported in the literature, however, suggested that the observed effects may be attributable to smoking rather than to drinking habits.     

Interaction between bovine collagen and glycolic acid peeling: A proposal of a new protocol

For the past 10 years the alfa-hydroxyacids and the bovine collagen injection have been used for peeling and the correction of multiple skin diseases. Until now, such progressive achievement has occurred in separate parallels just like the indications that have been held distinct. However, the studies carried out in order to clarify the mechanical action of the two substances have shown a common and fundamental denominator: the stimulation of synthesis of the new collagen in the patient's skin. On the basis of these results and the existence of common clinical indications of the use of glycolic acid and collagen, the authors have worked out a protocol involving a combined and contemporary application in progressive steps. They developed the rationales of such protocol and analyzed the results of its application on a number of carefully selected patients for a clinical comparison and on a sample of rats for a histological comparison. They have concluded that the contemporary use of glycolic acid and bovine collagen is a simple and safe method whose synergy action leads to more intense and long-lasting effects than the ones observed in the isolated application of the two substances. The authors have also obtained interesting and significant histological results.     

Evaluation of the safety of a non-animal stabilized hyaluronic acid (NASHA – Q-Medical, Sweden) in European countries: a retrospective study from 1997 to 2001

BACKGROUND: In Europe, several filler devices are currently on the market for use in aesthetic dermatology and some of them cause severe, permanent, adverse reactions. Since 1996 a non-animal stabilized hyaluronic acid (NASHA) from Q-Medical, Sweden, has been introduced and is becoming a leading product in aesthetic dermatology. Hyaluronic acid has no species specificity and skin testing is not recommended before treatment. OBJECTIVE: Our purpose was to evaluate the incidence of adverse reactions from 1997 to 2001 and the safety of NASHA after injections into the skin for aesthetic reasons. METHOD: Surveys were sent to physicians in European countries that agreed to participate. This is a retrospective study. A total of 12 344 syringes were sold by the Q-Medical to these physicians and we evaluated the total number of patients treated to 35% of this number (4320). We separated immediate hypersensitivity reactions from delayed reactions and analysed infectious and other types of reactions. RESULTS: From 1997 until 2001, 34 cases of hypersensitivity were reported: 16 cases of immediate hypersensitivity and 18 cases of delayed. The global risk of sensitivity is 0.8%. Since 2000, the amount of protein in the raw product has decreased and the incidence of hypersensitivity reactions is around 0.6%. As 50% of these reactions are immediate and resolved within less than 3 weeks, the risk of strong but transient, delayed reaction is around 0.3%. Four cases of abscess were reported. They were all sterile. No bacterial infection was found. Herpetic recurrence is possible after lip augmentation according to the technique of injection. No systemic reactions were reported. CONCLUSION: NASHA is a very useful and safe filler product. Skin testing does not seem to be necessary.     

Effects of mycophenolic acid on IL-6 expression of human renal proximal and distal tubular cells in vitro.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine which regulates immune responses and host defence mechanisms. IL-6 has been found to be increased in certain inflammatory conditions of the kidney, in which tubular epithelial cells play a pivotal role. Human renal tubular cells express IL-6. Until now no data about the effect of the immunosuppressant drug mycophenolic acid (MPA) on IL-6 expression were available. METHODS: Proximal and distal tubular epithelial cells (PTC/DTC) have been isolated immunomagnetically. Confluent monolayers were stimulated with interleukin-1beta (IL-1beta; 25 U/ml), IL-1beta+ MPA (0.25-50 micro M) or MPA alone for 48 h. Release of IL-6 protein into the supernatant was evaluated with an enzyme immunoassay, IL-6 mRNA expression was evaluated using the Quantikine mRNA kit. RESULTS: After IL-1beta stimulation, a highly significant 2.6- (PTC) and 3.8-fold (DTC) upregulation of IL-6 expression was detectable. IL-6 mRNA was upregulated by IL-1beta [1.57- (PTC) and 2.03-fold (DTC)]. MPA inhibited this cytokine-induced IL-6 expression in a dose-dependent manner. Incubation with the lowest MPA concentration had no effect on the stimulated upregulation, whereas all higher doses significantly decreased IL-6 expression. Dexamethasone significantly inhibited the cytokine-induced IL-6 protein release in PTC, but not in DTC. CONCLUSIONS: In this study we demonstrated for the first time an inhibitory effect of MPA on the stimulated IL-6 expression of renal tubular epithelial cells. In contrast to older data, which showed a synergistic upregulation of the expression of a CC-chemokine by a combination of cytokines and MPA, in the present study we could demonstrate an immunosuppressive effect of MPA on the expression of an important cytokine.     

Treatment of essential tremor with the barbiturate T2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid).

The effect of the barbiturate T2000 (1,3-dimethoxymethyl-5,5-diphenyl-barbituric acid; DMMDPB) on essential tremor, given in twice daily doses of 400 and 300 mg, was assessed in two brief, randomized, placebo-controlled, parallel-group, double-blinded, single-center trials in 12 and 22 patients, respectively. These trials represent the first clinical use of T2000 for a specific indication. The primary endpoint was the change in the mean scores of the treated and control groups based on the Fahn-Tolosa-Marin tremor scale. In the first study of 12 patients treated with 400 mg or placebo twice daily for 14 days, the mean change from baseline at day 14 was 19.3 (P < 0.0001) in the treated group and 9.0 (P = 0.0121) in the control group. Using a two-factor mixed ANOVA model to evaluate within group and between group changes, the effect of T2000 was significantly different from that of the placebo group (P = 0.03). In the second study of 22 patients treated with 300 mg of T2000 or placebo twice daily for 20 days, statistically significant changes were seen in treated patients compared to baseline, but the ANOVA model did not demonstrate a significant treatment effect of T2000 compared to placebo. When the treated groups from each study are compared, the 800-mg daily group is significantly different from the 600-mg daily group (P = 0.02). Some treated patients in each study, but no placebo patients, experienced marked improvement. These results support further evaluation of T2000 in the treatment of essential tremor.     

大鼠脑内儿茶酚胺类递质及其代谢物的同时提取及反向高效液相测定法

目的建立一种操作简便、高效的测定脑组织中去甲肾上腺素(NA)、肾上腺素(AD)、多巴胺(DA)、3,4二羟基苯乙酸(DOPAC)及高香草酸(HVA)的方法,为有关药物作用机理的研究提供实验手段.方法以有机溶剂提取,高效液相色谱--电化学检测器(HPLC-EC)测定大鼠纹状体、皮质、下丘脑NA、AD、DA、DOPAC及HVA的含量.结果测得NA、AD、DA、DOPAC及HVA的绝对回收率依次分别为:80.3%±12.4%,86.5%±14.3%,90.3%±12.1%,89.5%±17.2%、87.6%±[13].2%.线性范围0.2～20ng,批内与批间变异系数分别小于8%及10%.结论该方法具有简便、迅速、回收率较高的特点,便于实验室应用.     

Involvement of Apoptosis in 3-nitropropionic Acid-induced Ischemicl Tolerance to Transient Focal Cerebral Ischemia in Rats

Preconditioningofbraintissueswithsub lethalstressesorstimulicanresultinresistancetosubse quentlethalischemiceventsinaresponsecalledis chemictolerance .Recently ,severalstudieshaveshownthatasinglesystemicdoseof 2 0mg/kg 3 NPAcausednohistopathologicalabnorm…     

福建产舟山眼镜蛇毒细胞毒素的快速分离纯化及鉴定

目的 从舟山眼镜蛇毒中分离纯化细胞毒素(CTX)，并鉴定其理化性质。方法 采用SP—Sephadex C-25阳离子交换色谱及Sephasil Peptide C18反相高效液相色谱法从舟山眼镜蛇毒中分离纯化CTX，SDS—PAGE(Tris—Tricine系统)鉴定纯度，Edman降解法测定N端氨基酸序列。结果 粗毒经阳离子交换色谱，得到14个蛋白峰，其中第X～XⅢ峰具CTX活性；再分别经反相色谱纯化，得到4个CTX．总得率为32.48％；SDS—PAGE显示为均一蛋白，分子量依次为：7．28，7．33，7．24和7．38kD；测定它们N端20个氨基酸序列。结论 采用阳离子交换和反相高效液相色谱可快速、高效地从眼镜蛇毒中获得4个CTX纯品。