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971.
Veselinović T Schorn H Vernaleken IB Schiffl K Klomp M Gründer G 《Journal of clinical psychopharmacology》2011,31(2):214-220
Antipsychotics are the most common cause of pharmacologically induced hyperprolactinemia. Although this adverse effect was the subject of numerous observations, the mechanisms and promotive factors were not completely investigated yet. Increased awareness of clinical consequences of hyperprolactinemia implicates the necessity for further examinations. The aim of this randomized, single-blinded, placebo-controlled study was to do a systematic examination of the effects of different antidopaminergic mechanisms on prolactin secretion in healthy volunteers. A 7-day intervention was performed with aripiprazole, haloperidol, or reserpine. Prolactin levels changed significantly in the haloperidol (from 177.2 ± 74.6 to 350.7 ± 202.6 mU/L; P < 0.0001) and in the reserpine groups (from 149.6 ± 80.2 to 540.3 ± 280.8 mU/L; P < 0.0001) but not after aripiprazole (from 160.9 ± 65.0 to 189.6 ± 209.6 mU/L; P = 0.69) or placebo (from 211.6 ± 113.4 mU/L to 196.1 ± 85.6 mU/L; P = 0.8). After haloperidol and reserpine, increases in prolactin were significantly more pronounced in women than in men. Furthermore, in women using hormonal contraception, the increase in prolactin was significantly greater than in those without additional estrogen supply. These results demonstrate that the effect of antipsychotic drugs on prolactin levels strongly depends on their mechanism of action. Reserpine, a vesicular monoamine transporter type 2 blocker, causes the most distinct increase. This implies that D? receptor blockade on the lactotrophs is not the sole major cause leading to hyperprolactinemia. The partial agonistic effect of aripiprazole was sufficient to maintain prolactin on physiologic levels. The strong influences of sex and hormonal contraception underline the sensitizing effect of estrogens to the antipsychotic-induced prolactin increase. 相似文献
972.
AIMS
This study aimed to test whether a pharmacokinetic simulation model could extrapolate nonclinical drug data to predict human efavirenz exposure after single and continuous dosing as well as the effects of concomitant rifampicin and further to evaluate the weight-based dosage recommendations used to counteract the rifampicin–efavirenz interaction.METHODS
Efavirenz pharmacokinetics were simulated using a physiologically based pharmacokinetic model implemented in the Simcyp™ population-based simulator. Physicochemical and metabolism data obtained from the literature were used as input for prediction of pharmacokinetic parameters. The model was used to simulate the effects of rifampicin on efavirenz pharmacokinetics in 400 virtual patients, taking into account bodyweight and CYP2B6 phenotype.RESULTS
Apart from the absorption phase, the simulation model predicted efavirenz concentration–time profiles reasonably well, with close agreement with clinical data. The simulated effects of rifampicin co-administration on efavirenz treatment showed only a minor decrease of 16% (95% confidence interval 13–19) in efavirenz area under the concentration–time curve, of the same magnitude as what has been clinically observed (22%). Efavirenz exposure depended on CYP2B6 phenotype and bodyweight. Increasing the efavirenz dose during concomitant rifampicin was predicted to be most successful in patients over 50 kg regardless of CYP2B6 status.CONCLUSIONS
Our findings, although based on a simulation approach using limited in vitro data, support the current recommendations for using a 50 kg bodyweight cut-off for efavirenz dose increment when co-treating with rifampicin. 相似文献973.
Tomić M Vasković D Tovilović G Andrić D Penjišević J Kostić-Rajačić S 《Archiv der Pharmazie》2011,344(5):287-291
Five groups of previously synthesized and initially screened non-substituted and 4-halogenated arylpiperazin-1-yl-ethyl-benzimidazoles were estimated for their in-vitro binding affinities at the rat D(2) , 5-HT(2A) , and α(1) -adrenergic receptors. Among all these compounds, 2-methoxyphenyl and 2-chlorophenyl piperazines demonstrate the highest affinities for the tested receptors. The effects of 4-halogenation of benzimidazoles reveal that substitution with bromine may greatly increase the affinity of the compounds for the studied receptors, while the effect of substitution with chlorine is less remarkable. Most of the tested components show 5-HT(2A)/D(2) pK(i) binding ratios slightly above or less than 1, while only 4-chloro-6-(2-{4-[3-(trifluoromethyl)phenyl]piperazin-1-yl}ethyl)-1H-benzimidazole expresses an appropriate higher binding ratio (1.14), which was indicated for atypical neuroleptics. This compound exhibits a non-cataleptic action in rats and prevents d-amphetamine-induced hyperlocomotion in mice, which suggest its atypical antipsychotic potency. 相似文献
974.
975.
976.
Durzyńska J Pacholska-Bogalska J Kaczmarek M Hanć T Durda M Skrzypczak M Goździcka-Józefiak A 《Journal of medical virology》2011,83(2):267-271
The aim of the study was to develop a multiplex PCR (mPCR) for a rapid and simultaneous detection of herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), and human cytomegalovirus (HCMV) DNA in squamous oral cells obtained from adolescents. Accuracy of the method was tested in a group of 513 adolescents, almost 11% of subjects were positive for infection with herpes viruses. Correlations with gender, age, and place of residence were sought. A similar incidence of HSV-2 and HCMV was found (4.3% and 5.4%, respectively) and the incidence of HSV-1 was the lowest (1%) in the study group. Conversely to HSV-2, HCMV was detected mostly in the youngest individuals. The same occurrence of all viruses was observed in boys and girls. The mPCR method described is suggested as a useful tool for epidemiologic studies of active herpes infections. 相似文献
977.
Plyusnina A Krajinović LC Margaletić J Niemimaa J Nemirov K Lundkvist Å Markotić A Miletić-Medved M Avšič-Županc T Henttonen H Plyusnin A 《Journal of medical virology》2011,83(1):108-114
In Europe, Dobrava-Belgrade (DOBV), Saaremaa (SAAV), and Puumala (PUUV) viruses are known to cause hemorrhagic fever with renal syndrome (HFRS). All three hantaviruses are now found in Croatia. Lung tissue samples of 315 Apodemus mice trapped in 2003-2004 were screened for the presence of hantaviral N-Ag and 20 mice (6.3%) were found either strongly positive or weak/suspected-positive. Partial sequences of hantavirus M and S segments were recovered by RT-PCR from six mice and subjected to (phylo)genetic analysis that revealed the presence of four novel strains of DOBV and one of SAAV. Curiously, one of the newly described DOBV strains was found in Apodemus agrarius mouse, that is, not in the traditional host, A. flavicollis mice, suggesting a spillover event. S segment sequences recovered previously from HFRS cases [Markoti? et al., 2002] were confirmed as DOBV sequences; one of which appeared particularly close to the prototype Slovenian DOBV isolate. Taken together with earlier data on PUUV in Croatia, these results show a co-circulation of three European hantavirus pathogens in this country. So far, not a single SAAV sequence has been recovered from HFRS patients either in Croatia or neighboring Slovenia and Hungary nor in Slovakia suggesting a somewhat lower fequency of acute SAAV infection in humans in this part of Europe than for example in the Baltics. 相似文献
978.
Matovi? V Buha A Bulat Z Duki?-?osi? D Miljkovi? M Ivani?evi? J Kotur-Stevuljevi? J 《Food and chemical toxicology》2012,50(3-4):552-557
The study was designed to evaluate and compare the effects of single oral (or) and intraperitoneal (i.p.) cadmium (Cd) administration on parameters of oxidative stress in liver of rats. Furthermore, investigation on protective effects of magnesium (Mg) or and i.p. pretreatment on the same parameters was performed. Wistar rats were administrated oral dose of Cd (30 mg Cd/kg b.w.)/Cd+Mg (30 mg Cd/kg b.w., 50 mg Mg/kg b.w.) or i.p. dose of Cd (1.5 mg Cd/kg b.w.)/Cd+Mg (1.5 mg Cd/kg b.w., 3 mg Mg/kg b.w.) and sacrificed after 24 h. In liver homogenates superoxide anion, malondialdehyde, non-protein sulfhydryl groups, total sulfhydryl groups content, and superoxide dismutase activity were determined. Cadmium intoxication caused the increase of superoxide anion and malondialdehyde levels and had negative effect on investigated parameters of antioxidant defense system, except on total sulfhydryl groups. The negative effect was more emphasized after i.p. Cd administration. Oral Mg pretreatment induced more pronounced positive effect than Mg given intraperitoneally that can be attributed, at least partly, to Cd and Mg interactions on the level of GIT. On the basis of the obtained results it can be concluded that both Cd and Cd+Mg effects on parameters of oxidative stress in rats liver are route-dependent. 相似文献
979.
Jasminka Mrđanović Saša Jungić Slavica Šolajić Višnja Bogdanović Vladimir Jurišić 《Food and chemical toxicology》2012
The widespread use of antineoplastic drugs in cancer treatment increased concern about possible hazard to workers involved in the preparation and administration of these drugs. In the present study, the effects of commercial antioxidative drug Oligogal Se® on genome protection were analyzed in 15 nurses handling the antineoplastic drugs at the Oncology Department in comparison to twenty healthy volunteers. The nurses took antioxidant mixture Oligogal Se®, consisting of vitamins C, E, A and selenium, one capsule per day, over a period of 6 months. Genome damage was measured in peripheral blood lymphocytes by usage of sister chromatid exchange test and the cytokinesis-block micronuclei test. The frequency of sister chromatid exchange (SCE) and micronuclei (MN) in the exposed group was significantly higher when compared to the control group (SCE, p < 0.05; MN, p < 0.01 respectively). After antioxidant supplementation, the frequency of sister chromatid exchange and micronuclei decreased (p < 0.05) when compared with the values from the beginning of the study, but were still above the values of the control group. The effects of confounding factors such as cigarette smoking and cytostatics exposure time were also evaluated. The data indicated that Oligogal Se® contributed to the decreasing of genome damages in workers handling the cytostatics. 相似文献
980.
Milašinović N Knežević-Jugović Z Milosavljević N Filipović J Kalagasidis Krušić M 《International journal of pharmaceutics》2012,436(1-2):332-340
The series of poly(N-isopropylacrylamide-co-itaconic acid) hydrogels, with lipase from Candida rugosa as a model protein, were synthesized by free radical copolymerization. The composition of hydrogels was varied by monomers ratio, crosslinking agent concentration and amounts of lipase, which was loaded by in situ polymerization. All samples were characterized regarding morphology. The investigation of hydrogel swelling properties revealed their pH and temperature sensitive character. Protein loading efficiency, release profiles and the specific activity yield of the released lipase were also investigated as a function of hydrogel composition, protein content and pH, at the physiological temperature of 37°C. Copolymers of N-isopropylacrylamide and itaconic acid presented high lipase loading efficiency. Another very important feature of these copolymers was that the protein release kinetic strongly depended on the pH value of the medium. The diffusion exponents values around 1 denoted that these hydrogel compositions could be adjusted to follow near zero-order kinetics. Namely, hydrogel formulations released low amounts of lipase at pH 2.20, but much higher released protein quantities were observed at pH 6.80 enabling these copolymers to be attractive candidates as site specific protein oral drug delivery systems. 相似文献