Biochemical evidence for the involvement of central serotonergic neurotransmission in the action of the antidepressant drug Medifoxamine

Medifoxamine, an antidepressant agent which has an original chemical structure, has been shown through in vitro studies, utilising radioligand binding in tissue homogenates, to bind with moderately high affinity to 5-HT_1c and 5-HT₂ receptor subtypes and to 5-HT uptake sites (IC₅₀ 950, 980, and 1,500 nM, respectively). It has been shown to bind in vivo to rat brain 5-HT₂ receptors after acute treatment with high dose (50 mg/kg, i.e., 133.9 μmol/kg). After 14 days continuous treatment with low dose (20 mg/kg, 53.6 μmol/kg), a decrease in the capacity of [³H]-5-HT uptake and a dose-dependent down-regulation of 5-HT₂ receptors in rat cerebral cortex were observed. These results indicate that medifoxamine, which has been shown previously to act through dopaminergic systems, interacts also with central serotonergic neurotransmission and particularly with the 5-HT₂ receptors, which could contribute to its antidepressant effect.     

THE INTERACTION BETWEEN ENALAPRILAT AND SELECTED α-ADRENOCEPTOR ANTAGONISTS IN ISOLATED RAT TAIL ARTERIES

1. Isolated perfused rat tail artery preparations were used to investigate the effects of the angiotensin converting enzyme inhibitor enalaprilat on the actions of a series of α-adrenoceptor antagonists. The agonist used was phenylephrine. 2. Enalaprilat (1 μmol/L) potentiated the competitive α₁-adrenoceptor antagonist actions of phentolamine (10–100 nmol/L) and yohimbine (0.3–3.0 μmol/L) as well as the non-competitive antagonist action of phenoxybenzamine (50–100 pmol/L). 3. The competitive α₁-adrenoceptor antagonist action of prazosin (1–10 nmol/L) was not affected by enalaprilat. 4. For the competitive α₁-adrenoceptor antagonists, including prazosin, there appeared to be an inverse relationship between antagonist potency and the extent of potentiation by enalaprilat. 5. The results support the hypothesis and angiotensin II modulates vascular smooth muscle α₁-adrenoceptor function.     

高频电磁场对工人行为功能的影响

采用世界卫生组织推荐的神经行为核心测试组合（ＷＨＯ－ＮＣＴＢ），对高频作业工人４１名（平均工龄１３．９ａ（年）及年龄、性别、文化程度与接触组相匹配的对照组工人３９名（平均工龄１３．３ａ）分别进行了行为功能测试。结果表明高频作业工人部分情感状态得分和某些行为功能得分与对照组相比差异有显著性。长期接触高频电磁场可能引起工人情感状态改变，记忆力减退、注意力分散及心理运动稳定度下降。     

Ontogeny of behavioral sensitization to cocaine

The ontogeny of the behavioral effects of acute cocaine administration and behavioral sensitization to cocaine in rat pups was investigated. Acute behavior stimulating effects of cocaine were observed in pups as young as 7 postnatal days (PND) old, although they needed a higher dose of cocaine than adult rats to evoke the same motor effects. An adult dose-response curve pattern of stereotypy and locomotion to acute cocaine treatment was observed at PND 21, and of rearing at PND 28. Rats aged PND 7, 14, 21, 28, and 56 received repeated injections of saline or cocaine (15 mg/kg) twice a day for 5 consecutive days. After a 3-week period of abstinence, sensitization to a challenge dose of cocaine was assessed. Cocaine-induced stereotyped behavior was enhanced significantly only in rats in which cocaine pretreatment was initiated on PND 21, 28, and 56, but not earlier on PND 7 and 14. Adult female rats given repeated cocaine injections on PND 56–60 showed significantly greater sensitization than males, but no such sex difference was observed in pups given cocaine repeatedly on PND 21–25 or 28–32. These results show clearly that cocaine-induced behavioral sensitization in rats occurred only when subchronic cocaine administration was commenced on PND 21 or later.     

A rapid and sensitive method for measuring monooxygenase activities in hepatocytes cultured in 96-well plates

Summary Measurement of biotransformation activities in cells is of great importance for drug metabolism and toxicologic studies. It is currently done by measuring the enzymatic activities in partially purified microsomes. In the present work we report on a rapid, easy, sensitive, and reproducible fluorimetric assay for quantifying cytochrome P450-dependent monooxygenase activities (P450IA1, P450IIB1) in hepatocytes cultured in 96-well plates. The procedure involves the direct determination of enzymatic activities in intact hepatocytes while avoiding cell homogenization, thereby permitting use of a the reduced number of cells and allowing cultured cells to be used in later experiments. Substrates (7-ethoxyresorufin, 7-pentoxyresorufin) are added to culture medium and metabolized by hepatocytes. After enzymatic deconjugation, the fluorescent resorufin present in culture medium is quantified by means of a microplate fluorimetric reader. Major advantages of this technique, as compared to other available methods, are: a) no cell disruption is required; b) activity can be measured with a very small number of cells; c) rapid processing time; and d) possibility of performing repeated assays with the same cell monolayer.     

Effect of pindolol on endocrine and temperature responses to buspirone in healthy volunteers

Ten healthy subjects received buspirone (30 mg orally) with and without pre-treatment with the 5-HT1A receptor antagonist, pindolol (80 mg over 3 days). Following pindolol treatment the growth hormone and hypothermic responses to buspirone were significantly decreased. There was also a delay in the onset of the prolactin response to buspirone but the total amount of prolactin secretion, calculated as area under the curve, was not significantly reduced. The data suggest that the growth hormone and hypothermic responses to buspirone in humans are mediated by 5-HT1A receptors, but an explanation founded on pharmacokinetic factors cannot presently be excluded. Both this latter possibility and the lack of selectivity of pindolol for 5-HT receptors indicate the need for the further neuroendocrine studies of the mode of action of buspirone, preferably with more selective 5-HT1A receptor antagonists.     

Adverse reactions to non-ionic contrast media with special regard to high-risk patients

Non-ionic contrast media (CM) are proven to be significantly safer than the high osmolar ionic contrast media (HOCM). Nevertheless deaths are reported after administration of non-ionic agents. The aim of the study was to investigate the rate of adverse reactions to non-ionic CM with special regard to high-risk patients and the effects of premedication with H1-and H2-receptor antagonists.In a prospective study conducted over about 2 years 12 995 examinations with intravenous or intra-arterial non-ionic CM were evaluated. Premedication with H1-and H2-antagonists was used in 1276 high-risk patients with known adverse reaction to CM, history of allergy or severe cardiac or pulmonary disease. 229 patients received no premedication inspite of known risk factors. In total, there were 143 (1.10%) adverse reactions (mild in 0.58%, moderate in 0.41% and severe in 0.05%). In high-risk patients there were adverse reactions in 4.37% without and in 1.57% with premedication. There were no severe adverse reactions in the high-risk patients after premedication. The age of the patient, CM dosage and CM concentration were not shown to be risk factors in the present study. In conclusion, the additional premedication with H1- and H2-antagonists could be an effective agent to reduce the risk of mild and moderate adverse reactions and to avoid severe adverse reactions in high-risk patients. Correspondence to: U. Fink     

Anabolic and catabolic hormonal response of elite runners to training at high altitude

A 2-week training period 2000 meters above sea level performed by 6 male elite Swedish runners influenced neither basal anabolic (total and non-sex hormone-binding globulin (SHBG)-bound testosterone (NST) and insulin-like growth factor-1 (IGF-1) nor catabolic (cortisol) hormones when comparing serum levels prior to and after the training camp. The anabolic vs catabolic hormone balance, expressed as the NST: cortisol ratio, also remained unchanged as well as SHBG and body mass. Thus, training at 2000 meters above sea level, often practised by elite runners to improve performance in competition at sea level, does not result in a catabolic situation after return to sea level, as measured by peripheral hormones. However, the adaptation to high altitude was associated with a slight (NS) decrease in testosterone as well as in anabolic vs catabolic balance as measured the third day at high altitude. Simultaneously, a decrease in subjective performance was claimed by the runners, but could not be shown by objective measurements. From day 3 to day 9 at high altitude, all runners claimed a subjective recuperation of performance. Total and non-SHBG-bound testosterone increased significantly from day 3 at high altitude to the first post-camp sea-level test. The results reflect the necessity of adaptation when travelling to races at different altitudes. The Swedish runners had significantly higher cortisol, total testosterone and NST levels compared with basal values of a group of 17 elite Kenyan runners living and training at high altitude. Since the NST cortisol and IGF-1 values were not lower, a catabolic state or malnutrition was not likely to be present. The results might reflect an adaptation to altitude or ethnic variations.     

女孩雌激素受体基因6号内含子区域两个新SNPs位点报道

目的：在女性性早熟患儿中检测雌激素受体基因6号外显子及内含子基因序列可能存在的突变。方法：PCR扩增雌激素受体基因6号外显子及内含子，对扩增产物进行DNA序列分析。结果：在6号内含子一侧，发现两个100％连锁的单核苷酸多态性(SNPs)，分别为．53G—67A和53T—67G。结论：这一对单核苷酸多态性并不引起氨基酸的替代，与女孩性早熟的发生也无关，但是否和其他疾病有连锁关系尚待进一步探讨。     

Susceptibility to ketoconazole of Candida albicans strains from sequentially followed HIV-1 patients with recurrent oral candidosis

The MIC values of the antifungal drug ketoconazole were evaluated on 66 Candida albicans strains. These strains were isolated from 26 HIV-1 infected patients with oral recurrent candidosis. Each episode of oral candidosis observed in these patients was orally treated with ketoconazole (200 mg/day) until the clinical disappearance of the lesions. The most frequent MIC values were 20 micrograms/ml and 10 micrograms/ml, observed in 37 and 19 isolates respectively. Only strains from five patients showed changes in their susceptibility to ketoconazole. This fact could indicate that a different strain causes the subsequent reappearance of the oral lesions, rather than the drug selecting resistant fungal strains. Our results stress the role of host characteristics in the occurrence of candidal infections, pointing to the progressing failure of the immunological response as the most important factor responsible for the recurrence of oral candidosis during HIV-1 infection.