Evaluation of the central anticholinergic activity of antidepressants. Comparison of two experimental methods

The anticholinergic effect of atropine, imipramine, clomipramine and metapramine was evaluated on oxotremorine induced trembling in the mouse as well as on contractions of the isolated guinea pig ileum induced by electrical stimulation of the mesenteric plexus. The ED 50 and IC 50 which expressed the anticholinergic activity of these substances, were found to be identifically distributed for both methods. Activity, in decreasing order was found to be: atropine much greater than imipramine greater than clomipramine greater than metapramine. There was a good correlation between results from the two methods (r = 0.97). The method using the stimulated guinea pig ileum would therefore seem suitable for characterisation of potential anticholinergic activity of a molecule.     

Surgical approach for pericardiectomy: a comparative study between median sternotomy and left anterolateral thoracotomy

Pericardiectomy is the definitive treatment for constrictive pericarditis but the best surgical approach remains controversial. In this study we compared the results of pericardiectomy performed on 36 patients with constrictive pericarditis between 1995 and 2001. Pericardiectomy was performed by median sternotomy in 15 patients and by left anterolateral thoracotomy in 21 patients. All patients were reviewed at 6 weeks post operatively. Both groups of patients were similar in age, sex distribution, NYHA shortness of breath status, aetiology, presenting symptoms and duration of symptoms. Mortality was similar in the two groups with three deaths (14.2%) in the thoracotomy group and two deaths (13.3%) in the median sternotomy group. NYHA status improved in both thoracotomy (3.0+/-0.8 to 1.6+/-0.7; P=3.3x10(-6)) and median sternotomy (2.9+/-0.7 to 1.5+/-0.6; P=2.8x10(-5)) groups. The degree of improvement was not significant between the two groups (P=0.63). In addition ionotropic support and postoperative hospital stay were similar between the two groups. There was a higher incidence of wound infections (23.8 versus 6.6%; P=0.13) and pulmonary complications (23.8 versus 13.3%; P=0.33) associated with thoracotomy. In conclusion pericardiectomy improves NYHA status in all patients and mortality rates are similar in both the approaches.     

Comparative bioavailability study of two ketoconazole tablet preparations

The bioavailability of a generic preparation of ketoconazole (Zorinax from Xepa-Soul Pattinson, Malaysia) was evaluated in comparison with the innovator product (Nizoral from Janssen Pharmaceutica, Switzerland). Eighteen healthy male volunteers participated in the study conducted according to a two-way crossover design. The bioavailability was compared using the parameters, total area under the plasma concentration-time curve (AUC0-infinity), peak plasma concentration (Cmax) and time to reach peak plasma concentration (Tmax). No statistically significant difference was observed between the values of the two products in all the three parameters. Moreover, the 90% confidence interval for the ratio of the logarithmic transformed AUC0-infinity and Cmax values of Zorinax over Nizoral was found to lie between 0.82-1.04 and 0.83-1.02, respectively, being within the acceptable equivalence limit of 0.80-1.25. These findings indicate that the two preparations are comparable in the extent and rate of absorption. In addition, the elimination rate constant (ke) and apparent volume of distribution (Vd) were calculated. For both parameters, there was no statistically significant difference between the values obtained from the data of the two preparations. Moreover, the values are comparable to those reported in the literature.     

Disruption of morphine‐conditioned place preference by a δ2‐opioid receptor antagonist: study of μ‐opioid and δ‐opioid receptor expression at the synapse

The addictive properties of morphine limit its clinical use. Learned associations that develop between the abused opiate and the environment in which it is consumed are engendered through Pavlovian conditioning processes. Disruption of the learned associations between the opiate and environmental cues may be a therapeutic approach to prevent morphine dependence. Although a role for the δ‐opioid receptor in the regulation of the rewarding properties of morphine has already been shown, in this study we further characterized the role of the δ‐opioid receptor in morphine‐induced conditioned responses by examining the effect of a selective δ2‐opioid receptor antagonist (naltriben), using a conditioned place preference paradigm in rats. Additionally, we used a subcellular fractionation technique to analyze the synaptic localization of μ‐opioid and δ‐opioid receptors in the hippocampus, in order to examine the molecular mechanisms that may underlie this morphine‐induced conditioned behavior. Our data show that the administration of 1 mg/kg naltriben (but not 0.1 mg/kg) prior to morphine was able to block morphine‐induced conditioned place preference. Interestingly, this naltriben‐induced disruption of morphine conditioned place preference was associated with a significant increase in the expression of the δ‐opioid receptor dimer at the postsynaptic density. In addition, we also observed that morphine conditioned place preference was associated with an increase in the expression of the μ‐opoid receptor in the total homogenate. Overall, these results suggest that modulation of the δ‐opioid receptor expression and its synaptic localization may constitute a viable therapeutic approach to disrupt morphine‐induced conditioned responses.     

一个男运动员的性腺机能低下与富含胡萝卜素饮食的关系(英文)

目的:报道了一个年轻男运动员大量摄入胡萝卜素后引发性腺机能低下的独特病例。病例报告:一名20岁的患者,在先前一年里坚持自己设计的高胡萝卜素、低动物脂肪的饮食,就诊时症状为肌肉逐渐萎缩、身体活动能力以及性欲减低、勃起功能下降。临床上,他表现出明显的胡萝卜素过量的体征:掌心和脚底都呈黄色。当他的饮食正常化二周后,胡萝卜素 B 值达到了正常范围的上限。方法:在恢复均衡饮食前和恢复均衡饮食3、6和12个月后,分别进行下丘脑、垂体和睾丸功能的重复刺激测试。结果:在均衡饮食数月后,促性腺激素和性腺类固醇由最初测得的非常低的基础值和刺激值逐渐恢复正常,并且胡萝卜素 B 值也有所恢复。诊断9—12个月后,荷尔蒙分泌物和性反应完全恢复。结论:这是第一个与摄入过量胡萝卜素有关的下丘脑式性腺机能低下的病例。     

Effect of volume of porogens on the porosity of PLGA scaffolds in pH-controlled environment

Poly(lactic-co-glycolic acid) (PLGA) is a well-studied biodegradable polymer used in drug delivery and other medical applications such as in tissue regeneration. It is often necessary to impart porosity within the scaffold (microparticles) in order to promote the growth of tissue during the regeneration process. Sodium chloride and ammonium bicarbonate have been extensively used as porogens in the generation of porous microstructure. In this study, we compared the effect of volumes (250?μl, 500?μl and 750?μl) of two porogens, sodium chloride (1.71 M) and ammonium bicarbonate (1.71 M), on the porosity of PLGA microparticles.     

Metformin administration was associated with a modification of LH,prolactin and insulin secretion dynamics in women with polycystic ovarian syndrome

Aim. To elucidate the dynamics of FSH, LH, prolactin (PRL), TSH and insulin secretion in women with polycystic ovarian syndrome (PCOS) treated with metformin (MET).

Patients and methods. In a prospective, controlled and randomised trial, 32 women with PCOS and 32 with normal cycle were recruited to receive MET (850 mg b.i.d.) or placebo (n: 16 for each subgroup) for an average of 40 days. Pituitary function and insulin secretion were assessed before and after intervention by GnRH-TRH tests and oral glucose tolerance test induced insulin response.

Results. Basal and area under the response curve (AURC) LH values were higher in PCOS than in normal controls before MET and declined following treatment in the former group (P < 0.05). Ovulatory PCOS responders had lower basal LH, AURC_LH and AURC_PRL values during MET than anovulatory cases (P < 0.05 for all) and AURCins was lower in ovulatory than anovulatory PCOS before and on MET (P < 0.02–P < 0.05), with a rise of QUICKY index in the former group during MET treatment (P < 0.05). FSH and TSH were similar.

Conclusions. MET administration lowered LH activity in all PCOS women and in ovulatory responders and also compromised PRL stimulated secretion in the latter cases. These findings were indicative of an effect of MET on pituitary activity.     

Ploidy of spermatogenic cells of men with non-mosaic Klinefelter’s syndrome as measured by a computerized cell scanning system

PurposeThis study aims to characterize the origin of testicular post-meiotic cells in non-mosaic Klinefelter’s syndrome (KS).MethodsThe study included testicular tissue specimens from 11 non-mosaic KS patients, with (6 positive) and without (5 negative) spermatozoa presence. The obtained testicular cells were affixed and stained for morphology followed by fluorescence in situ hybridization (FISH) for centromeric probes X, Y, and 18. We used a computerized automated cell scanning system that enables simultaneous viewing of morphology and FISH in the same cell.ResultsA total of 12,387 cells from the positive cases, 11,991 cells from the negative cases, and 1,711 cells from the controls were analyzed. The majority of spermatogonia were 47, XXY in both the positive and negative KS cases (88.9 ± 4.76 % and 90.6 ± 4.58 %) as were primary spermatocytes (76.8 ± 8.14 % and 79.6 ± 7.30 %). The respective rates of secondary spermatocytes and post-meiotic cells (round, elongating spermatids and sperm cells) were 1.1 ± 1.39 % in the positive cases, 2.9 ± 3.33 % in the negative cases, compared to 67.6 ± 6.22 % in the controls (P < 0.02). Pairing of both 18 and XY homologous chromosomes in 46,XY primary spermatocytes was 2.5 ± 2.31 % and 3.4 ± 2.39 %, respectively, compared to 19.8 ± 8.95 % in the control group (P < 0.02) and in 47,XXY primary spermatocytes in 2.4 ± 3.8 % in the positive group and 3.2 ± 2.26 % in the negative group.ConclusionsThis study presents data to indicate that the majority of primary spermatocytes in the testes of non-mosaic KS patients are 47,XXY and could possibly develop into post-meiotic cells.Keyword: Ploidy, Testicular suspension, Klinefelter’s syndrome, Spermatogenic cells