The effect of different calcium antagonists and a calcium agonist on the metabolism of propranolol by isolated rat hepatocytes

Summary— The influence of the dihydropyridine calcium entry blockers nicardipine, amlodipine, nifedipine, isradipine and of the dihydropyridine calcium entry promotor BAY K 8644 on the disappearance rate of propranolol by isolated rat hepatocytes was compared to the effect of diltiazem and verapamil, two non-dihydropyridine calcium channel blockers and known inhibitors of hepatic cytochrome P450 mixed function oxidases. All compounds dose-dependently inhibited the disappearance rate of propranolol. Nicardipine and isradipine were more potent in inhibiting the disappearance rate of propranolol than the other dihydropyridines and than diltiazem and verapamil. The inhibitory effect of nicardipine on the disappearance rate of propranolol was not stereoselective and was not influenced by age.     

Aggregated IgE mimic interleukin-3-induced histamine synthesis by murine hematopoietic progenitors

Similar to interleukin-3 (IL-3), IgE acts on murine bone marrow cells by inducing histamine production. This effect does not result from degranulation of histamine-containing cells, but from histamine synthesis, as assessed by the following findings. (1) The histamine content of freshly isolated bone marrow cells is too low to account for the increase in extracellular histamine levels. (2) Neither IL-3 nor IgE induced histamine production in the presence of the specific inhibitor of histidine decarboxylase (HDC), the histamine-forming enzyme. (3) Both the enzymatic activity and the mRNA expression of HDC were enhanced in response to IL-3 or IgE. Artificial aggregation or formation of IgE immune complexes augmented ther effect on histamine synthesis, indicating that the aggregated form is responsible for this biologic activity. Yet, it is apparently not mediated by Fc epsilon RI because their cross-linkage by dinitrophenyl bovine serum albumin after presensitization with IgE did not induce histamine production by hematopoietic progenitors. Among other aggregated isotypes tested, only IgG2a and, to a lesser extent, IgG1 had a consistent but lower effect, whereas IgM and IgA were completely inactive. The target cells of IL-3 and IgE in terms of histamine synthesis do not belong to mature bone marrow populations, especially mast cells. They copurify with hematopoietic progenitors in the low-density layers of a discontinuous Ficoll gradient where they represent around 5% of the cells, as determined by in situ hybridization. This percentage remained the same, regardless of whether the cells were stimulated by IgE or IL-3 alone or by a combination of both, suggesting a common responder cell. In accordance with this notion, histamine-producing cells could not be distinguished from each other on the basis of density, size and internal structure, or rhodamine (Rh) retention. Finally, the effect of IgE is not caused by the induction of IL-3 because anti-IL-3 antibodies did not abrogate the effect of IgE.     

Hungry bone syndrome in a child following parathyroid surgery.

The rare hungry bone syndrome was encountered in a 15-year-old child after the removal of a parathyroid adenoma. Contrary to the hypocalcemias caused by the removal of all parathyroid glands or transient ischemia after parathyroid surgery, in which the serum inorganic phosphorus level is usually normal, both serum calcium and inorganic phosphorus levels are decreased in hungry bone syndrome in the early postoperative period. Vigorous calcium supplementation and vitamin D are required for prolonged periods.     

基于受体结构的药物分子设计系统:维甲类分子与其结合蛋白之间相互作用的研究

大分子解剖程序,配体分子契合适配和DOCK程序,以及计算化学的其它程序等,已集成为基于受体结构和分子间相互作用的进行分子设计的软件系统,定名为BIOS(Biomolecularinteractionsandorientationsimulator)。BIOS软件可在普通的微机上运行。使用BIOS分别剥离了细胞浆维甲结合蛋白(CRBP)和副睾维甲酸结合蛋白(E-RABP)两种蛋白的配体结合腔,剥离是围绕配体以同样的分子距离进行的。从而得到了芳香性残基分布相似的两个结合腔,其结合位点的几何排布却有相当差别。揭示出的结合腔已用于一系列的维甲类化合物的DOCK研究。E-RABP的结合腔可做为设计新维甲类分子的模板。     

Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11

In a large collaborative screening project, 370 men with idiopathic azoospermia or severe oligozoospermia were analysed for deletions of 76 DNA loci in Yq11. In 12 individuals, we observed de novo microdeletions involving several DNA loci, while an additional patient had an inherited deletion. They were mapped to three different subregions in Yq11. One subregion coincides to the AZF region defined recently in distal Yq11. The second and third subregion were mapped proximal to it, in proximal and middle Yq11, respectively. The different deletions observed were not overlapping but the extension of the deleted Y DNA in each subregion was similar in each patient analysed. In testis tissue sections, disruption of spermatogenesis was shown to be at the same phase when the microdeletion occurred in the same Yq11 subregion but at a different phase when the microdeletion occurred in a different Yq11 subregion. Therefore, we propose the presence of not one but three spermatogenesis loci in Yq11 and that each locus is active during a different phase of male germ cell development. As the most severe phenotype after deletion of each locus is azoospermia, we designated them as: AZFa, AZFb and AZFc. Their probable phase of function in human spermatogenesis and candidate genes involved will be discussed.      

Photic driving in migraine: correlations with clinical features

Fifty-eight migraineurs were. studied by intermediate frequency steady-state visual evoked potentials (SSVEPs) during headache-free periods. Sex, age, age of onset of migraine, duration of illness, type of migraine, side of pain, sleep .wake disorders, and frequency of migraine attacks did not correlate with any SSVEP abnormalities. On the other hand, visual responsiveness was significantly increased in subjects with family history of migraine, and in those with autonomic symptoms. Our results may indicate that a genetic predisposition to migraine underlies the observed abnormal visual response in migraineurs.     

Nonpalpable breast lesions: recommendations for biopsy based on suspicion of carcinoma at mammography

Carcinoma was found in 30% (119 of 400) of biopsy specimens obtained for mammographically suspicious but nonpalpable findings. The authors reviewed the mammograms of these 400 cases without knowledge of the biopsy results and placed each examination into one of four groups based on their suspicion for carcinoma: minimal (n = 82), slight (n = 91), moderate (n = 174), and high (n = 53). In 127 cases, mammograms showed either minimally suspicious calcifications (n = 33) or minimally (n = 49) or slightly (n = 45) suspicious masses. A 4.7% (six of 127) rate of carcinoma was found in these groups; five of the six cancers were in situ. Had follow-up mammography been done rather than biopsy for these 127 less suspicious lesions, it is probable that the delay in diagnosis would not have altered overall prognosis. In the remaining 273 patients, the positive predictive value of mammography for carcinoma would have risen from 30% (119 of 400) to 41% (113 of 273). The authors conclude that in the management of suspicious nonpalpable mammographic findings, the rate of carcinoma for lesions at biopsy can approximate 40%. This is almost double the rate of most published series.     

Effects of omega-3 essential fatty acids against formaldehyde-induced nephropathy in rats

The aim of this study was to examine the toxicity of formaldehyde (FA) on the kidney and the protective effects of omega-3 essential fatty acids against these toxic effects. Twenty-one male Wistar rats were divided into three groups. Rats in Group I comprised the controls, while the rats in Group II were injected every other day with FA. Rats in Group III received omega-3 fatty acids daily while exposed to FA. At the end of the 14-day experimental period, all rats were killed by decapitation and the kidneys removed. Some of the kidney tissue specimens were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities, and malondialdehyde (MDA) levels. The remaining kidney tissue specimens were used for light microscopic evaluation. The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in rats treated with FA compared with those of the controls. Furthermore, in the microscopic examination of this group, glomerular and tubular degeneration, vascular congestion and tubular dilatation were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered omega-3 fatty acids while exposed to FA. Additionally, kidney damage caused by FA was decreased and structural appearance was similar to that of the control rats in this group. In conclusion, it was determined that FA-induced kidney damage was prevented by administration of omega-3 essential fatty acids.     

STI/HIV Risks for Mexican Migrant Laborers: Exploratory Ethnographies

The influx of Latino laborers into the U.S. and the confluence of migration-driven factors in an environment ripe for risk-taking have the potential to exacerbate already rising STI/HIV rates among migrants and their social networks at both the home and receiving regions. This paper focuses on Mexican migrant laborers who are among the most marginalized and exploited Latinos in the U.S. This study used ethnographic methods to delineate the sociocultural and spatial contexts and social organization of migrant farmwork, and examined how intertwined individual and environmental factors render migrant farmworkers vulnerable to STI/HIV risks. Findings indicate the presence of a number of factors in the study population of Mexican migrant workers (N = 23)—such as poverty, limited education, physical/social/cultural isolation, long work hours, constant mobility, hazardous work conditions, limited access to health care, low rates of condom use, multipartnering, and use of sexworkers—which increase their risks for STI/HIV transmission. To be successful, prevention efforts need to focus not only on condom education and HIV awareness and testing, but also on reducing migrants’ social isolation and understanding their social networks.