Suppression of testosterone and estradiol-17beta-induced dysplasia in the dorsolateral prostate of Noble rats by bromocriptine

We, and others, have previously described the histological changes that occur in the prostate gland of intact Noble (NBL) rats following prolonged hormonal treatment. Dysplasia, a pre-neoplastic lesion, develops specifically in the dorsolateral prostates (DLPs) of NBL rats treated for 16 weeks with a combined regimen of testosterone (T) and estradiol-17beta (E2) (T + E2-treated rats). Concurrent with DLP dysplasia induction, the dual hormone regimen also elicits hyperprolactinemia, in addition to an elevation of nuclear type II estrogen binding sites (type II EBS), no alteration in estrogen receptors (ER), and marked epithelial cell proliferation in the dysplastic foci. The aim of this study was to investigate whether the dual hormone action is mediated via E2-induced hyperprolactinemia. Bromocriptine (Br), at a dose of 4 mg/kg body wt per day, was used to suppress pituitary prolactin (PRL) release. Serum PRL levels were lowered from values of 341 +/- 50 ng/ml in T + E2-treated rats to 32 +/- 10 ng/ml in Br co-treated animals. The latter values were comparable to those in untreated control rats. In addition, Br co-treatment effectively inhibited the evolution of dysplasia (six out of eight rats) and the often associated inflammation (five out of eight rats) in most animals. In contrast, Br co-treatment did not suppress the T + E2- induced type II EBS elevation nor alter ER levels in the DLPs of these rats, when compared with T + E2-treated rats. These data extend the many previous studies that have detailed marked influences of PRL on rat prostatic functions. However, the current study is the first to implicate PRL in prostatic dysplasia induction in vivo.      

Measurement of benzene oxide in the blood of rats following administration of benzene

Although it is generally assumed that metabolism of benzene proceeds through an initial step involving oxidation to benzene oxide (BO) by CYP450 in the liver, the production of BO has never been unambiguously confirmed in animals dosed with benzene. Furthermore, prevailing hypotheses of the mechanism by which benzene causes cancer have ignored the possibility that BO might play a direct role, despite the fact that BO is electrophilic, binds covalently to cell macromolecules and is presumably genotoxic. A likely reason for this lack of attention to the role of BO in the carcinogenesis of benzene is the presumption that this epoxide is too reactive to escape the hepatocyte after it is formed. We employed gas chromatography-mass spectrometry to measure BO in the blood of F344 rats, both in vitro and up to 24 h following oral administration of benzene. Surprisingly, BO was relatively stable in rat blood at 37 degrees C (estimated half-life = 7.9 min) and, after administering a single dosage of 400 mg benzene/kg body wt, a blood concentration of 90 nM BO (8.5 ng/ml) was measured for approximately 9 h. Using a published PBPK model we estimate that approximately 4.3% of the metabolized dose of benzene was released as BO from the liver into blood. This confirms that BO is, indeed, formed from metabolism of benzene and is sufficiently stable to be distributed throughout the body at levels which are likely to be greater than those of the other electrophilic benzene metabolites.      

Effect of tetrandrine on cellular electrophysiology and calcium uptake of myocardium in guinea pigs and dogs

目的　本文旨在研究汉防已甲素对豚鼠及狗的心肌动作电位 (AP)、收缩力及肌浆网钙吸收的作用。方法　用玻璃微电极的方法 ,研究用药后心肌细胞AP、dV/dt、峰张力 (PT)及dT/dt等指标的改变 ,并用生化方法估价用药后心肌肌浆网钙吸收率及无机磷释放等指标的变化。结果　汉防已甲素起着浓度依赖性和频率依赖性负性变力性作用 ,且缩短了动作电位时程。汉防已甲素抑制心肌dT(E) /dt和dT(L) /dt,也抑制了心肌张力 ,并降低了慢动作电位的dV/dt和幅度 ,这些暗示汉防已甲素可阻止慢钙通道。另外 ,与Thapsigargin(一种特异性肌浆网Ca2 ATP酶抑制剂 )进行了比较 ,汉防已甲素较之更为明显地抑制了心肌的收缩。结论　汉防已甲素是一种植物性广谱钙离子拮抗剂。它不仅阻止电压操纵的钙通道 (象其它作者所报导的那样 ) ,而且在影响Ca2 ATP酶及肌浆网钙释放通道方面也起着重要的作用。我们的资料提示钙通道对心肌收缩似乎比肌浆网更为关键。     

Metabolic control and diet in Finnish diabetic adolescents

The effects of dietary, clinical and demographic factors on metabolic control in 105 diabetic adolescents were studied. All patients had diabetes for longer than two years and a daily insulin dose greater than 0.5 IU/kg body weight. Low body mass index, high social class, high number of daily eating occasions, high day-to-day variation in energy intake, high number of urine tests and a long interval between insulin injection and eating were associated with good metabolic control. Many of these determinants reflect also the general compliance with the diabetic regimen. The results stress the importance of good coordination between insulin injections and eating habits.     

A follow-up study of the diet of Finnish diabetic adolescents

Changes with age and time in energy-adjusted food consumption and nutrient intake of 74 diabetic subjects initially aged 12-17 years were studied. Food consumption was measured by the 48-h recall method. During the three-year follow-up (from 1985 to 1988), the proportion of carbohydrate of total energy intake decreased from 49% to 47%, that of fat increased from 33% to 36% and that of protein decreased slightly. The densities of fibre and several vitamins decreased in the diet of the diabetic adolescents. These unfavourable changes in the diet of diabetic adolescents took place with increasing age and duration of diabetes, while virtually no changes with time were detected.     

香港华人妇女产后抑郁危险因素的前瞻性研究

目的：产后抑郁是一种常见的精神障碍，对产妇、新生儿和其它家庭成员导致广泛的伤害。产后抑郁的病因学研究大多是基于西方样本，对其中的社会文化原因也缺乏实证研究。本研究从人口学、心理社会及种族文化因素等方面探讨中国妇女产后抑郁症状学的决定因素。方法：在大学附属综合医院产前门诊连续收集登记的中国孕妇959例，从她们第一次产前检查开始评估（基线），以后分别在孕期的最后3个月、产后即刻和产后3个月时评估。调查涉及的危险因素分6个方面：人口学和社会经济背景，躯体疾病及精神疾病病史，产前抑郁情绪，围生期应激源，人际关系，和种族文化环境。采用等级回归进行分析。因变量是产后3个月时的抑郁评分。结果：决定产后抑郁症状学的因素有：目前的生活事件，缺乏社会支持，婚姻不满意，既往有故意自伤史，以及产前存在抑郁情绪。婆媳关系不好和没有陪月在产后阶段也与抑郁评分高有关联。结论：西方研究所确立的产后抑郁危险因素大体适用于中国妇女。产褥期的社会文化特点同样对产妇情绪有影响。     

Chromatin conformation of the H19 epigenetic mark

Genomic imprinting in mammals is an epigenetic process that results in differential expression of the two parental alleles. The tightly linked murine H19 and Igf2 genes are reciprocally imprinted: H19 is expressed from the maternal chromosome while Igf2 is expressed from the paternal chromosome. A single regulatory region in the 5' flank of the H19 gene has been implicated in silencing both genes. On the paternal chromosome, this region is heavily methylated at CpG residues, leading to repression of the H19 gene. The mechanism by which the same region in an unmethylated state on the maternal chromosome silences Igf2 is less well understood. We have probed the chromatin structure of the region by assessing its sensitivity to nuclease digestion. Two regions of nuclease hypersensitivity that are specific to the maternal chromosome were identified. These coincide with the region that is most heavily methylated on the paternal chromosome. As is the case with paternal methylation, hypersensitivity is present in all tissues surveyed, irrespective of H19 expression. We suggest that the chromatin structure of the maternal 5' flank of the H19 gene may represent an epigenetic mark involved in the silencing of Igf2.