Estrogen Receptor β Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells

Alternaria toxins are considered as emerging mycotoxins, however their toxicity has not been fully evaluated in humans. Alternariol (AOH), the most prevalent Alternaria mycotoxin, was previously reported to be genotoxic and to affect hormonal balance in cells; however, its direct molecular mechanism is not known. The imbalance in androgen/estrogen ratio as well as chronic inflammation are postulated as factors in prostate diseases. The environmental agents affecting the hormonal balance might participate in prostate carcinogenesis. Thus, this study evaluated the effect of two doses of AOH on prostate epithelial cells. We observed that AOH in a dose of 10 µM induces oxidative stress, DNA damage and cell cycle arrest and that this effect is partially mediated by estrogen receptor β (ERβ) whereas the lower tested dose of AOH (0.1 µM) induces only oxidative stress in cells. The modulation of nuclear erythroid-related factor 2 (Nrf2) was observed in response to the higher dose of AOH. The use of selective estrogen receptor β (ERβ) inhibitor PHTPP revealed that AOH-induced oxidative stress in both tested doses is partially dependent on activation of ERβ, but lack of its activation did not protect cells against AOH-induced ROS production or DNA-damaging effect in case of higher dose of AOH (10 µM). Taken together, this is the first study reporting that AOH might affect basic processes in normal prostate epithelial cells associated with benign and malignant changes in prostate tissue.     

Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers to alcoholism,substance abuse and schizophrenia in Southwestern American Indians

Alcoholism is one of a group of common psychiatric diseases which are well-defined clinically and strongly influenced genetically, but which are likely to be highly heterogeneous in causation, genetically and otherwise. Dopamine is a key neurotransmitter in drug-mediated reinforcement. Based on association studies with the Taq1A downstream marker, the D2 dopamine receptor has been proposed to be the “Reward Deficiency Syndrome Gene.” Ser311Cys, a naturally occurring variant which largely inactivates transduction after D2 receptor activation, was abundant (0.16) in a Southwestern American Indian population we studied. Therefore, we were able to provide a critical test of the D2 hypothesis of vulnerability to alcoholism by evaluating Ser311Cys and also the intron-2 STR and Taq1A markers at this locus in a total of 459 subjects, including 373 sib pairs, from large families. The result is that neither alcoholism, substance use disorders nor schizophrenia show a relationship to Ser311Cys genotype, even when the 15 Cys311/Cys311 homozygous individuals are compared to others. Furthermore, sib pair analysis incorporating information across all three sib pair categories: concordant affected, discordant and concordant unaffected revealed no effect of DRD2 genotype or haplotype on alcoholism or substance use disorder. Am. J. Med. Genet. 74:386–394, 1997. © 1997 Wiley-Liss, Inc.     

Thromboprophylaxis in patients with multiple organ injuries--is there an alternative to low-molecular-weight heparins (LMWH)?

The number of body injuries keeps growing and that is mostly due to increasing number of car accidents. How to prevent thrombosis in such cases is still under discussion with the biggest issue being the proper timing. Most of the input to such discussion usually comes from extrapolating data from other studies, which is hardly of help for treatment of such group of patients. The authors focus on collection and analysis of most recent data and recommendations that are available in literature. They show that low-molecular-weight heparins are by far the most common, if not sole pharmacologic means of thromboembolism prevention in patients with numerous body injuries.     

Long‐term follow‐up of Wilson Disease: natural history,treatment, mutations analysis and phenotypic correlation

Background and aims: Wilson disease (WD) is an inherited disorder of copper metabolism. When treated, the outcome can be excellent, although the long‐term survival has yet to be well documented. The aim of this study was to describe the long‐term outcome of a cohort of patients with WD and to assess those factors affecting the phenotypic manifestation of WD. Methods: The presence of mutations to the ATP7B gene, the clinical manifestations, treatments and the long‐term outcomes were analysed retrospectively in 117 patients with WD (59 men and 58 women, aged at evaluation 38.5 ± 11, range 16–63 years). Results: Fifty‐five patients with a neurological presentation, 51 patients with a hepatic presentation and 11 asymptomatic patients were followed up for an average of 15.1 ± 10 years (median 12 years, range 1–41 years). The H1069Q ATP7B gene mutation was the most frequent genetic variant (54.3%); the frequency of this mutation did not differ between patients with either the hepatic or the neurological presentation (P=0.099). d ‐penicillamine or zinc salts (81 and 17% respectively) were used for treatment, and three patients underwent liver transplantation. The majority of symptomatic patients became asymptomatic, or improved, during the follow‐up (82% patients with hepatic presentation, 69% with neurological presentation). The long‐term survival of patients with WD did not differ from that of the general Czech population (P=0.95). Conclusions: Long‐term follow‐up shows a satisfactory response in the great majority of adequately treated patients with WD and survival coincides with that of the general population.     

Pregnancy outcomes and deliveries following laparoscopic transsection of uterine vessels: a pilot study

OBJECTIVE: To assess pregnancy outcomes and deliveries after laparoscopic uterine artery transsection (LTUV) in symptomatic women with fibroids. SETTING: Department of Obstetrics and Gynecology, Endoscopic Training Center, Baby Friendly Hospital, Kladno, Czech Republic. DESIGN: One hundred and fifty three patients underwent laparoscopic transsection of uterine vessels during a 4-year period. RESULTS: Nine of the 21 women desiring pregnancy conceived spontaneously and one after anovulation treatment. The average age of the women was 32.4 years, and the range was 26-39 years. Two women had vaginal delivery at term and one delivered vaginally at 31 weeks secondary to premature preterm rupture of membrane (PROM). Four others delivered at term by cesarean section. One woman with placenta previa was delivered by cesarean section 3 weeks before term. Mean birth weight was 3199 g (range 1710-3910 g). One spontaneous abortion was reported in the first trimester of pregnancy. One case of undesired pregnancy occurred. An extrauterine pregnancy was reported in this woman. CONCLUSION: LTUV is a minimally invasive operative procedure, that preserves the uterus and ovarian blood supply and allows for the achievement of pregnancy in women with symptomatic fibroids. Fetal growth and umbilical Doppler findings remained normal in all cases. An increased risk for preterm delivery and cesarean section was found in this small series.     

Aquagenic syringeal acrokeratoderma

A case of a 32-year-old woman with aquagenic syringeal acrokeratoderma is presented. This case is the eleventh to report this condition. As with previously reported cases, the condition presents in young women and results in edema of the palms with visibly prominent eccrine ducts after brief exposure to water. The patient responded to aluminum chloride applied topically. Prior cases are reviewed.     

Type 2 diabetes susceptibility single-nucleotide polymorphisms are not associated with polycystic ovary syndrome

Two cohorts of women with polycystic ovary syndrome (PCOS), comprising 400 probands and affected sisters in 365 families and a case-control group including 395 women with PCOS and 171 healthy women with regular menstrual cycles, were studied to determine whether single-nucleotide polymorphisms (SNPs) identified as susceptibility loci in genomewide association studies of type 2 diabetes are also associated with PCOS. None of the 18 allelic variants in 10 genes previously shown to be associated with type 2 diabetes were found to be associated with PCOS, but some were associated with indices of beta cell function.