Antiproliferative effect of mifepristone (RU486) on human neuroblastoma cells (SK-N-SH): in vitro and in vivo studies

RU486 (mifepristone), a glucocorticoid and progesterone receptor antagonist, has been reported to exert antiproliferative effects on tumor cells. Experiments were performed to analyze the effects of RU486 on the proliferation of the human neuroblastoma, both in vitro and in vivo, using the human neuroblastoma SK-N-SH cell line. The exposure in vitro of SK-N-SH cells to RU486 revealed a dose-dependent inhibition of 3H-thymidine incorporation due to a rapid but persistent inhibition of MAPKinase activity and ERK phosphorylation. A significant decrease of SK-N-SH cell number was evident after 3, 6, and 9 days of treatment (up to 40% inhibition), without evident cell death. The inhibitory effect exerted by RU486 was not reversed by the treatment of the cells with dexamethasone or progesterone. Moreover, RU486 induced a shift in SK-N-SH cell phenotypes, with an almost complete disappearance of the neuronal-like and a prevalence of the epithelial-like cell subtypes. Finally, the treatment with RU486 of nude mice carrying a SK-N-SH cell xenograft induced a strong inhibition (up to 80%) of tumor growth. These results indicated a clear effect of RU486 on the growth of SK-N-SH neuroblastoma cells that does not seem to be mediated through the classical steroid receptors. RU486 acted mainly on the more aggressive component of the SK-N-SH cell line and its effect in vivo was achieved at a concentration already used to inhibit oocyte implantation.

Evaluation of frxA and rdxA gene mutations in clinical metronidazole resistance Helicobacter pylori isolates

Metronidazole resistance is an important factor related to failure in the treatment of Helicobacter pylori. The mutation in the rdxA and frxA genes is the most important cause of resistance to metronidazole. Since the resistance rate of metronidazole is high in our region, we decided to assess the frequency of these mutations among H. pylori clinical isolates. Antral gastric biopsy specimens were cultured and minimal inhibitory concentrations (MICs) of metronidazole were determined by the E-test method. The rdxA and frxA genes were amplified in all isolates through the use of PCR with the specific primers. PCR products were purified for sequencing. The resultant sequences were compared with the wild type reference sequences to find any possible mutations. According to our findings, the rate of metronidazole resistance was 77%, with the MICs ranging from 0.25-1 μg/ml for metronidazole- sensitive group and from 16-256 μg/ml for resistance group. H. pylori isolates containing a single mutation in rdxA or frxA genes demonstrated a low MIC (8-16 μg/ml), while those containing mutations in both genes showed a higher MIC (32-256 μg/ml). In this study, all resistant H. pylori isolates contained single or multiple nucleotide substitutions in the mentioned genes. Nevertheless, no nucleotide substitutions were found in the sensitive clinical isolates. The results of our study showed that the mutations in rdxA are mostly related to metronidazole resistance, and mutations in frxA are able to enhance H. pylori resistance.

South American Guidelines for Cardiovascular Disease Prevention and Rehabilitation / Diretriz Sul-Americana de Prevenção e Reabilitação Cardiovascular

In this document, the Inter-American Committee of Cardiovascular Prevention and Rehabilitation, together with the South American Society of Cardiology, aimed to formulate strategies, measures, and actions for cardiovascular disease prevention and rehabilitation (CVDPR). In the context of the implementation of a regional and national health policy in Latin American countries, the goal is to promote cardiovascular health and thereby decrease morbidity and mortality. The study group on Cardiopulmonary and Metabolic Rehabilitation from the Department of Exercise, Ergometry, and Cardiovascular Rehabilitation of the Brazilian Society of Cardiology has created a committee of experts to review the Portuguese version of the guideline and adapt it to the national reality. The mission of this document is to help health professionals to adopt effective measures of CVDPR in the routine clinical practice. The publication of this document and its broad implementation will contribute to the goal of the World Health Organization (WHO), which is the reduction of worldwide cardiovascular mortality by 25% until 2025. The study group's priorities are the following: • Emphasize the important role of CVDPR as an instrument of secondary prevention with significant impact on cardiovascular morbidity and mortality; • Join efforts for the knowledge on CVDPR, its dissemination, and adoption in most cardiovascular centers and institutes in South America, prioritizing the adoption of cardiovascular prevention methods that are comprehensive, practical, simple and which have a good cost/benefit ratio; • Improve the education of health professionals and patients with education programs on the importance of CVDPR services, which are directly targeted at the health system, clinical staff, patients, and community leaders, with the aim of decreasing the barriers to CVDPR implementation.

Com este documento, o Comitê Interamericano de Prevenção e Reabilitação Cardiovascular, em posição conjunta com a Sociedade Sul-Americana de Cardiologia, mostra seu interesse no desenvolvimento de estratégias, medidas e intervenções para a prevenção e a reabilitação cardiovascular. Com o objetivo de implementar na América Latina uma política de saúde regional e nacional dos países membros, tem-se o objetivo de promover a saúde cardiovascular e, consequentemente, diminuir a morbimortalidade. O grupo de estudos em Reabilitação Cardiopulmonar e Metabólica do Departamento de Exercício, Ergometria e Reabilitação Cardiovascular de Sociedade Brasileira de Cardiologia (DERC/SBC) criou uma comissão de experts para revisar a versão em português e adaptá-la à realidade nacional. Este documento tem como missão principal auxiliar os profissionais de saúde a alcançarem medidas efetivas de prevenção e reabilitação cardiovascular (RCV) na prática clínica diária. Com a difusão deste documento, bem como com a sua implementação de forma mais abrangente, contribuiremos com a meta da Organização Mundial de Saúde de diminuir a mortalidade cardiovascular no mundo em 25% até o ano de 2025. As prioridades deste grupo de trabalho são: • Enfatizar o caráter prioritário da RCV como instrumento de prevenção secundária com importante impacto na morbimortalidade cardiovascular; • Unir esforços para melhorar o conhecimento da RCV, sua difusão e aplicação na maioria dos centros e institutos cardiovasculares da América do Sul, priorizando a utilização de um método de prevenção cardiovascular integral, prático, de fácil aplicação e de custo/benefício comprovado; • Melhorar a educação do pessoal da saúde e dos pacientes por meio de programas educativos dirigidos, que permitam envolver diretamente os sistemas de saúde, pessoal médico, pacientes e líderes comunitários sobre a importância dos serviços de RCV, a fim de diminuir as barreiras para a sua implantação.

Molecular screening of virulence genes in high-level gentamicin-resistant Enterococcus faecalis and Enterococcus faecium isolated from clinical specimens in Northwest Iran.

Purpose: The present study screened clinical isolates of Enterococcus faecalis and Enterococcus faecium to determine the prevalence of high-level gentamicin-resistant enterococci and the potential virulence genes among them. Materials and Methods: Clinical enterococcal isolates were obtained from three university teaching hospitals in Northwest Iran. Isolated enterococci were identified phenotypically followed by antibiotic susceptibility testing. Multiplex PCR was performed for the detection of genus, species-specific targets, gentamicin resistance, and potential virulence genes. Results: Of 220 enterococcal isolates, 133 (60.45%) isolates were identified as high-level gentamicin-resistant. Of these isolates, 79 (59.4%) and 54 (40.6%) were E. faecalis and E. faecium, respectively. All high-level gentamicin-resistant strains carried aac(6′)Ie-aph(2″)Ia. Of 220 isolates, 65.9% were positive for gelE, and 55%, 53.6%, 51.8%, and 49.5% of isolates were positive for cpd, asa1, ace, and esp, respectively. Phenotypically detected β-haemolytic strains (19.54%) were found to possess cylL ls MAB. Conclusion: The study revealed that high-level gentamicin-resistance was related to the presence of aac(6′)Ie-aph(2″)Ia. Isolated enterococci harboured potential virulence determinants, which were more common among E. faecalis than among E. faecium strains.

[The effect of family counseling programs on prevention of psychological abuse of elderly women]

Attention to psychological abuse of old women as a vulnerable group and its complications are important issues. We performed this study to determine the effect of family counseling program on prevention of psychological abuse of elderly women. This is a semi-experimental study. We selected 30 old women referring to clinics of an educational hospital in Tehran by simple randomization. Data collecting instruments included demographic sheets about old person and family members and a questionnaire about psychological abuse, which were completed by interview. An observational checklist about behavioral symptoms was completed at 3 interview sessions by family and old person at home. Then 6 counseling sessions were established. Duration of every session was 1:30 up to 2 hours. After two months and in the last three sessions, final evaluation was conducted by again completing data collecting instruments. Study results showed that 90% of abusers were woman and family dysfunction was the reason of abuse in 43.3% of cases. Mean score of psychological abuse showed a significant decrease after counseling, using dependent t-test and Wilcoxon test [p<0.001]. Also, mean score of behavioral symptoms of abuse showed a statistically significant decrease after counseling, using dependent t-test and Wilcoxon [p<0.001]. Pearson correlation coefficient [r=0.90] showed that there was a significant correlation between psychological abuse and behavioral symptoms. Regarding positive effect of family counseling programs on reduction of psychological abuse of old women, it is suggested that effect of family counseling programs in reduction of other types of abuse be determined