S-aryl(tetramethyl)isothiouronium salts as potential antimicrobial agents, II

Several S-Aryl(tetramethyl)isothiouronium salts were prepared and their antimicrobial activities determined in vitro on different strains of bacteria and fungi. Their structure-effect relationships were compared with those of a series of salts previously studied and the possible influences of decomposition kinetics and surface tension were examined.     

Tadalafil in the treatment of erectile dysfunction

Oral phosphodiesterase-5 inhibitors have emerged as the preferred first-line treatment for erectile dysfunction worldwide because of patient convenience, efficacy, and safety. Clinical trials have shown that tadalafil significantly enhances erectile function across a wide range of etiologies and provides a prolonged period of effectiveness independent of food or alcohol. In this review, the pharmacokinetic and pharmacodynamic characteristics, efficacy, and safety of tadalafil are discussed.     

Chemically modified tetracyclines induce cytotoxic effects against J774 tumour cell line by activating the apoptotic pathway

Here, we have studied the effects of chemically modified tetracyclines (CMTs) on apoptosis both at the level of the cytoplasmic proteolytic caspase cascade, and on Bcl-2 and c-myc mRNA expression in the J774 macrophage cell line. The results indicate that CMTs induce morphological changes consistent with apoptotic events, as clearly demonstrated both by the acridine orange and ethidium bromide staining, and by TUNEL and fragmentation ELISA assays. Furthermore, the analysis of the cell cycle by flow cytometry shows an evident apoptotic sub-G0G1 peak, without important modifications in the cell cycle distribution. CMTs induce programmed cell death (PCD) in a dose-dependent manner and CMT-8 is the strongest among them. CMT-1 and CMT-8 activate mainly caspase-8 as attested by the inhibitory effects of Z-VAD-fmk and Z-IEDT-fmk on CMT-induced apoptosis. Part of CMT-induced PCD is due to the activation of caspase-9, since it is reduced by the specific caspase-9 inhibitor, Z-LEHD-fmk. Besides, CMTs increase Bcl-2 and c-myc mRNA expression. Collectively, these data indicate that CMTs are potentially anti-tumour agents, since they strongly trigger apoptosis both activating the proteolytic system of the caspase family and modulating genes involved in PCD regulation.     

Reporter gene assay demonstrates functional differences in estrogen receptor activity in purified breast cancer cells: a pilot study

Tamoxifen has contributed to a dramatic reduction in breast cancer mortality and recent results indicate that aromatase inhibitors may further improve survival in some patients. Nevertheless, a substantial proportion of patients become resistant to treatment. To date, with the exception of estrogen receptor (ER) determination by ligand binding or immunohistochemical techniques, there has been no way of predicting which of several therapies is indicated in particular patients. We describe a novel assay using the adenoviral gene delivery system to assess ER function in breast cancer cells derived directly from patients. The purification and short-term culture of these cells has been recently described by our laboratory. Adenovirus containing an estrogen-regulated beta-galactosidase reporter gene (ERE-lacZ) was constructed and used to test ER activity in breast cancer cells derived from 18 patients with primary and 16 patients with metastatic cancer, under varying treatment schedules. The adenoviral assay enabled ER activity to be readily determined in purified cells from primary breast cancers and secondary sites. Breast cancers cells could be categorized on the basis of ER activity in the absence of ligand, the presence of estrogen or anti-estrogens. In primary breast cancers, our results correlated with ER determination by immunohistochemistry in 78% of cases. In patients who had become resistant to tamoxifen, however, we found some in whom reporter activity was stimulated by tamoxifen and others whose tumors were either still estrogen responsive or completely unresponsive, irrespective of the original ER content. Our findings indicate that this reporter assay could be useful in decisions regarding use of adjuvant endocrine therapies in breast cancer.     

Trajectories of posttraumatic stress disorder following myocardial infarction: a prospective study

BACKGROUND: This study examines the trajectories of posttraumatic stress disorder (PTSD) following myocardial infarction (MI). More specifically, it has 2 aims: (1) to examine whether the trajectory of PTSD is predicted by level of threat and the nature of initial reactions and (2) to examine the associations between the trajectory of PTSD and anxiety, somatization, health-related quality of life, and hospitalization 7 months following MI. METHOD: 116 MI patients were examined twice. At time 1, within a week of the patient's MI, acute stress disorder (ASD) was assessed and medical measures were obtained from patients' hospital records. At time 2, 7 months later, PTSD, anxiety, physical residuals, and health-related quality of life were assessed. Data were gathered in 1999. RESULTS: Six percent of the respondents had both ASD and PTSD, 10% did not have ASD but did have PTSD, and 12% had ASD but not PTSD. The trajectory of PTSD was associated with severity of anxiety, somatic complaints, and health-related quality of life. In addition, while the severity of MI did not predict the trajectory of PTSD, the perceived severity did. Patients without PTSD but with prior ASD did not differ in their initial reactions from those without ASD. CONCLUSION: These findings provide support for the considerable variability in the trajectory of the development of PTSD and suggest that although ASD is associated with subsequent PTSD, the predictive role of initial reactions is limited.     

Learning achievement and behavior at school of anemic and non-anemic infants

In a prospective study the learning achievement and behaviour of second grade children who were anemic in infancy (n = 20) was compared with that of non-anemic children (n = 55). All children received preventive care and were under surveillance from birth at the Community Health and Research Center of Hadassah in Jerusalem. The anemic children had a hemoglobin level of less than 10.5 g/dl whereas the comparison group had more than 11.5 g/dl at 9 months of age. The learning achievement score was significantly lower in the anemic group 9.3 S.D. 3.8, than in the non-anemic group 11.5 S.D. 2.9 (P = 0.009). The positive task orientation was also significantly lower in the anemic group, though on additional behavior scores no differences were found. Differences remained significant even after controlling for maternal education and sex of child in a multivariate analysis. It is possible that an iron deficiency state which persists during the critical period of brain development in infancy has long-lasting effects on cognitive functioning. Prevention of iron deficiency may contribute to promotion of child development and better achievement.