The effect of finasteride on the prostate gland in men with elevated serum prostate-specific antigen levels.

Prostate cancer is a disease associated with androgens. It has been hypothesized that reducing the conversion of testosterone (T) to dihydrotestosterone (DHT) in the prostate by the use of the drug finasteride, a 5alpha-reductase inhibitor, will reduce the incidence of prostate cancer. We investigated the chemopreventive potential of finasteride by evaluating its effect on the prostate gland of men with elevated serum prostate-specific antigen (PSA). Fifty-two men with elevated PSA and prostate sextant biopsies negative for cancer were randomized to receive finasteride 5 mg day(-1) (27 patients) or no medication (25 patients) for 12 months and were rebiopsied at 12 months. The biopsies were evaluated for the presence of cancer, the proportion of glandular and hyperplastic tissue, and the presence of high-grade prostatic intraepithelial neoplasia (PIN). Epithelial proliferation was assessed in the prestudy and 12-month biopsies by immunohistochemistry using antibody to proliferating cell nuclear antigen (PCNA). Serum blood samples were drawn at baseline and after 1, 3, 6 and 12 months of study. In the control group, serum levels of PSA and T were unchanged throughout the 12 months. In the finasteride group, PSA decreased 48% (P < 0.001), DHT decreased 67% (P < 0.001) and T increased 21% (P < 0.001). Histological evaluation of prestudy and 12-month biopsy specimens revealed that the finasteride group had a 30% reduction in the percentage of hyperplastic epithelial tissue (P = 0.002), although this decrease was not statistically significantly different between the finasteride and control groups (P = 0.11). In patients with PIN on prestudy biopsy, no change occurred in the PIN lesions with finasteride treatment. Finasteride also had no effect on the proliferation index of prostatic epithelial cells. Of the 27 patients treated with finasteride, eight (30%) had adenocarcinoma of the prostate detected on the 12-month biopsy, compared with one (4%) of the control patients (P = 0.025). In the treatment group, six cancers occurred in the eight patients with PIN on the prestudy biopsy; in the observation group no cancers were detected in the five patients with PIN on the prestudy biopsy (P = 0.021). Two cancers occurred in the 19 men in the treatment group with no evidence of PIN on the prestudy biopsy, compared with one cancer in the 20 men in the observation group with no evidence of PIN on the prestudy biopsy (P = 0.60). This study, using a novel model for evaluating short-term efficacy of chemopreventive or therapeutic agents in men at high risk of prostate cancer, provides little evidence that finasteride is an effective chemopreventive agent for prostate cancer in men with elevated PSA.     

Low versus standard dose intravenous alteplase in the treatment of acute ischemic stroke in Egyptian patients

Objectives:To assess low dose altepase outcome and safety in comparison with a standard-dose regimen for acute ischemic stroke treatment in Egyptian patients.Materials:An observational prospective cohort non-randomized single blinded study was carried out during the period from November 2017 to December 2018. Eighty Egyptian acute ischemic stroke patients, all eligible for intravenous alteplase, were subdivided into 2 groups (40 patients in each group). Patients were thrombolysed at a dose of 0.6 mg/kg in the first group and 0.9 mg/kg in the second group. Both groups were compared in regard to safety and outcome. Safety was expressed by the rate of symptomatic intracranial hemorrhage (SICH) and 3 months mortality, while outcome was expressed by favorable outcomes at three months (modified Rankin Scale [mRS] of 0 to 2).Results:In the first group, 69.2% (n=27) achieved favorable outcomes at 90 days compared with 64.1% (n=25) in the second group (p=0.631). Ninety-day mortality was 5% (n=2) in the first group versus 2.5% (n=1) in the second group (p=0.556). Symptomatic intracranial hemorrhage was noted in 3 patients in the second group and zero patients in the first group (p=0.077).Conclusion:Low-dose alteplase could be a practical alternative for Egyptian populations with acute ischemic stroke especially in 3 to 4.5 hours window.

Cerebrovascular stroke is the second death and the seventh disability leading cause worldwide.¹ Tissue-type plasminogen activator (tPA) alteplase was the first medication approved by the Food and Drug Administration (FDA) for the acute ischemic stroke (AIS) treatment on June 1996, within 3 hours of stroke onset with a recommended dose of 0.9 mg/kg (maximum 90mg).² In 2008, the safety of using alteplase within 3 to 4.5 hours of stroke onset was approved by the Safe Implementation of Treatments in Stroke International Stroke Thrombolysis Registry (SITS -ISTR)³ and the European Cooperative Acute Stroke Study (ECASS III).⁴ However, thrombolytic therapy use has not been widely adopted, especially in developing countries. The restricted time window (3 to 4.5 hours), intracerebral hemorrhage (ICH) risk and the drug high cost are major obstacles preventing its broad application.⁵ Coagulation and fibrinolysis responses differ among different races, which increase symptomatic intracerebral hemorrhage (SICH) risk with standard-dose alteplase⁶ in Asian populations, many Asian neurologists considered alteplase low dose to be a better alternative for ischemic stroke treatment. Many studies had been conducted in order to prove the efficacy and safety of Alteplase low dose.^7-9 One of these studies was the Japan Alteplase Clinical Trial (J-ACT) conducted by Yamaguchi et al¹⁰ According to this study, using a 0.6 mg/kg dose of intravenous recombinant tissue plasminogen activator (rtPA) in Japanese patients was safe and effective. Despite the relatively stroke high rate among Egyptian populations, 963/100,000 inhabitants, only less than 1% of stroke patients receive intravenous thrombolysis. A major reason for this is the drug cost.^11,12 Low-dose regimens (0.6 mg/kg) use will lower the economic burden of thrombolytic therapy in the community and will greatly promote the implementation of this therapy in Egypt. Our study aim was to assess the outcome and safety of alteplase low dose in comparison to the standard-dose regimen in AIS treatment in Egypt.     

Violent Crime in the Lives of Homeless Female Ex-Offenders

The cyclical pattern of violence in the lives of homeless female ex-offenders may precipitate ongoing substance use and recidivism; all of which have shown to be mounting public health issues affecting successful reentry. This paper, which analyzed baseline data from a longitudinal study of 126 female ex-offenders in Los Angeles and Pomona, California, highlighted the factors found to be associated with violent crime among homeless female ex-offenders. A multiple logistic regression model for whether or not the last conviction was for a violent offense indicated that poor housing (p = .011) and self-reported anger or hostility (p < .001) were significant correlates. An ordinal regression model for the number of violent offenses also indicated that affectionate support was associated with committing fewer number of violent crimes (p = .001), while positive social interactions (p = .007), and anger/hostility (p = .015) were associated with greater number of violent crimes. Implications for developing a comprehensive array of strategies that can mitigate the pattern of violence often seen in the lives of homeless female who have recently exited jails and prisons is discussed.     

Protective effect of aqueous extract of Allium sativum against zearalenone toxicity mediated by oxidative stress

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by several species of Fusarium in cereals and agricultural products. It has been implicated in several mycotoxicosis in farm animals and in humans. Several reports suggest that oxidative damage seems to be a key determinant of ZEN induced toxicity in vitro and in vivo.The aim of the current study was to evaluate the protective effects of aqueous extract of Allium sativum (AEA), against ZEN-induced cytotoxicity, reactive oxygen species (ROS) generation and DNA fragmentation in cultured Vero cells. Indeed, cytotoxicity effects were studied using MTT viability assay, ROS generation measurement and catalase activity induction. To check whether the oxidative stress induction was associated to DNA lesions, we looked for DNA fragmentation using Comet test.Our results indicated that ZEN induced several toxic effects and significant alterations mediated by oxidative stress mechanism. Treatment by ZEN combined to the lowest dose of AEA (250 μg/ml) showed a significant reduction of ZEN induced damages for all tested markers and a noticeable reduction of DNA fragmentation. It could be concluded that A. sativum aqueous extracts is effective in the protection against ZEN hazards. This could be relevant, particularly with the emergent demand for natural products which may counteract the detrimental toxic effects mediated by oxidative stress process and therefore prevents multiple human diseases.