The effect of finasteride on the expression of vascular endothelial growth factor and microvessel density: a possible mechanism for decreased prostatic bleeding in treated patients

PURPOSE: Several studies have confirmed the benefit of finasteride in limiting hematuria from benign prostatic hyperplasia. Vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis, and microvessel density have been independently evaluated in the mechanism of decreased bleeding observed in patients treated with finasteride. We evaluated the expression of VEGF and suburethral prostatic microvessel density in patients with benign prostatic hyperplasia treated with finasteride. MATERIALS AND METHODS: The study included 24 patients undergoing prostatic surgery for benign disease, of whom 12 were given finasteride for a minimum of 6 weeks before surgery and the remaining 12 served as controls. Sections from the prostatic urothelium and hyperplastic prostate were individually stained for CD34 specific for nascent blood vessels and VEGF. Analysis of each specimen was performed in a blinded fashion. Microvessel density was calculated by counting the number of positively stained blood vessels on 10 consecutive, nonoverlapping, high power fields within the suburethral and hyperplastic prostate compartments. VEGF expression was examined by immunohistochemistry. Statistical analysis of the results was performed using Student's t test. RESULTS: Prostatic suburethral VEGF expression and microvessel density were significantly lower in the finasteride group compared to controls (p <0.05). Differences in VEGF expression and microvessel density at the level of the hyperplastic prostate were not found to be significantly different between the 2 groups.CONCLUSIONS Decreased expression of VEGF by finasteride inhibits angiogenesis and significantly decreases microvessel density in prostatic suburethral tissue. This sequential relationship provides histochemical insight into the mechanism by which finasteride reduces prostatic urethral bleeding.     

Acute toxicity studies of Croton membranaceus root extract

Aim of the study

Croton membranaceus root and leaf extracts are used in the Bahamas to aromatize tobacco, in Nigeria to improve digestion, and in Ghana, for benign prostate hyperplasia. Despite claims of success there is paucity of information on its toxicity. The aim of this study was to determine if Croton membranaceus has acute toxicity properties.

Materials and methods

Roots were air-dried in a solar dryer for one week before milling. The powder was extracted with 96% ethanol, freeze-dried and re-extracted with distilled water and freeze-dried. 15 male Sprague-Dawley rats (180-200 g) were divided equally into 2 treatment groups [low dose (LD) and high dose (HD)], plus a control group (C). LD and HD received 1500 and 3000 mg/kg b.wt. Croton membranaceus aqueous extract, respectively, one time and observed for 14 days. Haematological [Full Blood Count and haemoglobin (Hb)], biochemical [bilirubin, alanine aminotransferase (ALA), aspartate aminotransferase (AST), total protein, albumin, globulin, alkaline phosphatise (ALP), γ-glutamyltranspetidase (GGT), urea, creatinine, creatinine kinase - Muscle and Brain (CK-MB), creatinine kinase - Total (CK-R)] examinations were performed.

Results

Control group's CK-MB (5444 ± 534 U/L) and LD group CK-MB (4014 ± 1016 U/L) were significantly different (p < 0.05). Control and the HD group CK-MB (3955 ± 1135 U/L) were significantly different (p < 0.05). Both LD and HD CK-R levels (697 ± 197 U/L and 732 ± 203 U/L, respectively), were lower than the control (1139 ± 220 U/L) at 48 h and 14 days (p < 0.05, p < 0.05, respectively). γ-GT levels of the HD group was 4.8 ± 0.4 U/L compared to the Control group value of 0.9 ± 0.2 U/L (p < 0.05).

Conclusions

Taking all factors into consideration, Croton membranaceus ingestion does not produce general acute toxicity. However, its creatinine kinase lowering ability could be explored.     

Robust multi-tissue gene panel for cancer detection

Background  

We have identified a set of genes whose relative mRNA expression levels in various solid tumors can be used to robustly distinguish cancer from matching normal tissue. Our current feature set consists of 113 gene probes for 104 unique genes, originally identified as differentially expressed in solid primary tumors in microarray data on Affymetrix HG-U133A platform in five tissue types: breast, colon, lung, prostate and ovary. For each dataset, we first identified a set of genes significantly differentially expressed in tumor vs. normal tissue at p-value = 0.05 using an experimentally derived error model. Our common cancer gene panel is the intersection of these sets of significantly dysregulated genes and can distinguish tumors from normal tissue on all these five tissue types.     

Comparative toxicities of 3 platinum‐containing chemotherapy regimens in relapsed/refractory lymphoma patients

Optimal salvage chemotherapy regimen for patients with relapsed or refractory Hodgkin and non‐Hodgkin lymphoma remains unclear but often based on platinum regimens. This retrospective study assesses in real life the toxicities profiles of patients with relapsed or refractory lymphoma treated with DHA (dexamethasone, high dose aracytine cytarabine) plus platinum salt (dexamethasone‐High dose aracytine (cis)platin (DHAP), dexamethasone‐High dose aracytine carboplatin (DHAC), or dexamethasone‐High dose aracytine Oxaliplatin (DHAOX)), from February 2007 to May 2013 in 2 French hospitals. Toxicities were recorded from medical files and assessed according to the National Cancer Institute Common Toxicity Criteria version 3.0. Potential risk factors of renal insufficiency were tested by univariate analyses. A total of 276 patients were treated: 168 with DHAP (60.9%), 79 with DHAOX (28.6%), and 29 with DHAC (10.5%). Rituximab was associated in 80.1% of patients (n = 221). Renal failure was reported in 97 patients, mainly with cisplatin regimen (86.6%) leading to 8.9% grade III to IV renal failure (P = .001). Renal insufficiency was reversible in most patients but remained persistent in 24, with all of them being treated with DHAP except 1. Cisplatin‐based regimen (50.0% versus 12.0%, P < .05) and female (44.6% versus 29.7%, P < .05) appeared to be at higher risks of renal failure. Platinum cumulative dose is a significant risk factor of nephrotoxicity. Hematologic toxicity was more frequent with carboplatin and cisplatin with at least 1 event (all toxicity grade) respectively in 79.3% and 71.4% of patients treated (P < .005). Auditory toxicity was mainly reported with cisplatin (n = 19; 4 grade I‐II and 15 grade III‐IV). Oxaliplatin was implicated in 77.6% of neurotoxicity (n = 59), mainly moderate (grade I‐II). In conclusion, DHAOX and DHAC regimens have more favorable toxicity profile than DHAP regimen. Their lack of renal toxicity makes them attractive regimens, which may be interesting for patients eligible for autologous stem cell transplantation. Nevertheless, these results have to be confirmed by the therapeutic efficacy of these 3 regimens.     

Vitamin A supplements are well tolerated with the pentavalent vaccine

The Expanded Programme on Immunisation provides an opportunity to deliver vitamin A supplements to young infants in order to improve their vitamin A status. However, concerns have been raised about the safety of administering high dose vitamin A supplements to infants less than 6 months of age in developing countries. A randomized controlled trial was carried out by the Kintampo Health Research Centre to assess the safety and immunogenicity of administering 15 mg retinol equivalent (RE)1 vitamin A alongside the pentavalent "diphtheria-polio-tetanus-Haemophilus influenzae b-hepatitis B vaccine" at 6, 10 and 14 weeks of age. All mothers received a post-partum supplement of 120 mg RE vitamin A as per national policy. Mothers of infants who had been vaccinated were visited 24 h after vaccination to assess the side effects of the vaccine. They were also interviewed about adverse events which may have occurred in the past 4 weeks since the child was vaccinated. There were significantly fewer reports of illnesses and fever in infants who had been given vitamin A compared to infants in the control group. The pentavalent vaccine was found to be tolerable when administered with vitamin A according to the WHO/EPI schedule for infant immunisation at 6, 10 and 14 weeks. There were few complaints made by the mothers of the children which were not thought to be related to giving vitamin A with the vaccines. There were six deaths in the trial, five in the intervention group and one in the control RR 4.65 (0.55-39.5), p = 0.12. Due to the high point estimate of 4.65, we wish to urge caution in administering high doses of vitamin A to young infants with the pentavalent vaccine at 6, 10 and 14 weeks of age.     

Interleukin-12 is necessary for the priming of CD4+ T cells required during the elicitation of HIV-1 gp120-specific cytotoxic T-lymphocyte function

The mechanism of the T-cell response and cytokine induction to restrict human immunodeficiency virus 1 (HIV-1) infection is not clear. During early infection, HIV-infected individuals have a high frequency of virus-specific cytotoxic T lymphocytes (CTLs) that effectively reduces the viral load. However, the CTLs are unable to clear the virus at later stages of infection, leading to disease progression. Dysregulation of cytokines like interleukin-12 (IL-12) and interferon-gamma (IFN-gamma) as a result of the interaction of HIV-1-specific T cells with antigen-presenting cells is one of the possible causes of CTL dysfunction. Secretion of IL-12 is reduced with the progression of HIV infection, correlating with impaired CTL function; however, the role of IL-12 in CTL regulation awaits elucidation. Here, we have studied the role of IL-12 in CTL dysfunction by using DNA immunization of wild-type (WT) and IL-12-deficient mice with HIV-1 gp120 complementary DNA. It was observed that the CTL response in IL-12-deficient mice was significantly less than that in WT mice. Our results further demonstrated that coimmunization with IL-12 vector restored the impaired CTL response in IL-12-deficient mice. However, immunization with IL-12 vector failed to rescue the CTL response in IFN-gamma deficient mice, suggesting that the CTL-promoting function of IL-12 is IFN-gamma-mediated. Our data suggest a phase-specific role of IL-12 in the CTL response, specifically in the priming of CD4+ T cells that provide help to CD8+ T cells. Our results also suggest that IL-12 is vital for the priming of antigen-specific T cells and plays an essential role in IFN-gamma induction in T cells.     

Prevalence and type of cerebral palsy in a British ethnic community: the role of consanguinity

Little is known about the prevalence of cerebral palsy (CP) within ethnic subgroups born in Britain. The Yorkshire Regional Cerebral Palsy Register has ascertained all cases of CP in children born within the Regional Health Authority boundary in 1985 to 1987 inclusive and diagnosed by 5 years of age. Birth registrations recorded by ethnic subgroups allowed us to determine the prevalence of CP within the Bradford District Health Authority (BDHA) boundaries by Asian and non-Asian ethnic subgroups. All the children with CP in BDHA were examined by one individual and careful family pedigrees recorded. We noted that BDHA had a high prevalence of CP; 3.87 to 4.16 per 1000. The prevalences in the non-Asian and Asian populations were 3.18, and between 5.48 and 6.42, per 1000, respectively. This difference was statistically significant (P=0.03). First cousin marriages occurred in 15 of the 39 Asian famines (51.7%) and nine of these families had another first or second degree family member with a similar type of CP to the index child. There was no consanguinity in the non-Asian families. These data highlight the increased need for services in some ethnic populations living in Britain and the likely genetic aetiology of a significant proportion of cases of CP in Asian families.     

Influence of the Fusogenic Agent Polyethylene Glycol on Attachment of Mycoplasma pneumoniae to Other Cells

The effect of fusogenic agents on the interaction of Mycoplasma pneumoniae with human lung fibroblasts was evaluated. A 60-s exposure of the fibroblasts to polyethylene glycol (molecular weight 200; 10%) significantly increased attachment of mycoplasmas to the fibroblasts.