A prospective randomized trial evaluating tissue effects of finasteride therapy in benign prostatic hyperplasia.

Finasteride is widely used for the treatment of benign prostatic hyperplasia (BPH). Its therapeutic efficacy is believed to be mediated through selective inhibition of prostatic 5alpha-reductase (type II). This prospective, controlled, randomized study examines various relationships between changes in tissue 5alpha-reductase isozyme activity, epithelial proliferative index and morphology in men with BPH treated with finasteride for 6 months, and correlates these with clinical response.

Expression of the transcription factor Ets-1 is an independent prognostic marker for relapse-free survival in breast cancer.

The transcription factor Ets-1 regulates the expression of several angiogenic and extracellular matrix remodeling factors, and might be implicated in disease progression of breast cancer. In the present study, the prognostic value of Ets-1 expression was assessed by quantitative real-time fluorescence RT-PCR in 123 sporadic primary breast cancer samples of patients with a median follow-up time of 62 months. Ets-1 expression levels correlated significantly with VEGF and PAI-1 in the same tissue.

Muscle uridine diphosphate-hexosamines do not decrease despite correction of hyperglycemia-induced insulin resistance in type 2 diabetes.

Animal studies suggest that overactivity of the hexosamine pathway, resulting in increased UDP-hexosamines [UDP-N-acetylglucosamine (UDP-GlcNAc) and UDP-N-acetylgalactosamine (UDP-GalNAc)] is an important mechanism by which hyperglycemia causes insulin resistance. This study was performed to test this hypothesis in patients with type 2 diabetes mellitus (DM). Eight obese patients with uncontrolled DM type 2 and severe insulin resistance were treated with iv insulin for 28 +/- 6 d aimed at euglycemia.

Dietary fatty acid composition during pregnancy and lactation in the rat programs growth and glucose metabolism in the offspring.

Aims/hypothesis: We investigated of the effects of fatty acid composition of the maternal diet on fetal and postnatal growth, morphology of the pancreas and glucose metabolism and muscle hexosamine concentrations in the adult offspring of rats.

Methods: High-fat diets enriched with either saturated or unsaturated fatty acids were fed to female adult rats 2 weeks before mating until the end of the weaning period. After weaning, the offspring was maintained on a diet with a balanced fatty acid content.

Analysis of expression of chorionic gonadotrophin transcripts in prostate cancer by quantitative Taqman and a modified molecular beacon RT-PCR.

Expression of human chorionic gonadotrophin (hCG) is associated with trophoblastic, testicular and other malignancies such as bladder, pancreatic, cervical, breast and prostate cancer. In the prostate, however, hCG expression, associated with neuroendocrine cells, is also found in normal tissue. Of the six highly homologous genes that all encode the beta-subunit of hCG, the beta 7 gene is reportedly the only gene expressed in several non-transformed tissues.

Serial plasma concentrations of atrial natriuretic peptide, plasma renin activity, aldosterone, and antidiuretic hormone in neonates on extracorporeal membrane oxygenation.

To obtain information on water and salt regulating hormones and volume homeostasis during neonatal extracorporeal membrane oxygenation (ECMO), serial determinations of atrial natriuretic peptide (ANP), plasma renin activity (PRA), aldosterone (Aldo), antidiuretic hormone (ADH), colloid-osmotic pressure (COP), osmolality (Osmol), and central venous pressure (CVP) before, during, and after neonatal ECMO in 10 neonates with meconium aspiration syndrome (MAS) were carried out. Mean gestational ages and birth weights were 41(+3) weeks (39(+6) - 42(+4)) and 4,063 gm (3,500-4700), respectively; mean age at start and duration of ECMO 29.3 (14-69) and 152.

Reduced adrenal response and increased mortality after systemic Klebsiella pneumoniae infection in interleukin-6-deficient mice.

During bacterial infections, both the immune system and the hypothalamus-pituitary-adrenal (HPA) axis are activated. The role of IL-6 in the activation of the HPA axis during bacterial sepsis is not fully understood. The aim of the present study was to investigate the role of endogenous IL-6 in a potentially lethal infection with Klebsiella pneumoniae and the concomitant activation of the HPA axis.

Reduced adrenal response to bacterial lipopolysaccharide in interleukin-6-deficient mice.

Administration of bacterial lipopolysaccharide (LPS) in rodents induces the release of pro-inflammatory cytokines [tumor necrosis factor (TNF), interleukin (IL)-1, IL-6] and of ACTH and corticosterone. IL-6 is probably an important cytokine in the interaction between the immune system and the hypothalamus-pituitary-adrenal (HPA) axis, but so far the role of IL-6 in lipopolysaccharide (LPS)-induced HPA activation has not been established unequivocally. We examined the effects of intraperitoneal administration of LPS (range 0.

Implications of progesterone metabolism in MA-10 cells for accurate measurement of the rate of steroidogenesis.

In virtually all studies with MA-10 cells, progesterone RIAs have been used to measure steroid synthesis. To test whether progesterone is a stable end product, we investigated the metabolism of added tritiated progesterone and pregnenolone in MA-10 cells over a period of 3 h. Steroids were then extracted, separated by HPLC, and identified by GC/MS.

Short-term glucosamine infusion does not affect insulin sensitivity in humans.

Overactivity of the hexosamine biosynthetic pathway may underlie hyperglycemia-associated insulin resistance, but to date human studies are lacking. Hexosamine pathway activation can be mimicked by glucosamine (GlcN). In the present placebo-controlled study we determined whether GlcN infusion affects insulin resistance in vivo.

Elevated serum endothelin-1 levels in patients with colorectal cancer; relevance for prognosis.

Background: It has been demonstrated that the Doppler Perfusion Index (DPI) is increased in patients who are at risk of developing liver metastases from colorectal cancer. It has been postulated that a circulating hormonal factor is involved in the relative vasoconstriction throughout the splanchnic bed. Endothelin-1 (ET-1), a potent vasoconstrictor which has been associated with tumor growth and is produced by colorectal tumors, may play an important role in this phenomenon.

Partial sequencing and tissue distribution of the canine isoforms of steroid 5alpha-reductase type I and type II.

Background: The dog is regarded to be a valid model to test the effects of 5alpha-reductase inhibitors on prostatic growth. However, limited information is available on the characteristics or even existence of 5alpha-reductase isozymes in this species.

Methods: Here, we set out to clone the cDNA of the dog isoforms of 5alpha-reductase type I and type II by a degenerate cloning strategy and to assess the tissue distribution of both transcripts and the enzymatic activity of the isozymes.

EORTC Receptor and Biomarker Study Group Report: a sandwich enzyme-linked immunosorbent assay for vascular endothelial growth factor in blood and tumor tissue extracts.

A four-antibody sandwich enzyme-linked immunosorbent assay (ELISA) for vascular endothelial growth factor (VEGF) for application in blood (serum and plasma) and tumor tissue extracts was set up within the framework of the EORTC Receptor and Biomarker Study Group (RBSG). Polyclonal antibodies against VEGF165 were raised in chickens and rabbits, and used in a previously described assay format. The assay was validated and characterized for use in serum, plasma and tumor tissue extracts.

EORTC receptor and biomarker study group report analytical and technical evaluation of a thymidine kinase radio-enzymatic assay in breast cancer cytosols.

Background: High thymidine kinase (TK) activity in cancer cells could counteract adjuvant chemotherapy directed at the inhibition of de novo DNA synthesis. TK is an independent prognostic factor in breast cancer patients receiving adjuvant chemotherapy.

Material And Methods: In this paper, we describe the effects of extraction and dilution buffer composition on TK enzymatic activity values obtained in breast cancer cytosols with the Prolifigen serum TK-REA kit (Sangtec Medical, Sweden).

Selectivity of finasteride as an in vivo inhibitor of 5alpha-reductase isozyme enzymatic activity in the human prostate.

The type II 5alpha-reductase inhibitor finasteride is used in the treatment of benign prostatic hyperplasia (BPH), reducing local production of the growth promoting androgen dihydrotestosterone (DHT). The effect of prolonged treatment with this time-dependent irreversible inhibitor on the recently described prostatic type I 5alpha-reductase, however, is not clear. Therefore, we assessed the effects of 5 mg.

Identification and partial characterization of two steroid 5 alpha-reductase isozymes in the canine prostate.

Background: The dog has been extensively used as an in vivo model to test the pharmacokinetics and effects on pathological prostatic growth of 5 alpha-reductase inhibitors. However, no information is available on the existence or characteristics of canine 5 alpha-reductase isozymes.

Methods: The 5 alpha-reduction of testosterone is analyzed in dog prostatic homogenates.

3 Alpha-hydroxysteroid oxidoreductase activities in dihydrotestosterone degradation and back-formation in rat prostate and epididymis.

The metabolism of dihydrotestosterone (DHT) and 5 alpha-androstane-3 alpha, 17 beta-diol (3 alpha-Adiol) was assessed in full homogenates of rat prostate and epididymis. The major degradational route of DHT was catalysed by the enzyme(s) 3 alpha-hydroxysteroid oxidoreductase (HSOR). Enzyme kinetic characteristics Vmax, Km and Vmax/Km ratio, were obtained for the NADP(H)- and NAD(H)-dependent interconversion of DHT and 3 alpha-Adiol at pH 7.

Differential subcellular distribution of rat prostatic steroid 5alpha-reductase isozyme activities.

The rat prostate, a classical androgen-target tissue, contains both known isozymes of steroid 5alpha-reductase. i.e.

Kinetic analysis of rat steroid 5alpha-reductase activity in prostate and epididymis homogenates at neutral pH: evidence for type I activity in epididymis.

Immunocytochemical studies and mRNA measurements have shown that the rat epididymis--like the rat prostate--expresses both rat steroid 5alpha-reductase isozymes, i.e. type I and II.

Kinetic analysis of steroid 5alpha-reductase activity at neutral pH in benign prostatic hyperplastic tissue: evidence for type I isozyme activity in the human prostate.

In human benign prostatic hyperplastic (BPH) tissue homogenates 5alpha-reduction of testosterone was examined at neutral pH. As Lineweaver-Burk and Eadie-Scatchard plots of estimated initial velocities against a wide range of substrate concentrations of 2 nM to 3.2 microM were non-linear, the existence of two 5alpha-reductase isozymes in this tissue was surmised.

Rat steroid 5 alpha-reductase kinetic characteristics: extreme pH-dependency of the type II isozyme in prostate and epididymis homogenates.

Reevaluating the assay for rat steroid 5 alpha-reductase isozymes in prostate and epididymis homogenates we encountered an extreme pH-dependency of the type II isozyme. The time-course of the metabolism of testosterone (T) to 17 beta-hydroxy-5 alpha-androstan-3-one (DHT) at acidic pH shows an initial burst when the homogenate is not brought to pH before the start of the incubation. Therefore, the rat type II 5 alpha-reductase isozyme does not follow Michaelian law under these conditions making a single time point measurement invalid.

Virus-induced airway hyperresponsiveness in the guinea-pig: possible involvement of histamine and inflammatory cells.

1. Guinea-pig tracheal contractions by histamine and by the cholinoceptor agonist, arecoline, are significantly enhanced (30% and 20%, respectively), 96 h after intra-tracheal inoculation with Parainfluenza-3 (PI-3) virus. 2.