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Environ Toxicol Chem. 2002 Jul;21(7):1456-61.
An assessment of in vitro androgenic activity and the identification of environmental androgens in United Kingdom estuaries.

Thomas KV, Hurst MR, Matthiessen P, McHugh M, Smith A, Waldock MJ.

Centre for Environment, Fisheries and Aquaculture Science, Burnham Laboratory, Burnham-on-Crouch, Essex, United Kingdom. k.v.thomaefas.co.uk

Environmental androgens are a group of compounds that to date have received very little attention. In this study, a yeast-based androgen screen (YAS) was used to determine the level of in vitro androgenic activity in seven United Kingdom estuaries. Surface water, sediment pore water, and sediment particulate material solvent extracts collected from Southampton Water, the Thames, Mersey, Tees, Tyne, Clyde, and Forth were tested for in vitro androgenic activity. Eleven of the 41 surface water samples collected displayed androgenic activity >2 ng dihydrotestosterone (DHT) equivalents/L (3-9 ng DHT/L), while eight of the 39 sediment pore waters collected showed activity >45 ng DHT/L (51-187 ng DHT/L). High levels of androgenic activity were determined in the solvent extracts of sediments, with 10 of 39 samples exhibiting a level of androgenic activity >454 ng DHT/kg (1,020-15,300 ng DHT/kg). In vitro YAS testing of five selected sewage treatment works (STW) effluents entering these estuaries showed that measurable levels (34-635 ng DHT/L) of androgenic activity were observed in those receiving only primary treatment (Howdon STW and Irvine Valley Sewer) at the time of the survey. A toxicity identification evaluation (TIE) study of Irvine Valley Sewer effluent using the YAS assay was used to identify the natural steroids/steroid metabolites dehydrotestosterone, androstenedione, androstanedione, 5beta-androstane-3alpha,11beta-diol-17-one, androsterone, and epi-androsterone as responsible for 99% of the in vitro activity determined in the effluent.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12109746&dopt=Abstract

Kidney Int. 2002 Aug;62(2):514-24.
Down-regulation of rat organic cation transporter rOCT2 by 5/6 nephrectomy.

Ji L, Masuda S, Saito H, Inui K.

Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto, Japan.

BACKGROUND: In rat kidneys, the organic ion transporters rOCT1, rOCT2, rOAT1 and rOAT3 are considered to mediate the basolateral uptake of various ionic compounds. However, their changes in chronic renal failure (CRF) are poorly understood. The present study examined the renal handling of organic ions and the expression of these transporters under CRF. METHODS: 5/6 Nephrectomized rats were used as the animal model of CRF. Renal handlings of cimetidine and paraaminohippuric acid (PAH) were examined by in vivo experiments. rOAT1, rOAT3, rOCT1 and rOCT2 expressions were determined by Western blotting. RESULTS: The tubular secretion rates of both PAH and cimetidine were markedly decreased in CRF rats. Although the distribution rates of PAH into the kidney cortex and medulla, and of cimetidine into the kidney cortex were maintained, the distribution rate of cimetidine into the kidney medulla was significantly decreased in CRF rats. The expression level of the rOCT2 protein was markedly depressed in CRF rats, but those of rOCT1, rOAT1 and rOAT3 were maintained. In addition, the plasma concentration of testosterone, a regulator of rOCT2 expression, was significantly reduced by CRF. Both the renal clearance of cimetidine and rOCT2 expression were recovered by the exogenous administration of testosterone in CRF rats. CONCLUSIONS: The levels of urinary excretion of cationic drugs, especially substrates for rOCT2, were reduced under CRF partly due to the reduced expression of rOCT2, and the lowered plasma level of testosterone was suggested to be responsible for the depressed rOCT2 expression in CRF.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12110012&dopt=Abstract

pacific.net.sg

BACKGROUND: Sildenafil citrate (Viagra), a selective inhibitor of cGMP-specific phosphodiesterase type-5, has been used as an oral therapeutic drug for erectile dysfunction. The present paper is a clinical study of the success rate and side-effects of the use of sildenafil in a multi-racial population in Singapore. METHODS: From April 1999 to May 2000, 1520 patients were given sildenafil citrate. Of these, 912 patients (mean age, 54.6 years; age range, 22-99 years) were followed up and evaluated for clinical efficacy and safety of the drug. The mean duration of erectile dysfunction (ED) and follow-up periods were 31.5 and 3.0 months, respectively. RESULTS: Satisfactory erections assessed by single global efficacy question (GEQ) occurred in 83% of patients, major side-effects in the form of flushing (3.48%), headache (1.97%), blurred vision (1.25%), giddiness (1.18%), warmth (1.11%) and others (4.92%) were recorded in 127 patients (13.9%). Racially, Chinese men with ED had higher efficacy (85.7%), compared to Indian men (74.2%) and Malay men (72.8%). With respect to comorbid profiles, an efficacy of 77.8% (n = 271), 83.9% (n = 292), 86.4% (n = 44) and 83.3% (n = 199) was recorded in diabetic, hypertensive, ischemic heart disease patients and in benign prostatic hyperplasia patients, respectively. Patients who smoked (n = 135) and drank alcohol (n = 118) showed an efficacy of 80%. Baseline hormonal profiles of luteinizing hormone, follicle stimulating hormone, testosterone and prolactin did not affect the success rates of sildenafil citrate. Many patients had earlier received other forms of treatment (medicated urethral suppository for erection (MUSE; 84.9%); vacuum devices (86.8%), traditional medicines (100%) and other oral medications (89.2%)), but this did not influence the success rate of sildenafil citrate. But patients previously treated with prostaglandin-E intracavernosal injections were less successful on sildenafil citrate (77.3%). In the total cohort, 50 mg sildenafil citrate was an effective dose in 49% of patients and 46.5% patients needed 100 mg sildenafil citrate, while 4.1% of the total cohort needed only 25 mg sildenafil citrate. CONCLUSION: Oral sildenafil citrate has been shown to be an effective, safe and well tolerated drug in Singaporean men with ED, as in men from other parts of the world.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12110094&dopt=Abstract

Int J Urol. 2002 Jun;9(6):347-53.
Stable maintenance of 5alpha-reductase activity in long-term subcultures of fibroblasts derived from the foreskin.

Nakae K, Tsuji M, Kuraoka T, Cho S, Cunha GR, Shima H.

Department of Urology, Hyogo College of Medicine, Nishinomiya, Japan.

BACKGROUND: There is up to a 50-fold variation in control subjects in current assays of 5alpha-reductase activity which makes interpretation difficult. It was therefore attempted in this study to establish an assay method which produced stable 5alpha-reductase activity in long-term subcultured foreskin fibroblasts. METHODS: Foreskin fibroblasts were obtained from three boys with phimosis (control subjects), three patients with Reifenstein syndrome and one patient with 5alpha-reductase deficiency (due to mutation L113P in exon 2 of the SRD5A2 gene). To maximize the number of cells in the DNA synthesis phase, cells were subcultured consistently to approximately 70% confluency. Thawed cells, frozen after the third subculture, were incubated for 24 h with [1beta,2beta-3H] testosterone. 5alpha-Reductase activity was expressed as the sum of formed [3H] 5alpha-reduced metabolites (separated by thin-layer chromatography). RESULTS: The full range of 5alpha-reductase activity in controls and patients with Reifenstein syndrome was 3.44-15.59 pmol/h per mg protein: a 4.53-fold variation. The activity in the patient with 5alpha- reductase deficiency was 0.52 pmol/h per mg protein. CONCLUSION: By the cell culture methods used in this study, which aimed to increase the number of cells in the DNA synthesis phase, foreskin fibroblasts maintained a considerably stable level of 5alpha-reductase activity during long-term subculture. Therefore, this assay method can be used for differential diagnosis of 5alpha-reductase deficiency from other relevant entities.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12110100&dopt=Abstract

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