The temporal burden of preparing catheters for re-use in adults with spinal cord injury: a cross-sectional study.

STUDY DESIGN: Cross-sectional OBJECTIVES: Neurogenic lower urinary tract dysfunction is common among people with spinal cord injury (SCI). Although single-use clean intermittent catheterization is recommended to facilitate routine bladder emptying, catheter re-use is common. Barriers associated with the preparation (i.e., cleaning) of catheters for re-use are unknown. This study examined barriers to catheter re-use in adult individuals with SCI by assessing (1) the time needed to clean a catheter, and (2) the perceived difficulty of the catheter cleaning routine. SETTING: Laboratory METHODS: Twenty individuals with chronic SCI ( ≥ 1 year since injury; Group 1 = 10 with tetraplegia; Group 2 = 10 with paraplegia) completed the study. Using a standardized cleaning procedure (i.e., Milton method), catheter cleaning was timed for each participant. Perceived difficulty was assessed using a 5-point Likert scale. Functional impairment was assessed with the Upper Extremity Motor Score (UEMS). RESULTS: Significant between-group differences were observed for total cleaning time (Group 1 = 1584.1 ± 179.8 s; Group 2 = 1321.0 ± 93.8 s, p = 0.004) and perceived difficulty [Group 1 = 2.6 (2, 3); Group 2 = 2 (1.7, 2.3), p = 0.028]. Total cleaning time was significantly correlated with UEMS (ρ = -0.709, p ≤ 0.001) and perceived difficulty (ρ = 0.468, p = 0.037). UEMS emerged as an independent predictor of total cleaning time (R2 = 0.745, ß = -0.833, p ≤ 0.001). CONCLUSIONS: Preparing catheters for re-use is time-intensive and difficult for people with higher SCI level, severity and more pronounced upper limb motor impairment, which was independently associated with total cleaning time. Performing this routine on a consistent basis would require a substantial time commitment and would have a profoundly negative impact on overall quality of life.

Livelihood benefits and costs from an invasive alien tree (Acacia dealbata) to rural communities in the Eastern Cape, South Africa.

The negative effects of invasive alien species (IAS) are increasingly invoked to justify widespread and usually top-down approaches for their management or eradication. However, very little of the research or discourse is based on investigating local perceptions, uses and struggles with IAS, and how their presence influences and changes local livelihoods. The objective of this study was to assess the perceptions and livelihood uses of Acacia dealbata by local communities at three localities in the montane grasslands of the Eastern Cape, South Africa, using a combination of random household interviews, focus group discussions and participatory tools. We calculated direct-use values for each product and household (based on quantity used and local prices) and disaggregated these by gender of the household head and wealth quartiles. The results revealed the dualistic role of A. dealbata in local livelihoods. On the one hand, A. dealbata was widely used for firewood (100% of households), tools (77%) and construction timber (73%), with limited use for traditional medicines and forage. The cumulative value of approximately ZAR 2870 (±US$224) per household per year (across all households) represents considerable cash saving to households, most of whom are quite poor by national and international measures. On the other hand, the increasing extent of A. dealbata (93% said it was increasing) exacerbates local household vulnerability though reported reductions in cultivated areas, crop yields and forage production, and allegedly higher risks of crime. This quandary is well encapsulated by the considerable majority of respondents (84%) not wanting higher extents and densities of A. dealbata, but an equally high majority not wanting its total removal from local landscapes. Most respondents disliked A. dealbata in fields, close to homesteads or along primary access routes, and were more tolerant of it away from such sites. Institutional and use dynamics have varied over several decades in response to the changing extent and densities of A. dealbata and the broader political and socio-economic contexts. These results indicate that greater efforts are required to understand perceptions and uses of IAS by the people who live with them, and to direct such understanding into more spatially and temporally contextualised response strategies where required.

Effect of omega-3 fatty acids supplementation during pregnancy on lung function in preschoolers: a clinical trial.

RATIONALE: Prenatal omega-3 fatty acids improve alveolarization, diminish inflammation, and improve pulmonary growth, but it is unclear whether these outcomes translate into improved postnatal lung function. OBJECTIVE: We assessed the effect of prenatal supplementation with docosahexaenoic acid (DHA) on offspring lung function through 60 months of age. METHODS: We included a cohort of 772 Mexican preschoolers whose mothers participated in a clinical trial (NCT00646360) of supplementation with DHA or a placebo from week 18-22 of gestation through delivery. MEASUREMENTS: The children were followed after birth and anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. The effect of DHA was tested using a longitudinal mixed effect models. RESULTS: Overall, mean (Standard Deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during follow up period were 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and -5.2 (1.6), -4.8 (1.7), -4.6 (1.6), respectively. There were no significant differences in pulmonary function by treatment group. DHA did not affect the average lung function or the trajectories through 60 months. CONCLUSIONS: Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.

Local wood demand, land cover change and the state of Albany Thicket on an urban commonage in the Eastern Cape, South Africa.

Understanding the rates and causes of land-use change is crucial in identifying solutions, especially in sensitive landscapes and ecosystems, as well as in places undergoing rapid political, socioeconomic or ecological change. Despite considerable concern at the rate of transformation and degradation of the biodiversity-rich Albany Thicket biome in South Africa, most knowledge is gleaned from private commercial lands and state conservation areas. In comparison, there is limited work in communal areas where land uses include biomass extraction, especially for firewood and construction timber. We used aerial photographs to analyze land use and cover change in the high- and low-use zones of an urban commonage and an adjacent protected area over almost six decades, which included a major political transition. Field sampling was undertaken to characterize the current state of the vegetation and soils of the commonage and protected area and to determine the supply and demand for firewood and construction timber. Between the 1950s and 1980s, there was a clear increase in woody vegetation cover, which was reversed after the political transition in the mid-1990s. However, current woody plant standing stocks and sustainable annual production rates are well above current firewood demand, suggesting other probable causes for the decline in woody plant cover. The fragmentation of woody plant cover is paralleled by increases in grassy areas and bare ground, an increase in soil compaction, and decreases in soil moisture, carbon, and nutrients.

Feasibility of parental collected nasal swabs for virus detection in young children with cystic fibrosis.

BACKGROUND: The detrimental role of viruses has been well described in CF, although the pattern of virus infections has not been investigated in a longitudinal study. The primary aim was to determine the feasibility of fortnightly parent collected swabs in young children with CF. METHODS: Children under three years with CF were recruited. Nasal swabs were collected by parents every fortnight and during periods of symptoms over 12 months. Nasal swabs were posted and virus detected using real-time PCR. RESULTS: Only 27% of the patients completed the study to 10 months, although 98% of the swabs returned were adequate for analysis. Mould was observed growing on 23% of the returned swabs. There was no evidence to demonstrate relationships with symptoms and viruses, prolonged symptoms, prolonged shedding or patterns of virus infections. CONCLUSIONS: This study highlights the need to further investigate the role of viruses in children with CF using a robust method of frequent collection in children for a longitudinal study, with appropriate storage and shipping techniques to avoid mould growth or other potential contaminants.

Food security in a perfect storm: using the ecosystem services framework to increase understanding.

Achieving food security in a 'perfect storm' scenario is a grand challenge for society. Climate change and an expanding global population act in concert to make global food security even more complex and demanding. As achieving food security and the millennium development goal (MDG) to eradicate hunger influences the attainment of other MDGs, it is imperative that we offer solutions which are complementary and do not oppose one another. Sustainable intensification of agriculture has been proposed as a way to address hunger while also minimizing further environmental impact. However, the desire to raise productivity and yields has historically led to a degraded environment, reduced biodiversity and a reduction in ecosystem services (ES), with the greatest impacts affecting the poor. This paper proposes that the ES framework coupled with a policy response framework, for example Driver-Pressure-State-Impact-Response (DPSIR), can allow food security to be delivered alongside healthy ecosystems, which provide many other valuable services to humankind. Too often, agro-ecosystems have been considered as separate from other natural ecosystems and insufficient attention has been paid to the way in which services can flow to and from the agro-ecosystem to surrounding ecosystems. Highlighting recent research in a large multi-disciplinary project (ASSETS), we illustrate the ES approach to food security using a case study from the Zomba district of Malawi.

Novel H6PDH mutations in two girls with premature adrenarche: 'apparent' and 'true' CRD can be differentiated by urinary steroid profiling.

CONTEXT: Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase (H6PDH, encoded by H6PD) cause apparent cortisone reductase deficiency (ACRD). H6PDH generates cofactor NADPH for 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1, encoded by HSD11B1) oxo-reductase activity, converting cortisone to cortisol. Inactivating mutations in HSD11B1 cause true cortisone reductase deficiency (CRD). Both ACRD and CRD present with hypothalamic-pituitary-adrenal (HPA) axis activation and adrenal hyperandrogenism. OBJECTIVE: To describe the clinical, biochemical and molecular characteristics of two additional female children with ACRD and to illustrate the diagnostic value of urinary steroid profiling in identifying and differentiating a total of six ACRD and four CRD cases. DESIGN: Clinical, biochemical and genetic assessment of two female patients presenting during childhood. In addition, results of urinary steroid profiling in a total of ten ACRD/CRD patients were compared to identify distinguishing characteristics. RESULTS: Case 1 was compound heterozygous for R109AfsX3 and a novel P146L missense mutation in H6PD. Case 2 was compound heterozygous for novel nonsense mutations Q325X and Y446X in H6PD. Mutant expression studies confirmed loss of H6PDH activity in both cases. Urinary steroid metabolite profiling by gas chromatography/mass spectrometry suggested ACRD in both cases. In addition, we were able to establish a steroid metabolite signature differentiating ACRD and CRD, providing a basis for genetic diagnosis and future individualised management. CONCLUSIONS: Steroid profile analysis of a 24-h urine collection provides a diagnostic method for discriminating between ACRD and CRD. This will provide a useful tool in stratifying unresolved adrenal hyperandrogenism in children with premature adrenarche and adult females with polycystic ovary syndrome (PCOS).

Use and users of municipal commonage around three small towns in the Eastern Cape, South Africa.

Municipal commonages surround many small towns throughout South Africa, and are an integral component of the national land reform programme. But little is known about their extent, use or value, and most appear to have limited or no management or investment. This paper reports on a survey of randomly selected households in three small towns in the Eastern Cape to ascertain the extent and purpose of use of municipal commonages. Between 27% and 70% of urban households used commonage depending on site. Key resources used were fuelwood, medicinal plants, and grazing of livestock. Typically, commonage using households were poorer and less educated than other urban residents, although the profile of users is unique for each town. Given the extensive use of commonage resources, and their contribution to the livelihoods of the poor, local municipalities need to develop and implement sound management strategies that account for all users of commonages, rather than the oft encountered focus on livestock owners and production.

The corticosteroid metabolic profile of the mouse.

Data are presented on the urinary corticosteroid metabolic profile of the mouse strain 129/svJ. Through the use of GC/MS we have characterized, or tentatively identified corticosterone (Kendall's compound B) metabolites of both the 11beta-hydroxy and 11-carbonyl (compound A) series in urine. Full mass spectra of the methyloxime-trimethylether derivatives of 15 metabolites are included in the paper as an aid to other researchers in the field. Metabolites ranged in polarity from tetrahydrocorticosterone (THB) to dihydroxy-corticosterone with dominance of highly polar steroids. We found that prior to excretion corticosterone can undergo oxidation at position 11beta, reduction at position 20 and A-ring reduction. Metabolites retaining the 3-oxo-4-ene structure can be hydroxylated at position 6beta- as well as at an unidentified position, probably 16alpha-. Saturated steroids can be hydroxylated at positions 1beta-, 6alpha-, 15alpha- and 16alpha. A pair of hydroxy-20-dihydro-corticosterone metabolites (OH-DHB) were the most important excretory products accounting for about 40% of the total. One metabolite of this type was identified as 6beta-hydroxy-DHB; the other, of similar quantitative importance was probably 16alpha-hydroxy-DHB. The ratio of metabolites of corticosterone (B) to those of 11-dehydro-corticosterone (A) was greater than 9:1, considerably higher than that for the equivalent "human" ratio of 1:1 for cortisol to cortisone metabolites. Results from this study allowed the evaluation of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) activity in mice with deleted glucose-6-phosphate transporter (G6PT). These mice had attenuated back-conversion of A to B resulting in an increased ratio of A-metabolites to B-metabolites [Walker EA, Ahmed A, Lavery GG, Tomlinson JW, Kim SY, Cooper MS, Stewart PM, 11beta-Hydroxysteroid dehydrogenase type 1 regulation by intracellular glucose-6-phosphate, provides evidence for a novel link between glucose metabolism and HPA axis function. J Biol Chem 2007;282:27030-6]. We believe this study is currently the most comprehensive on the urinary steroid metabolic profile of the mouse. Quantitatively less steroid is excreted in urine than in feces by this species but urine analysis is more straightforward and the hepatic metabolites are less subject to microbial degradation than if feces was analyzed.

Changes in fuelwood use and selection following electrification in the Bushbuckridge lowveld, South Africa.

Fuelwood is the primary energy source for domestic purposes throughout the developing world, in both urban and rural environments. Due to the detrimental impacts of biomass use on human and environmental health, many governments have sought to reduce its use through provision of potentially cleaner energies, of which electricity is the dominant form. Yet there are surprisingly few studies of changes in fuelwood use following the introduction of electricity, especially in rural areas of Africa. This paper reports on a longitudinal study of fuelwood use, using identical approaches, in five rural villages in the Bushbuckridge region of South Africa, spanning the period over which electricity became widely available. Almost a decade after the introduction of electricity, over 90% of households still used fuelwood for thermal purposes, especially cooking, and the mean household consumption rates over the 11-year period had not changed, even with a policy of 6 kWh per month of free electricity. The proportion of households purchasing fuelwood had increased, probably in response to a number of factors, including (i) increased fuelwood scarcity in the local environment as reflected by increased fuelwood collection times, changes in fuelwood species preferences, and ranking of scarcity by local collectors, and (ii) increases in the price of fuelwood well below that of other fuels and the prevailing inflation rate. Overall, there was an increase in the number of species harvested over the 11-year period. The implications of these findings for rural energy provision are discussed.

Linking Antley-Bixler syndrome and congenital adrenal hyperplasia: a novel case of P450 oxidoreductase deficiency.

The Antley-Bixler syndrome (ABS) is a multiple congenital malformation syndrome with craniosynostosis, radiohumeral synostosis, femoral bowing, choanal atresia or stenosis, joint contractures, urogenital abnormalities and, often, early death. Autosomal recessive and dominant inheritance have been postulated, as has fluconazole teratogenesis. Mutations in POR (P450 (cytochrome) oxidoreductase, an essential electron donor to enzymes participating in cholesterol biosynthesis), have been identified in some patients with the ABS phenotype. Recent evidence suggests that these mutations cause attenuated steroid hydroxylation, which in turn, causes congenital adrenal hyperplasia (CAH) with ambiguous genitalia in both sexes and glucocorticoid deficiency. Here, we report on a new patient with findings of both ABS and CAH that further illustrates how low maternal estriol at prenatal screening can serve as a marker steroid facilitating early diagnosis.

Living donor liver transplantation: histological abnormalities found on liver biopsies of apparently healthy potential donors.

OBJECTIVE: With the continued shortage of deceased donor grafts, living donor liver transplantation has become an option for adult liver transplant candidates. In the non-transplant setting, liver biopsy is typically carried out to evaluate clinical or biochemical hepatic dysfunction. In living donor liver transplantation, assessment of histological abnormalities that are undetectable by serological, biochemical and radiological methods might play an important role in donor and recipient outcome. METHODS: Seventy consecutive liver biopsies carried out as part of our evaluation of potential donor candidates for adult-to-adult or adult-to-child living donor liver transplants were analyzed. RESULTS: Of the 70 potential donor candidates who underwent liver biopsy for evaluation for living donor liver transplantation, 67% had an unexpected abnormality, of which steatosis was the most common abnormality (38.5%). A variety of other histopathological abnormalities were found including granulomas of unknown etiology (7%), chronic hepatitis (6%) and a microabscess. None of the histological abnormalities had been suspected despite extensive clinical, serological or radiological investigation. CONCLUSIONS: Among the 70 potential donor candidates for living donor liver transplantation, 34% had unremarkable liver biopsies. The most common abnormality was steatosis (38.5%). These findings suggest that all potential candidates for living donor liver transplants should undergo screening liver biopsies. The precise significance of these changes remains to be determined, including which of these changes are contraindications to liver transplantation. These findings may also have implications in the non-transplant setting as changes ascribed to specific etiologies for liver disease might include changes occurring in apparently healthy individuals.

11beta-hydroxysteroid dehydrogenase type 1 activity in lean and obese males with type 2 diabetes mellitus.

Glucocorticoids play an important role in the pathogenesis of obesity and insulin resistance. Impaired conversion of cortisone (E) to cortisol (F) by the type 1 isoenzyme of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) in obesity may represent a protective mechanism preventing ongoing weight gain and glucose intolerance. We have studied glucocorticoid metabolism in 33 male subjects with type 2 diabetes mellitus [age, 44.2 +/- 13 yr; body mass index (BMI), 31.1 +/- 7.5 kg/m(2) (mean +/- sd)] and 38 normal controls (age, 41.4 +/- 14 yr; BMI, 38.2 +/- 12.8 kg/m(2)). Circulating F:E ratios were elevated in the diabetic group and correlated with serum cholesterol and homeostasis model assessment-S. There was no difference in 11beta-HSD1 activity between diabetic subjects and controls. In addition, 11beta-HSD1 activity was unaffected by BMI in diabetic subjects. However, in control subjects, increasing BMI was associated with a reduction in the urinary tetrahydrocortisol+5alpha-tetrahydrocortisol:tetrahydrocortisone ratio (P < 0.05) indicative of impaired 11beta-HSD1 activity. The degree of inhibition correlated tightly with visceral fat mass. Changes in 11beta-HSD1 activity could not be explained by circulating levels of adipocytokines. Impaired E to F metabolism in obesity may help preserve insulin sensitivity and prevent diabetes mellitus. Failure to down-regulate 11beta-HSD1 activity in patients with diabetes may potentiate dyslipidemia, insulin resistance, and obesity. Inhibition of 11beta-HSD1 may therefore represent a therapeutic strategy in patients with type 2 diabetes mellitus and obesity.

Sirolimus-induced hyperlipidaemia in liver transplant recipients is not dose-dependent.

BACKGROUND: Sirolimus is a potent immunosuppressive medication that acts by inhibiting T-cell proliferation. It has been used in kidney transplantation because of its lack of nephrotoxicity. It is now being investigated in liver transplantation, but there are concerns about safety and long-term side effects such as dyslipidaemia. Hypertriglyceridaemia is a common adverse event seen with sirolimus use, and often does not respond to dose reduction or anti-lipemic drugs. METHOD: We report six patients who have developed significant hyperlipidaemia while receiving sirolimus, in spite of therapeutic trough levels. CONCLUSION: All six patients showed either resolution or improvement in lipid levels with discontinuation of sirolimus.

Paralogues of porcine aromatase cytochrome P450: a novel hydroxylase activity is associated with the survival of a duplicated gene.

The gonadal and placental paralogues of porcine aromatase cytochrome P450 (P450arom) were examined for novel catalytic properties to shed light on the evolutionary survival of duplicated copies of an enzyme critical to reproduction. Recombinant gonadal P450arom catalyzed the formation of a novel metabolite from testosterone, identified by gas chromatography/mass spectrometry and biochemical analyses as 1 beta-hydroxytestosterone (1 beta OH-T), in almost equal proportion to 17beta-estradiol (E(2)). This activity was absent in reactions with the porcine placental paralogue (or other orthologues) of P450arom and was minimal with androstenedione. Incubations with both porcine enzymes and with bovine and human P450arom demonstrated that 1 beta OH-T was not aromatizable, and 1 beta OH-T activated the androgen receptor of prostate cancer cells in vitro. Porcine testicular and follicular granulosa tissues synthesized 1 beta OH-T, which was also detected in testicular venous plasma. These results constitute the first of identification of a novel, perhaps potent, nonaromatizable metabolite of testosterone, whose synthesis (paradoxically) can be definitively ascribed to the activity of the gonadal paralogue of porcine P450arom. It probably represents an evolutionary gain of function associated with fixation and the survival of the genes after CYP19 duplication. Novel activities and adaptive functions may exist among other duplicated vertebrate aromatases.

Congenital hypopituitarism as a cause of undetectable estriol levels in the maternal triple-marker screen.

We are reporting a child with congenital panhypopituitarism, in whom deficient fetal steroidogenesis was suspected prenatally because of undetectable estriol levels measured in the maternal triple-marker screen. No fetal abnormalities were detected by ultrasonography. Amniocentesis demonstrated a normal 46,XX karyotype. Measurement of maternal urinary steroids failed to show elevation in the excretion of the major precursor for estriol, 16 alpha-hydroxydehydroepiandrosterone, indicating that the fetus did not have steroid sulfatase deficiency (placental sulfatase deficiency), the most common genetic cause of extremely low estriol. The steroid analysis excluded other rare single gene defects, including aromatase deficiency and 17 alpha-hydroxylase deficiency. We therefore suspected that the cause of low estriol in this fetus was adrenal insufficiency. Postnatal evaluation was consistent with panhypopituitarism, characterized by deficiency of all anterior pituitary hormones. Because this screen is now offered to more than half the pregnant women in the United States, reports of low estriol levels have become increasingly common. Therefore, it is essential that physicians be familiar with the various etiologies, perform the appropriate antenatal evaluation to determine the specific cause, and closely monitor both mother and child ante- and postnatally.

Measuring synthesis rates of muscle creatine kinase and myosin with stable isotopes and mass spectrometry.

We investigated a novel strategy for measuring the synthesis rate of proteins in skeletal and cardiac muscle. Mass isotopomer distribution analysis allows measurement of the isotopic enrichment of the true biosynthetic precursor for proteins (tRNA-amino acids), but cannot easily be applied to slow turnover muscle proteins due to insufficient isotope incorporation into multiply labeled species. Using a rapid turnover protein from the same tissue, however, might reveal tRNA-amino acid enrichment. We tested this strategy in rats on muscle creatine kinase (CK). A trypsinization peptide (3647u) containing 5 leucine repeats was identified by computer-simulated digestion of CK and then isolated from trypsin hydrolysates. Mass isotopomer abundances were determined by electrospray ionization-magnetic sector-mass spectrometry after in vivo administration of [(2)H(3)]leucine. Myosin heavy chain was also isolated and hydrolyzed to free amino acids. Muscle tRNA-amino acids were well labeled, by direct measurement. Enrichments of M(+1) and M(+2) mass isotopomers in the CK-peptide were measurable but low (consistent with a CK half-life of 3-10 days). Incorporation into skeletal muscle myosin indicated a half-life of 54 days. In conclusion, the general strategy of measuring protein kinetics by quantifying mass isotopomer abundances of mid-sized peptides from protein hydrolysates is effective, but CK does not turn over rapidly in muscle, contrary to previous reports. Identification of a rapid turnover muscle protein would be useful for this purpose.

Furosemide and 11beta-hydroxysteroid dehydrogenase activity, in man.

Mineralocorticoid receptors possess the same affinity for aldosterone and for cortisol and preferential binding of aldosterone is modulated by the 11 beta-hydroxysteroid dehydrogenase (11 beta-OHSD) enzyme, which converts cortisol to its inactive metabolite cortisone. Several endogenous or exogenous compounds able to inhibit the enzyme have been described and, as a consequence, produce the syndrome of apparent mineralocorticoid excess (AME) characterized by hypertension, hypokalemia, volume repletion and suppression of the renin-angiotensin-aldosterone system. High doses of furosemide, a diuretic that works in the luminal surface of the thick ascending limb of Henle's loop, have been reported to inhibit 11 beta-OHSD activity to the same extent as licorice in vivo and in vitro, in rat. The aim of our study was to verify the effect of the drug on 11 beta-OHSD activity in man at the doses currently used in clinical practice. We tested the activity of 11 beta-OHSD following both acute and protracted administration of furosemide. In the acute study, the drug was administered at low (40 mg i.v. in bolo) and high doses (infusion of 10 mg/kg bw i.v for six hours); the protracted furosemide administration consisted in 50 mg/day for 20 days, by mouth. The ratios between the cortisol metabolites tetrahydrocortisol plus allo-tetrahydrocortisol to tetra-hydrocortisone and urinary free cortisol to urinary free cortisone were used to measure the activity of 11 beta-OHSD. Urinary cortisol, cortisone and their metabolites were tested by a gas-chromatographic/mass spectrometric method. Neither acute nor prolonged administration of furosemide did affect the activity of 11 beta-OHSD although the drug was able to modify plasma aldosterone and PRA secretion and to determine hypokalemia. Our results suggest that furosemide does not play a significant role in 11 beta-OHSD modulation in humans, at least at the dosage used in clinical practice.

[Dehydroepiandrosterone metabolism by Epidermophyton floccosum]. / Metabolismus von Dehydroepiandrosteron durch Epidermophyton floccosum.

Steroid hormones may be relevant for the fungus-host relation in dermatophytoses. In contrast to most other hosts of dermatophytes, humans are characterized by a high cutaneous concentration of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulphate (DHEAS). To investigate whether the strictly anthropophilic dermatophyte Epidermophyton floccosum can metabolize this steroid hormone, cultures of E. floccosum were supplemented with DHEA. After 5 days of incubation the steroids in the culture supernatants were extracted and differentiated by gaschromatography and massspectrometry (GC-MS). The results show that a nearly complete metabolization of DHEA by E. floccosum leads to the formation of multiple new steroids/metabolites some of which have not been reported before. Therefore, this fungus could possibly mediate the hormone regulated cutaneous defense mechanisms of the host by an intraepidermal metabolization of DHEA.

Synthesis of ring B unsaturated estriols. Confirming the structure of a diagnostic analyte for Smith-Lemli-Opitz syndrome.

[structure: see text] Brief partial syntheses are described for ring B unsaturated estriols, which are candidate metabolites diagnostic for Smith-Lemli-Opitz syndrome prenatally. These steroids are also likely metabolites of the Premarin preparation used in estrogen replacement therapy. Equilin (8) was converted in three steps to 7-dehydroestriol, which was isomerized to 8-dehydroestriol. The simplicity of the transformations belies the lability of these previously inaccessible metabolites and their synthetic precursors.