Structure and solubility behaviour of zinc containing phosphate glasses.

The structure of phosphate glasses of general composition 10Na2O : (20 + x/2)ZnO : (20 + x/2)CaO : (50 -x)P2O5 (0 ≤x≤ 20) has been investigated using IR spectroscopy, 1D 31P and 43Ca MAS Bloch decay, 31P-31P double quantum MAS-NMR and 43Ca and 67Zn static NMR techniques, as well as neutron diffraction analysis. Zinc is shown to aid glass formation in this system. Glass transition temperature and density increase with increasing cation : phosphate ratio. However, free volume calculations show structures becoming significantly more compact from x = 5 to x = 10. The structural data confirm depolymerisation of the glasses with increasing cation : phosphate ratio. Zinc oxide is found to act in a network forming role in the system, with 67Zn NMR and neutron diffraction analysis confirming zinc exhibits predominantly four-coordinate geometry. Solubility in deionised water and tris/HCl buffer solution is seen to decrease significantly with increasing x-value. This is discussed in terms of water ingress and the degree of structural openness, associated with increased cross-linking and a decrease in concentration of P-O-P linkages. pH measurements confirm invert phosphate compositions maintain physiological pH levels on immersion in water and buffer solutions for up to four weeks.

How are condoms used in a family planning setting: evidence from Zimbabwe.

OBJECTIVES: (To determine the level and consistency of condom use among family planning clients at three family planning clinics in Zimbabwe.) DESIGN: A prospective cross sectional study. SETTING: The study was carried out at three Zimbabwe National Family Planning Council clinics. SUBJECTS: We interviewed 899 consecutive women seeking family planning services at these three clinics using a structured questionnaire. MAIN OUTCOME MEASURES: The prevalence of condom use among this population of family planning clients and the factors predicting condom use were the main outcome measures. We define dual method use (DMU) as the use of condoms in conjunction with another highly effective contraceptive and dual purpose use (DPU) as the use of condoms for both pregnancy and STI/HIV prevention. We measured self-reported condom use during the last 30 days prior to each interview. RESULTS: The prevalence of condom use among this population of family planning clients was 38%. Of all the study participants, 32% were DMU clients while 5% were DPU clients. Fifty eight percent of the DMU clients and 89% of the DPU clients clients reported consistent condom use respectively. Logistic regression analysis showed that young age and reporting high risk sexual behaviour were predictors of condom use. CONCLUSIONS: The level of condom use among this population of family plannig clients is too low for a country with such a high HIV prevalence. Condom users were more likely to report DMU than DPU. Those reporting DPU were more likely to report consistent condom use.

Determination of the relative NH proton lifetimes of the peptide analogue viomycin in aqueous solution by NMR-based diffusion measurement.

In aqueous solution, exchanging peptide NH protons experience two environments, that of the peptide itself with a relatively slow diffusion coefficient and that of the water solvent with a faster diffusion coefficient. Although in slow exchange on the NMR chemical shift timescale, the magnetic field gradient dependence of the NH peak intensities in an experiment used to measure diffusion coefficients reflects the relative time periods spent in the two environments and this allows the determination of the relative solvent accessibility of exchangeable protons in peptides or proteins. To test this approach, the magnetic field gradient dependent intensities of the chemically shifted amide and amine NH protons of the peptide antibiotic viomycin have been measured using the high resolution longitudinal-eddy-current-delay (LED) NMR method incorporating solvent water peak elimination by non-excitation. The NH resonances of viomycin have been assigned previously and their relative exchange rates determined. Here, the gradient dependence of each NH proton intensity is reported, and these, after a bi- exponential least squares fitting, yield the fractional lifetimes of the protons spent in the peptide and water environments during the diffusion period of the experiment.

A novel nonhepatic hydroxycholesterol 7 alpha-hydroxylase that is markedly stimulated by interleukin-1 beta. Characterization in the immature rat ovary.

During studies on the regulation of rat ovarian steroidogenic enzymes by interleukin-1 beta (IL-1 beta), we observed substantial metabolism of 25-hydroxycholesterol to two unusual polar products. This unexpected effect was observed both in isolated granulosa cells and in whole ovarian dispersates and was also induced by tumor necrosis factor alpha, but not by insulin-like growth factor I or follicle-stimulating hormone. The effect was dependent on time and the dose of IL-1 beta and was blocked by and IL-1 receptor antagonist. The formation of the polar metabolites was inhibited by ketoconazole and trilostane, but not by aminoglutethimide. Subsequent purification of these novel metabolites and analysis by gas chromatography/ mass spectrometry, NMR, and high performance liquid chromatography revealed them to be related 7 alpha-hydroxylated hydroxycholesterols (cholest-4-ene-7 alpha,25-diol-3-one and cholest-5-ene-3 beta,7 alpha,25-triol). IL-1 beta-stimulated ovarian 7 alpha-hydroxylase activity (3-10 pmol/min/mg of cellular protein) was nearly 4-fold that of control levels using 25-hydroxycholesterol as substrate. Activities at or below control levels were observed when IL-1 beta-treated cell sonicates were boiled or assayed in the presence of NADH (rather than NADPH), indicating that involvement of a nonenzymatic process was unlikely. IL-1 beta-stimulated 7 alpha-hydroxylase activity was inhibited to basal levels by a 10-fold excess of unlabeled 25- or 27-hydroxycholesterol, but not by cholesterol, pregnenolone, progesterone, testosterone, or dehydroepiandrosterone, suggesting that ovarian 7 alpha-hydroxylase is specific for hydroxycholesterols. Furthermore, when IL-1 beta-treated ovarian cultures were incubated with radiolabeled cholesterol or testosterone, no 7 alpha-hydroxylated products were observed. We were also unable to detect any mRNA transcripts for liver cholesterol 7 alpha-hydroxylase in IL-1 beta-stimulated ovarian cultures. This study describes an ovarian hydroxycholesterol 7 alpha-hydroxylase that differs from liver cholesterol 7 alpha-hydroxylase and from other nonhepatic progestin/ androgen 7 alpha-hydroxylases. The novel finding of the regulation of a 7 alpha-hydroxylase by IL-1 beta (and tumor necrosis factor alpha) suggests a unique role for cytokines in the regulation of cholesterol metabolism in the ovary and possibly other tissues.

Omega 1-decoupled 1H homonuclear shift-correlated nuclear magnetic resonance spectroscopy (COSYDEC) applied to steroids.

Problems of cross-peak overlap in two-dimensional 1H homonuclear shift-correlated (COSY) spectra of steroids can often be avoided by use of the omega 1-decoupled COSY (COSYDEC) method. The selection of experimental parameters is discussed, and COSYDEC spectra are illustrated for 17a-oxa-D-homoandrost-4-ene-3,17-dione (testololactone), testosterone, and 17 alpha-hydroxyprogesterone. In a good case, a COSYDEC spectrum obtained at 250 MHz allows cross-peak recognition and assignment with facility comparable to that available only at 500 MHz for normal COSY spectra.

Synthesis of 6 beta-hydroxyaldosterone by A6 (toad kidney) cells in culture.

Incubation of aldosterone with confluent layers of A6 (toad kidney) cells leads to its hydroxylation at the 6 beta-position. 6 beta-Hydroxyaldosterone is the major metabolite when the incubation is carried out at pH 6.8, whereas the product comprises 6 beta-hydroxy-17-isoaldosterone accompanied by some 6 beta-hydroxyapoaldosterone at pH 7.4. All products were identified by high-field 1H nuclear magnetic resonance spectroscopy. Control experiments indicated that the side-chain isomerization to form the 17-iso and apo derivatives occurs after the cytochrome P 450-dependent synthesis of 6 beta-hydroxyaldosterone.

18-substituted steroids--Part 17. 2 alpha-hydroxylated liver metabolites of aldosterone identified by high-field [1H]NMR spectroscopy.

11 beta,18-Epoxy-2 alpha,3 alpha,18,21-tetrahydroxy-5 alpha,17 alpha- pregnan-20-one (2 alpha-hydroxy-3 alpha,5 alpha-tetrahydro-17-isoaldosterone) and its apo isomer have been identified by high-field NMR studies, supported by thermospray HPLC/MS, to be among the major polar metabolites formed from incubation of aldosterone with rat liver microsomal fraction. Indications that unreduced 2 alpha-hydroxy-aldosterone is also present among the metabolites have still to be confirmed.

18-Substituted steroids. Part 15. 6 beta-Hydroxylation of aldosterone by liver.

6 beta-Hydroxyaldosterone and 6 beta-hydroxy-17-isoaldosterone, characterized by high-field NMR studies, are among the major polar metabolites formed from aldosterone by incubation with rat liver slices or microsomal fraction. It is uncertain at present whether the 17-iso product results from an enzymatic or a chemical inversion of configuration. Periodate degradation of the 6 beta-hydroxyaldosterone gave 6 beta-hydroxyaldosterone gamma-lactone, identical with a synthetic sample.