Acid-mediated conversion of methylene-interrupted bisepoxides to tetrahydrofurans: A biomimetic transformation

The acid-mediated transformation of syn and anti methylene interrupted cis,cis and cis,trans bisepoxides to tetrahydrofurans is high yielding, and demonstrates both regioselectivity and stereoselectivity. Trans,trans methylene interrupted bisepoxides do not yield tetrahydrofurans under the same conditions.

Evidence for persistent dysfunction of wild-type aldosterone synthase gene in glucocorticoid-treated familial hyperaldosteronism type I

Background In familial hyperaldosteronism type I (FH-I), glucocorticoid treatment suppresses adrenocorticotrophic hormone-regulated hybrid gene expression and corrects hyperaldosteronism. Objective To determine whether the wild-type aldosterone synthase genes, thereby released from chronic suppression, are capable of functioning normally. Methods We compared mid-morning levels of plasma potassium, plasma aldosterone, plasma renin activity (PRA) and aldosterone : PRA ratios, measured with patients in an upright position, and responsiveness of aldosterone levels to infusion of angiotensin II (AII), for 11 patients with FH-I before and during long-term (0.8-14.3 years) treatment with 0.25-0.75 mg/day dexamethasone or 2.5-10 mg/day prednisolone. Results During glucocorticoid treatment, hypertension was corrected in all. Potassium levels, which had been low (< 3.5 mmol/l) in two patients before treatment, were normal in all during treatment (mean 4.0 +/- 0.1 mmol/l, range 3.5-4.6). Aldosterone levels during treatment [13.2 +/- 2.1 ng/100 ml (mean +/- SEM)] were lower than those before treatment (20.1 +/- 2.5 ng/100 ml, P < 0.05). PRA levels, which had been suppressed before treatment (0.5 +/- 0.2 ng/ml per h), were unsuppressed during treatment (5.1 +/- 1.5 ng/ml per h, P < 0.01) and elevated (> 4 ng/ml per h) in six patients. Aldosterone : PRA ratios, which had been elevated (> 30) before treatment (101.1 +/- 25.9), were much lower during treatment (4.1 +/- 1.0, P < 0.005) and below normal (< 5) in eight patients. Surprisingly, aldosterone level, which had not been responsive (< 50% rise) to infusion of AII for all 11 patients before treatment, remained unresponsive for 10 during treatment. Conclusions Apparently regardless of duration of glucocorticoid treatment in FH-I, aldosterone level remains poorly responsive to AII, with a higher than normal PRA and a low aldosterone : PRA ratio. This is consistent with there being a persistent defect in functioning of wild-type aldosterone synthase gene. (C) Rapid Science Publishers ISSN 0263-6352.

An ESR and NMR study of the gamma radiolysis of a bisphenol-A based polycarbonate and a phthalic acid ester

A study of the gamma-radiolysis of the commercial polymers U-polymer, UP (Unitake) and polycarbonate, PC, (Aldrich) has been undertaken using ESR spectroscopy. The G-value of radical formation at 77 K has been found to be 0.31 +/- 0.01 for UP and 0.5 +/- 0.02 for PC. By using thermal annealing and spectral subtraction, the paramagnetic species formed on irradiation has been assigned. The effect of radiation on the chemical structure of UP and PC has been investigated at ambient temperature and at 423 K. The NMR results show that a new phenol type chain end is formed in the polymers on exposure to gamma-radiation. The G-value of formation of the new phenol ends was estimated to be 0.7 for PC (423 K) and 0.4 for UP (300 K). (C) 1998 John Wiley & Sons, Ltd.

Volatile products and new polymer structures formed on Co-60 gamma-radiolysis of poly(lactic acid) and poly(glycolic acid)

A gas product analysis has been conducted on gamma-irradiated samples of poly(lactic acid) (PLA) and poly(glycolic acid) (PGA) by means of gas chromatography. The major volatile products have been identified to be CO, CO2, CH4 and C2H6 for PLA, and CO and CO2 for PGA. In addition, the yield of evolved gases for PLA has been found to be 1.81 for CO2, 0.98 for CO, 0.026 for CH4 and 0.012 for C2H6; and that for PGA to be 1.70 for CO2 and 0.42 for CO. The new chain ends formed due to gamma-induced bond cleavage in PLA have been assigned to CH3-CH2-CO-O- and CH3-CH2-O-CO-, and the G values for formation of these chain ends were found to be 1.9 and 0.6, respectively. The G value for chain scission reported previously of 2.3 is comparable with that for the formation of the propanoic acid end group. (C) 1997 Elsevier Science Limited.

Molecular cocrystals of carboxylic acids. XXVII - An investigation into the use of triphenylphosphine oxide cocrystals for non-linear optics: the crystal structure of the adduct of triphenylphosphine oxide with N-methylpyrrole-2-carboxylic acid

Four adducts of triphenylphosphine oxide with aromatic carboxylic acids have been synthesized and tested for second-order non-linear optical properties. These were with N-methylpyrrole-2-carboxylic acid (I), indole-2-carboxylic acid (2), 3-dimethylaminobenzoic acid (3), and thiophen-2-carboxylic acid (4). Compound (1) produced clear, colourless crystals (space group P2(1)2(1)2(1) With a 9.892(1), b 14.033(1), c 15.305(1) Angstrom, Z 4) which allowed the structure to be determined by X-ray diffraction.

Nucleotide sequence of the nifH gene coding for nitrogen reductase in the acetic acid bacterium Acetobacter diazotrophicus

The nifH gene sequence of the nitrogen-fixing bacterium Acetobacter diazotrophicus was determined with the use of the polymerase chain reaction and universal degenerate oligonucleotide primers. The gene shows highest pair-wise similarity to the nifH gene of Azospirillum brasilense. The phylogenetic relationships of the nifH gene sequences were compared with those inferred from 16S rRNA gene sequences. Knowledge of the sequence of the nifH gene contributes to the growing database of nifH gene sequences, and will allow the detection of Acet. diazotrophicus from environmental samples with nifH gene-based primers.

cis-3-hydroxy-N-methyl-L-proline: a new amino acid from a southern Australian marine sponge, Dendrilla sp.

A specimen of the sponge Dendrilla sp. collected during commercial trawling operations in the Great Australian Eight, Australia, analyses for a very high natural abundance of the new amino acid cis-3-hydroxy-N-methyl-L-proline (1). The complete stereostructure for (1) was determined by spectroscopic analysis and chemical derivatization.

Amino acid synthesis in the symbiotic sea anemone Aiptasia pulchella

Symbiotic Aiptasia pulchella and freshly isolated zooxanthellae were incubated in (NaHCO3)-C-14 and NH4Cl for 1 to 240 min, and samples were analysed by reverse-phase high-performance liquid chromatography (HPLC) and an online radiochemical detector. NH4+ was first assimilated into C-14-glutamate and C-14-glutamine in the zooxanthellae residing in A. pulchella. The specific activities (dpm nmol(-1)) of C-14-glutamate and C-14-glutamine in vivo, were far greater in the zooxanthellae than in the host tissue, indicating that NH4+ was principally incorporated into the glutamate and glutamine pools of the zooxanthellae. C-14-alpha-ketoglutarate was taken up from the medium by intact A. pulchella and assimilated into a small amount of C-14-glutamate in the host tissue, but no C-14-glutamine was detected in the host fraction. The C-14-glutamate that was synthesized was most likely produced from transamination reactions as opposed to the direct assimilation of NH4+. The free aminoacid composition of the host tissue and zooxanthellae of A. pulchella was also measured. The results presented here demonstrate that NH4+ was initially assimilated by the zooxanthellae of A. pulchella.

Topical penetration of commercial salicylate esters and salts using human isolated skin and clinical microdialysis studies

Aims The penetration of active ingredients from topically applied anti-inflammatory pharmaceutical products into tissues below the skin is the basis of their therapeutic efficacy. There is still controversy as to whether these agents are capable of direct penetration by diffusion through the tissues or whether redistribution in the systemic circulation is responsible for their tissue deposition below the application site. Methods The extent of direct penetration of salicylate from commercial ester and salt formulations into the dermal and subcutaneous tissue of human volunteers was determined using the technique of cutaneous microdialysis. We also examined differences in the extent of hydrolysis of the methylester of salicylate applied topically in human volunteers and in vitro skin diffusion cells using full-thickness skin and epidermal membranes. Results The present study showed that whilst significant levels of salicylate could be detected in the dermis and subcutaneous tissue of volunteers treated with the methylsalicylate formulation, negligible levels of salicylate were seen following application of the triethanolamine salicylate formulation. The tissue levels of salicylate from the methylsalicylate formulation were approx. 30-fold higher than the plasma concentrations. Conclusion The absorption and tissue concentration profiles for the commercial methylsalicylate formulation are indicative of direct tissue penetration and not solely redistribution by the systemic blood supply.

Hepatic structure-pharmacokinetic relationships: The hepatic disposition and metabolite kinetics of a homologous series of O-acyl derivatives of salicylic acid

1 The hepatic disposition and metabolite kinetics of a homologous series of O-acyl (acetyl, propionyl, butanoyl, pentanoyl, hexanoyl and octanoyl) esters of salicylic acid (C2SA, C3SA, C4SA, C5SA, C6SA and C8SA, respectively) was determined using a single-pass, in-sills rat liver preparation. 2 The hepatic venous outflow profiles for the parent esters and the generated metabolite, salicylic acid (SA) were analysed by HPLC. Non-parametric moments analysis was used to determine the area under the curve (AUC'), mean transit time (MTT) and normalized variance (CV2) for the parent esters and generated SA. 3 Pregenerated SA ([C-14]-salicylic acid) was injected into each liver with the parent ester to determine its distribution characteristics. 4 The overall recovery of ester plus metabolite was 89% of the ester dose injected and independent of the ester carbon number, suggesting that ester extraction was due to hepatic metabolism to salicylic acid. 5 The metabolite AUC' value increased directly with the lipophilicity of the parent ester (from 0.12 for C2SA to 0.95 for C8SA). By contrast, the parent AUC' decreased with the lipophilicity (from 0.85 for C2SA to zero for C8SA). The metabolite MTT value also showed a trend to increase with the lipophilicity of the parent ester (from 15.72 s for C3SA to 61.97 s for C8SA). However, the parent MTT value shows no significant change across the series. 6 The two-compartment dispersion model was used to derive the kinetic parameters for parent ester, pregenerated SA and generated SA. Consequently, these parameters were used to estimate the values of AUG', MITT and CV2 for the parent ester and metabolite. The moments values obtained using the two-compartment dispersion model show similar trends to the corresponding moments values obtained from the outflow profiles using a non-parametric approach. 7 The more lipophilic aspirin analogues are more confined to the portal circulation after oral administration than aspirin due to their more extensive hepatic elimination avoiding systemic prostacyclin inhibition. Given that aspirin's selectivity as an anti-thrombotic agent has been postulated to be due to selective anti-platelet effects in the portal circulation, the more lipophilic and highly extracted analogues are potentially more selective anti-thrombotic agents than aspirin.

Selection of a strain of Aspergillus for the production of citric acid from pineapple waste in solid-state fermentation

Aspergillus foetidus ACR I 3996 (=FRR 3558) and three strains of Aspergillus niger ACM 4992 (=ATCC 9142), ACM 4993 (=ATCC 10577), ACM 4994 (=ATCC 12846) were compared for the production of citric acid from pineapple peel in solid-state fermentation. A. niger ACM 4992 produced the highest amount of citric acid, with a yield of 19.4 g of citric acid per 100 g of dry fermented pineapple waste under optimum conditions, representing a yield of 0.74 g citric acid/g sugar consumed. Optimal conditions were 65% (w/w) initial moisture content, 3% (v/w) methanol, 30 degrees C, an unadjusted initial pH of 3.4, a particle size of 2 mm and 5 ppm Fe2+. Citric acid production was best in flasks, with lower yields being obtained in tray and rotating drum bioreactors.

Evaluation of an immunoassay (EMIT) for mycophenolic acid in plasma from renal transplant recipients compared with a high-performance liquid chromatography assay

Mycophenolic acid is an immunosuppressant administered as a bioavailable ester, mycophenolate mofetil. The pharmacokinetics of mycophenolic acid have been reported to be variable. Accurate measurement of concentrations of this drug could be important to adjust doses. The aim of this study was to compare the enzyme-multiplied immunoassay technique (EMIT [Dade Behring; San Jose, CA, U.S.A.]) for mycophenolic acid with a high-performance liquid chromatographic (HPLC) assay using samples collected from renal transplant recipients. The HPLC assay used solid phase extraction and a C18 stationary phase with ultraviolet (UV) detection (254 nm). The immunoassay required no manual sample preparation. Plasma samples (n = 102) from seven patients, collected at various times after a dose, were analyzed using both methods. Both assays fulfilled quality-control criteria. Higher concentrations were consistently measured in patient samples when using EMIT. The mean (+/- standard deviation [SD]) bias (EMIT-HPLC) was 1.88 +/- 0.86 mg/L. The differences in concentrations were higher in the middle of a dosage interval, suggesting that a metabolite might have been responsible for overestimation. Measurement of glucuronide concentrations by HPLC demonstrated only a weak correlation between assay differences and glucuronide concentrations. If the crossreacting substance is active, EMIT could provide a superior measure of immunosuppression; if inactive, further work is needed to improve antibody specificity. In conclusion, it was found that EMIT overestimates the concentration of mycophenolic acid in plasma samples from renal transplant recipients compared with HPLC analysis.

Synchronization of estrus and fertility in zebu beef heifers treated with three estrus synchronization protocols

The effects on estrus and fertility of 3 estrus synchronization protocols were studied in Brahman beef heifers. In Treatment 1 (PGF protocol; n=234), heifers received 7.5 mg, im prostianol on Day 0 and were inseminated after observed estrus until Day 5. Treatment 2 (10-d NOR protocol; n=220) consisted of norgestomet (NOR; 3 mg, sc implant and 3 mg, im) and estradiol valerate (5 mg, im) treatment on Day -10, NOR implant removal and 400 IU, im PMSG on Day 0, and AI after observed estrus through to Day 5. Treatment 3 (14-d NOR+PGF protocol; n=168) constituted a NOR implant (3 mg, sc) on Day -14, NOR implant removal on Day 0, PGF on Day 16, and AI after observed estrus through to Day 21. All heifers were examined for return to estrus at the next cycle and inseminated after observed estrus. The heifers were then exposed to bulls for at least 21 d. During the period of estrus observation (5 d) after treatment, those heifers treated with the PGF protocol had a lower (P

Growth and lactic acid production in batch culture of Lactobacillus rhamnosus in a defined medium

To facilitate metabolic analysis, batch fermentations of Lactobacillus rhamnosus were carried out in a new defined medium. Biomass at 10.5 g/l and lactic acid at 67 g/l with a Y-P/S of 0.84 were achieved. The maximum specific growth rate and the average productivity were 0.49/h and 2.48 g/l.h, respectively. These are comparable to those of this organism and related organisms in complex media. Preliminary amino acid studies were also conducted, highlighting the importance of serine, asparagine, glutamine and cysteine. Kinetic analysis revealed that lactic acid production was predominantly growth-associated with growth associated and non-growth associated lactic acid constants of 0.389 mol/g-cell and 0.0025 mol/g-cell.h, respectively. Finally a kinetic model has been included to describe the fermentation of L. rhamnosus.

Novel composite membranes for gas separation: Preparation and performance

High performance composite membranes based on molecular sieving silica (MSS) were synthesized using sols containing silicon co-polymers (methyltriethoxysilane and tetraethylorthosilicate). Alpha alumina supports were treated with hydrochloric acid prior to sol deposition. Permselectivity of CO2 over CH4 as high as 16.68 was achieved whilst permeability of CO2 up to 36.7 GPU (10(-6) cm(3) (STP) cm(-2) . s(-1) . cm Hg-1) was measured. The best membrane's permeability was finger printed during various stages of the synthesis process showing an increase in CO2/CH4 permselectivity by over 25 times from initial support condition (no membrane film) to the completion of pore structure tailoring. Transport measurement results indicate that the membrane pretreated with HCl has highest permselectivity and permeation rate. In particular, there is a definite cut-off pore size between 3.3 and 3.4 angstroms which is just below the kinetic diameters of Ar and CH4. This demonstrates that the mechanism for the separation in the prepared composite membrane is molecular sieving (activated diffusion), rather than Knudsen diffusion.