Transformation of a monoterpene ketone, piperitenone, and related terpenoids using Mucor piriformis.

Biotransformation of piperitenone (I), 5,5-dimethyl-2-(1-methylethylidene)-cyclohexanone (II), and 2-(1-ethyl-1-propylidene)-5-methylcyclohexanone (III) was studied using a versatile fungal strain, Mucor piriformis. The organism initiates transformation of these compounds by hydroxylation at the allylic positions or at the tertiary carbon. Transformation of piperitenone (I) by this strain yielded 5-hydroxypiperitenone (Ic), 7-hydroxypiperitenone (Id), 7-hydroxypulegone (Ie), 10-hydroxypiperitenone (If), and 4-hydroxypiperitenone (Ig) as metabolites.

C-Phycocyanin, a selective cyclooxygenase-2 inhibitor, induces apoptosis in lipopolysaccharide-stimulated RAW 264.7 macrophages.

C-Phycocyanin (C-PC) is one of the major biliproteins of Spirulina platensis, a blue green algae, with antioxidant and radical scavenging properties. It is also known to exhibit anti-inflammatory and anti-cancer properties. However, the mechanism of action of C-PC is not clearly understood.

Stereoselective hydroxylation of 4-methyl-2-cyclohexenone in rats: its relevance to R-(+)-pulegone-mediated hepatotoxicity.

R-(+)-Pulegone, a monoterpene ketone, is a potent hepatotoxin. One of the major metabolites of pulegone has been shown to be p-cresol, a glutathione depletor and a known toxin. Allylic hydroxylation of 4-methyl-2-cyclohexenone results in the formation of p-cresol.

Efficient scavenging of hydroxyl radicals and inhibition of lipid peroxidation by novel analogues of 1,3,7-trimethyluric acid.

New water-soluble analogues of 1,3,7-trimethyluric acid with N-1 methyl replaced by various groups were prepared and evaluated for their ability to scavenge hydroxyl radicals as well as their protective potential against lipid peroxidation in erythrocyte membranes. The deoxyribose degradation method indicates that all the analogues tested effectively scavenge hydroxyl radicals and some of them show better activity than uric acid and methyluric acids. These effects are shown to be concentration dependent and are more potent at low concentrations (10-50 microM).

Biosynthesis of beta-substituted furan skeleton in the lower furanoterpenoids: a model study.

Furanoterpenes are widely distributed in the plant kingdom. In this study we have carried out enzymatic synthesis of simple furan compounds from the molecules containing an alpha-isopropylidene ketone unit and the role of cytochrome P450 in this biotransformation has been conclusively established. Eight model compounds (acyclic, monocyclic, and bicyclic, 1-8), having an alpha-isopropylidene ketone unit, were synthesized and incubated with PB-induced rat liver microsomes in the presence of NADPH and O(2).

Antioxidant and radical scavenging properties of 8-oxo derivatives of xanthine drugs pentoxifylline and lisofylline.

The antioxidant and radical scavenging properties of 8-oxo derivatives of pentoxifylline, lisofylline, enprofylline (3-propyl xanthine), and 1,7-dimethyl enprofylline were studied in vitro. The results show that 8-oxopentoxifylline and 8-oxolisofylline are significantly better hydroxyl and peroxyl radical scavengers and more potent inhibitors of t-butylhydroperoxide-induced lipid peroxidation in human erythrocyte membranes than the parent drugs. The hydroxyl radical scavenging property of 8-oxoenprofylline and its analogue 1,7-dimethyl-8-oxoenprofylline is marginally better than their corresponding xanthines.

Scavenging of peroxynitrite by phycocyanin and phycocyanobilin from Spirulina platensis: protection against oxidative damage to DNA.

Peroxynitrite (ONOO(-)) is known to inactivate important cellular targets and also mediate oxidative damage in DNA. The present study has demonstrated that phycocyanin, a biliprotein from spirulina platensis and its chromophore, phycocyanobilin (PCB), efficiently scavenge ONOO(-), a potent physiological inorganic toxin. Scavenging of ONOO(-) by phycocyanin and PCB was established by studying their interaction with ONOO(-) and quantified by using competition kinetics of pyrogallol red bleaching assay.

Crystal structure of a light-harvesting protein C-phycocyanin from Spirulina platensis.

The crystal structure of C-phycocyanin, a light-harvesting phycobiliprotein from cyanobacteria (blue-green algae) Spirulina platensis has been solved by molecular replacement technique. The crystals belong to space group P2(1) with cell parameters a = 107.20, b = 115.

Selective inhibition of cyclooxygenase-2 by C-phycocyanin, a biliprotein from Spirulina platensis.

We report data from two related assay systems (isolated enzyme assays and whole blood assays) that C-phycocyanin a biliprotein from Spirulina platensis is a selective inhibitor of cyclooxygenase-2 (COX-2) with a very low IC(50) COX-2/IC(50) COX-1 ratio (0.04). The extent of inhibition depends on the period of preincubation of phycocyanin with COX-2, but without any effect on the period of preincubation with COX-1.

C-phycocyanin: a potent peroxyl radical scavenger in vivo and in vitro.

C-Phycocyanin (from Spirulina platensis) effectively inhibited CCl(4)-induced lipid peroxidation in rat liver in vivo. Both native and reduced phycocyanin significantly inhibited peroxyl radical-induced lipid peroxidation in rat liver microsomes and the inhibition was concentration dependent with an IC(50) of 11.35 and 12.

Transformation of a monoterpene ketone, (R)-(+)-pulegone, a potent hepatotoxin, in Mucor piriformis.

Biotransformation of a monoterpene ketone, (R)-(+)-pulegone (I), a potent hepatotoxin, was studied using a fungal strain, Mucor piriformis. Eight metabolites, namely, 5-hydroxypulegone (II), piperitenone (III), 6-hydroxypulegone (IV), 3-hydroxypulegone (V), 5-methyl-2-(1-hydroxy-1-methylethyl)-2-cyclohexene-1-one (VI), 3-hydroxyisopulegone (VII), 7-hydroxypiperitenone (VIII), and 7-hydroxypulegone (IX), have been isolated from the fermentation medium and identified. GC analysis of the metabolites indicated that II was the major metabolite formed.

Purification and partial characterization of caffeine oxidase--A novel enzyme from a mixed culture consortium.

Cell-free extract prepared from a mixed culture consisting of strains belonging to the genera Klebsiella and Rhodococcus grown in the presence of caffeine contains a novel enzyme, caffeine (1,3, 7-trimethylxanthine) oxidase which catalyzes the oxidation of caffeine at the C-8 position to produce 1,3,7-trimethyluric acid. The enzyme was purified to homogeneity by a combination of ion-exchange and hydrophobic column chromatographies. Both native and SDS/PAGE of the purified enzyme showed a single protein band and the subunit molecular mass of the protein was determined to be 85 kDa.

Combination of multiple serum markers using an artificial neural network to improve specificity in discriminating malignant from benign pelvic masses.

A panel of four selected tumor markers, CA 125 II, CA 72-4, CA 15-3, and lipid-associated sialic acid, was analyzed collectively using an artificial neural network (ANN) approach to differentiate malignant from benign pelvic masses. A dataset of 429 patients, 192 of whom had malignant histology, was retrospectively used in the study. A prototype ANN classifier was developed using a subset of the data which included 73 patients with malignant conditions and 101 patients with benign conditions.

Metabolic disposition of a monoterpene ketone, piperitenone, in rats: evidence for the formation of a known toxin, p-cresol.

It was shown earlier that the monoterpene ketone, piperitenone (I) is one of the major metabolites of R-(+)-pulegone, a potent hepatotoxin. In the present studies, the metabolic disposition of piperitenone (I) was examined in rats. Piperitenone (I) was administered orally (400 mg/kg of the b.

Metabolic fate of S-(-)-pulegone in rat.

1. S-(-)-pulegone was administered orally to rat (250 mg/kg) and the nature of the urinary metabolites was investigated. Eleven metabolites, namely S-(-)-menthofuran, piperitone, piperitenone, p-cresol, 5-hydroxypulegone, 4-methylcyclohexenone, 3-methylcyclohexanone, isopulegone, pulegol, 7-hydroxypiperitone and benzoic acid, have been isolated from rat urine.

Hepatoprotective effect of C-phycocyanin: protection for carbon tetrachloride and R-(+)-pulegone-mediated hepatotoxicty in rats.

Effect of C-phycocyanin (from Spirulina platensis) pretreatment on carbontetrachloride and R-(+)-pulegone-induced hepatotoxicity in rats was studied. Intraperitoneal (i.p.

A novel pathway for the metabolism of caffeine by a mixed culture consortium.

A new oxidative pathway for the degradation of caffeine(1,3,7-Trimethylxanthine, I) by a mixed culture consisting of strains belonging to the genera Klebsiella and Rhodococcus is presented. The mixed culture does not initiate degradation by N-demethylation either complete or partial, but instead carries out oxidation at the C-8 position resulting in the formation of 1,3,7-trimethyluric acid (TMU, II) which further gets degraded to 3,6,8-trimethylallantoin (TMA, III). Both TMU and TMA are hitherto not shown to be formed in the microbial system.

Understanding artificial neural networks and exploring their potential applications for the practicing urologist.

Artificial neural networks (ANNs) are complex mathematical models that are distantly based on the human neuronal structure. They are capable of modeling elaborate biologic systems without making assumptions based on statistical distributions. Preliminary work has been reported on their application in urology.

Evaluation of prostAsure index in the detection of prostate cancer: a preliminary report.

Objectives: Although prostate-specific antigen (PSA) has revolutionized the detection of prostate cancer, it has definite limitations with respect to its clinical sensitivity and specificity. Because a substantial number (20% to 40%) of men undergoing radical prostatectomy have a PSA level of 4.0 ng/mL or less, any new test offering diagnostic improvement must perform well in patients whose PSA level is less than or equal to 4.

Purification and some of the properties of a novel secondary alcohol dehydrogenase from Alcaligenes eutrophus.

Alcaligenes eutrophus utilizing nerolidol, a sesquiterpene alcohol, as the sole source of carbon contains an inducible NAD(P)(+)-linked secondary alcohol dehydrogenase (SADH). The enzyme was purified to homogeneity by a combination of salt precipitation, ion exchange and affinity matrix chromatographies. The apparent molecular mass of the enzyme was estimated to be 139 KDa with four identical subunits of 38.

Evaluation of a new biochemical index for the estimation of bone demineralization using artificial intelligence.

The use of artificial neural networks (ANN) for the identification of a positive correlation between the QuiOs quotient, a single-valued indicator of bone mineral density, and multisite dual energy x-ray absorptiometry (DEXA) measurements is described. The measurements were obtained using the Hologic QDRR-2000 x-ray bone densitometer in a multicenter clinical trial including 374 female patients. The QuiOs quotient estimates bone mineral density and determines the severity of bone density loss.

Comparative study of a biochemical index for the estimation of bone demineralization and dual photon absorptiometry.

Multivariate classification methods were used to create an early detection technique for determining bone density. This biochemical index (QuiOs) is clinically useful as a potential adjunct in identifying the presence of biochemical deficiencies known to cause osteopenia and the devastating effects of osteoporosis. The test uses the following serum concentrations of a predetermined set of blood constituents: calcium, phosphorus, alkaline phosphatase (ALP), two alkaline phosphatase isoenzymes (liver and intestine), estradiol, and progesterone.

Role of neutral metabolites in microbial conversion of 3beta-acetoxy-19-hydroxycholest-5-ene into estrone.

Biotransformation of 3beta-acetoxy-19-hydroxycholest-5-ene (19-HCA, 6 g) by Moraxella sp. was studied. Estrone (712 mg) was the major metabolite formed.

Effects of menthofuran, a monoterpene furan on rat liver microsomal enzymes, in vivo.

Oral administration (250 mg/kg) of menthofuran, a monoterpene furan, to rats once daily for 3 days caused hepatotoxicity as judged by a significant increase in serum glutamate pyruvate transaminase (SGPT) and decreases in glucose-6-phosphatase and aminopyrine N-demethylase activities. Administration of menthofuran also resulted in a decrease in the levels of liver microsomal cytochrome P-450, whereas cytochrome b5 and NAD(P)H-cytochrome c reductase activities were not affected. These effects of menthofuran were both dose- and time-dependent.