Biotransformation

The extracellular and intracellular metabolites formed upon exposure of activated sludge microorganisms to a sublethal concentration of N-ethylmaleimide were monitored by liquid chromatography with ion trap mass spectrometry. The metabolite N-ethylsuccinimido-S-glutathione (m/z 433) was converted rapidly to N-(2-oxoethyl)-2,2-(propionylamino)propanamide (m/z 187) and N-ethylmaleamic acid (m/z 144).

Platelet activation is fundamentally involved in the initiation and development of atherosclerotic disease. It orchestrates
the triad of inflammation, atherosclerosis and thrombosis. Thienopyrindines are one of the most commonly prescribed
drugs for secondary prevention of cardiovascular diseases. Their mode of action is through irreversible inhibition of P2Y12
receptors on platelets and thereby antagonizing the effect of adenosine diphosphate (ADP) resulting in potent anti-platelet
effects. There are, however, emerging data over last decade, which indirectly support ADP-independent effects of thienopyridine
drugs with multiple beneficial modes of action in cardiovascular disease prevention. In this review, we focus on
the potential pleiotropic effects of thienopyridines.

Aerobic degradation experiments of Triclosan were performed in activated sludge to identify possible transformation products for this compound. During 7 days, the formation of biotransformation products such as 2,4-Dichlorophenol, 4-Chlorocatechol, 5-Hydroxy-Triclosan and other Monohydroxy-Triclosan derivatives as well as Dihydroxy-Triclosan-derivatives were observed. The structure of 5-Hydroxy-Triclosan was elucidated by NMR data for the first time in sludge degradation experiments. Additionally the production of a hitherto unknown transformation product in sludge, i.e., Triclosan-O-Sulfate was detected. During the incubations, the concentrations of this transformation product changed from zero to 330 μg L(-1). Based on the analysis of the biodegradation products, three types of reactions were identified: 1) chemical scission of ether bond to form phenols and catechols, 2) addition of OH moieties to the aromatic ring, and 3) adding of methyl or sulfate groups to the original hydrox...

Rationale: According to general view, aldehyde dehydrogenase-2 (ALDH2) catalyzes the high-affinity pathway of vascular nitroglycerin (GTN) bioactivation in smooth muscle mitochondria. Despite having wide implications to GTN pharmacology and raising many questions that are still unresolved, mitochondrial bioactivation of GTN in blood vessels is still lacking experimental support. Objective: In the present study, we investigated whether bioactivation of GTN is affected by the subcellular localization of ALDH2 using immortalized ALDH2-deficient aortic smooth muscle cells and mouse aortas with selective overexpression of the enzyme in either cytosol or mitochondria. Methods and Results: Quantitative Western blotting revealed that ALDH2 is mainly cytosolic in mouse aorta and human coronary arteries, with only approximately 15% (mouse) and approximately 5% (human) of the enzyme being localized in mitochondria. Infection of ALDH2-deficient aortic smooth muscle cells or isolated aortas with...

The relationship between biliary excretion in sandwich-cultured rat hepatocytes and in vivo in rats was examined. The biliary excretion of seven model substrates in 96-h sandwich-cultured rat hepatocytes was determined by differential cumulative uptake of substrate in the monolayers preincubated in standard buffer (intact bile canaliculi) and Ca2+-free buffer (disrupted bile canaliculi). Biliary excretion in vivo was quantitated in bile duct-cannulated rats. The biliary excretion index of model substrates, equivalent to the percentage of retained substrate in the canalicular networks, was consistent with the percentage of the dose excreted in bile from in vivo experiments. The in vitro biliary clearance of inulin, salicylate, methotrexate, [D-pen2,5]enkephalin, and taurocholate, calculated as the ratio of the amount excreted into the bile canalicular networks and the area under the incubation medium concentration-time profile ( approximately 0, approximately 0, 4.1 +/- 1.0, 12.6 +/-...

Alcohol clamping is a technique that maintains a constant breath alcohol Concentration (BrAC) for prolonged intervals, thereby reducing experimental variance in the timc course of organ exposure to alcohol, when compared with oral alcohol administration paradigms. ...

Sulfamethazine acetylation phenotype was determined in 49 patients with cancer of the colon or rectum, 41 old, and 45 young control subjects. Metabolic clearance of sulfamethazine, plasma ratio of N-acetylsulfamethazine:N-acetylsulfamethazine plus sulfamethazine and urinary ratio of N-acetylsulfamethazine:N-acetylsulfamethazine plus sulfamethazine were used to classify subjects into slow and fast acetylation phenotypes. All three measures gave similar results. The proportions of slow and fast acetylators were similar in both control groups and there were significantly more fast acetylators in the cancer group than in the control groups (chi 2 = 5.0-8.5; P less than 0.05). The data suggest that there may be an association between acetylation phenotype and colorectal carcinoma.

Background: Lactic acid bacteria-based fermentation clearly contributes to improving nutritional value and exhibits various health benefits. The demand for non-dairy functional beverages, such as fruit beverages, as an alternative vehicle for probiotics is increasing because of lifestyle choices or health conditions. Therefore, the objective of this study was to evaluate the anti-Salmonella potential and antioxidant activity of fermented fruit-based juice by lactic acid bacteria and its biotransformation. 

Methods: In this study, to produce the fermented fruit-based juice (FFJ), the mixed fruit juice (MFJ) was fermented by Lactobacillus plantarum and Lactobacillus salivarius for 72 hrs. The potential function, anti-Salmonella by the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and antibiofilm activities of FFJ against Salmonella Typhi DMST 22842 was evaluated. The antioxidative capacity was determined by DPPH and FRAP assay. The active volatile compounds were identified by GC-MS.

Results: A novel functional FFJ showed excellent growth capacity with 8 log CFU/mL of probiotics Lactobacillus plantarum and Lactobacillus salivarius. MIC and MBC values in the FFJ were 500 mg/mL after 72 hrs of fermentation. After 48hrs of fermentation, biofilm formation inhibition was significant (p < 0.05) with 95.27% ± 2.26% inhibition; biofilm metabolic activity inhibition was also significant (p < 0.05) with 89.25% ± 0.18% inhibition. The volatile compounds present in the FFJ were fruity flavors and aromas, most of have antimicrobial and antioxidant properties.  These compounds comprise various classes, including alcohols, organic acid, ester, and ketone. In both LAB fermentations, the most abundant volatile alcohol was isoamyl alcohol, followed by 1-hexanol and 2,3-Butanolone; acetic acid was only present in L. plantarum fermentation. In addition, DPPH radical scavenging and FRAP assay showed the mixed fruit juice had dramatically increased antioxidant activity after 48 hrs of fermentation.

Conclusion: The findings of this work indicate that the obtained fermented fruit-based juice (FFJ) showed excellent growth capacity of probiotics, Lactobacillus plantarum and Lactobacillus salivarius, and produced the volatile compounds from biotransformation. This not only improved fruit flavor and aroma, but also influenced antibacterial activity against the pathogen Salmonella Typhi DMST 22842, as well as increased antioxidant activity. Therefore, the FFJ could be a novel functional fermented drink for vegan and non-diary consumption.

Keywords: Lactic acid bacteria, Probiotics, Biotransformation, Non-dairy functional beverage, Anti-Salmonella

Purpose: Cyclophosphamide and thioTEPA are frequently used simultaneously in high-dose chemotherapy regimens. During a pharmacokinetic study of 31 courses in 20 patients of cyclophosphamide and its activated metabolite 4-hydroxycyclophosphamide given in the combination cyclophosphamide–thioTEPA–carboplatin, a sharp decrease in 4-hydroxycyclophosphamide concentration was observed immediately after the start of the thioTEPA infusion. A drug-drug interaction was suspected. This putative interaction was investigated in this study. Methods: Possible sequence dependency, due to inhibition of the formation of 4-hydroxycyclophosphamide by thioTEPA, was investigated by altering the sequence of infusion in three patients (four courses) receiving high-dose chemotherapy with cyclophosphamide (1000 or 1500 mg/m2 per day), thioTEPA (80 or 120 mg/m2 per day) and carboplatin (265 or 400 mg/m2 per day) in short infusions for four consecutive days. The pharmacokinetics of cyclophosphamide and 4-hydroxycyclophosphamide were established. Possible inhibition of the metabolism of cyclophosphamide and thioTEPA was investigated in human microsomes. Results: A striking sequence dependency of the pharmacokinetics of 4-hydroxycyclophosphamide was observed. Administration of thioTEPA 1 h prior to cyclophosphamide resulted in decreased Cmax (−62%) and AUC (−26%) values of 4-hydroxycyclophosphamide compared to those of thioTEPA administered 1 h after cyclophosphamide. In human microsomes an inhibition of the conversion of cyclophosphamide to 4-hydroxycyclophosphamide by thioTEPA was observed at clinically relevant concentrations with an IC50 of 23 μM. No inhibition of the formation of TEPA by cyclophosphamide was observed. Conclusions: ThioTEPA strongly inhibits the bioactivation of cyclophosphamide and this may decrease both efficacy and toxicity. Our results seriously question the practice of the simultaneous continuous infusion of cyclophosphamide and thioTEPA and suggest that the sequencing and scheduling of these two agents in high-dose chemotherapy regimens may be of critical importance.

Biodiesel, as an alternative fuel, is gradually receiving more popularity for use in internal combustion engines. However questions continue to arise with regard to its compatibility with elastomeric materials. The present work aims to investigate the comparative degradation of physical properties for different elastomers [e.g. ethylene propylene diene monomer (EPDM), silicone rubber (SR), polychloroprene (CR), polytetrafluroethylene (PTFE) and nitrile rubber (NBR)] upon exposure to diesel and palm biodiesel. Static immersion tests in B0(diesel), B10 (10% biodiesel in diesel), B20, B50 and B100(biodiesel) were carried out at room temperature (25 °C) for 1000 h. Different physical properties like, changes in weight and volume, hardness and tensile strength were measured at every 250 h of immersion time. Compositional changes in biodiesel due to exposure of different elastomers were investigated by Gas chromatography mass spectroscopy (GCMS). The overall sequence of compatible elastomers in palm biodiesel is found to be PTFE > SR > NBR > EPDM > CR.

http://www.sciencedirect.com/science/article/pii/S0360544210007139

The effect of Tochu tea, which is an aqueous extract of Eucommia ulmoides leaves and a popular-beverage in Japan, on the urine mutagenicity before and after ingestion of raw fish and cooked beef was studied using Salmonella typhimurium YG1024. Urines were collected from seven healthy, non-smoking Japanese women before and after ingestion of raw fish and cooked beef. In experiment 1,3 were in a control group and 4 were in a Tochu tea-drinking group (2000 ml per day). The mutagenicity of urine from the Tochu tea-drinking group was much lower. In experiment 2 the 7 women switched groups; the tea-drinking group became the control group, and the control group became the Tochu tea-drinking group. Again, the mutagenicity of urine collected from the Tochu tea-drinking group was much lower. These results suggest that the decrease in the mutagenicity of the urine from the Tochu tea-drinking group was due to the intake of Tochu tea, but not to individual differences. Thus, the ingestion of Toc...

In order to determine biogas potential of defatted silk worm pupae waste, anaerobic batch digestion was carried out in a 1-l bioreactor and, based on the results, further experiments were conducted in a 20-l KVIC (Khadi and Village Industries Commission) type digester under semi-...

Mutagenesis in S. typhimurium and in vitro induction of DNA single-strand breaks in primary rat hepatocytes (DNA-SSB) have been investigated for two new N-nitroso compounds, mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC). Mononitrosamidocaffeidine (MNAC) and tert.-(butyloxy)carbonyl-mononitrosamidocaffeidine (t-BOC-MNAC), both nitrosated derivatives of caffeidine with nitrosation at methylcarboxamide-N only, were also similarly studied. MNC, an asymmetric nitrosamine, failed to show mutagenicity in any of the tester strains used, and also did not induce DNA-SSB in rat hepatocytes. DNC, having both N-nitrosamide and N-nitrosamine groups in the molecule, showed direct mutagenicity in TA100, TA1535 and TA102. The mutagenic potential of the compound was found to increase on S9 activation. However, it was non-mutagenic in TA98 and TA1537. DNC also exhibited a high potential for inducing alkali-labile DNA-SSB in rat hepatocytes (70-78% C-T value) and was cytotoxic at concentrat...