In this study, a mild two-stage hydrothermal pretreatment was employed to optimally valorize industrial hemp (Cannabis sativa sp.) fibrous waste into sugars for Poly(3-hydroxybuyrate) (PHB) production using recombinant Escherichia coli LSBJ. Biomass was pretreated using hot water at 160, 180, and 200 °C for 5 and 10 min (15% solids), followed by disk refining.
View Article and Find Full Text PDFTo sustainably produce biodegradable polyhydroxybutyrate (PHB), this study investigated effects of process and metabolic limiting factors during bioconversion of acid whey (AW) to PHB, offering economic and environmental advantages for dairy industry. Recombinant Escherichia coli LSBJ was used to achieve high PHB yields by utilizing both lactose and lactic acid as carbon source. Up to 85% PHB accumulation was achieved during growth on the synthetic AW.
View Article and Find Full Text PDFApple pomace, the residue which is left out after processing of apple serves as a potential carbon source for the production of biopolymer, PHA (poly-hydroxyalkanoates). It is rich in carbohydrates, fibers and polyphenols. Utilization of these waste resources has dual societal benefit-waste management and conversion of waste to an eco-friendly biopolymer.
View Article and Find Full Text PDFThe recyclability of cellulase enzymes using zeolite and polyethylene glycol (PEG) was investigated. The cellulase enzymes from cellulose hydrolysate suspensions were adsorbed onto zeolite-β under typical working conditions (pH 5). PEG having a molecular weight of 200 Da and 20 kDa was used as an eluent to desorb the cellulase enzymes from zeolite-β.
View Article and Find Full Text PDFUnlabelled: Background/ Aims: Little is known about the effect of P450 oxidoreductase (POR) gene polymorphisms on the activities of CYPs with multiple genotypes.
Methods: We genotyped 102 human livers for 18 known POR single nucleotide polymorphisms (SNPs) with allelic frequencies greater than 1% as well as for 27 known SNPs in 10 CYPs. CYP enzyme activities in microsomes prepared from these livers were determined by measuring probe substrate metabolism by high performance liquid chromatograph.
Determining drug-metabolizing enzyme activities on an individual basis is an important component of personalized medicine, and cytochrome P450 enzymes (CYPs) play a principal role in hepatic drug metabolism. Herein, a simple method for predicting the major CYP-mediated drug clearance and is presented. Ten CYP-mediated drug metabolic activities in human liver microsomes (HLMs) from 105 normal liver samples were determined.
View Article and Find Full Text PDFExtensive inter-individual variations in pharmacokinetics are considered as a major reason for unpredictable drug responses. As the most important drug metabolic enzymes, inter-individual variations of cytochrome P450 (CYP) activities are not clear in human liver. In this paper, metabolic activities, gene polymorphisms and protein contents of 10 CYPs were determined in 105 human normal liver microsomes.
View Article and Find Full Text PDFHuman cytochrome P450 oxidoreductase (POR) provides electrons for all microsomal cytochromes P450 (P450s) and plays an indispensable role in drug metabolism catalyzed by this family of enzymes. We evaluated 100 human liver samples and found that POR protein content varied 12.8-fold, from 12.
View Article and Find Full Text PDFThe lack of information concerning individual variation in drug-metabolizing enzymes is one of the most important obstacles for designing personalized medicine approaches for hepatocellular carcinoma (HCC) patients. To assess cytochrome P450 (CYP) in the metabolism of endogenous and exogenous molecules in an HCC setting, the activity changes of 10 major CYPs in microsomes from 105 normal and 102 HCC liver tissue samples were investigated. We found that CYP activity values expressed as intrinsic clearance (CLint) differed between HCC patients and control subjects.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC) accompanied by severe liver dysfunction is a serious disease, which results in altered hepatic clearance. Generally, maintenance doses depend upon drug clearance, so individual dosage regimens should be customized for HCC patients based on the condition of patients. Based on clearance of CYP isoform-specific substrates at the microsomal level (CLM), microsomal protein per gram of liver (MPPGL), liver weight, hepatic blood flow, hepatic clearance values (CLH) for 10 CYPs in HCC patients (n=102) were extrapolated using a predictive bottom-up pharmacokinetic model.
View Article and Find Full Text PDFThe lack of information concerning individual variation in content and activity of human liver microsomal protein is one of the most important obstacles for designing personalized medicines. We demonstrated that the mean value of microsomal protein per gram of liver (MPPGL) was 39.46 mg/g in 128 human livers and up to 19-fold individual variations existed.
View Article and Find Full Text PDFHuman cytochrome b5 (Cyt b5) plays important roles in cytochrome P450 (CYP)-mediated drug metabolism. However, the expression level of Cyt b5 in normal human liver remains largely unknown. The effect of Cyt b5 on overall CYP activity in human liver microsomes (HLM) has rarely been reported and the relationship between Cyt b5 and the activity of polymorphic CYP has not been systematically investigated.
View Article and Find Full Text PDFBaicalin has been used as mainly bioactive constituent of about 100 kinds of traditional Chinese medicines in Chinese pharmacopoeia. The effect of baicalin on cytochrome P450 should be paid more attention because baicalin was used widely. The aim of this study was to investigate whether baicalin could inhibit CYP1A2 in pooled human liver microsomes (HLMs) and in rats in vivo and the gene polymorphisms could affect inter-individual variation in IC50 in 28 human livers.
View Article and Find Full Text PDFBaicalin purified from the root of Radix scutellariae is widely used in clinical practices. This study aimed to evaluate the effect of baicalin on the pharmacokinetics of nifedipine, a CYP3A probe substrate, in rats in vivo and in vitro. In a randomised, three-period crossover study, significant changes in the pharmacokinetics of nifedipine (2 mg/kg) were observed after treatment with a low (0.
View Article and Find Full Text PDFEthnopharmacological Relevance: Baicalin is one of the major bioactive constituents of Scutellariae Radix, the root of Scutellariae baicalensis Georgi and possesses a wide variety of pharmacological properties.
Aim Of The Study: To elucidate the effect of baicalin on the pharmacokinetics of theophylline in rats, focusing on plasma protein binding displacement and inhibition effect on CYP1A2 in vivo and in vitro.
Materials And Methods: The study was a randomized, three-period crossover design.
Baicalin has been shown to possess many pharmacological effects, including antiviral, antioxidant, anti-cancer and anti-inflammatory properties. In the current study, we reveal the inhibitory effects of baicalin on the metabolism of dextromethorphan (DXM), a dual probe substrate of CYP2D and CYP3A, in rats. Lineweaver-Burk plots demonstrated that baicalin inhibited the activities of CYP2D and CYP3A in a non-competitive manner in rat liver microsomes (RLMs).
View Article and Find Full Text PDFEur J Clin Pharmacol
September 2009
Background: The interleukin (IL)-4 and IL-4R genes are linked to allergic diseases and atopy and elevated serum IgE levels closely follow the presentation of penicillin allergy. We have evaluated the association between specific immunoglobulin (Ig)E, polymorphisms of IL-4Ralpha, and penicillin allergy.
Methods: Eight types of specific IgE to penicillins were detected with the radioallergosorbent test (RAST) in 242 patients with penicillin allergy and 220 control subjects.
The role of IgG antibodies in inducing or modifying allergic reaction has not been sufficiently clarified. The objective of this investigation is to elucidate the relationship between IgG antibodies and penicillin allergy, between IgG and IgE antibodies in allergic patients. Enzyme-linked immunosorbent assay and Radioallergosorbent test were used to examine eight kinds of specific IgG and IgE antibodies, including major antigenic determinants: benzylpenicilloyl (BPO), ampicilloyl (APO), amoxicilloyl (AXO) and phenoxomethylpenicilloyl (PVO), and minor antigenic determinants: benzylpenicillanyl (BPA), ampicillanyl (APA), amoxicillanyl (AXA) and phenoxomethylpenicillany (PVA), in the sera of 249 patients with penicillin allergy.
View Article and Find Full Text PDFObjective: The findings of numerous studies have suggested that both genetic and environmental influences are involved in the pathogenesis of allergic disease and atopy. We studied the polymorphisms in the interferon (IFN)-gamma (gamma) and IFN-gamma receptor 1 (IFNR1) gene with the aim of clarifying the relationships among these polymorphisms, penicillin allergy and anti-penicillin antibodies.
Methods: A restriction endonuclease fragment length polymorphism (RFLP)-PCR analysis and sequencing were used to study the IFNR1 and IFN-gamma polymorphisms.
Objective: Our aim was to investigate the hypothesis that the sera interleukin-10 (IL-10) level and polymorphic nucleotides within the IL-10 gene promoters would link to specific IgE and IgG production and the expression of penicillin allergy.
Methods: One hundred and two patients and 86 healthy subjects were chosen for assay of serum IL-10 level by enzyme-linked immunosorbent assay (ELISA) and type -1082 G/A and -819 C/T alleles by sequence-specific primer polymerase chain reaction (SSP-PCR). Radioallergosorbent test (RAST) and ELISA were used to examine eight types of specific immunoglobulin-E (IgE) and IgG antibodies, respectively, which included four types of antibodies to major and minor antigenic determinants.
Background: Thiopurine S-methyltransferase (TPMT) is an enzyme that catalyzed the S-methylation of thiopurine drugs. TPMT activity exhibits an interindividual variability, mainly as a result of genetic polymorphism. Patients with intermediate or deficient TPMT activity are at risk for toxicity after receiving standard doses of thiopurine drugs.
View Article and Find Full Text PDFBackground: Because of the pivotal role of the human leukocyte antigen (HLA) class II molecules in regulating the immune response and their extensive polymorphism, it is not surprising that particular HLA class II alleles have been implicated in susceptibility to allergic diseases and in restriction of the IgE responses to a variety of allergens. We investigated the relationship between HLA-DRB genotype and allergies to various penicillins and explored HLA-DRB restriction of IgE responses to these derivatives of penicillin.
Methods: Radioallergosorbent test was used to examine 8 kinds of specific IgE antibodies (4 major and 4 minor antigenic determinants) in the sera of 248 patients with an allergy to penicillins and 101 healthy subjects without any allergic reaction.
Eur J Clin Pharmacol
February 2006
Objective: Omeprazole, lansoprazole and rabeprazole have been widely used as proton pump inhibitors (PPIs). They can be metabolized in the liver by CYP2C19, a polymorphic enzyme, and have a wide inter-individual variability with respect to drug response. In the investigation reported here, we examined the kinetic characteristics of the three PPIs in healthy Chinese subjects in relation to CYP2C19 genotype status.
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