Electricity production from municipal solid waste using microbial fuel cells.

The organic content of municipal solid waste has long been an attractive source of renewable energy, mainly as a solid fuel in waste-to-energy plants. This study focuses on the potential to use microbial fuel cells to convert municipal solid waste organics into energy using various operational conditions. The results showed that two-chamber microbial fuel cells with carbon felt and carbon felt allocation had a higher maximal power density (20.12 and 30.47 mW m(-2) for 1.5 and 4 L, respectively) than those of other electrode plate allocations. Most two-chamber microbial fuel cells (1.5 and 4 L) had a higher maximal power density than single-chamber ones with corresponding electrode plate allocations. Municipal solid waste with alkali hydrolysis pre-treatment and K3Fe(CN)6 as an electron acceptor improved the maximal power density to 1817.88 mW m(-2) (~0.49% coulomb efficiency, from 0.05-0.49%). The maximal power density from experiments using individual 1.5 and 4 L two-chamber microbial fuel cells, and serial and parallel connections of 1.5 and 4 L two-chamber microbial fuel cells, was found to be in the order of individual 4 L (30.47 mW m(-2)) > serial connection of 1.5 and 4 L (27.75) > individual 1.5 L (20.12) > parallel connection of 1.5 and 4 L (17.04) two-chamber microbial fuel cells . The power density using municipal solid waste microbial fuel cells was compared with information in the literature and discussed.

High CYP2C19 phenotypic variability in gastrointestinal cancer patients.

PURPOSE: CYP2C19 contributes to the metabolism of several chemotherapeutic agents. The CYP2C19 homozygous null function genotype strongly predicts activity phenotype in healthy populations. An additional acquired loss of function has been reported in up to one-third of cancer patients. It is not known whether this phenomenon also occurs in patients with earlier stage or in resected disease. METHODS: This study investigated whether acquired loss of CYP2C19 function was detectable in patients with stage III-IV or resected gastrointestinal cancer. CYP2C19 genotype was determined in 49 patients, and subjects were probed for CYP2C19 activity on three test occasions. RESULTS: An acquired loss of CYP2C19 activity was observed in 20% of stage III-IV and 17% of resected patients at the first test. Significant (p < 0.01) genotype-phenotype discordance was observed in both groups. There were no direct associations between this discordance and inflammatory markers, tumour burden or chemotherapeutic history. Notably, hepatic CYP2C19 function was not stable over time and phenotype conversion occurred in 23 patients over the period of testing. CONCLUSION: Reliance on germ-line genotype to infer a poor metaboliser status could substantially underestimate the number of patients with deficient CYP2C19 function. This could compromise the interpretation of genotype-based clinical association studies.

A population-based study on trend in incidence of distal radial fractures in adults in Taiwan in 2000-2007.

UNLABELLED: This population-based study was conducted using claims data obtained from the National Health Insurance to investigate the trend in incidence of distal radial fractures in adults in Taiwan from 2000 to 2007. Our results revealed an increasing trend, particularly among women >50 years of age. INTRODUCTION: This population-based study used insurance claims data from 2000 to 2007 obtained from the National Health Research Institute to investigate the longitudinal trend in distal radial fractures in adults ≥20 years old in Taiwan. METHODS: We estimated the age- and gender-specific annual incidence rates of distal radial fracture and compared the differences in distribution by sociodemographic status between patients with and those without distal radial fracture and the differences in incidence rates between 2000 and 2007. RESULTS: The incidence of fracture was higher in women than in men. The overall female-to-male rate ratios were 1.52 in 2000 (12.3 vs 8.06 per 10,000 persons) and 1.89 in 2007 (18.9 vs 10.0 per 10,000 persons). There was marked increase in age-specific incidence beginning in the 50-54-year age group, particularly among women. CONCLUSION: These results imply the need for more effective intervention for the prevention of subsequent fracture and disability, particularly for perimenopausal women.

Do 5-fluorouracil therapies alter CYP2C19 metaboliser status?

PURPOSE: To report a case of altered CYP2C19 metaboliser status following 5-fluorouracil treatment. METHODS: A 78-year-old male with stage III colorectal adenocarcinoma was prescribed with weekly iv 5-fluorouracil and folinic acid (FU/FA). Fourteen weeks after starting FU/FA, the patient was enrolled in a clinical study to investigate the role of tumour burden on drug metabolising enzyme activity. CYP2C19 genotype was determined and the activity of CYP2C19 was measured using proguanil (PG) as a probe substrate. A metabolic ratio (PG/CG) for CYP2C19 activity was determined on three separate occasions, 7 days apart. RESULTS: The patient was homozygous wild type (CYP2C19*1/*1), and on the first test, the metabolic ratio was concordant with the extensive metaboliser genotype. However, at day 14 and day 21, the metabolic capacity of this enzyme had decreased, and the subject had become a poor metaboliser (PG/CG > 30). The patient developed grade III hand and foot syndrome at day 10 of the study during the period of null CYP2C19 activity. CONCLUSIONS: Although 5FU is not a substrate for hepatic drug metabolising CYP enzymes, it may interfere with the synthesis of CYP2C19. Decreased activity of a related enzyme, CYP2C9, following 5FU has been reported previously. Down regulation of CYP2C9 and CYP2C19 synthesis by 5FU therapies may explain the adverse effect of 5FU on the clinical disposition of warfarin and phenytoin.

CYP2C19 pharmacogenetics in advanced cancer: compromised function independent of genotype.

CYP2C19 is a drug-metabolising enzyme involved in the metabolism of a number of chemotherapeutic agents including cyclophosphamide. Variants of the CYP2C19 gene result in a loss of function polymorphism, which affects approximately 3% of the Caucasian population. These individuals are poor metabolisers (PM) of a wide range of medications including omeprazole (OMP). In healthy subjects PM can be identified through homozygous variant genotype. However, a discordance between CYP2C19 genotype and phenotype has been reported previously in a small study of cancer patients. To investigate whether CYP2C19 activity was decreased in patients with advanced cancer, CYP2C19 genotype was determined in 33 advanced cancer patients using PCR-RFLP analysis for the two important allelic variants (*2,681G>A and *3,636G>A) and the activity of the enzyme was evaluated using the CYP2C19 probe drug OMP. The activity of the drug-metabolising enzyme CYP2C19 was severely compromised in advanced cancer patients, resulting in a PM status in 37% of the patients who had normal genotype. This is significantly (P<0.0005) higher than that would be predicted from the genotypic status of these patients. There was no evidence of a correlation between compromised CYP2C19 activity and any of the proinflammatory cytokines or acute phase response proteins studied. However, there was preliminary evidence of an association between PM status and low body mass (P=0.03). There is increasing interest in using pharmacogenetics to 'individualise medicine', however, the results of this study indicate that in a cancer population genotyping for CYP2C19 would significantly underestimate the number of phenotypic PM of drugs, such as cyclophosphamide, which may be metabolised by this enzyme.

The use of dextromethorphan to treat repetitive self-directed scratching, biting, or chewing in dogs with allergic dermatitis.

OBJECTIVE: To evaluate the efficacy of oral dextromethorphan in dogs with a repetitive behavior problem (self-licking, self-chewing, and self-biting associated with chronic allergic dermatitis). ANIMALS: Fourteen dogs with chronic allergic dermatitis were enrolled in the study. Twelve dogs completed the study. PROCEDURE: The dogs were treated for 2 weeks each with dextromethorphan (2 mg/kg BID) and placebo in a randomized, double blind, crossover designed study. A dermatology score, including an assessment of affected areas of the integument and the level of self-directed behavior, was generated before and following each 2-week phase of the study. Owners were required to record daily the amount of time they spent with their dog and the amount of time that the dog was observed to be engaged in any of the specified self-directed behaviors. RESULTS: The percent of the observed time that the dogs were reported to be involved in self-directed behaviors was significantly less during the 2-week active drug treatment phase. The pruritus score component of the dermatology score also was significantly less during the active treatment phase. In addition, a dermatologist-rated global assessment was more favorable in 11 of 12 dogs following the active treatment phase. CONCLUSIONS: Dextromethorphan significantly reduces the percentage of time that allergic dogs spend self-licking, self-chewing, and self-biting. CLINICAL RELEVANCE: Dextromethorphan may be a useful adjunct in the management of self-directed behaviors associated with allergic dermatitis and possibly in other repetitive behaviors as well.

Teratogenicity of recently introduced medications in human pregnancy.

OBJECTIVE: To determine how long it takes after a new drug is marketed to establish whether or not its use by pregnant women is likely to pose a substantial teratogenic risk. METHODS: We used standard clinical teratology resources to assess the teratogenic risks in human pregnancy of therapeutic treatment with 468 drugs approved by the US Food and Drug Administration between 1980 and 2000. The teratogenic risk of each treatment was classified using the current online version of TERIS into one of three categories: 1) no risk, minimal risk, or unlikely to produce an increased risk; 2) associated with a small, moderate, or high risk; or 3) risk undetermined. RESULTS: We found that the teratogenic risk in human pregnancy was still undetermined for 91.2% of drug treatments approved in the United States between 1980 and 2000. The proportion of treatments classified as having an "undetermined" teratogenic risk was more than 80% for drugs approved for marketing 0-4, 5-9, 10-14, or 15-20 years ago, but the highest proportion of drugs with an "undetermined" teratogenic risk was found among those approved 15-20 years ago. The agreement between TERIS risk ratings and Food and Drug Administration Use-in-Pregnancy Categories for 163 drugs that had been assessed by both systems was poor (kappa +/- standard error = 0.082 +/- 0.042). CONCLUSION: We conclude that inadequate information is available for pregnant women and their physicians to determine whether the benefits exceed the teratogenic risks for most drug treatments introduced in the past 20 years.

Transcription repression of human hepatitis B virus genes by negative regulatory element-binding protein/SON.

A negative regulatory element (NRE) is located immediately upstream of the upstream regulatory sequence of core promoter and second enhancer of human hepatitis B virus (HBV). NRE represses the transcription activation function of the upstream regulatory sequence of core promoter and the second enhancer. In this study, we described the cloning and characterization of an NRE-binding protein (NREBP) through expression cloning. NREBP cDNA is 8266 nucleotides in size and encodes a protein of 2386 amino acids with a predicted molecular mass of 262 kDa. Three previously described cDNAs, DBP-5, SONB, and SONA, are partial sequence and/or alternatively spliced forms of NREBP. The genomic locus of the NREBP/SON gene is composed of 13 exons and 12 introns. The endogenous NREBP protein is localized in the nucleus of human hepatoma HuH-7 cells. Antibody against NREBP protein can specifically block the NRE binding activity present in fractionated nuclear extracts in gel shifting assays, indicating that NREBP is the endogenous nuclear protein that binds to NRE sequence. By polymerase chain reaction-assisted binding site selection assay, we determined that the consensus sequence for NREBP binding is GA(G/T)AN(C/G)(A/G)CC. Overexpression of NREBP enhances the repression of the HBV core promoter activity via NRE. Overexpression of NREBP can also repress the transcription of HBV genes and the production of HBV virions in a transient transfection system that mimics the viral infection in vivo.

Repression of enhancer II activity by a negative regulatory element in the hepatitis B virus genome.

Enhancer II of human hepatitis B virus has dual functions in vivo. Located at nucleotides (nt) 1646 to 1741, it can stimulate the surface and X promoters from a downstream position. Moreover, the same sequence can also function as upstream regulatory element that activates the core promoter in a position- and orientation-dependent manner. In this study, we report the identification and characterization of a negative regulatory element (NRE) upstream of enhancer II (nt 1613 to 1636) which can repress both the enhancer and upstream stimulatory function of the enhancer II sequence in differentiated liver cells. This NRE has marginal inhibitory effect by itself but a strong repressive function in the presence of a functional enhancer II. Mutational analysis reveals that sequence from nt 1616 to 1621 is required for repression of enhancer activity by the NRE. Gel shift analysis reveals that this negative regulatory region can be recognized by a specific protein factor(s) present at the 0.4 M NaCl fraction of HepG2 nuclear extracts. The discovery of the NRE indicates that HBV gene transcription is controlled by combined effects of both positive and negative regulation. It also provides a unique system with which to study the mechanism of negative regulation of gene expression.

Effect of liposomes on suspension stability.

The effect of positively charged liposomes on the stability of negatively charged indomethacin particle suspensions was investigated by adsorption, microelectrophoresis, sedimentation volume, and redispersibility. It was found that flocculation occurred in the neighborhood of the zero point of charge of the liposome:indomethacin suspensions. This resulted from the operation of van der Waals attraction under the condition of nil electrostatic repulsion. Correlation among the results of adsorption, microelectrophoresis, sedimentation volume, and redispersibility was good. The mixing effect of the suspension was examined by microelectrophoresis and confirmed by sedimentation volume and redispersibility. Results indicate that there was no difference between the method of dilution of the liposome:indomethacin concentrated suspension after mixing and the method of dilution of liposomes prior to mixing with the indomethacin suspension. This was due to interaction depending on the charge density of the particles.

Mechanisms for activation and inhibition of carboxypeptidase A catalyzed hydrolyses of peptides and esters.

3,3-Diphenylpropanoate (DPP) activates the carboxypeptidase A catalyzed hydrolysis of benzoylglycyl-L-phenylalanine (BzGly-L-Phe) (Ka = 2.1 x 10 (-3) M) and inhibits ester hydrolysis uncompetitively (K1 =2.1 X 10 (-3) M). A common modifier binding site located adjacent to the peptide and ester substrate binding sites is proposed. The forms of the pathways proposed for activation and inhibition are remarkably similar.