Coffee consumption protects human lymphocytes against oxidative and 3-amino-1-methyl-5H-pyrido[4,3-b]indole acetate (Trp-P-2) induced DNA-damage: results of an experimental study with human volunteers.

Aim of the study was to investigate the impact of coffee on DNA-stability in humans. DNA-damage was monitored in lymphocytes of eight individuals with single cell gel electrophoresis assays before and after consumption of 600 ml coffee (400 ml paper filtered and 200 ml metal filtered/d) for five days. Under standard conditions, no alteration of DNA-migration was seen, but a strong reduction of DNA-migration attributable to endogenous formation of oxidised purines and pyrimidines was detected with restriction enzymes; furthermore DNA-damage caused by reactive oxygen radicals (H2O2 treatment) and by the heterocyclic aromatic amine 3-amino-1-methyl-5H-pyrido[4,3-b]indole-acetate was significantly reduced after coffee consumption by 17% and 35%, respectively. Also in in vitro experiments, inhibition of H2O2 induced DNA-damage was observed with coffee at low concentrations (相似文献   

Reduction in antioxidant defenses may contribute to ochratoxin A toxicity and carcinogenicity.

Ochratoxin A (OTA) is a renal carcinogen in rodents. Its human health significance is unclear. It likely depends upon the mechanism of carcinogenesis. In a previous microarray study a reduction in nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)-dependent gene expression was observed in the kidney but not in the liver of rats fed OTA up to 12 months. Nrf2 regulates detoxification and antioxidant gene expression. The present report shows that OTA decreased the protein expression of several markers of the Nrf2-regulated gene battery in kidney in vivo indicating that the effects observed at mRNA level may be of biological significance. The OTA-mediated Nrf2 response could be reproduced in an NRK renal cell line and in primary hepatocyte cultures. In in vitro systems, an OTA-mediated inhibition of Nrf2 activity was demonstrated by electrophoretic mobility shift and Antioxidant Regulatory Element-driven luciferase reporter assays. The reduction of Nrf2-regulated gene expression resulted in oxidative DNA damage as evidenced by formation of abasic sites in vitro and confirmed in kidney in vivo. All OTA-mediated effects observed were prevented by pretreatment of cell cultures with inducers of Nrf2 activity. Our data suggest that reduction of cellular defense against oxidative stress by Nrf2 inhibition may be a plausible mechanism of OTA nephrotoxicity and carcinogenicity.     

Target controlled infusion of ketamine as analgesia for TIVA with propofol

PURPOSE: To determine the accuracy of a target controlled infusion system for ketamine and to assess its suitability for the provision of analgesia when used in conjunction with a propofol infusion in spontaneously breathing patients. METHODS: Nineteen, adult, ASA I-III patients scheduled for elective surgery were studied. After premedication with 20 mg temazepam an appropriate plasma concentration of ketamine was selected and, when the target controlled infusion (TCI) system indicated that this had been achieved, anesthesia was induced and maintained using a propofol infusion. The plasma ketamine concentration was measured at predetermined intervals and cardiovascular and respiratory parameters recorded at 10 min intervals. Patients were reviewed in recovery and 24 hr postoperatively to assess the adequacy of their recovery and the presence of any undesirable side effects. RESULTS: The TCI system had a median performance error against predicted plasma concentrations of 18.9% (SE 2.5%) and a median absolute performance error of 23.3% (SE 2.3%). Divergence was 20.3% (SE 30.1%) and wobble was 12.9% (SE 2.1%). There was a mean decrease in arterial pressure of 6.4% (SD 19.7%) and a mean increase in heart rate of 4.3% (SD 17.4%). Little respiratory depression occurred and all patients made a rapid postoperative recovery with none describing unpleasant dreams or hallucinations. CONCLUSION: The TCI system provided a clinically acceptable degree of control of the plasma ketamine concentration although some further improvement should be possible by amending the pharmacokinetic model. Clinically the combination with a propofol infusion proved to be a satisfactory anesthetic technique.     

Should a psychiatrist report a bus driver’s alcohol and drug abuse? An ethical dilemma

Denial of alcohol or drug abuse, and of its possible consequences, can complicate medical and psychiatric care. We present the case of an HIV-positive bus driver with substance abuse who initially denied ongoing use of alcohol and of other drugs, but later admitted to both. The psychiatrist’s duty to protect the patient’s confidentiality, coupled with concerns about public safety, created an ethical dilemma. In discussing this dilemma we stress the importance of preserving confidentiality, both to facilitate treatment and also to further the safety of others.     

The coffee-specific diterpenes cafestol and kahweol protect against aflatoxin B1-induced genotoxicity through a dual mechanism

The diterpenes cafestol and kahweol (C&K) have been identified in animal models as two potentially chemoprotective agents present in green and roasted coffee beans. It has been postulated that these compounds may act as blocking agents by producing a co-ordinated modulation of multiple enzymes involved in carcinogen detoxification. In this study, we investigated the effects of C&K against the covalent binding of aflatoxin B1 (AFB1) metabolites to DNA. Male Sprague-Dawley rats were treated with increasing amounts of a mixture of C&K in the diet (0-6200 p.p.m.) for 28 and 90 days. A dose-dependent inhibition of AFB1 DNA-binding was observed using S9 and microsomal subcellular fractions from C&K-treated rat liver in an in vitro binding assay. Significant inhibition was detected at 2300 p.p.m. and maximal reduction of DNA adduct formation to nearly 50% of the control value was achieved with 6200 p.p.m. of dietary C&K. Two complementary mechanisms may account for the chemopreventive action of cafestol and kahweol against aflatoxin B1 in rats. A decrease in the expression of the rat activating cytochrome P450s (CYP2C11 and CYP3A2) was observed, as well as a strong induction of the expression of the glutathione-S- transferase (GST) subunit GST Yc2, which is known to detoxify highly the most genotoxic metabolite of AFB1. These data and the previously demonstrated effects of C&K against the development of 7,12- dimethylbenz[a]anthracene (DMBA)-induced carcinogenesis at various tissue sites suggest the potential widespread effect of these coffee components against chemical carcinogenesis.