Cytotoxicity, thiol depletion and inhibition of O6-methylguanine-DNA methyltransferase by various aldehydes in cultured human bronchial fibroblasts

Lipid peroxidation aldehydes of the 4-hydroxy-, ß-unsaturatedtype, as well as the tobacco-smoke related , ß-unsaturatedaldehyde, acrolein, were highly cytotoxic and decreased theintracellular thiol content in cultured human bronchial fibroblastsafter treatment with micromolar concentrations. In comparison,formaldehyde and acetaldehyde were less toxic and 100- to 300-foldhigher doses were required to affect cell survival or thiollevels. The unsaturated aldehydes also markedly inhibited theDNA repair enzyme O⁶-methylguanine-DNA methyltransferase knownto have a cysteine residue in its active site, but had no effecton the activity of uracil-DNA glycosylase. Our results indicatethat reactive aldehydes of either exogenous or endogenous originhave direct cytotoxic effects and may also make cells more susceptibleto other toxic chemicals due to an impairment in cellular defensemechanisms, e.g., DNA repair and detoxification by systems requiringglutathione.     

Medical Marijuana Laws,Marijuana Use,and Opioid-Related Outcomes among Women in the United States

BackgroundIn the context of the opioid epidemic, a limited but growing body of literature has found state medical marijuana laws (MMLs) to be associated with lower levels of opioid prescribing. However, robust evidence linking state MMLs with individual-level opioid-related outcomes is lacking, particularly among women. This finding is especially true for pregnant and parenting women, who have been disproportionately affected by the opioid crisis.MethodsUsing data drawn from the 2002–2014 National Survey on Drug Use and Heath, the study uses a difference-in-differences estimation strategy to compare opioid-related outcomes (opioid misuse initiation, opioid misuse in the past month and past year, and opioid use disorder) among all women, pregnant women, and parenting women in states with and without MMLs (before and after implementation). The study also investigates the impact of MMLs on marijuana use and marijuana use disorder.ResultsThe findings indicate that MMLs were not associated with opioid misuse, opioid misuse initiation, or opioid use disorder among all women, pregnant women, and parenting women. These laws were, however, positively correlated with marijuana use and marijuana use disorder among all women and women with children. In addition, MMLs were associated with an increase in the frequency of opioid misuse for pregnant women and a decrease in the frequency of opioid misuse for parenting women.ConclusionsThis finding suggests that, although medical marijuana may be viewed by some as a substitute for opioid analgesics, MMLs may not be an effective policy tool to tackle the opioid epidemic among women, especially pregnant and parenting women.     

Plötzlicher Brustschmerz und Unterleibsschmerzen

Notfall + Rettungsmedizin - Der plötzliche Brust- und der plötzliche Unterleibsschmerz gehören zu den häufigsten Gründen, die Patienten in die Notaufnahme führen. Das...     

Health state utilities associated with treatment process for oral and injectable GLP-1 receptor agonists for type 2 diabetes

Quality of Life Research - Previous research suggests that treatment process can have an influence on patient preference and health state utilities. This study examined preferences and estimated...     

Youth Mental Health First Aid: Examining the Influence of Pre-Existing Attitudes and Knowledge on Training Effectiveness

Journal of Prevention - Youth Mental Health First Aid (YMHFA) is a gatekeeper training designed to assist professionals in their identification and response to youth mental illness. Despite...     

MDA in plasma as a biomarker of exposure to pyrolysed MDI-based polyurethane: correlations with estimated cumulative dose and genotype for N-acetylation

The object of this study was to investigate whether exposure of pipe-layers to thermal degradation products of diphenylmethane diisocyanate (MDI) could be assessed by analysing 4,4-methylenedianiline (MDA) in hydrolysed plasma and urine, and whether the genotype for N-acetylation affected these biomarker levels. Blood and urine samples were drawn from 30-pipe-layers who had been welding polyurethane (PUR) insulated pipes during the preceding 3 months. MDA in hydrolysed plasma and urine was determined with a gas chromatography-mass spectrometry technique, and genotype for N-acetylation was analysed with a polymerase chain reaction technique. MDA in plasma was detected in 18 of the 30 pipe-layers. Their plasma concentrations of MDA varied from 0.05 to 8.48 g/1. There was a significant negative correlation between time since last welding of PUR-insulated pipes and P-MDA (r _s = 0.50, P = 0.005). There was also a significant positive correlation between the estimated number of welded PUR-insulated pipes during the preceding 3 months and P-MDA (r _s = 0.68, P = < 0.001). No significant association between genotype of N-acetylation and P-MDA was observed in a multiple regression analysis when adjustment was made for the estimated cumulative exposure to thermal degradation products of MDI. MDA in urine was detected in only four of the 30 pipe-layers. These four subjects had been welding PUR pipes on the same day as the sampling, or on the day before. The present results indicate the spot plasma samples analysed for MDA may give a rather good estimate of exposure to MDI during the preceding months. P-MDA, but not U-MDA, therefore seems to be a useful biomarker of long-term exposure to MDI. The individual N-acetylation capacity did not affect the plasma levels of MDA.     

Effect of acupuncture compared with placebo-acupuncture at P6 as additional antiemetic prophylaxis in high-dose chemotherapy and autologous peripheral blood stem cell transplantation: a randomized controlled single-blind trial.

PURPOSE: The purpose is to investigate an additional antiemetic effect to ondansetron with needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture in patients undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation. EXPERIMENTAL DESIGN: Eighty patients who were admitted to hospital for high-dose chemotherapy and autologous peripheral blood stem cell transplantation were included into a randomized placebo-controlled single-blind trial. The patients were randomized to receive acupuncture (n = 41) or noninvasive placebo acupuncture (n = 39) at the acupuncture point P6 30 min before first application of high-dose chemotherapy and the day after. All patients received 8 mg ondansetron/day i.v. as basic antiemetic prophylaxis. The main outcome measure was the rate of patients who either had at least one episode of vomiting or required any additional antiemetic drugs on the first 2 days of chemotherapy. RESULTS: The main outcome measure showed no significant difference (P = 0.82): 61% failure in the acupuncture group and 64% in the placebo acupuncture group (95% confidence interval of 3% difference: -18.1 and 24.3%). Comparing nausea, episodes of vomiting or retching and number of additionally required antiemetic drugs did not provide any discrepancy with the main result. CONCLUSIONS: This study suggests that in combination with ondansetron i.v., invasive needle acupuncture at P6 compared with nonskin-penetrating placebo acupuncture has no additional effect for the prevention of acute nausea and vomiting in high-dose chemotherapy.     

Sibutramine treatment in obesity: initial eating behaviour in relation to weight loss results and changes in mood.

The aim of the study was to study the role of initial eating behaviour for subsequent weight loss in treatment with sibutramine (Reductil, Meridia) an anti-obesity drug enhancing satiety, and also to assess changes in mood during the treatment. The participants were 36 obese patients with a mean BMI of 39 kg m(-2). Eating behaviour was assessed with the three factor eating questionnaire (TFEQ), and depressive features with the comprehensive psychopathological rating scale (CPRS). Sibutramine (15 mg) was administered daily. The TFEQ restraint scale was negatively related to 6 months weight loss. In particular, strategic dieting behaviour and a more controlled attitude towards self-regulation were negatively related to weight loss. A positive non-placebo controlled change in mood was found already after 2 months treatment. The changes in mood were not related to the weight loss. Patients with more unrestrained eating seem to have reduced their amount of food intake more radically with enhanced satiety, manifested by greater weight loss. Physiologically enhanced satiety could have the greatest weight loss effect for patients whose eating is more governed by hunger drives and appetite rather that by conscious efforts and cognitive control.