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1. The gastroprotective activity of two azomethine prodrugs of (R)-alpha-methylhistamine was examined in lesions induced by absolute ethanol (1 ml/rat intragastrically for 1 h). 2. Pretreatment with (R)-alpha-methylhistamine as well as with the prodrugs (30 and 100 mg/kg intragastrically [IG]) significantly reduced macroscopically visible lesions caused by ethanol, with protection being almost complete at 100 mg/kg. 3. Histologically, in rats pretreated with the three compounds at a dose of 100 mg/kg, the evidence of damage was rare, with the appearance of gastric mucosa being similar in the different groups. 4. Present results are suggestive of a local component in the protective activity of (R)-alpha-methylhistamine.

In biomedical scientific investigations, expositions of findings are conceptually simplest when they comprise comparisons of discrete groups of individuals or involve discrete features or characteristics of individuals. But the descriptive benefits of categorization become outweighed by their limitations in studies involving dose-response relationships, as in many teratogenic and environmental exposure studies. This article addresses a pair of categorization issues concerning the effects of prenatal alcohol exposure that have important public health consequences: the labeling of individuals as fetal alcohol syndrome (FAS) versus fetal alcohol effects (FAE) or alcohol-related neurodevelopmental disorder (ARND), and the categorization of prenatal exposure dose by thresholds. We present data showing that patients with FAS and others with FAE do not have meaningfully different behavioral performance, standardized scores of IQ, arithmetic and adaptive behavior, or secondary disabilities. Similarly overlapping distributions on measures of executive functioning offer a basis for identifying alcohol-affected individuals in a manner that does not simply reflect IQ deficits. At the other end of the teratological continuum, we turn to the reporting of threshold effects in dose-response relationships. Here we illustrate the importance of multivariate analyses using data from the Seattle, Washington, longitudinal prospective study on alcohol and pregnancy. Relationships between many neurobehavioral outcomes and measures of prenatal alcohol exposure are monotone without threshold down to the lowest nonzero levels of exposure, a finding consistent with reports from animal studies. In sum, alcohol effects on the developing human brain appear to be a continuum without threshold when dose and behavioral effects are quantified appropriately.

AbstractThe efficacy of thyroid (FNAB) processed by liquid‐based cytology (LBC) in Hashimoto's Thyroiditis (HT) in two reference periods, is evaluated. The morphologic features of 820 cases with both methods and the cyto‐histological comparison are analyzed. The diagnosis of hyperplastic nodules (HN) in HT, its mimickers especially in presence of oxyphilic cells and the role of immunocytochemistry (IHC) are studied.150 cases of HT processed by conventional smear (CS) in 1996–98 and 670 with LBC in 2005–2007,were included. The majority of FNAB were carried out under USguidance and fixed with ethyl alcohol for the CS. LBC material was rinsed in the Cytolit solution, processed according to the manufacturer's recommendations. Among the 150 CS, 83 were HT while 67 were HN in HT; in the second triennium 245 LBC were HT and 425 were HN in HT. In the first period a follow‐up (including a second FNA or surgery) was done in 92 cases, in the second period in 116.In the surgical group 97.1% in the first period were benign (all HT and 34/36 HN) and 2.8% malignant(all HN). In 2005–2007, 94% were benign (15 HT and 45/49 HN) and 6%malignant. Thirty HN from the second triennium had ICC for HBME‐1 and Galectin‐3 resulting negative in 93.5%. Among these cases, 10 had a benign histology and a concordant negative ICC.LBC can be used as a valid method for HT, especially for the possible application of ICC to HN, and it allows a correct preoperative selection of lesions Diagn. Cytopathol. 2011; © 2011 Wiley‐Liss, Inc.

Although extreme weather events have played a constant role in human history, heatwaves (HWs) have become more frequent and intense in the past decades, causing concern especially in light of the increasing evidence on climate change. Despite the increasing number of reviews suggesting a relationship between heat and health, these reviews focus primarily on mortality, neglecting other important aspects. This systematic review of reviews gathered the available evidence from research syntheses conducted on HWs and health. Following the PRISMA guidelines, 2232 records were retrieved, and 283 reviews were ultimately included. Information was extracted from the papers and categorized by topics. Quantitative data were extracted from meta-analyses and, when not available, evidence was collected from systematic reviews. Overall, 187 reviews were non-systematic, while 96 were systematic, of which 27 performed a meta-analysis. The majority evaluated mortality, morbidity, or vulnerability, while the other topics were scarcely addressed. The following main knowledge gaps were identified: lack of a universally accepted definition of HW; scarce evidence on the HW-mental health relationship; no meta-analyses assessing the risk perception of HWs; scarcity of studies evaluating the efficacy of adaptation strategies and interventions. Future efforts should meet these priorities to provide high-quality evidence to stakeholders.

Abstract Aims Despite a general decline in tobacco use in the last decades, the prevalence of tobacco smoking in individuals with alcohol use disorder (AUD) remains substantial (45–50%). Importantly, the co-use of both substances potentiates the adverse effects, making it a significant public health problem. Substantial evidence suggests that AUD and Tobacco use disorder (TUD) may share common mechanisms. Targeting these mechanisms may therefore provide more effective therapy. Numerous studies describe a potential role of the endogenous opioid system in both AUD and TUD. Reviewing this literature, we aim to evaluate the efficacy of molecules that target the opioid system as promising therapeutic interventions for treating alcohol and tobacco co-use disorders. Methods We provide a synthesis of the current epidemiological knowledge of alcohol and tobacco co-use disorders. We evaluate clinical and preclinical research that focuses on the regulation of the endogenous opioid system in alcohol, nicotine, and their interactions. Results The epidemiological data confirm that smoking stimulates heavy drinking and facilitates alcohol craving. Pharmacological findings suggest that treatments that are efficacious in the dual addiction provide a beneficial treatment outcome in comorbid AUD and TUD. In this regard, MOP, DOP and NOP-receptor antagonists show promising results, while the findings prompt caution when considering KOP-receptor antagonists as a treatment option in alcohol and tobacco co-use disorders. Conclusions Existing literature suggests a role of the opioid system in sustaining the high comorbidity rates of AUD and TUD. Molecules targeting opioid receptors may therefore represent promising therapeutic interventions in ‘heavy drinking smokers.’

Background and Aims: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. Approach and Results: C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD+/NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. Conclusions: Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.