The other targets of alcohol use disorder : The systemic effects of alcohol abuse

Drinking alcohol is an established and normalised practice in our society, even though it can physically harm us. High-risk alcohol drinking patterns can increase the chance of negative consequences for the drinkers or their environment. The liver is by far the organ most affected by alcohol abuse; however, alcohol use disorder is a systemic disease which affects a wide range of organs and psychological processes. Other systems that can be affected by continued alcohol consumption include the immune, neurological, and cardiovascular systems. In addition, alcohol can lead to epigenetic alterations that may be transmitted from one generation to the nex

Quantum times of arrival for multiparticle states

Using the concept of crossing state and the formalism of second quantization, we propose a prescription for computing the density of arrivals of particles for multiparticle states, both in the free and the interacting case. The densities thus computed are positive, covariant in time for time independent hamiltonians, normalized to the total number of arrivals, and related to the flux. We investigate the behaviour of this prescriptions for bosons and fermions, finding boson enhancement and fermion depletion of arrivals.Comment: 10 a4 pages, 5 inlined figure

TJ-41 Induces Apoptosis and Potentiates the Apoptotic Effects of 5-FU in Breast Cancer Cell Lines

Recent studies suggest that TJ-41, a herbal drug, possesses chemotherapeutic effects. Accordingly, this study was undertaken to investigate the anticarcinogenic effects of TJ-41 on human breast cancer cells lines. TJ-41 inhibited the proliferation of human breast cancer cell lines dose dependently. Flow cytometric analysis showed that this decrease in DNA synthesis is to be associated with induction of apoptosis. In both cell lines, apoptosis was abolished by caspase-9 inhibitor Z-LEHD-fmk but was weakly inhibited by caspase-8 inhibitor Z-IETD-fmk, indicating that caspase-9 activation was involved in TJ-41 induced apoptosis. Additionally, TJ-41 stimulated phosphorylation of c-Jun NH2-terminal kinase (JNK) and pretreatment of breast cancer cells with JNK inhibitor SP600125 completely abolished TJ-41 induced apoptosis. Our data also demonstrate that combined treatment of TJ-41 and 5-FU significantly potentiates the apoptotic effects of 5-FU in both breast cancer cell lines. Taken together, these data suggest that TJ-41 might provide a novel chemotherapeutic treatment for breast cancer

Markers Of Inflammation And Mortality In A Cohort Of Patients With Alcohol Dependence

Inflammation and intestinal permeability are believed to be paramount features in the development of alcohol-related liver damage. We aimed to assess the impact of 3 surrogate markers of inflammation (anemia, fibrinogen, and ferritin levels) on mid-term mortality of patients with alcohol dependence. This longitudinal study included patients with alcohol dependence admitted for hospital detoxification between 2000 and 2010. Mortality was ascertained from clinical charts and the mortality register. Associations between markers of inflammation and all-cause mortality were analyzed with mortality rates and Cox proportional hazards regression models. We also performed a subgroup analysis of mortality rates in patients with anemia, based on their mean corpuscular volume (MCV). We included 909 consecutive patients with alcohol dependence. Patients were mostly male (80.3%), had a median age of 44 years (interquartile range [IQR]: 38-50), and upon admission, their median alcohol consumption was 192 g/day (IQR: 120-265). At admission, 182 (20.5%) patients had anemia; 210 (25.9%) had fibrinogen levels > 4.5 mg/dL; and 365 (49.5%) had ferritin levels > 200 ng/mL. At the end of follow-up (median 3.8 years [IQR: 1.8-6.5], and a total of 3861.07 person-years), 118 patients had died (12.9% of the study population). Cox regression models showed that the presence of anemia at baseline was associated with mortality (hazard ratio [HR]: 1.67, 95% confidence interval [CI]: 1.11-2.52, P< 0.01); no associations were found between mortality and high fibrinogen or high ferritin levels. A subgroup of patients with anemia was analyzed and compared to a control group of patients without anemia and a normal MCV. The mortality ratios of patients with normocytic and macrocytic anemia were 3.25 (95% CI: 1.41-7.26; P< 0.01) and 3.39 (95% CI: 1.86-6.43; P< 0.01), respectively. Patients with alcohol dependence admitted for detoxification had an increased risk of death when anemia was present at admission. More accurate markers of systemic inflammation are needed to serve as prognostic factors for poor outcomes in this subset of patients

Liver Ultrasound Abnormalities in Alcohol Use Disorder

Alcohol-related liver disease is the most common alcohol-related medical illness, and it is the major driver of liver-related deaths worldwide. However, no screening guidelines currently exist for the early detection of liver disease in patients with risky drinking or those with alcohol use disorder. Moreover, most patients with alcohol-related liver fibrosis, which is the main prognostic factor of progression to end-stage liver disease, have normal blood tests. Abdominal ultrasound is a cheap and readily available diagnostic procedure that is rarely used in patients with alcohol use disorder without overt liver disease. In addition, abdominal ultrasound can detect other forms of liver disease, which are not uncommon in patients with unhealthy alcohol use, and can have a negative impact on the natural history of alcohol-related liver disease. In this chapter we will review the current knowledge about the use of liver ultrasound in patients with alcohol use disorder for the early detection of alcohol-related liver disease, as well as the potential use to detect other forms of liver disease. We will also briefly discuss other methods for the noninvasive detection of liver steatosis and/or liver fibrosis in patients with alcohol use disorder

Markers of Monocyte Activation, Inflammation, and Microbial Translocation Are Associated with Liver Fibrosis in Alcohol Use Disorder

Background: The association between markers of inflammation (interleukin (IL)-6 and IL-10), monocyte activation (sCD163 and sCD14), and microbial translocation (lipopolysaccharide (LPS) and LPS binding protein) and liver fibrosis in patients with alcohol use disorder (AUD) and no overt liver disease is not well established. Methods: We studied patients admitted for treatment of AUD at two hospitals in Barcelona. Advanced liver fibrosis (ALF) was defined as FIB-4 > 3.25. Results: A total of 353 participants (76.3% male) were included and 94 (26.5%) had ALF. In adjusted correlation analyses, sCD163, sCD14, IL-6, IL-10, and LPS binding protein levels directly correlated with FIB-4 values (adjusted correlation coefficients 0.214, 0.452, 0.317, 0.204, and 0.171, respectively). However, LPS levels were inversely associated with FIB-4 (-0.283). All plasma marker levels in the highest quartile, except LPS, were associated with ALF (sCD163, sCD14, IL-6, IL-10, and LPS binding protein: adjusted odds ratio (aOR) 11.49 (95% confidence interval 6.42-20.56), 1.87 (1.11-3.16), 2.99 (1.79-5.01), 1.84 (1.11-3.16), and 2.13 (1.30-3.50), respectively). Conversely, LPS levels in the lowest quartile were associated with ALF (aOR 2.58 (1.48-4.58), p < 0.01). Conclusion: In AUD patients, plasma levels of the markers of inflammation, monocyte activation, and microbial translocation are associated with ALF

Protocol de diagnòstic i tractament del virus de l’hepatitis C per persones drogodependents

Hepatitis C; Drogodependents; Tractament; DiagnòsticHepatitis C; Drogodependientes; Tratamiento; DiagnósticoHepatitis C; Drug addicts; Treatment; DiagnosisProtocol operatiu de coordinació i atenció integrada entre els centres d’atenció i seguiment (CAS) que fan atenció ambulatòria a les drogodependències, i els serveis hospitalaris encarregats del tractament de la infecció i de la patologia hepàtica pel VHC (serveis de patologia digestiva, unitat d’hepatologia, medicina interna i malalties infeccioses)

Alcohol Consumption during Pregnancy : Analysis of Two Direct Metabolites of Ethanol in Meconium

Alcohol consumption in young women is a widespread habit that may continue during pregnancy and induce alterations in the fetus. We aimed to characterize prevalence of alcohol consumption in parturient women and to assess fetal ethanol exposure in their newborns by analyzing two direct metabolites of ethanol in meconium. This is a cross-sectional study performed in September 2011 and March 2012 in a series of women admitted to an obstetric unit following childbirth. During admission, socio-demographic and substance use (alcohol, tobacco, cannabis, cocaine, and opiates) during pregnancy were assessed using a structured questionnaire and clinical charts. We also recorded the characteristics of pregnancy, childbirth, and neonates. The meconium analysis was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to detect the presence of ethyl glucuronide (EtG) and ethyl sulfate (EtS). Fifty-one parturient and 52 neonates were included and 48 meconium samples were suitable for EtG and EtS detection. The median age of women was 30 years (interquartile range (IQR): 26-34 years); EtG was present in all meconium samples and median concentration of EtG was 67.9 ng/g (IQR: 36.0-110.6 ng/g). With respect to EtS, it was undetectable (<0.01 ng/g) in the majority of samples (79.1%). Only three (6%) women reported alcohol consumption during pregnancy in face-to-face interviews. However, prevalence of fetal exposure to alcohol through the detection of EtG and EtS was 4.2% and 16.7%, respectively. Prevention of alcohol consumption during pregnancy and the detection of substance use with markers of fetal exposure are essential components of maternal and child health