Stigmatization is common in patients with non-alcoholic fatty liver disease and correlates with quality of life.

BACKGROUND AND AIMS: Stigmatization is a well-documented problem of some diseases. Perceived stigma is common in alcohol-related liver disease and hepatitis C, but little information exists on stigma in patients with non-alcoholic fatty liver disease (NAFLD). Aim of the study was to investigate frequency and characteristics of perceived stigma among patients with NAFLD. METHODS: One-hundred and ninety-seven patients seen at the liver clinic were included: a study group of 144 patients with NAFLD, 50 with cirrhosis (34 compensated, 16 decompensated), and a control group of 53 patients with alcohol-related cirrhosis. Demographic, clinical, and laboratory data were collected. Quality-of-life was assessed by chronic liver disease questionnaire (CLDQ). Perceived stigma was assessed using a specific questionnaire for patients with liver diseases categorized in 4 domains: stereotypes, discrimination, shame, and social isolation. RESULTS: Perceived stigma was common in patients with NAFLD (99 patients, 69%) and affected all 4 domains assessed. The frequency was slightly higher, yet not significant, in patients with NAFLD cirrhosis vs those without (72% vs 67%, respectively; p = 0.576). In patients without cirrhosis perceived stigma was unrelated to stage of disease, since frequency was similar in patients with no or mild fibrosis compared to those with moderate/severe fibrosis (66% vs 68%, respectively). There were no differences in perceived stigma between patients with compensated cirrhosis and these with decompensated cirrhosis. Among patients with cirrhosis, stigmatization was more common in alcohol-related vs NAFLD-cirrhosis, yet differences were only significant in two domains. In patients with NAFLD, perceived stigma correlated with poor quality-of-life, but not with demographic or clinical variables. CONCLUSIONS: Perceived stigmatization is common among patients with NAFLD independently of disease stage, is associated with impaired quality-of-life, and may be responsible for stereotypes, discrimination, shame, and social isolation, which may affect human and social rights of affected patients.

Impact of alcohol consumption on clinical aspects of gambling disorder.

Similarities between gambling disorder and substance use disorders have been extensively described. To date, however, few studies using large clinical samples have been carried out that reliably assess the relationship between different levels of alcohol consumption and gambling disorders. The present study aimed to assess the impact of baseline alcohol consumption levels on the clinical profile in a large sample of treatment-seeking individuals. Nine hundred and fifty-one consecutive outpatients diagnosed with gambling disorder according to DSM-IV criteria were compared after being included in three alcohol consumption groups (low risk, abuse and risk of dependence) based on their total raw scores on the AUDIT questionnaire. Results showed a high prevalence of risk of alcohol dependence in GD patients who were immigrants, unemployed, and had a low level of education. A positive linear trend was also found between alcohol consumption level and the prevalence of other current and life-time comorbid mental disorders, and for the presence of drug abuse. Statistically significant differences were found between the three alcohol consumption groups in terms of the evolution and severity of the gambling disorder, self-directedness personality trait, and levels of general psychopathology, hostility and paranoid ideation. In conclusion, the results showed an association between increased alcohol consumption and greater dysfunction.

Characterization and chromosomal organization of the murD-murC-ftsQ region of Corynebacterium glutamicum ATCC 13869.

The sequence of a 4.6-kb region of DNA from Corynebacterium glutamicum ATCC 13869 lying upstream from the ftsQ-ftsZ region has been determined. The region contains four genes with high similarity to the murD, ftsW, murG, and murC genes from different microorganisms. The products of these mur genes probably catalyse several steps in the formation of the precursors for peptidoglycan synthesis in C. glutamicum, whereas ftsW might play also a role in the stabilisation of the FtsZ ring during cell division. The murC gene product was purified to near homogeneity and its UDP-N-acetylmuramate: L-alanine adding activity was demonstrated. Northern analysis indicated that ftsW, murG and ftsQ are poorly expressed in C. glutamicum whereas murC and ftsZ are expressed at higher levels at the beginning of the exponential phase. Dicistronic (ftsQ-ftsZ) and monocistronic (murC and ftsZ) transcripts can be detected using specific probes and are in agreement with the lack of transcriptional terminators in the partially analysed dcw cluster. Disruption experiments performed in C. glutamicum using internal fragments of the ftsW, murG and murC genes allowed us to conclude that FtsW, MurG, and MurC are essential gene products in C. glutamicum.

Involvement of DivIVA in the morphology of the rod-shaped actinomycete Brevibacterium lactofermentum.

In Brevibacterium lactofermentum, as in many Gram-positive bacteria, a divIVA gene is located downstream from the dcw cluster of cell-division- and cell-wall-related genes. This gene (divIVA(BL)) is mostly expressed during exponential growth, and the protein encoded, DivIVA(BL,) bears some sequence similarity to antigen 84 (Ag84) from mycobacteria and was detected with monoclonal antibodies against Ag84. Disruption experiments using an internal fragment of the divIVA(BL) gene or a disrupted divIVA(BL) cloned in a suicide conjugative plasmid were unsuccessful, suggesting that the divIVA(BL) gene is needed for cell viability in BREV: lactofermentum. Transformation of BREV: lactofermentum with a multicopy plasmid containing divIVA(BL) drastically altered the morphology of the corynebacterial cells, which became larger and bulkier, and a GFP fusion to DivIVA(BL) mainly localized to the ends of corynebacterial cells. This localization pattern, together with the overproduction phenotype, suggests that DivIVA may be important in regulating the apical growth of daughter cells.

Different pharmacological properties of two equipotent antagonists (clozapine and rauwolscine) for 5-HT2B receptors in rat stomach fundus.

On the basis of the previously demonstrated constitutive activity in natural systems and the possibility of specific ligand-induced conformations, the aims of this study were: (i) to characterize the effects of two competitive antagonists (rauwolscine, RAU and clozapine, CLO) with very similar potencies for 5-HT(2B) receptors in a natural system (rat stomach fundus), and (ii) to evaluate a new method for detecting ligand-specific generated conformations through the study of the effects of RAU and CLO in 5-HT efficacy and in the time course of the response to the agonists. RAU and CLO behaved as competitive antagonists and showed similar potencies (pA(2) 7.56+/-0.25 and 7.50+/-0.30, respectively). However, RAU displayed greater efficacy than CLO in relaxing basal tension (10 microM CLO represented 64+/-6% of 10 microM RAU-induced relaxation). CLO partially reverted RAU-induced relaxation and RAU promoted an additional relaxation of maximal CLO-induced relaxation. This may indicate different degrees of inverse agonism. RAU also was more effective in generating insurmountable antagonism after long-term incubation (>3 hr) and modified the time course of the 5-HT(2B) response to 5-HT; conversely, CLO did not affect the time course of this response. This suggests that classical competitive antagonists may generate different specific conformational states and differential effects on receptor system regulation.

Influence of pH on the binding of diphenylmethylenepiperidines by 5-HT2B receptors in rat stomach fundus.

Cyproheptadine is one of the compounds exhibiting the highest activity at 5-HT2B receptors. In a previous work we analysed the relevance of the amino group in diphenylmethylenepiperidines (DPMP), which are open cyproheptadine analogues. Only compounds containing N-H or N-methyl motifs, showed significant 5-HT2B activity. Surprisingly, the corresponding quaternary ammonium salt demonstrated a total lack of activity. Therefore, the question arises whether protonation favours the interaction of these compounds with 5-HT2B receptors. Consequently, we studied the protonation influence (by varying the pH of the medium) on the antagonism of serotonin by some cyproheptadine analogues in rat stomach fundus. The main results were: 1) N-protonation increases the activity of DPMPs. 2) Alkaline pH facilitates the occurrence of a non-surmountable antagonism. 3) The contrast between the activity of protonated DPMPs and the lack of activity of the corresponding quaternary ammonium cation, suggests either that the latter is prevented from acting by steric hindrance, or that the mechanism by which protonation may increase the activity depends not only on the charge of the proton, but also on its ability to form hydrogen bonds.