Obesity – is it a genetic disorder?

Obesity is one of the most pressing problems in the industrialized world. Twin, adoption and family studies have shown that genetic factors play a significant role in the pathogenesis of obesity. Rare mutations in humans and model organisms have provided insights into the pathways involved in body weight regulation. Studies of candidate genes indicate that some of the genes involved in pathways regulating energy expenditure and food intake may play a role in the predisposition to obesity. Amongst these genes, sequence variations in the adrenergic receptors, uncoupling proteins, peroxisome proliferator-activated receptor, and the leptin receptor genes are of particular relevance. Results that have been replicated in at least three genome-wide scans suggest that key genes are located on chromosomes 2p, 3q, 5p, 6p, 7q, 10p, 11q, 17p and 20q. We conclude that the currently available evidence suggests four levels of genetic determination of obesity: genetic obesity, strong genetic predisposition, slight genetic predisposition, and genetically resistant. This growing body of research may help in the development of anti-obesity agents and perhaps genetic tests to predict the risk for obesity.     

The association between drinking motives and alcohol‐related consequences – room for biases and measurement issues?

Aims To investigate whether the predominant finding of generalized positive associations between self‐rated motives for drinking alcohol and negative consequences of drinking alcohol are influenced by (i) using raw scores of motives that may weight inter‐individual response behaviours too strongly, and (ii) predictor‐criterion contamination by using consequence items where respondents attribute alcohol use as the cause. Design Cross‐sectional study within the European School Survey Project on Alcohol and other Drugs (ESPAD). Setting School classes. Participants Students, aged 13–16 (n = 5633). Measurements Raw, rank and mean‐variance standardized scores of the Drinking Motives Questionnaire—Revised (DMQ‐R); four consequences: serious problems with friends, sexual intercourse regretted the next day, physical fights and troubles with the police, each itemized with attribution (‘because of your alcohol use’) and without. Findings As found previously in the literature, raw scores for all drinking motives had positive associations with negative consequences of drinking, while transformed (rank or Z) scores showed a more specific pattern: external reinforcing motives (social, conformity) had negative and internal reinforcing motives (enhancement, coping) had non‐significant or positive associations with negative consequences. Attributed consequences showed stronger associations with motives than non‐attributed ones. Conclusion Standard scoring of the Drinking Motives Questionnaire (Revised) fails to capture motives in a way that permits specific associations with different negative consequences to be identified, whereas use of rank or Z‐scores does permit this. Use of attributed consequences overestimates the association with drinking motives.     

Hepatitis C virus infection during pregnancy and the newborn period – are they opportunities for treatment?

The worldwide prevalence of hepatitis C virus (HCV) infection in pregnant women is estimated to be between 1 and 8% and in children between 0.05% and 5%. While parenteral transmission is still common in children living in developing countries, perinatal transmission is now the leading cause of HCV transmission in developed countries. The absence of an HCV vaccine or approved therapy during pregnancy means that prevention of vertical transmission is still not possible. However, a low vertical transmission rate of 3-5%, a high rate of spontaneous clearance (25-50%) and delayed morbidity have resulted in HCV being overlooked in pregnant women and their infants. Yet a study of the natural history in mothers and children demonstrates that the prognosis of HCV can vary greatly and should be taken seriously. Factors known to increase the risk of perinatal transmission include HIV coinfection and higher maternal viral loads, while elective C-section and withholding breastfeeding have not been demonstrated to reduce vertical transmission. Current guidelines for the diagnosis of persistent perinatal infection require a positive anti-HCV test in infants born to infected mothers after 12 months or two positive HCV RNA tests at least 6 months apart. Current HCV treatment options using pegylated interferon and ribavirin are both unsuitable for use in pregnancy and infancy. However, new agents currently in preclinical phases of development, along with the recently identified association between single-nucleotide polymorphisms within the IL28 gene and treatment response, may serve to create a therapeutic window for these patients.     

Is α‐actinin a target for pathogenic anti‐DNA antibodies in lupus nephritis?

Objective

Following recent reports that pathogenic murine anti‐DNA antibodies bind to α‐actinin, it was obviously of interest to assess the ability of human pathogenic anti–double‐stranded DNA (anti‐dsDNA) antibodies to bind this antigen. Both human monoclonal anti‐DNA antibodies and antibodies affinity purified from the sera of patients with systemic lupus erythematosus (SLE) were investigated.

Methods

An enzyme‐linked immunosorbent assay was established to measure immunoglobulin binding to α‐actinin. Antibodies binding dsDNA were purified from the sera of SLE patients who either had active renal disease or had never had renal disease. Serum samples were selected at times when the patients' sera exhibited high IgG binding to dsDNA. The binding of supernatants from 3 high‐affinity human anti‐dsDNA IgG hybridomas (RH14, B3, and DIL‐6) and 7 human IgM anti‐DNA hybridomas was also investigated.

Results

A greater proportion of anti‐dsDNA IgG–binding antibodies purified from patients with renal disease bound to α‐actinin than did those purified from the sera of patients without renal disease. The specificity of binding to the 100‐kd α‐actinin molecule was confirmed by Western blotting. The pathogenic human antibodies RH14 and B3 bound strongly to α‐actinin, while nonpathogenic DIL‐6 bound very weakly. RT84, the IgM antibody that binds dsDNA with the highest affinity, exhibited the greatest binding to α‐actinin.

Conclusion

The results of our study support the findings of previous studies using murine anti‐DNA monoclonal antibodies, which suggest that pathogenic anti‐dsDNA antibodies cross‐react with α‐actinin.

     

3‐(2,4‐Dimethoxybenzylidene)‐anabaseine: A promising candidate drug for Alzheimer's disease?

3‐(2,4‐Dimethoxybenzylidene)‐anabaseine is an analog of the paralytic alkaloid, anabaseine, from the ribbon worms Amphiporus sp., that shows numerous properties, in particular an agonist activity on alpha7 nicotinic acetylcholine receptors. This article reviews these properties and explains to what extent they could be valuable to control symptomatology and/or neurodegeneration in Alzheimer's disease. Geriatr Gerontol Int 2012; 12: 365–371 .     

Overlap syndrome: an indication for sleep studies?

Background  

The coexistence of obstructive sleep apnea (OSA) and chronic obstructive pulmonary diseases (COPD) is known as overlap syndrome (OS); it occurs in 10–20% of patients with OSA. Patients with OS have a higher risk of pulmonary hypertension and worse nocturnal hypoxemia than those with either disease alone. Differences may be seen according to severity of COPD, anthropometric measures, and polysomnography (PSG) features of patients. Recent studies have suggested that long-term use of continuous positive airway pressure for OSA is associated with worsening of coexistent COPD. This stresses the importance of identifying this subgroup of patients in order to provide adequate therapy.     

Sensitivity and specificity of Anti‐HBc screening assays – which assay is best for blood donor screening?

Compared to HIV and hepatitis C virus, the residual infectious risk of hepatitis B virus (HBV) posed by blood products is about 10 times higher. In addition to HBsAg testing, screening for anti-HBc was recommended by the German Advisory Committee Blood in March 2005. Prevalence of anti-HBc in German blood donors was investigated at five test sites located in different geographic regions. In total, 12,000 blood donors were screened for anti-HBc by PRISM HBcore, and a statistically representative number of these were tested with Abbott Murex anti-HBc total, bioMérieux Hepanostika anti-HBc uniform, Bio-Rad Monolisa anti-HBc PLUS and Dade Behring Enzygnost anti-HBc. Anti-HBc repeat reactive samples were tested for anti-HBs, anti-HBe and HBV DNA by individual donation NAT. The mean prevalence of anti-HBc was 1.75% in donors that had not been tested for anti-HBc in the past. The percentage of anti-HBs in anti-HBc repeat reactive donors was 93.7%. Samples that were additionally reactive for anti-HBe were anti-HBc reactive in all tested assays. The sample to cut-off (S/Co) values for anti-HBc were lower (competitive assays) in samples that were also positive for anti-HBe, when compared to samples that were only anti-HBc reactive. Most commercially available anti-HBc assays provide sufficient sensitivity for routine screening purposes, and lacking specificity is no longer a serious issue for most of them. Assay differences were recognized for samples that were anti-HBc only reactive. The overall loss of 1.75% of positive testing donors can be significantly reduced to 0.45% by implementation of re-entry procedures for donors with an anti-HBs titre of over 100 IU/l and negative by sensitive ID-NAT.