HLA-class 1 and class 2 antigens in Turkish patients with pemphigus

BACKGROUND: Pemphigus is an autoimmune disease which is more frequently seen in certain ethnic groups such as Jews. It is thought that exogenous factors may induce pemphigus in genetically predisposed individuals. Recent reports on HLA antigens indicate an increased frequency of HLA-class II antigens particularly HLA-DR4 among Jewish patients. Herein we investigated the antigen frequencies of HLA-A, B, C, HLA-DR and DQ in Turkish patients with pemphigus. METHODS: HLA class I and II antigens were typed by microdroplet lymphocyte cytotoxicity test in 33 patients with pemphigus and 100 healthy individuals. RESULTS: HLA-B35, B44, CW4, DR4, DR14, DQ8 and DQ4 antigens were significantly high in the study group whereas HLA-DR11, DQ7 and DQ2 antigens were high among the controls. The most striking differences were observed in HLA class II antigens. HLA DR14-DQ8 and HLA B35-DR14 haplotypes were the most frequently observed ones in the study group. CONCLUSIONS: We postulate that HLA-B35, B44, CW4, DR4, DR14, DQ4 and DQ8 antigens may be responsible for susceptibility to pemphigus while HLA-DR11, DQ7 and DQ2 antigens may have a protective role in the Turkish population.     

Levofloxacin-Ceftriaxone Combination Attenuates Lung Inflammation in a Mouse Model of Bacteremic Pneumonia Caused by Multidrug-Resistant Streptococcus pneumoniae via Inhibition of Cytolytic Activities of Pneumolysin and Autolysin

In this study, our objective was to determine whether a synergistic antimicrobial combination in vitro would be beneficial in the downregulation of pneumococcal virulence genes and whether the associated inflammation of the lung tissue induced by multidrug-resistant Streptococcus pneumoniae infection in vivo needs to be elucidated in order to consider this mode of therapy in case of severe pneumococcal infection. We investigated in vivo changes in the expression of these virulence determinants using an efficacious combination determined in previous studies. BALB/c mice were infected with 10⁶ CFU of bacteria. Intravenous levofloxacin at 150 mg/kg and/or ceftriaxone at 50 mg/kg were initiated 18 h postinfection; the animals were sacrificed 0 to 24 h after the initiation of treatment. The levels of cytokines, chemokines, and C-reactive protein (CRP) in the serum and lungs, along with the levels of myeloperoxidase and nitric oxide the inflammatory cell count in bronchoalveolar lavage fluid (BALF), changes in pneumolysin and autolysin gene expression and COX-2 and inducible nitric oxide synthase (iNOS) protein expression in the lungs were estimated. Combination therapy downregulated inflammation and promoted bacterial clearance. Pneumolysin and autolysin expression was downregulated, with a concomitant decrease in the expression of COX-2 and iNOS in lung tissue. Thus, the combination of levofloxacin and ceftriaxone can be considered for therapeutic use even in cases of pneumonia caused by drug-resistant isolates.     

Suaahara in Nepal: An at‐scale,multi‐sectoral nutrition program influences knowledge and practices while enhancing equity

The burden of undernutrition in South Asia is greater than anywhere else. Policies and programmatic efforts increasingly address health and non‐health determinants of undernutrition. In Nepal, one large‐scale integrated nutrition program, Suaahara, aimed to reduce undernutrition among women and children in the 1,000‐day period, while simultaneously addressing inequities. In this study, we use household‐level process evaluation data (N = 480) to assess levels of exposure to program inputs and levels of knowledge and practices related to health, nutrition, and water, sanitation, and hygiene (WASH). We also assess Suaahara's effect on the differences between disadvantaged (DAG) and non‐disadvantaged households in exposure, knowledge, and practice indicators. All regression models were adjusted for potential confounders at the child‐, maternal‐, and household levels, as well as clustering. We found a higher prevalence of almost all exposure and knowledge indicators and some practice indicators in Suaahara areas versus comparison areas. A higher proportion of DAG households in Suaahara areas reported exposure, were knowledgeable, and practiced optimal behaviors related to nearly all maternal and child health, nutrition, and WASH indicators than DAG households in non‐Suaahara areas and sometimes even than non‐DAG households in Suaahara areas. Moreover, differences in some of these indicators between DAG and non‐DAG households were significantly smaller in Suaahara areas than in comparison areas. These results indicate that large‐scale integrated interventions can influence nutrition‐related knowledge and practices, while simultaneously reducing inequities.     

GATA-1 as a regulator of mast cell differentiation revealed by the phenotype of the GATA-1low mouse mutant

Here it is shown that the phenotype of adult mice lacking the first enhancer (DNA hypersensitive site I) and the distal promoter of the GATA-1 gene (neo Delta HS or GATA-1(low) mutants) reveals defects in mast cell development. These include the presence of morphologically abnormal alcian blue(+) mast cells and apoptotic metachromatic(-) mast cell precursors in connective tissues and peritoneal lavage and numerous (60-70% of all the progenitors) "unique" trilineage cells committed to erythroid, megakaryocytic, and mast pathways in the bone marrow and spleen. These abnormalities, which were mirrored by impaired mast differentiation in vitro, were reversed by retroviral-mediated expression of GATA-1 cDNA. These data indicate an essential role for GATA-1 in mast cell differentiation.     

Psychological trauma in a relief worker--a case report from earthquake-struck areas of north Pakistan

Vicarious traumatization is now a well-known entity and may have negative influences on those that are involved in rescue efforts in any disaster or traumatic events. Healthcare workers work with trauma survivors and witness an immense array of gruesome and ghastly images. This work has the potential to cause those engaged in rescue efforts to become affected subconsciously. Job-related stress may cause psychological symptoms in care providers who provide support and listen to the survivors' account of trauma. A therapist working in disaster situations may become a victim of psychological anguish--undermining their physical and mental well-being as well as their profession, adversely affecting their traumatized patients, and leading to a counter-productive therapist-survivor relationship. This significant theme of secondary trauma must be recognized in relief workers at early stages and must be addressed at an individual as well as organizational level. The key may lie in turning to social supports, adapting positive coping mechanisms, and subsequently seeking mental health consultation. Further research is required in this area to determine the best resolution.     

Naturally occurring variations in the human cholinesterase genes: heritability and association with cardiovascular and metabolic traits

Cholinergic neurotransmission in the central and autonomic nervous systems regulates immediate variations in and longer-term maintenance of cardiovascular function with acetylcholinesterase (AChE) activity that is critical to temporal responsiveness. Butyrylcholinesterase (BChE), largely confined to the liver and plasma, subserves metabolic functions. AChE and BChE are found in hematopoietic cells and plasma, enabling one to correlate enzyme levels in whole blood with hereditary traits in twins. Using both twin and unrelated subjects, we found certain single nucleotide polymorphisms (SNPs) in the ACHE gene correlated with catalytic properties and general cardiovascular functions. SNP discovery from ACHE resequencing identified 19 SNPs: 7 coding SNPs (cSNPs), of which 4 are nonsynonymous, and 12 SNPs in untranslated regions, of which 3 are in a conserved sequence of an upstream intron. Both AChE and BChE activity traits in blood were heritable: AChE at 48.8 ± 6.1% and BChE at 81.4 ± 2.8%. Allelic and haplotype variations in the ACHE and BCHE genes were associated with changes in blood AChE and BChE activities. AChE activity was associated with BP status and SBP, whereas BChE activity was associated with features of the metabolic syndrome (especially body weight and BMI). Gene products from cDNAs with nonsynonymous cSNPs were expressed and purified. Protein expression of ACHE nonsynonymous variant D134H (SNP6) is impaired: this variant shows compromised stability and altered rates of organophosphate inhibition and oxime-assisted reactivation. A substantial fraction of the D134H instability could be reversed in the D134H/R136Q mutant. Hence, common genetic variations at ACHE and BCHE loci were associated with changes in corresponding enzymatic activities in blood.