Impact of obesity on autoimmune arthritis and its cardiovascular complications

Obesity can instigate and sustain a systemic low-grade inflammatory environment that can amplify autoimmune disorders and their associated comorbidities. Metabolic changes and inflammatory factors produced by the adipose tissue have been reported to aggravate autoimmunity and predispose the patient to cardiovascular disease (CVD) and metabolic comorbidities. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are autoimmune arthritic diseases, often linked with altered body mass index (BMI). Severe joint inflammation and bone destruction have a debilitating impact on the patient's life; there is also a staggering risk of cardiovascular morbidity and mortality. Furthermore, these patients are at risk of developing metabolic symptoms, including insulin resistance resulting in type 2 diabetes mellitus (T2DM). In addition, arthritis severity, progression and response to therapy can be markedly affected by the patient's BMI. Hence, a complex integrative pathogenesis interconnects autoimmunity with metabolic and cardiovascular disorders. This review aims to shed light on the network that connects obesity with RA, PsA, systemic lupus erythematosus and Sj?gren's syndrome. We have focused on clarifying the mechanism by which obesity affects different cell types, inflammatory factors and traditional therapies in these autoimmune disorders. We conclude that to further optimize arthritis therapy and to prevent CVD, it is imperative to uncover the intricate relation between obesity and arthritis pathology.     

Anti-Vibriocholerae IgY Antibody Inhibits Mortality in Suckling Mice Model

Background

Regarding to the importance of cholera in Iran and the potential advantages of egg yolk antibody (IgY) for immunotherapy, the aim of this study was to produce IgY antibody against V. cholerae Lipopolysaccharide (LPS) and determine its potential for V. cholerae treatment.

Nitrite mediates cytoprotection after ischemia/reperfusion by modulating mitochondrial function

Nitrite, once thought to be an inert biomarker of NO formation, is now recognized as an endocrine storage pool of bioactive NO. While nitrite mediates a number of hypoxic responses, one of its most robust effects is its ability to confer cytoprotection after ischemia/reperfusion in a number of organs and models. The mechanism of this cytoprotection appears to be mediated at the level of the mitochondrion. Here we review the studies demonstrating that nitrite is cytoprotective in the heart and describe the mechanism of this cytoprotection, which involves the post-translational modification of complex I leading to the modulation of mitochondrial reactive oxygen species generation at reperfusion. The mechanism of nitrite-dependent cytoprotection will be compared to other cytoprotective agents including NO and ischemic preconditioning.     

Role of inhaled nitric oxide as a selective pulmonary vasodilator in pediatric cardiac surgical practice

Our aim was to assess the role of inhaled nitric oxide (NO) therapy in post operative cases of congenital heart defects who developed pulmonary arterial hypertensive (PAH) crisis and had no response with conventional management. From February '95 to January '97, inhaled NO therapy was used in 21 children. Age ranged from 2 months to 9 years (mean 5.6 years) and duration of therapy ranged from 1 to 13 days. Of 21 patients, 17 responded well with 5–20 ppm while 4 did not. The preoperative mean pulmonary systolic pressure was 88 mm Hg against mean systemic pressure of 96 mm Hg. Post operatively, their PA pressure reduced to 62 mm Hg, with systemic pressure of 98 mm Hg. After using inhaled NO, PA pressure dropped to 24 mm Hg (mean systolic) (p<0.007), after excluding the non responders. Of 4 non responders, two died due to irreversible pulmonary vascular disease and remaining two died due to residual defects. The study shows that inhaled NO is a selective pulmonary vasodilator, which is useful in postoperative PAH crisis and also reduces the transpulmonary gradient in single ventricle repair cases. It is safe and effective for prolonged use. It is very useful in Indian perspective, when more number of cases with congenital heart defects (CHD) alongwith severe PAH are encountered routinely.     

Evidence of DNA methylation in the neurofibromatosis type 1 (NF1) gene region of 17q11.2

Modification of mammalian DNA by the methylation of cytosinein CpG dinucleotides is a complex phenomenon involved in a numberof cellular and developmental processes. In a particular, thecharacteristic hypermutability of CpGs may be a major contributorof point mutations leading to human genetic disease. We havehypothesized that DNA methylation contributes to mutations inthe gene causing neurofibromatosis type 1 (NF1), one of themost common genetic disorders in humans and a disease whereup to half of all cases are the result of sporadic germlinemutations, usually in the paternally-derived allele. We haveused two experimental approaches to analyze patterns of DNAmethylation at CpG dinucleotides in the NF1 gene region. Southernanalyses using isoschizomeric restriction pairs have revealedDNA methylation in areas flanking the NF1 gene region, whilePCR-methylation assays have shown that methylation occurs bothon genomic sequences flanking the NF1 gene and within the codingregion of the gene itself. We suggest that methylated CpG dinucleotideswithin and around the highly mutable NF1 gene serve as a reservoirwithin which C-T transitions contribute to the high frequencyof spontaneous germline mutations associated with the disease.