Environmental Factors Related to Multiple Sclerosis in Indian Population

Background

Multiple sclerosis (MS) is less prevalent among Indians when compared to white populations. Genetic susceptibility remaining the same it is possible that environmental associations may have a role in determining disease prevalence.

Aims

To determine whether childhood infections, vaccination status, past infection with Helicobacter pylori (H.pylori), diet, socioeconomic and educational status were associated with MS.

Material and Methods

139 patients and 278 matched control subjects were selected. A validated environmental exposure questionnaire was administered. Estimation of serum H.pylori IgG antibody was done by ELISA. Patients and controls were genotyped for HLA-DRB1*15:01.

Results

In our cohort a significant association was seen with measles (p <0.007), vegetarian diet (p < 0.001, higher educational status (p <0.0001) and urban living (p <0.0001). An inverse relationship was seen with H.Pylori infection and MS (p <0.001). Measles infection (OR 6.479, CI 1.21- 34.668, p< 0.029) and high educational status (OR 3.088, CI 1.212- 7.872, p< 0.018) were significant risk factors associated with MS. H.pylori infection was inversely related to MS (OR 0. 319, CI 0.144- 0.706, p <0.005).

Conclusions

Environmental influences may be important in determining MS prevalence.     

To hydrolyze or not to hydrolyze: the dilemma of platelet-activating factor acetylhydrolase

Mounting ambiguity persists around the functional role of the plasma form of platelet-activating factor acetylhydrolase (PAF-AH). Because PAF-AH hydrolyzes PAF and related oxidized phospholipids, it is widely accepted as an anti-inflammatory enzyme. On the other hand, its actions can also generate lysophosphatidylcholine (lysoPC), a component of bioactive atherogenic oxidized LDL, thus allowing the enzyme to have proinflammatory capabilities. Presence of a canonical lysoPC receptor has been seriously questioned for a multitude of reasons. Animal models of inflammation show that elevating PAF-AH levels is beneficial and not deleterious and overexpression of PAF receptor (PAF-R) also augments inflammatory responses. Further, many Asian populations have a catalytically inert PAF-AH that appears to be a severity factor in a range of inflammatory disorders. Correlation found with elevated levels of PAF-AH and CVDs has led to the design of a specific PAF-AH inhibitor, darapladib. However, in a recently concluded phase III STABILITY clinical trial, use of darapladib did not yield promising results. Presence of structurally related multiple ligands for PAF-R with varied potency, existence of multi-molecular forms of PAF-AH, broad substrate specificity of the enzyme and continuous PAF production by the so called bi-cycle of PAF makes PAF more enigmatic. This review seeks to address the above concerns.     

Lipopolysaccharide Cross-Tolerance Delays Platelet-Activating Factor-Induced Sudden Death in Swiss Albino Mice: Involvement of Cyclooxygenase in Cross-Tolerance

Lipopolysaccharide (LPS) signaling through Toll-like receptor-4 (TLR-4) has been implicated in the pathogenesis of many infectious diseases. Some believe that TLR-mediated pathogenicity is due, in part, to the lipid pro-inflammatory mediator platelet-activating factor (PAF), but this has been questioned. To test the direct contribution of PAF in endotoxemia in murine models, we injected PAF intraperitoneally into Swiss albino mice in the presence and absence of LPS. PAF alone (5 μg/mouse) caused death within 15–20 min, but this could be prevented by pretreating mice with PAF-receptor (PAF-R) antagonists or PAF-acetylhydrolase (PAF-AH). A low dose of LPS (5 mg/kg body wt) did not impair PAF-induced death, whereas higher doses (10 or 20 mg/kg body wt) delayed death, probably via LPS cross-tolerance. Cross-tolerance occurred only when PAF was injected simultaneously with LPS or within 30 min of LPS injection. Tolerance does not appear to be due to an abundant soluble mediator. Histologic examination of lungs and liver and measurement of circulating TNF-α and IL-10 levels suggested that the inflammatory response is not diminished during cross-tolerance. Interestingly, aspirin, a non-specific cyclooxygenase (COX) inhibitor, partially blocked PAF-induced sudden death, whereas NS-398, a specific COX-2 inhibitor, completely protected mice from the lethal effects of PAF. Both COX inhibitors (at 20 mg/kg body wt) independently amplified the cross-tolerance exerted by higher dose of LPS, suggesting that COX-derived eicosanoids may be involved in these events. Thus, PAF does not seem to have a protective role in endotoxemia, but its effects are delayed by LPS in a COX-sensitive way. These findings are likely to shed light on basic aspects of the endotoxin cross-tolerance occurring in many disease conditions and may offer new opportunities for clinical intervention.     

Sodium Fluoride and Fluoride Contaminated Ground Water Induced Altered Reproductive Performances in Male Rats

Biological Trace Element Research - Present study was undertaken to investigate the toxic effect of sodium fluoride (NaF)– and fluoride (F)-contaminated ground water on reproductive...