Hypothalamic digoxin,cerebral dominance,and Golgi body/lysosomal function

The present study assessed the biochemical differences of glycoconjugate metabolism between right hemispheric dominant and left hemispheric dominant individuals. The isoprenoid metabolites--digoxin and dolichol, glycoconjugates, and lysosomal enzymes--were studied. The results showed that right hemispheric dominant individuals had increased (i) HMG CoA reductase activity and elevated digoxin levels, and (ii) increased dolichol and glycoconjugate levels with reduced lysosomal stability. Left hemispheric dominant individuals had the opposite patterns. Right hemispheric dominance represents a hyperdigoxinemic state with membrane sodium-potassium ATPase inhibition. Left hemispheric dominance represents the reverse pattern with hypodigoxinemia and membrane sodium-potassium ATPase stimulation. Cerebral dominance can regulate glycoconjugate metabolism (golgi body/lysosomal function).     

Hypothalamic digoxin,hemispheric dominance,and neuroimmune integration

The isoprenoid pathway produces three key metabolites--digoxin (membrane Na(+)-K+ ATPase inhibitor, regulator of neurotransmitter transport, and immunomodulatory agent), dolichol (regulatory of N-glycosylation of proteins), and ubiquinone (free-radical scavenger). The pathway was assessed in systemic lupus erythematosis with neuropsychiatric manifestations, slow viral diseases (subacute sclerosing panencephalitis [SSPE], and Creutzfeldt-Jakob disease [CJD]) and patients with recurrent respiratory infections. This was also studied for comparison in patients with right hemispheric and left hemispheric dominance. The isoprenoid pathway was upregulated with increased digoxin synthesis in patients with neurolupus, SSPE, and CJD, and in those with right hemispheric dominance. The tryptophan catabolites were increased and the tyrosine catabolites reduced. In these patients the dolichol and glycoconjugate levels were elevated and lysosomal stability was reduced. The ubiquinone levels were low and free-radical levels increased in these patients. The membrane cholesterol:phospholipid ratios were increased and membrane glycoconjugates reduced. On the other hand, in patients with recurrent respiratory infection and left hemispheric dominance, the reverse patterns and hypodigoxinemia with a downregulated isoprenoid pathway were noticed. The isoprenoid pathway is important in the pathogenesis of neurolupus, CJD, SSPE, and recurrent respiratory infections. Hypothalamic digoxin and chemical hemispheric dominance play an important role in the regulation of immunity.     

Interaction of p-hydroxybenzoic esters with beta-cyclodextrin

In the present investigation, the complex formation of beta-cyclodextrin (betaCD) with p-hydroxybenzoic esters (parabens) was studied by mixing betaCD with methyl, ethyl, propyl and butyl parabens, respectively, in aqueous solutions and subjecting the resultant mixtures individually to the following processes: occasional shaking for 24 h at 25 degrees C, continuous shaking using shaker bath for 24 h at 25 degrees C, intermittent ultrasonification for 90 min at 25 degrees C, autoclaving at 115 degrees C for 30 min and freeze-drying followed by reconstitution with distilled water. The degrees of interaction between betaCD and the parabens subjected to the various processes were evaluated, using the membrane dialysis method. The difference in the method of processing did not affect the degree of interaction significantly. However, the degree of interaction was found to increase proportionally with the concentration of betaCD. The alkyl group of the parabens was also found to affect the extent of interaction. Compared to methyl paraben, the degree of interaction of ethyl paraben was observed to be lower. Interestingly, further increase in the size of the alkyl group significantly enhanced the extent of interaction. Studies using 1H-NMR showed that the extent of interaction depended on how well the parabens could fit into the betaCD cavity.     

Efficacy and Toxicity Profile of Methotrexate Chloroquine Combination in Treatment of Active Rheumatoid Arthritis

Background

The present study was conducted to study the efficacy and toxicity profile of methotrexate chloroquine combination in treatment of active rheumatoid arthritis.

Methods

24 patients of rheumatoid arthritis confirming to revised American Rheumatism Association (ARA) criteria were studied prospectively for twenty months. Clinical evaluation was made every 3 months. Clinical disease variables measured at each visit were number of joints with swelling, number of joints with tenderness and pain, duration of morning stiffness and physician and patient assessment of disease activity. Blood counts, liver function tests and other adverse effects due to drugs were monitored every 2 months.

Results

10 patients demonstrated more than 50% improvement. 4 patients withdrew from study, 2 because of excessive nausea and vomiting and 2 because of noncompliance. Other side effects noted were hyperpigmentation, photosensitivity, skin rashes, raised transaminases and stomatitis.

Conclusion

Methotrexate chloroquine combination has good efficacy and toxicity profile. Gastrointestinal side effects are most common and usually responsible for the discontinuation of the drugs.Key Words: Rheumatoid arthritis, Methotrexate, Chloroquine, Efficacy, Toxicity     

Isoprenoid pathway dysfunction in human male infertility

The isoprenoid pathway produces 3 key metabolites: digoxin (membrane sodium-potassium ATPase inhibitor and regulator of neurotransmitter transport), dolichol (regulates N-glycosylation of proteins), and ubiquinone (free radical scavenger). The pathway was assessed in patients with human male infertility (oligospermia and decreased motility). It was also studied for comparison in patients with right hemispheric, left hemispheric, and bihemispheric dominance. The results of the study showed that the isoprenoid pathway was upregulated with increased digoxin synthesis in all 3 groups of patients. There was also a reduction in membrane Na(+)-K(+) ATPase activity and serum magnesium levels. There was an increase in tryptophan catabolites and a reduction in tyrosine catabolites. The dolichol and glycoconjugate levels increased and lysosomal stability was reduced with increased serum lysosomal enzymes in all 3 groups. The ubiquinone levels were low and free radicals increased. The cholesterol:phospholipid ratio increased and glycoconjugate was reduced in the membrane of these patients. This pattern correlated with those in right hemispheric dominance. The significance of these factors in the pathogenesis of human male infertility is discussed.     

Cutaneous melioidosis and necrotizing fasciitis caused by Burkholderia pseudomallei

In areas where melioidosis is endemic, stress on the healthcare system is substantial. Because clinical manifestations are protean, the illness is difficult to diagnose, and cutaneous Burkholderia pseudomallei infections can progress to necrotizing fasciitis. While it is and uncommon complication of cutaneous melioidosis, necrotizing fasciitis is potentially fatal and requires aggressive management, including early diagnosis, appropriate antibiotics selection and operative débridement.