The Journal of the Association of Physicians of India
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J Assoc Physicians India · Jul 2003
ReviewOrally effective drugs for kala-azar (visceral leishmaniasis): focus on miltefosine and sitamaquine.
Currently there are no effective orally administered drugs or visceral leishmaniasis or kala-azar, a parasitic disease affecting about 0.5 million people a year, majority of whom are in India and adjacent areas of Nepal. Symptoms of affected patients are fever, cachexia, hepatosplenomegaly and pancytopenia. The disease is usually fatal, if left untreated. ⋯ Few studies of phase II clinical trials mainly conducted in Kenya with another drug, sitamaquine or kalazaquine (WR 6026), an 8-aminoquinoline has also shown promise as an orally effective agent (in a dose of 1 mg/kg/day for two weeks) for visceral leishmaniasis. These Studies with two orally effective compounds, it appears, will open new vistas for orally effective, affordable and acceptable drugs in the armamentarium for the treatment of kala-azar. It is expected that in future we would have effective ways to prevent and treat all forms of leishmaniasis without discomforting the patient.
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NF-kappaB activation, and elevated concentrations of macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1(IL-1), IL-6, free radicals, inducible nitric oxide (iNO), and stress hyperglycemia occurs in sepsis and this leads to systemic inflammatory response and myocardial depression seen in sepsis and septic shock. Conversely, insulin suppresses production of MIF, TNF-alpha, IL-1, IL-6, and free radicals, enhances endothelial NO generation, and enhances the production of anti-inflammatory cytokines IL-4, and IL-10, corrects stress hyperglycemia and improves myocardial function. This supports my earlier proposal that insulin (with or without glucose and potassium) therapy to maintain euglycemia suppresses the inflammatory response, improves myocardial function, and thus, is of benefit in acute myocardial infarction, sepsis andseptic shock.