The high rate of occurrence of enteric fever in children <5 years and also of infections caused by Salmonella paratyphi A in India calls for critical re-assessment of vaccination strategy. Nalidixic acid resistance and rising MICs of fluoroquinolones in Salmonella spp pose a new global threat requiring debate on the optimum treatment of enteric fever.
A retrospective, hospital-based study at Safdarjang Hospital, India, was undertaken between January 1999 and December 2003 to estimate age-related epidemiological, clinical and microbiological characteristics in enteric fever cases. A total of 750 blood-culture-proven cases of enteric fever were studied. The majority of cases occurred in children aged 5-12 years and 24.8% of cases were in children up to 5 years of age. Salmonella serotypes showed an age-related predilection, with paratyphoid fever more common in adults. Classically-described clinical features of the disease were comparable among patients under and above 5 years of age. Hepatomegaly, anaemia and complications in general were more frequent in children up to 5 years of age. The antimicrobial resistance pattern, irrespective of Salmonella serotype, did not reveal a statistically significant difference across age groups for the different antibiotics tested. Multidrug resistance was seen only in Salmonella enterica serotype Typhi but not in S. Paratyphi A isolates. However, resistance to nalidixic acid was comparable in both serotypes. Age-related differences of serotype isolation rates, clinical presentation and associated complications are noteworthy for better case management and policy planning. More epidemiological studies regarding reasons for age-related differential serotype patterns would enable and guide public health strategies to contain enteric fever in endemic locations.
Plasma membrane (PM) Ca2+ pump is a Ca+-Mg2+-ATPase that expels Ca2+ from cells to help them maintain low concentrations of cytosolic Ca2+ . There are no known extracellularly acting PM Ca2+ pump inhibitors, as digoxin and ouabain are for Na+ pump. In analogy with digoxin, we define caloxins as extracellular PM Ca2+ pump inhibitors and describe caloxin 2A1. Caloxin 2A1 is a peptide obtained by screening a random peptide phage display library for binding to the second extracellular domain (residues 401-413) sequence of PM Ca2+ pump isoform 1b. Caloxin 2A1 inhibits Ca2+-Mg2+-ATPase in human erythrocyte leaky ghosts, but it does not affect basal Mg2+-ATPase or Na+-K+-ATPase in the ghosts or Ca2+-Mg2+-ATPase in the skeletal muscle sarcoplasmic reticulum. Caloxin 2A1 also inhibits Ca2+-dependent formation of the 140-kDa acid-stable acylphosphate, which is a partial reaction of this enzyme. Consistent with inhibition of the PM Ca2+ pump in vascular endothelium, caloxin 2A1 produces an endothelium-dependent relaxation that is reversed by N(G)-nitro-L-arginine methyl ester. Thus caloxin 2A1 is a novel PM Ca2+ pump inhibitor selected for binding to an extracellular domain.
10mg tablet; administered once daily. The drug is well tolerated. Based on the presently available data montelukast may be an alternative treatment for mild persistent asthma as monotherapy where ICS cannot be administered. It is also an alternative to LABA as an add-on therapy to ICS for moderate to severe persistent asthma. The other indications for use of montelukast include: allergic rhinitis, exercise induced bronchoconstriction and aspirin-induced asthma.
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