Fatal renal failure as the first manifestation of sarcoidosis diagnosed on necropsy in a young man: a case report

Renal involvement as the first manifestation of sarcoidosis is rare and has never been reported in India. This report describes a 35 year old man who was admitted to the emergency department with a clinical diagnosis of acute on chronic renal failure, secondary to obstructive uropathy. Postmortem examination unexpectedly revealed disseminated sarcoidosis.     

MPTP metabolites inhibit rat brain glutathione S-transferases

1-Methyl-4-phenyl-2,3-dihydropyridinium and 1-methyl-4-phenyl-pyridinium species, metabolites of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, non-competitively inhibit glutathione S-transferases of rat brain in vitro. The Ki values for 1-methyl-4-phenyl-2,3-dihydropyridinium bromide and 1-methyl-4-phenyl-pyridinium bromide are 0.67 and 0.3 mM, respectively. Inhibition of these enzymes may lead to impairment of cellular defense mechanisms.     

ATP-Dependent colchicine transport by human erythrocyte glutathione conjugate transporter

We have recently demonstrated mutually inhibitory ATP-dependent transport of dinitrophenyl-S-glutathione (DNP-SG) and doxorubicin by DNP-SG ATPase purified from human erythrocyte membranes (S. Awasthi et al., 1998a,b). Our previous studies indicate a broad substrate specificity for this transport mechanism, including some P-glycoprotein substrates. Present studies were carried out to determine whether colchicine (COL), a classical P-glycoprotein substrate, could be transported by purified human erythrocyte DNP-SG ATPase reconstituted in artificial liposomes. We also investigated whether leukotriene C4 (LTC4), an endogenous proinflammatory glutathione-conjugate derived from arachidonic acid, would inhibit colchicine transport. Uptake of COL was compared in proteoliposomes reconstituted with the purified DNP-SG ATPase as well as control liposomes in the presence or absence of ATP. Increased colchicine uptake was observed upon addition of ATP to proteoliposomes, but not control liposomes. Uptake was linear with respect to the amount of vesicle protein used. Sensitivity to osmolarity was consistent with intravesicular COL accumulation. The ATP-dependent colchicine uptake was sensitive to temperature in a manner consistent with a protein-mediated transport process with activation energy of 7.3 kcal/mol. Time-dependent COL uptake by proteoliposomes in the presence of ATP was consistent with a single compartment model with an apparent rate constant of 0.21 +/- 0.02 min-1. Kinetic studies indicated a saturable behavior with respect to ATP (Km 2.3 +/- 0.7 mM) and colchicine (Km 4.3 +/- 0.2 microM). LTC4 was found to be a competitive inhibitor of COL transport (Kis 16.4 microM). Since DNP-SG ATPase is present in many tissues, it may play an important role in determining colchicine accumulation in cells. Increased LTC4 would tend to increase cellular COL accumulation.     

Under fives mortality in the urban slums of Lucknow

The main objective of this study was to elicit proportional cause specific mortality in the underfives in the urban slums of Lucknow in North India. The families with under five mortality in the 28 randomly selected slums in 1993 were located from the records of the slum health workers and verbal autopsy was conducted to assign a cause of death. There were 71 deaths among 2796 children. The annual under five mortality was 25.4 and the under five mortality rate was 126.7. After the neonatal period, “high fever” that could not be classified into any other disease incorporated in the verbal autopsy instrument, was the most common symptom associated with death, seen in 21.1% cases (95% C.I.: 15.5–34.4%) followed by these diseases: pheumonia in 19.7%, diarrhea in 18.3% and measles in 11.4%. “High fever” as the leading symptom associated with death is being reported for the first time from the urban slums of India. There is an urgent need to identify the underlying etiologies of death due to “high fever” and the policy implications are that children with fever must receive immediate and continued medical attention till the symptom persists.     

Tissue specific expression of sialic acid metabolic pathway: role in GNE myopathy

Journal of Muscle Research and Cell Motility - GNE myopathy is an adult-onset degenerative muscle disease that leads to extreme disability in patients. Biallelic mutations in the rate-limiting...     

An efficient and environmentally sustainable domino protocol for the synthesis of structurally diverse spiroannulated pyrimidophenazines using erbium doped TiO2 nanoparticles as a recyclable and reusable heterogeneous acid catalyst

An efficient and environmentally sustainable domino protocol has been presented for the synthesis of structurally diverse spiroannulated pyrimidophenazines involving a four component reaction of 2-hydroxynaphthalene-1,4-dione, benzene-1,2-diamine, cyclic ketones and amino derivatives in the presence of erbium doped TiO₂ nanoparticles as a recyclable and reusable heterogeneous acid catalyst. The present synthetic protocol features mild reaction conditions with operational simplicity, excellent yield with high purity, short reaction time and high atom economy with the use of a recoverable and reusable environmentally sustainable heterogeneous catalyst.

An efficient and environmentally sustainable domino protocol has been presented for the synthesis of structurally diverse spiroannulated pyrimidophenazines using erbium doped TiO₂ nanoparticles as a recyclable and reusable heterogeneous acid catalyst.