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Biomedical subjects

Avtar Singh

Publications and source records attributed to Avtar Singh.

6 recordsLinked to original sources
PubMed2005

The use of N-acetylcysteine for the prevention of hypertension in the reduced uterine perfusion pressure model for preeclampsia in Sprague-Dawley rats.

OBJECTIVE: To determine whether N-acetylcysteine attenuates abnormal changes in the reduced uterine perfusion pressure model. STUDY DESIGN: Twenty-four timed-pregnant Sprague-Dawley rats underwent sham surgery or the reduced uterine perfusion pressure procedure on day 15 of 22. Reduced uterine perfusion pressure animals were treated with N-acetylcysteine (100 mg/kg) or saline twice daily until delivery. On day 21 of 22, mean arterial pressure was determined and maternal tissue was collected and stored. Pups and pup brains were weighed. Statistical analysis was performed using 1-way analysis of variance and the Tukey-Kramer test with significance at P < .05. RESULTS: There was a significant increase in blood pressure with the reduced uterine perfusion pressure procedure (P = .016), which was alleviated by N-acetylcysteine (P = .044). There was a significant decrease in pup weight and brain weight with the reduced uterine perfusion pressure procedure (P = .043 and P = .046, respectively). N-acetylcysteine restored pup brain weight (P = .021) but had no significant effect on pup weight. CONCLUSION: N-acetylcysteine reduced blood pressure without adversely effecting fetal weight.

Acetylcysteine↗
PubMed2004

Attenuation of ischemia-reperfusion injury in a canine model of autologous renal transplantation.

BACKGROUND: This study examined the potential therapeutic effects of a combination therapy consisting of 5-aminoimidazole-4-carboxamide-1-beta-D-ribonucleoside (AICAR) and N-acetyl cysteine (NAC) to attenuate ischemia-reperfusion (I/R) injury in a canine model of autologous renal transplantation. METHODS: Male mongrel dogs (15-20 kg) underwent left nephrectomy followed by flushing and static preservation of the kidney in University of Wisconsin (UW) solution for 48 hr. The treatment group received AICAR (50 mg/kg) plus NAC (100 mg/kg) intravenously before the left nephrectomy. The compounds were added to the UW solution as well. All dogs underwent right nephrectomy 48 hr later followed by autotransplantation of the preserved left kidney. Treated dogs received a second dose of AICAR and NAC before implantation of the renal autograft. RESULTS: The treated dogs had excellent urine output posttransplant, with peak serum creatinine of 7.26 mg/dL on postoperative day (POD) 3 that normalized after 14 days. The control group were anuric and developed clinical symptoms of uremia on POD 1. Morphologic evaluation supported the protective effects of combination therapy. Immunohistochemical analysis revealed decrease of tumor necrosis factor-alpha, interferon-gamma, and inducible nitric oxide synthase; and TUNEL assay showed decreased apoptosis in the treated group. CONCLUSIONS: Combination therapy with AICAR and NAC attenuates renal I/R injury and improves the outcome of the transplanted kidney after prolonged cold preservation.

Acetylcysteine↗
PubMed2004

Active-site conformational changes associated with hydride transfer in proton-translocating transhydrogenase.

Transhydrogenase couples the redox (hydride-transfer) reaction between NAD(H) and NADP(H) to proton translocation across a membrane. The redox reaction is catalyzed at the interface between two components (dI and dIII) which protrude from the membrane. A complex formed from recombinant dI and dIII (the dI(2)dIII(1) complex) from Rhodospirillum rubrum transhydrogenase catalyzes fast single-turnover hydride transfer between bound nucleotides. In this report we describe three new crystal structures of the dI(2)dIII(1) complex in different nucleotide-bound forms. The structures reveal an asymmetry in nucleotide binding that complements results from solution studies and supports the notion that intact transhydrogenase functions by an alternating site mechanism. In one structure, the redox site is occupied by NADH (on dI) and NADPH (on dIII). The dihydronicotinamide rings take up positions which may approximate to the ground state for hydride transfer: the redox-active C4(N) atoms are separated by only 3.6 A, and the perceived reaction stereochemistry matches that observed experimentally. The NADH conformation is different in the two dI polypeptides of this form of the dI(2)dIII(1) complex. Comparisons between a number of X-ray structures show that a conformational change in the NADH is driven by relative movement of the two domains which comprise dI. It is suggested that an equivalent conformational change in the intact enzyme is important in gating the hydride-transfer reaction. The observed nucleotide conformational change in the dI(2)dIII(1) complex is accompanied by rearrangements in the orientation of local amino acid side chains which may be responsible for sealing the site from the solvent and polarizing hydride transfer.

Adenosine Diphosphate Ribose↗
PubMed2003

Interactions between transhydrogenase and thio-nicotinamide Analogues of NAD(H) and NADP(H) underline the importance of nucleotide conformational changes in coupling to proton translocation.

Transhydrogenase couples the reduction of NADP+ by NADH to inward proton translocation across mitochondrial and bacterial membranes. The coupling reactions occur within the protein by long distance conformational changes. In intact transhydrogenase and in complexes formed from the isolated, nucleotide-binding components, thio-NADP(H) is a good analogue for NADP(H), but thio-NAD(H) is a poor analogue for NAD(H). Crystal structures of the nucleotide-binding components show that the twists of the 3-carbothiamide groups of thio-NADP+ and of thio-NAD+ (relative to the planes of the pyridine rings), which are defined by the dihedral, Xam, are altered relative to the twists of the 3-carboxamide groups of the physiological nucleotides. The finding that thio-NADP+ is a good substrate despite an increased Xam value shows that approach of the NADH prior to hydride transfer is not obstructed by the S atom in the analogue. That thio-NAD(H) is a poor substrate appears to be the result of failure in the conformational change that establishes the ground state for hydride transfer. This might be a consequence of restricted rotation of the 3-carbothiamide group during the conformational change.

Binding Sites↗