Ischemia-Modified Albumin, Creatinine, And Paraoxonase-1 Levels in Serum of Patients Undergoing Intravenous Contrast-Enhanced Computed Tomography and Its Association with Contrast-Induced Nephropathy.

BACKGROUND: Following contrast-enhanced computed tomography (CECT) contrast-induced nephropathy (CIN) may occur in patients with renal insufficiency or diabetes. Creatinine, the most common marker of CIN, may not be an accurate measure of damage and is affected by many non-renal factors. Our aim was to evaluate ischemia-modified albumin (IMA) as an early CIN marker and correlate it with paraoxonase-1 (PON-1) and creatinine before and after CECT. METHODS: Forty-eight adult patients scheduled for intravenous CECT, regardless of indication or body region for CECT, were included in this prospective study. Venous blood samples were obtained 12-24 hours before and after contrast media (CM) administration. Ischemia-modified albumin and PON-1 were estimated using methods described by Bar-Or et al. and Dantoine et.al., respectively. Creatinine was estimated on an automated analyzer. RESULTS: Significant differences in IMA (P < 0.001) and PON-1 (P < 0.001) levels were found between pre- and post-CECT samples, while the difference for creatinine was not significant (p = 0.073). No correlation was found between IMA and PON-1 or IMA and creatinine in either the pre- or post-CECT samples. CONCLUSION: After CM administration patients are subjected to oxidative stress and/or ischemia, as revealed by elevated IMA and decreased PON-1 levels; however, creatinine levels, most commonly estimated to assess reduced renal function, did not reflect the condition accurately. IMA may be a sensitive marker for CIN but further studies are required to confirm its usefulness.

Structure, evolution and virtual screening of NDM-1 strain from Kolkata.

ß-lactam antibiotics are utilised to treat bacterial infection. ß-lactamase enzymes (EC 3.5.2.6) are produced by several bacteria and are responsible for their resistance to ß-lactam antibiotics like penicillin, cephamycins and carbapenems. New Delhi Metallo-ß-lactamase (NDM-1) is a gene that makes bacteria resistant to ß-lactam antibiotics. Preparing a compound against NDM-1 will require additional investment and development by drug manufacturers as the current antibiotics will not treat patients with NDM-1 resistance. NDM-1 of Kolkata showed convergent-type evolution with other NDM-1 producing strains. The modelled structure exhibited α-ß-α barrel-type domain along with Zn metallo-ß-lactamase N-terminal domain. Compounds belonging to cephalosporins (relatively resistant to ß-lactamase) and other antibiotics ceftaroline, ceftobiprole, piperacillin, penamecillin, azidocillin, cefonicid, tigecycline and colistin have exhibited better binding affinity with the modelled NDM-1.

Analysis of sequence, structure of GAPDH of Leishmania donovani and its interactions.

Drug resistance acquired by Leishmania donovani (Ldv) is a major problem in the treatment and control of visceral leishmaniasis (VL). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a major glycolytic enzyme has been targeted as is found in other protozoan which cause diseases like sleeping sickness. GAPDH gene of Ldv (AG83 strain) was amplified, sequenced, and modeled on the basis of crystal structure of Leishmania mexicana. The model of the Ldv GAPDH exhibited NAD-binding domain with Rossmann folding. Virtual screening of different experimentally proved compounds with the crystal and the modeled structures of GAPDH of Leishmania strains revealed diverse binding affinities of different compounds. Comparison of binding affinities (based on different programs) of compounds revealed that discovery studio v2.5 (Ligandfit) was able to predict the most hit compounds, the best hit compounds against GAPDH of Leishmania strains are hydrazine, vetrazine, and benzyl carbazate. It is predicted that patients suffering from both VL and cardiac disorders (atrial fibrillation) may benefit if they are treated with warfarin in conjunction with first-line antileishmanial therapies such as miltefosine and AmBisome.