The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces changes in the heme spin state of microsomal cytochrome P-450

In vitro studies on the nature of interaction of the neurotoxin MPTP with hepatic microsomal cytochrome P-450 were carried out. Spectral perturbation studies showed nitrogenous ligand type binding between MPTP and cytochrome P-450 with a peak at 423 nm and a broad trough at 400 nm. Scatchard analysis of MPTP-cytochrome P-450 binding suggested that MPTP binds to at least 2 species of cytochrome P-450--a high affinity binding species with an apparent spectral dissociation constant (Ks) of 372 microM and a low affinity species with Ks of 37.6 mM. EPR studies confirmed that MPTP is a type II substrate for the forms of cytochrome P-450 with which it interacts and causes a shift from the high spin state of cytochrome P-450 to the low spin state. MPTP is, thus, likely to be an effective inhibitor of cytochrome P-450.     

Racial differences in cardiac structure and function in essential hypertension.

OBJECTIVE--To assess racial differences in cardiac structure and function in patients presenting with previously untreated hypertension. DESIGN--Untreated black patients with hypertension were compared with untreated white patients matched for age and sex. Both groups had similar body mass indices, blood pressures, and reported duration of hypertension. SETTING--Cardiovascular risk factor clinic for outpatients. SUBJECTS--36 men and 22 women with untreated essential hypertension. MAIN OUTCOME MEASURES--Variables of heart structure and function on cross sectional and Doppler echocardiography. RESULTS--The black patients had a significantly greater interventricular septal thickness (mean 1.23 (95% confidence interval 1.14 to 1.33) v 1.09 (1.02 to 1.16) cm; P = 0.02) and posterior wall thickness (mean 1.14 (1.07 to 1.22) v 0.96 (0.88 to 1.03) cm; P = 0.001) than the white patients, although left ventricular internal diameter was not significantly different (mean 4.90 (4.68 to 5.12) v 4.82 (4.64 to 5.01) cm; P = 0.59). This resulted in a significantly greater left ventricular mass index (mean 151 (137 to 164) v 120 (107 to 133) g/m2; P = 0.001) and relative wall thickness (mean 0.47 (0.43 to 0.51) v 0.40 (0.37 to 0.42) cm; P = 0.004) in the black patients. Comparison of Doppler measures of left ventricular diastolic function showed a significantly longer isovolumic relaxation time in black patients (mean 107 (98 to 116) v 92 (83 to 101) ms; P = 0.02) compared with white patients, although peak early to atrial filling ratios were similar in both groups (mean 1.14 (0.95 to 1.32) v 1.04 (0.94 to 1.15); P = 0.37). CONCLUSION--Among previously untreated hypertensive patients, black subjects compared with white subjects have significantly higher left ventricular mass index and relative wall thickness, as well as more impairment of left ventricular function during diastole.     

Valorization of mutant Bacillus licheniformis M09 supernatant for green synthesis of silver nanoparticles: photocatalytic dye degradation,antibacterial activity,and cytotoxicity

Bioprocess and Biosystems Engineering - The present study reports the optimization of a green method for the synthesis of silver nanoparticles (AgNPs) via reduction of Ag+ ions using...     

Molecular Docking and Dynamic Simulation to Identify α7nAChR Binding Affinity of Flavonoids for the Treatment of Alzheimer's Disease

Background : Alpha-7-nicotinic acetylcholine receptor (α7nAChR), a ligand-gated ion channel is one of the important parts of the cholinergic pathway in the brain and has a remarkable role in Alzheimer's disease (AD). It has been documented that the modulation of α7nAChR with the help of phytoconstituent can be helpful in the treatment of AD. Method : The binding efficacy of fifty flavonoids was evaluated for human α7nAChR using molecular docking. The best two flavonoids shortlisted from docking analysis were then subjected to molecular dynamic simulations for 100 ns to analyze conformational binding stability with the target protein. Further, the druggability of the selected flavonoids was checked using in silico ADMET studies. Result : The top two flavonoids selected based on binding affinity toward the binding site of α7nAChR from molecular docking were amentoflavone (–9.1 kcal/mol) and gallocatechin (–8.8 kcal/mol). The molecular dynamics simulation revealed that amentoflavone and gallocatechin have a stable state during overall simulation time, lesser root mean deviation (RMSD) and root mean square fluctuation (RMSF), and complex of both compounds with protein is stable until 100 ns. Conclusion : The two flavonoids amentoflavone and gallocatechin are potential lead molecules that could be utilized as effective agonists of α7nAChR to combat Alzheimer's disease. Future in vitro and in vivo analyses are required to confirm their effectiveness.     

Leishmania Specific CD4 T Cells Release IFNγ That Limits Parasite Replication in Patients with Visceral Leishmaniasis

Visceral leishmaniasis (VL) is associated with increased circulating levels of multiple pro-inflammatory cytokines and chemokines, including IL-12, IFNγ, and TNFα, and elevated expression of IFNγ mRNA in lesional tissue such as the spleen and bone marrow. However, an immunological feature of VL patients is that their peripheral blood mononuclear cells (PBMCs) typically fail to respond to stimulation with leishmanial antigen. Unexpectedly, it was recently shown that Leishmania specific IFNγ, can readily be detected when a whole blood stimulation assay (WBA) is used. We sought to define the conditions that permit whole blood cells to respond to antigen stimulation, and clarify the biological role of the IFNγ found to be released by cells from VL patients. CD4+ T cells were found to be crucial for and the main source of the IFNγ production in Leishmania stimulated whole blood (WB) cultures. Complement, antibodies and red blood cells present in whole blood do not play a significant role in the IFNγ response. The IFNγ production was reduced by blockade of human leukocyte antigen (HLA)-DR, indicating that the response to leishmanial antigens observed in WB of active VL patients is a classical HLA- T cell receptor (TCR) driven reaction. Most importantly, blockade of IFNγ in ex-vivo splenic aspirate cultures demonstrated that despite the progressive nature of their disease, the endogenous IFNγ produced in patients with active VL serves to limit parasite growth.