Cyclosporin A in myelodysplastic syndrome: a preliminary report

Therapeutic approaches are not well established in patients with myelodysplastic syndrome (MDS). We evaluated response to cyclosporin A (CyA) in 19 cases with MDS who were enrolled for the study [13 refractory anemia (RA), 5 refractory anemia with excess of blasts (RAEB), and 1 refractory anemia with ringed sideroblasts (RARS)]. Bone marrow was normocellular in ten, hypercellular in five, and hypocellular in four cases. Fifteen patients were transfusion dependent and the rest were not transfusion dependent but with a hemoglobin range of 6.4–8.8 g% with a mean of 7.4 g%. CyA was given at a dose of 3–5 mg/kg per day. A major response was observed in seven patients with RA, which was sustained on follow-up. Four cases of RA showed minor response and two cases of RA did not respond to CyA therapy. A minor response was also seen in one RAEB and one RARS case, while one RAEB case that initially showed a major response relapsed on therapy. The first effect of therapy was evident after a mean period of 2.5 months. A rise in platelets and leukocyte count was seen in three and two cases, respectively. One case developed renal failure on therapy and later died of septicemia. Response to CyA was independent of bone marrow cellularity. CyA could be an effective mode of therapy in patients with MDS especially those having RA.     

Metoprolol--a new cardioselective beta-adrenoceptor blocking agent for treatment of tachyarrhythmias.

The antiarrhythmic effect of the cardioselective beta-adrenoceptor blocking agent metoprolol, given intravenously, was studied in 44 patients with various tachyarrhythmias, including patients with congestive heart failure and signs of digitalis intoxication. All patients with atrial tachycardia (12 cases) reverted to normal sinus rhythm. In 3 out of 18 patients with atrial fibrillation, sinus rhythm was restored, and in the others there was a significant reduction in ventricular rate. In 6 of 10 patients with ventricular ectopic beats, and 1 of 2 patients with ventricular tachycardia, the ectopic rhythm was abolished. The drug was well tolerated, without any significant changes in blood pressure, even by patients with signs of digitalis intoxication and varying degrees of pulmonary or peripheral circulatory congestion. Metoprolol is of clinical value for treatment of tachyarrhythmias, especially those of supraventricular origin.     

Eosinophilia: Rare cause of arterial thrombosis and cardioembolic stroke in childhood

Eosinophilia has been reported as a very rare cause of stroke in children.The thrombotic event may be either due to cardiac damage induced by eosinophils and their granular protein,that is,the major basic protein,or the systemic hypercoagulable state induced by eosinophilia.We report here a case of eosinophilia whose initial presentation was recurrent strokes and cardiac and arterial thrombosis.     

Hybrid BOA-GWO-PSO algorithm for mitigation of congestion by optimal reactive power management

The generation of power with load optimization, particularly in the current deregulated electricity market conditions, is a very important process for improved planning and operation of the grid. In addition, it is very important for the system not to experience problems due to congestion, have tensile stability, and protection to increase the share of electricity from renewable sources with the current supply system. This article presents load balancing with the butterfly optimization algorithm (BOA) in a hybridized form to minimize and maximize loads when used in pool and hybrid markets. The methods have been designed to prevent the drawbacks of BOA and generate a better trade-off between exploration and exploitation abilities by hybridizing it with particle swarm optimization (PSO) and gray wolf optimizer (GWO). Empirical research on other algorithms shows that proposed hybrid BOA-GWO-PSO algorithm performs better and shows potential in diverse problems. These studies give it a significant advantage over BOA in general, and when it is employed to solve complex optimization problems validated on benchmark IEEE 30 bus system. A comparative analysis has been conducted to validate the potency of the hybrid BOA-GWO-PSO approach with some conventional meta-heuristic algorithms. Analysis of results by mathematical validation on 23 benchmark functions and application in congestion management by optimal reactive power management (RPM) reveal that the proposed technique has the potent to solve real world optimization problems and is competitive with recent methods reported in state-of- art literature.     

Lead modification via computational studies: Synthesis of pyrazole-containing β-amino carbonyls for the treatment of type 2 diabetes

This article describes studies on the design, synthesis, and biological evaluation of pyrazole-containing β-amino carbonyl compounds ( 5a – 5q ) as DPP-4 inhibitors and anti-diabetic agents. In contrast, mannich reactions went smoothly with bismuth nitrate (Bi (NO₃)₃) catalyst in the presence of ethanol and produced pyrazole-containing β-amino carbonyl compounds in good yield. Molecular docking studies of designed derivatives with DPP-4 enzyme (PDB: 2OLE), compounds 5d , 5h , 5j , and 5k showed excellent interaction. 3D QSAR and pharmacophoric model studies were also carried out. ADMET parameters, pharmacokinetic properties, and in vivo toxicity studies further confirmed that all the designed compounds were found to have good bioavailability and were less toxic. Further, these compounds were evaluated as enzyme-based in vitro DPP-4 inhibitory activity, and 5d , 5h , 5i , 5j , and 5k exhibited IC₅₀ toward DPP-4 enzyme of 10.52, 10.41, 5.55, 4.16, and 7.5 nM, respectively. The most potent compound, 5j , was further selected for in vivo anti-diabetic activity using an STZ-induced diabetic mice model, and 5j showed a significant diabetic control effect.