Homology modeling,binding site identification,and docking study of human β-arrestin: an adaptor protein involved in apoptosis

β-Arrestins are well-known negative regulators of G-protein-coupled receptors (GPCRs) signaling. The present study is aimed to build human β-arrestins 3D structures by homology modeling followed by identification and characterization of binding sites and there by assessing druggability of the proteins. Based upon BLAST results, bovine β-arrestin (PDB ID:1G4M) was considered as a template for homology modeling. Homology models were constructed using MODELLER program, refined and validated using PROCHECK in which >97 % of residues present in the favored regions of the Ramachandran plots. Since there are no co-ordinates of ligands available in the template, we used various binding site prediction algorithms to predict different binding pockets on the modeled proteins. To examine the response of proteins toward various apoptosis inducers, molecular docking study was carried out. The identification of 3D structures, binding sites for various signaling molecules will guide us designing molecular tools for therapeutic intervention that may prove useful in numerous disorders associated with β-arrestin-GPCRs signaling.     

Synthesis, characterization, and antibacterial activity of a novel heterocyclic Schiff’s base and its metal complexes of first transition series

The synthesis of a series of some novel Schiff base complexes of Cu(II), Ni(II), Co(II), Mn(II), Zn(II) with a tetradentate Schiff base has been achieved by the reaction of malonyl hydrazide with dehydroacetic acid in ethanol under refluxing condition. All the synthesized metal complexes and ligand were characterized on the basis of elemental analysis, UV–Visible, ¹H and ¹³C NMR, IR spectroscopy and mass spectrometry. The IR spectral data suggest that azomethine N and enolic O atom are involved in coordination with metal ions, and the ligand behaves as a tetradentate ligand with ONNO donor atoms. The mass spectrum of the complexes reveals the formation of metal ligand bonding in stoichiometric ratio 1:1 (M:L). The UV–Visible data suggest the square planner geometry for the synthesized complexes. All compounds were screened for their antibacterial activity against gram-positive and gram-negative bacteria using Ampicillin as a standard drug. It has been found that metal complexes show enhanced activity as compared to ligand, and some modification in ligand structure may lead to better antibacterial agents in future.     

Quantitative determination of bioactive phenylethanoid glycosides in Clerodendrum phlomidis using HPTLC

A new validated high performance thin layer chromatographic method has been developed for the simultaneous determination of three bioactive phenylethanoid glycosides verbascoside (1), leucosceptoside A (2) and martynoside (3) in the roots of Clerodendrum phlomidis. Extraction efficiency of marker compounds was studied using normal (cold and hot), ultrasonic as well as microwave assisted extraction techniques with various solvents. Well resolved separation of marker compounds was achieved on silica gel 60F₂₅₄ plates using the mobile phase consisting of chloroform–methanol–water (7.8:2.0:0.2, v/v/v). Quantitation of marker compounds was carried out using the densitometric reflection/absorption mode at 460 nm after post-chromatographic derivatization with vanillin–sulphuric acid reagent. Method was validated for peak purity, precision, robustness and sensitivity etc., as per ICH guidelines. Report on the occurrence of phenylethanoid glycosides for the first time in C. phlomidis is of chemotaxonomic importance.     

An Unusual Case of Bilateral Multifocal Retinal Pigment Epithelial Detachment with Methanol-Induced Optic Neuritis

Purpose

To describe an unusual case of methanol-induced optic neuritis with bilateral multifocal extrafoveal serous retinal pigment epithelial (RPE) detachment.

Methods

Single case report.

Case Report

A 40-year-old male presented with acute bilateral loss of vision and history of consumption of adulterated alcohol. On examination, his vision was perception of light in the right eye and finger counting at 1-ft distance in the left eye. Pupillary reactions were sluggish. The optic discs were normal. An elevated lesion with subretinal serous fluid was present over macula adjacent to superior major vessel arcade in the right eye, which was confirmed as a large extrafoveal RPE detachment on fluorescein angiography. There were two more small RPE detachments in the right eye as well as in the left eye. All RPE detachments were extrafoveal in location. The patient was managed medically with intravenous methylprednisolone (1 g) in 500 ml of ringer lactate for three consecutive days. After three doses, visual acuity of both eyes was recorded as 20/20.

Conclusion

We herein report an unusual case of bilateral multifocal extrafoveal serous RPE detachment in a patient of methanol-induced optic neuritis. RPE detachments may be due to the toxic effect of methanol metabolites.     

Does initial Pirani score and age influence number of Ponseti casts in children?

Purpose

The prediction of number of casts in the Ponseti method has always remained a subject of interest. We investigated the correlation of the number of casts before tenotomy with the age and initial Pirani score in Ponseti treatment of club foot.

Methods

Inclusion criteria were idiopathic clubfeet corrected by Ponseti method requiring tenotomy for equinus correction in children up to ten years of age. Defaulters (noncompliance with serial casting schedule), children with postural, non idiopathic, previously surgically treated, recurrent clubfoot and clubfoot not requiring tenotomy were not included in this study. Further, children who did not require tenotomy were also excluded. ANOVA regression analysis was used for finding correlation between initial Pirani score, age in months and number of corrective casts prior to tenotomy.

Results

There were a total of 297 children (442 feet) in the study. The average age of the child at presentation was 10.3 months and the average initial Pirani score was 4.8. The average number of corrective casts was seven per child (range, two to18). The regression analysis showed both Pirani and age had positive correlation with number of casts, although weak (r² = 0.05–0.20). The initial Pirani scoring correlated ten times more than age (in months) to the number of casts.

Conclusion

The number of casts for correction in idiopathic clubfoot, although variable, is influenced by both initial Pirani score and age.