Design and Synthesis of Butenolide‐based Novel Benzyl Pyrrolones: Their TNF‐α based Molecular Docking with In vivo and In vitro Anti‐inflammatory Activity

A focused library of novel benzyl pyrrolones has been synthesized and their in silico molecular docking studies carried out against TNF‐α target. Among all the docked molecules, compound 3f showed best glide score of ?6.89. All the synthesized compounds were evaluated for in vivo anti‐inflammatory activity by carrageenan‐induced paw edema model. Compounds showing significant anti‐inflammatory activity were further tested for their in vitro TNF α expression. Compounds 3b and 2b were found to show significant inhibition of 76.22% and 71.47%, respectively after 5 h in comparison with standard drug indomethacin, which showed 80.98% inhibition of inflammation. Compounds 3b and 2b also suppressed TNF α level by 65.03% and 60.90% as compared indomethacin, which showed 68.84% of inhibition. Compound 3b showed significant analgesic activity of 60.04%, and its activity was comparable with indomethacin (64.04%). Compounds 3b and 2b were also tested for their effect on protein expression of COX‐2 and NF‐κB in the liver tissues. Compounds 3b and 2b were further evaluated for their gastric risk and lipid peroxidation action and showed superior GI safety along with reduction of LPO as compared to indomethacin. Hepatotoxicity study showed that these two compounds did not cause any damage to liver.     

Nanotechnology-mediated nose to brain drug delivery for Parkinson's disease: a mini review

Nose to brain delivery of neurotherapeutics have been tried by several researchers to explore the virtues of this route viz. circumvention of BBB, avoidance of hepatic metabolism, practicality, safety, ease of administration and non-invasiveness. Nanoparticle (NP) therapeutics is an emerging modality for the treatment of Parkinson's disease (PD) as it offers targeted delivery and enhances the therapeutic efficacy and/or bioavailability of neurotherapeutics. This review presents a concise incursion into the nanomedicines suitable for PD therapy delivered via naso-brain transport. Clinical signs of PD, its pathophysiology, specific genetic determinants, diagnosis and therapy involved have been hashed out. Properties of brain-targeting NPs, transport efficacy and various nanocarriers developed so far also been furnished. In our opinion, nanotechnology-enabled naso-brain drug delivery is an excellent means of delivering neurotherapeutics and is a promising avenue for researchers to develop new formulations for the effective management of PD.     

Syncope,seizure or both?

Ictal asystole (IA) is a rare phenomenon in patients with seizures with an incidence of 0.27–0.4% and has been proposed as a possible mechanism of sudden unexpected death in epilepsy patients (SUDEP). We present a case of a 53-year-old woman who initially presented with episodes of expressive aphasia and was treated with antiepileptic drugs (AEDs). While on therapy she experienced episodes of syncope. During her hospitalization for tapering of AEDs and 24-hour EEG monitoring, the patient developed a seizure followed by sinus bradycardia and an 18-second sinus pause, resulting in loss of consciousness and slowing of cerebral activity. Ten seconds after the return of cardiac activity, the EEG showed return of cerebral activity. A dual chamber pacemaker was implanted.     

Predictors of Left Ventricular Outflow Tract Obstruction After Transcatheter Mitral Valve Replacement

Objectives

The aim of this study was to evaluate the predictors of left ventricular outflow tract (LVOT) obstruction after transcatheter mitral valve replacement (TMVR).

Left ventricular myocardial performance in patients with dengue hemorrhagic fever and thrombocytopenia as assessed by two-dimensional speckle tracking echocardiography

ObjectivesWe obtained longitudinal, radial and circumferential strains in patients with dengue hemorrhagic fever (DhF) and thrombocytopenia using two-dimensional (2D) speckle tracking echocardiography to analyze left ventricular (LV) myocardial performance.MethodsIn this prospective study, 2D echocardiographic images of the left ventricle in the four-, three- and two-chamber views and parasternal short-axis views at the basal, mid and apical levels were obtained in 40 subjects: 20 patients (23 ± 8 years, 12 male) with DhF and thrombocytopenia and 20 healthy controls (23 ± 5 years, 11 male). Of the 20 patients, imaging was performed again in 19 at discharge after a hospital stay of 8 ± 1 days. Longitudinal, circumferential and radial strains were quantified and compared in an 18-segment model using a novel speckle tracking system.ResultsLeft ventricular global ejection fraction was reduced in patients with DhF at presentation as compared with controls (51.25 ± 0.96% vs. 59.32 ± 1.26%; p = 0.032). Peak longitudinal strain in patients with DhF was significantly attenuated in the subendocardial region compared with normal controls (p < 0.001). A significant increase in circumferential strain for patients with DhF was evident only in the subepicardial region (p = 0.009). Patients with DhF showed significantly higher radial strain than controls (p < 0.001). On multivariate analysis, subendocardial longitudinal strain independently predicted the duration of hospital stay in patients with DhF.ConclusionAssessment of speckle tracking echocardiography-derived LV mechanics helps in understanding myocardial mechanics in patients with DhF and thrombocytopenia. Identification of reduced LV longitudinal strain helps in understanding the mechanism of reduced LV myocardial performance seen in patients with DhF.     

Use of belimumab throughout pregnancy to treat active systemic lupus erythematosus—A case report

Background

Pregnancy can lead to flares in systemic lupus erythematosus (SLE), and the presence of SLE in pregnancy could lead to a poor outcome for the mother and the fetus.

Objective

To describe a patient whose active SLE (including lupus nephritis) was managed with the use of belimumab throughout pregnancy.

Methods

A case report and review of relevant literature is presented.

Results

A 38-year-old Caucasian woman with SLE was seen for advice regarding planning a pregnancy and management of her active lupus (cutaneous lupus, angioedema, lupus nephritis, leukopenia, and anti-phospholipid antibody syndrome) that could only be controlled by mycophenolate, a drug contraindicated in pregnancy. Azathioprine, hydroxychloroquine, rituximab, and moderate doses of prednisone were either unable to control her disease or led to unacceptable toxicity. After detailed discussions, she was treated with belimumab, which controlled her SLE and allowed withdrawal of mycophenolate. Belimumab was continued throughout the pregnancy, leading to well-controlled SLE and uneventful course, albeit with the presence of mild Ebstein?s anomaly in the baby.

Conclusion

To our knowledge, this is the first case report of belimumab use throughout pregnancy for controlling active SLE. Data from the belimumab pregnancy registry would be useful to confirm our findings and to further assess safety of this agent for use in pregnancy.     

Role of q-switched nd:yag laser in nevus of ota: a study of 25 cases

Background:

Nevus of Ota is common condition in Indian patients. The condition is more common in females, with a male-female ratio of 1:4.8.

Aim:

To evaluate long-term efficacy safety and stability of Q-switched ND:YAG laser in treatment of Nevus of Ota.

Design:

6 month follow-up of patients of Nevus of Ota, treated with Q-switched ND:YAG laser

Materials and Methods:

Twenty-five patients of Nevus of Ota were treated with Q-switched ND:YAG laser for a period of 1 year and 9 months; patient had fitzpatricks skin type 4 and 5; detailed history, clinical examination, ophthalmoscopy, and otoscopy was done in all cases; clinical photographs were taken before and after the completion of treatments. Six-month follow-up was done after the last session. Response to treatment was graded based on physician''s global assessment.

Result:

More than 70% improvement was seen in 15 patients (60%). Eight patients (32%) had moderate and two patients (8%) showed mild improvement.