Thiolated Polymeric Hydrogels for Biomedical Applications: A Review.

Hydrogels are a three-dimensional (3D) network of hydrophilic polymers. The physical and chemical crosslinking of polymeric chains maintains the structure of the hydrogels even when they are swollen in water. They can be modified with thiol by thiol epoxy, thiol-ene, thiol-disulfide, or thiol-one reactions.

Formulation optimization, in vitro and in vivo evaluation of agomelatine-loaded nanostructured lipid carriers for augmented antidepressant effects.

The present study was intended to prepare and optimize agomelatine-loaded nanostructured lipid carriers (AGM-NLCs) for augmented in vivo antidepressant potential. AGM-NLCs were optimized on several parameters including cumulative hydrophilic-lipophilic balance of surfactants, proportions of solid and liquid lipids, total amounts of drug and surfactants. AGM-NLCs were assessed for their physicochemical properties, in vitro AGM release and in vivo antidepressant effects in mice model.

Formulation of instant disintegrating buccal films without using disintegrant: An in-vitro study.

The current study was conducted to fabricate Metoclopramide HCL (MCH) and Sumatriptan succinate (SS) instant release buccal films (IRBF) without using any super disintegrant. The solvent casting method was used for the preparation of IRBFs and prepared IRBFs were physicochemically evaluated. Spectrophotometric analysis was done to determine the lambda max followed by the linearity determination of both drugs.

Formulation and evaluation of sustained release ocular inserts of betaxolol hydrochloride using arabinoxylan from Plantago ovata.

The purpose of the current studies was to develop ocular insert of betaxolol hydrochloride (BXH), using arabinoxylan (AX) as a film former. The inserts were prepared by sandwiching I mg of BXH between two films of AX. Six different formulations of ocular inserts were prepared in such a way that first three formulations contained varying concentrations of AX along with glycerol as plasticizer, whereas, rest of the formulations were added with 0.

Formulation development and in-vitro evaluation of gastroretentive drug delivery system of loxoprofen sodium: A natural excipients based approach.

The limitations of conventional type delivery systems to retain drug (s) in the stomach has resulted in the development of novel gastroretentive drug delivery system. We developed single-layer effervescent floating tablets of loxoprofen sodium for prolong delivery in the stomach using natural polymers xanthan gum, guar gum and semisynthetic polymer HPMCK4M. All the formulations (F1-F9) were developed by varying concentrations of xanthan gum and HPMCK4M while guar gum concentration was kept constant.

Transcatheter Mitral Valve Repair for Severe,Symptomatic Mitral Regurgitation in Patients with Left Ventricular Assist Devices.

Patients with symptomatic stage D heart failure who require left ventricular assist device (LVAD) support and suffer concomitant severe mitral regurgitation are often difficult to manage. One reason is due to cardiac anatomic constraints that limit optimization of the mechanical assist device. Typically, these patients are not candidates for repeat sternotomy with surgical mitral valve repair, and heart transplantation may not be feasible or timely.

Securing the Insecure: A First-Line-of-Defense for Body-Centric Nanoscale Communication Systems Operating in THz Band.

This manuscript presents a novel mechanism (at the physical layer) for authentication and transmitter identification in a body-centric nanoscale communication system operating in the terahertz (THz) band. The unique characteristics of the propagation medium in the THz band renders the existing techniques (say for impersonation detection in cellular networks) not applicable. In this work, we considered a body-centric network with multiple on-body nano-senor nodes (of which some nano-sensors have been compromised) who communicate their sensed data to a nearby gateway node.

Sensory organization for postural control in children with strabismus-A systematic review and meta-analysis.

Background: Postural control requires the interaction of somatosensory, vestibular and visual systems to prevent disequilibrium. Children with strabismus have an impaired visual input which can lead to postural control deficits.

Research Question: Does strabismus affect sensory organization for postural control in children?

Methods: A systematic comprehensive search of multiple electronic databases for relevant articles was performed using a predetermined search strategy.

Antidepressant-like effect of ethanol in mice forced swimming test is mediated via inhibition of NMDA/nitric oxide/cGMP signaling pathway.

There is evidence for a dramatic relationship between depression and alcohol consumption. Depressed patients may abuse ethanol because this agent reduces the symptoms of depression. In the current study, we aimed to investigate the NMDA/nitric oxide/cGMP pathway in the antidepressant-like effect of ethanol in an animal model of behavioral despair.

Licofelone, a dual cyclooxygenase/5-lipoxygenase inhibitor, reverses endotoxin-induced impaired atrial chronotropic responsiveness to cholinergic stimulation in rats.

Evidence show that endotoxemia is linked with tachycardia. The exact mechanism of tachycardia is not well-understood, but it seems that impaired cardiac chronotropic responsiveness to cholinergic stimulation plays a role in this phenomenon. The aim of this experiment was to study the effect of licofelone as a dual cyclooxygenase (COX)/5-lipoxygenase (5-LOX) inhibitor in modulation of atrial chronotropic hyporesponsiveness to cholinergic stimulation in endotoxemic rats, compared with hydrocortisone and indomethacin in in vitro and in vivo studies.

Nanostructured lipid carriers-mediated brain delivery of carbamazepine for improved in vivo anticonvulsant and anxiolytic activity.

The limited brain delivery of carbamezapine (CBZ) presents a major hurdle in the successful epilepsy treatment. The potential of carbamezapine-loaded nanostructured lipid carriers (CBZ-NLCs) for improved brain delivery is investigated in the current study. CBZ-NLCs were prepared by using binary mixture of trilaurin and oleic acid as a lipid core stabilized with Poloxamer 188, Tween 80 and Span 80.

In Silico, Cytotoxic and Antioxidant Potential of Novel Ester, 3-hydroxyoctyl -5-docosenoate Isolated from (L.) M.Bieb. Against HepG-2 Cancer Cells.

Background: Cancer is one of the chronic health conditions worldwide. Various therapeutically active compounds from medicinal plants were the current focus of this research in order to uncover a treatment regimen for cancer. (L.

Computer-aided design and synthesis of 3-carbonyl-5-phenyl-1-pyrazole as highly selective and potent BRAFV600E and CRAF inhibitor.

BRAF belongs to the upstream portion of the MAPK pathway, which is involved in cell proliferation and survival. When mutations occur in BRAF, downstream MEK and ERK are phosphorylated irrespective of RAS, resulting in melanoma-like cancer. Over the years, small molecules targeting BRAFV600E have been discovered to be very effective melanoma drugs, but they are known to cause the BRAF paradox.

Mechanical Circulatory Support in High-Risk Percutaneous Coronary Intervention.

Due to advancing age and increasing comorbidities, the current population has a higher incidence of complex coronary artery disease, often without surgical options for revascularization. In this setting, hemodynamic support devices are an important adjunct in the interventionist's toolbox as they allow for a safer, more effective procedure. The following paper reviews the indications of various available mechanical support devices, highlights their clinical data and technical parameters, and offers a practical approach towards appropriate patient and device selection.

Discovery of novel 4-aryl-thieno[1,4]diazepin-2-one derivatives targeting multiple protein kinases as anticancer agents.

A series of 4-aryl-thieno[1,4]diazepin-2-one were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Several compounds showed very potent antiproliferative activities toward both cell lines and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide (8a-8i, 9a-9m) and urea (10a-10d, 11a-11d) with diverse hydrophobic moieties.

Physicochemical Modifications and Nano Particulate Strategies for Improved Bioavailability of Poorly Water Soluble Drugs.

Background: Bioavailability is the segment of dose that is bioavailable for its therapeutic effect on the systemic circulation without any change in its characteristics, after administration by either route. It is one of the fundamental pharmacokinetic properties of drugs. It is important because, it defines the amount of drug to be administered for its intended therapeutic effect.

Effective use of nanocarriers as drug delivery systems for the treatment of selected tumors.

Nanotechnology has recently gained increased attention for its capability to effectively diagnose and treat various tumors. Nanocarriers have been used to circumvent the problems associated with conventional antitumor drug delivery systems, including their nonspecificity, severe side effects, burst release and damaging the normal cells. Nanocarriers improve the bioavailability and therapeutic efficiency of antitumor drugs, while providing preferential accumulation at the target site.

Novel scaffold evolution through combinatorial 3D-QSAR model studies of two types of JNK3 inhibitors.

JNK3 is an emerging target for neurodegenerative diseases including AD and PD, with histological selectivity. Specifically, in AD, JNK3 is the main protein kinase for APP phosphorylation, which is an important mechanism for Aβ processing, and a biomarker of Alzheimer's disease. Therefore, targeting JNK3 is a reasonable strategy for drug discovery in neurodegenerative diseases.

Randomized Study of Persistent Atrial Fibrillation Ablation: Ablate in Sinus Rhythm Versus Ablate Complex-Fractionated Atrial Electrograms in Atrial Fibrillation.

Background: Achieving long-term successful outcomes with ablation of persistent atrial fibrillation (AF) remains a clinical and procedural challenge. We aimed to assess 2 ablation strategies for persistent AF: pulmonary vein antral isolation (PVAI) in sinus rhythm after direct current cardioversion versus PVAI and ablation targeting complex-fractionated atrial electrograms while in AF.

Methods And Results: Between June 2009 and July 2013, patients with continuous persistent AF for ≥3 months were prospectively randomized to either direct current cardioversion before PVAI and posterior wall/septum ablation while in sinus rhythm (group 1), versus same ablation in group 1 in addition to complex-fractionated atrial electrogram ablation while in AF (group 2).

Discovery of highly selective CRAF inhibitors, 3-carboxamido-2H-indazole-6-arylamide: In silico FBLD design, synthesis and evaluation.

The recent success of vemurafenib shows the importance of selective BRAF V600E inhibition in melanoma. However, paradoxical activation by structurally diverse ATP-competitive RAF kinase inhibitors strongly suggests that selective CRAF inhibitors, not BRAF inhibitors, would be ideal for some Ras mutation cancer treatment. In this respect, we approached designing selective CRAF inhibitors starting from in silico fragment screening and synthesized a 3-carboxamido-2H-indazole-6-arylamide scaffold.

Discovery of 4-arylamido 3-methyl isoxazole derivatives as novel FMS kinase inhibitors.

A series of 4-arylamido 3-methyl isoxazoles were synthesized and evaluated for their antiproliferative activities against the A375P melanoma and U937 hematopoietic cell lines. Most compounds showed selective antiproliferative activity toward the U937 cell line and the activities were better than that of sorafenib, the reference standard. Derivatives were made as amide 5a-b, 6a-o and urea 7a-n, 8a-g with hydrophobic moieties, and one of the most potent inhibitor 6a, 5-methyl-N-(2-methyl-5-(3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamido)phenyl)isoxazole-4-carboxamide was found to be very potent inhibitor of FMS kinase (GI50 = 0.

Click approach to the discovery of 1,2,3-triazolylsalicylamides as potent Aurora kinase inhibitors.

A series of 1,2,3-triazolylsalicylamide derivatives has been developed from the antiproliferative agent 7 and was evaluated for their Aurora kinase inhibitory activity. The novel 1,2,3-triazolylsalicylamide scaffold could be readily assembled by Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition, allowing rapid access to the structurally diverse analogues. The synthesized 1,2,3-triazolylsalicylamide derivatives revealed a significant Aurora kinase inhibitory activity.

Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors.

The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative activities against the A375P human melanoma cell line and the U937 human leukemic monocyte lymphoma cell line are described. Potent antiproliferative effects were found from 9l, 9s and 10c; 10c was found to be a highly potent and selective BRAF V600E and CRAF inhibitor (IC50=38.3 nM and 8.