Discovery of 1-(Cyclopropylmethyl)-2-(Dibenzo[b,d]Thiophen-2-yl)-1H-Benzo[d]Imidazole-5-Carboxylic Acid as Orally Bioavailable EP4 Receptor Antagonist.

The prostaglandin E (PGE) regulates several biological processes via interaction with 1 of 4 E-type prostanoid receptors (EP1-EP4). The E-type prostanoid receptor 4 (EP4) is expressed primarily on myeloid cells, T lymphocytes, and tumor cells, and has emerged as a major contributor to PGE-mediated enhancement of tumor survival pathways and as a suppressor of innate and adaptive antitumor immune responses. To date, significant work on the discovery of EP4 receptor antagonists has been carried out, but no compound has been approved for use in humans yet.

Investigation of Antibiotic-Releasing Biodegradable Composite Bone Cements for Treating Experimental Chronic Maxillofacial Bone Infection.

Chronic osteomyelitis of the maxillofacial bones (i.e., jaw bones) is a persistent infection that requires effective treatment.

Effect of an Autotaxin Inhibitor, 2-(4-Chlorophenyl)-7-methyl-8-pentylimidazo[1,2-] Pyrimidin-5(8)-one (CBT-295), on Bile Duct Ligation-Induced Chronic Liver Disease and Associated Hepatic Encephalopathy in Rats.

The role of autotaxin (ATX)-lysophosphatidic acid (LPA) is yet to be explored in the context of liver cirrhosis and associated encephalopathy. Our objective of this study was to evaluate the role of an ATX inhibitor in biliary cirrhosis and associated hepatic encephalopathy in rats. The preliminary investigation revealed significant impairment in liver function, which eventually led to the development of hepatic encephalopathy.

Biomaterials-Based Strategies to Enhance Angiogenesis in Diabetic Wound Healing.

Amidst the present healthcare issues, diabetes is unique as an emerging class of affliction with chronicity in a majority of the population. To check and control its effects, there have been huge turnover and constant development of management strategies, and though a bigger part of the health care area is involved in achieving its control and the related issues such as the effect of diabetes on wound healing and care and many of the works have reached certain successful outcomes, still there is a huge lack in managing it, with maximum effect yet to be attained. Studying pathophysiology and involvement of various treatment options, such as tissue engineering, application of hydrogels, drug delivery methods, and enhancing angiogenesis, are at constantly developing stages either direct or indirect.

Inhibition of Autotaxin Ameliorates LPA-Mediated Neuroinflammation and Alleviates Neurological Dysfunction in Acute Hepatic Encephalopathy.

Growing evidence suggests an essential role of neuroinflammation in behavioral abnormalities associated with hepatic encephalopathy (HE). Here, we report the involvement of autotaxin-lysophosphatidic acid (LPA) signaling in HE's pathogenesis. We demonstrate that the autotaxin (ATX) inhibitor PF-8380 attenuates neuroinflammation and improves neurological dysfunction in the mouse model of HE.

Ratiometric pH Sensing, Photophysics, and Cell Imaging of Nonaromatic Light-Emitting Polymers.

Here, four nontraditional fluorescent polymers (s) of varying ,-dimethyl-2-propenamide (DMPA) and butyl prop-2-enoate (BPE) mole ratios, i.e., 2:1 (), 4:1 (), 8:1 (), and 16:1 (), are prepared via random polymerization in water.

Biological analysis of an innovative biodegradable antibiotic eluting bioactive glass/gypsum composite bone cement for treating experimental chronic MRSA osteomyelitis.

A multi-barrier antibiotics loaded biodegradable composite bone cement for resolving chronic osteomyelitis has been studied to understand the physico-mechanical properties, drug loading/eluting efficiency, and different merits and demerits prior to clinical application. After successful induction of bone infection in 28 rabbits using methicillin-resistant (MRSA) strains, calcium sulfate/bioactive glass based composite cement was implanted in 12 defects to assess its performance over parenteral therapy with microscopic and radiological examination for 90 days. The composite cement revealed acceptable physico-mechanical properties and controlled drug elution kinetics.

Structure-based discovery of (S)-2-amino-6-(4-fluorobenzyl)-5,6,11,11a-tetrahydro-1H-imidazo[1',5':1,6]pyrido[3,4-b]indole-1,3(2H)-dione as low nanomolar, orally bioavailable autotaxin inhibitor.

Inhibition of extracellular secreted enzyme autotaxin (ATX) represents an attractive strategy for the development of new therapeutics to treat various diseases and a few inhibitors entered in clinical trials. We herein describe structure-based design, synthesis, and biological investigations revealing a potent and orally bioavailable ATX inhibitor 1. During the molecular docking and scoring studies within the ATX enzyme (PDB-ID: 4ZGA), the S-enantiomer (Gscore = -13.

Surface characteristics of titanium dental implants with improved microdesigns: An in vivo study of their osseointegration performance in goat mandible.

Current trends in endosseous implant research are focused on the modification of microdesign of implants to achieve early and strong osseointegration. This study compares the influence of zinc doped hydroxyapatite (ZnHAp) coated, hydrothermally treated (HT) and machined Ti6Al4V (control) implants on osseointegration. The surface characterisation and microbial affinity test for implants were performed.

Fluorescent Guar Gum--Terpolymer via In Situ Acrylamido-Acid Fluorophore-Monomer in Cell Imaging, Pb(II) Sensor, and Security Ink.

The nonconventional purely aliphatic scalable and reusable fluorescent guar gum (GRGM)--acrylic acid--3-(-isopropylacrylamido)propanoic acid (NIPAPA)---isopropylacrylamide (GRGM--, i.e., ), was synthesized via of the optimum amount of GRGM and N- functionalized in situ protrusion of acrylamido-acid fluorophore-monomer, i.

Perovskite solar cell for photocatalytic water splitting with a TiO/Co-doped hematite electron transport bilayer.

Hydrogen production using a photoelectrochemical (PEC) route promises to be a clean and efficient way of storing solar energy for use in hydrogen-powered fuel cells. Iron oxide (α-FeO) is best suited to be used as a photoelectrode in PEC cells for solar hydrogen production due to its favorable band gap of ∼2.2 eV.

Understanding osteomyelitis and its treatment through local drug delivery system.

Chronic osteomyelitis is a major challenge in bone surgery. Conventional use of antibiotics is not an effective way to control the malaise due to so many reasons. Determination of optimal treatment strategy becomes difficult for the orthopaedic surgeons and as a consequence, the patients suffer not only from therapeutic failure but also due to adverse side effects of antibiotics and financial loss due to additional stay at hospitals.

A novel, multi-barrier, drug eluting calcium sulfate/biphasic calcium phosphate biodegradable composite bone cement for treatment of experimental MRSA osteomyelitis in rabbit model.

This article discloses the development of an effective and versatile technology to prepare a novel antibiotics-loaded biodegradable composite bone cement to treat methicillin-resistant Staphylococcal (MRSA) osteomyelitis and reports its detail in vitro characterization, drug loading efficiency, physico-mechanical properties, drug elution in simulated body fluid (SBF) and human plasma, merits and demerits over poly-methyl methacrylate (PMMA) cement. Chronic osteomyelitis in rabbit tibia (42) was induced by MRSA and composite cement was implanted to evaluate its safety and efficacy over PMMA cement and parenteral treated animals with histopathology, radiographs, bone/plasma drugs concentration, and SEM for 90days. The composite cement showed higher setting time, degradability, pH rise, injectability, in vitro drug elution but lesser mechanical strength than PMMA cement.

Safety and efficacy of additive and subtractive surface modification of Ti6Al4V endosseous implant in goat bone.

Growing interest of endosseous implant research is focused on surface modification to achieve early and strong osseointegration. The present study compared the behaviour of hydroxyapatite coated, zinc doped hydroxyapatite coated and hydrothermally treated titanium (Ti6Al4V) with machined Ti6Al4V implants (control) on osseointegration. The surface characterization and bacterial affinity test for implants were performed.

Counter anion dependent gradual spin transition in a 1D cobalt(ii) coordination polymer.

One Co(ii) SCO coordination polymer [Co(enbzpy)(μ1,5-dca)]n(PF6)n (·PF6) has been isolated and characterised structurally and magnetostructurally. The properties of ·PF6 are compared with the reported perchlorate analogue [Co(enbzpy)(μ1,5-dca)]n(ClO4)n (·ClO4). The gradual spin transition in ·PF6 in contrast to an abrupt spin transition with a hysteresis loop in ·ClO4 has been analysed in terms of structural factors.

Effect of combination treatment of S-amlodipine with peroxisome proliferator-activated receptor agonists on metabolic and cardiovascular parameters in Zucker fa/fa rats.

Background: Type 2 diabetes is a complex metabolic disorder characterized by hyperglycemia, impaired glucose tolerance and insulin resistance associated with dyslipidemia and hypertension. The available drugs are not sufficiently efficacious in reducing cardiovascular risk and restoring normal glucose metabolism associated with type 2 diabetes as a mono- or a combination therapy. The present study examined the combined effects of an antihypertensive (S-Amlodipine) and an insulin-sensitizing agent, peroxisome proliferator-activated receptor (PPAR) agonists (Pioglitazone and Ragaglitazar), on cardiovascular risk factors in aged diabetic and insulin-resistant Zucker fa/fa rats.

Determinants of health care seeking for diarrheal illness in young children in urban slums of Kolkata, India.

Maternal practices regarding children's health care have been recognized as an important factor associated with mortality rates among children < 5 years of age. We focused on health care-seeking practices of primary caretakers of children < 5 years of age with diarrheal disease in Kolkata. We interviewed caretakers of 1,058 children in a baseline survey and 6,077 children on six subsequent surveys.

Biological evaluation of RBx-0128, a potent and selective dipeptidyl peptidase-IV inhibitor in type 2 diabetes genetic model.

Aim: Dipeptidyl peptidase IV (DPP-IV) inhibition to modulate the incretin effect is a proven strategy to treat type 2 diabetes mellitus. The present study describes the pharmacological profile of a novel DPP-IV inhibitor RBx-0128, as an antidiabetic agent.

Material And Methods: DPP-IV assay was carried out to evaluate in vitro potency of RBx-0128 using human, mouse, and rat plasma as an enzyme source.

Evaluation of autologous bone marrow in wound healing in animal model: a possible application of autologous stem cells.

A study was conducted to evaluate the potential of autologous bone marrow-derived cells in comparison with buffy coat of autologous blood for rapid cutaneous wound healing in rabbit model. Three square full-thickness skin excisional wounds were created in 15 selected experimental animals (rabbit) divided randomly into three groups. The wound was treated with autologous bone marrow cells in plasma (group 1), buffy coat of blood in plasma (group 2) and autologous plasma as control (group 3).

Macro-to-micro porous special bioactive glass and ceftriaxone-sulbactam composite drug delivery system for treatment of chronic osteomyelitis: an investigation through in vitro and in vivo animal trial.

A systematic and extensive approach incorporating in vitro and in vivo experimentation to treat chronic osteomyelitis in animal model were made using antibiotic loaded special bioactive glass porous scaffolds. After thorough characterization for porosity, distribution, surface charge, a novel drug composite were infiltrated by using vacuum infiltration and freeze-drying method which was subsequently analyzed by SEM-EDAX and studied for in vitro drug elution in PBS and SBF. Osteomyelitis in rabbit was induced by inoculation of Staphylococcus aureus and optimum drug-scaffold were checked for its efficacy over control and parenteral treated animals in terms of histopathology, radiology, in vivo drug concentration in bone and serum and implant-bone interface by SEM.

Nature of action of Sitagliptin, the dipeptidyl peptidase-IV inhibitor in diabetic animals.

Objective: The aim of this study was to evaluate the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin with respect to mode of inhibition and its in vivo duration of inhibition and efficacy in type 2 diabetes animal model.

Materials And Methods: DPP-IV enzyme assay was carried out in human plasma (10 μL) or human recombinant enzyme (10 ng) using H-Gly-Pro-AMC as a substrate. The competitive nature was estimated by plotting IC(50) values measured at different substrate concentrations on the Y axis and substrate concentration on the X axis.