Hit-to-lead optimization of novel phenyl imidazole carboxamides that are active against Leishmania donovani.

Visceral leishmaniasis is a potentially fatal disease caused by the parasitic protists, Leishmania donovani and L. infantum. Current treatments remain unsuitable due to cost, the need for hospitalization, variable efficacy against different species, toxicity and emerging resistance.

Development of an Intranasal Gel for the Delivery of a Broadly Acting Subunit Influenza Vaccine.

Influenza virus is a major cause of death on a global scale. Seasonal vaccines have been developed to combat influenza; however, they are not always highly effective. One strategy to develop a more broadly active influenza vaccine is the use of multiple rounds of layered consensus buildings to generate recombinant antigens, termed computationally optimized broadly reactive antigen (COBRA).

Overcoming reduced antibiotic susceptibility in intracellular Salmonella enterica serovar Typhimurium using AR-12.

Host-directed therapies (HDTs) could enhance the activity of traditional antibiotics. AR-12 is a promising HDT against intracellular pathogens including Salmonella enterica serovar Typhimurium, and has been shown to act through modulation of autophagy and the Akt kinase pathway. Since AR-12 does not inhibit the growth of planktonic bacteria but only works in conjunction with the infected host-cell, we hypothesized that AR-12 could enhance the activity of antibiotics in less-susceptible strains in the intracellular host environment.

Nano- and Microformulations to Advance Therapies for Visceral Leishmaniasis.

Visceral leishmaniasis (VL) is a deadly, vector-borne, neglected tropical disease endemic to arid parts of the world and is caused by a protozoan parasite of the genus . Chemotherapy is the primary treatment for this systemic disease, and multiple potent therapies exist against this intracellular parasite. However, several factors, such as systemic toxicity, high costs, arduous treatment regimen, and rising drug resistance, are barriers for effective therapy against VL.

Formulation of host-targeted therapeutics against bacterial infections.

The global burden of bacterial infections is rising due to increasing resistance to the majority of first-line antibiotics, rendering these drugs ineffective against several clinically important pathogens. Limited transport of antibiotics into cells compounds this problem for gram-negative bacteria that exhibit prominent intracellular lifecycles. Furthermore, poor bioavailability of antibiotics in infected tissues necessitates higher doses and longer treatment regimens to treat resistant infections.

Injectable cellulose-based hydrogels as nucleus pulposus replacements: Assessment of in vitro structural stability, ex vivo herniation risk, and in vivo biocompatibility.

Current treatments for intervertebral disc degeneration and herniation are palliative only and cannot restore disc structure and function. Nucleus pulposus (NP) replacements are a promising strategy for restoring disc biomechanics and height loss. Cellulose-based hydrogel systems offer potential for NP replacement since they are stable, non-toxic, may be tuned to match NP material properties, and are conducive to cell or drug delivery.

Injectable, redox-polymerized carboxymethylcellulose hydrogels promote nucleus pulposus-like extracellular matrix elaboration by human MSCs in a cell density-dependent manner.

Low back pain is a major cause for disability and is closely linked to intervertebral disc degeneration. Mechanical and biological dysfunction of the nucleus pulposus in the disc has been found to initiate intradiscal degenerative processes. Replacing or enriching the diseased nucleus pulposus with an injectable, stem cell-laden biomaterial that mimics its material properties can provide a minimally invasive strategy for biological and structural repair of the tissue.

Thermoresponsive, redox-polymerized cellulosic hydrogels undergo in situ gelation and restore intervertebral disc biomechanics post discectomy.

Back and neck pain are commonly associated with intervertebral disc (IVD) degeneration. Structural augmentation of diseased nucleus pulposus (NP) tissue with biomaterials could restore degeneration-related IVD height loss and degraded biomechanical behaviors; however, effective NP replacement biomaterials are not commercially available. This study developed a novel, crosslinked, dual-polymer network (DPN) hydrogel comprised of methacrylated carboxymethylcellulose (CMC) and methylcellulose (MC), and used in vitro, in situ and in vivo testing to assess its efficacy as an injectable, in situ gelling, biocompatible material that matches native NP properties and restores IVD biomechanical behaviors.

Recognition of possible risk factors for clinically significant drug-drug interactions among Indian people living with HIV receiving highly active antiretroviral therapy and concomitant medications.

Background: Greatest challenges for clinician is to recognize risk factors for clinically significant drug interactions (CSDIs). There is a lack of awareness about CSDIs among healthcare professionals in India.

Objective: To recognize all possible risk factors for drug-drug interactions (DDIs) and to identify clinically significant drug interactions (CSDIs), the prevalence, pattern of occurrence of DDIs in People Living with HIV (PLW-HIV) receiving highly active antiretroviral therapy (HAART) and concomitant medications.

Development of crosslinked methylcellulose hydrogels for soft tissue augmentation using an ammonium persulfate-ascorbic acid redox system.

Hydrogels composed of methylcellulose are candidate materials for soft tissue reconstruction. Although photocrosslinked methylcellulose hydrogels have shown promise for such applications, gels crosslinked using reduction-oxidation (redox) initiators may be more clinically viable. In this study, methylcellulose modified with functional methacrylate groups was polymerized using an ammonium persulfate (APS)-ascorbic acid (AA) redox initiation system to produce injectable hydrogels with tunable properties.

Lower crosslinking density enhances functional nucleus pulposus-like matrix elaboration by human mesenchymal stem cells in carboxymethylcellulose hydrogels.

Engineered constructs represent a promising treatment for replacement of nucleus pulposus (NP) tissue. Recently, photocrosslinked hydrogels comprised of methacrylated carboxymethylcellulose (CMC) were shown to support chondrogenic differentiation of encapsulated human mesenchymal stem cells (hMSCs) and promote accumulation of NP-like extracellular matrix (ECM). The objective of this study was to investigate the influence of CMC crosslinking density, by varying macromer concentration and modification (i.

Injectable carboxymethylcellulose hydrogels for soft tissue filler applications.

Disease, trauma and aging all lead to deficits in soft tissue. As a result, there is a need to develop materials that safely and effectively restore areas of deficiency. While autogenous fat is the current gold standard, hyaluronic acid (HA) fillers are commonly used.

Prevalence of dental anxiety and its relation to age and gender in coastal Andhra (Visakhapatnam) population, India.

Background: Dental fear, anxiety and phobia have consistently been reported as widespread problems that persist despite the technological advances that have made dentistry less painful and less uncomfortable. The aim of this study was to assess the prevalence of dental anxiety (DA) and its relation to age and sex among Coastal Andhra (Visakhapatnam) population.

Materials And Methods: A randomized controlled study was designed among 340 individuals at GITAM Dental College and Hospital, Visakhapatnam.

The reliability of Fishman method of skeletal maturation for age estimation in children of South Indian population.

Introduction: Determining the age of a person in the absence of documentary evidence of birth is essential for legal and medico-legal purpose. Fishman method of skeletal maturation is widely used for this purpose; however, the reliability of this method for people with all geographic locations is not well-established.

Aims And Objectives: In this study, we assessed various stages of carpal and metacarpal bone maturation and tested the reliability of Fishman method of skeletal maturation to estimate the age in South Indian population.

Injectable redox-polymerized methylcellulose hydrogels as potential soft tissue filler materials.

There is a significant clinical need for long-lasting, injectable materials for soft tissue reconstruction. Methylcellulose (MC) is an FDA-approved polysaccharide derivative of cellulose that is inexpensive, renewable, and biocompatible, and may serve as an alternative to existing synthetic and natural fillers. In this study, MC was modified with functional methacrylate groups and polymerized using a redox-initiation system to produce hydrogels with tunable properties.

Association between Medication Adherence Outcomes and Adverse Drug Reactions to Highly Active Antiretroviral Therapy in Indian Human Immunodeficiency Virus-Positive Patients.

In India, interruptions to highly active antiretroviral therapy (HAART) are due to adverse drug reactions. This study was aimed to assess the association between HAART adherence and adverse drug reactions (ADRs) in human immunodeficiency virus (HIV) patients. This prospective study was conducted at a Medicine department in a South Indian tertiary care teaching hospital.

A prospective study of highly active antiretroviral therapy in Indian human immunodeficiency virus positive patients.

Background: There are no studies performed in India on the safety of highly active antiretroviral therapy (HAART) combinations which focus on the base-line CD4+ T-cell count. Further, no data on risk factors for Adverse drug reactions (ADRs) to HAART and there is a lack of data on CD4+ T-cell count recovery after HAART.

Objectives: The aim of this study was to assess risk factors for ADRs to HAART.

Evaluation of incidence of zidovudine induced anemia in Indian human immunodeficiency virus positive patients in comparison with stavudine based highly active antiretroviral therapy.

Objectives: In patients infected with human immunodeficiency virus (HIV), zidovudine has been known to cause a severe anemia that resolves promptly when the drug is stopped. The study was aimed to assess the incidence, the pattern of occurrence of zidovudine induced anemia, causality, severity, predictability, preventability and to identify risk factors for zidovudine induced anemia in Indian HIV positive patients in comparision with stavudine based highly active antiretroviral therapy (HAART).

Methods: This was a prospective observational study conducted over a period of 6 months by clinical pharmacists.

Re-expansion pulmonary oedema: revisited.

A case of re-expansion pulmonary oedema (RPO) following chest tube insertion for left spontaneous pneumothorax is reported. There were no severe symptoms and routine chest radiograph done four hours after tube thoracostomy showed features of pulmonary oedema in the re-expanded left lung. RPO is an uncommon complication of rapid pleural drainage of air or fluid with potentially serious cardiopulmonary manifestations but appears to run a benign course if there is no prior systemic hypoxaemia and if pneumothorax is drained without suction.