Drug Repurposing and Orphan Disease Therapeutics

Drug repurposing (or drug repositioning) is an innovative way to find out the new indications of a drug that already exists in the market with known therapeutic indications. It offers an effective way to drug developers or the pharmaceutical companies to identify new targets for FDA-approved drugs. Less time consumption, low cost and low risk of failure are some of the advantages being offered with drug repurposing. Sildenafil (Viagra), a landmark example of a repurposed drug, was introduced into the market as an antianginal drug. But at present, its use is repurposed as drug for erectile dysfunction. In a similar way, numerous drugs are there that have been successfully repurposed in managing the clinical conditions. The chapter would be highlighting the various drug repurposing strategies, drugs repurposed in the past and the current status of repurposed drugs in the orphan disease therapeutics along with regulatory guidelines for drug repurposing

DOCTOR OF MEDICINE AND DIPLOMATE OF NATIONAL BOARD COURSES IN INDIA–ISSUES AND EQUIVALENCE: A COMPARATIVE ANALYSIS

India is the only country in the world running two different doctoral courses for doctors, i.e., Doctor of Medicine (MD) and Diplomate of National Board (DNB). DNB course was introduced in 1975 to overcome shortage of specialist doctors and medical teachers. Both courses have centralized entry examination, similar tenure period, academic and clinical activities, and research exposure and exit examination (in the host institute in MD examination and in designated exit exam centre in institute other than poarent institute in case of DNB examination). Initially, the Ministry of Health and Family Welfare and Medical Council of India (MCI) established the equivalence between two. Discrimination started since October 2012 through MCI gazette notification for DNB trainees from non-MCI recognized institutes with regards to teacher appointment. DNB doctors were united to raise their voice against this. While the Government of India (GOI) is in favor of equivalence between two, MCI is against the same. Recently, MCI is dissolved and is going to be replaced by the National Medical Commission and positive outcome is expected for the DNB side. A recent notification is issued toward equivalence of two courses provided candidate completed DNB course from hospitals with minimum 500 beds. Evaluating quality of education on the basis of number of beds seems unjustifiable as there are many better indicators of quality of medical education. The NMC act also retained the same 500 bed criteria. Taking into account the view point of benefit of population and improvement in medical education in India, it is desirable to reconsider the issue by the Government of India (GOI) and to act accordingly. To enhance the standard of current medical education, higher standards should be imposed in curriculum and centralized exit examination to be made compulsory for both the courses

A systematic review for the development of Alzheimer’s disease in in vitro models: a focus on different inducing agents

Alzheimer’s disease (AD) is the most common progressive neurodegenerative disease and is associated with dementia. Presently, various chemical and environmental agents are used to induce in-vitro models of Alzheimer disease to investigate the efficacy of different therapeutic drugs. We screened literature from databases such as PubMed, ScienceDirect, and Google scholar, emphasizing the diverse targeting mechanisms of neuro degeneration explored in in-vitro models. The results revealed studies in which different types of chemicals and environmental agents were used for in-vitro development of Alzheimer-targeting mechanisms of neurodegeneration. Studies using chemically induced in-vitro AD models included in this systematic review will contribute to a deeper understanding of AD. However, none of these models can reproduce all the characteristics of disease progression seen in the majority of Alzheimer’s disease subtypes. Additional modifications would be required to replicate the complex conditions of human AD in an exact manner. In-vitro models of Alzheimer’s disease developed using chemicals and environmental agents are instrumental in providing insights into the disease’s pathophysiology; therefore, chemical-induced in-vitro AD models will continue to play vital role in future AD research. This systematic screening revealed the pivotal role of chemical-induced in-vitro AD models in advancing our understanding of AD pathophysiology and is therefore important to understand the potential of these chemicals in AD pathogenesis

Lung Cancer Classification from Histologic Images using Capsule Networks

Cancer is one of the most dangerous and invasive disease in the human body. Lung cancer has the highest mortality rate amongst the other cancers. Therefore, detection and classification has become critical for the diagnosis of lung cancers. The manual determination of cancer from histology slides require expert supervision and takes time. Computer vision systems using Convolutional Neural Network (CNN) have shown remarkable performance in automated detection of cancers. But the current CNN based system have some limitations. In this study the state-of the art Capsule Networks are used for lung cancers classification from histopathology images. Capsule Network does have the capability to preserve the orientation, pose and texture which is achieved by the vector transformation of the extracted features. For pre-processing the images were stain normalized. The classification performance of the model is evaluated using Matthew’s correlation coefficient (MCC), specificity, sensitivity, false negative and false positive rate and accuracy. The Capsule Network implemented in the study achieved 0.99 MCC score and 99% accuracy for lung cancer classification

Formulation and Evaluation of Diltiazem Hydrochloride Gels for the Treatment of Anal Fissures

The treatment for chronic anal fissure (CAF) has undergone a transformation in recent years from surgical to medical. Both the approaches share the common goal of reducing the spasm of anal sphincter. Though surgical treatment has a high success rate but it can permanently impair fecal continence in large number of patients. Smooth muscle relaxation seems to be a novel way by which more than 60% of the patients can be cured with the topical use of the agents. In the present investigation, diltiazem hydrochloride gels were prepared using FDA recommended polymers [hydroxypropylmethyl cellulose (HPMC), methylcellulose (MC) and polyethylene oxide (PEO grade 301 and 303)] for topical application in CAF. Increasing the concentration of the polymer significantly increased the consistency of the gels. All the formulations exhibited pseudoplastic flow with no thixotropy. The values of flow index (n) were found to be less than one for all the gels confirming the shear thinning behaviour of all the gels. HPMC and MC gels were found to be stable at accelerated stability conditions while the bioadhesion of PEO gels was highest. Even after exposure to heat and humidity, no significant change was observed in the content uniformity, pH, clarity, texture profile analysis and rheological properties of the HPMC and MC gels. The rheograms and various power law equation parameters of these gels were found comparable at various time points in the accelerated stability study. However, PEO gels failed in accelerated stability studies at one month sample. When four selected gel formulations (HPMCL4, MCL3, P1BL3 and P3BL3.5) were applied topically by six patients each, Gastrointestinal Quality of Life Index (GIQLI) score of each patient was improved at the end of 8 weeks. No adverse effects were reported by any of the patients. Hence 2% DTZ gel was found to be effective in the treatment of anal fissures

Chalcones as an Emerging Lead Molecule for Antimalarial Therapy: A Review

Chalcones (1, 3, diaryl-2-propen-1-ones), are one of the plant secondary metabolite belonging to flavonoid family and has been widely explored in past decennium for its various pharmacological activities including antimalarial activity. Plasmodium aspartate proteases and cysteine proteases are the promising targets in malarial chemotherapy to overcome the drug resistance. Chalcones supposed to show antimalarial activity by inhibiting either Plasmodium aspartate proteases or cysteine proteases. This review covers the mechanism of action, previous reported studies showing antimalarial activity of natural and synthetic chalcones and its derivatives along with future prospects to fight against drug resistant malaria. These compounds provide an option of developing inexpensive, synthetic therapeutic antimalarial agents and may serve as lead compounds for development of drug in near future

Neuroprotective effect of pioglitazone on acute phase changes induced by partial global cerebral ischemia in mice

793-799Present study was carried out to investigate the possible neuroprotective effect of pioglitazone, an antidiabetic agent, peroxisome proliferator-activated receptor (PPAR) agonist on acute phase changes in mice model of cerebral ischemia induced by Bilateral Common Carotid artery Occlusion (BCCAO). BCCAO model was used to induce partial global cerebral ischemia. BCCAO induced significant brain infarct size and edema in saline treated control group along with high increase in oxidative stress showed by increase lipid peroxidation and decreased levels of antioxidants like superoxide superoxide dismutage, catalase, glutathione peroxidase. Pioglitazone (20 mg/kg, orally) administration showed neuroprotective effects by reducing cerebral infarct size significantly as compared to control group. Postischemic seizure susceptibility was also reduced as number of positive responders decreased to a significant number. Brain edema was subsided to a significant level. Pioglitazone reduced the plasma TNF- α levels as compared to ischemia group significantly. Pioglitazone treatment also improved all the antioxidants levels showing activity against oxidative stress induced by BCCAO. Pioglitazone showed neuroprotection against ischemic insult suggesting the role of PPAR agonist in neuroprotective agents

Challenges of drug-resistant malaria

Over the past six decades, the drug resistance of Plasmodium falciparum has become an issue of utmost concern. Despite the remarkable progress that has been made in recent years in reducing the mortality rate to about 30% with the scaling-up of vector control, introduction of artemisinin-based combination therapies and other malaria control strategies, the confirmation of artemisinin resistance on the Cambodia–Thailand border threatened all the previous success. This review addresses the global scenario of antimalarial resistance and factors associated with it, with the main emphasis on futuristic approaches like nanotechnology and stem cell therapy that may impede resistant malaria, along with novel medications which are preparing to enter the global antimalarial market. These novel studies are likely to escalate over the coming years and will hopefully help to reduce the burden of malaria