In Silico Analysis to Link Insulin Resistance, Obesity and Ageing with Alzheimer's Disease.

The process of ageing accompanies several metabolic diseases. With ageing, fats accumulate to increase the visceral and abdominal adiposity leading to hyperinsulinemia, insulin resistance, obesity and several other diseases. Drosophila melanogaster is often used to study the ageing process and its related disorders. Therefore, in this study, we performed an in silico analysis to relate the process of ageing and insulin resistance. We analysed the data of insulin-resistant Drosophila from the GEO database and compared it with the data from the literature survey. We observed that 98 genes were common in both the models, and they showed gene modulations related to metabolic pathways, fatty acid metabolism, insulin resistance and neural receptor-ligand binding pathways. Analysis of the REACTOME database against human data revealed that the TRKB signalling pathway is commonly affected. The TRKB-mediated BDNF pathway is a major regulator of memory loss. We further analysed the common genes in Alzheimer's disease and compared the fly data with human data to identify the diseases related to these common genes. Then, we performed a literature survey to provide protective mechanisms for the TRKB signalling pathway activation, mediated through polyphenols. We treated the flies with sesamol-conjugated lipoic acid derivative (a phenolic compound) at hormetic doses to evaluate its effect on the memory of flies.

Problems of Face Recognition in Patients with Behavioral Variant Frontotemporal Dementia.

INTRODUCTION: Faces are very special as they are most essential for social cognition in humans. It is partly understood that face processing in its abstractness involves several extra striate areas. One of the most important causes for caregiver suffering in patients with anterior dementia is lack of empathy. This apart from being a behavioral disorder could be also due to failure to categorize the emotions of the people around them. PATIENTS AND METHODS: Inlusion criteria: DSM IV for Bv FTD Tested for prosopagnosia - familiar faces, famous face, smiling face, crying face and reflected face using a simple picture card (figure 1). EXCLUSION CRITERIA: Advanced illness and mixed causes. OBSERVATIONS: 46 patients (15 females, 31 males) 24 had defective face recognition. (mean age 51.5),10/15 females (70%) and 14/31males(47. Familiar face recognition defect was found in 6/10 females and 6/14 males. Total- 40%(6/15) females and 19.35%(6/31)males with FTD had familiar face recognition. Famous Face: 9/10 females and 7/14 males. Total- 60% (9/15) females with FTD had famous face recognition defect as against 22.6%(7/31) males with FTD Smiling face defects in 8/10 female and no males. Total- 53.33% (8/15) females. Crying face recognition defect in 3/10 female and 2 /14 males. Total- 20%(3/15) females and 6.5%(2/31) males. Reflected face recognition defect in 4 females. RESULTS: Famous face recognition and positive emotion recognition defect in 80%, only 20% comprehend positive emotions, Face recognition defects are found in only 45% of males and more common in females. CONCLUSION: Face recognition is more affected in females with FTD There is differential involvement of different aspects of the face recognition could be one of the important factor underlying decline in the emotional and social behavior of these patients. Understanding these pathological processes will give more insight regarding patient behavior.

A quality by design approach to understand formulation and process variability in pharmaceutical melt extrusion processes.

OBJECTIVES: In this study, the principles of quality by design (QbD) have been uniquely applied to a pharmaceutical melt extrusion process for an immediate release formulation with a low melting model drug, ibuprofen. METHODS: Two qualitative risk assessment tools - Fishbone diagram and failure mode effect analysis - were utilized to strategically narrow down the most influential parameters. Selected variables were further assessed using a Plackett-Burman screening study, which was upgraded to a response surface design consisting of the critical factors to study the interactions between the study variables. In process torque, glass transition temperature (Tg ) of the extrudates, assay, dissolution and phase change were measured as responses to evaluate the critical quality attributes (CQAs) of the extrudates. The effect of each study variable on the measured responses was analysed using multiple regression for the screening design and partial least squares for the optimization design. KEY FINDINGS: Experimental limits for formulation and process parameters to attain optimum processing have been outlined. A design space plot describing the domain of experimental variables within which the CQAs remained unchanged was developed. CONCLUSIONS: A comprehensive approach for melt extrusion product development based on the QbD methodology has been demonstrated. Drug loading concentrations between 40- 48%w/w and extrusion temperature in the range of 90-130°C were found to be the most optimum.

Melt extrusion: process to product.

INTRODUCTION: Niche applicability and industrial adaptability have led hot melt extrusion (HME) techniques to gain wide acceptance and have, therefore, solidified their place in the array of pharmaceutical research and manufacturing operations. Melt extrusion's momentum has resulted in extensive research publications, reviews and patents on the subject for over a decade. Currently, > 50% of the new drug candidates are speculated to be highly lipophilic and thus poorly bioavailable. HME is a key technology for these and other formulation and processing issues. AREAS COVERED: Various approaches have been addressed using HME in developing solid molecular dispersions and have demonstrated viability to provide sustained, modified and targeted drug delivery resulting in improved bioavailability. This review provides a holistic perspective on HME from equipment, processing and materials to its varied applications in oral delivery (immediate release, sustained release, taste masking, enteric and targeted release, as well as trans-drug delivery), oral mucosal, dermal, ungual and intravaginal systems. EXPERT OPINION: Interest in HME as a pharmaceutical process continues to grow and the potential of automation and reduction of capital investment and labor costs has earned this technique a necessary consideration as a drug delivery solution.