A Profile for Predicting Attrition from Exercise in Older Adults

The purpose of this study was to determine a profile for predicting attrition among older adults involved in a 12-month exercise program. The parent study was a single-blinded randomized controlled trial. The study took place between 2006 and 2009 within a university setting. Older adults (N?=?179) completed baseline assessments of functional performance and psychosocial measures. Participants who were randomized, elected to receive treatment, and did not complete the exercise program were considered “dropouts” (n?=?35). Those who completed the program (n?=?144) were classified as “completers.” A latent profile analysis revealed two distinct patterns of memory complaints, self-efficacy to overcome barriers to exercise, balance performance, and stair performance. Dropouts were nearly twice as likely to be members of the profile that exhibited a higher degree of memory complaints, lower self-efficacy for overcoming exercise barriers, poorer single leg balance, and longer times to walk down stairs. The results provide an initial validation of a profile for discriminating between “dropouts” and “completers,” one that may have considerable utility for screening older adults prior to study entry.     

Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation

This study was undertaken to determine the influence of Aloe vera (AV) on changes induced in pulmonary tissue of cigarette smoke (CS) inhaling mice. CS inhalation for 4 weeks caused pulmonary damage as evident by histoarchitectural alterations and enhanced serum and tissue lactate dehydrogenase (LDH) activities. CS inhalation also led to increased mucin production as revealed by mucicarmine and Alcian Blue‐Periodic Acid Schiff (AB‐PAS) staining. Studies on bronchoalveolar lavage fluid (balf) of CS exposed animals revealed structural changes in phospholipids and increase in surface tension when compared with control counterparts. These changes were accompanied by enhanced nitric oxide (NO) levels, citrulline levels, peroxidative damage, and differential modulation of antioxidant defense system. AV administration (seven weeks, 500 mg/kg b.w. daily) to CS inhaling mice led to modulation of CS induced pulmonary changes as revealed by lesser degree of histoarchitectural alterations, lesser mucin production, decreased NO levels, citrulline levels, peroxidative damage, and serum LDH activity. AV treatment to CS inhaling mice was associated with varying response to antioxidant defense system, however balf of CS + AV treated animals did not exhibit appreciable changes when compared with that of CS exposed animals. These observations suggest that AV has the potential to modulate CS induced changes in the pulmonary tissue which could have implications in management of CS associated pulmonary diseases, however, further investigations are required to explore its complete mechanism of action. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 999–1013, 2015.     

The Structure of Glycosaminoglycans and their Interactions with Proteins

Glycosaminoglycans (GAGs) are important complex carbohydrates that participate in many biological processes through the regulation of their various protein partners. Biochemical, structural biology and molecular modelling approaches have assisted in understanding the molecular basis of such interactions, creating an opportunity to capitalize on the large structural diversity of GAGs in the discovery of new drugs. The complexity of GAG–protein interactions is in part due to the conformational flexibility and underlying sulphation patterns of GAGs, the role of metal ions and the effect of pH on the affinity of binding. Current understanding of the structure of GAGs and their interactions with proteins is here reviewed: the basic structures and functions of GAGs and their proteoglycans, their clinical significance, the three‐dimensional features of GAGs, their interactions with proteins and the molecular modelling of heparin binding sites and GAG–protein interactions. This review focuses on some key aspects of GAG structure–function relationships using classical examples that illustrate the specificity of GAG–protein interactions, such as growth factors, anti‐thrombin, cytokines and cell adhesion molecules. New approaches to the development of GAG mimetics as possible new glycotherapeutics are also briefly covered.     

Harnessing public domain data to discover and validate therapeutic targets

Introduction: Discovering, developing and validating new disease treatments is a challenging and time-consuming endeavor. Successful drug discovery hinges on selecting the best drug targets with relevance to human disease and evidence that modulating them will be beneficial for patients. Open data initiatives are increasingly placing such knowledge into the public domain.

Areas covered: In this review, the authors discuss emerging resources such as Open Targets which integrate key information to prioritize target-disease connections. Researchers can use it, along with other resources, to select potential new therapeutic targets to initiate drug discovery projects. They also discuss public resources such as DrugBank and ChEMBL that offer potential tools to interrogate these targets.

Expert opinion: In our opinion, publically available resources are democratizing and connecting information, enabling disease experts to access and prioritize targets of interest in ways that were not possible a few years ago. Moreover, there are several modalities in addition to small molecule perturbation to modulate a target’s activity. Drug discovery scientists can now utilize these new resources to simultaneously evaluate a much larger number of targets than previously possible.     

Optimized and Validated Stability Indicating RP-HPLC Method for Estimation of Nadolol

Pharmaceutical Chemistry Journal - A stability indicating RP-HPLC method for the determination of nadolol was developed and validated using Enable C18 (250 mm × 4.6 mm, 5 μm) column with...     

Hepatoprotective Bile Acid Co-Drug of Isoniazid: Synthesis,Kinetics and Investigation of Antimycobacterial Potential

Pharmaceutical Chemistry Journal - The long-course treatment of tuberculosis with isoniazid (INH) leads to hazardous side effects on liver and poor patient compliance. To overcome these toxic...     

Transcending the skin barrier to deliver peptides and proteins using active technologies

Peptides and proteins have been investigated as promising therapeutic agents over the past decade. These macromolecules are conventionally administered by the parenteral route because oral delivery is associated with degradation in the gastrointestinal tract. Transdermal delivery presents a promising alternative route of drug delivery, avoiding pain associated with parenteral administration and degradation issues associated with oral delivery. However, the barrier properties of skin limit delivery to only small, moderately lipophilic molecules. Hence, hydrophilic macromolecules like peptides and proteins cannot passively permeate across skin. Active physical enhancement approaches such as iontophoresis electroporation, microneedles treatment, and sonophoresis have been developed to assist transdermal delivery of peptides and proteins. This review describes active physical transdermal enhancement approaches for transdermal delivery of peptides and proteins. The mechanisms associated with each technique and important parameters governing transdermal delivery of peptides and proteins are discussed in detail. Combinations of enhancement techniques for synergistic enhancement in protein and peptide delivery are also discussed.     

Intranasal Delivery of Chitosan Nanoparticles for Migraine Therapy

Objective

The objective of the research was to formulate and evaluate sumatriptan succinate-loaded chitosan nanoparticles for migraine therapy in order to improve its therapeutic effect and reduce dosing frequency.

Material and Methods

The Taguchi method design of experiments (L9 orthogonal array) was applied to obtain the optimized formulation. The sumatriptan succinate-loaded chitosan nanoparticles (CNPs) were prepared by ionic gelation of chitosan with tripolyphosphate anions (TPP) and Tween 80 as surfactant.

Results

The CNPs had a mean size of 306.8 ± 3.9 nm, a zeta potential of +28.79 mV, and entrapment efficiency of 75.4 ± 1.1%. The in vitro drug release of chitosan nanoparticles was evaluated in phosphate buffer saline pH 5.5 using goat nasal mucosa and found to be 76.7 ± 1.3% within 28 hours.

Discussion

The release of the drug from the nanoparticles was anomalous, showing non-Fickian diffusion indicating that drug release is controlled by more than one process i.e. the superposition of both phenomena, a diffusion-controlled as well as a swelling-controlled release. This is clearly due to the characteristics of chitosan which easily dissolves at low pH, thus a nasal pH range of 5.5 ± 0.5 supports it very well. The mechanism of pH-sensitive swelling involves protonation of the amine groups of chitosan at low pH. This protonation leads to chain repulsion, diffusion of protons and counter ions together with water inside the gel, and the dissociation of secondary interactions.

Conclusion

The results suggest that sumatriptan succinate-loaded chitosan nanoparticles are the most suitable mode of drug delivery for promising therapeutic action.