Molecular targets in arthritis and recent trends in nanotherapy

Due to its severity and increasing epidemiology, arthritis needs no description. There are various forms of arthritis most of which are disabling, very painful, and common. In spite of breakthroughs in the field of drug discovery, there is no cure for arthritis that can eliminate the disease permanently and ease the pain. The present review focuses on some of the most successful drugs in arthritis therapy and their side effects. Potential new targets in arthritis therapy such as interleukin-1β, interleukin-17A, tumor necrosis factor alpha, osteopontin, and several others have been discussed here, which can lead to refinement of current therapeutic modalities. Mechanisms for different forms of arthritis have been discussed along with the molecules that act as potential biomarkers for arthritis. Due to the difficulty in monitoring the disease progression to detect the advanced manifestations of the diseases, drug-induced cytotoxicity, and problems with drug delivery; nanoparticle therapy has gained the attention of the researchers. The unique properties of nanoparticles make them highly attractive for the design of novel therapeutics or diagnostic agents for arthritis. The review also focuses on the recent trends in nanoformulation development used for arthritis therapy. This review is, therefore, important because it describes the relevance and need for more arthritis research, it brings forth a critical discussion of successful drugs in arthritis and analyses the key molecular targets. The review also identifies several knowledge gaps in the published research so far along with the proposal of new ideas and future directions in arthritis therapy.

GM3 ganglioside and phosphatidylethanolamine-containing lipids are adipose tissue markers of insulin resistance in obese women

AimsThe association between central obesity and insulin resistance reflects the properties of visceral adipose tissue. Our aim was to gain further insight into this association by analysing the lipid composition of subcutaneous and omental adipose tissue in obese women with and without insulin resistance.MethodsSubcutaneous and omental adipose tissue and serum were obtained from 29 obese non-diabetic women, 13 of whom were hyperinsulinemic. Histology, and lipid and gene profiling were performed.ResultsIn omental adipose tissue of obese, insulin-resistant women, adipocyte hypertrophy and macrophage infiltration were accompanied by an increase in GM3 ganglioside and its synthesis enzyme ST3GAL5; in addition, phosphatidylethanolamine (PE) lipids were increased and their degradation enzyme, PEMT, decreased. ST3GAL5 was expressed predominantly in adipose stromovascular cells and PEMT in adipocytes. Insulin resistance was also associated with an increase in PE lipids in serum.InterpretationThe relevance of these findings to insulin resistance in humans is supported by published mouse studies in which adipocyte GM3 ganglioside, increased by the inflammatory cytokine tumour necrosis factor-α, impaired insulin action, and PEMT was required for adipocyte lipid storage. Thus, in visceral adipose tissue of obese humans, an increase in GM3 ganglioside secondary to inflammation may contribute to insulin resistance and a decrease in PEMT may be a compensatory response to adipocyte hypertrophy.International Journal of Obesity accepted article preview online, 26 October 2015. doi:10.1038/ijo.2015.223.

Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance

© 2015 Elsevier B.V. Ketamine, N-methyl- d-aspartate (NMDA) receptor antagonist and anti-inflammatory agent, has rapid therapeutic effects in a subset of patients with more intractable forms of depression. Irregular proinflammatory cytokine and acute-reactive protein levels have been reported in clinical and preclinical depression research. We explored the association between the rapid antidepressant-like effects of ketamine and peripheral proinflammatory profile in a model of antidepressant-resistance. Male Wistar rats were pre-treated with ACTH-(1-24) 100. μg/d or saline (0.9%) for 14. d. Antidepressant-like effects were assessed with the forced swim test (FST). Ketamine (10. mg/kg) significantly reduced immobility duration in saline-pretreated control animals. In contrast, a divergent response was observed in ACTH-pretreated antidepressant resistant animals, with 50% responders and 50% non-responders. Plasma samples were analyzed via enzyme-linked immunosorbent assay (ELISA) for interleukin 6 (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP). Levels of CRP and TNFα differentiated ketamine responders and non-responders.

Histological, growth and 7-ethoxyresorufin 0-deethylase (EROD) activity responses of greenback flounder Rhombosolea tapirina to contaminated marine sediment and diet

Pathological abnormalities and mixed function oxygenase (MFO) enzyme changes are frequently used as indicators of anthropogenic contaminant exposure and effect. However, there is a paucity of research investigating the effects of contaminated sediment on native Australian benthic teleosts. As part of an ecotoxicological assessment of contaminated marine sediments in northern Tasmania, CYP1A induction, histological and growth response of the greenback flounder, Rhombosolea tapirina, exposed to contaminated marine sediments were examined. Hatchery reared flounder were exposed to reference sediment, contaminated sediment or contaminated sediment and diet for 6 weeks. CYP1A induction, using the ethoxyresorufin-O-deethylase (EROD) assay, and the histological and growth response in the flounder were examined on cessation of the exposure trial. Significant differences were found between treatments in histological, growth and EROD response. Exposure to contaminated sediment and diet elicited a multi-organ histological response: principally partial and total epidermal erosion and multifocal necrosis of the liver. The prevalence of total epidermal erosion was greatest with exposure to disturbed contaminated sediment (66.65±16.65%). The prevalence of multifocal necrosis of the liver was greatest with exposure to contaminanted sediment and diet (66.65±16.65%). Growth reduction, measured as percentage growth inhibition, was evident in flounder exposed to contaminated sediment and diet (18.2±11.99%). Additionally, exposure to contaminated sediment and diet elicited elevated induction of the EROD liver detoxification enzyme (139.65±24.22 pmol/min/mg protein) compared to exposure to contaminated sediment and non-contaminated diet (6.25±0.81 pmol/min/mg) indicating the presence and potential bioavailability of xenobiotics via food. Further, more inhibited growth and histological alteration associated with exposure to contaminated sediment and diet suggest contaminants in Deceitful Cove sediment are cytotoxic.