Influence of different viscosity grade cellulose-based polymers on the development of valsartan controlled release tablets

This work is based on formulating and optimizing controlled release (CR) valsartan (160 mg) tablets using different viscosity grades of the cellulosic polymer. The objective was to develop an effective once-daily drug delivery system of this cardiovascular agent. Central composite design was used for designing the formulations. Polymers used were Methocel® K4M, K15M and K100M. Compatibility of excipients with active was studied through FT-IR. Micromeritic properties were determined and formulations exhibiting appropriate flow characteristics were compressed. Swelling behavior and in vitro buoyancy effect were studied and response surface curves were constructed to optimize the formulation. Multi-point dissolution profiles of valsartan CR tablets at pH 1.2, 4.5 and 6.8 were obtained. Model-dependent and model-independent methods were performed including f2, stability test as per ICH guidelines and ANOVA. FT-IR studies revealed the compatibility of valsartan with all excipients. Formulation K4T9 (containing 25% K4M polymer) was selected to be the best optimized trial, based on physical properties and controlled release profile (23% at 4 h, 82% at 16 h and 100% at 24 h). Results of buoyancy and swelling behavior indicated that HPMC-K4M polymer exhibited excellent floating lag time and swelling indexes. In vitro drug release kinetics showed that formulation K4T9 displayed Korsmeyer–Peppas drug release pattern with r value > 0.99. The manufacturing process of K4T9 was also found to be reproducible with a shelf life period of 41 and 36 months at room temperature and accelerated conditions, respectively. Valsartan CR matrix-based formulation was successfully prepared with Methocel K4M retardant.     

Genomics and Epigenomics of Gestational Diabetes Mellitus: Understanding the Molecular Pathways of the Disease Pathogenesis

One of the most common complications during pregnancy is gestational diabetes mellitus (GDM), hyperglycemia that occurs for the first time during pregnancy. The condition is multifactorial, caused by an interaction between genetic, epigenetic, and environmental factors. However, the underlying mechanisms responsible for its pathogenesis remain elusive. Moreover, in contrast to several common metabolic disorders, molecular research in GDM is lagging. It is important to recognize that GDM is still commonly diagnosed during the second trimester of pregnancy using the oral glucose tolerance test (OGGT), at a time when both a fetal and maternal pathophysiology is already present, demonstrating the increased blood glucose levels associated with exacerbated insulin resistance. Therefore, early detection of metabolic changes and associated epigenetic and genetic factors that can lead to an improved prediction of adverse pregnancy outcomes and future cardio-metabolic pathologies in GDM women and their children is imperative. Several genomic and epigenetic approaches have been used to identify the genes, genetic variants, metabolic pathways, and epigenetic modifications involved in GDM to determine its etiology. In this article, we explore these factors as well as how their functional effects may contribute to immediate and future pathologies in women with GDM and their offspring from birth to adulthood. We also discuss how these approaches contribute to the changes in different molecular pathways that contribute to the GDM pathogenesis, with a special focus on the development of insulin resistance.     

Measurement of anthocyanins and other phytochemicals in purple wheat

The major anthocyanin composition of normal purple wheat and heat stressed purple wheat were measured using HPLC, LC–MS/MS and the pH differential method. The lignan secoisolariciresinol diglucoside (SDG) and melatonin content were also measured. Total anthocyanin profile of normal purple wheat (491.3 mg/kg) was significantly (P < 0.05) lower than that of the heat stressed purple wheat (522.7 mg/kg). Thirteen major anthocyanins were isolated and cyanidin 3-glucoside was the predominant anthocyanin in purple wheat. Using the pH differential method, the total anthocyanin content of normal (500.6 mg/kg) and heat stressed (526.0 mg/kg) purple wheat were similar to those observed using HPLC. The SDG content of normal and heat stressed purple wheat were 770 and 520 μg/kg, while melatonin content was 4 and 2 μg/kg, respectively. The presence of SDG and melatonin in addition to anthocyanins may contribute to the health benefits associated with consumption of coloured cereal grains.     

Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses

Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine–glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine–glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.     

Is visual imagery really visual? Overlooked evidence from neuropsychology.

Does visual imagery engage some of the same representations used in visual perception? The evidence collected by cognitive psychologists in support of this claim has been challenged by three types of alternative explanation: Tacit knowledge, according to which subjects use nonvisual representations to simulate the use of visual representations during imagery tasks, guided by their tacit knowledge of their visual systems; experimenter expectancy, according to which the data implicating shared representations for imagery and perception is an artifact of experimenter expectancies; and nonvisual spatial representation, according to which imagery representations are partially similar to visual representations in the way they code spatial relations but are not visual representations. This article reviews previously overlooked neuropsychological evidence on the relation between imagery and perception, and discusses its relative immunity to the foregoing alternative explanations. This evidence includes electrophysiological and cerebral blood flow studies localizing brain activity during imagery to cortical visual areas, and parallels between the selective effects of brain damage on visual perception and imagery. Because these findings cannot be accounted for in the same way as traditional cognitive data using the alternative explanations listed earlier, they can play a decisive role in answering the title question. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Laser in situ keratomileusis: literature review of a developing technique

We reviewed papers published in peer-reviewed journals describing techniques and results of laser in situ keratomileusis (LASIK) and summarized the instruments used, nomograms, preoperative and postoperative refractions, predictability, outcome, safety, and complications. We performed a similar review of abstracts published in the abstract books of the 1996 meeting of the International Society of Refractive Surgery, the 1997 meeting of the Association for Research in Vision and Ophthalmology, and the 1997 meeting of the American Society of Cataract and Refractive Surgery. The number of LASIK and photorefractive keratectomy (PRK) patients described in the abstracts were sorted by city. Mean weighted latitudes were calculated and compared for each procedure. The mean preoperative refraction in the papers was -12.59 diopters (D), which was statistically higher than that in the abstracts, -8.71 D (P < .001), and the mean postoperative refraction, -1.10 and + 0.93 D, respectively. The mean percentage of cases within +/- 1.00 D was 67.0% in the papers and 82.5% in the abstracts. Uncorrected visual acuity (UCVA) of 20/40 or better was achieved in 49.2% of eyes in the papers and 83.2% of those in the abstracts; a UCVA of 20/20 or better was achieved in 22.0 and 56.6%, respectively. The portion of eyes that lost two or more lines of best corrected visual was 8.0% in the papers and 0.9% in the abstracts. Complications in the papers included irregular flap (4.0%), incomplete cut (2.5%), free cap (4.9%), perforated lenticule (2.6%), short flap (3.0%), sliding flap (1.4%), interface debris (6.8%), central island (5.3%), decentration (4.7%), epithelial ingrowth (4.3%), induced astigmatism (5.1%), wrinkles (5.9%), haze (8.7%), night vision problems (14.0%), and reoperation (8.2%), Mean latitude for LASIK cases (27.00 degrees +/- 13.73 [SD] was significantly lower than that for PRK cases (42.85 +/- 11.7 degrees). Visual outcomes of LASIK surgery show significant improvements when recent abstracts are compared with published papers. This may reflect continued improvement in the surgical techniques, surgeons' skills, and visual outcomes.     

The influence of sad mood on cognition.

Neuroimaging has identified an overlapping network of brain regions whose activity is modulated by mood and cognition. Studies of depressed individuals have shown changes in perception, attention, memory, and executive functions. This suggests that mood has a pervasive effect on cognition. Direct evidence of the effect of sad mood on cognition is surprisingly limited, however. Published studies have generally addressed a single cognitive ability per study because the fleeting nature of laboratory-induced mood precludes extended testing, and robust findings are limited to mood effects on memory for emotional stimuli. In this study, sad mood was induced and prolonged, enabling the effects of mood to be assessed for an array of abilities, including those that share neural substrates with sad mood and those affected by depression. Sad mood affected memory for emotional words and facial emotion recognition, but not the other processes measured, with a significant nonuniformity of effect over tasks. These results are consistent with circumscribed effects of sad mood on certain emotion-related cognitive processes, but not on cognition more generally. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A Parallel Proximal Splitting Method for Disparity Estimation from Multicomponent Images Under Illumination Variation

Proximal splitting algorithms play a central role in finding the numerical solution of convex optimization problems. This paper addresses the problem of stereo matching of multi-component images by jointly estimating the disparity and the illumination variation. The global formulation being non-convex, the problem is addressed by solving a sequence of convex relaxations. Each convex relaxation is non trivial and involves many constraints aiming at imposing some regularity on the solution. Experiments demonstrate that the method is efficient and provides better results compared with other approaches.