PREPARATION AND EVALUATION OF EXTENDED RELEASE NIMESULIDE TABLET BASED ON DIFFUSION CONTROLLED MECHANISM

Now a days the concept of controlled release is quiet popular amongst the formulation scientists. The aim of thisstudy was to develop a once-daily sustained release matrix tablet of Nimesulide using hydroxyl propylmethylcellulose (HPMC K4M) as release controlling factor and to evaluate drug release parameters as per variousrelease kinetic models. The tablets were prepared using wet granulation method. Total of five batches were preparedfrom which two selected batches were further evaluated. Different dissolution models were applied to drug releasedata in order to evaluate release mechanisms and kinetics. The “n” Value of both batches indicates that the drugrelease mechanism follows “Anomalous Transport”. From all these data it is quite clear that batch F2 is optimized asits release kinetic was found to be as per Korsmeyer Peppas model rather than first order of F4

Comparison of remineralizing effect of organic and inorganic fluoride by evaluation of microhardness and quantitative analysis of calcium and phosphorus ratio on enamel surface: an in-vitro study

Background Enamel is a highly mineralized tissue of the body which is composed of 96% inorganic salts and 4% organic matter. Enamel is permeable to water and ions, particularly cations and low molecular weight substances. The enamel continues to mature even after eruption with mineral replacing protein. Recently, the interest on the development of calcium phosphate-based remineralization technology has been increased that led to the development of various remineralizing agents like Fluoride, CPP-ACP (Tooth Mouse plus), Bioglass (Novamin), Ozone, Xylitol, Sensistat etc. Aim Aim of the present in vitro study was to evaluate and compare the remineralizing effect of Organic fluoride (AmF) and inorganic fluoride (NaF) by evaluating Vickers microhardness and quantitative analysis of Calcium and Phosphorus ratio on enamel surface using Scanning Electron Microscope-Energy Dispersive X-ray analysis. Materials and methods Sixteen maxillary central incisors were decoronated at the cementoenamel junction and mounted in cylindrical moulds filled with self-cure acrylic resin. Artificial demineralized lesions were created on the enamel surface by suspending them in 0.1 M Citric acid buffer at pH of 3.2 for 72 hrs. The samples were then randomly divided into two groups and labelled, Group A – remineralized with NaF for 3 minutes twice daily for one week and Group B - remineralized with AmF for 3 minutes twice daily for one week. Microhardness and SEM-EDX analysis were done before demineralization, after demineralization and after remineralization. Results Data were analyzed by comparing the mean values between the groups using independent sample t-test. The intra-group analysis was done using repeated-measures ANOVA with posthoc Bonferroni test, and a p-value of <0.05 was considered statistically significant. Conclusion OrganicFluoride resulted in better remineralization than inorganic Fluoride. After remineralization for one week, enamel samples treated with AmF demonstrated a statistically significant increase in mean microhardness and Ca:P ratio when compared to enamel samples treated with NaF

Preservation of parathyroid glands during thyroid and neck surgery

The parathyroid glands are situated in close proximity to the thyroid gland. They have an important endocrine function maintaining calcium and phosphate homeostasis in the body by the secretion of parathormone (PTH), which is responsible for this function. The parathyroid glands are commonly damaged during thyroid surgeries. This could lead to transient or permanent hypoparathyroidism in 30% of cases. Preservation of the parathyroid glands, is an important and integral part of thyroidectomy and other surgical interventions in the neck. The main principle underlying this is a thorough understanding of parathyroid anatomy in relation to the thyroid gland and other important structures in the area. There can also be significant variation in the anatomical location of the glands. Various techniques and methods have been described for parathyroid preservation. They include intraoperative identification utilizing indocyanine green (ICG) fluorescence, carbon nanoparticles, loupes, and microscopes. The techniques of surgery (meticulous capsular dissection), expertise, central compartment neck dissection, preoperative vitamin D deficiency, extent and type of thyroidectomy are the risk factors associated with damaged thyroids, inadvertent parathyroidectomy and subsequent hypoparathyroidism. Parathyroid Autotransplantation is a treatment option for inadvertent parathyroidectomy. Ultimately, the best way to assure normal parathyroid function is to preserve them in situ intraoperatively undamaged

Atlas construction and spatial normalisation to facilitate radiation-induced late effects research in childhood cancer

Reducing radiation-induced side effects is one of the most important challenges in paediatric cancer treatment. Recently, there has been growing interest in using spatial normalisation to enable voxel-based analysis of radiation-induced toxicities in a variety of patient groups. The need to consider three-dimensional distribution of doses, rather than dose-volume histograms, is desirable but not yet explored in paediatric populations. In this paper, we investigate the feasibility of atlas construction and spatial normalisation in paediatric radiotherapy. We used planning computed tomography (CT) scans from twenty paediatric patients historically treated with craniospinal irradiation to generate a template CT that is suitable for spatial normalisation. This childhood cancer population representative template was constructed using groupwise image registration. An independent set of 53 subjects from a variety of childhood malignancies was then used to assess the quality of the propagation of new subjects to this common reference space using deformable image registration (i.e., spatial normalisation). The method was evaluated in terms of overall image similarity metrics, contour similarity and preservation of dose-volume properties. After spatial normalisation, we report a dice similarity coefficient of 0.95±0.05, 0.85±0.04, 0.96±0.01, 0.91±0.03, 0.83±0.06 and 0.65±0.16 for brain and spinal canal, ocular globes, lungs, liver, kidneys and bladder. We then demonstrated the potential advantages of an atlas-based approach to study the risk of second malignant neoplasms after radiotherapy. Our findings indicate satisfactory mapping between a heterogeneous group of patients and the template CT. The poorest performance was for organs in the abdominal and pelvic region, likely due to respiratory and physiological motion and to the highly deformable nature of abdominal organs. More specialised algorithms should be explored in the future to improve mapping in these regions. This study is the first step toward voxel-based analysis in radiation-induced toxicities following paediatric radiotherapy

Aerobic exercise in obese diabetic patients with chronic kidney disease: a randomized and controlled pilot study

<p>Abstract</p> <p>Background</p> <p>Patients with obesity, diabetes, and chronic kidney disease (CKD) are generally physically inactive, have a high mortality rate, and may benefit from an exercise program.</p> <p>Methods</p> <p>We performed a 24-week randomized controlled feasibility study comparing aerobic exercise plus optimal medical management to medical management alone in patients with type 2 diabetes, obesity (body mass index [BMI] > 30 kg/m²), and stage 2-4 CKD (estimated glomerular filtration rate [eGFR] 15-90 mL/min/1.73 m²with persistent proteinuria). Subjects randomized to exercise underwent thrice weekly aerobic training for 6 followed by 18 weeks of supervised home exercise. The primary outcome variable was change in proteinuria.</p> <p>Results</p> <p>Seven subjects randomized to exercise and 4 control subjects completed the study. Exercise training resulted in an increase in exercise duration during treadmill testing, which was accompanied by slight but insignificant decreases in resting systolic blood pressure and 24-hour proteinuria. Exercise did not alter GFR, hemoglobin, glycated hemoglobin, serum lipids, or C-reactive protein (CRP). Caloric intake and body weight and composition also did not change with exercise training.</p> <p>Conclusion</p> <p>Exercise training in obese diabetic patients with CKD is feasible and may have clinical benefits. A large-scale randomized controlled trial to determine the effects of exercise on renal functions, cardiovascular fitness, inflammation, and oxidative stress in diabetic patients with CKD is planned.</p

Links between a biomarker profile, cold ischaemic time and clinical outcome following simultaneous pancreas and kidney transplantation

© 2018 Elsevier Ltd. In sepsis, trauma and major surgery, where an explicit physiological insult leads to a significant systemic inflammatory response, the acute evolution of biomarkers have been delineated. In these settings, Interleukin (IL) -6 and TNF-α are often the first pro-inflammatory markers to rise, stimulating production of acute phase proteins followed by peaks in anti-inflammatory markers. Patients undergoing SPKT as a result of diabetic complications already have an inflammatory phenotype as a result of uraemia and glycaemia. How this inflammatory response is affected further by the trauma of major transplant surgery and how this may impact on graft survival is unknown, despite the recognised pro-inflammatory cytokines’ detrimental effects on islet cell function. The aim of the study was to determine the evolution of biomarkers in omentum and serum in the peri-operative period following SPKT. The biochemical findings were correlated to clinical outcomes. Two omental biopsies were taken (at the beginning and end of surgery) and measured for CD68+ and CD206+ antibodies (M1 and M2 macrophages respectively). Serum was measured within the first 72 h post-SPKT for pro- and anti-inflammatory cytokines (IL -6, -10 and TNF-α), inflammatory markers (WCC and CRP) and endocrine markers (insulin, C-peptide, glucagon and resistin). 46 patients were recruited to the study. Levels of M1 (CD68+) and M2 (CD206+) macrophages were significantly raised at the end of surgery compared to the beginning (p = 0.003 and p < 0.001 respectively). Levels of C-peptide, insulin and glucagon were significantly raised 30 min post pancreas perfusion compared to baseline and were also significantly negatively related to prolonged cold ischaemic time (CIT) (p < 0.05). CRP levels correlated significantly with the Post-Operative Morbidity Survey (p < 0.05). The temporal inflammatory marker signature after SPKT is comparable to the pattern observed following other physiological insults. Unique to this study, we find that CIT is significantly related to early pancreatic endocrine function. In addition, this study suggests a predictive value of CRP in peri-operative morbidity following SPKT

Lignan Derivatives from Krameria lappacea Roots Inhibit Acute Inflammation in Vivo and Pro-inflammatory Mediators in Vitro

The roots of Krameria lappacea are used traditionally against oropharyngeal inflammation. So far, the astringent and antimicrobial properties of its proanthocyanidin constituents are considered to account for the anti-inflammatory effect. The aim of the present study was to characterize pharmacologically a lipophilic extract of K. lappacea roots and several isolated lignan derivatives (111) in terms of their putative anti-inflammatory activity. The dichloromethane extract (ID50 77 \u3bcg/cm2) as well compounds 111 (ID50 0.310.60 \u3bcmol/cm2) exhibited topical antiedematous properties comparable to those of indomethacin (ID50 0.29 \u3bcmol/cm2) in a mouse ear in vivo model. Two of the most potent compounds, 2-(2-hydroxy-4-methoxyphenyl)-5-(3-hydroxypropyl)benzofuran (5) and (+)-conocarpan (7), were studied regarding their time-dependent edema development and leukocyte infiltration up to 48 h after croton oil-induced dermatitis induction, and they showed activity profiles similar to that of hydrocortisone. In vitro studies of the isolated lignan derivatives demonstrated the inhibition of NFkB, cyclooxygenase-1 and -2, 5-lipoxygenase, and microsomal prostaglandin E2 synthase-1 as well as antioxidant properties, as mechanisms possibly contributing to the observed in vivo effects. The present findings not only support the ethnopharmacological use of K. lappacea roots but also reveal that the isolated lignan derivatives contribute strongly to the anti-inflammatory activity of this herbal drug