3,656 research outputs found
METHOD DEVELOPMENT AND VALIDATION OF A REVERSED-PHASE LIQUID CHROMATOGRAPHIC METHOD FOR THE SIMULTANEOUS ESTIMATION OF SELECTED ANTIDIABETIC DRUGS IN THE PRESENCE OF THEIR DEGRADATION PRODUCTS
   Objective: This study was designed to conduct forced degradation and validation studies for the simultaneous estimation of metformin, sitagliptin, pioglitazone, and glimepiride.Methods: Analytes were separated on an Agilent XDB-C18, 150 × 4.6 mm, 5 μm column using an isocratic elution mode having mobile phase composition of 20 mM potassium dihydrogen phosphate buffer (pH 4.0):acetonitrile (65:35% v/v). Analytes were detected at a wavelength of 225 nm. The optimized method was validated as per the ICH Q2 guidelines.Results: The retention times of metformin, sitagliptin, pioglitazone, and glimepiride were 3.47, 4.83, 5.83, and 9.44 min, respectively. The linearity was 25–100 μg/ml for metformin, 2.5–10 μg/ml for sitagliptin, 1–4 μg/ml for pioglitazone, and 0.75–3 μg/ml for glimepiride. The correlation coefficient for calibration curves was >0.99, and accuracy was between 98 and 102% for each analyte. Inter- and intra-day precisions were calculated <2% relative standard deviation for each analyte.Conclusion: A significant degradation was observed in the presence of acidic, basic, neutral, oxidative, and photolytic stress conditions. The method is simple, precise, accurate, robust, and reproducible and was able to successfully separate and quantify metformin, sitagliptin, pioglitazone, and glimepiride in the presence of their degradation products
Putting Evidence into Practice: The PLoS Medicine Series on Global Mental Health Practice
The PLoS Medicine editors announce the launch of a new series on Global Mental Health Practice, and issue a call for papers
Diabetes Health, Residence & Metabolism in Asians: the DHRMA study, research into foods from the Indian subcontinent - a blinded, randomised, placebo controlled trial
<p>Abstract</p> <p>Background</p> <p>Coronary heart disease (CHD) is highly prevalent amongst the South Asian communities in Britain. The reasons for this excess CHD risk are multifactorial, but in part relate to a susceptibility to diabetes mellitus - where the aberrant metabolism of non-esterified fatty acids (NEFA) and glucose are likely to underpin vascular disease in this population. Dietary intervention is an important and first line approach to manage increased CHD risk. However, there is limited information on the impact of the South Asian diet on CHD risk.</p> <p>Methods/Design</p> <p>The Diabetes Health, Residence & Metabolism in Asians (DHRMA) study is a blinded, randomised, placebo controlled trial that analyses the efficacy of reduced glycaemic index (GI) staples of the South Asian diet, in relation to cardio-metabolic risk factors that are commonly perturbed amongst South Asian populations - primarily glucose, fatty acid and lipoprotein metabolism and central adiposity. Using a 10-week dietary intervention study, 50 healthy South Asians will be randomised to receive either a DHRMA (reduced GI) supply of chapatti (bread), stone ground, high protein wheat flour and white basmati rice (high bran, unpolished) or commercially available (leading brand) versions chapatti wheat flour and basmati rice. Volunteers will be asked to complete a 75g oral glucose tolerance test at baseline and at 10-weeks follow-up, where blood metabolites and hormones, blood pressure and anthropometry will also be assessed in a standardised manner.</p> <p>Discussion</p> <p>It is anticipated that the information collected from this study help develop healthy diet options specific (but not exclusive) for South Asian ethnic communities.</p> <p>Trial registration</p> <p>Current Controlled Trials <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=ISRCTN02839188">ISRCTN02839188</a></p
Development and characterization of controlled release mucoadhesive tablets of captopril
El estudio actual trata del desarrollo de los comprimidos mucoadhesivos de captopril, que se diseñaron con el fin de prolongar el tiempo de permanencia gástrica después de la administración oral. Se formularon matrices de comprimidos de captopril mediante diferentes polímeros mucoadhesivos, tales como goma guar, goma xantana, hidroxipropilmetilcelulosa K4M y K15M, a varias concentraciones. Los comprimidos se evaluaron según sus propiedades físicas, uniformidad del contenido, índice de inflamación, fuerza de bioadhesión y liberación farmacológica in vitro. La inflamación se incrementó cuando la concentración y la viscosidad de HPMC aumentaron. Los comprimidos formulados solamente con goma guar y goma xantana se descompusieron con mayor rapidez y se disolvieron completamente en un rango de 5-7 horas, mientras que los comprimidos con HPMC permanecieron intactos y mostraron una liberación lenta de hasta 11-12 horas. Se observó que la formulación F10 con HPMC K15M y goma xantana (1:1) tenía una fuerza bioadhesiva máxima de 31,59±0,05 g y la liberación farmacológica in vitro fue del 91,85%, al final de un periodo de 12 horas con un mecanismo de difusión no de Fick. Los estudios de estabilidad de lotes optimizados mostraron que no hay cambios en la fuerza bioadhesiva y la liberación in vitro cuando se mantiene bajo condiciones de diferentes temperaturas durante 60 días. Se concluyó que la formulación F10 presenta la mejor fuerza bioadhesiva y liberación farmacológica.The present investigation concerns the development of mucoadhesive tablets of Captopril which were designed to prolong the gastric residence time after oral administration. Matrix tablets of Captopril were formulated using different mucoadhesive polymers such as guar gum, xanthan gum, hydroxyl propyl methyl cellulose K4M and K15M in various ratios. The tablets were evaluated for physical properties, content uniformity, swelling index, bioadhesive strength and in-vitro drug release. Swelling was increased as the concentration and viscosity of HPMC increases. Tablets formulated using guar gum and xanthan gum alone were eroded faster and dissolved completely within 5-7 hr, while tablet containing HPMC remain intact and provided slow release up to 11-12 hr. It was evident from the study that the formulation F10 containing HPMC K15M and xanthan gum (1:1) exhibited maximum bioadhesive strength of 31.59±0.05 gm and in vitro drug release was found to be 91.85 % at the end of 12 hr with non-fickian diffusion mechanism. The stability studies of optimized batch showed that there was no change in bioadhesive strength and in-vitro release when stored at different temperature condition for 60 days. It was concluded that formulation F10 shows the better bioadhesive strength and drug release
Widening access to cardiovascular healthcare: community screening among ethnic minorities in inner-city Britain – the Healthy Hearts Project
<p>Abstract</p> <p>Background</p> <p>The burden of cardiovascular disease (CVD) in Britain is concentrated in inner-city areas such as Sandwell, which is home to a diverse multi-ethnic population. Current guidance for CVD risk screening is not established, nor are there specific details for ethnic minorities. Given the disparity in equitable healthcare for these groups, we developed a 'tailored' and systematic approach to CVD risk screening within communities of the Sandwell locality. The key anticipated outcomes were the numbers of participants from various ethnic backgrounds attending the health screening events and the prevalence of known and undiagnosed CVD risk within ethnic groups.</p> <p>Methods</p> <p>Data was collected during 10 health screening events (September 2005 and July 2006), which included an assessment of raised blood pressure, overweight, hyperlipidaemia, impaired fasting glucose, smoking habit and the 10 year CVD risk score. Specific features of our approach included (i) community involvement, (ii) a clinician who could deliver immediate attention to adverse findings, and (iii) the use of an interpreter.</p> <p>Results</p> <p>A total of 824 people from the Sandwell were included in this study (47% men, mean age 47.7 years) from community groups such as the Gujarati Indian, Punjabi Indian, European Caucasian, Yemeni, Pakistani and Bangladeshi. A total of 470 (57%) individuals were referred to their General Practitioner with a report of an increased CVD score – undetected high blood pressure in 120 (15%), undetected abnormal blood glucose in 70 (8%), undetected raised total cholesterol in 149 (18%), and CVD risk management review in 131 (16%).</p> <p>Conclusion</p> <p>Using this systematic and targeted approach, there was a clear demand for this service from people of various ethnic backgrounds, of whom, one in two needed review from primary or secondary healthcare. Further work is required to assess the accuracy and clinical benefits of this community health screening approach.</p
An integrated general practice and pharmacy-based intervention to promote the use of appropriate preventive medications among individuals at high cardiovascular disease risk: protocol for a cluster randomized controlled trial
Background: Cardiovascular diseases (CVD) are responsible for significant morbidity, premature mortality, and economic burden. Despite established evidence that supports the use of preventive medications among patients at high CVD risk, treatment gaps remain. Building on prior evidence and a theoretical framework, a complex intervention has been designed to address these gaps among high-risk, under-treated patients in the Australian primary care setting. This intervention comprises a general practice quality improvement tool incorporating clinical decision support and audit/feedback capabilities; availability of a range of CVD polypills (fixed-dose combinations of two blood pressure lowering agents, a statin ± aspirin) for prescription when appropriate; and access to a pharmacy-based program to support long-term medication adherence and lifestyle modification.
Methods: Following a systematic development process, the intervention will be evaluated in a pragmatic cluster randomized controlled trial including 70 general practices for a median period of 18 months. The 35 general practices in the intervention group will work with a nominated partner pharmacy, whereas those in the control group will provide usual care without access to the intervention tools. The primary outcome is the proportion of patients at high CVD risk who were inadequately treated at baseline who achieve target blood pressure (BP) and low-density lipoprotein cholesterol (LDL-C) levels at the study end. The outcomes will be analyzed using data from electronic medical records, utilizing a validated extraction tool. Detailed process and economic evaluations will also be performed.
Discussion: The study intends to establish evidence about an intervention that combines technological innovation with team collaboration between patients, pharmacists, and general practitioners (GPs) for CVD prevention.
Trial registration: Australian New Zealand Clinical Trials Registry ACTRN1261600023342
Robot-assisted laparoscopic transperitoneal pelvic lymphadenectomy and metastasectomy for melanoma: initial report of two cases
Robotic pelvic lymphadenectomy is a well established procedure in the urologic and gynecologic literature. To our knowledge robotic pelvic lymphadectomy for metastatic melanoma has yet to be described. Herein we present the first report of robot-assisted pelvic lymphadenectomy in malignant melanoma. After placement of six laparoscopic ports (12 mm camera, three 8-mm robotic ports, 12-mm and 5-mm assistant ports) the DaVinci S robot (Intuitive Surgical, CA, USA) was docked in standard fashion with the patient in low lithotomy. In both cases the patients had enlarged pelvic lymph nodes on computed tomography and complete excision of these masses was accomplished along with complete lymphadenectomy extending from Cooper’s ligament to just below the hypogastric artery in case 1 and to level of the bifurcation of aorta in case 2. A PK Maryland Dissector and monopolar scissors were used for dissection. Both patients were discharged on postoperative day #1. Robotic pelvic lymphadenectomy can be safely used for management of patients with metastatic melanoma involving the pelvic lymph nodes. Compared with the standard open procedure, pelvic lymphadenectomy with robotic assistance is associated with excellent vision and minimum morbidity
Development of an in vitro periodontal biofilm model for assessing antimicrobial and host modulatory effects of bioactive molecules
Background:
Inflammation within the oral cavity occurs due to dysregulation between microbial biofilms and the host response. Understanding how different oral hygiene products influence inflammatory properties is important for the development of new products. Therefore, creation of a robust host-pathogen biofilm platform capable of evaluating novel oral healthcare compounds is an attractive option. We therefore devised a multi-species biofilm co-culture model to evaluate the naturally derived polyphenol resveratrol (RSV) and gold standard chlorhexidine (CHX) with respect to anti-biofilm and anti-inflammatory properties.<p></p>
Methods:
An in vitro multi-species biofilm containing <i>S. mitis, F. nucleatum, P. Gingivalis</i> and <i>A. Actinomycetemcomitans</i> was created to represent a disease-associated biofilm and the oral epithelial cell in OKF6-TERT2. Cytotoxicity studies were performed using RSV and CHX. Multi-species biofilms were either treated with either molecule, or alternatively epithelial cells were treated with these prior to biofilm co-culture. Biofilm composition was evaluated and inflammatory responses quantified at a transcriptional and protein level.<p></p>
Results:
CHX was toxic to epithelial cells and multi-species biofilms at concentrations ranging from 0.01-0.2%. RSV did not effect multi-species biofilm composition, but was toxic to epithelial cells at concentrations greater than 0.01%. In co-culture, CHX-treated biofilms resulted in down regulation of the inflammatory chemokine IL-8 at both mRNA and protein level. RSV-treated epithelial cells in co-culture were down-regulated in the release of IL-8 protein, but not mRNA.<p></p>
Conclusions:
CHX possesses potent bactericidal properties, which may impact downstream inflammatory mediators. RSV does not appear to have bactericidal properties against multi-species biofilms, however it did appear to supress epithelial cells from releasing inflammatory mediators. This study demonstrates the potential to understand the mechanisms by which different oral hygiene products may influence gingival inflammation, thereby validating the use of a biofilm co-culture model.<p></p>
Abrasive water jet drilling of advanced sustainable bio-fibre-reinforced polymer/hybrid composites : a comprehensive analysis of machining-induced damage responses
This paper aims at investigating the effects of variable traverse speeds on machining-induced damage of fibre-reinforced composites, using the abrasive water jet (AWJ) drilling. Three different types of epoxy-based composites laminates fabricated by vacuum bagging technique containing unidirectional (UD) flax, hybrid carbon-flax and carbon fibre-reinforced composite were used. The drilling parameters used were traverse speeds of 20, 40, 60 and 80 mm/min, constant water jet pressure of 300 MPa and a hole diameter of 10 mm. The results obtained depict that the traverse speed had a significant effect with respect to both surface roughness and delamination drilling-induced damage responses. Evidently, an increase in water jet traverse speed caused an increase in both damage responses of the three samples. Significantly, the CFRP composite sample recorded the lowest surface roughness damage response, followed by C-FFRP, while FFRP exhibited the highest. However, samples of FFRP and hybrid C-FFRP recorded lowest and highest delamination damage responses, respectively. The discrepancy in both damage responses, as further validated with micrographs of colour video microscopy (CVM), scanning electron microscopy (SEM) and X-ray micro-computed tomography (X-ray μCT), is attributed to the different mechanical properties of the reinforced fibres, fibre orientation/ply stacking and hybridisation of the samples.Peer reviewe
A patient with metastatic melanoma presenting with gastrointestinal perforation after dacarbazine infusion: a case report
<p>Abstract</p> <p>Introduction</p> <p>We report a rare case of gastrointestinal perforation following dacarbazine infusion for metastatic melanoma. The condition is attributed to a responding malignant melanoma in the gastrointestinal tract.</p> <p>Case presentation</p> <p>A 52-year-old Caucasian man presented with abdominal pain and distension, malaise, night sweats, dysphagia and early satiety. A computed tomography scan showed massive ascites, lymphadenopathy and liver lesions suspect for metastases. An upper gastrointestinal endoscopy was performed and revealed multiple dark lesions of 5 mm to 10 mm in his stomach and duodenum.</p> <p>When his skin was re-examined, an irregular pigmented lesion over the left clavicle measuring 15 mm × 8 mm with partial depigmentation was found. Histological examination of a duodenal lesion was consistent with a diagnosis of metastatic melanoma. The patient deteriorated and his level of lactate dehydrogenase rapidly increased. The patient was started on systemic treatment with dacarbazine 800 mg/m<sup>2 </sup>every three weeks and he was discharged one day after the first dose. On the sixth day he was readmitted with severe abdominal pain. A chest X-ray showed the presence of free intraperitoneal air that was consistent with gastrointestinal perforation. His lactate dehydrogenase level had fallen from 6969U/L to 1827U/L, supporting the conclusion that the response of gastrointestinal metastases to dacarbazine had resulted in the perforation of the patient's bowel wall. A laparotomy was discussed with the patient and his family but he decided to go home with symptomatic treatment. He died 11 days later.</p> <p>Conclusion</p> <p>Melanoma can originate in, as well as metastasize to, the gastrointestinal tract. Gastrointestinal perforations due to responding tumors are a well-known complication of systemic treatment of gastrointestinal lymphomas. However, as the response rate of metastatic melanoma to dacarbazine is only 10% to 20%, and responses are usually only partial, perforation due to treatment response in metastatic melanoma is rare.</p> <p>Medical oncologists should be aware of the risk of bowel perforation after starting cytotoxic chemotherapy on patients with gastrointestinal metastases.</p
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