Formulation and evaluation of controlled release matrix tablet of diltiazem HCl by using HPMC and guar gum as polymeric matrix material.

Objetivos: En el presente trabajo se describe el desarrollo de comprimidos matriciales de clorhidrato de diltiazem.Métodos: Se obtienen comprimidos matriciales mediante el uso de goma guar y HPMC. Se estudian distintas formulaciones en las que se cambia la composición de estos materiales matriciales como controladores de la cesión. Los comprimidos se prepararon por el método de granulación húmeda y se evaluaron uniformidad de contenido, índice de hinchamiento, estabilidad y velocidad de liberación.Resultados: La capacidad de hinchamiento aumenta con el porcentaje utilizado de HPMC. Las formulaciones F7, F8 y F9 son las que muestran mejores características de liberación. Los estudios de estabilidad de la formulación seleccionada demuestran una buena resistencia a la rotura, capacidad de hinchamiento y control de la velocidad de disolución durante el estudio de estabilidad.Conclusiones: Las formulaciones F7, F8 y F9 tienen unas buenas propiedades de control de liberación del fármaco durante al menos 8 horas. La cinética de liberación se pueden ajustar a un orden cero.Aim: The present investigation concerns the development of controlled release matrix tablet of Diltiazem HCl.Methods: Matrix tablet of Diltiazem HCl was formulated by using HPMC and Guar gum as a polymeric matrix forming materials in various concentrations (%w/w) to study their ability to retard the release. The tablets were prepared by wet granulation method and evaluated for physical properties, content uniformity, swelling index, stability and in-vitro drug release.Results: Swelling was increased as the concentration and viscosity of HPMC increases. Tablets formulated using guar gum and HPMC alone were gave initial burst effect followed by controlled release for 8 hr. It was evident from the study that the formulationsF7,F8 &F9 have optimum swelling index and in vitro drug release up to 44% in 8hrs. The stability studies of optimized batch showed that there was no change in hardness, swelling index and in-vitro release up to 12 weeks.Conclusions: The batches F7, F8 and F9 possessed the high potential to release the drug gradually for more than 8 hours. The zero-order release kinetic indicates concentration independent drug release ensuring that the formulated tablet showed promising result to be a sustained release formulation

Clinical Features and Outcomes of Idiopathic Pulmonary Alveolar Proteinosis in Korean Population

Idiopathic pulmonary alveolar proteinosis (PAP) is a rare disorder in which lipoproteinaceous material accumulates within alveoli. There were few reports on Asian populations with idiopathic PAP. We retrospectively reviewed 38 patients with idiopathic PAP in Korea. We assessed clinical features, therapeutic efficacy and outcomes of whole lung lavage in patients with idiopathic PAP. The mean age at diagnosis was 52 yr. Eighty six percent of patients were symptomatic at diagnosis. Dyspnea and cough were the most common symptoms. Crackles were the most common physical examination finding. On pulmonary function test, a mild restrictive ventilatory defect was common, with a predicted mean forced vital capacity (FVC) of 77% and forced expiratory volume in one second (FEV1) of 84.6%. Diffusing capacity was disproportionately reduced at 67.7%. Arterial blood gas analysis revealed hypoxemia with a decreased PaO2 of 69.0 mmHg and an increased D(A-a)O2 of 34.2 mmHg. After whole lung lavage, PaO2, D(A-a)O2 and DLCO were significantly improved, but FVC and total lung capacity (TLC) were not different. This is the first multicenter study to analyze 38 Korean patients with idiopathic PAP. The clinical features and pulmonary parameters of Korean patients with idiopathic PAP are consistent with reports in other published studies. Whole lung lavage appears to be the most effective form of treatment

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Formulación y evaluación de liberación controlada matriz del comprimido de Diltiazem HCl utilizando goma de guar HPMC y como material de matriz polimérica

Aim: The present investigation concerns the development of controlled release matrix tablet of Diltiazem HCl. Methods: Matrix tablet of Diltiazem HCl was formulated by using HPMC and Guar gum as a polymeric matrix forming materials in various concentrations (%w/w) to study their ability to retard the release. The tablets were prepared by wet granulation method and evaluated for physical properties, content uniformity, swelling index, stability and in-vitro drug release. Results: Swelling was increased as the concentration and viscosity of HPMC increases. Tablets formulated using guar gum and HPMC alone were gave initial burst effect followed by controlled release for 8 hr. It was evident from the study that the formulationsF7,F8 &F9 have optimum swelling index and in vitro drug release up to 44% in 8hrs. The stability studies of optimized batch showed that there was no change in hardness, swelling index and in-vitro release up to 12 weeks. Conclusions: The batches F7, F8 and F9 possessed the high potential to release the drug gradually for more than 8 hours. The zero-order release kinetic indicates concentration independent drug release ensuring that the formulated tablet showed promising result to be a sustained release formulation.Objetivos: En el presente trabajo se describe el desarrollo de comprimidos matriciales de clorhidrato de diltiazem. Métodos: Se obtienen comprimidos matriciales mediante el uso de goma guar y HPMC. Se estudian distintas formulaciones en las que se cambia la composición de estos materiales matriciales como controladores de la cesión. Los comprimidos se prepararon por el método de granulación húmeda y se evaluaron uniformidad de contenido, índice de hinchamiento, estabilidad y velocidad de liberación. Resultados: La capacidad de hinchamiento aumenta con el porcentaje utilizado de HPMC. Las formulaciones F7, F8 y F9 son las que muestran mejores características de liberación. Los estudios de estabilidad de la formulación seleccionada demuestran una buena resistencia a la rotura, capacidad de hinchamiento y control de la velocidad de disolución durante el estudio de estabilidad. Conclusiones: Las formulaciones F7, F8 y F9 tienen unas buenas propiedades de control de liberación del fármaco durante al menos 8 horas. La cinética de liberación se pueden ajustar a un orden cero