Design, development and in vitro characterization of Pioglitazone loaded mucoadhesive buccal devices

Aim: The mucoadhesive buccal patches were developed and evaluated for systemic administration of Pioglitazone in the oral cavity. Pioglitazone belongs to a novel class of oral antidiabetic drugs known as Thiazolidinediones. Materials and Methods: The mucoadhesive buccal patches of Pioglitazone was formulated using Eudragit RS100 and HPMC K4M (mucoadhesive polymer) and were prepared by solvent casting method. Different patch formulations were evaluated for its physical parameters like thickness uniformity, swelling index, surface pH, uniformity of weight, folding endurance, mucoadhesive strength and in vitro parameters like drug content uniformity and drug release studies, and ex vivo parameters like mucoadhesion time. Results: Data for the parameters was found to be: thickness uniformity (0.27±0.45mm); uniformity of weight (40.81±0.66 mg), surface pH (6.5), folding endurance (>300), drug content uniformity (98.58±2.05%), swelling index (131±0.79%), mucoadhesive strength (38.20±1.75), in vitro drug release studies (95.18±1.98%) and ex vivo mucoadhesion, time of optimized formulation (4±1.26 h). The data was also fitted to different kinetic models to illustrate its anomalous (non-fickian) diffusion. Conclusions: The result revealed that Pioglitazone loaded buccal patches was most suitable mode of drug delivery for promising therapeutic action. Buccal patches of Pioglitazone can prove to be potential pharmaceutical dosage form for sustaining the drug release and reducing the dose frequency.Objetivo: Los parches de mucoadherente bucal fueron desarrollados y evaluados por la administración sistémica de la pioglitazona en la cavidad oral. Pioglitazona pertenece a una clase nueva de medicamentos antidiabéticos orales conocida como tiazolidindionas. Material y Método: los parches mucoadherente bucal de pioglitazona fue formulado con Eudragit RS100 y HPMC K4M (polímero mucoadherentes) y fueron elaboradas por el método de fundición solvente. Se evaluaron diferentes formulaciones de parches mediante parámetros físicos como uniformidad de espesor, índice de hinchazón, pH de la superficie, uniformidad de peso, resistencia al plegado, fuerza mucoadherentes y parámetros in vitro como uniformidad de contenido del fármaco y estudios de liberación y estudios ex vivo del tiempo de mucoadhesión del fármaco. Resultados: Los resultados obtenidos para los parámetros estudiados fueron: uniformidad de espesor, 0.27±0.45 mm; uniformidad de peso, 40.81±0.66 mg; pH superficial, 6.5; resistencia al plegado, > 300. Los ensayos in vitro dieron los siguientes resultados: uniformidad de contenido del fármaco, 98.58±2.05%; índice de hinchazón, 131±0.79%; fuerza mucoadherente, 38.20±1.75; y tiempo de liberación del farmaco (95.18±1.98%) y el ensayo ex vivo del tiempo de mucoadhesión del fármaco fue de 4±1.26 h. Los datos también se ajustaron a distintos modelos cinéticos para ilustrar su difusión anómala (no Fickian). Conclusiones: El resultado reveló que los parches bucales de pioglitazona fue el modo más adecuado de fármacos de acción terapéutica prometedora. Los Parches bucales de pioglitazona pueden resultar una potencial forma de dosificación farmacéutica para sostener la liberación del fármaco y reducir la frecuencia de la dosis.The authors are thankful to Panacia Biotec, Baddi (H.P.) India for providing the Pioglitazone as a gift sample. We are also thankful to the Board of Trustees, Bharat Institute of Technology, Meerut, India for providing necessary facilities to carry out this research work

Infuence of chemically synthesized copper nanoparticles and cupric ions on oxalate oxidation system in germinating Sorghum grain

58-63We have earlier reported the effects of chemically synthesized copper nanoparticles (CuNPs) on oxalate oxidase (OxOx) activity, extracted from the shoot tissue of germinating grain sorghum i.e. in vitro. Here, we tried to study this effect in vivo and compare it with those of Cu2+. We describe herein, characterization of CuNPs and their effects on oxalate oxidation system i.e. OxOx activity, total oxalate and H2O2 content in vivo i.e. in shoot tissues/leaves of germinating grain Sorghum (Sorghum vulgare L). To achieve it, grain sorghum seeds were grown up to 10 days in laboratory, irrigated with Hoagland’s solution containing either CuNPs (1.0 ppm) or Cu2+ (1.0 ppm) after 4 days of germination. Control were irrigated with Hoagland solution only. The shoot/leaves of the seedling plants were harvested at 4, 6, 8 and 10 day of germination and analysed quantitatively for OxOx activity, soluble protein, H2O2 and total oxalate. The growth of the Sorghum seedling plants supplemented with CuNPs and Cu2+ was decreased significantly (P 2+. CuNPs decreased the activity of OxOx but Cu2+ had no effect at day 10. Both CuNPs and Cu2+ decreased the specific activity of OxOx and H2O2 content but increased total oxalate content at day 10. The decrease in H2O2 content in both CuNPs and Cu2+ supplemented shoot tissues with concomitant increase in oxalate content confirmed the decreased activity of OxOx in CuNPs and Cu2+ supplemented seedling plants

Optimization of structural and optical properties of sputter deposited TiO2 thin films by controlling deposition parameters

735-739Titanium oxide (TiO2) thin films have been deposited onto highly cleaned soda lime glass substrates by DC magnetron reactive sputtering system. The Ti target with purity 99.99% is sputtered by argon gas in the sputtering chamber. Oxygen gas with purity 99.99% is introduced during the deposition process into the sputtering chamber as reactive gas for the synthesis of titanium oxide. Structural and optical properties of TiO2 thin films have been characterized by X-ray diffraction (XRD), Raman spectroscopy and UV-Vis. spectroscopy. The effect of substrate temperature and sputtering power on the optical properties of TiO2 thin films has been studied. The XRD and Raman spectroscopy of as-deposited films are used to study the structural properties of TiO2 as a function of substrate temperature and sputtered power. The structural studies show the crystalline nature of TiO2 thin films. The narrowing of energy band gap of sputtered deposited TiO2thin films was studied using UV-Vis. spectroscopy

Infuence of chemically synthesized copper nanoparticles and cupric ions on oxalate oxidation system in germinating Sorghum grain

We have earlier reported the effects of chemically synthesized copper nanoparticles (CuNPs) on oxalate oxidase (OxOx) activity, extracted from the shoot tissue of germinating grain sorghum i.e. in vitro. Here, we tried to study this effect in vivo and compare it with those of Cu2+. We describe herein, characterization of CuNPs and their effects on oxalate oxidation system i.e. OxOx activity, total oxalate and H2O2 content in vivo i.e. in shoot tissues/leaves of germinating grain Sorghum (Sorghum vulgare L). To achieve it, grain sorghum seeds were grown up to 10 days in laboratory, irrigated with Hoagland’s solution containing either CuNPs (1.0 ppm) or Cu2+ (1.0 ppm) after 4 days of germination. Control were irrigated with Hoagland solution only. The shoot/leaves of the seedling plants were harvested at 4, 6, 8 and 10 day of germination and analysed quantitatively for OxOx activity, soluble protein, H2O2 and total oxalate. The growth of the Sorghum seedling plants supplemented with CuNPs and Cu2+ was decreased significantly (P <0.1) at all growth stages compared to control. This inhibitory effect of CuNPs was higher than Cu2+. CuNPs decreased the activity of OxOx but Cu2+ had no effect at day 10. Both CuNPs and Cu2+ decreased the specific activity of OxOx and H2O2 content but increased total oxalate content at day 10. The decrease in H2O2 content in both CuNPs and Cu2+ supplemented shoot tissues with concomitant increase in oxalate content confirmed the decreased activity of OxOx in CuNPs and Cu2+ supplemented seedling plants

Global, regional, and national burden of colorectal cancer and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Funding: F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia, I.P. (FCT), in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy i4HB; FCT/MCTES through the project UIDB/50006/2020. J Conde acknowledges the European Research Council Starting Grant (ERC-StG-2019-848325). V M Costa acknowledges the grant SFRH/BHD/110001/2015, received by Portuguese national funds through Fundação para a Ciência e Tecnologia (FCT), IP, under the Norma Transitória DL57/2016/CP1334/CT0006.proofepub_ahead_of_prin

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries

Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019

Background Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r2=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−28·4 to −2·9) for all diabetes, and by 21·0% (–33·0 to −5·9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (−13·6% [–28·4 to 3·4]) and for type 1 diabetes (−13·6% [–29·3 to 8·9]). Interpretation Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations.publishedVersio

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio