A correlative model to predict in vivo AUC for nanosystem drug delivery with release rate-limited absorption

Purpose. Drug release from nanosystems at the sites of either absorption or effect biophase is a major determinant of its biological action. Thus, in vitro drug release is of paramount importance in gaining insight for the systems performance in vivo. Methods. A novel in vitro in vivo correlation, IVIVC, model denoted as double reciprocal area method was presented and applied to 19 drugs from 55 nano formulations with total 336 data, gathered from literature. Results. The proposed model correlated the in vitro with in vivo parameters with overall error of 12.4 ± 3.9%. Also the trained version of the model predicted the test formulations with overall error of 15.8 ± 3.7% indicating the suitability of the approach. A theoretical justification was provided for the model considering the unified classical release laws. Conclusion. The model does not necessitate bolus intravenous drug data and seems to be suitable for IVIVC of drugs with release rate-limited absorption

Comparison of quality of work life in rural family physicians and other general physicians in Iran

Background: Job satisfaction of physicians in family physician team is considered as one of the important factors for health system. The aim of the preent study was to compare the quality of work life (QoWL) in rural family physicians and general physicians with private clinics in Kurdistan province.Methods: A cross-sectional study was conducted among 103 general physicians including 50 rural family physicians and 53 general physicians with private clinics in Kurdistan province in 2016. The data were collected using QoWL questionnaire and analyzed using SPSS, v. 16. Descriptive statistics including frequency, percentage, mean, and standard deviation (SD) were used to describe the data and to examine the relationship between the variables, T-test was run.Results: The QoWL of rural family physicians with a mean of 55 (SD = 7.6) was higher than average scores. But QoWL of other general physicians with a mean of 47.7 (SD = 13.5) was lower than average scores. The results of t-test showed that there was a significant difference between QoWL of family physicians and other general physicians (t = 82.3, p = 0.001). In rural family physicians, there is a significant association between the QoWL and gender (t=2.7, P = 0.009) as well as native status (t=2.53, P = 0.004). In general physicians with private clinics, the QoWL of native physicians was higher than that of non-native physicians (t = 4.3, P = 0.001).Conclusion: The QoWL of rural family physicians is better than that of others general physicians, even though it is unsatisfactory in both studied groups. Therefore, improving the QoWL of rural family physicians, especially female and non-native rural family physicians, is recommended because promoting the rural family physicians' satisfaction can decrease the likelihood of turnover, and thus increase service quality and responsiveness, as a goal of the health system

Preparation and physicochemical characterization of prazosin conjugated PLGA nanoparticles for drug delivery of flutamide

In the current work, a sustained drug delivery system of flutamide (FLT) was developed using Poly(D,L‑lactide-co-glycolide) (PLGA) decorated bypoly(ethylene glycol) (PEG) grafted prazosin (PLGA-PEG-Praz) as a targeting moiety. In a multi-step reaction, PLGA was linked to PEG and prazosin. The structure of the synthesized polymers was confirmed by FTIR and 1 H-NMR. Flutamide-loaded nanoparticles were prepared by quasi-emulsion solvent diffusion technique. The nanoparticles were evaluated for size, zeta potential, polydispersity index, drug crystallinity, loading efficiency, and release properties. Also, the physicochemical properties of the nanoparticles were analyzed using Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry, and Powder X-Ray Diffractometry (XRD). The particle size of nanoparticles was ranged between 191 and 249 nm. Loading efficiency of nanoparticles was about 43%-69%. Results showed a steady release rate for nanoparticles compared to that of a pure drug powder. SEM characterization confirmed that particles were in nanosize range. DSC and XRPD results verified a decrease in drug crystallinity in the prepared formulations. In conclusion, the results of this study showed that PLGA-PEG-Praz nanoparticles could be a good choice to improve the physicochemical properties of the drug and these formulations can increase Flutamide efficac

Kinetic analysis of drug release from nanoparticles

PURPOSE. Comparative drug release kinetics from nanoparticles was carried out using conventional and our novel models with the aim of finding a general model applicable to multi mechanistic release. Theoretical justification for the two best general models was also provided for the first time. METHODS. Ten conventional models and three models developed in our laboratory were applied to release data of 32 drugs from 106 nanoparticle formulations collected from literature. The accuracy of the models was assessed employing mean percent error (E) of each data set, overall mean percent error (OE) and number of Es less than 10 percent. RESULTS. Among the models the novel reciprocal powered time (RPT), Weibull (W) and log-probability (LP) ones produced OE values of 6.47, 6.39 and 6.77, respectively. The OEs of other models were higher than 10%. Also the number of errors less than 10% for the models was 84.9, 80.2 and 78.3 percents of total number of data sets. CONCLUSIONS. Considering the accuracy criteria the reciprocal powered time model could be suggested as a general model for analysis of multi mechanistic drug release from nanoparticles. Also W and LP models were the closest to the suggested model RPT

Evaluation of Nephroprotective and Antidiabetic Effects of Gundelia tournefortii Aqueous Extract on Diabetic Nephropathy in Male Mice

Background and objectives: Due to the rapid growth of global interest in use of ethno medicinal plants, their effects and safety assessment have become substantial. Gundelia tournefortii has been used as antioxidant, anti-inflammatory, antipyretic, anti-fungal, and antibacterial agent. In the present study, nephrprotective and antidiabetic properties of Gundelia tournefortii aqueous extract (GTAE) on diabetic mice has been assessed. Methods: Seventy mice were used and diabetes was induced by administration of 150 mg/kg of alloxan monohydrate intraperitoneally in 60 mature male mice and they were randomly divided into 6 groups. Also one group (10 mice) was considered as the negative control group which received normal saline. The treatment groups received glibenclamide 10 mg/kg (G10) and 5, 10, 20 and 40 mg/kg of GTAE through gavage for 20 days. Also, one group was considered as the non-diabetic control. On the last day, levels of blood glucose, urea and creatinine were measured in serum. After tissue processing, 5 μm sections of the kidneys were prepared and were stained by hematoxylin and eosin and used for stereological analysis. Results: GTAE at all doses and G10 significantly (p≤0.05) reduced the raised levels of blood glucose, creatinine and urea as compared to the untreated diabetic mice. Multipledoses of GTAE and G10 significantly (p≤0.05) decreased the volume and length of renal structures, compared to the diabetic untreated group. Conclusion: According to the obtained results, GTAE groups can regulate the levels of biochemical parameters and inhibit kidney damages in alloxan induced diabetic mice. It appears that GTAE can be suggested for treatment of diabetes as an anti-diabetic supplement or drug

The Incidence and Geographical Distribution of Brucellosis in Iran Using Geographic Information System and Prediction of its Incidence in 2021

Background: Brucellosis is one of the most challenging health issues in many developing countries including Iran. The purpose of this study is to investigate the incidence and geographical distribution of brucellosis using Geographic Information System (GIS) and to predict its incidence in Iran in 2021. Method: This is a descriptive-analytical cross-sectional study, which contains spatial and climatic information along with the prevalence rate of brucellosis in Iran. Disease information was obtained from the National Center for Infectious Diseases Management during 2011-2015. Then, Arc GIS version 9.3 was used to plot the geographical maps for the incidence and frequency of the disease. Using the Raster calculator tool, the disease prediction map for the future was plotted. For proper spatial distribution of hot and cold spots, Getis-Ord-Gi statistic was employed. Results: The highest incidence of brucellosis during 2009-2015 was observed in the western provinces of Iran (North Khorasan, South Khorasan and Razavi Khorasan provinces). The incidence of brucellosis in Iran decreased from 2009 to 2011 but it exhibited an increasing trend from 2011 to 2014. The provinces of Kurdistan, Lorestan, Ilam, Zanjan and Kermanshah may be among the hot spots in terms of brucellosis incidence in 2021. Conclusion: We predicted significant variations in brucellosis risk distribution in Iran in the coming years. In the western and northwestern provinces, which are among the high risk areas for the incidence of this disease in the future, this disease can pose a serious health threat to the residents of these areas

Development and characterization of solid dispersion of piroxicam for improvement of dissolution rate using hydrophilic carriers

Introduction: The main objective of this study was preparation and characterization of solid dispersion of piroxicam to enhance its dissolution rate. Methods: Solid dispersion formulations with different carriers including crospovidone, microcrystalline cellulose and Elaeagnus angustifolia fruit powder and with different drug: carrier ratios were prepared employing cogrinding method. Dissolution study of the piroxicam powders, physical mixtures and solid dispersions was performed in simulated gastric fluid and simulated intestinal fluid using USP Apparatus type II. The physical characterization of formulations were analyzed using powder X ray diffraction (PXRD), particle size analyzer and differential scanning calorimetry (DSC). Interactions between the drug and carriers were evaluated by Fourier transform infrared (FT-IR) spectroscopic method. Results: It was revealed that all of three carriers increase the dissolution rate of piroxicam from physical mixtures and especially in solid dispersions compared to piroxicam pure and treated powders. PXRD and DSC results were confirmed the reduction of crystalline form of piroxicam. FT-IR analysis did not show any physicochemical interaction between drug and carriers in the solid dispersion formulations. Conclusion: Dissolution rate was dependent on the type and ratio of drug: carrier as well as pH of dissolution medium. Dissolution data of formulations were fitted well in to the linear Weibull as well as non-linear logistic and a suggested models

Perfluorocarbons: A perspective of theranostic applications and challenges

Perfluorocarbon (PFC) are biocompatible compounds, chemically and biologically inert, and lacks toxicity as oxygen carriers. PFCs nanoemulsions and nanoparticles (NPs) are highly used in diagnostic imaging and enable novel imaging technology in clinical imaging modalities to notice and image pathological and physiological alterations. Therapeutics with PFCs such as the innovative approach to preventing thrombus formation, PFC nanodroplets utilized in ultrasonic medication delivery in arthritis, or PFC-based NPs such as Perfluortributylamine (PFTBA), Pentafluorophenyl (PFP), Perfluorohexan (PFH), Perfluorooctyl bromide (PFOB), and others, recently become renowned for oxygenating tumors and enhancing the effects of anticancer treatments as oxygen carriers for tumor hypoxia. In this review, we will discuss the recent advancements that have been made in PFC’s applications in theranostic (therapeutics and diagnostics) as well as assess the benefits and drawbacks of these applications

Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: The number of individuals living with dementia is increasing, negatively affecting families, communities, and health-care systems around the world. A successful response to these challenges requires an accurate understanding of the dementia disease burden. We aimed to present the first detailed analysis of the global prevalence, mortality, and overall burden of dementia as captured by the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, and highlight the most important messages for clinicians and neurologists. METHODS: GBD 2016 obtained data on dementia from vital registration systems, published scientific literature and surveys, and data from health-service encounters on deaths, excess mortality, prevalence, and incidence from 195 countries and territories from 1990 to 2016, through systematic review and additional data-seeking efforts. To correct for differences in cause of death coding across time and locations, we modelled mortality due to dementia using prevalence data and estimates of excess mortality derived from countries that were most likely to code deaths to dementia relative to prevalence. Data were analysed by standardised methods to estimate deaths, prevalence, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs; computed as the sum of YLLs and YLDs), and the fractions of these metrics that were attributable to four risk factors that met GBD criteria for assessment (high body-mass index [BMI], high fasting plasma glucose, smoking, and a diet high in sugar-sweetened beverages). FINDINGS: In 2016, the global number of individuals who lived with dementia was 43·8 million (95% uncertainty interval [UI] 37·8-51·0), increased from 20.2 million (17·4-23·5) in 1990. This increase of 117% (95% UI 114-121) contrasted with a minor increase in age-standardised prevalence of 1·7% (1·0-2·4), from 701 cases (95% UI 602-815) per 100 000 population in 1990 to 712 cases (614-828) per 100 000 population in 2016. More women than men had dementia in 2016 (27·0 million, 95% UI 23·3-31·4, vs 16.8 million, 14.4-19.6), and dementia was the fifth leading cause of death globally, accounting for 2·4 million (95% UI 2·1-2·8) deaths. Overall, 28·8 million (95% UI 24·5-34·0) DALYs were attributed to dementia; 6·4 million (95% UI 3·4-10·5) of these could be attributed to the modifiable GBD risk factors of high BMI, high fasting plasma glucose, smoking, and a high intake of sugar-sweetened beverages. INTERPRETATION: The global number of people living with dementia more than doubled from 1990 to 2016, mainly due to increases in population ageing and growth. Although differences in coding for causes of death and the heterogeneity in case-ascertainment methods constitute major challenges to the estimation of the burden of dementia, future analyses should improve on the methods for the correction of these biases. Until breakthroughs are made in prevention or curative treatment, dementia will constitute an increasing challenge to health-care systems worldwide

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