Removal of Estrogen Hormones (17-Estradiol and Estrone) from Aqueous Solutions Using Rice Husk Silica

The aim of this study was to investigate the removal of estrogen hormones (17β-estradiol and estrone) from aqueous solutions using rice husk extracted silica. Rice husk was collected from rice factories in Mazandaran province (Iran) and the adsorbent was prepared in a furnace at 800 °C for 4 h, after acid leaching with hydrochloric and sulfuric acid mixture. Optimal operating parameters for estrogen removal were determined, including initial pH values (4–9), adsorbent dosages (0.5, 1, 1.5, and 2 g L–1), contact times (30, 60, 90, and 120 min), and initial concentrations of 17β-estradiol and estrone (10, 40, 70 and 100 ng L–1); one-factor-at-a-time method was used. The method of electrochemiluminescence was used to measure the concentration of hormones. Kinetic adsorption models and adsorption isotherms were also studied. The maximum removal efficiency (%) of 17β-estradiol (E2) and estrone (E1) hormones of 95.5 and 93.1 %, respectively, was obtained at optimal conditions of pH 4, 1.5 g L–1 of adsorbent dosage, 60 min of contact time and 10 ng L–1 initial concentrations of E2 and E1. Pseudo first-order kinetic model and Langmuir adsorption isotherm had the best fit with experimental data for both estrogen hormones, following nonlinear regression procedure. Rice husk silica could be considered as effective and accessible adsorbent for removal of estrogenic hormones. This work is licensed under a Creative Commons Attribution 4.0 International License

Evaluating the Effects of Umifenovir Compared to Lopinavir/Ritonavir in the Management of Patients with COVID-19: A Randomized Controlled Trial

Background. Due to the lack of specific safe medications for the treatment of COVID-19, medications used for other similar conditions are being tested to alleviate the condition of COVID-19 patients, resulting in acceptable outcomes in some cases. Umifenovir (Arbidol®) is used to treat influenza viruses by inhibiting the fusion of the virus with the host cell. According to previous findings, umifenovir may inhibit SARS-CoV-2 infection by interfering with the release of SARS-CoV-2 from inside the cell. This study aimed to determine the effects of umifenovir, a fusion inhibitor, versus lopinavir/ritonavir in treating patients with COVID-19. Methods. This study was a randomized controlled trial consisting of 90 confirmed COVID-19 patients divided into the lopinavir/ritonavir group and the umifenovir group. The lopinavir/ritonavir group received 100/25 mg twice, while the umifenovir group was given 200 mg thrice a day, in both groups, for seven days. Outcomes included mortality rate and the need for mechanical ventilation or intensive care unit admission. Length of stay in the hospital and ICU and the lab tests trend were also assessed. Results. The mortality rate and the need for admission to the ICU were significantly lower in the umifenovir group (8% vs. 27.5%; P-value = 0.02). Moreover, The levels of white blood cells were also lower in the umifenovir group than in the control group by day 10 (6.2 (5.3-7.4) vs. 10.8 (9.9-13); P-value <0.001). Conclusions. Umifenovir may reduce the need for admission to the ICU and mortality rate in patients with COVID-19 compared with lopinavir/ritonavir. The lab test trends were also in favor of umifenovir use.

STAT3-mediated apoptotic-enhancing function of sclareol against breast cancer cells and cell sensitization to cyclophosphamide

Sclareol is an organic compound with potential anti-tumor effects against various cancer types. However, its precise molecular mechanism in the suppression of tumor growth has not been fully elucidated. In the present study, the anti-proliferative and apoptosis-inducing effects of sclareol with cyclophosphamide were investigated in breast cancer cells and the involvement of the JAK/ STAT pathway was evaluated. For this purpose, MCF-7 breast cancer cells were cultured and treated with various concentrations of sclareol to determine its IC50. Cell viability was measured by MTT assay and apoptosis was assessed by flow cytometric analysis of annexin V binding. Gene and protein expression were examined by real-time PCR and Western blotting, respectively. The activity of caspase enzymes was also measured. The results showed that sclareol significantly reduced cell viability and triggered cell death and its co-administration with cyclophosphamide enhanced its anti-cancer properties. Additionally, sclareol up-regulated the expression of p53 and BAX and reduced the expression of Bcl-2. Docking studies indicated an interaction between sclareol and STAT3 which was proved by attenuation of STAT3 phosphorylation after treatment of the cells with sclareol. Sclareol was also capable of suppressing the function of IL-6 in modulating the expression of apoptosis-associated genes. Altogether these data suggest the potential of sclareol as an anti-cancer agent and demonstrate that a combination of sclareol with cyclophosphamide might serve as an effective chemotherapeutic approach resulting in improvements in the treatment of breast cancer. © 2020, Iranian Journal of Pharmaceutical Research. All rights reserved

Osjetljiva spektrofotometrijska metoda za određivanje antagonista H2-receptora uz uporabu N-bromsukcinimida i p-aminofenola

A simple, accurate and sensitive spectrophotometric method for determination of H2-receptor antagonists: cimetidine (CIM), famotidine (FAM), nizatidine (NIZ), and ranitidine hydrochloride (RAN) has been full developed and validated The method was based on the reaction of these drugs with NBS and subsequent measurement of the excess N-bromosuccinimide by its reaction with p-aminophenol to give a violet colored product (max at 552 nm). Decrease in the absorption intensity (A) of the colored product, due to the presence of the drug, was correlated with its concentration in the sample solution. Different variables affecting the reaction were carefully studied and optimized. Under optimal conditions, linear relationships with good correlation coefficients (0.9988-0.9998) were found between A values and the corresponding concentrations of the drugs in a concentration range of 830, 622, 625, and 420 g mL1 for CIM, FAM, NIZ, and RAN, respectively. Limits of detection were 1.22, 1.01, 1.08, and 0.74 g mL1 for CIM, FAM, NIZ, and RAN, respectively. The method was validated in terms of accuracy, precision, ruggedness, and robustness; the results were satisfactory. The proposed method was successfully applied to the analysis of the above mentioned drugs in bulk substance and in pharmaceutical dosage forms; percent recoveries ranged from 98.5 0.9 to 102.4 0.8% without interference from the common excipients. The results obtained by the proposed method were comparable with those obtained by the official methods.Razvijena je i validirana ispravna, jednostavna i osjetljiva spektrofotometrijska metoda za određivanje antagonista H2-receptora: cimetidina (CIM), famotidina (FAM), nizatidina (NIZ) i ranitidin hidroklorida (RAN). Metoda se temelji na reakciji tih ljekovitih tvari s N-bromsukcinimidom (NBS). Višak N-bromsukcinimida određuje se nakon reakcije s p-aminofenolom s kojim daje ljubičasti produkt (max pri 552 nm). Smanjenje apsorpcijskog intenziteta (A) obojenog produkta, zbog prisutnosti ljekovite tvari korelirano je s njegovom koncentracijom u otopini uzorka. Proučavane su različite varijable koje utječu na reakciju. Linearno koncentracijsko područje za CIM, FAM, NIZ i RAN, s koeficijentom korelacije od 0,9988 do 0,9998, iznosi 830, 622, 625 odnosno 420 g mL1. Granice detekcije bile su 1,23, 1,02, 1,09 i 0,75 g mL1 za CIM, FAM, NIZ, odnosno RAN. Predložena metoda je uspješno primijenjena za analizu navedenih ljekovitih tvari i ljekovitih pripravaka. Nepreciznost od 0,7 do 1,2% i visoka ispravnost (analitički povrat između 98,5 i 102,4%), bez interferencije uobičajenih pomoćnih tvari, ukazuju na dobru analitičku metodu. Rezultati dobiveni predloženom metodom usporedivi su s rezultatima dobivenim službenom metodom

Continuous wavelet transform methods for the simultaneous determinations and dissolution profiles of valsartan and hydrochlorothiazide in tablets

ABSTRACT Continuous wavelet transform (CWT) was proposed for the simultaneous determination and dissolution profiles of valsartan (VAL) and hydrochlorothiazide (HCT) in tablets, without the use of a chemical separation procedure. The CWT approach was applied to the original UV spectra and their ratio spectra in the optimal wavelength ranges. After testing several wavelet families, Mexican hat function-CWT and Daubechies7-CWT (mexh-CWT and db7-CWT, respectively) were found to be suitable for the transformation of the original UV spectra. In the following procedure, mexh-CWT and Coiflets3-CWT (coif3-CWT) were found to be appropriate for the signal analysis of ratio spectra (RS) of VAL/HCT and HCT/VAL. Calibration graphs for VAL and HCT were obtained by measuring db7-CWT and mexh-CWT amplitudes in the transformation of the original absorption spectra and RS-coif-CWT and RS-mexh-CWT amplitudes in the transformation of the ratio spectra. The validity and applicability of the proposed CWT methods were evaluated through the analysis of an independent set of synthetic binary mixtures consisting of VAL and HCT. The proposed signal processing methods were then successfully applied to the simultaneous quantitative evaluation and simultaneous dissolution profiles of the related drugs in commercial tablets, with good agreement reported for the experimental results

A randomized, double-blind, placebo-controlled investigation of BCc1 nanomedicine effect on survival and quality of life in metastatic and non-metastatic gastric cancer patients

Background: Currently, the main goal of cancer research is to increase longevity of patients suffering malignant cancers. The promising results of BCc1 in vitro and vivo experiments made us look into the effect of BCc1 nanomedicine on patients with cancer in a clinical trial. Methods: The present investigation was a randomized, double-blind, placebo-controlled, parallel, and multicenter study in which 123 patients (30-to-85-year-old men and women) with metastatic and non-metastatic gastric cancer, in two separate groups of BCc1 nanomedicine or placebo, were selected using a permuted block randomization method. For metastatic and non-metastatic patients, a daily dose of 3000 and 1500 mg was prescribed, respectively. Overall survival (OS) as the primary endpoint and quality of life (measured using QLQ-STO22) and adverse effects as the secondary endpoints were studied. Results: In metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (174 days 95% confidence interval (CI) 82.37-265.62) than in placebo (62 days 95% CI 0-153.42); hazard ratio (HR): 0.5 95% CI 0.25-0.98; p = 0.046. In non-metastatic patients, the median OS was significantly higher in BCc1 nanomedicine (529 days 95% CI 393.245-664.75) than in placebo (345 days 95% CI 134.85-555.14); HR: 0.324 95% CI 0.97-1.07; p = 0.066. The QLQ-STO22 assessment showed a mean difference improvement of 3.25 and 2.29 (p value > 0.05) in BCc1 nanomedicine and a mean difference deterioration of - 4.42 and - 3 (p-value < 0.05) in placebo with metastatic and non-metastatic patients, respectively. No adverse effects were observed. Conclusion: The findings of this trial has provided evidence for the potential capacity of BCc1 nanomedicine for treatment of cancer. Trial registration IRCTID, IRCT2017101935423N1. Registered on 19 October 2017, http://www.irct.ir/ IRCT2017101935423N1 © 2019 The Author(s)

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990�2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: The burden of inflammatory bowel disease (IBD) is rising globally, with substantial variation in levels and trends of disease in different countries and regions. Understanding these geographical differences is crucial for formulating effective strategies for preventing and treating IBD. We report the prevalence, mortality, and overall burden of IBD in 195 countries and territories between 1990 and 2017, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods: We modelled mortality due to IBD using a standard Cause of Death Ensemble model including data mainly from vital registrations. To estimate the non-fatal burden, we used data presented in primary studies, hospital discharges, and claims data, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to ensure consistency between measures. Mortality, prevalence, years of life lost (YLLs) due to premature death, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were estimated. All of the estimates were reported as numbers and rates per 100 000 population, with 95 uncertainty intervals (UI). Findings: In 2017, there were 6·8 million (95 UI 6·4�7·3) cases of IBD globally. The age-standardised prevalence rate increased from 79·5 (75·9�83·5) per 100 000 population in 1990 to 84·3 (79·2�89·9) per 100 000 population in 2017. The age-standardised death rate decreased from 0·61 (0·55�0·69) per 100 000 population in 1990 to 0·51 (0·42�0·54) per 100 000 population in 2017. At the GBD regional level, the highest age-standardised prevalence rate in 2017 occurred in high-income North America (422·0 398·7�446·1 per 100 000) and the lowest age-standardised prevalence rates were observed in the Caribbean (6·7 6·3�7·2 per 100 000 population). High Socio-demographic Index (SDI) locations had the highest age-standardised prevalence rate, while low SDI regions had the lowest age-standardised prevalence rate. At the national level, the USA had the highest age-standardised prevalence rate (464·5 438·6�490·9 per 100 000 population), followed by the UK (449·6 420·6�481·6 per 100 000). Vanuatu had the highest age-standardised death rate in 2017 (1·8 0·8�3·2 per 100 000 population) and Singapore had the lowest (0·08 0·06�0·14 per 100 000 population). The total YLDs attributed to IBD almost doubled over the study period, from 0·56 million (0·39�0·77) in 1990 to 1·02 million (0·71�1·38) in 2017. The age-standardised rate of DALYs decreased from 26·5 (21·0�33·0) per 100 000 population in 1990 to 23·2 (19·1�27·8) per 100 000 population in 2017. Interpretation: The prevalence of IBD increased substantially in many regions from 1990 to 2017, which might pose a substantial social and economic burden on governments and health systems in the coming years. Our findings can be useful for policy makers developing strategies to tackle IBD, including the education of specialised personnel to address the burden of this complex disease. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

The global, regional, and national burden of inflammatory bowel disease in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background The burden of inflammatory bowel disease (IBD) is rising globally, with substantial variation in levels and trends of disease in different countries and regions. Understanding these geographical differences is crucial for formulating effective strategies for preventing and treating IBD. We report the prevalence, mortality, and overall burden of IBD in 195 countries and territories between 1990 and 2017, based on data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017. Methods We modelled mortality due to IBD using a standard Cause of Death Ensemble model including data mainly from vital registrations. To estimate the non-fatal burden, we used data presented in primary studies, hospital discharges, and claims data, and used DisMod-MR 2.1, a Bayesian meta-regression tool, to ensure consistency between measures. Mortality, prevalence, years of life lost (YLLs) due to premature death, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) were estimated. All of the estimates were reported as numbers and rates per 100 000 population, with 95% uncertainty intervals (UI). Findings In 2017, there were 6.8 million (95% UI 6.4-7.3) cases of IBD globally. The age-standardised prevalence rate increased from 79.5 (75.9-83.5) per 100 000 population in 1990 to 84.3 (79.2-89.9) per 100 000 population in 2017. The age-standardised death rate decreased from 0.61 (0.55-0.69) per 100 000 population in 1990 to 0.51 (0.42-0.54) per 100 000 population in 2017. At the GBD regional level, the highest age-standardised prevalence rate in 2017 occurred in high-income North America (422.0 [398.7-446.1] per 100 000) and the lowest age-standardised prevalence rates were observed in the Caribbean (6.7 [6.3-7.2] per 100 000 population). High Sociodemographic Index (SDI) locations had the highest age-standardised prevalence rate, while low SDI regions had the lowest age-standardised prevalence rate. At the national level, the USA had the highest age-standardised prevalence rate (464.5 [438.6-490.9] per 100 000 population), followed by the UK (449.6 [420.6-481.6] per 100 000). Vanuatu had the highest age-standardised death rate in 2017 (1.8 [0.8-3.2] per 100 000 population) and Singapore had the lowest (0.08 [0.06-0.14] per 100 000 population). The total YLDs attributed to IBD almost doubled over the study period, from 0.56 million (0.39-0.77) in 1990 to 1.02 million (0.71-1.38) in 2017. The age-standardised rate of DALYs decreased from 26.5 (21.0-33.0) per 100 000 population in 1990 to 23.2 (19.1-27.8) per 100 000 population in 2017. Interpretation The prevalence of IBD increased substantially in many regions from 1990 to 2017, which might pose a substantial social and economic burden on governments and health systems in the coming years. Our findings can be useful for policy makers developing strategies to tackle IBD, including the education of specialised personnel to address the burden of this complex disease. Copyright (C) 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017

Background Understanding the patterns of HIV/AIDS epidemics is crucial to tracking and monitoring the progress of prevention and control efforts in countries. We provide a comprehensive assessment of the levels and trends of HIV/AIDS incidence, prevalence, mortality, and coverage of antiretroviral therapy (ART) for 1980–2017 and forecast these estimates to 2030 for 195 countries and territories. Methods We determined a modelling strategy for each country on the basis of the availability and quality of data. For countries and territories with data from population-based seroprevalence surveys or antenatal care clinics, we estimated prevalence and incidence using an open-source version of the Estimation and Projection Package—a natural history model originally developed by the UNAIDS Reference Group on Estimates, Modelling, and Projections. For countries with cause-specific vital registration data, we corrected data for garbage coding (ie, deaths coded to an intermediate, immediate, or poorly defined cause) and HIV misclassification. We developed a process of cohort incidence bias adjustment to use information on survival and deaths recorded in vital registration to back-calculate HIV incidence. For countries without any representative data on HIV, we produced incidence estimates by pulling information from observed bias in the geographical region. We used a re-coded version of the Spectrum model (a cohort component model that uses rates of disease progression and HIV mortality on and off ART) to produce age-sex-specific incidence, prevalence, and mortality, and treatment coverage results for all countries, and forecast these measures to 2030 using Spectrum with inputs that were extended on the basis of past trends in treatment scale-up and new infections. Findings Global HIV mortality peaked in 2006 with 1·95 million deaths (95% uncertainty interval 1·87–2·04) and has since decreased to 0·95 million deaths (0·91–1·01) in 2017. New cases of HIV globally peaked in 1999 (3·16 million, 2·79–3·67) and since then have gradually decreased to 1·94 million (1·63–2·29) in 2017. These trends, along with ART scale-up, have globally resulted in increased prevalence, with 36·8 million (34·8–39·2) people living with HIV in 2017. Prevalence of HIV was highest in southern sub-Saharan Africa in 2017, and countries in the region had ART coverage ranging from 65·7% in Lesotho to 85·7% in eSwatini. Our forecasts showed that 54 countries will meet the UNAIDS target of 81% ART coverage by 2020 and 12 countries are on track to meet 90% ART coverage by 2030. Forecasted results estimate that few countries will meet the UNAIDS 2020 and 2030 mortality and incidence targets. Interpretation Despite progress in reducing HIV-related mortality over the past decade, slow decreases in incidence, combined with the current context of stagnated funding for related interventions, mean that many countries are not on track to reach the 2020 and 2030 global targets for reduction in incidence and mortality. With a growing population of people living with HIV, it will continue to be a major threat to public health for years to come. The pace of progress needs to be hastened by continuing to expand access to ART and increasing investments in proven HIV prevention initiatives that can be scaled up to have population-level impact