Comparing the effects of prednisolone and promethazine in the treatment of hyperemesis gravidarum: a double-blind, randomized clinical trial

Background: Nausea and vomiting during pregnancy is one of the most frequent obstetric problems of unknown etiology and there is no definitive treatment for it. The purpose of this study was to compare the effects of prednisolone and promethazine in the treatment of hyperemesis gravidarum. Materials and Methods: This double-blind clinical trial study was conducted on 70 pregnant women, with a singleton pregnancy at less than 16 weeks of gestation, with hyperemesis gravidarum. Women were randomly divided into two groups to receive either prednisolone (5mg) or promethazine (25mg) three times daily they received capsules with similar shapes but different codes. The dose of medication was tapered down after the first week and it was discontinued after two weeks. Finally, women were studied for relapse symptoms during the treatment and two weeks post-treatment. Results: There was a significant difference in the improvement of symptoms between the two groups during the course of treatment and also two weeks post-treatment (P=0.001). Moreover, there was no significant difference between the two groups in the frequency of nausea and vomiting during the first 4 days, in the 14th day of the treatment and 2 weeks post-treatment (P=0.07). Conclusion: Results show that both prednisolone and promethazine are effective to control hyperemesis gravidarum

Arsenic compounds toxicity

Arsenic compounds toxicity have been reported of many parts of the world. Those are one of global clinical problems that affect all body organs and many cases of death every year. Arsenic compounds exist in environment and human body as form of inorganic and organic arsenic. Inorganic arsenic includes arsenite (As III) and arsenate (As V). The inorganic arsenics can be methylated to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in vivo. Aasenic, especially inorganic arsenic is well absorbed (80-90) from the gastrointestinal tract, distributed in the body, often metabolized by methylation, and then primarily excreted into urine. Methylation of inorganic arsenic compounds is considered as a detoxification process. Arsenic compounds cause to DNA damage, lipid peroxidation, and decreased antioxidant defense levels. The wide human exposure to arsenic compound especial inorganic arsenic in different sources throughout the world causes great concern for human health. Long term exposure to arsenic can lead to cancer of skin and internal organs eg., the liver, lung, kidney and bladder, also high mortality rate. The noncancerous effects of ingesting arsenic include clinical manifestation in gastrointestinal, cardiovascular, pulmonary, immunological, neurological systems, endocrine glands (e.g. diabetes) and skin. There are some laboratories tests available to diagnose poisoning can measure arsenic in blood, urine, hair, and fingernails. The urine test is the most reliable for detecting arsenic exposure. Arsenic toxicity can be life threating and necessitates supportive therapy (administration crystalloid fluids, inotropic drugs and treatment of cardiac dysrhythemias), decontamination (GI tract irrigation & use activated charcoal in some patients), chelating agents that should be initiated as soon as in arsenic toxicity. These chelating agents include: BAL (British anti lewisite, dimercaprol), 2,3-dimercaptosuccinic acid (DMSA. Succimer), dimercaptopropane sulfoxid acid (DMPS), and also, long term follow-up of these patients. This review article offer to ascertain: a) find out contamination areas that exposure to arsenic to the people by water, food, soil and air; b) common diseases of arsenic poisoning in human; c) education level, awareness and treatment of contaminated people

Antihyperglycemic and antioxidant activity of Viscum album extract

The antihyperglycemic and antioxidant effects of water extract of local Viscum album in alloxanizedrats were investigated. This study performed during 2009 in Babol University of medical sciences (Mazandaran Province, Iran). V. album leaves growing on oaks collected and extracted with hot water. The 90 animals that were used in this investigation were male Wistar rats. 60 rats were gavaged with 500 and 1000 mg/kg/day of V. album extract. One hour after final feeding, freshly prepared alloxan injected subcutaneously. Then blood glucose level was measured according to glucose oxidase method. The antioxidant activity of serum was determined by FRAP assay and serum insulin level was measured with ELISA. The administration of V. album extract (500 and 1000 mg/kg/day) significantly reduced the increase in serum glucose concentration in alloxan-hyperglycemic rats. Both the extracts from V. album enhance the serum insulin level as compared to control rats. Serum antioxidant activity in low dose of extract was significantly higher at 48 and 72 h after alloxan injection. Serum antioxidant activity in the high dose was significantly higher at 24, 48 and 72 h. This study demonstrated that V. album extract reduced the blood glucose and increases the antioxidant power of alloxanized-rats. Much more work is clearly needed before phytotherapy for diabetes can be advanced to the clinic. © 2011 Academic Journals

New 4,5-diphenylimidazole-acetamide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors: synthesis, in vitro and in silico enzymatic and toxicity evaluations

Herein, a new series of 4,5-diphenylimidazole-acetamide-1,2,3-triazole hybrids as potent α-glucosidase inhibitors was designed and synthesized. All the synthesized compounds exhibited excellent inhibition potencies (IC50 values = 55.6–149.2 μM) against α-glucosidase when compared with the standard inhibitor acarbose (IC50 = 750.0 μM). Among the newly synthesized compounds, 4-methyl, 4-methoxy, and 2,3-dichloro derivatives exhibited the highest anti-α-glucosidase activities and were also non-cytotoxic against human normal dermal fibroblast cells. In silico druglikeness, ADME, and toxicity studies of these compounds were performed and obtained results were compared with acarbose. All the synthesized compounds were also inactive against α-amylase in comparison to acarbose. Kinetic study of the most potent compound, 4-methyl derivative, against α-glucosidase demonstrated that this compound is a competitive inhibitor. Furthermore, in silicoinduced fit docking and molecular dynamic studies were performed to further investigate the interaction, orientation, and conformation of these compounds over the active site of α-glycosidase. Graphic abstract: [Figure not available: see fulltext.

Assessment of activity levels for CYP2D6*1, CYP2D6*2, and CYP2D6*41 genes by population pharmacokinetics of dextromethorphan

The pharmacokinetics of dextromethorphan (DM) is markedly influenced by cytochrome P450 2D6 (CYP2D6) enzyme polymorphisms. The aim of this study was to quantify the effects of the CYP2D6*1, *2, and *41 variants on DM metabolism in vivo and to identify other sources of pharmacokinetic variability. Concentrations of DM and dextrorphan (DO) in plasma and urine were evaluated in 36 healthy Caucasian men. These volunteers participated in three clinical studies and received a single oral dose of 30 mg DM-HBr. Data were modeled simultaneously using the population pharmacokinetics NONMEM software. A five-compartment model adequately described the data. The activity levels of the alleles assessed differed significantly. The clearance attributable to an individual CYP2D6*1 copy was 2.5-fold higher as compared with CYP2D6*2 (5,010 vs. 2,020 l/h), whereas the metabolic activity of CYP2D6*41 was very low (85 l/h). Urinary pH was confirmed as a significant covariate for DM renal clearance. These results refine genotype-based predictions of pharmacokinetics for DM and presumably for other CYP2D6 substrates as well

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017

Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030. Funding: Bill & Melinda Gates Foundation. © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Measuring progress from 1990 to 2017 and projecting attainment to 2030 of the health-related Sustainable Development Goals for 195 countries and territories: a systematic analysis for the Global Burden of Disease Study 2017

Background: Efforts to establish the 2015 baseline and monitor early implementation of the UN Sustainable Development Goals (SDGs) highlight both great potential for and threats to improving health by 2030. To fully deliver on the SDG aim of “leaving no one behind”, it is increasingly important to examine the health-related SDGs beyond national-level estimates. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 (GBD 2017), we measured progress on 41 of 52 health-related SDG indicators and estimated the health-related SDG index for 195 countries and territories for the period 1990–2017, projected indicators to 2030, and analysed global attainment. Methods: We measured progress on 41 health-related SDG indicators from 1990 to 2017, an increase of four indicators since GBD 2016 (new indicators were health worker density, sexual violence by non-intimate partners, population census status, and prevalence of physical and sexual violence [reported separately]). We also improved the measurement of several previously reported indicators. We constructed national-level estimates and, for a subset of health-related SDGs, examined indicator-level differences by sex and Socio-demographic Index (SDI) quintile. We also did subnational assessments of performance for selected countries. To construct the health-related SDG index, we transformed the value for each indicator on a scale of 0–100, with 0 as the 2·5th percentile and 100 as the 97·5th percentile of 1000 draws calculated from 1990 to 2030, and took the geometric mean of the scaled indicators by target. To generate projections through 2030, we used a forecasting framework that drew estimates from the broader GBD study and used weighted averages of indicator-specific and country-specific annualised rates of change from 1990 to 2017 to inform future estimates. We assessed attainment of indicators with defined targets in two ways: first, using mean values projected for 2030, and then using the probability of attainment in 2030 calculated from 1000 draws. We also did a global attainment analysis of the feasibility of attaining SDG targets on the basis of past trends. Using 2015 global averages of indicators with defined SDG targets, we calculated the global annualised rates of change required from 2015 to 2030 to meet these targets, and then identified in what percentiles the required global annualised rates of change fell in the distribution of country-level rates of change from 1990 to 2015. We took the mean of these global percentile values across indicators and applied the past rate of change at this mean global percentile to all health-related SDG indicators, irrespective of target definition, to estimate the equivalent 2030 global average value and percentage change from 2015 to 2030 for each indicator. Findings: The global median health-related SDG index in 2017 was 59·4 (IQR 35·4–67·3), ranging from a low of 11·6 (95% uncertainty interval 9·6–14·0) to a high of 84·9 (83·1–86·7). SDG index values in countries assessed at the subnational level varied substantially, particularly in China and India, although scores in Japan and the UK were more homogeneous. Indicators also varied by SDI quintile and sex, with males having worse outcomes than females for non-communicable disease (NCD) mortality, alcohol use, and smoking, among others. Most countries were projected to have a higher health-related SDG index in 2030 than in 2017, while country-level probabilities of attainment by 2030 varied widely by indicator. Under-5 mortality, neonatal mortality, maternal mortality ratio, and malaria indicators had the most countries with at least 95% probability of target attainment. Other indicators, including NCD mortality and suicide mortality, had no countries projected to meet corresponding SDG targets on the basis of projected mean values for 2030 but showed some probability of attainment by 2030. For some indicators, including child malnutrition, several infectious diseases, and most violence measures, the annualised rates of change required to meet SDG targets far exceeded the pace of progress achieved by any country in the recent past. We found that applying the mean global annualised rate of change to indicators without defined targets would equate to about 19% and 22% reductions in global smoking and alcohol consumption, respectively; a 47% decline in adolescent birth rates; and a more than 85% increase in health worker density per 1000 population by 2030. Interpretation: The GBD study offers a unique, robust platform for monitoring the health-related SDGs across demographic and geographic dimensions. Our findings underscore the importance of increased collection and analysis of disaggregated data and highlight where more deliberate design or targeting of interventions could accelerate progress in attaining the SDGs. Current projections show that many health-related SDG indicators, NCDs, NCD-related risks, and violence-related indicators will require a concerted shift away from what might have driven past gains—curative interventions in the case of NCDs—towards multisectoral, prevention-oriented policy action and investments to achieve SDG aims. Notably, several targets, if they are to be met by 2030, demand a pace of progress that no country has achieved in the recent past. The future is fundamentally uncertain, and no model can fully predict what breakthroughs or events might alter the course of the SDGs. What is clear is that our actions—or inaction—today will ultimately dictate how close the world, collectively, can get to leaving no one behind by 2030. Funding: Bill & Melinda Gates Foundation. © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens