Protective effects of setarud (IMOD�) on development of diet-induced hypercholesterolemia in rabbits

Background: A new herbal drug setarud (IMOD�) containing selenium, carotene, and flavonoids, was expected to have positive effects on lipid metabolism and liver functions, due to the nature of its primary components. This study was designed to determine effectiveness of the drug in reducing the risk of development of diet-induced hypercholesterolemia in laboratory animals. Methods: Two groups of male rabbits (n=10 per group) as: intact and control groups on regular chow, were fed a high-cholesterol diet, and two experimental groups were maintained on the same diet and treated with different daily doses (0.02 g/kg and 0.04 g/kg) of setarud (brand name IMOD®, Pars Roos, Iran). The treatment groups were then compared with the intact and control groups and with one another for the effects of the drug which was determined by changes in blood sugar, serum lipid levels, and liver function tests. Results: Results showed that drug had important benefits in alleviating the impact of high-cholesterol diet on serum lipids and liver function markers in drug-treated groups relative to hyperlipidemic controls (p < 0.001). A more favorable modification of total cholesterol and triglyceride levels and the atherogenic index was found in animals, which received 0.04 g/kg drug, as compared to the 0.02 g/kg dose group (p < 0.05). Assessment of serum total protein, albumin, transaminases, and bilirubin levels showed that no changes in liver function of control and drug-treated animals during the period of the study. Conclusion: From the results of this study it may concluded that setarud has dose-dependent positive effects on liver and lipid metabolism and may acts as an effective antihyperglycemic agent

Sub-chronic toxicity study of a novel herbal-based formulation (Semelil) on dogs

Semelil (ANGIPARS�), a novel herbal-based compound containing extract of Melilotus officinalis, was formulated for treatment of chronic wounds, especially diabetic foot ulcer. The purpose of this study was to investigate safety and toxicity effects of intramuscular administration of Semelil in dogs. Preliminary one-month study with Semelil was performed on 8 male and female dogs divided into 2 groups, test and control, four animals each. Semelil was administered intramuscularlyat a dose of 0.07 ml/kg body wt. once a day to the animals of the test group, while the control group received sterile saline. During experiments, general state of the animals including the dynamics of body weight changes, appetite, motor activity and behavior, hair condition, ECG parameters, rectal temperature of animals and data of hematological and biochemical tests were monitored for signs of toxicity and side-effects. Finally, morphology and histology analyses were performed using standard methods. No adverse health or toxicity effects were observed through the course of the study. No damaging consequences of Semelil injections on the functional state of main organs of the experimental animals were found. This observation gave a good evidence of a favorable safety profile compatible with potential therapeutic use of Semelil

A Mutation in HOXA2 Is Responsible for Autosomal-Recessive Microtia in an Iranian Family

Microtia, a congenital deformity manifesting as an abnormally shaped or absent external ear, occurs in one out of 8,000-10,000 births. We ascertained a consanguineous Iranian family segregating with autosomal-recessive bilateral microtia, mixed symmetrical severe to profound hearing impairment, and partial cleft palate. Genome-wide linkage analysis localized the responsible gene to chromosome 7p14.3-p15.3 with a maximum multi-point LOD score of 4.17. In this region, homeobox genes from the HOXA cluster were the most interesting candidates. Subsequent DNA sequence analysis of the HOXA1 and HOXA2 homeobox genes from the candidate region identified an interesting HOXA2 homeodomain variant: a change in a highly conserved amino acid (p.Q186K). The variant was not found in 231 Iranian and 109 Belgian control samples. The critical contribution of HoxA2 for auditory-system development has already been shown in mouse models. We built a homology model to predict the effect of this mutation on the structure and DNA-binding activity of the homeodomain by using the program Modeler 8v2. In the model of the mutant homeodomain, the position of the mutant lysine side chain is consistently farther away from a nearby phosphate group; this altered position results in the loss of a hydrogen bond and affects the DNA-binding activity. © 2008 The American Society of Human Genetics

Exploring the Effects of Vitamin D Supplementation on Cognitive Functions and Mental Health Status in Subjects under Methadone Maintenance Treatment

Objectives:Vitamin D deficiency may be linked to several mental complications including cognitive deficits, depression, and anxiety in patients under methadone maintenance treatment (MMT). This study was designed to explore the effect of vitamin D supplementation on cognitive functions and mental health parameters in subjects under MMT.Methods:This randomized, double-blinded, placebo-controlled clinical trial was carried out among 64 patients under MMT. Participants were randomly allocated to receive either 50,000 IU vitamin D supplements (n=32) or placebo (n=32) every 2 weeks for 24 weeks. Cognitive functions and mental health parameters were taken at baseline and posttreatment to evaluate relevant variables.Results:After the 24-week intervention, compared with the placebo, serum 25(OH) vitamin D levels significantly increased in participants who received vitamin D supplements (β 14.50; 95 confidence interval CI, 13.17-15.83; P<0.001). In addition, compared with the placebo, subjects who received vitamin D had a significant reduction in Iowa Gambling Task (β-6.25; 95% CI,-8.60 to-3.90; P<0.001), and significant increases in Verbal Fluency Test (β 2.82; 95% CI, 0.78-4.86; P=0.007), Immediate Logic Memory (β 1. 32; 95% CI, 0.27-2.37; P=0.01), Reverse Digit Span (β 2.06; 95% CI, 1.18-2.94; P<0.001) and visual working memory (β 0.75; 95% CI, 0.33-1.16; P=0.001). Also, vitamin D supplementation significantly improved BDI (β-2.76; 95% CI,-3.97 to-1.55; P<0.001) compared with the placebo. When we applied Bonferroni correction, LM-Immediate (P=0.07) became nonsignificant, and other mental health parameters did not alter.Conclusions:Overall, taking 50,000 IU vitamin D supplements every 2 weeks for 24 weeks by patients under MMT had beneficial effects on cognitive functions and some mental health parameters. Further studies are needed to confirm our findings. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved

Acute Haemodynamic Changes During Haemodialysis Do Not Exacerbate Gut Hyperpermeability

© 2019 The Author(s)Introduction: The gastrointestinal tract is a potential source of inflammation in dialysis patients. In-vitro studies suggest breakdown of the gut barrier in uraemia leading to increased intestinal permeability and it is hypothesised that haemodialysis exacerbates this problem due to mesenteric ischemia induced by blood volume changes during treatment. Method: The effect of haemodialysis on intestinal permeability was studied in ten haemodialysis patients and compared with five controls. Intestinal permeability was assessed by measuring the differential absorption of four orally administered sugar probes which provides an index of small and whole bowel permeability. A multi-sugar solution (containing lactulose, rhamnose, sucralose and erythritol) was orally administered after an overnight fast. Plasma levels of all sugar probes were measured hourly for 10hrs post-administration. In haemodialysis patients, the procedure was carried out twice – once on a non-dialysis day and once immediately after haemodialysis. Results: Area under curve (AUC) for lactulose: rhamnose (L:R) ratio and sucralose: erythritol (S:E) ratio was similar post-dialysis and on non-dialysis days. AUC for L:R was higher in haemodialysis patients compared to controls (0.071 vs. 0.034,p=0.001), AUC for S:E ratio was not significantly different. Levels of lactulose, sucralose and erythritol were elevated and retained for longer in haemodialysis patients compared to controls due to dependence of sugars on kidney function for clearance. Conclusion: We found no significant acute changes in intestinal permeability in relation to the haemodialysis procedure. Valid comparison of intestinal permeability between controls and haemodialysis patients was not possible due to the strong influence of kidney function on sugar levels.Peer reviewedFinal Published versio

Global, regional, and national age-sex-specific mortality and life expectancy, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

BACKGROUND: Assessments of age-specific mortality and life expectancy have been done by the UN Population Division, Department of Economics and Social Affairs (UNPOP), the United States Census Bureau, WHO, and as part of previous iterations of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD). Previous iterations of the GBD used population estimates from UNPOP, which were not derived in a way that was internally consistent with the estimates of the numbers of deaths in the GBD. The present iteration of the GBD, GBD 2017, improves on previous assessments and provides timely estimates of the mortality experience of populations globally. METHODS: The GBD uses all available data to produce estimates of mortality rates between 1950 and 2017 for 23 age groups, both sexes, and 918 locations, including 195 countries and territories and subnational locations for 16 countries. Data used include vital registration systems, sample registration systems, household surveys (complete birth histories, summary birth histories, sibling histories), censuses (summary birth histories, household deaths), and Demographic Surveillance Sites. In total, this analysis used 8259 data sources. Estimates of the probability of death between birth and the age of 5 years and between ages 15 and 60 years are generated and then input into a model life table system to produce complete life tables for all locations and years. Fatal discontinuities and mortality due to HIV/AIDS are analysed separately and then incorporated into the estimation. We analyse the relationship between age-specific mortality and development status using the Socio-demographic Index, a composite measure based on fertility under the age of 25 years, education, and income. There are four main methodological improvements in GBD 2017 compared with GBD 2016: 622 additional data sources have been incorporated; new estimates of population, generated by the GBD study, are used; statistical methods used in different components of the analysis have been further standardised and improved; and the analysis has been extended backwards in time by two decades to start in 1950. FINDINGS: Globally, 18·7% (95% uncertainty interval 18·4–19·0) of deaths were registered in 1950 and that proportion has been steadily increasing since, with 58·8% (58·2–59·3) of all deaths being registered in 2015. At the global level, between 1950 and 2017, life expectancy increased from 48·1 years (46·5–49·6) to 70·5 years (70·1–70·8) for men and from 52·9 years (51·7–54·0) to 75·6 years (75·3–75·9) for women. Despite this overall progress, there remains substantial variation in life expectancy at birth in 2017, which ranges from 49·1 years (46·5–51·7) for men in the Central African Republic to 87·6 years (86·9–88·1) among women in Singapore. The greatest progress across age groups was for children younger than 5 years; under-5 mortality dropped from 216·0 deaths (196·3–238·1) per 1000 livebirths in 1950 to 38·9 deaths (35·6–42·83) per 1000 livebirths in 2017, with huge reductions across countries. Nevertheless, there were still 5·4 million (5·2–5·6) deaths among children younger than 5 years in the world in 2017. Progress has been less pronounced and more variable for adults, especially for adult males, who had stagnant or increasing mortality rates in several countries. The gap between male and female life expectancy between 1950 and 2017, while relatively stable at the global level, shows distinctive patterns across super-regions and has consistently been the largest in central Europe, eastern Europe, and central Asia, and smallest in south Asia. Performance was also variable across countries and time in observed mortality rates compared with those expected on the basis of development. INTERPRETATION: This analysis of age-sex-specific mortality shows that there are remarkably complex patterns in population mortality across countries. The findings of this study highlight global successes, such as the large decline in under-5 mortality, which reflects significant local, national, and global commitment and investment over several decades. However, they also bring attention to mortality patterns that are a cause for concern, particularly among adult men and, to a lesser extent, women, whose mortality rates have stagnated in many countries over the time period of this study, and in some cases are increasing

The reactivity of human serum natural autoantibodies with certain autoantigens increases along with aging

Introduction Natural autoantibodies (NAAs) that recognize autoantigens are mainly generated in the absence of any apparent immunization with foreign antigens (Ags). These antibodies maintain the body homeostasis through functions, such as inhibition of tumor angiogenesis, detection of structural changes in autoantigens, and exertion of anti-inflammatory impacts. The human body is shown to go through immunological and physiological changes during aging. However, data regarding the potential variations in the binding activity of NAAs is still scarce. Therefore, in this study, we were about to explore the trend through which the reactivity of serum NAAs with several autoantigens varies with advancing age. Materials and methods Serum samples were prepared from healthy individuals of seven age intervals: (0) cord blood, (1) infancy, (2) childhood, (3) adolescence, (4) early adulthood, (5) middle adulthood, and (6) late adulthood (the elderly). The mean immune reactivity (MIR) of the sera with 24 human autoantigens that were obtained from Immunculus research center (Russia) was determined using ELISA and inter-group comparisons were also performed. Results In general, the MIR of serum natural antibodies with the autoantigens was shown to follow an upward trend with advancing age so that the lowest and highest MIRs were detected in the cord blood and late adulthood samples, respectively. Moreover, the results of the inter-group comparisons indicated that the MIRs of the first, second, fourth, and sixth groups were significantly higher than those of their previous groups, i.e. zero, first, third, and fifth groups, respectively. Conclusion This study showed that the reactivity of human tissue-specific and non-specific NAAs with autoantigens varied along with aging. Regarding the crucial roles NAAs play in maintaining the body homeostasis, the variation in their concentration at different age intervals might account for the immunological and pathological changes that occur in the elderly. © 2013 Published by Elsevier Masson SAS

Curcumin mitigates the fibrillation of human serum albumin and diminishes the formation of reactive oxygen species

The formation of amyloid fibrils are thought to contribute to pathogenesis of many amyloids associated human diseases. Here the impact of curcumin on amyloid formation of human serum albumin (HSA) was studied. Incubation of HSA at 68°C under physiologic pH led to amyloid fibril formation. Thioflavin T (ThT) fluorescence was used for determination of amyloid fibril formation. Atomic force microscopy experiments indicated different fibril structure of HSA incubated with or without curcumin. The monitoring of the changes in reactive oxygen species (ROS) levels upon incubation of curcumin with HSA showed a significant decrease in ROS levels. Similar experiments were also carried out in the presence of aflatoxin M1 (AFM1) and lead (Pb) ions. Our results indicated that AFM1 and Pb ions promote the fibrillation of HSA and accelerate ROS production, which were inhibited in the presence of curcumin. Thus, curcumin mitigates protein fibrillation activity and diminishes ROS generation. © 2015 Bentham Science Publishers