Search results for: serum biomarkers

Authors: Mesih Kocamuftuoglu, Gonca Ozan, Enver Ozan, Nalan Kaya, Sema Temizer Ozan

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Metabolic Syndrome, one of the common metabolic disorder, occurs with co-development of insulin resistance, obesity, dislipidemia and hypertension problems. Insulin resistance appears to play a pathogenic role in the metabolic syndrome. Also, there is a relationship between insulin resistance and infertility as known. Turmeric (Curcuma longa L.) a polyphenolic chemical is widely used for its coloring, flavoring, and medicinal properties, and exhibits a strong antioxidant activity. In this study, we assess the effects of turmeric on rat uterine tissue in metabolic syndrome model induced by high fructose diet. Thirty-two adult female Wistar rats weighing 220±20 g were randomly divided into four groups (n=8) as follows; control, fructose, turmeric, and fructose plus turmeric. Metabolic syndrome was induced by fructose solution 20% (w/v) in tap water, and turmeric (C.Longa) administered at the dose of 80 mg/kg body weight every other day by oral gavage. After the experimental period of 8 weeks, rats were decapitated, serum and uterine tissues were removed. Serum lipid profile, glucose, insülin levels were measured. Uterine tissues were fixed for histological analyzes. The uterine tissue sections were stained with hematoxylin-eosin (H & E) stain, then examined and photographed on a light microscope (Novel N-800Mx20). As a result, fructose consumption effected serum lipids, insulin levels, and insulin resistance significantly. Endometrium and myometrium layers were observed in normal structure in control group of uterine tissues. Perivascular edema, peri glandular fibrosis, and inflammatory cell increase were detected in fructose group. Sections of the fructose plus turmeric group showed a significant improvement in findings when compared to the fructose group. Turmeric group cell structures were observed similar with the control group. These results demonstrated that high-fructose consumption could change the structure of the uterine tissue. On the other hand, turmeric administration has beneficial effects on uterine tissue at that dose and duration when administered with fructose.

Keywords: metabolic syndrome, rat, turmeric, uterus

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Authors: Samira Akdader-Oudahmane, Assia Kamel, Lynda Lakabi, Michael Bruce Zimmermann, Zohra Hamouli-Said, Djamila Meskine

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Background: Iodine is a trace element whose adequate intakes are essential during pregnancy to promote the correct growth and development of the fetus. Iodine deficiency is the cause of several disorders in foetal development, and thyroid disorders during pregnancy are associated with an increased risk of miscarriage or premature birth. The aim of this study was to assess the iodine status and thyroid function of pregnant women (PW) in northern Algeria. Methods: Healthy PW were recruited from an urban area (Algiers). Spot urine and venous blood samples were collected to assess iodine status (urinary iodine concentration, UIC) and serum thyroid hormones (TSH, FT4), and anti-thyroid peroxidase antibodies (TPO-Ab) concentrations. Results: The median UIC for the PW (n=172) in Algiers was 246,74µg/L, 244,68 µg/L, and 220,63µg/L, respectively, during the first, second, and third trimesters of pregnancy. Mean TSH and FT4 concentrations were within reference ranges in all groups of women. Among PW, 72.7%, 75.4%, and 75.5% in the first, second and third trimester were TPO-Ab+. Among PW, 14%, 10%, and 10% in the first, second and third trimester, respectively, with TPO -Ab+ had subclinical hypothyroidism. An analysis of the variations in the levels of the serum parameters (FT4, TSH and anti-TPO antibodies) was analyzed according to the UIC intervals admitted and show that these marker are predictive of thyroid function. Conclusion: In northern Algeria, median UICs indicate iodine sufficiency in PW. About 75% of PW are TPO-Ab+ and the prevalence of subclinical hypothyroidism is high.

Keywords: thyroid, pregnant woman, urinary iodine, subclinical hypothyroidism

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Authors: Rizvi Hasan

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Male factor infertility due to abnormalities in prolactin levels is encountered in a significant proportion. This was a case-control study carried out to determine the effects of prolactin abnormalities in normal males with infertility, recruiting 297 male infertile patients with informed written consent. All underwent a Basic Seminal Fluid Analysis (BSA) and endocrine profiles of FSH, LH, testosterone and prolactin (PRL) hormones using the random access chemiluminescent immunoassay method (normal range 2.5-17ng/ml). Age, weight, and height matched voluntary controls were recruited for comparison. None of the cases had anatomical, medical or surgical disorders related to infertility. Among the controls; mean age 33.2yrs ± 5.2, BMI 21.04 ± 1.39kgm-2, BSA 34×106, a number of children fathered 2±1, PRL 6.78 ± 2.92ng/ml. Of the 297 patients, 28 were hyperprolactinaemic while one was hypoprolactinaemic. All the hyperprolactinaemic patients had oligoasthenospermia, abnormal morphology and decreased viability. The serum testosterone levels were markedly lowered in 26 (92.86%) of the hyperprolactinaemic subjects. In the other 2 hyperprolactinaemic subjects and the single hypoprolactinaemic subject, the serum testosterone levels were normal. FSH and LH were normal in all patients. The 29 male patients with abnormalities in their serum PRL profiles were followed up for 12 months. The 28 patients suffering from hyperprolactinaemia were treated with oral bromocriptine in a dose of 2.5 mg twice daily. The hypoprolactinaemic patient defaulted treatment. From the follow-up, it was evident that 19 (67.86%) of the treated patients responded after 3 months of therapy while 4 (14.29%) showed improvement after approximately 6 months of bromocriptine therapy. One patient responded after 1 year of therapy while 2 patients showed improvements although not up to normal levels within the same period. Response to treatment was assessed by improvement in their BSA parameters. Prolactin abnormalities affect the male reproductive system and semen parameters necessitating further studies to ascertain the exact role of prolactin on the male reproductive tract. A parallel study was carried out incorporating 200 male white rats that were grouped and subjected to variations in their serum PRL levels. At the end of 100 days of treatment, these rats were subjected to morphological studies of their male reproductive tracts.Varying morphological changes depending on the levels of PRL changes induced were evident. Notable changes were arrest of spermatogenesis at the spermatid stage, a reduced testicular cellularity, a reduction in microvilli of the pseudostratified epithelial lining of the epididymis, while measurement of the tubular diameter showed a 30% reduction compared to normal tissue. There were no changes in the vas deferens, seminal vesicles, and the prostate. It is evident that both hyperprolactinaemia and hypoprolactinaemia have a direct effect on the morphology and function of the male reproductive tract. The morphological studies carried out on the groups of rats who were subjected to variations in their PRL levels could be the basis for infertility in male human beings.

Keywords: male factor infertility, morphological studies, prolactin, seminal fluid analysis

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Authors: D. S. Mohale, A.V. Chandewar

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Study was undertaken to investigate the effect of imipramine on various biochemical parameters and oxidative stress markers in short and long term depression on rats. Rats were subjected for short (21 days) and long term (84 days) social isolation for and checked for depression on force swim test and tail suspension method. Various markers of oxidative stress like lipid peroxidation (LPO), reduced glutathione (GSH), Supersoxide dismutase (SOD), catalase (CAT) and biochemical parameters like Serum glutamate oxaloacetate transaminase (SGOT), Serum glutamate pyruate transaminase (SGPT), and blood glucose were determined in depressed, control, imipramine and Vitamin E treated group. The rats displayed an increase in depression on force swim test and tail suspension method relative to control. There was significant increase in the level of LPO and decrease in the levels of GSH, SOD and CAT after short and long term depression. Increased oxidative stress in depression which may leads to alteration of biochemical parameters. Treatment with imipramine an tricyclic antidepressant significantly decreases in level of LPO, SGOT, SGPT and increase in the levels of GSH, SOD and CAT in long term depression.

Keywords: depression, oxidative stress, lipid peroxidation, reduced glutathione

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Authors: Sabrina Sebbane, Alina Elena Parvu

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Introduction: Santolina rosmarinifolia is a plant of the Santolina genus, a family made of medicinal plants widely used. Some of the Santolina species have been proven to have potent anti-inflammatory and anti-oxidant effects. However, no in vivo study has been made to demonstrate this in Santolina rosmarinifolia. The aim of our study is to experimentally evaluate the potential anti-inflammatory and anti-oxidant effects of Santolina rosmarinifolia plant extracts on acute inflammation in rats. These effects are defined by measuring the modifications on nitric oxide, reactive oxygen species and anti-oxidant response in serum. Materials and Methods: Rats were divided into 5 groups (n=6). Three groups were given Santolina rosmarinifolia extract by gavage in different concentrations(100%, 50%, 25%) for a week. Inflammation was induced by i.m injection of turpentine oil on the 8th day. One group was only given turpentine oil and the fifth group acted as control and was given only saline solution. Blood was collected and serum separated. Global tests were used to measure the oxidative stress, total oxidative status (TOS), total antioxidant reactivity (TAR) and the modified method of Griess assay to measure NO synthesis. Malondilaldehyde (MDA) and thiols levels were also assessed. Results: Santolina rosmarinifolia did not significantly change the TOS levels (p > 0.05). Santolina rosmarinifolia 25% and 50% decreased significantly the TAR levels (p < 0.001). Santolina 100% didn't have a significant effect on TAR (p > 0.05). All concentrations of Santolina rosmarinifolia increased the oxidative stress index (OSI) significantly(p < 0.05). Santolina rosmarinifolia 100% significantly decreased NO synthesis (p value < 0.05). In the diluted Santolina groups, no significant effect on NO synthesis was observed. In the groups treated with Santolina 100% and Santolina rosmarinifolia 50%, thiols concentration were significantly higher compared to the inflammation group (p < 0.02). A higher stimulatory effect was found in the Santolina 25% group (p value < 0.05). MDA levels were not significantly modified by the administration of Santolina rosmarinifolia (p > 0.05). Conclusion: All three solutions of Santolina rosmarinifolia had no important effect on oxidant production. However, Santolina rosmarinifolia solutions had a positive effect by increasing the thiols concentration in the serum of the models. The sum of all the effects produced by the administration of Santolina did not show a significant decrease of nitro-oxidative stress. Further experiments including smaller concentrations of Santolina rosmarinifolia will be made. Santolina rosmarinifolia should also be tested as a curative treatment.

Keywords: inflammation, MDA, nitric oxide, santolina rosmarinifolia, thiols, TAR, TOS

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Authors: Gwo-Hwa Wan, Tai-Ho Hung, Fen-Fang Chung, Wan-Ying Lee, Hui-Ching Yang

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Air pollutant exposure results in elevated concentrations of oxidative stress and inflammatory biomarkers in general populations. Increased concentrations of inflammatory biomarkers in pregnant women would be associated with preterm labor and low birth weight. To our best knowledge, the associations between air pollutants exposure and inflammation in pregnant women and fetuses are unknown, as well as their effects on fetal growth. This study aimed to evaluate the influences of outdoor air pollutants in northern Taiwan areas on the inflammatory biomarker (high sensitivity C-reactive protein, hs-CRP) concentration in the blood of healthy pregnant women and how the biomarker impacts fetal growth. In this study, 38 healthy pregnant women who are in their first trimester and live in northern Taiwan area were recruited from the Taipei Chang Gung Memorial Hospital. Personal characteristics and prenatal examination data (e.g., blood pressure) were obtained from recruited subjects. The concentrations of inflammatory mediators, hs-CRP, in the blood of healthy pregnant women were analyzed. Additionally, hourly data of air pollutants (PM10, SO2, NO2, O3, CO) concentrations were obtained from air quality monitoring stations in Taipei area, established by the Taiwan Environmental Protection Administration. The definition of lag 0 and lag 01 are the exposure to air pollutants on the day of blood withdrawal, and the average exposure to air pollutants one day before and on the day of blood withdrawal, respectively. The statistical analyses were conducted using SPSS software version 22.0 (SPSS, Inc., Chicago, IL, USA). This analytical result indicates that the healthy pregnant women aged between 28 and 42 years old. The body mass index before pregnancy averaged 21.51 (sd = 2.51) kg/m2. Around 90% of the pregnant women had never smoking habit, and 28.95% of them had allergic diseases. Approximately around 84% and 5.26% of the pregnant women worked at indoor and outdoor environments, respectively. The mean hematocrit level of the pregnant women was 37.10%, and the hemoglobin levels were ranged between 10.1 and 14.7 g/dL with 12.47 g/dL of mean value. The blood hs-CRP concentrations of healthy pregnant women in the first trimester ranged between 0.32 and 32.5 mg/L with 2.83 (sd = 5.69) mg/L of mean value. The blood hs-CRP concentrations were positively associated with ozone concentrations at lag 0-14 (r = 0.481, p = 0.017) in healthy pregnant women. Significant lag effects were identified in ozone at lag 0-14 with a positive excess concentration of blood hs-CRP.

Keywords: air pollutant, hs-CRP, pregnant woman, ozone, first trimester

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Authors: Sara Segura, Diego Nuñez, Miryam Villamil

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In this work, we studied the microscale interaction of foreign substances with blood inside an artificial transparent artery system that represents medium and small muscular arteries. This artery system had channels ranging from 75 μm to 930 μm and was fabricated using glass and transparent polymer blends like Phenylbis(2,4,6-trimethylbenzoyl) phosphine oxide, Poly(ethylene glycol) and PDMS in order to be monitored in real time. The setup was performed using a computer controlled precision micropump and a high resolution optical microscope capable of tracking fluids at fast capture. Observation and analysis were performed using a real time software that reconstructs the fluid dynamics determining the flux velocity, injection dependency, turbulence and rheology. All experiments were carried out with fully computer controlled equipment. Interactions between substances like water, serum (0.9% sodium chloride and electrolyte with a ratio of 4 ppm) and blood cells were studied at microscale as high as 400nm of resolution and the analysis was performed using a frame-by-frame observation and HD-video capture. These observations lead us to understand the fluid and mixing behavior of the interest substance in the blood stream and to shed a light on the use of implantable devices for drug delivery at arteries with different Endothelial dysfunction. Several substances were tested using the artificial artery system. Initially, Milli-Q water was used as a control substance for the study of the basic fluid dynamics of the artificial artery system. However, serum and other low viscous substances were pumped into the system with the presence of other liquids to study the mixing profiles and behaviors. Finally, mammal blood was used for the final test while serum was injected. Different flow conditions, pumping rates, and time rates were evaluated for the determination of the optimal mixing conditions. Our results suggested the use of a very fine controlled microinjection for better mixing profiles with and approximately rate of 135.000 μm3/s for the administration of drugs inside arteries.

Keywords: artificial artery, drug delivery, microfluidics dynamics, arteriosclerosis

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Authors: Esra Bora, Alper Omeroglu, Zeynep Pelin Polat, Oguzhan Kara, Fatih Akdogan, Sema Ucak Basat

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Hyponatremia is one of the most encountered electrolyte imbalance among all medical fields. It has a wide range of symptoms as well as complications from fatigue to loss of consciousness. Although a lot of factors can cause low sodium levels in serum, combining specific medications can lead to severe hyponatremia in a rapid onset which can cause high mortality and morbidity. The objective of this case report was to underline that prescribing specific medications disregarding their side effects can cause this common electrolyte imbalance but in a more severe manner. In this case report, we present a 46-year-old male patient with a serum sodium level of 104 mEq/L who consumed hydrochlorothiazide for hypertension and was under treatment with selective serotonin reuptake inhibitors (SSRIs) for major depression. The patient had tonic-clonic seizures at the second hour of the treatment and intubation was needed due to loss of consciousness and hypoxia. After proper replacement of sodium with hypertonic solutions in intensive care unit for nine days, extubation indicated. Even in healthy young males, hyponatremia due to two separately prescribed medications can lead life-threatening hyponatremia. Physicians should be aware of the side effects of diuretics, especially hydrochlorothiazides and SSRIs and their combinations.

Keywords: diuretics, hydrochlorothiazide, hyponatremia, SSRI

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Authors: M. Skibinska, A. Rajewska-Rager, M. Dmitrzak-Weglarz, N. Lepczynska, P. Sibilski, P. Kapelski, J. Pawlak, J. Twarowska-Hauser

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Introduction: Neurotrophic factors have been implicated in neuropsychiatric disorders. Brain-Derived Neurotrophic Factor (BDNF) influences neuron differentiation in development as well as synaptic plasticity and neuron survival in adulthood. BDNF is widely studied in mood disorders and has been proposed as a biomarker for depression. BDNF is synthesized as precursor protein – proBDNF. Both forms are biologically active and exert opposite effects on neurons. Aim: The aim of the study was to examine the serum levels of BDNF and proBDNF in unipolar and bipolar young patients below 24 years old during hypo/manic, depressive episodes and in remission compared to healthy control group. Methods: In a prospective 2 years follow-up study, we investigated alterations in levels of BDNF and proBDNF in 79 patients (23 males, mean age 19.08, SD 3.3 and 56 females, mean age 18.39, SD 3.28) diagnosed with mood disorders: unipolar and bipolar disorder compared with 35 healthy control subjects (7 males, mean age 20.43, SD 4.23 and 28 females, mean age 21.25, SD 2.11). Clinical characteristics including mood, comorbidity, family history, and treatment, were evaluated during control visits and clinical symptoms were rated using the Hamilton Depression Rating Scale and Young Mania Rating Scale. Serum BDNF and proBDNF concentrations were determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Serum BDNF and proBDNF levels were analysed with covariates: sex, age, age > 18 and < 18 years old, family history of affective disorders, drug-free vs. medicated status. Normality of the data was tested using Shapiro-Wilk test. Levene’s test was used to calculate homogeneity of variance. Non-parametric Tests: Mann-Whitney U test, Kruskal-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient were applied in analyses The statistical significance level was set at p < 0.05. Results: BDNF and proBDNF serum levels did not differ between patients at baseline and controls as well as comparing patients in acute episode of depression/hypo/mania at baseline and euthymia (at month 3 or 6). Comparing BDNF and proBDNF levels between patients in euthymia and control group no differences have been found. Increased BDNF level in women compared to men at baseline (p=0.01) have been observed. BDNF level at baseline was negatively correlated with depression and mania occurence at 24 month (p=0.04). BDNF level at 12 month was negatively correlated with depression and mania occurence at 12 month (p=0.01). Correlation of BDNF level with sex have been detected (p=0.01). proBDNF levels at month 3, 6 and 12 negatively correlated with disease status (p=0.02, p=0.008, p=0.009, respectively). No other correlations of BDNF and proBDNF levels with clinical and demographical variables have been detected. Discussion: Our results did not show any differences in BDNF and proBDNF levels between depression, mania, euthymia, and controls. Imbalance in BDNF/proBDNF signalling may be involved in pathogenesis of mood disorders. Further studies on larger groups are recommended. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: bipolar disorder, Brain-Derived Neurotrophic Factor (BDNF), proBDNF, unipolar depression

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Authors: Rasheed F. G., Hassan H. A., Shehu F. A., Mukhtar M. M., Muhammad Y. Y., Ibrahim S. S., Shehu D., Abdulsalam K., N. Abdullahi

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A cross sectional randomized, descriptive cross sectional study was conducted on the frequency of GSTT1 null alleles in patients diagnosed with type-2-diabetes mellitus (T2DM). A total of 40 patients with T2DM and 10 non-diabetic controls were included in the study. GSTT1 null-alleles genotyping was carried out using multiplex PCR amplification to amplify GSTT1 gene (460bp) while using β-globulin (250bp) as an internal control. The results showed that 55% of T2DM patients had BMI within reference limits, 13% are overweight. Additionally, patients with T2DM were found to have significantly higher (p<0.05) serum levels of glucose, total cholesterol, triglyceride and low density lipoprotein. Furthermore, the presence of null genotype of GSTT1 (deletion in GSTT1) was observed in 28% of diabetic patients. Subjects with GSTT1 deletion have significantly higher (p<0.05) levels of serum glucose, low-density lipoprotein and total cholesterol when compared with individuals without deletion (diabetic and non-diabetic). This results suggests that the deletion of GSTT1 gene might serve as a predisposing factor in the development of T2DM and dyslipideamia

Keywords: diabetes, glutathione-S-transferase, lipid profile, PCR, polymorphism.

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Authors: A. V. Shrirao, N. I. Kochar, A. V. Chandewar

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The flower extract of Butea monosperma herb has been used traditionally in India for medicinal purposes. The plant has been reported to treat hyperglycemia and associated hyperlipidemia. Hyperlipidemia and oxidative stress are known to accelerate coronary artery disease and progression of atherosclerotic lesions. The present work was undertaken to investigate the possible antihyperlipidemic and antioxidative effect of Butea monosperma flowers on hyperlipidemic rats. Hyperlipidemia was induced in rats by a single intraperitonial (i.p.) injection of Triton WR 1339 (400 mg/kg) and it showed sustained elevated levels of serum cholesterol and triglyceride. Ethanolic extract of Butea monosperma flowers (Et-BM) (250 and 500 mg/kg/day) was administered to normal and hyperlipidemic rats for 14 days. Serum and liver tissue were analyzed at three different time intervals for lipid profile and antioxidants enzymes and the activity were compared to the cholesterol-lowering drug, Atorvastatin (10 mg/kg). Parameters were altered during hyperlipidemia and reverted back to near normal values after Et-BM treatment or standard drug Atorvastatin. Lipid peroxidation decreased whereas the activities of superoxide dismutase, glutathione peroxidase and catalase increased in Et-BM treated rats. Pronounced changes were observed at 500 mg/kg of Et-BM for 2 weeks and it was comparable to the standard drug Atorvastatin. The current study provides strong evidence that Et-BM has a remarkable beneficial effect in treating hyperlipidemia and ROS without any side effects at the dosage and duration studied.

Keywords: antioxidant, butea monopserma, hyperlipidemia, triton WR 1339

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Authors: Bassma A. Abdelhaleem, Mamdouh A. Abdulrhman, Nagwa I. Mohamed

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Malnutrition in children is an increasing problem worldwide which may result in both short and long-term irreversible negative health outcomes. Severe Acute Malnutrition (SAM) affects more than 18 million children each year, mostly living in low-income settings. SAM contributes to 45% of all deaths in children less than five years of age. Honey is a natural sweetener, containing mainly monosaccharides (up to 80%), disaccharides (3–5%), water (17–20%), and a wide range of minor constituents such as vitamins, minerals, proteins, amino acids, enzymes, and phytochemicals, mainly phenolic acids, and flavonoids. Honey has been used in many cultures around the world due to its known nutritional and medicinal benefits including the treatment of hypercholesterolemia. Despite its use since ancient times yet little is known about its potential benefits for malnourished children. Honey has the potential to be an affordable solution for malnourished low-income children as it is nutrient-dense and calorie dense food, easily absorbed, highly palatable, enhances appetite, and boosts immunity. This study assessed the effect of clover honey supplementation on the anthropometric measurements and lipid profile of malnourished infants and children. A prospective interventional clinical trial was conducted between November 2019 to November 2020, on 40 malnourished infants and children divided into two groups: Group A (20 children; 11 males and 9 females) received honey in a dose of 1.75ml/kg/dose, twice weekly for 12 weeks and Group B (20 children; 6 males and 14 females) received placebo. Written informed consent was obtained for parents/guardians. Patients were recruited from the Pediatric Nutrition Clinic at Ain Shams University. Anthropometric measurements (weight, height, body mass index, head circumference, and mid-arm circumference) and fasting serum cholesterol levels were measured at baseline and after 3 months. The 3-month honey consumption had a statistically highly significant effect on increasing weight, height, and body mass index and lowering fasting serum cholesterol levels in primary malnourished infants and children. Weight, height, body mass index, and fasting serum cholesterol level before honey consumption were (9.49 ± 2.03, 81.45 ± 8.31, 14.24 ± 2.15, 178.00 ± 20.91) and after 3 months of honey consumption were (10.91 ± 2.11, 84.80 ± 8.23, 15.07 ± 2.05, 162.45 ± 19.73) respectively with P-value < 0.01. Our results showed a significant desirable effect of honey consumption on changes in nutritional status based on weight, height, and body mass index, and has a favourable effect on lowering fasting serum cholesterol levels. These results propose the use of honey as an affordable solution to improve malnutrition, particularly in low-income countries. However, further research needs to weigh benefits against potential harms including the risk of botulinum toxin that is historically associated with honey consumption in early childhood.

Keywords: clinical trial, dyslipidemia, honey, malnutrition

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Authors: Allison Herlene Du Plessis, Dalena (R.M.) Van Rooyen, Wilma Ten Ham-Baloyi, Sihaam Jardien-Baboo

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Introduction: Women die in pregnancy and childbirth for five main reasons—severe bleeding, infections, unsafe abortions, hypertensive disorders (pre-eclampsia and eclampsia), and medical complications including cardiac disease, diabetes, or HIV/AIDS complicated by pregnancy. In 2015, WHO classified sepsis as the third highest cause for maternal mortalities in the world. Chorioamnionitis is a clinical syndrome of intrauterine infection during any stage of the pregnancy and it refers to ascending bacteria from the vaginal canal up into the uterus, causing infection. While the incidence rates for chorioamnionitis are not well documented, complications related to chorioamnionitis are well documented and midwives still struggle to identify this condition in time due to its complex nature. Few diagnostic methods are available in public health services, due to escalated laboratory costs. Often the affordable biomarkers, such as C-reactive protein CRP, full blood count (FBC) and WBC, have low significance in diagnosing chorioamnionitis. A lack of screening impacts on effective and timeous management of chorioamnionitis, and early identification and management of risks could help to prevent neonatal complications and reduce the subsequent series of morbidities and healthcare costs of infants who are health foci of perinatal infections. Objective: This integrative literature review provides an overview of current best research evidence on the screening of women at risk for chorioamnionitis. Design: An integrative literature review was conducted using a systematic electronic literature search through EBSCOhost, Cochrane Online, Wiley Online, PubMed, Scopus and Google. Guidelines, research studies, and reports in English related to chorioamnionitis from 2008 up until 2020 were included in the study. Findings: After critical appraisal, 31 articles were included. More than one third (67%) of the literature included ranked on the three highest levels of evidence (Level I, II and III). Data extracted regarding screening for chorioamnionitis was synthesized into four themes, namely: screening by clinical signs and symptoms, screening by causative factors of chorioamnionitis, screening of obstetric history, and essential biomarkers to diagnose chorioamnionitis. Key conclusions: There are factors that can be used by midwives to identify women at risk for chorioamnionitis. However, there are a paucity of established sociological, epidemiological and behavioral factors to screen this population. Several biomarkers are available to diagnose chorioamnionitis. Increased Interleukin-6 in amniotic fluid is the better indicator and strongest predictor of histological chorioamnionitis, whereas the available rapid matrix-metalloproteinase-8 test requires further testing. Maternal white blood cells count (WBC) has shown poor selectivity and sensitivity, and C-reactive protein (CRP) thresholds varied among studies and are not ideal for conclusive diagnosis of subclinical chorioamnionitis. Implications for practice: Screening of women at risk for chorioamnionitis by health care providers providing care for pregnant women, including midwives, is important for diagnosis and management before complications arise, particularly in resource-constraint settings.

Keywords: chorioamnionitis, guidelines, best evidence, screening, diagnosis, pregnant women

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Authors: Vladyslav Povoroznyuk, Anna Musiienko, Nataliia Dzerovych, Roksolana Povoroznyuk, Oksana Ivanyk

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Deficiency and insufficiency of Vitamin D is a pandemic of the 21^st century. Obesity patients have a lower level of vitamin D, but the literature data are contradictory. The purpose of this study is to investigate deficiency and insufficiency vitamin D in postmenopausal women with obesity. We examined 1007 women aged 50-89 years. Mean age was 65.74±8.61 years; mean height was 1.61±0.07 m; mean weight was 70.65±13.50 kg; mean body mass index was 27.27±4.86 kg/m², and mean 25(OH) D levels in serum was 26.00±12.00 nmol/l. The women were divided into the following six groups depending on body mass index: I group – 338 women with normal body weight, II group – 16 women with insufficient body weight, III group – 382 women with excessive body weight, IV group – 199 women with obesity of class I, V group – 60 women with obesity of class II, and VI group – 12 women with obesity of class III. Level of 25(OH)D in serum was measured by means of an electrochemiluminescent method - Elecsys 2010 analyzer (Roche Diagnostics, Germany) and cobas test-systems. 34.4% of the examined women have deficiency of vitamin D and 31.4% insufficiency. Women with obesity of class I (23.60±10.24 ng/ml) and obese of class II (22.38±10.34 ng/ml) had significantly lower levels of 25 (OH) D compared to women with normal body weight (28.24±12.99 ng/ml), p=0.00003. In women with obesity, BMI significantly influences vitamin D level, and this influence does not depend on the season.

Keywords: obesity, body mass index, vitamin D deficiency, vitamin D insufficiency, postmenopausal women, age

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Authors: Bindu Kumari, Bindu Kumari Singh

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Endosulfan is known to be one of the highly toxic agricultural pesticides commonly used in our societies. With the widespread use of Endosulfan in agriculture, human beings are most likely to be exposed to it, either orally by eating Endosulfan-contaminated foods or by nose and whole body inhalation in the farms during its application. The present study was conducted to observe the changes in the serum uric acid level of the Swiss albino rats due to the administration of Endosulfan. 3.0 mg Endosulfan/kg body weight was daily administered orally to albino rats for 28 days period. Alterations in their K.F.T. parameters were recorded at a regular interval of 7 days within this 28 days period and were compared with those of control rats. All rats were monitored for any observable toxic symptoms throughout the experimental period and they also were weighted weekly to monitor body weight gain. Alteration recorded in K.F.T. parameters within the groups were due to Endosulfan exposure and serum uric acid level was significantly elevated in the 3mg/kg dose group. Pathological changes of rats treated with Endosulfan were observed with typical signs of toxicity. Uric acid is a heterocyclic compound formed as an end product of metabolism of purine nucleotides. It forms ions and salts known as urate and acid urate which are harmful to our health. Uric acid clearance is one of the numerous important functions of the kidney. Defects in this process resulted in Gout, kidney stone or Kidney failure.

Keywords: KFT parameters, blood uric acid level, endosulfan, eat

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Authors: C. Sancho Salvatierra, J. M. Martinez Nieto, R. García Gonzalez-Gordon, M. I. Martinez Bellido

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Introduction: Nature could act as an asset for human health protecting against possible diseases and promoting the state of both physical and mental health. Goals: This paper aims to determine which natural elements present evidence that show positive influence on human health, on which particular aspects and how. It also aims to determine the best biomarkers to measure such influence. Method: A systematic literature review was carried out. First, a general free text search was performed in databases, such as Scopus, PubMed or PsychInfo. Secondly, a specific search was performed combining keywords in order of increasing complexity. Also the Snowballing technique was used and it was consulted in the CSIC’s (The Spanish National Research Council). Databases: Of the 130 articles obtained and reviewed, 80 referred to natural elements that influenced health. These 80 articles were classified and tabulated according to the nature elements found, the health aspects studied, the health measurement parameters used and the measurement techniques used. In this classification the results of the studies were codified according to whether they were positive, negative or neutral both for the elements of nature and for the aspects of health studied. Finally, the results of the 80 selected studies were summarized and categorized according to the elements of nature that showed the greatest positive influence on health and the biomarkers that had shown greater reliability to measure said influence. Results: Of the 80 articles studied, 24 (30.0%) were reviews and 56 (70.0%) were original research articles. Among the 24 reviews, 18 (75%) found positive results of natural elements on health, and 6 (25%) both positive and negative effects. Of the 56 original articles, 47 (83.9%) showed positive results, 3 (5.4%) both positive and negative, 4 (7.1%) negative effects, and 2 (3.6%) found no effects. The results reflect positive effects of different elements of nature on the following pathologies: diabetes, high blood pressure, stress, attention deficit hyperactivity disorder, psychotic, anxiety and affective disorders. They also show positive effects on the following areas: immune system, social interaction, recovery after illness, mood, decreased aggressiveness, concentrated attention, cognitive performance, restful sleep, vitality and sense of well-being. Among the elements of nature studied, those that show the greatest positive influence on health are forest immersion, natural views, daylight, outdoor physical activity, active transport, vegetation biodiversity, natural sounds and the green residences. As for the biomarkers used that show greater reliability to measure the effects of natural elements are the levels of cortisol (both in blood and saliva), vitamin D levels, serotonin and melatonin, blood pressure, heart rate, muscle tension and skin conductance. Conclusions: Nature is an asset for health, well-being and quality of life. Awareness programs, education and health promotion are needed based on the elements that nature brings us, which in turn generate proactive attitudes in the population towards the protection and conservation of nature. The studies related to this subject in Spain are very scarce. Aknowledgements. This study has been promoted and partially financed by the Environmental Foundation Jaime González-Gordon.

Keywords: health, green areas, nature, well-being

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Authors: Macie Matta, Ahmad Jabri, Stephanie Jackson

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Introduction: In the absence of hypotension, pulmonary embolism (PE) causing right ventricular dysfunction or strain, whether confirmed by imaging or cardiac biomarkers, is deemed to be an intermediate-risk category. Urgent treatment of intermediate-risk PE can prevent progression to hemodynamic instability and death. Management options include thrombolysis, thrombectomy, or systemic anticoagulation. We aim to evaluate the short-term outcomes of a half-dose tissue plasminogen activator (tPA) for the management of intermediate-risk PE. Methods: We retrospectively identified adult patients diagnosed with intermediate-risk PE between the years 2000 and 2021. Demographic data, lab values, imaging, treatment choice, and outcomes were all obtained through chart review. Primary outcomes measured include major bleeding events and in-hospital mortality. Patients on standard systemic anticoagulation without receiving thrombolysis or thrombectomy served as controls. Patient data were analyzed using SAS®️ Software (version 9.4; Cary, NC) to compare individuals that received half-dose tPA with controls, and statistical significance was set at a p-value of 0.05. Results: We included 57 patients in our final analysis, with 19 receiving tPA. Patient characteristics and comorbidities were comparable between both groups. There was a significant difference between PE location, presence of acute deep vein thrombosis, and peak troponin level between both groups. The thrombolytic cohort was more likely to demonstrate a 60/60 sign and thrombus in transit finding on echocardiography than controls. The thrombolytic group was more likely to have major bleeding (17% vs 7.9%, p= 0.4) and in-hospital mortality (5.3% vs 0%, p=0.3); however, this was not statistically significant. Patients who received half-dose tPA had non-significantly higher rates of major bleeding and in-hospital mortality. Larger scale, randomized control trials are needed to establish the benefit and safety of thrombolytics in patients with intermediate-risk PE.

Keywords: pulmonary embolism, half dose thrombolysis, tissue plasminogen activator, cardiac biomarkers, echocardiographic findings, major bleeding event

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Authors: Pouya Khaleghi

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Dental implants are a successful treatment modality for restoring both function and aesthetics. Dental implant treatment has predictive results in the replacement of the lost teeth and has a high success rate even in the long term. The most important factor which is responsible for the positive course of implant treatment is the process of osseointegration between the implant structure and the host’s bone tissue. During recent years, many studies have focused on surgical and prosthetic factors, as well as the implant-related factors. However, implant failure still occurs despite the improvements that have led to the increased survival rate of dental implants, which suggests the possible role of some host-related risk factors. Vitamin D is a fat-soluble vitamin regulating calcium and phosphorus metabolism in tissues. The role of vitamin D in bone healing has been under investigation for several years. Vitamin D deficiency has also been associated with impaired and delayed callus formation and fractures healing; however, the role of vitamin D has not been clarified. Therefore, it is extremely important to study the phenomenon of a connection formed between bone tissue and the surface of a titanium implant and find correlations between the 25- hydroxycholecalciferol concentration in blood serum and the course of osseointegration. Because the processes of bone remodeling are very dynamic in the period of actual osseointegration, it is necessary to obtain the correct concentration of vitamin D3 metabolites in blood serum. In conclusion, the correct level of 25-hydroxycholecalciferol on the day of surgery and vitamin D deficiency treatment have a significant influence on the increase in the bone level at the implant site during the process of osseointegration assessed radiologically.

Keywords: implant, osseointegration, vitamin d, dental

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Authors: Kalpana Poudel-Tandukar

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Background: Human Immunodeficiency Virus (HIV) infection has been frequently associated with vitamin D deficiency and depression. Vitamin D deficiency increases the risk of depression in people without HIV. We assessed the cross-sectional and prospective associations between serum concentrations of 25-hydroxyvitamin D (25[OH]D) and depression in a HIV-positive people. Methods: A survey was conducted among 316 HIV-positive people aged 20-60 years residing in Kathmandu, Nepal for a cross-sectional association at baseline, and among 184 participants without depressive symptoms at baseline who responded to both baseline (2010) and follow-up (2011) surveys for prospective association. The competitive protein-binding assay was used to measure 25(OH)D levels and the Beck Depression Inventory-Ia method was used to measure depression, with cut off score 20 or higher. Relationships were assessed using multiple logistic regression analysis with adjustment of potential confounders. Results: The proportion of participants with 25(OH)D level of <20ng/mL, 20-30ng/mL, and >30ng/mL were 83.2%, 15.5%, and 1.3%, respectively. Only four participants with 25(OH)D level of >30ng/mL were excluded in the further analysis. The mean 25(OH)D level in men and women were 15.0ng/mL and 14.4ng/mL, respectively. Twenty six percent of participants (men:23%; women:29%) were depressed. Participants with 25(OH)D level of < 20 ng/mL had a 1.4 fold higher odds of depression in a cross-sectional and 1.3 fold higher odds of depression after 18 months of baseline compared to those with 25(OH)D level of 20-30ng/mL (p=0.40 and p=0.78, respectively). Conclusion: Vitamin D may not have significant impact against depression among HIV-positive people with 25(OH)D level below normal ( > 30ng/mL).

Keywords: depression, HIV, Nepal, vitamin D

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Authors: Leili Iranirad, Mohammad Saleh Sadeghi, Seyed Fakhreddin Hejazi, Negar Vakili Razlighi

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Objective: Contrast-induced nephropathy (CIN) or contrast-induced acute kidney injury (CI-AKI) is an unknown acute kidney injury (AKI) occurring after exposure to contrast media (CM). Contrast agents are most often used for diagnostic procedures or therapeutic angiographic interventions. Recently, Na/K citrate as a urine alkalinization has been evaluated for the prevention of CIN. We conducted this experiment to evaluate the efficiency of Na/K citrate on CIN in high-risk patients treated with cardiac catheterization. Methods: A prospective randomized clinical trial was conducted on 400 patients having moderate to high-risk factors for CIN treated with elective percutaneous coronary intervention (PCI) and were assigned randomly to the control group or the Na/K citrate group. The Na/K citrate group (n=200) received 5 g Na/K citrate solution, which was diluted in 200 mL water two h before and four hours after the first administration and intravenous hydration for two h prior to and six h after the procedure, while the control group (n=200) only received intravenous hydration. Serum creatinine (SCr) was calculated prior to the contrast exposure and after 48 h. CIN was described as a 25% increase in creatinine of serum (SCr) or >0.5 mg/dl 48 h after contrast administration. Results: CIN was observed in 33 patients (16.5%) in the control group and in 6 patients (3%) in the Na/K citrate group. A significant variation was recorded in the CIN incidence between the two groups 48 h after the radiocontrast agent administration (p < 0.001). Conclusion: Our results show that Na/K citrate is useful and substantially reduces the incidence of CIN.

Keywords: contrast media, citrate, PCI

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Authors: Maha Mohamed Hady Ali, M. A. El-Sayed

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Camel (Camelus dromedarius) is very important animal in many arid and semi-arid zones of tropical and subtropical regions as it serves as dual purpose providing meat and milk for human and as draft animal. Camel, like other animal must receive all essential nutrients despite the hostile environment. A study was conducted to evaluate the nutritional status of some micro-minerals of camel under Egyptian environmental condition. Forty five blood samples were collected from apparently healthy male camels with an average age between 2-6 years at the slaughter house in Cairo province, Egypt. The animals were fed mainly on berseem (Trifolium alexandrinum) or concentrate with straw before slaughtering. The collected serum and feedstuff samples were subjected to copper, iron, selenium and zinc analysis using Atomic absorption spectrophotometer. The data showed variation in the level of copper, iron, selenium and zinc in the serum of the dromedary camel as well as in the feedstuffs. Furthermore, the results indicated that the micro- minerals status of feeds may not always reflected as such in camel blood suggesting some role of bioavailability. The main reason for the lack of such reflection seems to be the wide diversity exists in the surrounding environment (forages and plants) as well as the bioavailability of such minerals. Since the requirement of micro-minerals have not been established for camel, more researches must be focused on this topic.

Keywords: camel, copper, egypt, feed stuff, iron, selenium, zinc

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Authors: Christina Williams, Mehari Weldemariam, Ann M. Farese, Thomas J. MacVittie, Maureen A. Kane

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Radiation exposure results in dose-dependent and time-dependent multi-organ damage. Drug development of medical countermeasures (MCM) for radiation-induced injury occurs under the FDA Animal Rule because human efficacy studies are not ethical or feasible. The FDA Animal Rule requires the representation of both sexes and describes several uses for biomarkers in MCM drug development studies. Currently, MCMs are limited and there is no FDA-approved biomarker for any radiation injury. Sex as a variable is essential to identifying biomarkers and developing effective MCMs for acute radiation exposure (ARS) and delayed effects of acute radiation exposure (DEARE). These studies aim to address the death of information on sex differences that have not been determined by studies that included only male, single-sex cohorts. Studies have reported differences in radiosensitivity according to sex. As such, biomarker discovery for radiation-induced damage must consider sex as a variable. This study evaluated the plasma proteomic profile of Rhesus macaque non-human primates after different exposures and doses, as well as time points after radiation. Exposures and doses included total body irradiation between 5-7.5 Gy and partial body irradiation with 5% bone marrow sparing at 9, 9.5 and 10 Gy. Timepoints after irradiation included days 1, 3, 60, and 180, which encompassed both acute radiation syndromes and delayed effects of acute radiation exposure. Bottom-up proteomic analyses of plasma included equal numbers of males and females. In the control animals, few proteomic differences are observed between the sexes. In the irradiated animals, there are a few sex differences, with changes mostly consisting of proteins upregulated in the female animals. Multiple canonical pathways were upregulated in irradiated animals relative to the control animals when subjected to pathway analysis, but differential responses between the sexes are limited. These data provide critical baseline differences according to sex and establish sex differences in non-human primate models relevant to drug development of MCM under the FDA Animal Rule.

Keywords: ionizing radiation, sex differences, plasma proteomics, biomarker discovery

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Authors: Homa Torabizadeh, Mohaddeseh Mikani

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Inulinase from Aspergillus niger was covalently immobilized on magnetic nanoparticles (MNPs/Fe₃O₄) covered with soy protein isolate (SPI/Fe₃O₄) functionalized by bovine serum albumin (BSA) nanoparticles. MNPs are promising enzyme carriers because they separate easily under external magnetic fields and have enhanced immobilized enzyme reusability. As MNPs aggregate simply, surface coating strategy was employed. SPI functionalized by BSA was a suitable candidate for nanomagnetite coating due to its superior biocompatibility and hydrophilicity. Fe₃O₄@SPI-BSA nanoparticles were synthesized as a novel carrier with narrow particle size distribution. Step by step fabrication monitoring of Fe₃O₄@SPI-BSA nanoparticles was performed using field emission scanning electron microscopy and dynamic light scattering. The results illustrated that nanomagnetite with the spherical morphology was well monodispersed with the diameter of about 35 nm. The average size of the SPI-BSA nanoparticles was 80 to 90 nm, and their zeta potential was around −34 mV. Finally, the mean diameter of fabricated Fe₃O₄@SPI-BSA NPs was less than 120 nm. Inulinase enzyme from Aspergillus niger was covalently immobilized through gluteraldehyde on Fe₃O₄@SPI-BSA nanoparticles successfully. Fourier transform infrared spectra and field emission scanning electron microscopy images provided sufficient proof for the enzyme immobilization on the nanoparticles with 80% enzyme loading.

Keywords: high fructose syrup, inulinase immobilization, functionalized magnetic nanoparticles, soy protein isolate

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Authors: Shalini Menon, K. Girish Kumar

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Norepinephrine (NE) is one of the naturally occurring catecholamines which act both as a neurotransmitter and a hormone. Catecholamine levels are used for the diagnosis and regulation of phaeochromocytoma, a neuroendocrine tumor of the adrenal medulla. The development of simple, rapid and cost-effective sensors for NE still remains a great challenge. Herein, a dual-channel sensor has been developed for the determination of NE. A mixture of AgNO₃, NaOH, NH₃.H₂O and cetrimonium bromide in appropriate concentrations was taken as the working solution. To the thoroughly vortexed mixture, an appropriate volume of NE solution was added. After a particular time, the fluorescence and absorbance were measured. Fluorescence measurements were made by exciting at a wavelength of 400 nm. A dual-channel optical sensor has been developed for the colorimetric as well as the fluorimetric determination of NE. Metal enhanced fluorescence property of nanoparticles forms the basis of the fluorimetric detection of this assay, whereas the appearance of brown color in the presence of NE leads to colorimetric detection. Wide linear ranges and sub-micromolar detection limits were obtained using both the techniques. Moreover, the colorimetric approach was applied for the determination of NE in synthetic blood serum and the results obtained were compared with the classic high-performance liquid chromatography (HPLC) method. Recoveries between 97% and 104% were obtained using the proposed method. Based on five replicate measurements, relative standard deviation (RSD) for NE determination in the examined synthetic blood serum was found to be 2.3%. This indicates the reliability of the proposed sensor for real sample analysis.

Keywords: norepinephrine, colorimetry, fluorescence, silver nanoparticles

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Authors: Majid Farsadrooh, Mehran Feizi-Dehnayebi

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Serum albumin is the most abundant protein that is present in the circulatory system of a wide variety of organisms. Although it is a significant macromolecule, it can contribute to osmotic blood pressure and also, plays a superior role in drug disposition and efficiency. Molecular docking simulation can improve in silico drug design and discovery procedures to propound a lead compound and develop it from the discovery step to the clinic. In this study, the molecular docking simulation was applied to select a lead molecule through an investigation of the interaction of the two anticancer drugs (Alitretinoin and Abemaciclib) with Human Serum Albumin (HSA). Then, a series of new compounds (a-e) were suggested using lead molecule modification. Density functional theory (DFT) including MEP map and HOMO-LUMO analysis were used for the newly proposed compounds to predict the reactivity zones on the molecules, stability, and chemical reactivity. DFT calculation illustrated that these new compounds were stable. The estimated binding free energy (ΔG) values for a-e compounds were obtained as -5.78, -5.81, -5.95, -5,98, and -6.11 kcal/mol, respectively. Finally, the pharmaceutical properties and toxicity of these new compounds were estimated through OSIRIS DataWarrior software. The results indicated no risk of tumorigenic, irritant, or reproductive effects and mutagenicity for compounds d and e. As a result, compounds d and e, could be selected for further study as potential therapeutic candidates. Moreover, employing molecular docking simulation with the prediction of pharmaceutical properties helps to discover new potential drug compounds.

Keywords: drug design, anticancer, computational studies, DFT analysis

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Authors: Hanan A. Soliman, Mohamed A. El-Desouky, Walaa G. Hozayen, Rasha R. Ahmed, Amal K . Khaliefa

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Aim: The objective of this study is to investigate the hypoglycemic, hypolipidemic, and hepatoprotective effects of the aqueous extract of parsley, basil, and chicory whole plant in normal and dexamethasone (Dex) rats. Materials and Methods: 50 female albino rats were used in this study and divided into 5 groups (for each 10). Group (1) fed basal diet and maintained as negative control group. Group (2) received Dex in a dose of (0.1 mg/kg b. wt.). Groups 3, 4, and 5 were treated with Dex along with three different plant extracts of parsley, basil, and chicory (2 g/kg b. wt.), (400 mg/kg b. wt.), and (100 mg/kg b. wt.), respectively. Results: All these groups were treated given three times per week for 8 consecutive weeks. Dex-induced alterations in the levels of serum glucose, triglyceride, cholesterol, low-density lipoprotein-cholesterol levels and cardiovascular indices and serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase activities, liver thiobarbituric acid (TBARS) levels increased, while high-density lipoprotein-cholesterol, total protein, albumin, and liver glutathione (GSH) levels decreased. On the other hand, plant extracts succeeded to modulate these observed abnormalities resulting from Dex as indicated by the reduction of glucose, cholesterol, TBARS, and the pronounced improvement of the investigated biochemical and antioxidant parameters. Conclusions: It was concluded that probably, due to its antioxidant property, parsley, basil, and chicory extracts have hepatoprotective effects in Dex-induced in rats.

Keywords: antioxidants, dexamethasone, hyperglycemia, hyperlipidemia

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Authors: Majid Afkhami, Maryam Ehsanpour, Reza Khoshnood, Zahra Khoshnood, Rastin Afkhami

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Marine pollution is a global environmental problem. Different human activities on land, in the water and in the air contribute to the contamination of seawater, sediments and organisms with potentially toxic substances. Contaminants can be natural substances or artificially produced compounds. After discharge into the sea, contaminants can stay in the water in dissolved form or they can be removed from the water column through sedimentation to the bottom sediments. Histopathological alterations can be used as indicators for the effects of various anthropogenic pollutants on organisms and are a reflection of the overall health of the entire population in the ecosystem. These histo pathological biomarkers are closely related to other biomarkers of stress since many pollutants have to undergo metabolic activation in order to be able to provoke cellular change in the affected organism. In order to make evaluation of the effects of oil pollution, some heavy metals bioaccumulation and explore their histopathological effects on hepatocytes of Oriental sole (Euryglossa orientalis) and Deep flounder (Psettodes erumei), fishes caught from two areas of north coast of the Persian Gulf: Bandar Abbass and Bandar Lengeh. Concentrations of Ni and V in liver of both species in two sampling regions were in following order: Bandar abbass Bandar lengeh; also between two species, these quantities were higher in P. erumei than E. orientalis in both sampling regions. Histopathology of the liver shows some cellular alterations including: degeneration, necrosis and tissue disruption, and histopathological effects were severe in P. erumei than E. orientalis. Results showed that Bandar Abbass region was more polluted than Bandar Lengeh, and because Ni and V were oil pollution indicators, and two flat fishes were benthic, they can receive considerable amount of oil pollution through their biological activities like feeding. Also higher amounts of heavy metal concentrations and major histopathological effects in E. orientalis showed strong relationship between benthic habitat of the fish and amounts of received pollutants from water and sediments, because E. orientalis is more related to the bottom than P. erumei.

Keywords: heavy metals, flatfishes, Persian Gulf, oil pollution

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Authors: Elena K. Schneider, Johnny X. Huang, Vincenzo Carbone, Mark Baker, Mohammad A. K. Azad, Matthew A. Cooper, Jian Li, Tony Velkov

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Ivacaftor is a novel CF trans-membrane conductance regulator (CFTR) potentiator that improves the pulmonary function for cystic fibrosis patients bearing a G551D CFTR-protein mutation. Because ivacaftor is highly bound (>97%) to plasma proteins, there is the strong possibility that co-administered CF drugs that compete for the same plasma protein binding sites and impact the free drug concentration. This in turn could lead to drastic changes in the in vivo efficacy of ivacaftor and therapeutic outcomes. This study compares the binding affinity of ivacaftor and co-administered CF drugs for human serum albumin (HSA) and α1-acid glycoprotein (AGP) using surface plasmon resonance and fluorimetric binding assays that measure the displacement of site selective probes. Due to their high plasma protein binding affinities, drug-drug interactions between ivacaftor are to be expected with ducosate, montelukast, ibuprofen, dicloxacillin, omeprazole and loratadine. The significance of these drug-drug interactions is interpreted in terms of the pharmacodynamic/pharmacokinetic parameters and molecular docking simulations. The translational outcomes of the data are presented as recommendations for a staggered treatment regimen for future clinical trials which aims to maximize the effective free drug concentration and clinical efficacy of ivacaftor.

Keywords: human α-1-acid glycoprotein, binding affinity, human serum albumin, ivacaftor, cystic fibrosis

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Authors: Ljiljana Stojković, Manja Zec, Maja Zivkovic, Maja Bundalo, Marija Glibetić, Dragan Alavantić, Aleksandra Stankovic

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Cardiovascular disease (CVD) is associated with alterations in DNA methylation, the latter modulated by dietary polyphenols. The present pilot study (part of the original clinical study registered as NCT02800967 at www.clinicaltrials.gov) aimed to investigate the impact of 4-week daily consumption of polyphenol-rich Aronia melanocarpa juice on Long Interspersed Nucleotide Element-1 (LINE-1) methylation in peripheral blood leukocytes, in subjects (n=34, age of 41.1±6.6 years) at moderate CVD risk, including an increased body mass index, central obesity, high normal blood pressure and/or dyslipidemia. The goal was also to examine whether factors known to affect DNA methylation, such as folate intake levels, MTHFR C677T gene variant, as well as the anthropometric and metabolic parameters, modulated the LINE-1 methylation levels upon consumption of polyphenol-rich Aronia juice. The experimental analysis of LINE-1 methylation was done by the MethyLight method. MTHFR C677T genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism method. Folate intake was assessed by processing the data from the food frequency questionnaire and repeated 24-hour dietary recalls. Serum lipid profile was determined by using Roche Diagnostics kits. The statistical analyses were performed using the Statistica software package. In women, after vs. before the treatment period, a significant decrease in LINE-1 methylation levels was observed (97.54±1.50% vs. 98.39±0.86%, respectively; P=0.01). The change (after vs. before treatment) in LINE-1 methylation correlated directly with MTHFR 677T allele presence, average daily folate intake and the change in serum low-density lipoprotein cholesterol, while inversely with the change in serum triacylglycerols (R=0.72, R2=0.52, adjusted R2=0.36, P=0.03). The current results imply potential cardioprotective effects of habitual polyphenol-rich Aronia juice consumption achieved through the modifications of DNA methylation pattern in subjects at CVD risk, which should be further confirmed. Hence, the precision nutrition-driven modulations of DNA methylation may become targets for new approaches in the prevention and treatment of CVD.

Keywords: Aronia melanocarpa, cardiovascular risk, LINE-1, methylation, peripheral blood leukocytes, polyphenol

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Authors: Iván Castelló, Georgiana Stoica, Emilio Palomares, Fernando Bravo

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We present herein two colour encoded silica nanospheres (2nanoSi) for the fluorescence quantitative ratiometric determination of trypsin in humans. The system proved to be a faster (minutes) method, with two times higher sensitivity than the state-of-the-art biomarkers based sensors for cystic fibrosis (CF), allowing the quantification of trypsin concentrations in a wide range (0-350 mg/L). Furthermore, as trypsin is directly related to the development of cystic fibrosis, different human genotypes, i.e. healthy homozygotic (> 80 mg/L), CF homozygotic (< 50 mg/L), and heterozygotic (> 50 mg/L), respectively, can be determined using our 2nanoSi nanospheres.

Keywords: cystic fibrosis, trypsin, quantum dots, biomarker, homozygote, heterozygote

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