THE ANTI-HYPERCHOLESTEROLEMIC EFFECT OF ULVAN POLYSACCHARIDE EXTRACTED FROM THE GREEN ALGA ULVAFASCIATA ON AGED HYPERCHOLESTEROLEMIC RATS

Objective: This study aims to evaluate the relation between hypercholesterolemia and aging, beside the role of Ulva fasciata polysaccharides (UFP)aqueous extracts in lowering cholesterol in aged hypercholesterolemia-induced rats was demonstrated.Method: A total of 140 male Wister rats weighing 120±10 g, 6-9 months old were used. Hypercholesterolemia was induced in rats by feeding ratshigh-fat diet (cholesterol), cholesterol was orally administrated at a dose of (30 mg/0.3 ml olive oil/1 kg animal) 5 times a week for 12 consecutiveweeks, lard fat was mixed with normal diet (1 kg of animal lard was added to 5 kg of normal diet), the occurrence of hypercholesterolemia wasdetermined by measuring the lipid profile (TC, LDL-C, high-density lipoprotein-cholesterol [HDL-C], triglyceride [TG]), the old hypercholesterolemic(HC) rats were only used.Results: The antihypercholesterolemic (HC) effects of ulvan, the sulfated polysaccharide extracted from the green alga Ulvafasciata, in aged rats,were studied. Algal treatment declared a significant reduction in serum total lipid level while, elevation of high-density lipoprotein-cholesterol levelwas noticed in HC rats. Moreover, the algal treatment significantly decreased serum liver and kidney functions biomarkers and improved the hepaticantioxidant levels in hyperlipidemic aged rats. In addition, ulvan administration significantly suppressed the expression of tumor necrosis factoralpha,myeloperoxidaseand cell vascularand intracellularadhesionmolecules-1,whileincreasedthe anti-inflammatorycytokinelevel;interleukin-10.Furthermore,the histopathologicalexaminationof aorta,liverandkidneyof HC-treatedratsindicatedthatthe Ulvafasciatapolysaccharides(UFP),isapotentnaturalhypolipidemicnutraceuticalforthe ameliorationof hyperlipidemiain aged rats.Conclusion: It could be concluded that, in comparison with the standard anti-HC drug (fluvastatin) used in this study, both cold and hot UFP algalextracts of U. fasciata demonstrated appreciable anti-hypercholesterolemic property, in addition to their antioxidant activity even in the old HC stressed rats. Thus, it could be used as a natural lipid regulator.Keywords: Ulvafasciata, Hypercholesterolemia, Polysaccharides, Rats, Sulfated polysaccharides, Aging, Hyper-cholesterolemia

Molecular markers as a prognostic system for hepatocellular carcinoma

AbstractThe gene expression profile p16, c-erbB-3 and bcl2 in hepatocellular carcinoma (HCC) patients with and without associated HCV infection, was assessed. Forty-eight subjects were included in the study and divided equally into two groups: HCC with and without HCV associated infection. Adjacent paracancerous tissues were assessed as control samples. Correlations with various clinico-pathological parameters of the tumour were assessed: stage, grade, and tumour size. The c-erbB-3 oncogene was expressed in 83.33% (40/48) of the total HCC sample and in 31.25% (15/48) of the noncancerous lesions. C-erbB-3 was expressed in 87.5% (21/24) of the HCC cases with associated HCV infection and in 79.16% (19/24) of the HCC cases without associated HCV infection. Gene expression of c-erbB-3 was significantly correlated with the clinico-pathological parameters of the tumour. P16 gene expression was found in 12.5% (6/48) of the total HCC sample and in 25% (12/48) of the para-cancerous lesions. P16 was expressed in 12.5% (3/24) of HCC cases with and without associated HCV infection. Gene expression of p16 exhibited significant negative correlation with clinico-pathological parameters of the tumour. Bcl2 gene expression was found in 20.8% (10/48) of the total HCC sample and in the para-cancerous lesions. Bcl2 was expressed in 20.8% (5/24) of the HCC cases with and without HCV associated infection. Gene expression of bcl2 did not show significant correlations with the clinico-pathological parameters of the tumour. In conclusion, gene expression profiles of p16 and c-erbB-3 could be used as prognostic molecular markers in HCC

Signaling mechanisms of a water soluble curcumin derivative in experimental type 1 diabetes with cardiomyopathy

BACKGROUND: Curcumin exhibits anti-diabetic activities, induces heme-oxygenase-1 (HO-1) and is an inhibitor of transcriptional co-activator p300. A novel water soluble curcumin derivative (NCD) has been developed to overcome low invivo bioavailability of curcumin. We evaluated the effect of the NCD on signaling mechanisms involved in cardiomyocyte hypertrophy and studied whether its action is mediated via inducible HO-1. MATERIALS AND METHODS: Rats were divided into controls, controls receiving NCD, diabetic, diabetic receiving NCD, diabetic receiving pure curcumin, diabetic receiving HO inhibitor, zinc protoporphyrin IX (ZnPP IX) and diabetic receiving NCD and ZnPP IX. NCD and curcumin were given orally. After 45 days, cardiac physiologic parameters, plasma glucose, insulin, glycated hemoglobin (GHb), HO-1 gene expression and HO activity in pancreas and cardiac tissues were assessed. Gene expression of p300, atrial natriuretic peptide (ANP) and myocyte enhancer factor 2 (MEF2A and MEF2C) were studied. RESULTS: NCD and curcumin decreased plasma glucose, GHb and increased insulin levels significantly in diabetic rats. This action may be partially mediated by induction of HO-1 gene. HO-1 gene expression and HO activity were significantly increased in diabetic heart and pancreas. Diabetes upregulated the expression of ANP, MEF2A, MEF2C and p300. NCD and curcumin prevented diabetes-induced upregulation of these parameters and improved left ventricular function. The effect of the NCD was better than the same dose of curcumin

Carotid Intima-Media Thickness in Children with Overweight/Obesity: A Single-center Study

Our study aimed to assess Carotid artery Intima-Media Thickness (CIMT) in a group of children with overweight/obesity as a good predictor for atherosclerosis.We included 39 prepubertal children with Body Mass Indexes (BMI) above 85% for age and sex; 23% overweight, and 77% obese. Twenty matched non-obese healthy children were enrolled to compare CIMT results. About 44% of the cases had abnormal blood pressure, ~39% had dyslipidemia, and ~74% had an unhealthy metabolic state.We observed higher CIMT in cases than controls, with no significant difference between overweight and obese status (at a confidence interval of 95% and P < 0.05). CIMT was positively associated with the BMI of the whole study group, and with HC and triglyceride in the children with obesity. CIMT was significantly higher among children with overweight/obesity than in average weight children, regardless of their metabolic status or blood pressure stage

Growth and Final Height in Children with Autoimmune Hepatitis; A long term observation

Background: Abnormal growth in children with autoimmune hepatitis (AIH) is anticipated, either due to hepatic affection or the growth inhibitory effects of corticosteroids. We aimed to describe children's anthropometry with AIH, and study the factors affecting height.Methods: The present observational study investigates the anthropometric measures of 28 children with AIH followed at a university hospital for 9.5±3 years. We calculated the initial AIH score, the Child-Pugh score, and the pediatric end-stage liver disease score (PELD), follow-up anthropometry, and corticosteroid history. We defined abnormal growth as under nutrition (underweight, wasting, stunting), short stature, overweight, and obesity.Results: At AIH diagnosis, children had a mean age of 7.4±3.1 years, ranging from 2 to 13.8; among whom ~20% had ascites, ~79% had jaundice, and ~82% had type 1 AIH, ~70% had a definite diagnosis of AIH, ~64% were Child-Pugh Score B, ~64% showed severe fibrosis/cirrhosis, and the median PELD score was 8.1 (0.1-12.1). At follow-up, their mean age was 15.9±1.6 years, with mean corticosteroid duration of 7.1±3.1 years, and remission occurred in 50%. We observed a significant improvement in the initial rates of underweight (46.4% vs. 17.8%), mainly stunted, and increased rates of overweight/obesity (14.3% vs. 32.2%). The final rates of height affection without weight affection were comparable to the initials (28.6% vs. 32.1%). Cases with abnormally low final height had significantly more frequent Child-Pugh Score B, higher PELD score, and severe hepatic fibrosis at presentation, with no difference regarding the continuation/ total duration of steroids.Conclusion: the final height in children with AIH is significantly affected by the disease severity at presentation and not the continuation or the duration of corticosteroids use.Background: Abnormal growth in children with autoimmune hepatitis (AIH) is anticipated, either due to hepatic affection or the growth inhibitory effects of corticosteroids. We aimed to describe children's anthropometry with AIH, and study the factors affecting height.Methods: The present observational study investigates the anthropometric measures of 28 children with AIH followed at a university hospital for 9.5±3 years. We calculated the initial AIH score, the Child-Pugh score, and the pediatric end-stage liver disease score (PELD), follow-up anthropometry, and corticosteroid history. We defined abnormal growth as under nutrition (underweight, wasting, stunting), short stature, overweight, and obesity.Results: At AIH diagnosis, children had a mean age of 7.4±3.1 years, ranging from 2 to 13.8; among whom ~20% had ascites, ~79% had jaundice, and ~82% had type 1 AIH, ~70% had a definite diagnosis of AIH, ~64% were Child-Pugh Score B, ~64% showed severe fibrosis/cirrhosis, and the median PELD score was 8.1 (0.1-12.1). At follow-up, their mean age was 15.9±1.6 years, with mean corticosteroid duration of 7.1±3.1 years, and remission occurred in 50%. We observed a significant improvement in the initial rates of underweight (46.4% vs. 17.8%), mainly stunted, and increased rates of overweight/obesity (14.3% vs. 32.2%). The final rates of height affection without weight affection were comparable to the initials (28.6% vs. 32.1%). Cases with abnormally low final height had significantly more frequent Child-Pugh Score B, higher PELD score, and severe hepatic fibrosis at presentation, with no difference regarding the continuation/ total duration of steroids.Conclusion: the final height in children with AIH is significantly affected by the disease severity at presentation and not the continuation or the duration of corticosteroids use

SULPHATED POLYSACCHARIDES (SPS) FROM THE GREEN ALGA ULVA FASCIATA EXTRACT MODULATES LIVER AND KIDNEY FUNCTION IN HIGH FAT DIET-INDUCED HYPERCHOLESTEROLEMIC RATS

Objective: Hypercholesterolemia (HC) was frequently associated with oxidative stress, and release of inflammatory cytokines is to determine the hypolipidemic effects of sulphated polysaccharides from seaweed Ulva fasciata algal extracts through measuring the activities of some parameters related to liver and kidney functions in the serum of hypercholesterolemic rats as compared to normal one.Methods: Different groups of rats were administered a high cholesterol diet. Liver and kidney functions, inflammatory cytokines (TNF-α, CRP, MPO and IL-10), oxidative stress (GSH, MDA and NO), in addition to cell adhesion molecules (ICAM-1 and VCAM-1) were assessed before and after treatment with the algal polysaccharides. In addition, histological examination of liver and kidney were performed to confirm the biochemical findings.Results: The obtained results showed that oxidative stress and inflammatory markers associated with hypercholesterolemia were significantly increased in HC-rats. The histopathological examination of liver and kidney demonstrated severe degeneration with diffuse vacuolar degeneration, necrosis and the presence of fatty droplets. In addition; nephron-histological examination revealed, mild glomerular injury with mild vascular and inflammatory changes. Treatment with the algal sulphated polysaccharides effectively improved these disorders and diminished the formation of fatty liver, as well as renal dysfunction more than the reference drug; fluvastatin. Conclusion: It could be concluded that the consumption of UFP (Ulva fasciata polysaccharides), may be associated with attenuation of inflammatory markers, amelioration of fatty liver and improvement of renal dysfunction, that in turn lead to counteract hypercholesterolemia and its related disorders; such as obesity, and heart disease.Keywords: Non-alcoholic fatty liver disease, Seaweed, Ulva fasciata, Hypercholesterolemia, Hypolipidemic activity, Sulphated polysaccharides (SPs

Efficacy of Mesenchymal Stem Cells in Suppression of Hepatocarcinorigenesis in Rats: Possible Role of Wnt Signaling

<p>Abstract</p> <p>Background</p> <p>The present study was conducted to evaluate the tumor suppressive effects of bone marrow derived mesenchymal stem cells (MSCs) in an experimental hepatocellular carcinoma (HCC) model in rats and to investigate the possible role of Wnt signaling in hepato-carcinogenesis.</p> <p>Methods</p> <p>Ninety rats were included in the study and were divided equally into: Control group, rats which received MSCs only, rats which received MSCs vehicle only, HCC group induced by diethylnitroseamine (DENA) and CCl_<b>4</b>, rats which received MSCs after HCC induction, rats which received MSCs before HCC induction. Histopathological examination and gene expression of Wnt signaling target genes by real time, reverse transcription-polymerase chain reaction (RT-PCR) in rat liver tissue, in addition to serum levels of ALT, AST and alpha fetoprotein were performed in all groups.</p> <p>Results</p> <p>Histopathological examination of liver tissue from animals which received DENA-CCl₄only, revealed the presence of anaplastic carcinoma cells and macro-regenerative nodules type II with foci of large and small cell dysplasia. Administration of MSCs into rats after induction of experimental HCC improved the histopathological picture which showed minimal liver cell damage, reversible changes, areas of cell drop out filled with stem cells. Gene expression in rat liver tissue demonstrated that MSCs downregulated <it>β-catenin</it>, proliferating cell nuclear antigen (<it>PCNA</it>), <it>cyclin D </it>and <it>survivin </it>genes expression in liver tissues after HCC induction. Amelioration of the liver status after administration of MSCs has been inferred by the significant decrease of ALT, AST and Alpha fetoprotein serum levels. Administration of MSCs before HCC induction did not show any tumor suppressive or protective effect.</p> <p>Conclusions</p> <p>Administration of MSCs in chemically induced HCC has tumor suppressive effects as evidenced by down regulation of Wnt signaling target genes concerned with antiapoptosis, mitogenesis, cell proliferation and cell cycle regulation, with subsequent amelioration of liver histopathological picture and liver function.</p

Relation of Asthma Control with Quality of Life among a Sample of Egyptian Asthmatic School Children

BACKGROUND: Asthma is considered a chronic health illness that not only resulted in physical symptoms but also emotional effects. It is; therefore, so important to assess the quality of life of asthmatic patients besides their level of disease control. AIM: To determine the correlation of asthma control with the health-related quality of life (HRQOL) of asthmatic children in Egypt. METHODS: One hundred and twenty-eight asthmatic Egyptian children were enrolled in the study. They were subjected to asthma severity grading, asthma control questionnaire (ACQ) and pediatric asthma quality of life questionnaire (PAQLQ). Studied cases were taken from 6 primary and preparatory schools, Giza governorate. RESULTS: The mean child control score was significantly higher in not well-controlled asthmatics compared to well-controlled asthmatics (p &lt; 0.005). The not well controlled asthmatic children showed significantly lower activity limitation score, symptoms score, and overall asthmatic score compared to controlled asthmatic children (p &lt; 0.05). The severity of asthma shows significant positive correlation with symptoms score, emotional function score and overall asthmatic score (p &lt; 0.05). CONCLUSION: The quality of life for the asthmatic children is strongly correlated with the level of asthma control and severity

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication