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Are therapeutic diets an emerging additional choice in autism spectrum disorder management?

World Journal of Pediatrics 2018年第3期14卷 215-223页

作者： M.gogou g.kolios 2nd Department of Pediatrics School of MedicineUniversity General Hospital AHEPAAristotle University of ThessalonikiThessaloníkiGreece Laboratory of Pharmacology School of MedicineDemocritus University of ThraceAlexandroupolisGreece

Background A nutritional background has been recognized in the pathophysiology of autism and a series of nutritional interventions have been considered as complementary therapeutic options. As available treatments and interventions are not effective in all individuals, new therapies could broaden management options for these patients. Our aim is to provide current literature data about the effect of therapeutic diets on autism spectrum disorder. Data sources A systematic review was conducted by two reviewers independently. Prospective clinical and preclinical stud-ies were considered. Results Therapeutic diets that have been used in children with autism include ketogenic and gluten/casein-free diet. We were able to identify 8 studies conducted in animal models of autism demonstrating a beneficial effect on neurophysiological and clinical parameters. Only 1 clinical study was found showing improvement in childhood autism rating scale after implemen-tation of ketogenic diet. With regard to gluten/casein-free diet, 4 clinical studies were totally found with 2 of them showing a favorable outcome in children with autism. Furthermore, a combination of gluten-free and modified ketogenic diet in a study had a positive effect on social affect scores. No serious adverse events have been reported. Conclusions Despite encouraging laboratory data, there is controversy about the real clinical effect of therapeutic diets in patients with autism. More research is needed to provide sounder scientific evidence.

关键词： Autism Children gluten/casein-free diet Ketogenic diet Therapeutic diet

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Octreotide induces caspase activation and apoptosis in human hepatoma Hepg2 cells

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World Journal of gastroenterology 2011年第3期17卷 313-321页

作者： Nikos J Tsagarakis Ioannis Drygiannakis Antonis g Batistakis george kolios Elias A Kouroumalis Liver Research Laboratory School of MedicineUniversity of Crete Laboratory of Pharmacology School of MedicineDemocritus University of Thrace Department of gastroenterology and Hepatology University Hospital of Heraklion

AIM: To investigate the role of octreotide on cellular proliferation and apoptosis of human hepatoma (Hepg2) cells. METHODS: We studied cellular proliferation, apoptosis and the possible internal caspase-mediated apoptosis pathway involved, after treatment of Hepg2 carcinoma cells with octreotide in comparison with the apoptosis caused by tumor necrosis factor-α (TNF-α). Activities of caspase-3, caspase-9, caspase-8 and caspase-2 were studied, while apoptosis was investigated through detection of DNA fragmentation and through identification of apoptotic cells with the annexin-V/propidium iodide flow cytometric method. RESULTS: After an initial increase in Hepg2 cellular proliferation, a significant inhibition was observed with 10-8 mol/L octreotide, while TNF-α dose-dependently decreased proliferation. Early and late apoptosis was significantly increased with both substances. Octreotide significantly increased caspase-3, caspase-8 and caspase-2 activity. TNF-α signifi cantly increased only caspase-2. Cellular proliferation was decreased after treatment with octreotide or TNF-α alone but, in contrast to TNF-α, octreotide decreased proliferation only at concentrations of 10-8 mol/L, while lower concentrations increased proliferation. CONCLUSION: Our findings are suggestive of caspasemediated signaling pathways of octreotide antitumor activity in Hepg2 cells, and indicate that measurements of serum octreotide levels may be important, at least in clinical trials, to verify optimal therapeutic drug concentrations.

关键词： Octreotide Hepatocellular carcinoma Apoptosis Caspases Somatostatin

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Role of Kupffer cells in the pathogenesis of liver disease

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World Journal of gastroenterology 2006年第46期12卷 7413-7420页

作者： george kolios Vassilis Valatas Elias Kouroumalis Depart-ment of gastroenterology and Hepatology University Hospital and Medical School University of Crete Heraklion Greece

Kupffer cells, the resident liver macrophages have long been considered as mostly scavenger cells responsible for removing particulate material from the portal circulation. However, evidence derived mostly from animal models, indicates that Kupffer cells may be implicated in the pathogenesis of various liver diseases including viral hepatitis, steatohepatitis, alcoholic liver disease, intrahepatic cholostasis, activation or rejection of the liver during liver transplantation and liver fibrosis. There is accumulating evidence, reviewed in this paper, suggesting that Kupffer cells may act both as effector cells in the destruction of hepatocytes by produdng harmful soluble mediators as well as antigen presenting cells during viral infections of the liver. Moreover they may represent a significant source of chemoattractant molecules for cytotoxic CD8 and regulatory T cells. Their role in fibrosis is well established as they are one of the main sources of TgFβ1 production, which leads to the transformation of stellate cells into myofibroblasts. Whether all these variable functions in the liver are mediated by different Kupffer cell subpopulations remains to be evaluated. In this review we propose a model that demonstrates the role of Kupffer cells in the pathogenesis of liver disease.

关键词： Kupffer cells Liver disease Hepatic injury Liver fibrosis Hepatocellular carcinoma Hepatitis Steatohepatitis

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Role of exercise in preventing and restoring gut dysbiosis in patients with inflammatory bowel diseases:A review

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World Journal of gastroenterology 2021年第30期27卷 5037-5046页

作者： Tilemachos Koutouratsas Anastassios Philippou george kolios Michael Koutsilieris Maria gazouli Department of Basic Medical Sciences Laboratory of BiologyMedical SchoolNational and Kapodistrian University of AthensAthens 11527Greece Department of Basic Medical Sciences Laboratory of PhysiologySchool of MedicineNational and Kapodistrian University of AthensAthens 11527Greece Department of Medicine Laboratory of PharmacologyDemocritus University of ThraceAlexandroupolis 68100Greece

Inflammatory bowel diseases(IBD)include a spectrum of chronic inflammatory disorders of the gastrointestinal tract whose pathogenesis is yet to be *** intestinal microbiome has been studied as a causal component,with certain microbiotic alterations having been observed in subtypes of *** exercise is a modulator of the intestinal microbiome,causing shifts in its composition that are partially corrective of those observed in IBD;furthermore,physical exercise may be beneficial in patients with certain IBD *** review studies the effects of physical exercise on the human gut microbiome while investigating pathophysiologic mechanisms that could explain physical activity’s clinical effects on patients with IBD.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn’s disease Pouchitis Microbiome Exercise

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Probiotics: Shaping the gut immunological responses

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World Journal of gastroenterology 2024年第15期30卷 2096-2108页

作者： Eirini Filidou Leonidas Kandilogiannakis Anne Shrewsbury george kolios Katerina Kotzampassi Faculty of Medicine Laboratory of PharmacologyDemocritus University of ThraceAlexandroupolis 68100Greece Department of Surgery Aristotle University of ThessalonikiThessaloniki 54636Greece

Probiotics are live microorganisms exerting beneficial effects on the host’s health when administered in adequate *** the most popular and adequately studied probiotics are bacteria from the families Lactobacillaceae,Bifidobacteriaceae and *** of them have been shown,both in vitro and in vivo studies of intestinal inflammation models,to provide favorable results by means of improving the gut microbiota composition,promoting the wound healing process and shaping the immunological *** intestinal conditions,such as inflammatory bowel diseases(IBD),are characterized by an imbalance in microbiota composition,with decreased diversity,and by relapsing and persisting inflammation,which may lead to mucosal *** the results of the clinical studies investigating the effect of probiotics on patients with IBD are still controversial,it is without doubt that these microorganisms and their metabolites,now named postbiotics,have a positive influence on both the host’s microbiota and the immune system,and ultimately alter the topical tissue *** influence is achieved through three axes:(1)By dis-placement of potential pathogens via competitive exclusion;(2)by offering protection to the host through the secretion of various defensive mediators;and(3)by supplying the host with essential *** will analyze and discuss almost all the in vitro and in vivo studies of the past 2 years dealing with the possible favorable effects of certain probiotic genus on gut immunological responses,highlighting which species are the most beneficial against intestinal inflammation.

关键词： Probiotics Lactobacillaceae Bifidobacteriaceae Saccharomyces Intestinal inflammation Immune responses

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Promoter methylation status of hMLH1,MgMT,and CDKN2A/p16 in colorectal adenomas

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World Journal of gastroenterology 2010年第28期16卷 3553-3560页

作者： Vasiliki Psofaki Chryssoula Kalogera Nikolaos Tzambouras Dimitrios Stephanou Epameinondas Tsianos Konstantin Seferiadis georgios kolios Laboratory of Clinical Chemistry University of Ioannina Medical School45500 IoanninaGreece Laboratory of Biochemistry University Hospital of IoanninaLeoforos S.Niarchou45500 IoanninaGreece Hepatogastroenterology Unit of Internal Medicine University Hospital of IoanninaLeoforos S.Niarchou45500 IoanninaGreece Laboratory of Pathology University Hospital of IoanninaLeoforos S.Niarchou45500 IoanninaGreece

AIM:To investigate aberrant DNA methylation of Cpg islands and subsequent low-or high-level DNA microsatellite instability(MSI)which is assumed to drive colon carcinogenesis. METHODS:DNA of healthy individuals,adenoma(tu-bular or villous/tubulovillous)patients,and colorectal carcinoma patients who underwent colonoscopy was used for assessing the prevalence of aberrant DNA methylation of human DNA mismatch repair gene mutator L homologue 1(hMLH1),Cyclin-dependent kinase inhibitor 2A(CDKN2A/p16),and O-6-methylguanine DNA methyltransferase(MgMT),as well as their rela- tion to MSI. RESULTS:The frequency of promoter methylation for each locus increased in the sequence healthy tissue/adenoma/*** showed the highest frequency in each *** and CDKN2A/p16 presented a statistically significant increase in promoter methylation between the less and more tumorigenic forms of colorectal adenomas(tubular vs tubullovillous and villous adenomas).All patients with tubulovillous/villous adenomas,as well as all colorectal cancer patients,showed promoter methylation in at least one of the examined *** findings suggest a potentially crucial role for methylation in the polyp/adenoma to cancer progres- sion in colorectal *** and methylation seem to be interdependent,as simultaneous hMLH1, CDKN2A/p16,and MgMT promoter methylation was present in 8/9 colorectal cancer patients showing the MSI phenotype. CONCLUSION:Methylation analysis of hMLH1,CD- KN2A/p16,and MgMT revealed specific methylation profiles for tubular adenomas,tubulovillous/villous adenomas,and colorectal cancers,supporting the use of these alterations in assessment of colorectal tumorigenesis.

关键词： Promoter methylation Microsatellite instability Human DNA mismatch repair gene mutator L homologue 1 O-6-methylguanine DNA methyltransferase Cyclin-dependent kinase inhibitor 2A

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Corticotropin-releasing factor receptor subtype 2 in human colonic mucosa: Down-regulation in ulcerative colitis

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World Journal of gastroenterology 2013年第9期19卷 1416-1423页

作者： Ekaterini Chatzaki Peter A Anton Mulugeta Million Maria Lambropoulou Theodoros Constantinidis george kolios Yvette Taché Dimitri E grigoriadis Neurocrine Biosciences Inc. San Diego CA 92121 United States Laboratory of Pharmacology Faculty of Medicine Democritus University of Thrace 68100 Alexandroupolis Greece Center for HIV Prevention Research Division of Digestive Diseases University of California at Los Angeles and VA Greater Los Angeles Healthcare System Los Angeles CA 90073 United States Digestive Diseases Research Center and Center for Neurobiology of Stress Division of Digestive Diseases University of California at Los Angeles and VA Greater Los Angeles Healthcare System Los Angeles CA 90073 United States Laboratory of Histology-Embryology Faculty of Medicine Democritus University of Thrace 68100 Alexandroupolis Greece Laboratory of Hygiene and Environmental Protection Faculty of Medicine Democritus University of Thrace 68100 Alexandroupolis Greece

AIM: To assess corticotropin-releasing factor receptor 2 (CRF 2 ) expression in the colon of healthy subjects and patients with ulcerative colitis (UC). METHODS: We examined CRF2 gene and protein expression in the distal/sigmoid colonic mucosal biopsies from healthy subjects and patients with UC (active or disease in remission), human immunodeficiency virus (HIV) and functional bowel disease (FBD) by reverse transcriptionpolymerase chain reaction and immunofluorescence. RESULTS: gene expression of CRF2 was demonstrated in the normal human colonic biopsies, but not in the human colorectal adenocarcinoma cell line Caco2. Receptor protein localization showed immunoreactive CRF 2 receptors in the lamina propria and in the epithelial cells of the distal/sigmoid biopsy samples. Interestingly, CRF 2 immunoreactivity was no longer observed in epithelial cells of patients with mild-moderately active UC and disease in remission, while receptor protein expression did not change in the lamina propria. No differences in CRF 2 expression profile were observed in distal/sigmoid intestinal biopsies from HIV infection and FBD patients, showing no signs of inflammation. CONCLUSION: The down-regulation of the CRF2 receptor in the distal/sigmoid biopsies of UC patients is indicative of change in CRF 2 signalling associated with the process of inflammation.

关键词： Colonic mucosa Corticotropin-releasing factor Corticotropin-releasing factor receptor Human immunodeficiency virus Ulcerative colitis Urocortin

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Characterization of the interaction of nanobubble ultrasound contrast agents with human blood components

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Bioactive Materials 2023年第1期19卷 642-652页

作者： Michaela B.Cooley Eric C.Abenojar Dana Wegierak Anirban Sen gupta Michael C.kolios Agata A.Exner Department of Biomedical Engineering Case Western Reserve UniversityClevelandOH44106United States Department of Radiology Case Western Reserve UniversityClevelandOH44106United States Department of Physics Ryerson UniversityTorontoOntarioM5B 2K3Canada Institute for Biomedical Engineering and Science Technology A Partnership Between Ryerson University and St.Michael’s HospitalTorontoOntarioM5B 1T8Canada

Nanoscale ultrasound contrast agents,or nanobubbles,are being explored in preclinical applications ranging from vascular and cardiac imaging to targeted drug delivery in *** sub-micron particles are approximately 10x smaller than clinically available *** allows them to effectively traverse compromised physiological barriers and circulate for extended periods of *** various aspects of nanobubble behavior have been previously examined,their behavior in human whole blood has not yet been ***,herein we examined,for the first time,the short and long-term effects of blood components on nanobubble acoustic *** observed differences in the kinetics of backscatter from nanobubble suspensions in whole blood compared to bubbles in phosphate buffered saline(PBS),plasma,or red blood cell solutions(RBCs).Specifically,after introducing nanobubbles to fresh human whole blood,signal enhancement,or the magnitude of nonlinear ultrasound signal,gradually increased by 22.8±13.1%throughout our experiment,with peak intensity reached within 145 *** contrast,nanobubbles in PBS had a stable signal with negligible change in intensity(􀀀1.7±3.2%)over 8 *** the same conditions,microbubbles made with the same lipid formulation showed a􀀀56.8±6.1%decrease in enhancement in whole *** confocal,fluorescent,and scanning electron microscopy analysis revealed attachment of the nanobubbles to the surface of RBCs,suggesting that direct interactions,or hitchhiking,of nanobubbles on RBCs in the presence of plasma may be a possible mechanism for the observed *** phenomenon could be key to extending nanobubble circulation time and has broad implications in drug delivery,where RBC interaction with nanoparticles could be exploited to improve delivery efficiency.

关键词： Nanobubbles Ultrasound contrast agents Red blood cells Hitchhiking Ultrasound Drug delivery

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Evaluation of the Reliability Performance of Failure Criteria for Composite Structures

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World Journal of Mechanics 2012年第3期2卷 162-170页

作者： Athanasios J. kolios Stefano Proia Offshore Process and Energy Engineering Department Cranfield University Cranfield UK

Evolution of materials, following the design requirements of special structures, has shifted interest towards development of composite members able to meet strength requirements “tailored” to specific applications. These members can provide appropriate, more cost effective structures, however absence of generic design guidelines raise constraints towards derivation of optimized structures. Reliability-based assessment can overcome this limitation by ensuring that acceptable levels of target reliability are achieved throughout their service life. This paper presents a methodology for reliability assessment of composite members based on appropriate limit state functions derived according to fundamental failure criteria, Tsai-Hill and Tsai-Wu, applicable to composite materials. The methodology that is proposed employs a Stochastic Response Surface Method (SRSM) which combines in discrete steps FEA modelling, numerical simulations and analytical probabilistic assessment techniques, allowing use of commercial and custom developed specialized numerical tools. Application of the proposed methodology on a complex composite structural geometry will illustrate its efficiency and evaluate the reliability performance of the limit states derived and examined.

关键词： Composite members Stochastic Response Surface Method Tsai-Hill and Tsai-Wu Failure Criteria

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Elderly patients with non-cardiac admissions and elevated highsensitivity troponin:the prognostic value of renal function

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World Journal of Cardiology 2021年第10期13卷 566-573页

作者： Ioanna Samara Stavroula Tsiara Michail I Papafaklis Konstantinos Pappas georgios kolios Nikolaos Vryzas Lampros K Michalis Eleni T Bairaktari Christos S Katsouras Second Department of Cardiology University Hospital of IoanninaIoannina 45110Greece Second Department of Internal Medicine University Hospital of IoanninaIoannina 45110Greece Laboratory of Biochemistry University Hospital of IoanninaIoannina 45110Greece Laboratory of Clinical Chemistry School of Health SciencesFaculty of MedicineUniversity of IoanninaIoannina 45110Greece

BACKgROUND High-sensitivity cardiac troponin(hs-cTn)levels are frequently elevated in elderly patients presenting to the emergency department for non-cardiac ***,most studies on the role of elevated hs-cTn in elderly populations have investigated the prognostic value of hs-cTn in patients with a specific diagnosis or have assessed the relationship between hs-cTn and *** To investigate the in-hospital prognosis of consecutive elderly patients admitted to the Internal Medicine Department with acute non-cardiac events and increased hs-cTnI *** In this retrospective study,we selected patients who were aged≥65 years and admitted to the Internal Medicine Department of our hospital between January 2019 and December 2019 for non-cardiac *** patients were those who had hs-cTnI concentrations≥100 ng/*** investigated the independent predictors of in-hospital mortality by multivariable logistic regression *** One hundred and forty-six patients(59%female)were selected with an age range from 65 to 100(mean±SD:85.4±7.61)*** median hs-cTnI value was 284.2 ng/*** 72(49%)patients the diagnosis of hospitalization was an infectious *** overall in-hospital mortality was 32%(47 patients).Individuals who died did not have higher hs-cTnI levels compared with those who were discharged alive(median:314.8 vs 282.5 ng/L;P=0.565).There was no difference in mortality in patients with infectious vs non-infectious disease(29%vs 35%).Multivariable analysis showed that age(OR 1.062 per 1 year increase,95%CI:1.000-1.127;P=0.048)and creatinine levels(OR 2.065 per 1 mg/dL increase,95%CI:1.383-3.085;PgFRgnant condition in elderly patients admitted to the hospital for non-cardiac *** presence of severe renal impairment is a marker of extremely high in-hospital mortality.

关键词： Internal medicine High sensitivity troponin Elderly Non-cardiac admissions Renal function Prognosis

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