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Absence of Na^+/sugar cotransport activity in Barrett's metaplasia

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World Journal of Gastroenterology 2008年第9期14卷 1365-1369页

作者： Lisa J murray Owen Tully David S Rudolph marysue Whitby mary C Valenzano Giancarlo mercogliano james J Thornton james m mullin Lankenau Institute for medical Research WynnewoodPAUnited States Saint Joseph's UniversityDepartment of BiologyPhiladelphiaPA 19096United States Lankenau Hospital Department of Medicine WynnewoodPA 19096United States Lankenau Hospital Department of MedicineWynnewoodPA 19096 United States Lankenau Institute for medical Research WynnewoodPAUnited States Lankeanu Hospital Division of GastroenterologyWynnewood PA 19096United States Lankeanu Hospital Division of GastroenterologyWynnewoodPA 19096United States

AIm:To evaluate the presence of Na+-dependent, active, sugar transport in Barrett's epithelia as an intestinal biomarker, based on the well-documented, morphological intestinal phenotype of Barrett's esophagus (BE). mETHODS: We examined uptake of the nonmeta- bolizable glucose analogue, alpha-methyl-D-glucoside (AmG), a substrate for the entire sodium glucose cotransporter (SGLT) family of transport proteins. During upper endoscopy, patients with BE or with uncomplicated gastroesophageal reflux disease (GERD) allowed for duodenal, gastric fundic, and esophageal mucosal biopsies to be taken. Biopsies were incubated in bicarbonate-buffered saline (KRB) containing 0.1 mmol/L 14C-AmG for 60 min at 20℃. Characterized by abundant SGLT, duodenum served as a positive control while gastric fundus and normal esophagus, known to lack SGLT, served as negative controls. RESULTS: Duodenal biopsies accumulated 249.84 ± 35.49 (SEm) picomoles AmG/μg DNA (n = 12), gastric fundus biopsies 36.20 ± 6.62 (n = 12), normal esophagus 12.10 ± 0.59 (n = 3) and Barrett's metaplasia 29.79 ± 5.77 (n = 8). There was a statistical difference (P m duodenum and each other biopsy site but there was no statistically significant difference between normal esophagus and BE biopsies. 0.5 mmol/L phlorizin (PZ) inhibited AmG uptake into duodenal mucosa by over 89%, but had nosignificant effect on AmG uptake into gastric fundus, normal esophagus, or Barrett's tissue. In the absence of Na+ (all Na+ salts replaced by Li+ salts), AmG uptake in duodenum was decreased by over 90%, while uptake into gastric, esophageal or Barrett's tissue was statistically unaffected. CONCLUSION: Despite the intestinal enterocyte phenotype of BE, Na+-dependent, sugar transport activity is not present in these cells.

关键词： Barrett's esophagus Cancer Biomarker Sodium glucose cotransporters Glucose transport Alphamethyl-D-glucoside Phlorizin Esophagus metaplasia

Transepithelial leak in Barrett's esophagus patients: The role of proton pump inhibitors

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World Journal of Gastroenterology 2012年第22期18卷 2793-2797页

作者： Christopher Farrell melissa morgan Owen Tully Kevin Wolov Keith Kearney Benjamin Ngo Giancarlo mercogliano james J Thornton mary Carmen Valenzano james m mullin Division of Gastroenterology Lankenau Hospital Wynnewood PA 19096 United States Lankenau Institute for medical Research Wynnewood PA 19096 United States

AIm： To determine if the observed paracellular sucrose leak in Barrett＇s esophagus patients is due to their pro- ton pump inhibitor （PPI） use. mETHODS： The in vivo sucrose permeability test was administered to healthy controls, to Barrett＇s patients and to non-Barrett＇s patients on continuous PPI thera- py. Degree of leak was tested for correlation with pres- ence of Barrett＇s, use of PPIs, and length of Barrett＇s segment and duration of PPI use. RESULTS： Barrett＇s patients manifested a near 3-fold greater, upper gastrointestinal sucrose leak than healthy controls. A decrease of sucrose leak was ob- served in Barrett＇s patients who ceased PPI use for 7 *** initial introduction of PPI use （in a PPI-na＇ive population） results in dramatic increase in sucrose leak, long-term, continuous PPI use manifested a slow spon- taneous decline in leak. The sucrose leak observed in Barrett＇s patients showed no correlation to the amount of Barrett＇s tissue present in the esophagus. CONCLUSION： Although future research is needed to determine the degree of paracellular leak in actual Barrett＇s mucosa, the relatively high degree of leak ob- served with in vivo sucrose permeability measurement of Barrett＇s patients reflects their PPI use and not their Barrett＇s tissue perse.

关键词： Barrett's esophagus Sucrose Tight junc-tion Paracellular, Omeprazole Proton pump inhibitor Transepithelial

Zinc and gastrointestinal disease

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World Journal of Gastrointestinal Pathophysiology 2014年第4期5卷 496-513页

作者： Sonja Skrovanek Katherine DiGuilio Robert Bailey William Huntington Ryan Urbas Barani mayilvaganan Giancarlo mercogliano james m mullin Lankenau Institute for medical Research Lankenau Medical CenterWynnewood PA 19096 United States Division of Gastroenterology Lankenau Medical Center Wynnewood PA 19096 United States The Department of medicine Lankenau Medical Center Wynnewood PA 19096 United States

This review is a current summary of the role that both zinc deficiency and zinc supplementation can play in the etiology and therapy of a wide range of gastrointestinal diseases. The recent literature describing zinc action on gastrointestinal epithelial tight junctions and epithelial barrier function is described. Zinc enhancement of gastrointestinal epithelial barrier function may figure prominently in its potential therapeutic action in several gastrointestinal diseases.

关键词： Zinc Tight junction Nutrition Nutraceutical micronutrient

Sieving characteristics of cytokine-and peroxide-induced epithelial barrier leak:Inhibition by berberine

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World Journal of Gastrointestinal Pathophysiology 2016年第2期7卷 223-234页

作者： Katherine m DiGuilio Christina m mercogliano Jillian Born Brendan Ferraro Julie To Brittany mixson Allison Smith mary Carmen Valenzano james m mullin Lankenau Institute for medical Research Lankenau Medical Center Departments of Biology and Biomedical Engineering Drexel University

AIm: To study whether the inflammatory bowel disease (IBD) colon which exhibits varying severity and cytokine levels across its mucosa create varying types of transepithelial leak. mETHODS: We examined the effects of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-1-β (IL1β) and hydrogen peroxide (H2O2) - singly and in combinations - on barrier function of CACO-2 cell layers. Our focus was on the type (not simply the magnitude) of transepithelial leak generated by these agents as measured by transepithelial electrical resistance (TER) and transepithelial flux of 14C-D-mannitol, 3H-Lactulose and 14C-Polyethylene glycol as radiolabeled probe molecules. The isoquinoline alkaloid, berberine, was then examined for its ability to reduce specific types of transepithelial leak. RESULTS: Exposure to TNF-α alone (200 ng/mL; 48 h) induced a 50% decrease in TER, i.e., increased leak of Na+ and Cl- - with only a marginal but statistically significant increase in transepithelial leak of 14C-mannitol (Jm). Exposure to TNF-α + IFN-γ (200 ng/mL; 48 h) + IL1β (50 ng/mL; 48 h) did not increase the TER change (from TNF-α alone), but there was now a 100% increase in Jm. There however was no increase in transepithelial leak of two larger probe molecules, 3H-lactulose and 14C-polyethylene glycol (PEG). However, exposure to TNF-α + IFN-γ + IL1β followed by a 5 h exposure to 2 mmol/L H2O2 resulted in a 500% increase in 14C-PEG leak as well as leak to the luminal mitogen, epidermal growth factor. CONCLUSION: This model of graded transepithelial leak is useful in evaluating therapeutic agents reducing IBD morbidity by reducing barrier leak to various luminal substances.

关键词： Intestine Crohn’s disease Tight junction Ulcerative colitis CACO-2 Berberine micronutrient Cytokine

Probing turbulence in galaxies with fast radio burst scintillation

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Science China(Physics,mechanics & Astronomy) 2024年第1期67卷 177-178页

作者： james m.Cordes Department of Astronomy the Cornell Center for Astrophysics and Planetary ScienceCornell UniversityIthaca NY 14853USA

Interstellar scintillation(ISS)is a well-known phenomenon observed from pulsars in the milky *** comprises intensity variations *** and frequency caused by constructive and destructive interference from multipath propagation,which is due to diffraction from fluctuations in electron density in the interstellar medium(ISm)on scales as small as~100 *** density fluctuations appear to be part of a turbulence process combined with discrete structures in electron density from other astrophysical processes;together these fluctuations extend to scales of pc or larger.

关键词： scales galaxies turbulence

Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control:The pathobiology and therapeutic implications

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World Journal of Diabetes 2024年第3期15卷 311-317页

作者： Dania Blaibel Cornelius james Fernandez Joseph m Pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Endocrinology and metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(Dm)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated ***,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also *** World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et *** is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical *** editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled Dm during rapid glycaemic control.

关键词： Diabetes mellitus microvascular complications Diabetic retinopathy Treatment induced neuropathy of diabetes Diabetic nephropathy Charcot’s neuropathy

Diabetes and tuberculosis:An emerging dual threat to healthcare

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World Journal of Diabetes 2024年第7期15卷 1409-1416页

作者： Sahana Shetty Joseph m Pappachan Cornelius james Fernandez Department of Endocrinology Kasturba Medical CollegeManipalManipal Academy of Higher EducationManipal 576104KarnatakaIndia Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom

Tuberculosis(TB)remains a huge global healthcare challenge even in the 21^(st) century though the prevalence has dropped in developed countries in recent *** mellitus(Dm)is an important risk factor for the development and perpetuation of TB owing to the immune dysfunction in patients with *** coexistence of both diseases in the same individual also aggravates disease severity,complications,and chance of treatment failure because of gross immune alterations posed by Dm as well as *** complex cellular and humoral immunological factors are involved in the dangerous interaction between TB and Dm,some of which remain unknown even *** is highly important to identify the risk factors for TB in patients with Dm,and vice versa,to ensure early diagnosis and management to prevent complications from this ominous *** their research study published in the recent issue of the World Journal of Diabetes,Shi et al elaborate on the factors associated with the development of TB in a large cohort of Dm patients from *** such research output from different regions of the world is expected to improve our knowledge to fight the health devastation posed by TB in patients with diabetes.

关键词： Tuberculosis Diabetes mellitus Immune dysfunction Treatment failure multi-drug resistant tuberculosis

Diabetic cardiomyopathy:Emerging therapeutic options

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World Journal of Diabetes 2024年第8期15卷 1677-1682页

作者： Cornelius james Fernandez Sahana Shetty Joseph m Pappachan Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of Endocrinology Kasturba Medical CollegeManipal Academy of Higher EducationManipal 576104KarnatakaIndia Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

Diabetic cardiomyopathy(DbCm)is a common but underrecognized complication of patients with diabetes mellitus(Dm).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and cardiac autonomic neuropathy are mostly known with reasonable therapeutic options,the mechanisms and management options for DbCm are still not fully *** its early stages,DbCm presents with diastolic dysfunction followed by heart failure(HF)with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately *** from prompt control of Dm with lifestyle changes and antidiabetic medications,disease-modifying therapy for DbCm includes prompt control of hypertension and dyslipidemia inherent to patients with Dm as in other forms of heart diseases and the use of treatments with proven efficacy in HF.A basic study by Zhang et al,in a recent issue of the World Journal of Diabetes elaborates the potential pathophysiological alterations and the therapeutic role of teneligliptin in diabetic mouse models with *** this preliminary basic study might help to improve our understanding of DbCm and offer a potential new management option for patients with the disease,the positive results from such animal models might not always translate to clinical practice as the pathobiology of DbCm in humans could be ***,such experimental studies can encourage more scientific efforts to find a better solution to treat patients with this enigmatic disease.

关键词： Diabetic cardiomyopathy Diabetic cardiomyopathy Heart failure Pathobiology Teneligliptin

Non-pharmacological interventions for diabetic peripheral neuropathy:Are we winning the battle?

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World Journal of Diabetes 2024年第4期15卷 579-585页

作者： Dania Blaibel Cornelius james Fernandez Joseph m Pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom

Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited available in-terventions for symptom control and curtailing disease *** pharma-cologic aspect of management is mainly centred on pain control,however,there are several important aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower limb health,which pharmacotherapy does not ***,published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy,to reach a desired,however modest *** is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain *** their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters,Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment *** previous studies also support these findings,larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are ***,given the satisfactory safety profile and the positive results found in these studies,it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.

关键词： Diabetic peripheral neuropathy Diabetes mellitus Pharmacotherapy Acupuncture Neuropathic pain Nonpharmacological intervention