Background and aims: Ulcerative colitis (UC) is characterised by refractory in flammatory ulceration and damage to the colon.The mechanisms underlying impaired healing have yet to be defined. As transglutaminase expre...Background and aims: Ulcerative colitis (UC) is characterised by refractory in flammatory ulceration and damage to the colon.The mechanisms underlying impaired healing have yet to be defined. As transglutaminase expression resulting in mat rix protein cross linking is associated with increased wound healing in a rat mo del of colitis, we hypothesised that different types of transglutaminase might a lso play a role in UC. Patients end methods: Endoscopic and histological indices were studied in 26 patients with UC (10 active and 16 inactive) and in 20 norma l controls undergoing colonoscopy. Transglutaminase activity was evaluated in pl asma (factor XIIIa) by a radioenzymatic metho- d. Factor XIIIa, tissue and keratinocyte transglutaminase protein content, and mRNA expression in the colon were evaluated by western blot analysis and semiqu antitative reverse transcription-polymerase chain reaction (RT-PCR),respectively. Colon ic location of transglutaminases and their reaction products, the -(γ-glutamy l)lysine bonds, was evaluated by immunohistochemistry using specific monoclonal antibodies.Results: Transglutaminase activity was significantly lower in the pla sma of patients with active UC (4.2 (2.4) mU/ml;p< 0.05 v controls) than in thos e with inactive UC and controls(10.6 (2.2) and 12.1 (1.7) mU/ml). As shown by we stern blot,protein levels of tissue transglutaminase and factor XIIIa were uncha nged in active UC compared with inactive disease and controls, while the keratin ocyte form was reduced in active UC. Tissue transglutaminase and factor XIIIa im munostaining was strongly present in damaged areas colocalising with isopeptide bonds. In contrast, the keratinocyte form was almost absent in active UC and loc alised in the upper part of the crypts in normal subjects. RT-PCR showed upregu lation of tissue transglutaminase mRNA in active UC (320%compared with controls ) while keratinocyte transglutaminase gene expression was downregulated in activ e UC. Conclusions: The results of the present study support the concept that, in the damaged colon,transglutaminases are needed in response to chronic injury an d underline the key role of these enzymes in mucosal healing.展开更多
Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sam...Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.展开更多
Aim To investigate the effect in berberine chloride (BER) on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium (DSS) solution or distil...Aim To investigate the effect in berberine chloride (BER) on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium (DSS) solution or distilled water freely with different doses of BER (15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1) or sallcylazosulfapyridine (SASP, 520 mg·kg^-1), and solvent (0. 2 mL/10 mg Wt) once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index (DAI). Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and malondialdehyde (MDA) content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 ( ICAM-1 ) proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.展开更多
A useful helicobacter pylori-induced gastritis model using BALB/c mice was established for mimicking of human gastritis induced by Helicobacter pylori (H. pylori). The H. pylori isolates were obtained freshly from a...A useful helicobacter pylori-induced gastritis model using BALB/c mice was established for mimicking of human gastritis induced by Helicobacter pylori (H. pylori). The H. pylori isolates were obtained freshly from a human complex ulcer patient. BALB/c mice were fasted for 24 h and then 0.25 mL of 0.2 mol·L -1 NaHCO 3 was administered after by gavage to each mouse and 0.5 mL of 10 9 colonies formation unit per milliliter (CFU/mL) of H. pylori was administered 15 min. On the 3 rd day and 5 th day, the H. pylori inoculations were repeated. The inoculated mice were sacrificed in batch on the 5 th day, in the 2 nd week, 3 rd week and 4 th week. The gastric mucous membrane near pyloric portion was removed, treated and then cultured under microaerobic condition for detection of H.pylori. The remainders of the gastric membrane were fixed by 10% formaldehyde solution for pathological detection. The results showed that the H. pylori could be separated from the gastric membranes of inoculated mice. Obvious invasion of inflammatory cells in the gastric membranes of inoculated mice could be observed from pathological sections. It can be concluded that the inoculating fresh human H. pylori isolates can produce mouse gastritis. This model of BALB/c mice can be used for evaluating the therapeutic agents for the treatment of gastritis induced by H. pylori.展开更多
AIMS To study the relationship between the modern clinical and pathohistological classification and TCM Syndrome-Typing of chronic ulcerative colitis (CUC). METHODS Totally 452 patients with CUC were clas- sified acco...AIMS To study the relationship between the modern clinical and pathohistological classification and TCM Syndrome-Typing of chronic ulcerative colitis (CUC). METHODS Totally 452 patients with CUC were clas- sified according to the standards of TCM Syndrome- Typing set up in the Conference of the Combination of the Chinese-Western Medicine on Digestive Diseases in Linfen. The relevant changes between both classifica- tions were analyzed and compared through the colonofiberscopic and pathohistological examination. RESULTS The type of retention of damp-heat in inte- rior is more commonly seen in the patients with initial onset of disease (P<0.01). There is no significant difference among other TCM Syndrome-Typing groups in patients with chronic persistent and recurrent disease (P>0.05). The congestion,edema,reduction of goblet cells and the infiltration of neutrophils are patho- logically common to all TCM Syndrome-Typing groups. Mucosal ulcer is dominant in damp-heat syndrome while crypt ulcer is dominant in the types of spleen-stomach asthenia and spleen-kidney Yang deficiency (P< 0.01). CONCLUSIONS There appears a certain relation- ship between the TCM syndrome typing and pathohis- tological changes of the colonal mucosa of CUC.展开更多
AIMS The relationship between Helicobacter pylori (Hp) and gastric epithelia in chronic gastritis and in petic ulcer was studied by transmission electron mi- croscopy (TEM). METHODS Seventy-five gastric antral biopsy ...AIMS The relationship between Helicobacter pylori (Hp) and gastric epithelia in chronic gastritis and in petic ulcer was studied by transmission electron mi- croscopy (TEM). METHODS Seventy-five gastric antral biopsy speci- mens from the patients examined by six other methods for Hp were fixed in glutaraldehyde and treated with tanin acid before OsO_4 staining than routinely prooessed for TEM studies (at least 4 semi- thin sections oriented for ultrathin sections in each sample). RESULTS The bacilli were detected by TEM within gastric mucosa in 53 of 55 patients infected with Hp. Ultrathin sections especially stained with tanin acid re- vealed clearly glycocalyx by which the bacillus was connected with the epithelium. As the bacilli grouped as colony and breed,the adjacent mucous cells degerated and characterized by erosion of the juxtalu- minal cytoplasm,vacuolation or blebs,even desqua- mation of cell. Evidence was accumulated to show that the baoilli were located in the lumen attracted neu- trophils which intended to migrate into intercellular space of epithelia or into the lumen to exert the effect of Hp phagocytosis. CONCLUSIONS The sensitivity and specificity of Hp diagnosis by TEM is respectively 96% and 95%. Tanin acid is suitable for the preservation of glycocalyx of cell. The colonized bacilli,usually with the wide periplasmic pools,contributed to the spectrum degen- eration of epithelia,including mucous neck cells. If Hp infection persists,the degeneration and regeneration of mucous neck cells alternatively carried on and ultimate- ly the generative stem cells were damaged,as the result,the chronic atrophy gastritis could occure.展开更多
Introduction. We report on a patient who progressively developed polymorphic expressions of neutrophilic dermatosis (Sneddon- Wilkinson subcorneal pustulosis and pyoderma gangrenosum) associated with p-antineutrophil ...Introduction. We report on a patient who progressively developed polymorphic expressions of neutrophilic dermatosis (Sneddon- Wilkinson subcorneal pustulosis and pyoderma gangrenosum) associated with p-antineutrophil cytoplasmic antibodies (p-ANCA), while receiving propylthiouracil for hyperthyroidism. To our knowledge, such associations have never been published so far. Case- report. A 40 year-old woman was treated with propylthiouracil for Graves’disease. After 16 months of therapy, she noted flares of pustular lesions surrounded with erythematous halo mainly localized on the trunk. The lesions became chronic, and were not improved by potent topical corticosteroids. When first seen in our department in February 2003, the eruption was typical of Sneddon-Wilkinson subcorneal pustulosis. This diagnosis was confirmed by the histological examination of a skin biopsy of a pustule. One month later, she developed an inflammatory progressively ulcerative lesion on the right ankle, typical of pyoderma gangrenosum. The diagnosis was confirmed by the histological examination of a skin biopsy taken on the evolving border of the lesion and showed polynuclear neutrophilic infiltration without vasculitis. Direct immunofluorescence was negative. The presence of serum anti-myeloperoxydase p-ANCA was known for this patient since October 2002. No IgA monoclonal gammapathy was revealed on extensive biological check-up. Systemic oral corticosteroid therapy (1 mg/kg/day) dramatically improved skin lesions with complete healing within 8 weeks. Discussion. Propylthiouracil is well known to induce the occurrence of ANCA in 20 to 64p. 100 of patients treated for Graves’disease. The mechanisms involved are badly recognized so far. Cutaneous vasculitis, glomerulonephritis and polychondritis may be clinically associated with those antibodies. Rare observations of neutrophilic dermatosis, mostly Sweet’ s syndrome, have been described in patients with propylthiouracil- induced ANCA. One case-report described a 44 year-old woman who developed pyoderma gangrenosum associated with propylthiouracil-inducedp- ANCA.These manifestations usually appear within 2 years, as our patient. The data in the literature,allows us to report the polymorphic expressions of neutrophilic dermatosis in this patient with p-ANCA which could be related to propylthiouracil. Such association of Sneddon-Wilkinson subcorneal pustulosis and pyoderma gangrenosum with p- ANCA has never been described in this endocrinologic context so far. Furthermore we propose that neutrophilic dermatosis should be inscribed in the list of side effects induced by propylthiouracil therapy.展开更多
Ulcerative colitis (UC) and Crohn's disease (CD) are the major forms of idiopathic inflammatory bowel disease (IBD). Both UC and CD are debilitating chronic disorders that afflict millions of individuals throug...Ulcerative colitis (UC) and Crohn's disease (CD) are the major forms of idiopathic inflammatory bowel disease (IBD). Both UC and CD are debilitating chronic disorders that afflict millions of individuals throughout the world with symptoms which impair function and quality of life. The etiology of IBD is inadequately understood and therefore, drug therapy has been empirical instead of being based on sound understanding of IBD pathogenesis. This is a major factor for poor drug efficacy and drug related side effects that often add to the disease complexity. The development of biologicals notably infliximab to intercept tumor necrosis factor (TNF)-α reflects some progress, albeit major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF-α, interleukin (IL)-Iβ, IL-6 and IL-8 for which activated peripheral granulocytes and monocytes/macrophages (GH) are major sources. Further, in IBD, peripheral GHs are elevated with activation behavior, increased survival time and are found in vast numbers within the inflamed intestinal mucosa; they are suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral blood GMs should be appropriate targets of therapy. The Adacolumn is a medical device developed for selective depletion of GH by receptor-mediated adsorption (GHA). Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid nai've patients (the best responders), GHA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GHA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety and short disease duration appear good predictors of response to GMA and based on the available data, GMA seems to have an excellent safety profile.展开更多
Underweight and specific nutrient deficiencies are frequent in adult patients with inflammatory bowel disease(IBD).In addition,a significant number of children with IBD,especially Crohn's disease(CD) have impaired...Underweight and specific nutrient deficiencies are frequent in adult patients with inflammatory bowel disease(IBD).In addition,a significant number of children with IBD,especially Crohn's disease(CD) have impaired linear growth.Nutrition has an important role in the management of IBD.In adults with CD,enteral nutrition(EN) is effective in inducing clinical remission of IBD,although it is less efficient than corticosteroids.Exclusive EN is an established primary therapy for pediatric CD.Limited data suggests that EN is as efficient as corticosteroids for induction of remission.Additional advantages of nutritional therapy are control of inflammation,mucosal healing,positive benefits to growth and overall nutritional status with minimal adverse effects.The available evidence suggests that supplementary EN may be effective also for maintenance of remission in CD.More studies are needed to confirm these findings.However,EN supplementation could be considered as an alternative or as an adjunct to maintenance drug therapy in CD.EN does not have a primary therapeutic role in ulcerative colitis.Specific compositions of enteral dietselemental diets or diets containing specific components-were not shown to have any advantage over standard polymeric diets and their place in the treatment of CD or UC need further evaluation.Recent theories suggest that diet may be implicated in the etiology of IBD,however there are no proven dietary approaches to reduce the risk of developing IBD.展开更多
Smoking is an important environmental factor in inflammatory bowel disease (IBD) with differing effects in ulcerative colitis (UC) and Crohn's disease (CD). Never smoking and formerly smoking increase the risk ...Smoking is an important environmental factor in inflammatory bowel disease (IBD) with differing effects in ulcerative colitis (UC) and Crohn's disease (CD). Never smoking and formerly smoking increase the risk of UC, whereas smoking exacerbates the course of CD. The potential mechanisms involved in this dual relationship are yet unknown. A reasonable assumption is that smoking has different effects on the small and large intestine. This assumption is based on animal and human studies that show that the effects of smoking/nicotine on CD and UC depend on the site of inflammation and not on the type of disease.展开更多
AIM: To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS: Mongolian ge...AIM: To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS: Mongolian gerbils were infected with wild type (WT) H pylori type Ⅰ strain B128 or its isogenic mutant B128 △cag γ (defective type Ⅳ secretion). After seven months of infection, H pylori was reisolated from antrum and corpus and Hpylori DNA was analyzed by seminested polymerase chain reaction (PCR). Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined. RESULTS: The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno-histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals andthose developing transmural inflammation and pancreatitis were significantly increased. Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas CONCLUSION: H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.展开更多
AIM: To investigate the role of gastric mucosa at the secretion of sTREM-1 in peptic ulcer.METHODS: Seventy two patients were enrolled; 35 with duodenal, 22 with gastric ulcer and 26 with chronic gastritis. Patients...AIM: To investigate the role of gastric mucosa at the secretion of sTREM-1 in peptic ulcer.METHODS: Seventy two patients were enrolled; 35 with duodenal, 22 with gastric ulcer and 26 with chronic gastritis. Patients were endoscoped and gastric juice was aspirated. Patients with duodenal and gastric ulcer underwent a second endoscopy post-treatment. Biopsies were incubated in the absence/presence of endotoxins or gastric juice. Supernatants were collected and sTREM-2 and TNF~ were measured by enzyme immunoabsorbent assays. Scoring of gastritis was performed before and after treatment according to updated Sydney score.RESULTS: Patients with duodenal and gastric ulcer and those with chronic gastritis had similar scores of gastritis, sTREM-1 was higher in supernatants of tissue samples of H pylori-positive than of H pylori-negative patients with gastric ulcer. Median (± SE) sTREM-1 was found increased in supernatants of patients with gastric ulcer before treatment (203.21 ± 88.91 pg/1000 cells) compared to supernatants either from the same patients post-treatment (8.23 ± 5.79 pg/1000 cells) or from patients with chronic gastritis (6.21 ± 0.71 pg/1000 cells) (P 〈 0.001 and 〈 0.001, respectively). Similar differences for sTREM-1 were recorded among LPS-stimulated tissue samples of patients (P = 0.001). Similar differences were not found for TNFα. Positive correlations were found between sTREM-1 of supernatants from patients with both duodenal and gastric ulcer before treatment and the degree of infiltration of neutrophils and monocytes.CONCLUSION: sTREM-1 secreted by the gastric mucosa is an independent mechanism connected to the pathogenesis of peptic ulcer, sTREM-1 was released at the presence of H pylori from the inflamed gastric mucosa in the field of gastric ulcer.展开更多
AIM:To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa:i.e.those with Helicobacter pylori(H pylori)gastritis or atrophic gastritis,who have a high ris...AIM:To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa:i.e.those with Helicobacter pylori(H pylori)gastritis or atrophic gastritis,who have a high risk of gastric cancer or peptic ulcer diseases.METHODS:Among 162 Japanese outpatients,pepsinogen-(Pg-)and(Pg)were measured using a conventional Japanese technique,and the European GastroPanel examination(Pg and Pg,gastrin-17 and H pylori antibodies).Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa,H pylori non-atrophic gastritis or atrophic gastritis.RESULTS:Pg-and Pg assays with the GastroPanel and the Japanese method showed a highly significant correlation.For methodological reasons,however,serum Pg-,but not Pg,was twice as high with the GastroPanel test as with the Japanese test.The biomarker assays revealed that 5%of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies.GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis.When compared to the endoscopic biopsy findings,the GastroPanel examination classified the patients into groups with "healthy" or "diseased" stomach mucosa with 94% accuracy,95% sensitivity and 93% specifi city.CONCLUSION:Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.展开更多
文摘Background and aims: Ulcerative colitis (UC) is characterised by refractory in flammatory ulceration and damage to the colon.The mechanisms underlying impaired healing have yet to be defined. As transglutaminase expression resulting in mat rix protein cross linking is associated with increased wound healing in a rat mo del of colitis, we hypothesised that different types of transglutaminase might a lso play a role in UC. Patients end methods: Endoscopic and histological indices were studied in 26 patients with UC (10 active and 16 inactive) and in 20 norma l controls undergoing colonoscopy. Transglutaminase activity was evaluated in pl asma (factor XIIIa) by a radioenzymatic metho- d. Factor XIIIa, tissue and keratinocyte transglutaminase protein content, and mRNA expression in the colon were evaluated by western blot analysis and semiqu antitative reverse transcription-polymerase chain reaction (RT-PCR),respectively. Colon ic location of transglutaminases and their reaction products, the -(γ-glutamy l)lysine bonds, was evaluated by immunohistochemistry using specific monoclonal antibodies.Results: Transglutaminase activity was significantly lower in the pla sma of patients with active UC (4.2 (2.4) mU/ml;p< 0.05 v controls) than in thos e with inactive UC and controls(10.6 (2.2) and 12.1 (1.7) mU/ml). As shown by we stern blot,protein levels of tissue transglutaminase and factor XIIIa were uncha nged in active UC compared with inactive disease and controls, while the keratin ocyte form was reduced in active UC. Tissue transglutaminase and factor XIIIa im munostaining was strongly present in damaged areas colocalising with isopeptide bonds. In contrast, the keratinocyte form was almost absent in active UC and loc alised in the upper part of the crypts in normal subjects. RT-PCR showed upregu lation of tissue transglutaminase mRNA in active UC (320%compared with controls ) while keratinocyte transglutaminase gene expression was downregulated in activ e UC. Conclusions: The results of the present study support the concept that, in the damaged colon,transglutaminases are needed in response to chronic injury an d underline the key role of these enzymes in mucosal healing.
基金This work was supported by the National Natural Science Foundation (82273506,82273508)the Hunan Provincial Health Commission Scientific Research Plan Project (D202304128334),China。
文摘Objective:The causal relationship between eczema and autoimmune diseases has not been previously reported.This study aims to evaluate the causal relationship between eczema and autoimmune diseases.Methods:The two‐sample Mendelian randomization(MR)method was used to assess the causal effect of eczema on autoimmune diseases.Summary data from the Genome-Wide Association Study Catalog(GWAS)were obtained from the Integrative Epidemiology Unit(IEU)database.For eczema and autoimmune diseases,genetic instrument variants(GIVs)were identified according to the significant difference(P<5×10−8).Causal effect estimates were generated using the inverse‐variance weighted(IVW)method.MR Egger,maximum likelihood,MR-PRESSO,and MR-RAPS methods were used for alternative analyses.Sensitivity tests,including heterogeneity,horizontal pleiotropy,and leave-one-out analyses,were performed.Finally,reverse causality was assessed.Results:Genetic susceptibility to eczema was associated with an increased risk of Crohn’s disease(OR=1.444,95%CI 1.199 to 1.738,P<0.001)and ulcerative colitis(OR=1.002,95%CI 1.001 to 1.003,P=0.002).However,no causal relationship was found for the other 6 autoimmune diseases,including systemic lupus erythematosus(SLE)(OR=0.932,P=0.401),bullous pemphigoid(BP)(OR=1.191,P=0.642),vitiligo(OR=1.000,P=0.327),multiple sclerosis(MS)(OR=1.000,P=0.965),ankylosing spondylitis(AS)(OR=1.001,P=0.121),rheumatoid arthritis(RA)(OR=1.000,P=0.460).Additionally,no reverse causal relationship was found between autoimmune diseases and eczema.Conclusion:Eczema is associated with an increased risk of Crohn’s disease and ulcerative colitis.No causal relationship is found between eczema and SLE,MS,AS,RA,BP,or vitiligo.
基金AProject of the Health Bureau of Chongqing (No.2004-B-31)
文摘Aim To investigate the effect in berberine chloride (BER) on experimental ulcerative colitis in mice. Methods BALB/C mice in 6 groups were allowed to drink either 4% dextran sulfate sodium (DSS) solution or distilled water freely with different doses of BER (15 mg·kg^-1, 45 mg·kg^-1, 150 mg·kg^-1) or sallcylazosulfapyridine (SASP, 520 mg·kg^-1), and solvent (0. 2 mL/10 mg Wt) once a day for 7 d, respectively. The symptom of ulcerative colitis was evaluated by disease activity index (DAI). Myeloperoxidase (MPO) and superoxide dismutase (SOD) activities and malondialdehyde (MDA) content were determined by HE staining and immunohistochemistry of expressions of NF-κB p65 and intercellular adhesion molecule 1 ( ICAM-1 ) proteins to observe the damage to colon tissues and possible mechanisms. Results DAI, MPO activity, MDA content and expressions of ICAM-1 and NF-κB p65 were markedly increased, while SOD activity decreased in DSS-treated mice. Treatment of mice with different doses of BER or SASP significantly decreased DAI, MPO activity and MDA content, improved histological changes of colon tissues, blunted the expressions of NF-κB p65 and ICAM-1 proteins, and enhanced SOD activity. Conclusion Berberine chloride has excellent therapeutic effect on ulcerative colitis caused by DSS in mice. The possible mechanism may be related to its antioxidant and anti-inflammatory activities associated with inhibiting the NF-κB activation and ICAM-1 expression.
文摘A useful helicobacter pylori-induced gastritis model using BALB/c mice was established for mimicking of human gastritis induced by Helicobacter pylori (H. pylori). The H. pylori isolates were obtained freshly from a human complex ulcer patient. BALB/c mice were fasted for 24 h and then 0.25 mL of 0.2 mol·L -1 NaHCO 3 was administered after by gavage to each mouse and 0.5 mL of 10 9 colonies formation unit per milliliter (CFU/mL) of H. pylori was administered 15 min. On the 3 rd day and 5 th day, the H. pylori inoculations were repeated. The inoculated mice were sacrificed in batch on the 5 th day, in the 2 nd week, 3 rd week and 4 th week. The gastric mucous membrane near pyloric portion was removed, treated and then cultured under microaerobic condition for detection of H.pylori. The remainders of the gastric membrane were fixed by 10% formaldehyde solution for pathological detection. The results showed that the H. pylori could be separated from the gastric membranes of inoculated mice. Obvious invasion of inflammatory cells in the gastric membranes of inoculated mice could be observed from pathological sections. It can be concluded that the inoculating fresh human H. pylori isolates can produce mouse gastritis. This model of BALB/c mice can be used for evaluating the therapeutic agents for the treatment of gastritis induced by H. pylori.
文摘AIMS To study the relationship between the modern clinical and pathohistological classification and TCM Syndrome-Typing of chronic ulcerative colitis (CUC). METHODS Totally 452 patients with CUC were clas- sified according to the standards of TCM Syndrome- Typing set up in the Conference of the Combination of the Chinese-Western Medicine on Digestive Diseases in Linfen. The relevant changes between both classifica- tions were analyzed and compared through the colonofiberscopic and pathohistological examination. RESULTS The type of retention of damp-heat in inte- rior is more commonly seen in the patients with initial onset of disease (P<0.01). There is no significant difference among other TCM Syndrome-Typing groups in patients with chronic persistent and recurrent disease (P>0.05). The congestion,edema,reduction of goblet cells and the infiltration of neutrophils are patho- logically common to all TCM Syndrome-Typing groups. Mucosal ulcer is dominant in damp-heat syndrome while crypt ulcer is dominant in the types of spleen-stomach asthenia and spleen-kidney Yang deficiency (P< 0.01). CONCLUSIONS There appears a certain relation- ship between the TCM syndrome typing and pathohis- tological changes of the colonal mucosa of CUC.
基金Supported by Science Foundation of Xiamen.No.95801.
文摘AIMS The relationship between Helicobacter pylori (Hp) and gastric epithelia in chronic gastritis and in petic ulcer was studied by transmission electron mi- croscopy (TEM). METHODS Seventy-five gastric antral biopsy speci- mens from the patients examined by six other methods for Hp were fixed in glutaraldehyde and treated with tanin acid before OsO_4 staining than routinely prooessed for TEM studies (at least 4 semi- thin sections oriented for ultrathin sections in each sample). RESULTS The bacilli were detected by TEM within gastric mucosa in 53 of 55 patients infected with Hp. Ultrathin sections especially stained with tanin acid re- vealed clearly glycocalyx by which the bacillus was connected with the epithelium. As the bacilli grouped as colony and breed,the adjacent mucous cells degerated and characterized by erosion of the juxtalu- minal cytoplasm,vacuolation or blebs,even desqua- mation of cell. Evidence was accumulated to show that the baoilli were located in the lumen attracted neu- trophils which intended to migrate into intercellular space of epithelia or into the lumen to exert the effect of Hp phagocytosis. CONCLUSIONS The sensitivity and specificity of Hp diagnosis by TEM is respectively 96% and 95%. Tanin acid is suitable for the preservation of glycocalyx of cell. The colonized bacilli,usually with the wide periplasmic pools,contributed to the spectrum degen- eration of epithelia,including mucous neck cells. If Hp infection persists,the degeneration and regeneration of mucous neck cells alternatively carried on and ultimate- ly the generative stem cells were damaged,as the result,the chronic atrophy gastritis could occure.
文摘Introduction. We report on a patient who progressively developed polymorphic expressions of neutrophilic dermatosis (Sneddon- Wilkinson subcorneal pustulosis and pyoderma gangrenosum) associated with p-antineutrophil cytoplasmic antibodies (p-ANCA), while receiving propylthiouracil for hyperthyroidism. To our knowledge, such associations have never been published so far. Case- report. A 40 year-old woman was treated with propylthiouracil for Graves’disease. After 16 months of therapy, she noted flares of pustular lesions surrounded with erythematous halo mainly localized on the trunk. The lesions became chronic, and were not improved by potent topical corticosteroids. When first seen in our department in February 2003, the eruption was typical of Sneddon-Wilkinson subcorneal pustulosis. This diagnosis was confirmed by the histological examination of a skin biopsy of a pustule. One month later, she developed an inflammatory progressively ulcerative lesion on the right ankle, typical of pyoderma gangrenosum. The diagnosis was confirmed by the histological examination of a skin biopsy taken on the evolving border of the lesion and showed polynuclear neutrophilic infiltration without vasculitis. Direct immunofluorescence was negative. The presence of serum anti-myeloperoxydase p-ANCA was known for this patient since October 2002. No IgA monoclonal gammapathy was revealed on extensive biological check-up. Systemic oral corticosteroid therapy (1 mg/kg/day) dramatically improved skin lesions with complete healing within 8 weeks. Discussion. Propylthiouracil is well known to induce the occurrence of ANCA in 20 to 64p. 100 of patients treated for Graves’disease. The mechanisms involved are badly recognized so far. Cutaneous vasculitis, glomerulonephritis and polychondritis may be clinically associated with those antibodies. Rare observations of neutrophilic dermatosis, mostly Sweet’ s syndrome, have been described in patients with propylthiouracil- induced ANCA. One case-report described a 44 year-old woman who developed pyoderma gangrenosum associated with propylthiouracil-inducedp- ANCA.These manifestations usually appear within 2 years, as our patient. The data in the literature,allows us to report the polymorphic expressions of neutrophilic dermatosis in this patient with p-ANCA which could be related to propylthiouracil. Such association of Sneddon-Wilkinson subcorneal pustulosis and pyoderma gangrenosum with p- ANCA has never been described in this endocrinologic context so far. Furthermore we propose that neutrophilic dermatosis should be inscribed in the list of side effects induced by propylthiouracil therapy.
文摘Ulcerative colitis (UC) and Crohn's disease (CD) are the major forms of idiopathic inflammatory bowel disease (IBD). Both UC and CD are debilitating chronic disorders that afflict millions of individuals throughout the world with symptoms which impair function and quality of life. The etiology of IBD is inadequately understood and therefore, drug therapy has been empirical instead of being based on sound understanding of IBD pathogenesis. This is a major factor for poor drug efficacy and drug related side effects that often add to the disease complexity. The development of biologicals notably infliximab to intercept tumor necrosis factor (TNF)-α reflects some progress, albeit major concern about their side effects and lack of long-term safety and efficacy profiles. However, IBD seems to be perpetuated by inflammatory cytokines like TNF-α, interleukin (IL)-Iβ, IL-6 and IL-8 for which activated peripheral granulocytes and monocytes/macrophages (GH) are major sources. Further, in IBD, peripheral GHs are elevated with activation behavior, increased survival time and are found in vast numbers within the inflamed intestinal mucosa; they are suspected to be major factors in the immunopathogenesis of IBD. Hence, peripheral blood GMs should be appropriate targets of therapy. The Adacolumn is a medical device developed for selective depletion of GH by receptor-mediated adsorption (GHA). Clinical data show GMA, in patients with steroid dependent or steroid refractory UC, is associated with up to 85% efficacy and tapering or discontinuation of steroids, while in steroid nai've patients (the best responders), GHA spares patients from exposure to steroids. Likewise, GMA at appropriate intervals in patients at a high risk of clinical relapse suppresses relapse thus sparing the patients from the morbidity associated with IBD relapse. Further, GHA appears to reduce the number of patients being submitted to colectomy or exposure to unsafe immunosupressants. First UC episode, steroid naivety and short disease duration appear good predictors of response to GMA and based on the available data, GMA seems to have an excellent safety profile.
文摘Underweight and specific nutrient deficiencies are frequent in adult patients with inflammatory bowel disease(IBD).In addition,a significant number of children with IBD,especially Crohn's disease(CD) have impaired linear growth.Nutrition has an important role in the management of IBD.In adults with CD,enteral nutrition(EN) is effective in inducing clinical remission of IBD,although it is less efficient than corticosteroids.Exclusive EN is an established primary therapy for pediatric CD.Limited data suggests that EN is as efficient as corticosteroids for induction of remission.Additional advantages of nutritional therapy are control of inflammation,mucosal healing,positive benefits to growth and overall nutritional status with minimal adverse effects.The available evidence suggests that supplementary EN may be effective also for maintenance of remission in CD.More studies are needed to confirm these findings.However,EN supplementation could be considered as an alternative or as an adjunct to maintenance drug therapy in CD.EN does not have a primary therapeutic role in ulcerative colitis.Specific compositions of enteral dietselemental diets or diets containing specific components-were not shown to have any advantage over standard polymeric diets and their place in the treatment of CD or UC need further evaluation.Recent theories suggest that diet may be implicated in the etiology of IBD,however there are no proven dietary approaches to reduce the risk of developing IBD.
文摘Smoking is an important environmental factor in inflammatory bowel disease (IBD) with differing effects in ulcerative colitis (UC) and Crohn's disease (CD). Never smoking and formerly smoking increase the risk of UC, whereas smoking exacerbates the course of CD. The potential mechanisms involved in this dual relationship are yet unknown. A reasonable assumption is that smoking has different effects on the small and large intestine. This assumption is based on animal and human studies that show that the effects of smoking/nicotine on CD and UC depend on the site of inflammation and not on the type of disease.
基金Supported by grants from the Deutsche Forschungsgemeinschaft (SFB576) to RH and (RI 972/3-1) to GRthe Federal Ministry of Education and Research (BMBF) (NGFN-2) to RHby US Public Health Service Grants P01 DK062041 and R01DK45729 to JLM
文摘AIM: To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS: Mongolian gerbils were infected with wild type (WT) H pylori type Ⅰ strain B128 or its isogenic mutant B128 △cag γ (defective type Ⅳ secretion). After seven months of infection, H pylori was reisolated from antrum and corpus and Hpylori DNA was analyzed by seminested polymerase chain reaction (PCR). Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined. RESULTS: The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno-histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals andthose developing transmural inflammation and pancreatitis were significantly increased. Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas CONCLUSION: H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.
文摘AIM: To investigate the role of gastric mucosa at the secretion of sTREM-1 in peptic ulcer.METHODS: Seventy two patients were enrolled; 35 with duodenal, 22 with gastric ulcer and 26 with chronic gastritis. Patients were endoscoped and gastric juice was aspirated. Patients with duodenal and gastric ulcer underwent a second endoscopy post-treatment. Biopsies were incubated in the absence/presence of endotoxins or gastric juice. Supernatants were collected and sTREM-2 and TNF~ were measured by enzyme immunoabsorbent assays. Scoring of gastritis was performed before and after treatment according to updated Sydney score.RESULTS: Patients with duodenal and gastric ulcer and those with chronic gastritis had similar scores of gastritis, sTREM-1 was higher in supernatants of tissue samples of H pylori-positive than of H pylori-negative patients with gastric ulcer. Median (± SE) sTREM-1 was found increased in supernatants of patients with gastric ulcer before treatment (203.21 ± 88.91 pg/1000 cells) compared to supernatants either from the same patients post-treatment (8.23 ± 5.79 pg/1000 cells) or from patients with chronic gastritis (6.21 ± 0.71 pg/1000 cells) (P 〈 0.001 and 〈 0.001, respectively). Similar differences for sTREM-1 were recorded among LPS-stimulated tissue samples of patients (P = 0.001). Similar differences were not found for TNFα. Positive correlations were found between sTREM-1 of supernatants from patients with both duodenal and gastric ulcer before treatment and the degree of infiltration of neutrophils and monocytes.CONCLUSION: sTREM-1 secreted by the gastric mucosa is an independent mechanism connected to the pathogenesis of peptic ulcer, sTREM-1 was released at the presence of H pylori from the inflamed gastric mucosa in the field of gastric ulcer.
文摘AIM:To study the value of serum biomarker tests to differentiate between patients with healthy or diseased stomach mucosa:i.e.those with Helicobacter pylori(H pylori)gastritis or atrophic gastritis,who have a high risk of gastric cancer or peptic ulcer diseases.METHODS:Among 162 Japanese outpatients,pepsinogen-(Pg-)and(Pg)were measured using a conventional Japanese technique,and the European GastroPanel examination(Pg and Pg,gastrin-17 and H pylori antibodies).Gastroscopy with gastric biopsies was performed to classify the patients into those with healthy stomach mucosa,H pylori non-atrophic gastritis or atrophic gastritis.RESULTS:Pg-and Pg assays with the GastroPanel and the Japanese method showed a highly significant correlation.For methodological reasons,however,serum Pg-,but not Pg,was twice as high with the GastroPanel test as with the Japanese test.The biomarker assays revealed that 5%of subjects had advanced atrophic corpus gastritis which was also verified by endoscopic biopsies.GastroPanel examination revealed an additional seven patients who had either advanced atrophic gastritis limited to the antrum or antrum-predominant H pylori gastritis.When compared to the endoscopic biopsy findings,the GastroPanel examination classified the patients into groups with "healthy" or "diseased" stomach mucosa with 94% accuracy,95% sensitivity and 93% specifi city.CONCLUSION:Serum biomarker tests can be used to differentiate between subjects with healthy and diseased gastric mucosa with high accuracy.