Inflammatory bowel disease (IBD) is traditionally con- sidered to be common in the Western world, and its incidence has sharply increased since the early 1950s. In contrast, until the last decade, low prevalence and i...Inflammatory bowel disease (IBD) is traditionally con- sidered to be common in the Western world, and its incidence has sharply increased since the early 1950s. In contrast, until the last decade, low prevalence and incidence rates have been reported from other parts of the world including Eastern Europe, South America, Asia and the Pacific region. Recent trends indicate a change in the epidemiology of IBD with previously low incidence areas now reporting a progressive rise in the incidence, while in West European and North American countries the figures have stabilized or slightly increased, with decreasing incidence rates for ulcerative colitis. Some of these changes may represent differences in diagnostic practices and increasing awareness of the disease. The quality of studies is also variable. Additional epidemio- logic studies are needed to better define the burden of illness, explore the mechanism of association with envi- ronmental factors, and identify new risk factors.展开更多
AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccin/um oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis. METHODS: ...AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccin/um oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis. METHODS: Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4% Evans blue passage after i.p. injection of 0.05 mol/L acetic acid. RESULTS: In the mice treated with OP, colonic macroscopic scores (1.1 ± 0.4 vs 2.7, P 〈 0.01) and the total square area of damage (10 ± 2 vs 21 ± 7, P 〈 0.01) were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42 ± 11 vs 112 ± 40, P 〈 0.01) and enhance the amount of mucus of colitis mice (0.9 ± 0.1 vs 0.4 ± 0.1, P 〈 0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6 ± 0.7 vs 5.1 ± 0.8, P 〈 0.01). OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161 ± 34 vs 241 ± 21, P 〈 0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141 ± 50 vs 235 ± 37, P 〈 0.05). CONCLUSION: Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP, on acetic acid-induced colitis in mice was detected. A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.展开更多
AIM: To investigate whether microproteinuria in patients with inflammatory bowel disease (IBD) is associated with the disease activity or the treatment with 5-aminosalicylic acid (5-ASA). METHODS: We prospective...AIM: To investigate whether microproteinuria in patients with inflammatory bowel disease (IBD) is associated with the disease activity or the treatment with 5-aminosalicylic acid (5-ASA). METHODS: We prospectively studied microproteinuria in 86 consecutive patients with IBD, 61 with ulcerative colitis (UC) and 25 with Crohn's disease (CD), before as well as 2 and 6 months after their inclusion in the study. Forty-six patients received 5-ASA for a period of 28.8 months (range 1-168 too). Microalbuminuria (mALB) and urine levels of the renal tubular proteins β2-microglobulin (β2mGLB) and β-N-acetyI-D-glucosamidase (β-NAG) as well as the creatinine clearance were determined in a 12-h overnight urine collection. Tumor necrosis factor-α (TNF-α) serum levels were also measured. RESULTS: A total of 277 measurements (194 in UC patients and 83 in CD patients) were performed. The prevalence of abnormal microoproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for B2mGLB, and 11.3% and 8.4% for β-NAG, respectively, mALB was not associated with IBD activity. β2mGLB and B-NAG urine levels were correlated to UC activity (UCAI: P〈0.01; UCEI: P〈0.005). mALB in UC patients and β-NAG urine levels in CD patients were related to TNF-α serum levels. An association was noticed between microproteinuria and smoking habit. Treatment with 5-ASA was not correlated to the severity of microproteinuria or to the changes of creatinine clearance.CONCLUSION: Microproteinuria is mainly associated with UC and its activity but not affected by 5-ASA.展开更多
AIM: To investigate the single nucleotide polymorphism (SNPs) distribution of NOD2/CARD15 (R702W, G908R), OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease (IBD). METHODS: A to...AIM: To investigate the single nucleotide polymorphism (SNPs) distribution of NOD2/CARD15 (R702W, G908R), OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease (IBD). METHODS: A total of 61 patients with Crohn's disease (CD), 151 patients with ulcerative colitis (UC), and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction (PCR-SSP) or by restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 (0/61 with CD) and 1.3% (2/151 with UC). CONCLUSION: Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients.展开更多
AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polym...AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.展开更多
STAT3 has been known as a mediator for gene expression induced by many important cytokines. Recent studies have suggested that STAT3 has important functions in regulation of both innate and adaptive immunity. Loss of ...STAT3 has been known as a mediator for gene expression induced by many important cytokines. Recent studies have suggested that STAT3 has important functions in regulation of both innate and adaptive immunity. Loss of STAT3 in immune cells caused severe inflammation in response to pathogens. This review discusses the recent progress and suggests directions for the future research on this interesting molecule.展开更多
AIM: To determine by brain functional magnetic resonance imaging (fMRI) whether cerebral processing of non-visceral stimuli is altered in irritable bowel syndrome (IBS) patients compared with healthy subjects. To...AIM: To determine by brain functional magnetic resonance imaging (fMRI) whether cerebral processing of non-visceral stimuli is altered in irritable bowel syndrome (IBS) patients compared with healthy subjects. To circumvent spinal viscerosomatic convergence mechanisms, we used auditory stimulation, and to identify a possible influence of psychological factors the stimuli differed in their emotional quality. METHODS: In 8 IBS patients and 8 controls, fMRI measurements were performed using a block design of 4 auditory stimuli of different emotional quality (pleasant sounds of chimes, unpleasant peep (2000 Hz), neutral words, and emotional words). A gradient echo T2*weighted sequence was used for the functional scans. Statistical maps were constructed using the general linear model. RESULTS: To emotional auditory stimuli, IBS patients relative to controls responded with stronger deactivations in a greater variety of emotional processing regions, while the response patterns, unlike in controls, did not differentiate between distressing or pleasant sounds. To neutral auditory stimuli, by contrast, only IBS patients responded with large significant activations. CONCLUSION: Altered cerebral response patterns to auditory stimuli in emotional stimulus-processing regions suggest that altered sensory processing in IBS may not be specific for visceral sensation, but might reflect generalized changes in emotional sensitivity and affectire reactivity, possibly associated with the psychological comorbidity often found in IBS patients.展开更多
AIM: To evaluate the prevalence of hepatitis B virus (HBV) infection in inflammatory bowel disease (IBD) patients that followed up in our hospital and try to identify the possible risk factors involved in this infecti...AIM: To evaluate the prevalence of hepatitis B virus (HBV) infection in inflammatory bowel disease (IBD) patients that followed up in our hospital and try to identify the possible risk factors involved in this infection transmission. METHODS: This was a cross-sectional study for which 176 patients were selected according to their arrival for the medical interview. All these patients had already IBD diagnosis. The patient was interviewed and a questionnaire was filled out. RESULTS: In the group of 176 patients whom we examined, we found that 17% (30) were anti-HBc positive. Out of 30 patients with positive anti-HBc, 2.3% (4) had positive HBsAg and negative HBV-DNA. In an attempt to identify the possible HBV infection transmission risk factors in IBD patients, it was observed that 117 patients had been submitted to some kind of surgical procedure, but only 24 patients had positive anti-HBc (P = 0.085). It was also observed that surgery to treat IBD complications was not a risk factor for HBV infection transmission, since we did not get a statically significant P value. However, IBDpatients that have been submitted to surgery to treat IBD complications received more blood transfusions then patients submitted to other surgical interventions (P = 0.015). CONCLUSION: There was a high incidence of positive anti-HBc (17%) and positive HBsAg (2.3%) in IBD patient when compared with the overall population (7.9%).展开更多
Theories explaining the etiopathogenesis of inflammatory bowel disease (IBD) have been proposed ever since Crohn's disease (CD) and ulcerative colitis (UC) were recognized as the two major forms of the disease....Theories explaining the etiopathogenesis of inflammatory bowel disease (IBD) have been proposed ever since Crohn's disease (CD) and ulcerative colitis (UC) were recognized as the two major forms of the disease. Although the exact cause(s) and mechanisms of tissue damage in CD and UC have yet to be completely understood, enough progress has occurred to accept the following hypothesis as valid: IBD is an inappropriate immune response that occurs in genetically susceptible individuals as the result of a complex interaction among environmental factors, microbial factors, and the intestinal immune system. Among an almost endless list of environmental factors, smoking has been identified as a risk factor for CD and a protective factor for UC. Among microbial factors, no convincing evidence indicates that classical infectious agents cause IBD, while mounting evidence points to an abnormal immune response against the normal enteric flora as being of central importance. Gut inflammation is mediated by cells of the innate as well as adaptive immune systems, with the additional contribution of non-immune cells, such as epithelial, mesenchymal and endothelial cells, and platelets.展开更多
AIM: To evaluate the role of microcirculatory disorder (MCD) and the therapeutic effectiveness ;of tetramethylpyrazine (TMP) on intestinal mucosa injury in rats with acute necrotizing pancreatitis (ANP).METHODS...AIM: To evaluate the role of microcirculatory disorder (MCD) and the therapeutic effectiveness ;of tetramethylpyrazine (TMP) on intestinal mucosa injury in rats with acute necrotizing pancreatitis (ANP).METHODS: A total of 192 Sprague-Dawley rats were randomly divided into three groups: normal control group (C group), ANP group not treated with TMP (P group), ANP group treated with TMP (T group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 mL/kg). C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP (10 mL/kg) via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase (MPO) expressed intraceUularly in azurophilic granules of neutrophils.RESULTS: The blood flow was significantly lower in P group than in C group (P 〈 0.01). The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group (P 〈 0.01). The blood flow of intestine was significantly higher in T group than in P group after 2 h (P 〈 0.01). The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group (P 〈 0.01 or P 〈 0.05). There was a negative correlation between intestinal blood flow and MPO activity (r = -0.981, P 〈 0.01) as well as between intestinal blood flow and pathologic scores (r = -0.922, P 〈 0.05).CONCLUSION: MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.展开更多
AIM: To evaluate the safety and efficacy of a long- term therapy with infliximab in Crohn’s disease (CD) and ulcerative colitis (UC) patients retrospectively. METHODS: The medical charts of 50 patients (40 CD and 10 ...AIM: To evaluate the safety and efficacy of a long- term therapy with infliximab in Crohn’s disease (CD) and ulcerative colitis (UC) patients retrospectively. METHODS: The medical charts of 50 patients (40 CD and 10 UC), who received after a loading dose of 3 infl iximab infusions scheduled re-treatments every 8 wk as a maintenance protocol, were reviewed. RESULTS: Median (range) duration of treatment was 27 (4-64) mo in CD patients and 24.5 (6-46) mo in UC patients. Overall, 32 (80%) CD and 9 (90%) UC patients showed a sustained clinical response or remission throughout the maintenance period. Three CD patients shortened the interval between infusions. Eight (20%) CD patients and 1 UC patient underwent surgery for flare up of disease. Nine out of 29 CD and 4 out of 9 UC patients, who discontinued infliximab scheduled treatment, are still relapse-free after a median of 16 (5-30) and 6.5 (4-16) mo following the last infusion, respectively. Ten CD patients (25%) and 1 UC patient required concomitant steroid therapy during maintenance period, compared to 30 (75%) and 9 (90%) patients at enrolment. Of the 50 patients, 16 (32%) experienced at least 1 adverse event and 3 patients (6%) were diagnosed with cancer during maintenance treatment. CONCLUSION: Scheduled infl iximab strategy is effective in maintaining long-term clinical remission both in CD and UC and determines a marked steroid sparing effect. Long-lasting remission was observed following infliximab withdrawal.展开更多
The objective of this report is to give an overall view of the epidemiological, clinical, diagnostic and therapeutic features of Cytomegalovirus (CMV) infection in inflammaton/ bowel disease (IBD). A review of pub...The objective of this report is to give an overall view of the epidemiological, clinical, diagnostic and therapeutic features of Cytomegalovirus (CMV) infection in inflammaton/ bowel disease (IBD). A review of published reports on this topic was carried out, with particular attention paid to the selection of patients included in studies and the diagnostic methods employed. CMV is frequently associated with IBD. In some cases, CMV infection is as- sociated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. The use of anti-viral therapy in IBD is controversial and an empirical study with controls is needed. The natural history of CMV infection related to the development and treatment of IBD has not been clarified but it is important to take it in consideration because of the possibility of viral persistence in the immunocompromised host and viral interaction with the immune system.展开更多
AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt) mice were given 5...AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelialinjury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modu-lated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.展开更多
Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in combination therapy to improve efficacy and con- co...Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in combination therapy to improve efficacy and con- comitant drug pharmacokinetics, or in chemoprevention against inflammatory bowel disease (IBD)-related co- lonic carcinoma has not yet been completely elucidated. Therapeutic success of mesalazine may be optimized by a combination of high dose and low frequency of dos- age to improve compliance. Therefore, due to its supe- rior safety profile and pharmacokinetic characteristics, mesalazine is preferable to sulphasalazine. This paper reviews the literature concerning mechanisms of action, indications and off-label use, pharmacokinetic properties and formulations, therapeutic efficacy, compliance, pae- diatric indications, chemoprevention, and safety issues and adverse event profile of mesalazine treatment versus sulphasalazine. It also highlights these controversies in order to clarify the potential benefits of mesalazines in IBD therapy and evidence for its use.展开更多
Despite the new and ever expanding array of medications for the treatment of inflammatory bowel disease (IBD), there are still clear indications for operative management of IBD and its complications. We present an ove...Despite the new and ever expanding array of medications for the treatment of inflammatory bowel disease (IBD), there are still clear indications for operative management of IBD and its complications. We present an overview of indications, procedures, considerations, and controversies in the surgical therapy of IBD.展开更多
The inflammatory bowel disease, Crohn's disease and ulcerative colitis, are polygenic disorders with important environmental interactions. To date, the most widely adopted approach to identifying susceptibility ge...The inflammatory bowel disease, Crohn's disease and ulcerative colitis, are polygenic disorders with important environmental interactions. To date, the most widely adopted approach to identifying susceptibility genes in complex diseases has involved genome wide linkage studies followed by studies of positional candidate genes in loci of interest. This review encompasses data from studies into novel candidate genes implicated in the pathogenesis of inflammatory bowel disease. Novel techniques to identify candidate genes-genome wide association studies, yeast-two hybrid screening, microarray gene expression studies and proteomic profiling, are also reviewed and their potential role in unravelling the pathogenesis of inflammatory bowel disease are discussed.展开更多
文摘Inflammatory bowel disease (IBD) is traditionally con- sidered to be common in the Western world, and its incidence has sharply increased since the early 1950s. In contrast, until the last decade, low prevalence and incidence rates have been reported from other parts of the world including Eastern Europe, South America, Asia and the Pacific region. Recent trends indicate a change in the epidemiology of IBD with previously low incidence areas now reporting a progressive rise in the incidence, while in West European and North American countries the figures have stabilized or slightly increased, with decreasing incidence rates for ulcerative colitis. Some of these changes may represent differences in diagnostic practices and increasing awareness of the disease. The quality of studies is also variable. Additional epidemio- logic studies are needed to better define the burden of illness, explore the mechanism of association with envi- ronmental factors, and identify new risk factors.
基金the Program of Presidium of the Russian Acad.Sci. <>, the Russian Fund forBasic Research, No. 06-04-48079 the Program for LeadingScientific Schools, No. 5796.2006.4
文摘AIM: To study isolation and chemical characterization of pectin derived from the common cranberry Vaccin/um oxycoccos L. (oxycoccusan OP) and the testing of its preventive effect on experimental colitis. METHODS: Mice were administrated orally with OP two days prior to a rectal injection of 5% acetic acid and examined for colonic damage 24 h later. Colonic inflammation was characterized by macroscopical injury and enhanced levels of myeloperoxidase activity measured spectrophotometrically with o-phenylene diamine as the substrate. The mucus contents of the colon were determined by the Alcian blue dye binding method. Vascular permeability was estimated using 4% Evans blue passage after i.p. injection of 0.05 mol/L acetic acid. RESULTS: In the mice treated with OP, colonic macroscopic scores (1.1 ± 0.4 vs 2.7, P 〈 0.01) and the total square area of damage (10 ± 2 vs 21 ± 7, P 〈 0.01) were significantly reduced when compared with the vehicle-treated colitis group. OP was shown to decrease the tissue myeloperoxidase activity in colons (42 ± 11 vs 112 ± 40, P 〈 0.01) and enhance the amount of mucus of colitis mice (0.9 ± 0.1 vs 0.4 ± 0.1, P 〈 0.01). The level of colonic malondialdehyde was noted to decrease in OP-pretreated mice (3.6 ± 0.7 vs 5.1 ± 0.8, P 〈 0.01). OP was found to decrease the inflammatory status of mice as was determined by reduction of vascular permeability (161 ± 34 vs 241 ± 21, P 〈 0.01). Adhesion of peritoneal neutrophils and macrophages was also shown to decrease after administration of OP (141 ± 50 vs 235 ± 37, P 〈 0.05). CONCLUSION: Thus, a preventive effect of pectin from the common cranberry, namely oxycoccusan OP, on acetic acid-induced colitis in mice was detected. A reduction of neutrophil infiltration and antioxidant action may be implicated in the protective effect of oxycoccusan.
文摘AIM: To investigate whether microproteinuria in patients with inflammatory bowel disease (IBD) is associated with the disease activity or the treatment with 5-aminosalicylic acid (5-ASA). METHODS: We prospectively studied microproteinuria in 86 consecutive patients with IBD, 61 with ulcerative colitis (UC) and 25 with Crohn's disease (CD), before as well as 2 and 6 months after their inclusion in the study. Forty-six patients received 5-ASA for a period of 28.8 months (range 1-168 too). Microalbuminuria (mALB) and urine levels of the renal tubular proteins β2-microglobulin (β2mGLB) and β-N-acetyI-D-glucosamidase (β-NAG) as well as the creatinine clearance were determined in a 12-h overnight urine collection. Tumor necrosis factor-α (TNF-α) serum levels were also measured. RESULTS: A total of 277 measurements (194 in UC patients and 83 in CD patients) were performed. The prevalence of abnormal microoproteinuria in UC and CD patients was 12.9% and 6.0% for mALB, 22.7% and 27.7% for B2mGLB, and 11.3% and 8.4% for β-NAG, respectively, mALB was not associated with IBD activity. β2mGLB and B-NAG urine levels were correlated to UC activity (UCAI: P〈0.01; UCEI: P〈0.005). mALB in UC patients and β-NAG urine levels in CD patients were related to TNF-α serum levels. An association was noticed between microproteinuria and smoking habit. Treatment with 5-ASA was not correlated to the severity of microproteinuria or to the changes of creatinine clearance.CONCLUSION: Microproteinuria is mainly associated with UC and its activity but not affected by 5-ASA.
基金Doctoral Natural Science Fund of Guangdong Province, China, No. 04300361
文摘AIM: To investigate the single nucleotide polymorphism (SNPs) distribution of NOD2/CARD15 (R702W, G908R), OCTN1 1672CFT and OCTN2-207G/C in Chinese patients with inflammatory bowel disease (IBD). METHODS: A total of 61 patients with Crohn's disease (CD), 151 patients with ulcerative colitis (UC), and 200 unrelated healthy controls were genotyped. Genotyping was performed by sequence specific primer polymerase chain reaction (PCR-SSP) or by restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: Among the subjects in our study groups, including patients with CD, UC and healthy controls, none had OCTN and CARD15 variants and very rare IBD family history was found in our patients with the percentage of 0 (0/61 with CD) and 1.3% (2/151 with UC). CONCLUSION: Our results indicate that although OCTN or CARD15 variation is associated with susceptibility to IBD in Western populations, these might be rare and may not be associated with susceptibility to IBD in Chinese patients.
文摘AIM: To examine the expression of metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the colonic mucosa of patients with ulcer- ative colitis (UC). METHODS: Reverse transcription-polymerase chain re- action (RT-PCR) and immunohistochemistry were used to study the expression of MMP-1 and TIMP-1 at both mRNA and protein levels in patients with UC and con- trols. The relationship between MMP-1 mRNA, TIMP-1 mRNA, MMP-1 mRNA/TIMP-1 mRNA ratio and the sever- ity of clinical symptoms of the patients with UC were also analyzed. RESULTS: The expression of MMP-1 mRNA and TIMP-1 mRNA in the ulcerated and inflamed colonic mucosa was signifi cantly higher than that in the non-inflamed colonic mucosa (P < 0.001), but there was no statistically signif i- cant difference in the non-inflamed colonic mucosa of UC patients and normal controls (P > 0.05). The mRNA ex- pression of MMP-1 and TIMP-1 in ulcerated colonic mu- cosa of UC patients was increased by 80-fold and 2.2-fold, respectively when compared with the normal controls. In the inflamed colonic mucosa, the increase was 30-fold and 1.6-fold, respectively. Immunohistochemical analy- sis showed that among the ulcerated, inflamed, and non-inflamed colonic mucosae of UC patients and the normal controls, the positive rate of MMP-1 expression was 87%, 87%, 40% and 35% respectively, and the positive rate of TIMP-1 expression was 89%, 89%, 80% and 75%, respectively. Furthermore, the expression of MMP-1 mRNA, TIMP-1 mRNA and the MMP-1 mRNA/ TIMP-1 mRNA ratio were correlated with the severity of clinical symptoms (P <0.05).CONCLUSION: Excessive expression of MMP-1 in the diseased colonic mucosa causes excessive hydrolysis of the extracellular matrix (ECM) and ulceration in UC pa-tients. MMP-1 mRNA, TIMP-1 mRNA and MMP-1 mRNA/ TIMP-1 mRNA ratio can be used as biomarkers to judge the severity of clinical symptoms in patients with UC. Exogenous TIMP-1 or MMP-1 inhibitor therapy is a novel treatment for patients with UC.
文摘STAT3 has been known as a mediator for gene expression induced by many important cytokines. Recent studies have suggested that STAT3 has important functions in regulation of both innate and adaptive immunity. Loss of STAT3 in immune cells caused severe inflammation in response to pathogens. This review discusses the recent progress and suggests directions for the future research on this interesting molecule.
文摘AIM: To determine by brain functional magnetic resonance imaging (fMRI) whether cerebral processing of non-visceral stimuli is altered in irritable bowel syndrome (IBS) patients compared with healthy subjects. To circumvent spinal viscerosomatic convergence mechanisms, we used auditory stimulation, and to identify a possible influence of psychological factors the stimuli differed in their emotional quality. METHODS: In 8 IBS patients and 8 controls, fMRI measurements were performed using a block design of 4 auditory stimuli of different emotional quality (pleasant sounds of chimes, unpleasant peep (2000 Hz), neutral words, and emotional words). A gradient echo T2*weighted sequence was used for the functional scans. Statistical maps were constructed using the general linear model. RESULTS: To emotional auditory stimuli, IBS patients relative to controls responded with stronger deactivations in a greater variety of emotional processing regions, while the response patterns, unlike in controls, did not differentiate between distressing or pleasant sounds. To neutral auditory stimuli, by contrast, only IBS patients responded with large significant activations. CONCLUSION: Altered cerebral response patterns to auditory stimuli in emotional stimulus-processing regions suggest that altered sensory processing in IBS may not be specific for visceral sensation, but might reflect generalized changes in emotional sensitivity and affectire reactivity, possibly associated with the psychological comorbidity often found in IBS patients.
文摘AIM: To evaluate the prevalence of hepatitis B virus (HBV) infection in inflammatory bowel disease (IBD) patients that followed up in our hospital and try to identify the possible risk factors involved in this infection transmission. METHODS: This was a cross-sectional study for which 176 patients were selected according to their arrival for the medical interview. All these patients had already IBD diagnosis. The patient was interviewed and a questionnaire was filled out. RESULTS: In the group of 176 patients whom we examined, we found that 17% (30) were anti-HBc positive. Out of 30 patients with positive anti-HBc, 2.3% (4) had positive HBsAg and negative HBV-DNA. In an attempt to identify the possible HBV infection transmission risk factors in IBD patients, it was observed that 117 patients had been submitted to some kind of surgical procedure, but only 24 patients had positive anti-HBc (P = 0.085). It was also observed that surgery to treat IBD complications was not a risk factor for HBV infection transmission, since we did not get a statically significant P value. However, IBDpatients that have been submitted to surgery to treat IBD complications received more blood transfusions then patients submitted to other surgical interventions (P = 0.015). CONCLUSION: There was a high incidence of positive anti-HBc (17%) and positive HBsAg (2.3%) in IBD patient when compared with the overall population (7.9%).
基金Supported by a grant from the Broad Medical Research Program toS.D
文摘Theories explaining the etiopathogenesis of inflammatory bowel disease (IBD) have been proposed ever since Crohn's disease (CD) and ulcerative colitis (UC) were recognized as the two major forms of the disease. Although the exact cause(s) and mechanisms of tissue damage in CD and UC have yet to be completely understood, enough progress has occurred to accept the following hypothesis as valid: IBD is an inappropriate immune response that occurs in genetically susceptible individuals as the result of a complex interaction among environmental factors, microbial factors, and the intestinal immune system. Among an almost endless list of environmental factors, smoking has been identified as a risk factor for CD and a protective factor for UC. Among microbial factors, no convincing evidence indicates that classical infectious agents cause IBD, while mounting evidence points to an abnormal immune response against the normal enteric flora as being of central importance. Gut inflammation is mediated by cells of the innate as well as adaptive immune systems, with the additional contribution of non-immune cells, such as epithelial, mesenchymal and endothelial cells, and platelets.
基金Supported by Zhenjiang Science and Technology Committee, No. SH2002015
文摘AIM: To evaluate the role of microcirculatory disorder (MCD) and the therapeutic effectiveness ;of tetramethylpyrazine (TMP) on intestinal mucosa injury in rats with acute necrotizing pancreatitis (ANP).METHODS: A total of 192 Sprague-Dawley rats were randomly divided into three groups: normal control group (C group), ANP group not treated with TMP (P group), ANP group treated with TMP (T group). An ANP model was induced by injection of 50 g/L sodium taurocholate under the pancreatic membrane (4 mL/kg). C group received isovolumetric injection of 9 g/L physiological saline solution using the same method. T group received injection of TMP (10 mL/kg) via portal vein. Radioactive biomicrosphere technique was used to measure the blood flow at 0.5, 2, 6 and 12 h after the induction of ANP. Samples of pancreas, distal ileum were collected to observe pathological changes using a validated histology score. Intestinal tissues were also used for examination of myeloperoxidase (MPO) expressed intraceUularly in azurophilic granules of neutrophils.RESULTS: The blood flow was significantly lower in P group than in C group (P 〈 0.01). The pathological changes were aggravated significantly in P group. The longer the time, the severer the pathological changes. The intestinal MPO activities were significantly higher in P group than in C group (P 〈 0.01). The blood flow of intestine was significantly higher in T group than in P group after 2 h (P 〈 0.01). The pathological changes were alleviated significantly in T group. MPO activities were significantly lower in T group than in P group (P 〈 0.01 or P 〈 0.05). There was a negative correlation between intestinal blood flow and MPO activity (r = -0.981, P 〈 0.01) as well as between intestinal blood flow and pathologic scores (r = -0.922, P 〈 0.05).CONCLUSION: MCD is an important factor for intestinal injury in ANP. TMP can ameliorate the condition of MCD and the damage to pancreas and intestine.
文摘AIM: To evaluate the safety and efficacy of a long- term therapy with infliximab in Crohn’s disease (CD) and ulcerative colitis (UC) patients retrospectively. METHODS: The medical charts of 50 patients (40 CD and 10 UC), who received after a loading dose of 3 infl iximab infusions scheduled re-treatments every 8 wk as a maintenance protocol, were reviewed. RESULTS: Median (range) duration of treatment was 27 (4-64) mo in CD patients and 24.5 (6-46) mo in UC patients. Overall, 32 (80%) CD and 9 (90%) UC patients showed a sustained clinical response or remission throughout the maintenance period. Three CD patients shortened the interval between infusions. Eight (20%) CD patients and 1 UC patient underwent surgery for flare up of disease. Nine out of 29 CD and 4 out of 9 UC patients, who discontinued infliximab scheduled treatment, are still relapse-free after a median of 16 (5-30) and 6.5 (4-16) mo following the last infusion, respectively. Ten CD patients (25%) and 1 UC patient required concomitant steroid therapy during maintenance period, compared to 30 (75%) and 9 (90%) patients at enrolment. Of the 50 patients, 16 (32%) experienced at least 1 adverse event and 3 patients (6%) were diagnosed with cancer during maintenance treatment. CONCLUSION: Scheduled infl iximab strategy is effective in maintaining long-term clinical remission both in CD and UC and determines a marked steroid sparing effect. Long-lasting remission was observed following infliximab withdrawal.
文摘The objective of this report is to give an overall view of the epidemiological, clinical, diagnostic and therapeutic features of Cytomegalovirus (CMV) infection in inflammaton/ bowel disease (IBD). A review of published reports on this topic was carried out, with particular attention paid to the selection of patients included in studies and the diagnostic methods employed. CMV is frequently associated with IBD. In some cases, CMV infection is as- sociated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. The use of anti-viral therapy in IBD is controversial and an empirical study with controls is needed. The natural history of CMV infection related to the development and treatment of IBD has not been clarified but it is important to take it in consideration because of the possibility of viral persistence in the immunocompromised host and viral interaction with the immune system.
基金Supported by Instituto de Salud Carlos Ⅲ (C03/02), FEDER funds, Fundación Canaria de Investigación (PI 21/02), and Spanish Ministry of Education to CM (EX2004-0396)
文摘AIM: To study whether matrix metalloproteinase-9 (MMP-9) is a key factor in epithelial damage in the dextran sodium sulphate (DSS) model of colitis in mice.METHODS: MMP-9-deficient and wild-type (wt) mice were given 5% DSS in drinking water for 5 d followed by recovery up to 7 d. On d 5 and 12 after induction of colitis, gelatinases, MMP-2 and MMP-9, were measured in homogenates of colonic tissue by zymography and Western blot, whereas tissue inhibitor of metalloproteinases (TIMPs) were measured by reverse zymography. The gelatinolytic activity was also determined in supernatants of polymorphonuclear leukocytes (PMN) isolated from mice blood. Moreover, intestinal epithelial cells were stimulated with TNF-α to study whether these cells were able to produce MMPs. Finally, colonic mucosal lesions were measured by microscopic examination. RESULTS: On d 5 of colitis, the activity of MMP-9 was increased in homogenates of colonic tissues (0.24 ± 0.1 vs 21.3 ± 6.4, P < 0.05) and PMN from peripheral blood in wt (0.5 ± 0.1 vs 10.4 ± 0.7, P < 0.05), but not in MMP-9-deficient animals. The MMP-9 activity was also up-regulated by TNF-α in epithelial intestinal cells (2.5 ± 0.5 vs 14.7 ± 3.0, P < 0.05). Although colitis also led to increase of TIMP-1 activity, the MMP-9/TIMP-1 balance remained elevated. Finally, in the MMP-9-deficient colitic mice both the extent and severity of intestinal epithelialinjury were significantly attenuated when compared with wt mice. CONCLUSION: We conclude that DSS induced colitis is markedly attenuated in animals lacking MMP-9. This suggests that intestinal injury induced by DSS is modu-lated by MMP-9 and that inhibition of this gelatinase may reduce inflammation.
基金Supported by research grants from Astrazeneca (Zoetermeer, The Netherlands), Ferring BV (Hoofddorp, The Netherlands), P and G Pharmaceuticals (Cincinnati, United States), ALTANA Pharma BV (Hoofddorp, The Netherlands), and Tramedico BV (Weesp, The Netherlands), Falk Company (Freiburg, Germany), and Ferring International (Copenhagen, Denmark)
文摘Mesalazine is a safe drug, although adverse events may be seen in a minority of patients. This applies also to pregnant women and children. The role of mesalazine in combination therapy to improve efficacy and con- comitant drug pharmacokinetics, or in chemoprevention against inflammatory bowel disease (IBD)-related co- lonic carcinoma has not yet been completely elucidated. Therapeutic success of mesalazine may be optimized by a combination of high dose and low frequency of dos- age to improve compliance. Therefore, due to its supe- rior safety profile and pharmacokinetic characteristics, mesalazine is preferable to sulphasalazine. This paper reviews the literature concerning mechanisms of action, indications and off-label use, pharmacokinetic properties and formulations, therapeutic efficacy, compliance, pae- diatric indications, chemoprevention, and safety issues and adverse event profile of mesalazine treatment versus sulphasalazine. It also highlights these controversies in order to clarify the potential benefits of mesalazines in IBD therapy and evidence for its use.
文摘Despite the new and ever expanding array of medications for the treatment of inflammatory bowel disease (IBD), there are still clear indications for operative management of IBD and its complications. We present an overview of indications, procedures, considerations, and controversies in the surgical therapy of IBD.
文摘The inflammatory bowel disease, Crohn's disease and ulcerative colitis, are polygenic disorders with important environmental interactions. To date, the most widely adopted approach to identifying susceptibility genes in complex diseases has involved genome wide linkage studies followed by studies of positional candidate genes in loci of interest. This review encompasses data from studies into novel candidate genes implicated in the pathogenesis of inflammatory bowel disease. Novel techniques to identify candidate genes-genome wide association studies, yeast-two hybrid screening, microarray gene expression studies and proteomic profiling, are also reviewed and their potential role in unravelling the pathogenesis of inflammatory bowel disease are discussed.