scholarly journals HYPERHOMOCYSTEINEMIA LEAD TO TRANSMURAL INFLAMMATION OF COLON AND INCREASE SEVERITY OF DISEASE IN ACETIC ACID-INDUCED COLITIS IN RAT

Author(s):  
Lamda Souad ◽  
Naimi Dalila ◽  
Aggoun Cherifa

Objective: The present study was designed to evaluate the effect of hyperhomocysteinemia (Hhcy) induced by feeding rats high methionine diet on the colon wall. Colonic damages caused by Hhcy were compared with those induced by acetic –acid induced colitis.Methods: Sprague-Dawley rats (200-250g) were divided into four groups: group C (control), group M (received 1 g/kg methionine p. o. during 15 d), group A (colitis was induced by transrectal administration of acetic acid 4% on 8th day) and group MA (received methionine and acetic acid). At the end of the study, plasma homocysteine, C-reactive protein (CRP) and leukocytes (WBC) count were evaluated, all rats were sacrificed and distal 8 cm of the colon was dissected. Colon was weighed for disease activity index (DAI) and injuries were assessed macroscopically and histologically.Results: High methionine diet induced significant (P<0.001) increase of homocysteine (hcy), CRP levels and WBC count compared to control. Acetic acid rats showed a significant decrease of WBC count. Mixed treatment caused a significant increase of hcy, CRP and a significant decrease of WBC count. Our results showed that Hhcy causes significant damages and immune cells infiltration in all layers of the colonic wall.Conclusion: The present investigation demonstrated that Hhcy increased the major inflammatory markers as CRP and leukocytes count and produced transmural colitis in rats. Effect of Hhcy is more toxic on the colonic wall than acetic acid indeed while acetic acid lesions are localized in mucosa and submucosa the lesions of hcy extend to the all layers (mucosa, submucosa and muscularis propria). Acetic acid induced colitis in hyperhomocysteinemic rats increased the severity of colitis.

Author(s):  
Lamda Souad ◽  
Naimi Dalila ◽  
Aggoun Cherifa

Objective: The present study was designed to evaluate the effect of hyperhomocysteinemia (Hhcy) induced by feeding rats high methionine diet on the colon wall. Colonic damages caused by Hhcy were compared with those induced by acetic –acid induced colitis.Methods: Sprague-Dawley rats (200-250g) were divided into four groups: group C (control), group M (received 1 g/kg methionine p. o. during 15 d), group A (colitis was induced by transrectal administration of acetic acid 4% on 8th day) and group MA (received methionine and acetic acid). At the end of the study, plasma homocysteine, C-reactive protein (CRP) and leukocytes (WBC) count were evaluated, all rats were sacrificed and distal 8 cm of the colon was dissected. Colon was weighed for disease activity index (DAI) and injuries were assessed macroscopically and histologically.Results: High methionine diet induced significant (P<0.001) increase of homocysteine (hcy), CRP levels and WBC count compared to control. Acetic acid rats showed a significant decrease of WBC count. Mixed treatment caused a significant increase of hcy, CRP and a significant decrease of WBC count. Our results showed that Hhcy causes significant damages and immune cells infiltration in all layers of the colonic wall.Conclusion: The present investigation demonstrated that Hhcy increased the major inflammatory markers as CRP and leukocytes count and produced transmural colitis in rats. Effect of Hhcy is more toxic on the colonic wall than acetic acid indeed while acetic acid lesions are localized in mucosa and submucosa the lesions of hcy extend to the all layers (mucosa, submucosa and muscularis propria). Acetic acid induced colitis in hyperhomocysteinemic rats increased the severity of colitis.


2019 ◽  
Vol 13 (7) ◽  
pp. 949-953 ◽  
Author(s):  
Wolfgang Kruis ◽  
Phuong Nguyen ◽  
Julia Morgenstern ◽  
Wolfgang Ramlow ◽  
Axel Dignaß ◽  
...  

Abstract Background and Aims In active ulcerative colitis [UC] refractory to mesalazine, escalation to either steroids or immunosuppression is common practice. The efficacy and safety of alternative escalation therapy with a novel leukocyte apheresis device were studied. Methods This was a prospective, randomized, controlled multicentre pilot study comparing leukocyte apheresis with prednisolone in refractory UC (disease activity index [DAI] ≥ 4 and ≤8). Group A received weekly apheresis over five consecutive weeks. Group P received oral prednisolone 40 mg/day tapered to 0 mg at week 6. The primary end point was steroid-free clinical remission [DAI ≤ 2] at week 12. Clinical response was also analysed. Results Twenty-four patients were enrolled, 13 of whom were randomized into group A and 11 into group P. Clinical remission off steroids at week 12 was achieved in 3/12 patients [25.0%] with apheresis and 2/10 [20.0%] with prednisolone [p = 1.0]. The response rate after 12 weeks was 75.0% in group A and 50.0% in group P. Mean DAI scores improved in both treatment groups [p = 0.008]. C-reactive protein decreased from 6.0 ± 5.3 to 3.8 ± 3.7 mg/L at 12 weeks in group A and increased from 5.2 ± 6.0 to 6.3 ± 7.9 mg/mL in group P. Both treatments were well tolerated. No unexpected serious adverse events were seen in group A. In group P one symptomatic infection with Clostridium difficile occurred. Conclusions In patients with active UC refractory to mesalazine a novel leukocyte apheresis showed promising results. A comparison with prednisolone revealed similar therapeutic effectivity and excellent safety, providing the chance to escalate without systemic steroids.


2015 ◽  
Vol 65 (3) ◽  
pp. 339-347
Author(s):  
Hijová Emília ◽  
Śoltésová Alena ◽  
Salaj Rastislav ◽  
Kuzma Jozef ◽  
Strojný Ladislav ◽  
...  

Abstract The aim of this study was to investigate the influence of prebiotic inulin diet intervention on the activity of β-glucuronidase and counts of coliforms and lactobacilli in fresh caecal digesta, cytokine levels (IL-6, IL-8) and transcription nuclear factor kappa beta (NFkB) activities in the colon tissue and blood samples of rats with dextran sulphate sodium (DSS) induced acute colitis. Male Sprague-Dawley rats (8 per group) were randomly divided into three groups: Control, Acute colitis and Prebiotic. Colitis was induced using 5% DSS in drinking water for 7d. DSS application significantly increased the activity of β-glucuronidase (p<0.001), increased counts of coliform bacteria and decreased lactobacilli count (p<0.05) in comparison to the control group. Serum and tissue levels of IL-6 and IL-8 as well as tissue NFkB activities showed an increased expression in the acute colitis group. These results correspond to the average value of the disease activity index score (DAI) and revealed the maximum DAI score (6.5) in the acute colitis group. A decrease in the DAI score (4.13) was observed after application of the prebiotic inulin. Inulin diet intervention positively modified the number of microorganims and decreased β-glucuronidase activity. Colon tissue activities of NFkB were significantly suppressed (p<0.001). The synthesis of proinflammatory cytokines IL-6 (p<0.01) in the serum and in the colon tissue, as well as tissue IL-8 (p<0.05) in the prebiotic group were downregulated. These findings indicate that the dietary intake of inulin suppressed the expression of the observed markers, which play an important role in the inflammatory process, which predisposes to the use of inulin in the prevention or treatment of acute colitis in human and veterinary medicine.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Cem Çekiç ◽  
Adnan Kırcı ◽  
Sezgin Vatansever ◽  
Fatih Aslan ◽  
Huriye Erbak Yılmaz ◽  
...  

Background. Syndecan-1 (SDC-1), a member of the family of heparan sulfate proteoglycans, plays an important role in the resolution of inflammation. This study aimed to investigate the relationship between SDC-1 and disease activity in Crohn’s disease (CD).Methods. Serum samples of 54 patients with CD and 30 healthy controls were obtained. First, SDC-1 levels of the CD patients were compared to the control group. Subsequently, SDC-1 levels were analyzed in patients with CD in active and remission periods. Finally, SDC-1 efficacy in predicting disease activity was evaluated by performing correlation analysis between SDC-1 and C-reactive protein (CRP) and Crohn’s disease activity index (CDAI).Results. SDC-1 level was higher in the CD group (61.9 ± 42.6 ng/mL) compared with the control group (34.1 ± 8.0 ng/mL)p=0.03. SDC-1 levels were higher in active CD patients (97.1 ± 40.3 ng/mL) compared with those in remission (33.7 ± 13.5 ng/mL)p<0.001. A significant positive correlation was found between SDC-1 and CRP (r=0.687,p<0.001) and between SDC-1 and CDAI (r=0.747,p<0.001).Conclusion. Serum levels of SDC-1 are higher in CD compared to the normal population and can be an effective marker of disease severity.


Molecules ◽  
2019 ◽  
Vol 25 (1) ◽  
pp. 76 ◽  
Author(s):  
Liuhong Zhang ◽  
Ning Cao ◽  
Yuwen Wang ◽  
Youxu Wang ◽  
Chao Wu ◽  
...  

Ulcerative colitis (UC) is usually accompanied with symptoms of abdominal pain, diarrhea, and bloody stool, which impair the quality of life of patients. Previous studies have shown that Andrographis paniculata extracts, which have andrographolide (AND) as their main compound, can relieve UC symptoms in patients. The aim of the study was to investigate the alleviating effect of AND on UC using the oxazolone (OXZ)-induced UC rat model. A total of 66 healthy male Sprague Dawley rats were used to evaluate the efficacy and mechanism of AND on UC (n = 11 per group) and grouped into control, model, SASP (sulfasalazine, positive control group, 500 mg/kg), AND-L (40 mg/kg), AND-M (80 mg/kg), and AND-H (120 mg/kg). The colonic disease activity index (DAI), colon length, spleen coefficient, pathological damage, and inflammation-related cytokine and protein expression levels were used as indices for evaluation. Results showed that the AND groups had reduced DAI and mortality, and significantly improved colon length and spleen coefficient compared with the model group. Furthermore, OXZ-induced histological injury was relieved significantly after AND treatment due to an improved crypt structure and reduced infiltration of inflammatory cells. Moreover, AND inhibited myeloperoxidase (MPO) activity and the secretion of interleukin-4 (IL-4), IL-13, and tumor necrosis factor α (TNF-α). The results of the anti-inflammatory mechanism revealed that AND blocked the signal transduction by reducing IL-4/IL-13 specific binding to IL-4 receptor (IL-4R) and inhibiting the phosphorylation of the signal transducer and activator of transcription 6 (p-STAT6). In conclusion, aside from natural plants, AND may be a candidate ingredient for UC therapy.


2020 ◽  
Vol 1 (3) ◽  
pp. 01-04
Author(s):  
Dejan Spasovski

Introduction: To determine the effects of non-treated seronegative rheumatoid arthritis (RA) on proximal renal tubule, sensitivity of Alanine aminopeptidase (AAP), g-glutamyltransferase (g--GT), β2 microglobulin in urine β2M), as well as relation with rheumatoid factor (RF) and C-Reactive protein (CRP), DAS 28 disease activity index. Methods: RF was determined by agglutination test (Latex RF test, while kinetic methods were used for determination of Alanine aminopeptidase (AAP) and g-glutamyltransferase (g-GT), as well as MEIA (Micro particle Enzyme Immunoassay) to determine β2 microglobulin in urine. Samples (serum and urine) of 70 participants were examined (35 RA not treated, 35 health control group). Results: In 35 RF negative RA, AAP enzymuria was present in 12 (34.28%) patients, g-GT was present in 7 patients (20%), while β2 microglobulin was present in 3 patients (8.57%). In the healthy control group, 4 patients showed AAP positivity (11.42%), 2 patients g-GT positivity (5.71%) and 1 patient showed presence of β2 microglobulin in urine (2.85). RF was not present in any patient (0%). Conclusion: AAP has a higher sensitivity of g-GT and b2 microglobulin in the detection of asymptomatic renal lesions in non treated seronegative RA.


2018 ◽  
Vol 2018 ◽  
pp. 1-9
Author(s):  
Kai Wang ◽  
Tongjia Zhu ◽  
Haijun Wang ◽  
Jinxin Yang ◽  
Shuaishuai Du ◽  
...  

CD4+CD25+Foxp3+ Tregs control the immune response and maintain immune homeostasis. This study examined whether Tregs can affect mouse enteritis and the Foxp3 (Forkhead transcription factor) transcriptional pathway. Mouse CD4+CD25+ Treg cells were labelled using CFSE (5,6-carboxyfluorescein diacetate succinimidyl ester) and transferred to enteritis model mice. The mice were randomly divided into an enteritis group, a Treg-infusion group, a Treg-inhibiting group, and a control group. Histopathology, ELISA, flow cytometry, western blot, immunohistochemistry, and immunofluorescence were performed. Our results demonstrated that CD4+CD25+ Tregs were successfully transferred. The disease activity index (DAI) scores in the Tregs-infusion group were lower than those of the enteritis and Tregs-inhibiting groups. The number of goblet cells and inflammatory cells was reduced, and the levels of IL-1β, TNF-α, NO, and PGE2 were significantly decreased in the Tregs-infusion group compared to those in the enteritis group (p<0.05). The number of CD4+CD25+Foxp3+ Tregs and CD4+IL-17A+ Th17 cells in the mesenteric lymph nodes differed significantly from the enteritis and Tregs-inhibiting groups (p<0.05). There were more Foxp3+ Tregs and Smad3 and NFAT2 infiltrated into the duodenum after adoptive transfer of CD4+CD25+ Tregs, which was a significant difference relative to the enteritis group (p<0.05). This study demonstrated that adoptive transfer of CD4+CD25+ Tregs can decrease mouse enteritis. Foxp3 expression may be improved through the Smad3 and NFAT2 signalling pathways.


Author(s):  
J. Santoantonio ◽  
L. Yazigi ◽  
E. I. Sato

The purpose of this study was to investigate the personality characteristics in adolescents with SLE. The research design is a case-control study by means of the Rorschach Method and the Wechsler Intelligence Scale. Study group: 30 female adolescents with lupus, 12–17 years of age. The SLE Disease Activity Index was administered during the period of psychological evaluation. Control group: 32 nonpatient adolescents were matched for age, sex, and socioeconomic level. In the Wechsler Intelligence Scale the mean IQ of the experimental group was significantly lower than that of the control group (77 and 98, respectively, p < .001). In the Rorschach, the lupus patients showed greater difficulty in interpersonal interactions, although they displayed the resources to process affect and to cope with stressful situations. A positive moderate correlation (p = .069) between the activity index of the disease and the affect constriction proportion of the Rorschach was observed: the higher the SLEDAI score, the lower the capacity to process affect. There is a negative correlation between the activity index of the disease and the IQ (p = .001): with a higher activity index of the disease, less intellectual resources are available.


Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1490.3-1491
Author(s):  
K. Inoue ◽  
K. Misaki ◽  
N. Dobashi ◽  
M. Miyazaki ◽  
Y. Mako ◽  
...  

Background:Prednisolone (PSL) and HCQ are key drugs in the therapy of SLE. However, since PSL induce many harmful adverse events, PSL is preferred to be reduced especially in the maintenance therapy. The efficacy of HCQ for reducing the dose of PSL has not been revealed yet. So, we focused on the cessation of PSL under the treatment of HCQ with conventional SLE therapy.Objectives:The aim of this study is to evaluate the efficacy and the safety of HCQ as co-treatment in the standard therapy of SLE.Methods:SLE patients (n=30) under the maintenance therapy were enrolled in this study. Dose of PSL, titer of anti-DNA antibody, WBC count, serum complement and SLE disease activity index (SLEDAI) were examined retrospectively at 0 and 12 months after administration of HCQ.Results:Baseline patient-characteristics are as follows (mean±S.E); the age of patients was 54.4±3.2 years old, 21 patients (70%) were female, the disease duration was 108.5±25.2 months, SLEDAI was 4.0±0.9, the dose of PSL was 10.3±1.7 mg/day, the titer of anti-DNA antibody was 7.3±1.8 IU/ml, C3 was 85±4.3 mg/dl and C4 was 18±1.6 mg/dl.The mean dose of PSL was reduced with statistically significance (pre-administration of HCQ:10.3±1.7 mg/day, 24 months after administration of HCQ:2.2±0.3 mg/day,p<0.0001). Furthermore, in this observation period, 6 patients could achieve the cessation of PSL.SLEDAI was also significantly reduced (4.0±0.9 vs 1.0±0.3,p<0.01).There was no statistical significance between before treatment by HCQ and after treatment in the titer of anti-DNA antibody (7.3±1.8 vs 2.8±1.6 IU/ml,p=0.06), WBC count (6208±4.9 vs 5096±3.3 /μl,p=0.06) and serum complement level (C3 85±4.3 mg/dl vs 89±4.0 mg/dl,p=0.52, C4 18±1.6 mg/dl vs 19±1.4 mg/dl,p=0.45). Relapse of SLE was clarified in only one patient.As for adverse events (AEs), Severe bacterial infection (n=4), herpes zoster (n=1) and patellar tendon rupture (n=1) were revealed. All cases of the AEs were fully recovered.Conclusion:Our study suggested that co-treatment with HCQ on standard SLE therapy could be enable to prevent the flare of SLE and reduce the dose of PSL with statistical significance. In some cases, we could achieve the cessation of PSL treatment.References:None.Disclosure of Interests:None declared


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