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PubMedDate not supplied

[Inhibitors of proteolytic enzymes in the blood serum of patients with diphyllobothriasis].

The proteinase inhibitors alpha 1-protease inhibitor (alpha 1-antitrypsin) and alpha 2-macroglobulin have been determined in 24 patients with diphyllobothriasis (D. latum and D. dendriticum), with their activity expressed in conventional units per ml serum inhibiting or binding the activity of 1 unit of trypsin, respectively. The specific activity of alpha 1-protease inhibitor and alpha 2-macroglobulin proved to be twice (46.2%) and thrice (32.7%) lower, respectively, despite a significant decrease in the total protein serum level. The ratio between these 2 parameters was 9.86 +/- 1.4, it being equal to 5.3 +/- 0.12 in the control. The authors believe that the reduced activity of alpha 1-protease inhibitor may be a protective response of the host to the invasion. Reduced activity is suggested to promote to chronic intestinal inflammation. Decreased activity of alpha 2-macroglobulin is accounted for by damages in its synthesis by monocyte-macrophage elements and probably by enhanced binding with proteinases of the parasite.

Blood Proteins↗
PubMed2006

Colon cleansing: a popular, but misunderstood natural therapy.

Intestinal inflammation and leaky gut syndrome can be at the root of many health problems. Colon cleansing is a popular therapy among alternative practitioners, but many myths surround it. The scientifically inaccurate way many traditional healers try to explain therapeutic mechanisms is one of the obstacles that inhibits dialog between traditional healers and practitioners of modern medicine. The therapy actually has clinical value, but the explanations used to promote the therapies are the stuff of herbal legends, not scientific fact. The concept of cleansing is actually a metaphorical explanation for a therapy that improves detoxification via the liver and gastrointestinal tract and reduces inflammation or irritation to mucous membranes of the GI tract.

Cathartics↗
PubMed2006

[Inflammatory bowel diseases: in search of novel cytokines and genes].

Inflammatory bowel diseases are chronic idiopathic intestinal disorders that have diverse manifestations such as diarrhea, rectal bleeding, abdominal pain, weight loss, fever and extraintestinal manifestations. The current concept regarding their immunopathogenesis is that, in a genetically susceptible host, an aberrant response of the mucosa associated lymphoid tissue (MALT) towards a non-pathogenic microorganism, elicits the cascade that culminates in intestinal inflammation. In this issue of HAREFUAH, Waterman M & al have screened IBD vs. control population in search of a genetic association between IBD and the interleukin 13 polymorphism 2044+G/A, on chromosome 5. Although they have found no such association, the editorial addresses the importance of cytokines and novel genes for the understanding of the immunopathogenesis of inflammatory bowel diseases, and its treatment.

Cytokines↗
PubMedDate not supplied

[Simultaneous occurrence of Crohn's and Bechterew's disease].

The author describes a case-history of concomitant manifestation of classical Bekhterev's disease (HLA B 27 positive) which preceded by 10 years the detection of Crohn's disease of the stomach, terminal ileum and rectum. The author discusses the relationship of the two diseases in particular with regard to the probable defined extraintestinal manifestation of Crohn's disease. The concurrent presence of the two diseases causes difficulties when assessing the humoral activity. For ankylosing spondylarthritis with a manifest or silent intestinal inflammation 5-aminosalicylic acid is the drug of choice. Early detection of the two diseases is important for therapy and prognosis.

Adult↗
PubMed1990

[The role of arachidonic acid metabolism in the pathophysiology of chronic inflammatory intestinal diseases].

Crohn's disease and ulcerative colitis are chronic inflammatory diseases of the bowel with unknown etiology. Alterations of intestinal and systemic immuno-regulation are probably of importance in the pathophysiology of both diseases. Moreover, recent studies suggest that polymorphonuclear granulocytes and probably macrophages are of particular importance in the initiation of an acute flare of the disease. Interest has therefore focused on arachidonic acid metabolites, in particular leukotrienes and prostaglandins, which are important mediators in granulocyte and macrophage activation and chemotaxis. The pathophysiologic importance of various leukotriene derivatives, particularly LTB4, has been well established whereas the actions of prostaglandins in vivo, in particular PGE2, are controversial. Numerous anti-inflammatory drugs such as glucocorticoids and salicylic acid derivatives have been successfully used to treat intestinal inflammation. One possible mechanism of action is the modulation of arachidonic acid metabolism and thus regulation of the genesis of active inflammatory mediators.

Anti-Inflammatory Agents↗
PubMedDate not supplied

[Crohn's disease of the colon. History].

During the 18th, 19th, and at the beginning of the 20th century, various observations of inflammatory lesions of the colon and small intestine were published, which were different of tuberculosis to which was at that time attributed every chronical small intestinal inflammatory disease. It was only in 1932, that in a very important paper, Crohn, Ginsburg and Oppenheimer defined the terminal ileitis, afterwards called regional enteritis, and finally more simply Crohn's disease. Twenty years later, in 1952, Crohn's disease of the colon, confused until that date with colonic tuberculosis and with ulcerative colitis, was also identified as a separate entity. Since that time, the number of reported cases has tremendously increased through its is impossible to state whether the incidence of the disease has really increased or whether the diagnosis is done earlier and more precisely. Even today, the exacts limits of the disease are difficult to precise, since the causal agent of the disease is unknown, and that no biological test is completely secure. The present work reports 60 observations of chronic colitis, associated or not with small intestinal inflammation.

Crohn Disease↗
PubMedDate not supplied

Assessment of the role of platelet-activating factor in an animal model of inflammatory bowel disease.

Using a rat model of chronic colitis, the role of PAF-acether as a mediator of intestinal inflammation was assessed. Rats were treated with a specific PAF-acether antagonist, BN52021, during the first 4 days after induction of colitis, or during the period of 4-7 days after induction of colitis. The effects of treatment with BN52021 were compared to those of treatment with 5-aminosalicylic acid. BN52021 and 5-aminosalicyclic acid were without significant effect on colonic damage score when administered intracolonically on days 1-4 after induction of colitis. However, when given on days 4-7 after induction of colitis, both drugs significantly accelerated the healing of ulcers and reduced the incidence of adhesions and diarrhea. Intraperitoneal administration of BN52021 also resulted in a significant reduction of colonic damage scores, while administration of 5-aminosalicyclic acid via this route was without significant effect. Using an in vitro superfusion system, the effects of PAF-acether on contractility of segments of ascending colon were assessed. Tissue segments from normal rats contracted to doses of PAF-acether as low as 0.5 pg. However, non-inflamed segments of ascending colon from rats in which colitis was induced 2 weeks earlier were relatively insensitive to PAF-acether. The results of the present study demonstrate that PAF-acether is unlikely to play an important role in the acute inflammatory response in this model, but may be important in the prolongation of inflammation and ulceration in this model. The studies on contractility of ascending colon suggest that changes in tissue sensitivity to PAF-acether may occur as a consequence of inflammation.

Aminosalicylic Acids↗
PubMed1989

Amyloidosis in pigtailed macaques (Macaca nemestrina): pathologic aspects.

The pathologic aspects of 248 cases of amyloidosis in pigtailed macaques (Macaca nemestrina) at the Washington Regional Primate Research Center from 1971 through 1985 were studied. Amyloid was present in the spleen, liver and gastrointestinal (GI) tract, either alone or in combination, in nearly 75% of the monkeys. Its occurrence declined with age in the spleen and the GI tract, but increased with age in the liver. Both intestinal inflammation and retroperitoneal fibromatosis were strongly associated with amyloid deposition in the GI tract. Monkeys with histopathologic findings of enteritis or enterocolitis and glomerulonephritis were at increased risk of developing amyloidosis. Forty cases of amyloidosis with a history of chronic diarrhea had type AA amyloid by histochemical tests.

Age Factors↗
PubMed1983

Health problems in a newly established fur farming area in Eastern Finland.

Health problems of newly established fur farms were defined in Kuopio Province. Three methods of data collection were used: 1) interviews with local farmers 2) authors' personal observations and 3) determination of endoparasitic infestation. Sanitation on farms were found to be rather good. The most commonly occurring diseases were urinary tract inflammations, intestinal infections and ectoparasites. However, health conditions were found to be satisfactory and most problems were of economic nature.

Animal Husbandry↗
PubMed1995

Budesonide in glucocorticoid dependent chronic active Crohn's disease; a pilot study.

Patients with chronic active Crohn's disease are dependent on systemic glucocorticosteroids. The aim of the study was to investigate the efficacy of budesonide, a topically selective glucocorticosteroid, as therapy in these patients. We investigated 20 patients with chronic active Crohn's disease. During the last 6 months prior to the study the patients had a median Crohn's disease activity index (CDAI) of 193 (interquartile range: 122-230) (monthly controls) with a median prednisolone dosage of 14 mg per day (9-20). Budesonide was given 3 to 6 mg daily and prednisolone was weaned within one month. The patients were seen monthly for 6 months. Treatment was considered not successful, if under budesonide therapy CDAI was above 200 and increased more than 60 points despite weaning of prednisolone. Only 5 patients remained in the study for 6 months without deterioration. All other patients (75%) dropped out. The reasons for drop out of the study were worsening in 11 cases, the occurrence of extraintestinal manifestations without signs of severe intestinal inflammation in one case and noncompliance in 3 cases. Worsening could be confirmed by an increase not only of CDAI but also of biochemical parameters of inflammation in all cases. Our data show clearly, that in the dosage investigated budesonide was not effective in chronic active Crohn's disease. Further investigations are needed to evaluate higher dosages of budesonide versus conventional glucocorticosteroids.

Administration, Oral↗
PubMed1995

Faecal alpha 1-antitrypsin concentration in the diagnosis and management of patients with pouchitis.

OBJECTIVE: To investigate the role of faecal alpha 1-antitrypsin concentration in the diagnosis and management of patients with ileal pouch-anal anastomosis. DESIGN: Prospective study. METHODS: Fifty-two measurements of faecal alpha 1-antitrypsin concentration were taken from 33 patients operated on for ulcerative colitis. RESULTS: Patients with active pouchitis (44.4 +/- 7.1 mg%) had a three-fold higher mean faecal alpha 1-antitrypsin concentration than patients in remission (13.7 +/- 1.3 mg%; P < 0.0001), than patients who had never had pouchitis (14.4 +/- 2.3 mg%; P < 0.003) and than patients with incontinent ileostomies (12.7 +/- 1.3 mg%; P < 0.004). Faecal alpha 1-antitrypsin measurements were 80% sensitive and 97% specific for active pouchitis. A significant positive correlation between the pouchitis disease activity index and faecal protein loss was observed (r = 0.702; P < 0.0001). The correlations between protein loss and other parameters were weaker (protein loss versus clinical score, r = 0.309; versus endoscopic score, r = 0.583; and versus histologic score, r = 0.558). CONCLUSION: Faecal alpha 1-antitrypsin concentration is a good indicator of the degree of intestinal inflammation in pouchitis and may be useful as a quantitative index of disease activity in prospective studies.

Adult↗
PubMed1995

The forms and the levels of fecal PMN-elastase in patients with colorectal diseases.

OBJECTIVES: To compare the form of polymorphonuclear leukocyte (PMN)-elastase in feces with that in plasma and to investigate the usefulness of measuring fecal PMN-elastase levels in patients with colorectal diseases. METHODS: We examined PMN-elastase complexed with alpha 1-antitrypsin (alpha 1-AT), chymotrypsin, and alpha 2-macroglobulin by ELISA in feces and plasma. Fecal levels of total PMN-elastase were determined in patients with colonic polyp (N = 19), colonic cancer (N = 20), ulcerative colitis (UC; N = 36), colonic Crohn's disease (CD; N = 26), and in control subjects (N = 20). RESULTS: Most PMN-elastase was not complexed with alpha 1-AT, chymotrypsin, or alpha 2-macroglobulin in feces, whereas most plasma PMN-elastase was complexed with alpha 1-AT. Fecal concentrations and daily fecal excretion of PMN-elastase were significantly increased in patients with active UC (medians 54.8 micrograms/g, 15.14 mg/day) and active CD (41.5 micrograms/g, 10.24 mg/day) compared to those values in control subjects (0.6 micrograms/g, 0.11 mg/day) and in patients with colonic cancer (2.5 micrograms/g, 0.33 mg/day). In inactive UC and CD, these values (3.4 micrograms/g, 0.52 mg/day and 5.2 micrograms/g, 0.59 mg/day, respectively) were significantly lower than in active UC and CD, respectively. In UC, all patients whose rectal biopsies showed infiltration of PMN had high fecal PMN-elastase levels. CONCLUSIONS: Our results suggest that the measurement of fecal PMN-elastase concentrations are useful for monitoring the disease activity of UC and CD, especially when evaluating whether intestinal inflammation has disappeared completely.

Adult↗
PubMed1994

Clostridium difficile diarrhea: pathogenesis, epidemiology, and treatment.

Clostridium difficile, the bacterium responsible for antibiotic-associated diarrhea and colitis, has become a significant cause of morbidity and prolonged hospital stays, largely because of the increasing use of broad-spectrum antibiotics. This gram-positive organism, which can lay dormant in its spore form in the environment for extended periods of time, proliferates in the colon when the normal colonic flora is compromised by antibiotic use. C. difficile produces intestinal inflammation and diarrhea through the elaboration of two protein exotoxins, toxin A and toxin B. The spectrum of clinical manifestations ranges from mild diarrhea that resolves with the cessation of the offending antibiotic, to fulminant pseudomembranous colitis complicated by megacolon and perforation. Our ability to meet the challenge offered by this organism has been enhanced by the development of new diagnostic modalities as well as the development of new therapeutic regimens. Through further investigation of the structure and function of toxins A and B and further study of the interaction of C. difficile with the normal colonic flora, advances will continue to be made in the prevention and treatment of antibiotic-associated colitis.

Anti-Bacterial Agents↗
PubMed1993

The disease pattern of elderly medical patients in Rwanda, central Africa.

In a study of the disease pattern of the elderly in Rwanda, all patients aged 60 or more, hospitalized in a one-year period at the Medical Department, University Hospital, Butare, were examined prospectively. One hundred and ninety-two patients were included; most were subsistence farmers having a mainly vegetarian diet and living in large families. Infections (37.5% of the patients) and liver cirrhosis (31.8%) were the problems most frequently encountered. Primary hepatocellular cancer was diagnosed in 5.7% of the patients and was the most frequent malignancy. The hospitalized elderly occupied 17.5% of the available beds in the Medical Department. Their disease pattern was different from that of younger patients, making heavier demands on the medical resources. Malaria and upper intestinal inflammation were less frequent in the elderly; liver cirrhosis, primary hepatocellular cancer, pneumonia, prostatic cancer, cardiovascular pathology, chronic renal pathology and chronic lung disease were more prevalent. Several age-related conditions frequently observed in industrialized countries (e.g. coronary heart disease, stroke, gallstones, renal cysts, dementia) were rare. The study thus illustrates the concept of 'secondary aging': to the primary changes induced by the aging process, additional alterations are added which depend upon the environment and the lifestyle, resulting in a varying disease pattern. Health policies thus must take into account that the demographic transition in developing countries may result in a pattern of diseases different from that seen in industrialized countries; care must be taken when transposing data obtained from elderly populations in industrialized countries.

Aged↗
PubMed1995

Therapeutic efficacy of N-3 polyunsaturated fatty acid in experimental Crohn's disease.

We investigated the therapeutic efficacy of n-3 polyunsaturated fatty acids (PUFAs) on trinitro-benzene sulfonic acid (TNBS)-induced colitis in the rats, which condition is considered an experimental Crohn's disease (CD). In rats with TNBS-induced colitis, feeding with an elemental diet (ED) plus 2% n-3 PUEA-rich perilla oil significantly suppressed plasma leukotriene (LT) B4 and ulcer index compared to that in rats fed with ED plus 2% n-6 PUFA-rich safflower oil (34.2 +/- 12.3 s 63.8 +/- 13.2 pg/ml and 8.8 +/- 12.1 vs 66.4 +/- 33.1, P < 0.01, respectively). Moreover, the plasma LTB4 and the ulcer index were significantly correlated (P < 0.05). Feeding with ED plus 2% alpha-linolenic acid (A-LA)-rich vegetable oil significantly reduced plasma LTB4 and colonic weight compared to that in rats fed with ED plus 2% eicosapentaenoic acid (EPA)/docosahexaenonic acid (DHA)-rich fish oil in this model (61.6 +/- 10.5 vs 85.0 +/- 20.9 pg/ml and 0.83 +/- 0.13 vs 0.96 +/- 0.08g, P < 0.05, respectively). This study suggested that dietary fat manipulation with perilla oil can reduce colonic damage and that this is correlated with the suppression of plasma LTB4. The therapeutic efficacy of A-LA in controlling intestinal inflammation in experimental CD may be superior to that of EPA and DHA.

Animals↗
PubMed1996

Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5.

In this study, we investigate whether human inflammatory bowel disease (IBD) (ulcerative colitis and Crohn's disease) is associated with altered lymphokine secretion profiles, as recently found in various animal models of chronic intestinal inflammation. In initial studies, we determined the proliferative responses of purified lamina propria (LP) CD4+ T cells from patients with IBD under defined conditions of T cell stimulation. We found that IBD LP CD4+ T cells in comparison with control LP CD4+ T cells have diminished TCR/CD3 pathway proliferative responses, whereas CD2/CD28 accessory pathway proliferative responses are relatively preserved. In further studies centering on lymphokine production, we showed that LP T cells from inflamed Crohn's disease mucosa manifest increased IFN-gamma secretion compared with control LP T cells, particularly when stimulated via the CD2/CD28 pathway. Subsequent ELISPOT analysis indicated that this was due to an increased number of IFN-gamma-secreting CD4+ T cells. In contrast, IL-4 and IL-5 production by Crohn's disease LP T cells was decreased compared with that of control LP T cells. Of interest, IL-2 production by Crohn's disease LP T cells was also reduced, as was IL-2 production by peripheral blood T cells. In parallel studies, LP T cells from inflamed ulcerative colitis mucosa stimulated via either the TCR/CD3/CD28 or CD2/CD28 produced increased amounts of IL-5, again when measured either as secreted IL-5 or by ELISPOT analysis. Such increased IL-5 production was not associated with increased IL-4 secretion and, in contrast to Crohn's disease, ulcerative colitis LP T cell production of IL-2 and IFN-gamma was normal. Taken together, these studies provide strong evidence that the immunopathologic process characteristic of the two major forms of IBD is associated with very different cytokine secretion patterns. These different patterns may determine the type of inflammatory process present.

CD2 Antigens↗
PubMed1996

Mucosal addressin cell adhesion molecule-1: a structural and functional analysis demarcates the integrin binding motif.

The leukocyte integrin receptor, alpha 4 beta 7, and the mucosal addressin cell adhesion molecule-1 (MAdCAM-1) are postulated to be important in regulating lymphocyte trafficking to normal intestine. Here we provide the first description of MAdCAM-1 expression in inflamed intestine. Using mouse models of experimentally induced colitis, we show a concordant increase in MAdCAM-1 expression associated with increased cellular infiltrates in areas of intestinal inflammation. To understand more of the molecular nature of the interactions between MAdCAM-1 and its leukocyte ligand, the alpha 4 beta 7 integrin receptor, we have analyzed the structural and functional properties of chimeric recombinant MAdCAM-1 proteins in vitro. Using site-directed mutagenesis and molecular modeling, we demarcate the alpha 4 beta 7 binding motif as three linear residues within the C-D loop in the first domain of MAdCAM-1. Mutation of residue L40, D41, or T42 in the first domain completely abrogates alpha 4 beta 7+ cell binding and cellular activation. Mutagenesis of other residues in the first domain do not impact these functions. We have modeled peptides based on the predicted structure of the alpha 4 beta 7 integrin binding motif on MAdCAM-1 and are able to show specific and selective blocking of cell binding. These observations suggest that the amino acid residues LDT on MAdCAM-1 play a role in the interaction with alpha 4 beta 7 in cell adherence and cell activation.

Amino Acid Sequence↗
PubMed1997

Histopathologic features of T-cell mediated colonic injury induced with 2,4-dinitrofluorobenzene in BALB/c mice.

The aim of the study was to reveal the histopathologic features of intestinal inflammation as demonstrated in BALB/c mice, using the challenge of 2,4-dinitrofluorobenzene (DNFB) with or without previous sensitization. Forty mice were randomized into 5 groups. Two groups of animals were treated with rectal enema of 0.2% or 1.0% of 2,4-dinitrofluorobenzene solution. Third group was pretreated with 2 sensitizing doses of DNFB. Two control groups were treated with PBS or acetone and vehicle enema only (acetone and olive oil). In order to assess the extent of colonic inflammation and damage, a histopathologic score scale was developed. In contrast to scanty superficial ulcerations and mild edema observed in the control group of animals, edema, ulcerations, hemorrhage, necrosis and infiltration of inflammatory cells were observed in experiment groups treated with enema of DNFB. Total score of lesion as well almost all inflammatory parameters of injury observed were highest in previously sensitized animals. The results of this study clearly demonstrated the pattern of colonic inflammation induced with DNFB using the histopathologic scoring scale system.

Animals↗