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K Geboes

Publications and source records attributed to K Geboes.

At least 55 records · Page 3Linked to original sources
PubMed2003

On the existence and location of cardiac mucosa: an autopsy study in embryos, fetuses, and infants.

BACKGROUND: The incidence of gastric cardiac adenocarcinoma has increased in the last decades. Gaining insight into the pathogenesis of this lesion is hampered by the limited knowledge of the origin and histology of cardiac mucosa (CM). Currently, the location, extent, and even the existence of CM are controversial. AIMS: We studied the development of the gastro-oesophageal junction (GOJ) in embryos, fetuses, and infants to clarify if CM is a normal structure at birth and where it is located. SUBJECTS: Twenty one autopsy cases were evaluated ranging in age from 13 weeks' gestational age (GA) to seven months. METHODS: The distal oesophagus and proximal part of the stomach were embedded entirely. Serial sections were stained with haematoxylin-eosin and alcian blue/periodic acid-Schiff. The following parameters were measured: length of abdominal oesophagus; length of columnar lined oesophagus; length of CM; and distance from CM to angle of His. RESULTS: CM was present in all evaluated sections. Its mean length varied throughout gestation. A maximum value was reached at a GA of 16 weeks (1.2 mm). After term delivery it was very short (0.3-0.6 mm). CM was proximal to, or straddled, the angle of His in all cases. During gestation, the mucin staining pattern of the CM was to a high degree similar to that of the developing pyloric mucosa. CONCLUSIONS: CM develops during pregnancy and is present at birth as a normal structure. If the angle of His is taken as a landmark for the GOJ, CM is located in the distal oesophagus.

Aging↗
PubMed2002

Microscopic colitis with giant cells.

AIMS: Collagenous colitis and lymphocytic colitis are the two types of microscopic colitis with specific morphological features. In this report we describe a new histopathological subtype of microscopic colitis. METHODS AND RESULTS: Colonoscopy in four patients with chronic watery diarrhoea showed no macroscopic abnormalities. The random biopsies from the colon showed subepithelial multinucleated giant cells in combination with the features of collagenous colitis in three patients and lymphocytic colitis in one patient. These multinucleated giant cells were positive for CD68. The density of macrophages was highest in the most superficial part of the lamina propria. In one patient, a previous biopsy showed features consistent with collagenous colitis without multinucleated giant cells. Treatment with budesonide led to the disappearance of diarrhoea in all four patients. CONCLUSIONS: The clinical and histopathological features of the four presented patients indicate that there exists a histopathological subtype of microscopic colitis characterized by the presence of subepithelial multinucleated giant cells, which probably arise from fusion of subepithelial macrophages. Analysis of more patients with this histopathological subtype of microscopic colitis is necessary to determine whether they also form a clinically distinct group.

Aged↗
PubMed2002

Studies on the relationship between esophageal acid exposure, mucosal lesions and heartburn using an acid exposure sensor.

BACKGROUND: In vitro studies of a recently developed acid exposure sensor show that the sensor response (SR) to acid <pH 4 is linearly determined by the duration and degree of acidity. The aim was to determine whether SR correlates with the severity of acid-induced esophageal mucosal lesions and acid-induced heartburn. METHODS: HCl pH 1.5 or saline was infused into the feline esophagus for 5-20 min. Simultaneously, sensor measurements were performed below the infusion port. The histological damage was scored by an independent pathologist. In 15 normal subjects, HCl pH 1 was infused into the esophagus and the severity of the heartburn (0-5) was scored at 5-min intervals. In 10 subjects who experienced heartburn during acid perfusion, initial perfusion with HCl was repeated during heartburn induction time minus 5 min, followed by perfusion with the subject's own gastric juice, titrated to pH 2; heartburn severity was again scored at 5-min intervals. Acid exposure sensors positioned below the infusion port were removed at heartburn scores 1, 2 and 3. RESULTS: A good correlation was found between SR and the histological score for mucosal damage in the cat esophagus (r = 0.64, P < 0.005). There was a good relation between heartburn severity score and acid exposure time (r = 0.84, P < 0.001), and a significant but weaker relation between heartburn severity and SR. CONCLUSION: In cats, there is a good relation between the severity of acid-induced esophageal mucosal lesions and SR. In men, there is a significant correlation between the severity of acid-induced heartburn and the simultaneously measured SR. Therefore, SR measurement has the potential of yielding clinically relevant information in the investigation of GERD.

Adult↗
PubMed2002

Expression of T lymphocyte chemoattractants and activation markers in vernal keratoconjunctivitis.

BACKGROUND/AIMS: T lymphocytes are present in increased numbers in the conjunctiva of patients with vernal keratoconjunctivitis (VKC) and their activation has a central role in the pathogenesis of the chronic allergic inflammatory reactions seen in VKC. The aims of this study were to examine the expression of three recently described potent T lymphocyte chemoattractants, PARC (pulmonary and activation regulated chemokine), macrophage derived chemokine (MDC), and I-309, the MDC receptor CCR4, and T lymphocyte activation markers, CD25, CD26, CD62L, CD71, and CD30, and to correlate them with the counts of CD3(+) T lymphocytes in the conjunctiva of patients with VKC. METHOD: Conjunctival biopsy specimens from 11 patients with active VKC, and eight control subjects were studied by immunohistochemical techniques using a panel of monoclonal and polyclonal antibodies directed against PARC, MDC, I-309, CCR4, CD25, CD26, CD62L, CD71, and CD30. The numbers of positively stained cells were counted. The phenotype of inflammatory cells expressing chemokines was examined by double immunohistochemistry. RESULTS: In the normal conjunctiva, vascular endothelial cells in the upper substantia propria showed weak immunoreactivity for CD26. There was no immunoreactivity for the other antibodies. VKC specimens showed inflammatory cells expressing PARC, MDC, and I-309. The numbers of PARC(+) inflammatory cells were higher than the numbers of MDC(+) and I-309(+) inflammatory cells and the mean values of the three groups differed significantly (17.0 (SD 10.1); 9.5 (9.9), and 4.3 (7.9), respectively, p = 0.0117, ANOVA). The numbers of PARC(+) inflammatory cells had the strongest correlation with the numbers of CD3(+) T lymphocytes. Few CCR4(+) inflammatory cells were observed in only three specimens. Double immunohistochemistry revealed that all inflammatory cells expressing chemokines were CD68(+) monocytes/macrophages. The numbers of CD25(+) T lymphocytes were higher than the numbers of CD26(+), CD62L(+), CD71(+), and CD30(+) T lymphocytes and the mean values of the five groups differed significantly (46.2 (27.9), 30.7 (16.0), 20.1 (8.6), 7.8 (7.7), and 6.5 (4.0), respectively, p <0.001, ANOVA). The numbers of CD25(+) T lymphocytes had the strongest correlation with the numbers of CD3(+) T lymphocytes. CONCLUSION: These results suggest a potential role for PARC, MDC, and I-309 in attracting T lymphocytes into conjunctiva in VKC. T lymphocytes in VKC are activated and express several activation markers which might contribute to the pathogenesis of VKC.

Adolescent↗
PubMed2002

Influence of treatment on morphological features of mucosal inflammation.

Microscopic analysis of endoscopically obtained tissue samples is important for the diagnosis of several gastrointestinal disorders such as gastritis and chronic inflammatory bowel disease (IBD). Histologically disease activity is based on the presence of neutrophilic polymorphonuclear leucocytes in conjunction with epithelial damage. Effective eradication treatment for Helicobacter pylori related gastritis reduces active inflammation rapidly whereas chronic inflammation decreases only slowly. Similar findings have been obtained for IBD. A literature review of clinical drug trials in IBD and the effect of various drugs on the microscopic features of Crohn's disease and immunohistochemistry for different markers was performed. Diagnostic microscopic features and the features characteristic for disease activity vary with time and treatment. The more recently developed drugs used for Crohn's disease can induce mucosal healing.

Adult↗
PubMed2001

B7 interactions with CD28 and CTLA-4 control tolerance or induction of mucosal inflammation in chronic experimental colitis.

CD28-B7 interaction plays a critical costimulatory role in inducing T cell activation, while CTLA-4-B7 interaction provides a negative signal that is essential in immune homeostasis. Transfer of CD45RB(high)CD4(+) T cells from syngeneic mice induces transmural colon inflammation in SCID recipients. This adoptive transfer model was used to investigate the contribution of B7-CD28/CTLA-4 interactions to the control of intestinal inflammation. CD45RB(high)CD4(+) cells from CD28(-/-) mice failed to induce mucosal inflammation in SCID recipients. Administration of anti-B7.1 (but not anti-B7.2) after transfer of wild-type CD45RB(high)CD4(+) cells also prevented wasting disease with colitis, abrogated leukocyte infiltration, and reduced production of proinflammatory cytokines IL-2 and IFN-gamma by lamina propria CD4(+) cells. In contrast, anti-CTLA-4 treatment led to deterioration of disease, to more severe inflammation, and to enhanced production of proinflammatory cytokines. Of note, CD25(+)CD4(+) cells from CD28(-/-) mice similar to those from the wild-type mice were efficient to prevent intestinal mucosal inflammation induced by the wild-type CD45RB(high) cells. The inhibitory functions of these regulatory T cells were effectively blocked by anti-CTLA-4. These data show that the B7-CD28 costimulatory pathway is required for induction of effector T cells and for intestinal mucosal inflammation, while the regulatory T cells function in a CD28-independent way. CTLA-4 signaling plays a key role in maintaining mucosal lymphocyte tolerance, most likely by activating the regulatory T cells.

Abatacept↗
PubMed2001

Gelatinase B in vernal keratoconjunctivitis.

OBJECTIVES: To investigate the expression of gelatinase B in the conjunctiva of patients with vernal keratoconjunctivitis (VKC) and the cellular source of this enzyme. METHODS: Conjunctival biopsy specimens from 12 patients with active VKC and 12 control subjects were studied using immunohistochemical techniques and a monoclonal antibody against gelatinase B. The phenotype of gelatinase B(+) inflammatory cells was examined using double immunohistochemical analysis and monoclonal antibodies against eosinophil peroxidase or macrophage CD68. Quantitative zymography was used to compare the activity of gelatinase B in conjunctival biopsy specimens from 10 patients with active VKC and 7 control subjects. RESULTS: Gelatinase B was detected in a few polymorphonuclear cells in 8 control specimens. All VKC specimens showed gelatinase B immunoreactivity in the epithelial and stromal inflammatory infiltrate. Compared with control specimens, VKC specimens showed significantly more gelatinase B-positive cells (mean +/- SD, 40.8 +/- 29.9 vs 10.3 +/- 2.4; P<.02). Most gelatinase B-positive cells were eosinophils (90.2% +/- 3.6%). Zymography revealed that gelatinase B levels in VKC specimens were significantly higher than the levels found in normal conjunctiva (3780.3 +/- 3541.0 vs 610.1 +/- 397.1 scanning units; P<.03). CONCLUSIONS: These findings suggest overexpression of gelatinase B by eosinophils in VKC specimens and participation of gelatinase B in the pathologic changes in VKC. CLINICAL RELEVANCE: Control of the release and/or activation of gelatinase B in eosinophils may provide a new therapeutic strategy for treating VKC.

Adolescent↗
PubMed2001

Role of interleukin-12 in the induction of mucosal inflammation and abrogation of regulatory T cell function in chronic experimental colitis.

IL-12 promotes Th1 cell differentiation and cell-mediated immunity. In the present study, the potential role of IL-12 was analyzed in an experimental colitis model in scid mice reconstituted with syngeneic CD45RBhighCD4+ T cells. Real-time reverse transcription-PCR studies demonstrated that IL-12 p40 mRNA in inflamed colon is induced shortly after T cell transfer and maintained at a stable level after week 4, at the time when wasting disease starts. Administration of anti-IL-12 on days 0,14, and 28 (early treatment) or on days 28, 42, and 56 (delayed treatment) after T cell transfer, effectively prevented or, respectively cured wasting disease and colitis in scid recipients. Anti-IL-12 treatment abrogated mucosal inflammation with significantly diminished leukocyte infiltration (CD4 cells, macrophages) and CD54 expression, and down-regulated proinflammatory cytokines IFN-gamma and IL-2. Of note, although splenic CD4+ T cells are unable to induce disease as a result of the presence of regulatory CD45RBlow cells, splenic CD4+ T cells, preactivated by IL-12 and anti-CD3 in vitro, were highly pathogenic in inducing severe mucosal inflammation, suggesting that IL-12 and anti-CD3 abrogated regulatory T cell function. These findings indicate that IL-12 is important for the induction of experimental colitis through effects on proinflammatory cytokine production and on regulatory T cell function.

Animals↗
PubMed2001

Selective induction of CCL18/PARC by staphylococcal enterotoxins in mononuclear cells and enhanced levels in septic and rheumatoid arthritis.

Chemokines are mediators of innate and acquired immunity. CCL18, also designated pulmonary and activation-regulated chemokine (PARC), dendritic cell-derived CC chemokine-1 (DC-CK1), alternative macrophage activation-associated CC chemokine-1 (AMAC-1) and macrophage inflammatory protein-4 (MIP-4), was for the first time isolated from peripheral blood mononuclear cells (PBMC) and biochemically characterized. We found that CCL18/PARC protein is spontaneously secreted by PBMC and is selectively induced in PBMC by staphylococcal enterotoxins (SEA, SEB) and IL-4, but not by IFN-gamma and the CXCL8/IL-8 inducers lipopolysaccharide (LPS) or Concanavalin A. Human fibroblasts, chondrocytes and endothelial cells did not produce CCL18/PARC in response to inflammatory mediators such as measles virus, double-stranded RNA, LPS or IL-1beta, whereas up to 150 ng/ml of CCL2/MCP-1 was induced under these conditions. In synovial fluids from septic and rheumatoid arthritis patients, fourfold-enhanced CCL18/PARC levels (150 ng/ml) were detected compared to those in crystal-induced arthritis and osteoarthritis. In septic arthritis, the synovial levels of CCL18/PARC were fivefold higher than those of CXCL8/IL-8. Immunochemistry revealed CD68(+) monocytes/macrophages as the main CCL18/PARC-producing cell type in both PBMC and arthritic synovial tissue. In addition, CD1a(+) blood dendritic cells expressed CCL18/PARC. These findings suggest that monocytic cells respond to Gram-positive bacterial infection by the production of CCL18/PARC in the synovial cavity.

Arthritis, Infectious↗
PubMed2001

Expression of the inducible isoform of nitric oxide synthase in the retinas of human subjects with diabetes mellitus.

PURPOSE: Inducible nitric oxide synthase has been implicated in the pathogenesis of cerebral ischemic damage, in the angiogenic process and in diabetic vascular damage. This study was undertaken to determine whether inducible nitric oxide synthase is present in the retinas from human subjects with diabetes mellitus. METHODS: This was an experimental immunohistochemical prospective study. Ten postmortem eyes from five subjects with diabetes mellitus, 10 eyes from five subjects without diabetes and without known ocular disease, and two eyes from one subject with unilateral ocular ischemic syndrome secondary to severe carotid artery obstruction were examined. We used immunohistochemical techniques and antibodies directed against inducible nitric oxide synthase, glial fibrillary acidic protein, and vimentin. The main outcome measure was immunoreactivity for these antibodies. RESULTS: Immunoreactivity for inducible nitric oxide synthase was not observed in retinas from all subjects without diabetes and without ocular disease. Six retinas from three subjects with diabetes and nonproliferative retinopathy, and the retina from the eye with ocular ischemic syndrome showed immunoreactivity for inducible nitric oxide synthase in cells with elongated processes. Based on morphology and on glial fibrillary acidic protein and vimentin immunoreactivity, this inducible nitric oxide synthase immunoreactivity appeared to localize to retinal Müller glial cells. CONCLUSIONS: These observations suggest that Müller cells may be involved in the microvascular remodeling of the diseased retina and that high concentrations of nitric oxide produced by inducible nitric oxide synthase could contribute to neurotoxicity and angiogenesis that occur in diabetic retinopathy.

Adult↗
PubMed2001

Langerhans' cells in vernal keratoconjunctivitis express the costimulatory molecule B7-2 (CD86), but not B7-1 (CD80).

PURPOSE: Vernal keratoconjunctivitis (VKC) is associated with T-helper 2 (TH2)-like cell response and increased immunoglobulin (Ig) E production. Recent studies have suggested that interactions between costimulatory molecules B7 on antigen-presenting cells and CD28 on T cells are critical for successful antigen presentation and the development of the TH2 immune response. The objective of this study was to examine the expression of costimulatory molecules CD28, B7-1 (CD80) and B7-2 (CD86) in conjunctival biopsies from patients with active VKC and normal controls. METHODS: Conjunctival biopsy specimens from 15 subjects with active VKC, and 8 control subjects, were studied by immunohistochemical techniques using a panel of monoclonal and polyclonal antibodies directed against CD28, B7-1 and B7-2 molecules. The phenotype of inflammatory cells expressing costimulatory molecules was examined by sequential double immunohistochemistry. RESULTS: In the normal conjunctiva, B7-2 was expressed on a few mononuclear cells in the epithelium and substantia propria in 5 of 8 specimens. There was no immunoreactivity for CD28 or B7-1. In VKC specimens, few B7-1+ mononuclear cells were noted in the substantia propria in 7 of 15 specimens. B7-2 was expressed on mononuclear cells in the epithelium and substantia propria in all specimens. Compared with normal controls, VKC specimens showed significantly more mononuclear cells expressing B7-2 (30.5+/-14.1 vs 1.88+/-2.5; p < 0.001). In VKC specimens, the numbers of mononuclear cells expressing B7-2 were significantly higher than the numbers of mononuclear cells expressing B7-1 (30.5+/-14.1 vs 2.3+/-3.1; p < 0.001). CD28 was expressed on mononuclear cells in the epithelium and substantia propria in 14 specimens. Colocalisation studies revealed that the majority of mononuclear cells expressing B7-2 were CD1a+ Langerhans' cells, and that the mononuclear cells expressing CD28 were CD3+ T lymphocytes. CONCLUSIONS: B7-2 is more widely and prominently expressed by Langerhans' cells compared with B7-1. The interaction of B7-2 with CD28 may mediate the development of the TH2 immune response in VKC. Thus the manipulation of this pathway could be an important target for the development of future therapies in VKC.

Adolescent↗
PubMed2001

Expression of CD23/CD21 and CD40/CD40 ligand in vernal keratoconjunctivitis.

PURPOSE: The overproduction of immunoglobulin E (IgE) antibodies is associated with vernal keratoconjunctivitis (VKC). CD23/CD21 and CD40/CD40 ligand (CD40L) interactions have been proposed to be involved in the regulation of IgE synthesis. The purpose of the present study was to investigate the presence and distribution of CD23, CD21, CD40 and CD40L in the conjunctiva from patients with active VKC. METHODS: Conjunctival biopsy specimens from 8 subjects with active VKC and 6 control subjects were studied. We used immunohistochemical techniques and a panel of monoclonal antibodies (mAbs) directed against CD23, CD21, CD40 and CD40L. In addition, a panel of mAbs were used to characterise the composition of the inflammatory infiltrate. RESULTS: In the normal conjunctiva, basal epithelial cells and vascular endothelial cells in the upper substantia propria showed a constitutive very weak immunoreactivity for CD40. The immunoreactivity for CD23, CD21 and CD40L was absent. In VKC specimens, the stromal inflammatory infiltrate was orgnanised as a diffuse infiltrate and as small lymphoid follicles consisting of CD20+ B lymphocytes intermingled with smaller numbers of CD3+ T lymphocytes, and CD68+ monocytes/macrophages. Lymphocytes in the centre of the lymphoid follicles showed CD23 and CD21 immunoreactivity. CD40 immunoreactivity in epithelial cells and vascular endothelial cells was stronger in VKC specimens than in control eyes. Furthermore, the majority of mononuclear cells, including T and B lymphocytes, showed immunoreactivity for CD40. CD40L immunoreactivity was not detected. CONCLUSION: B lymphocytes in the lymphoid follicles expressing CD23, CD21 and CD40 are activated and might be precursors of IgE-producing B cells. These results suggest that the conjunctiva might contribute to IgE synthesis.

Adolescent↗
PubMed2001

Infliximab induces potent anti-inflammatory and local immunomodulatory activity but no systemic immune suppression in patients with Crohn's disease.

BACKGROUND: Anti-TNFalpha therapy with infliximab is effective for Crohn's disease. Infliximab neutralizes the biological activities of TNFalpha, a cytokine involved in host-defence against certain infections. AIM: To evaluate the effects of infliximab on the gut and peripheral immune system functions. METHODS: Biopsies and blood samples from three clinical trials of infliximab in Crohn's disease were analysed. Pharmacokinetics, changes in leucocyte counts and T cell subsets, T cell function, and cytokine profiles of lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were analysed. RESULTS: Infliximab has a serum half-life of 9.5 days and is still detectable in serum 8 weeks after infusion. Leucocyte counts showed consistent changes from baseline toward normal values after therapy. Monocytes and lymphocytes were modestly increased, while neutrophils were decreased 4 weeks after treatment. Lymphocyte subsets and T cell proliferative responses were not altered after therapy. The proportion of PBMCs capable of producing IFNgamma and TNFalpha did not change, while Th1 cytokine production by stimulated LPMC was decreased after infliximab therapy. CONCLUSION: The clinical efficacy of infliximab is based on local anti-inflammatory and immunomodulatory effects in the bowel mucosa, without generalized suppression of systemic immune functions in Crohn's disease patients.

Antibodies, Monoclonal↗
PubMed2001

Long-term lansoprazole treatment for gastro-oesophageal reflux disease: clinical efficacy and influence on gastric mucosa.

BACKGROUND: Long-term acid suppression is believed to accelerate atrophic gastritis in Helicobacter pylori-positive patients. The influence of long-term therapy with lansoprazole has not been examined. AIM: To study the clinical and endoscopic efficacy and histological evolution of gastric mucosa during 5 years of maintenance treatment with lansoprazole, 30 mg. METHODS: Seventy-eight patients with endoscopically proven oesophagitis were followed for 5 years. Biopsies taken at the start of the study, during follow-up and after 5 years were available for 73 patients. RESULTS: The total endoscopic relapse rate was 14.1%. At the start of the study, 34 patients were Helicobacter pylori negative and 39 were Helicobacter pylori positive (two atrophy, 25 antral gastritis, 12 pangastritis). At 5 years, no histological changes had occurred in Helicobacter pylori-negative patients. In the Helicobacter pylori-positive group, 20 patients developed pangastritis, six had normal histology and one had antral gastritis. Ten of the 12 patients with pangastritis had reduced antral activity. There was no increase in intestinal metaplasia, but there was a tendency towards regression of atrophy in the antrum and towards increased atrophy in the body of the stomach. CONCLUSIONS: Maintenance treatment with lansoprazole, 30 mg, is efficacious. The development of glandular atrophy and intestinal metaplasia was not accelerated in Helicobacter pylori-positive patients. Helicobacter pylori eradication must be considered only because of the higher cancer risk associated with chronic Helicobacter pylori-related gastritis.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed2001

Effects of anti-tumour necrosis factor, interleukin-10 and antibiotic therapy in the indometacin-induced bowel inflammation rat model.

BACKGROUND: The administration of indometacin to rats increases intestinal permeability and induces inflammatory pathology of the small bowel. This represents a potential model for Crohn's disease. AIMS: To analyse the pathogenic role of T cells, tumour necrosis factor and bacterial flora in indometacin-induced changes in small bowel permeability and inflammation. METHODS: Rats were given indometacin, 13 mg/kg, on day 1 and day 2. The effects of antibiotic (metronidazole, aztreonam and amoxicillin/clavulanic acid), anti- tumour necrosis factor and interleukin-10 therapy were evaluated. The parameters used were weight change, serum haemoglobin, chromium-51 ethylenediaminetetra-acetate permeability and macro-and microscopic score on day 5. Results in conventionally harboured rats were compared with those in T-cell-free rats. Additional in vitro experiments were carried out to test the effect of metronidazole on tumour necrosis factor production. RESULTS: Indometacin administration resulted in small bowel ulcers and inflammation, independently of T cells. Metronidazole was more potent than amoxicillin/clavulanic acid and anti-tumour necrosis factor in improving the indometacin-induced small bowel inflammation. Only part of the efficacy was through improvement of increased intestinal permeability. Aztreonam and interleukin-10 had no effect. Metronidazole also suppressed in vitro lipopolysaccharide-induced tumour necrosis factor production, suggesting a therapeutic effect of this drug through the inhibition of tumour necrosis factor. CONCLUSIONS: These data implicate anaerobic bacteria and tumour necrosis factor production, but not T cells, as essential elements of the pathogenesis of indometacin-induced small bowel inflammation. Tumour necrosis factor is also involved in the change in intestinal permeability. Metronidazole was the most efficacious drug in this model, probably because it suppressed anaerobic bacteria and directly inhibited tumour necrosis factor production.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed2001

Contractile effects and intracellular Ca2+ signalling induced by motilin and erythromycin in the circular smooth muscle of human colon.

Motilin has excitatory effects on the colon of the rabbit and the dog, but little is known of its effect on the human colon. The aim of this study was to investigate the effects induced by motilin and erythromycin A (EMA) on muscle strips and on single cells from primary cultures from human colon. Isotonic contraction was recorded in circular muscle strips from macroscopically normal resection specimens of patients operated on for colonic neoplasm. Agonist-induced intracellular Ca2+ ([Ca2+]i) signalling was studied in primary cultures of colonic smooth-muscle cells using the ratiometric Ca2+ indicator Indo 1, on a laser-scanning confocal epifluorescence microscope. In circular muscle strips, norleucine13-porcine motilin ([Nle13]-pm)and EMA induced tonic contractions with an EC50 of 92 +/- 21 nmol L(-1) and 31 +/- 16 micromol L(-1), respectively. The maximal contraction was 21 +/- 4% (motilin) and 33 +/- 12% (EMA) of the response to 10(-4) mol L(-1) acetylcholine (ACh). The motilin antagonist OHM-11526 (10(-5.5) mol L(-1)) abolished the effects of both [Nle13]-pm and EMA. Neither tetrodotoxin (10(-5.5) mol L(-1)), L-nitro-D-arginine methyl ester (L-NAME) (10(-3.5) mol L(-1)) nor guanethidine (10(-5) mol L(-1)) interfered with the effects of [Nle13]-pm or EMA. [Nle13]-pm (10(-11)-10(-6) mol L(-1)) induced rises of [Ca2+]i in cultured colonic myocytes. At 10(-6) mol L-1, 94% of the cells responded, and half of the cells responded at 1.4 nmol L(-1) [Nle13]-pm. 81% (35/43) and 95% (75/79) responded to EMA (10(-6) mol L(-1)) and acetylcholine (ACh, 10(-4) mol L(-1)), respectively. The motilin antagonist GM-109 inhibited motilin- and EMA-induced [Ca2+]i rises. In the absence of extracellular Ca2+, only 13% (7/52) of the cells responded to [Nle13]-pm (10(-6) mol L(-1)) vs. 90% (47/52) to ACh (10(-4) mol L(-1)). Motilin and EMA have direct excitatory effects on circular smooth muscle from the human colon and these effects are mediated via a smooth-muscle motilin receptor. These findings suggest that motilin may regulate colonic motility and that motilides may have therapeutic potential for the treatment of colonic hypomotility.

Acetylcholine↗
PubMed2001

Pathology of inflammatory bowel diseases (IBD): variability with time and treatment.

The diagnosis of chronic idiopathic IBD and the differential diagnosis between Crohn's disease and ulcerative colitis can be made in most cases on cumulative clinical, radiological, endoscopical, biochemical and pathological evidence. Diagnostic difficulties can however, occur in fulminant colitis, in early onset disease and in long-standing disease. The microscopic evaluation of disease activity is based on the presence of active inflammation. Effective medical treatment has however, an influence upon the morphology and the evolution of the lesions and hence can affect the diagnostic features and the microscopic features used for the assessment of disease activity. A literature review was performed on clinical drug trials in IBD and the effect of the drugs upon the microscopic features. Several studies have shown that the diagnostic microscopic features and the features characteristic for disease activity vary with time and treatment. For an adequate analysis of biopsy samples of patients with IBD the pathologist should be aware of the duration of the symptoms and the type of treatment given to the patient.

Journal Article↗