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Frequency of inflammatory bowel disease in offspring of couples both presenting with inflammatory bowel disease.

A private practice was surveyed for prevalence of inflammatory bowel disease (IBD) in husband-wife partners and in their children. Among approximately 2500 patients with IBD in our files, 19 couples were identified. They were subdivided into group A (n = 5) in which both partners had symptoms of IBD before marriage; group B (n = 7) in which only one spouse had IBD before marriage and the other partner experienced symptoms afterwards; and group C (n = 7) in which neither spouse had symptoms before marriage but IBD subsequently developed in both. In group B, the disease developed in the second spouse 2-16 years after marriage (mean, 6.4 years). In group C, IBD developed in the first spouse 0.3-41 years after marriage and in the second spouse 1-14 years after the first spouse (mean, 6.8 years). Thirty-five children have been born to 16 of the couples. Two children died before age 20. Of the surviving 33 children, IBD has already developed in 12 (36%). Among the other 21 unaffected children, 1 had uveitis at age 9 and 10 are still under the age of 21, perhaps too young to have yet developed IBD. The frequency of IBD in children was slightly higher if both parents had already developed IBD at the time of conception (67%) compared with when only 1 parent (50%) or neither parent (50%) had developed IBD when conception occurred. Although these data do not distinguish genetic from environmental factors, they show a higher risk of IBD in children when both parents have this illness.

Adult↗

Role of inflammatory responses in initiation of atherosclerosis: effects of anti-inflammatory drugs on cuff-induced leukocyte accumulation and intimal thickening of rabbit carotid artery.

Immediately after a cuff-sheathing of rabbit carotid artery, a large number of leukocytes adhered to injured endothelium then infiltrated into the media. These inflammatory responses were followed by an atherosclerotic change, intimal thickening, of the artery. A simultaneous injection of dexamethasone (10 mg/kg i.m.) inhibited the leukocyte accumulation by 74% when evaluated 18 h thereafter. Similarly, 39% inhibition was obtained with the same dose of FR110302, a potent 5-lipoxygenase inhibitor. On the other hand, the same dose of indomethacin, a cyclooxygenase inhibitor, had little effect on the leukocyte accumulation. The intimal thickening which was evaluated 3 weeks after the cuff-treatment was attenuated by a daily dose (10 mg/kg i.m.) of dexamethasone or FR110302 but not by one of indomethacin. The inhibition by the two former drugs were 91 and 58%, respectively. In vitro, the three drugs in concentrations up to 10 microM hardly affected endothelial adhesion of PMN which was induced by LPS or IL-1. Though 10 microM of FR110302 and indomethacin significantly decreased PMN chemotaxis induced by LTB4, the decreases were less than that at 10 microM dexamethasone. These results confirm a possible linkage between inflammation and atherosclerosis, and suggest that 5-lipoxygenase products contribute to the initiation and development of atherosclerosis.

Animals↗

Biological rhythms in the inflammatory response and in the effects of non-steroidal anti-inflammatory drugs.

It is well known that some signs and symptoms of rheumatoid arthritis (RA) vary within a day and between days, and the morning stiffness observed in RA patients has become one of the diagnostic criteria of the disease. Research carried out in the last 10 years confirmed these clinical observations, and circadian, circaseptan or circannual variations were detected in experimental inflammation and in patients with arthritis diseases. The human data showed also that large interindividual differences can be found in the symptoms of RA. The chronopharmacological studies carried out with the non-steroidal anti-inflammatory drugs (NSAID) revealed circadian and circannual variations in the effectiveness, toxicity and pharmacokinetics of NSAID. A review of the available data suggests that peak and trough values found in different arthritic diseases do not occur at the same hour of the day and that the side effects produced by NSAID are more important after the morning than the evening administration. This information should be used by clinicians to determine when to administer drugs to arthritic patients, to optimize the effectiveness of NSAID and/or to reduce the side effects of these drugs. These new data could also be useful to physicians who would like to individualize NSAID use in patients with different arthritic diseases.

Animals↗

Relationship between insulin resistance and inflammatory markers and anti-inflammatory effect of losartan in patients with type 2 diabetes and hypertension.

BACKGROUND: It is now well established that vascular inflammation and endothelial dysfunction associated with cardiovascular diseases contributes to insulin resistance. METHODS: We investigated the relationship between the homeostasis model assessment-insulin resistance index (HOMA-R) and various serum inflammatory markers and the effect of losartan on serum concentrations of these markers in patients with type 2 diabetes and hypertension. The patients were divided into 2 groups according to the value of HOMA-R with 60 patients with values=2.4 in Group A and 44 patients with values>2.5 in Group B. The variables were measured at baseline and after 6 months of treatment with losartan (50 mg/day). RESULTS: The HOMA-R concentrations were positively related to TNF-alpha (r=0.336, P<0.01) and inversely related to adiponectin (r=-0.405, P<0.01) and extracellular-superoxide dismutase (EC-SOD) (r=-0.452, P<0.01). Stepwise multiple regression analysis showed a significant relationship between HOMA-R and adiponectin (F=8.74) and EC-SOD (F=14.39). In Group B, losartan treatment significantly increased the serum concentrations of EC-SOD and adiponectin and decreased TNF-alpha and HOMA-R. CONCLUSION: Serum EC-SOD concentrations may be a sensitive biochemical marker of insulin resistance in patients with type 2 diabetes and hypertension and that losartan improves insulin sensitivity by increasing EC-SOD and adiponectin production and decreasing TNF-alpha production.

Anti-Inflammatory Agents↗

Reduced migration of fibroblasts in inflammatory bowel disease: role of inflammatory mediators and focal adhesion kinase.

BACKGROUND & AIMS: Crohn's disease (CD) and ulcerative colitis (UC) are associated with chronic tissue damage and continuous tissue repair. A central, but not well-characterized, event during this process is the migration of activated fibroblasts to the wound. METHODS: Human colonic lamina propria fibroblasts (CLPF) were isolated from patients with CD and UC and from healthy controls and were characterized by immunocytochemistry. Migration assays of CLPF were performed in the modified 48-well Boyden chamber. Focal adhesion kinase (FAK) and FAK autophosphorylation in migrating CLPF were determined by Western blotting. FAK mRNA expression was investigated by Northern blotting. RESULTS: The migration of CD-CLPF and UC-CLPF was significantly reduced when compared with control-CLPF. This was correlated with a decrease in FAK phosphorylation, whereas, in migrating control-CLPF, an increase was found. Similarly, the presence of the inflammatory mediators interferon (IFN)-gamma (50 ng/mL) or tumor necrosis factor (TNF) (30 ng/mL) in conditioned medium significantly reduced the migration of control-CLPF to 41% +/- 4% or 30% +/- 7%, respectively. Preincubation of control-CLPF with TNF (20 ng/mL) and IFN-gamma (10 ng/mL) for 3 days reduced their migratory response to 10% of control (P < 0.001), which also was correlated with a decrease in FAK phosphorylation. Culture of IFN-gamma/TNF-treated CLPF for a further 7 days without cytokines did not restore the migratory potential and FAK phosphorylation, indicating a persistent functional change. CONCLUSIONS: CD- and UC-CLPF have a reduced migratory potential compared with normal CLPF. That may be caused by contact with IFN-gamma and TNF. This loss of migratory potential was correlated with diminished FAK phosphorylation.

Adult↗

Local interactions between anandamide, an endocannabinoid, and ibuprofen, a nonsteroidal anti-inflammatory drug, in acute and inflammatory pain.

Anandamide, an endocannabinoid, is degraded by the enzyme fatty acid amide hydrolase which can be inhibited by nonsteroidal anti-inflammatory drugs (NSAIDs). The present work was designed to study the peripheral interactions between anandamide and ibuprofen (a non-specific cyclooxygenase inhibitor) in the rat formalin test. We first determined the ED50 for anandamide (0.018 microg +/- 0.009), ibuprofen (0.18 microg +/- 0.09), and their combination (0.006 microg +/- 0.002). Drugs were given 15 min before a 2.5% formalin injection into the dorsal surface of the right hind paw. Results were analyzed using isobolographic analysis. The antinociceptive interaction between anandamide and ibuprofen was synergistic. To further investigate the mechanisms by which the combination of anandamide with ibuprofen produced their antinociceptive effects, we used specific antagonists for the cannabinoid CB1 (AM251; 80 microg) and CB2 (AM630; 25 microg) receptors. We demonstrated that the antinociceptive effects of ibuprofen were not antagonized by either AM251 or AM630 and that those of anandamide were antagonized by AM251 but not by AM630. The synergistic antinociceptive effects of the combination of anandamide with ibuprofen were completely antagonized by AM251 but only partially inhibited by AM630. In conclusion, locally (hind paw) injected anandamide, ibuprofen or combination thereof decreased pain behavior in the formalin test. The combination of anandamide with ibuprofen produced synergistic antinociceptive effects involving both cannabinoid CB1 and CB2 receptors. Comprehension of the mechanisms involved needs further investigation.

Acute Disease↗

Omega-3 fatty acids (fish oil) as an anti-inflammatory: an alternative to nonsteroidal anti-inflammatory drugs for discogenic pain.

BACKGROUND: The use of NSAID medications is a well-established effective therapy for both acute and chronic nonspecific neck and back pain. Extreme complications, including gastric ulcers, bleeding, myocardial infarction, and even deaths, are associated with their use. An alternative treatment with fewer side effects that also reduces the inflammatory response and thereby reduces pain is believed to be omega-3 EFAs found in fish oil. We report our experience in a neurosurgical practice using fish oil supplements for pain relief. METHODS: From March to June 2004, 250 patients who had been seen by a neurosurgeon and were found to have nonsurgical neck or back pain were asked to take a total of 1200 mg per day of omega-3 EFAs (eicosapentaenoic acid and decosahexaenoic acid) found in fish oil supplements. A questionnaire was sent approximately 1 month after starting the supplement. RESULTS: Of the 250 patients, 125 returned the questionnaire at an average of 75 days on fish oil. Seventy-eight percent were taking 1200 mg and 22% were taking 2400 mg of EFAs. Fifty-nine percent discontinued to take their prescription NSAID medications for pain. Sixty percent stated that their overall pain was improved, and 60% stated that their joint pain had improved. Eighty percent stated they were satisfied with their improvement, and 88% stated they would continue to take the fish oil. There were no significant side effects reported. CONCLUSIONS: Our results mirror other controlled studies that compared ibuprofen and omega-3 EFAs demonstrating equivalent effect in reducing arthritic pain. omega-3 EFA fish oil supplements appear to be a safer alternative to NSAIDs for treatment of nonsurgical neck or back pain in this selective group.

Alprostadil↗

Helicobacter pylori and nonsteroidal anti-inflammatory drugs: interaction with proton pump inhibitor therapy for prevention of nonsteroidal anti-inflammatory drug ulcers and ulcer complications--future research needs.

Two recently reported studies of nonsteroidal anti-inflammatory drugs (NSAIDs), the Omeprazole versus Misoprostol for NSAID-induced Ulcer Management and the Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-associated Ulcer Treatment studies, concluded that omeprazole was superior to a subtherapeutic misoprostol or an ineffective dose of ranitidine for the endpoint, prevention of gastroduodenal ulcers in chronic NSAID users. Helicobacter pylori status was collected prospectively but was not reported. We report separate analyses for patients with unequivocal NSAID ulcers (H. pylori negative) and patients whose NSAID use was complicated by the presence of an active H. pylori infection. Omeprazole was superior to placebo for the prevention of ulcer recurrence in chronic NSAID users. However, omeprazole was not significantly better than a subtherapeutic dose of misoprostol for the prevention of gastroduodenal ulcers in chronic NSAID users. Misoprostol was superior to omeprazole for the prevention of gastric ulcers among those patients with unequivocal NSAID ulcers (8.2% vs 16.6%, respectively; P <0.05). Omeprazole was not statistically different from misoprostol for gastric ulcer prevention in those whose NSAID use was complicated by an active H. pylori infection. Ranitidine and omeprazole were also not statistically different for the prevention of unequivocal NSAID gastric ulcers (14.6% vs 11.6%, respectively; P = 0.56). That the Misoprostol Ulcer Complications Outcomes Safety Assessment (MUCOSA) trial found full-dose misoprostol to be more effective in ulcer prevention than it was in prevention of ulcer complications suggests that either many of the ulcer complications were related to H. pylori ulcers or that more antisecretory activity than can be provided with misoprostol is needed, or both. The question remains whether the combination of low-dose misoprostol plus an antisecretory drug (either an H(2)-receptor antagonist or a proton pump inhibitor) would provide superior results compared with either alone. That omeprazole was not superior to one half the dose of misoprostol used in the ulcer complication prevention, or MUCOSA, study indicates that it would not be prudent to suggest that ulcer prevention with omeprazole alone would be able to provide similar protection to misoprostol.

Anti-Inflammatory Agents, Non-Steroidal↗

Cathepsin D specifically cleaves the chemokines macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta, and SLC that are expressed in human breast cancer.

Cathepsin D (Cath-D) expression in human primary breast cancer has been associated with a poor prognosis. In search of a better understanding of the Cath-D substrates possibly involved in cancer invasiveness and metastasis, we investigated the potential interactions between this protease and chemokines. Here we report that purified Cath-D, as well as culture supernatants from the human breast carcinoma cell lines MCF-7 and T47D, selectively degrade macrophage inflammatory protein (MIP)-1 alpha (CCL3), MIP-1 beta (CCL4), and SLC (CCL21). Proteolysis was totally blocked by the protease inhibitor pepstatin A, and specificity of Cath-D cleavage was demonstrated using a large chemokine panel. Whereas MIP-1 alpha and MIP-1 beta degradation was rapid and complete, cleavage of SLC was slow and not complete. Mass spectrometry analysis showed that Cath-D cleaves the Leu(58) to Trp(59) bond of SLC producing two functionally inactive fragments. Analysis of Cath-D proteolysis of a series of monocyte chemoattractant protein-3/MIP-1 beta hybrids indicated that processing of MIP-1 beta might start by cleaving off amino acids located in the C-terminal domain. In situ hybridization studies revealed MIP-1 alpha, MIP-1 beta, and Cath-D gene expression mainly in the stromal compartment of breast cancers whereas SLC transcripts were found in endothelial cells of capillaries and venules within the neoplastic tissues. Cath-D production in the breast carcinoma cell lines MCF-7 and T47D, as assessed by enzyme-linked immunosorbent assay of culture supernatants and cell lysates, was not affected by stimulation with chemokines such as interleukin-8 (CXCL8), SDF-1 (CXCL12), and SLC. These data suggest that inactivation of chemokines by Cath-D possibly influences regulatory mechanisms in the tumoral extracellular microenvironment that in turn may affect the generation of the antitumoral immune response, the migration of cancer cells, or both processes.

Amino Acid Sequence↗

Platelets trigger a CD40-dependent inflammatory response in the microvasculature of inflammatory bowel disease patients.

BACKGROUND & AIMS: Platelets circulate in an activated state in patients with inflammatory bowel disease (IBD), but their role in the pathogenesis of IBD is unclear. The recent demonstration that activated platelets express CD40 ligand (L) provides a mechanism of interaction with CD40-positive endothelial cells, inducing them to produce proinflammatory mediators. We investigated whether platelets from patients with IBD express enhanced levels of CD40L and induce human intestinal microvascular endothelial cells (HIMEC) to up-regulate cell adhesion molecule (CAM) expression and secrete chemokines. METHODS: CD40L expression was assessed in resting and thrombin-activated platelets by flow cytometry and in mucosal microthrombi by confocal microscopy. Platelet-HIMEC cocultures were used to study CAM up-regulation, and interleukin (IL)-8 and RANTES production by HIMEC. RESULTS: IBD platelets expressed significantly higher CD40L levels than those of healthy subjects, and CD40L-positive platelets were detected in IBD-involved mucosa. Activated platelets up-regulated expression of intercellular adhesion molecule 1 and vascular cell adhesion molecule 1 as well as production of interleukin 8 by HIMEC in a CD40-dependent fashion. High levels of RANTES were present in platelet-HIMEC cocultures and platelets were identified as the source of this chemokine, which mediated T-cell adhesion to HIMEC. CONCLUSIONS: These results show that platelets can actively contribute to mucosal inflammation and represent a previously unrecognized component of IBD pathogenesis.

Blood Platelets↗

Copper(II) complexes of a nonsteroidal anti-inflammatory drug niflumic acid. Synthesis, crystal structure of tetrakis-mu-(2-[3-(trifluoromethyl) phenyl]aminonicotinato)bis(dimethylsulfoxide)-dicopper(II) complex at 190 K. Anti-inflammatory properties.

The synthesis and characterization of three complexes with a potent nonsteroidal anti-inflammatory drug niflumic acid {2-[3-(trifluoromethyl)phenyl]aminonicotinic acid} with formula [Cu(niflumato)2L] (L = H2O, DMSO = dimethylsulfoxide, DMF = N,N-dimethylformamide) were investigated. The crystal and molecular structure of the {Cu(niflumato)2(DMSO)}2 was reported. Crystallographic data are as follows: monoclinic system, space group P2(1)/n, Z = 2, a = 11.1318(8), b = 17.513(2), c = 15.336(1) A, beta = 103.316(8) degrees, V = 2909.4(4) A3. The structure was refined to R = 0.030 and wR = 0.037 for 3702 reflections with I > sigma (I). It consists of centrosymmetric binuclear units with the Cu-Cui (symmetry code i: 1-x, -y, 1-z) distance between two centrosymmetrically related ions of 2.6272(5) A. Each Cu(II) ion in [Cu2(DMSO)2(mu-niflumato)4] is coordinated to an apical dimethylsulfoxide O atom on the one hand and to the equatorial carbonyl and carboxylic O atoms of two crystallographically independent niflumate moieties and their centrosymmetric counterparts on the other hand. In spite of the low-temperature (190 K) crystal measurements, one L-CF3 grouping exhibits some disorder. The biological activities of these complexes were compared to that of niflumic acid. Niflumic acid and its various copper complexes significantly inhibited polymorphonuclear leukocyte (PMNL) oxidative metabolism, as assessed by chemiluminescence and O2- generation measurement. This effect was dose-dependent. All copper complexes exerted a similar inhibiting effect which was always significantly higher than that exerted by the parent drug.

Animals↗

In-situ detection of both inflammatory and anti-inflammatory cytokines in resting peripheral blood mononuclear cells during pregnancy.

INTRODUCTION: Local and possibly systemic curtailment of the maternal immune response is important for a successful pregnancy. Although the local milieu at the utero-placental interface is likely to harbor the most prominent alterations, it is suggested, at least in mice, that systemic immunity is also tolerized during pregnancy. In the present study, we investigated mRNA expression of the key immunomodulatory cytokines; interleukin (IL)-4, IL-10, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma during normal pregnancy. MATERIAL AND METHODS: In-situ hybridization (ISH) of cytokine mRNA in resting peripheral blood mononuclear cells (PBMCs) was used to detect the number of cells spontaneously expressing cytokines. Eleven women with normal gestations were followed during pregnancy as well as 8 weeks postpartum, and compared with 10 non-pregnant healthy controls. RESULTS: The numbers of IFN-gamma and IL-4 mRNA expressing cells were found to be significantly increased during pregnancy and postpartum compared with non-pregnant controls. Pregnant women and non-pregnant controls did not differ in their expression of TNF-alpha and IL-10. CONCLUSION: Our studies demonstrated increased numbers of both IFN-gamma and IL-4 mRNA expressing cells in blood suggesting that systemic immunomodulation, albeit partial, takes place during normal pregnancy. It is proposed that enhanced IL-4 expression, possibly in concert with other elevated anti-inflammatory immunomodulatory cytokines, curtail the potentially hazardous effects of IFN-gamma on systemic immunity during pregnancy.

Adult↗

Development of affinity labeling agents based on nonsteroidal anti-inflammatory drugs: labeling of the nonsteroidal anti-inflammatory drug binding site of 3 alpha-hydroxysteroid dehydrogenase.

Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effect by inhibiting the target enzyme cyclooxygenase (prostaglandin H2 synthase); however, little is known about the peptides comprising its NSAID binding site. Hydroxyprostaglandin dehydrogenases also bind NSAIDs, but their NSAID binding sites have not been well characterized. Using existing synthetic strategies, we have incorporated the bromoacetoxy affinity labeling moiety around the perimeter of two potent NSAIDs, indomethacin and mefenamate, a N-phenylanthranilate. The compounds synthesized were 1-(4-(bromoacetamido)benzyl)-5-methoxy-2-methylindole-3-acetic acid (1), 3-(2-(2-bromoacetoxy)ethyl)-1-(4-chlorobenzyl)-5-methoxy-2-methylindole (2), 4-(bromoacetamido)-N-(2,3-dimethylphenyl)anthranilic acid (3), N-(3-(bromoacetamido)phenyl)-anthranilic acid (4), and N-(4-(bromoacetamido)phenyl)anthranilic acid (5). To access whether these compounds have general utility in labeling NSAID binding sites, the compounds were evaluated as affinity labeling agents for 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD) from rat liver cytosol. This enzyme displays 9-, 11-, and 15-hydroxyprostaglandin dehydrogenase activity, is inhibited potently by NSAIDs, and is homologous to bovine lung prostaglandin F synthase. Compounds 1-5 were shown to affinity label the NSAID binding site of 3 alpha-HSD. They inactivated 3 alpha-HSD through an E.I complex in a time- and concentration-dependent manner with t1/2 values ranging from seconds to hours. Ligands that compete for the active site of 3 alpha-HSD (NAD+ and indomethacin) afforded protection against inactivation, and the inactivators could demonstrate competitive kinetics against 3 alpha-hydroxysteroid substrates by forming an E.NAD+.I complex.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxysteroid Dehydrogenases↗

Other anti-inflammatory uses of intranasal corticosteroids in upper respiratory inflammatory diseases.

Topical corticosteroids are an effective treatment for nasal polyposis and other conditions associated with rhinitis. There is evidence that asthma, otitis media with effusion, and acute sinusitis may all benefit from such therapy. Fluticasone propionate (FP) drops have been shown to reduce polyp size, and to improve nasal inspiratory flow, while avoiding the side-effects of, for example, topical betamethasone therapy. In small children with allergic rhinitis, fluticasone propionate aqueous nasal spray (FPANS) has been shown to be significantly more effective than ketotifen in relieving night and daytime symptoms, and nasal blockage. There is also preliminary evidence of efficacy in obstructive sleep apnoea and acute sinusitis. The advent of FP, with its low propensity to cause systemic side-effects, makes it possible to use topical corticosteroid therapy safely for prolonged periods to treat many inflammatory diseases of the upper respiratory tract.

Administration, Intranasal↗

Localization of pro-inflammatory (IL-12, IL-15) and anti-inflammatory (IL-11, IL-13) cytokines at the foetomaternal interface during murine pregnancy.

The involvement of some interleukins (ILs) in early and established pregnancy has been convincingly demonstrated, but little is known about the potential role of the more recently discovered ones. However, since many of these have positive or negative regulatory effects on both NK and T cells, it is highly probable that they also have regulatory functions in both implantation and placental development. Therefore, as a first step in tackling this problem, we have investigated whether several recently described pro- (IL-12, IL-15) and anti-inflammatory (IL-11, IL-13) cytokines were expressed at the uteroplacental interface by use of immunohistochemistry at different stages of gestation in mice. Each of these molecules was found at the foetomaternal interface, with specific distributions and patterns of expression depending on both the cytokine itself and the stage of pregnancy. The significance of these data is discussed.

Animals↗

Increased serum levels of macrophage inflammatory protein-3alpha in chronic viral hepatitis: prognostic importance of macrophage inflammatory protein-3alpha during interferon therapy in chronic hepatitis C.

Increased infiltration of lymphocytes and induction of damage and destruction of hepatocytes by these lymphocytes are characteristic features of chronic viral hepatitis. As chemokines attract lymphocytes to inflamed tissues, we studied macrophage inflammatory protein (MIP)-3alpha, a CC chemokine, in chronic viral hepatitis. The levels of MIP-3alpha were measured in the sera from 40 patients with chronic viral hepatitis and 30 control subjects by an enzyme-linked immunosorbent assay (detection limit of MIP-3alpha=7.8 pg/mL). The kinetics of MIP-3alpha were checked during interferon (IFN) therapy in 25 patients. The levels of MIP-3alpha in the sera were significantly higher in patients with chronic viral hepatitis (39.0 +/- 28.9 pg/mL) than control subjects (15.6 +/- 4.9 pg/mL; P < 0.0001) and in patients with severe (49.6 +/- 49.2 pg/mL) and moderate degree of hepatitis (50.9 +/- 27.1 pg/mL) than in mild disease (16.0 +/- 6.8 pg/mL; P < 0.05). A significant correlation was seen among serum MIP-3alpha levels with the levels of alanine aminotransferase (r=0.509, P < 0.0001), aspartate aminotransferase (r=0.505, P < 0.0001), and degrees of activity of hepatitis (r=0.592, P < 0.0001) and interface hepatitis (r=0.419, P=0.0066). The levels of MIP-3alpha were significantly increased in patients with hepatitis C 2 weeks after the start of therapy in IFN-responders, but, remained almost unchanged in IFN-nonresponders. These findings might be important not only for the understanding of immunoptahogenesis of hepatocellular damage in chronic hepatitis (CH) patients but also for a therapeutic strategy to control the local immune response in the liver. A prognostic value of MIP-3alpha during IFN therapy in patients with chronic hepatitis C is also shown.

Adult↗

The clustering of other chronic inflammatory diseases in inflammatory bowel disease: a population-based study.

BACKGROUND & AIMS: We aimed to discern the relative risk for several chronic inflammatory conditions in patients with ulcerative colitis (UC) and Crohn's disease. METHODS: We used the population-based University of Manitoba IBD Database that includes longitudinal files on all patients from all health system contacts identified by International Classification of Diseases, 9th revision, Clinical Modification codes for visit diagnosis. From the provincial database we extracted a control cohort matching the IBD patients 10:1 by age, sex, and geography. We considered a potential comorbid disease to be present if the patient had 5 or more health system contacts for that diagnosis. The comorbid disease period prevalence was analyzed separately for patients with UC and Crohn's disease and a prevalence ratio was calculated comparing the IBD populations with the matched cohort. RESULTS: There were 8072 cases of IBD from 1984 to 2003, including UC (n = 3879) and Crohn's disease (n = 4193). There was a mean of approximately 16 person-years of coverage for both patients and control patients. Both UC and Crohn's disease patients had a significantly greater likelihood of having arthritis, asthma, bronchitis, psoriasis, and pericarditis than population controls. An increased risk for chronic renal disease and multiple sclerosis was noted in UC but not Crohn's disease patients. The most common nonintestinal comorbidities identified were arthritis and asthma. CONCLUSIONS: The finding of asthma as the most common comorbidity increased in Crohn's disease patients compared with the general population is novel. These may be diseases with common causes or complications of one disease that lead to the presentation with another. Studies such as this should encourage further research into the common triggers in the organ systems that lead to autoimmune diseases.

Asthma↗

[Consensus of the Chronic Inflammatory Bowl Disease Study Group of the Austrian Society of Gastroenterology and Hepatology on the topic of "diagnosis and therapy of chronic inflammatory bowel diseases in adolescence"].

Although up to 20% of patients with Crohn's disease have their first flare during childhood or adolescence, there are no or only a few randomized, controlled studies. However, big differences and uncertainty may be observed between the diagnosis and therapy of pediatricians and gastroenterologists specialized for adults. In addition, special problems result from the enormous somatic and psychological evolution during adolescence. The diagnosis is done as in adult patients by enteroclysm and ileocolonoscopy (including multiple biopsies) whereas a deep sedoanalgesia or anesthesia should be performed routinely. Corticosteroids are the gold standard for therapy of Crohn's disease in the adolescence (especially in cases with high inflammatory activity), but also enteral nutrition over 4-12 weeks--or a combination of both. A recent randomized controlled study demonstrates the positive effect of 6-mercaptopurine in newly diagnosed patients with Crohn's disease in the adolescence. 5-aminosalicylates or the probably more effective azathioprine/6-mercaptopurine could be used for prevention of recurrence in Crohn's disease. The therapy of ulcerative colitis is performed as in adults including the very effective local rectal applications. An accompanying psychosomatic therapy is recommended especially in young patients with disturbed separation from the parents and inadequate coping. The indication for surgery is similar to adults. However, a specific indication for earlier surgery is given, if severe malabsorption and delay of growth takes place in spite of adequate therapy, because this delay of growth could be only caught up before puberty. A conservative therapeutic regimen is recommended in young patients with perianal Crohn's disease.

Adolescent↗