Dysregulation of mucosal immunity and inflammatory bowel diseases

Normal mucosal immunity is regulated in a delicate balance between up- and down-regulatory responses to dietal or bacterial antigens. Recent studies demonstrated that pathogenesis of inflammatory bowel disease could be dysregulation of the balance of mucosal immunity. Recent advances in animal models of inflammatory bowel disease, pathogenic roles of mucosal immunoregulatory T cells, cytokines and intestinal flora are reviewed.     

Isotretinoin in inflammatory bowel diseases

The presenilin 1 (PS1) gene, located on chromosome 14, is the major gene involved in the autosomal dominant forms of early onset Alzheimer's disease (AD). In order to estimate the frequency of de novo PS1 mutations, we have sequenced the PS1 open reading frame in 13 clinically diagnosed patients with no affected relatives, who had developed AD before the age of 50. In one case with onset at 37 years, we identified a missense mutation resulting in a methionine to lysine substitution at codon 139 of the PS1 gene. This substitution is the fourth identified at the same codon. This study, in agreement with previous reports, suggests that de novo PS1 mutations can occur but at a low frequency.     

Initiation of cigarette smoking: Is it related to parental smoking behavior?

Investigated 2 theories of parent-child smoking patterns: (a) that although there is a direct relationship between the cigarette smoking of parents and their teen-aged children, the observed influences are only transitory and do not endure to adulthood, and (b) the identification theory which predicts that a young adult's smoking behavior is directly related to his parents' smoking behavior. The smoking behavior and family stability of 251 undergraduates and their parents were studied. Results support the identification interpretation of the father-son smoking pattern, as father-son smoking behaviors were directly related in intact families. The variable of family intactness was a highly relevant moderator of the parent-son smoking pattern. The mother and daughter smoking patterns remained enigmatic. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Three-dimensional rectal ultrasonography in inflammatory bowel diseases

Authors used three-dimensional ultrasound technique in diagnosing chronic inflammatory bowel diseases to demonstrate its activity and complications. For their examinations they adopted high-(7.5 MHz) frequency rectal transducers which made it possible to depict the layers and environment of the intestinal wall. To complete endoscopy, the new method of examination is suitable to state the extent and depth of the process. In cases where they had been unable to find alterations by endoscopic examinations--though the patient had complaints--residual submucoses inflammation could be demonstrated by means of this method. This method has been employed to determine surrounding fluid, lymph node and fistula. The authors support this method by demonstrating cases. In their opinion the three-dimensional ultrasound examination is a suitable new method in the field of diagnostic, therapeutic and operational indications and follow up. The advantage of the method lies in its non-invasive and reproducible quality, its three-dimensional representation, and good resolution and its resolving power as opposed to earlier technique (fistulography) for avoiding infections.     

Unconventional imaging techniques in inflammatory bowel diseases

In patients with inflammatory bowel disease (IBD), radiologic examinations are important for diagnosis and treatment. With conventional X-ray examinations, mucosal abnormalities, ulcers and fistulas can be visualised, but no information on the extramural extension of the disease can be obtained. Newer radiologic modalities (ultrasound, CT and MRI) offer new diagnostic possibilities. With ultrasound IBD can be diagnosed with good confidence and it can differentiate between Crohn's disease and ulcerative colitis. CT and MRI are indicated not so much to diagnose the disease but rather to determine the severity and spread of disease activity (transmural and extramural inflammation) and to detect complications such as fistulas and abscesses.     

Relationship between smoking and colonic involvement in inflammatory bowel disease

The effects of smoking on the onset and clinical course of inflammatory bowel disease (IBD) have been widely debated. Although smoking appears to have a clearly unfavorable effect on the course in Crohn's Disease (CD), the relationship between smoking and localization of the disease is less clear. AIM: To evaluate, in our group of patients, the relationship between smoking and the development of ulcerative colitis (UC) or CD, and between smoking and the localization of CD in the large bowel or in other sites. PATIENTS AND METHODS: The smoking habits of 171 patients at the time of diagnosis were assessed with a questionnaire. Subjects were classified into three subgroups as smokers, nonsmokers and ex-smokers. Current smokers were grouped according to their level of consumption as those who smoked fewer than or more than 10 cigarettes per day. A total of 161 patients were studied (UC n = 69, CD n = 92). Patients with CD were divided into those with colonic disease and those with no colonic involvement. We evaluated the relationship between smoking and the form of IBD, localization (colonic or noncolonic) and the presence of perianal disease (PAD) in CD. The results were analyzed with the chi-squared test. RESULTS: Smoking was more frequent in patients with CD than in those with UC (72.8% vs 31.9%). Among patients with CD, more patients without colonic involvement were smokers (84.6% vs 64.2%). However, among patients with CD involving the colon, smoking was significantly more common (64.2%) than among patients who had UC (31.9%). CONCLUSIONS: Our findings confirm a relationship between smoking and CD. Smoking seems to be associated with some degree of protection of the colonic mucosa, especially in heavy smokers.     

Changes in cigarette smoking not observed following repeated cocaine self-administration.

Acute administration of some psychoactive drugs (e.g., cocaine, heroin, methadone, d-amphetamine) has been found to increase spontaneous cigarette smoking for 1-3 hr, but the effects of chronic drug administration have not been systematically studied. Computerized cigarette dispensers were used to study the effects of multiple daily cocaine administrations on cigarette smoking. Participants were 8 (5 male) cocaine-dependent cigarette smokers who resided on a closed clinical research ward and smoked an average of 16.7 cigarettes per day during the week prior to starting the study. During test sessions on Monday, Wednesday, and Friday of each week, participants could obtain either cocaine (25 mg iv) on 2 days or saline (1 ml iv) on the other day, 3 times per day at 2-hr intervals under double-blind conditions. The number of cigarettes dispensed during study days was analyzed in 2-hr increments. No significant cocaine effect was found. These findings fail to show a change in the number of cigarettes smoked after chronic cocaine self-administration over time intervals longer than 1-3 hr. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Influence of the smoking habit in the surgery of inflammatory bowel disease

The smoking habit is a key factor in the development of inflammatory bowel disease (IBD), but little information exists as to the relationship between smoking habit, the need of surgery and its complications. OBJECTIVES: To investigate the relationship between smoking habit, the need of surgery, their complications and clinical recurrence after surgery in Crohn's disease (CD) and ulcerative colitis (UC). METHODS: We studied a group of 62 patients (22 with UC and 40 with CD) with previous surgery. We analyzed the clinical and surgical characteristics of the disease. Smoking habit was established by a personal interview. This group of patients was compared with another control group of 202 patients (133 with UC and 69 with CD) with IBD without previous surgery. RESULTS: Smoking habit was similar between operated and non-operated patients for both UC (73% and 80% non-smokers) and CD (67% and 63% smokers) The number and type of complications after surgery were not related with smoking habit. In CD patients, although the recurrences did not depend on the smoking habit, they did occur earlier in smokers than in non smokers (83.6 +/- 21 vs 155 +/- 50 weeks, p = ns). CONCLUSIONS: The smoking habit does not seem to influence significantly the need of surgery and post surgical development of IBD, although in CD the smokers seems to present recurrence before non smokers.     

Interleukin-1 receptor antagonist in differential diagnosis of inflammatory bowel diseases

BACKGROUND: Immunoregulatory properties of cytokines may mediate disordered inflammatory events in inflammatory bowel diseases (IBDs). On the basis of data obtained in experimental colitis, the hypothesis has been advanced that in IBD the balance between interleukin-1 (IL-1) and the naturally occurring IL-1 receptor antagonist (IL-1ra) might influence disease expression. OBJECTIVE: We studied the profiles of IL-1ra and acute phase proteins produced by activated macrophages to determine whether the level of IL-1ra in peripheral blood is a marker of disease activity in IBD and a possible differential diagnostic marker. PATIENTS AND METHODS: Levels of IL-1ra, serum neopterin, urinary neopterin, alpha 1-glycoprotein and C-reactive protein (CRP) were measured in 80 patients with ulcerative colitis, Crohn's disease or infectious colitis. RESULTS: Levels of IL-1ra were markedly increased in patients with active ulcerative colitis or active Crohn's disease compared with those in patients with infectious colitis. Patients with active Crohn's disease had significantly higher serum IL-1ra levels than patients with active ulcerative colitis. Moreover, a positive correlation was found between levels of C-reactive protein, alpha 1-glycoprotein, and serum neopterin and the level of IL-1ra in active Crohn's disease but not in active ulcerative colitis, strongly suggesting that the pathogenesis of the two conditions differs. CONCLUSION: Levels of IL-1ra in the peripheral blood of patients with IBD are of clinical relevance, representing a potent marker of disease activity and a possible differential diagnostic marker.     

Exhaled nitric oxide is not elevated in the inflammatory airways diseases of cystic fibrosis and bronchiectasis

Airways inflammation has been associated with increased nitric oxide (NO) in the exhaled breath. It was, therefore, questioned whether exhaled NO could act as an indicator of the severity of airways inflammation in the chronic suppurative lung diseases cystic fibrosis (CF) and bronchiectasis. NO levels in a single exhalation were measured using a chemiluminescence analyser. Thirty-six patients with CF and 16 with bronchiectasis were studied and compared with 22 normal subjects and 35 asthmatic patients. All subjects were nonsmokers and all measurements were made when patients were clinically stable. In addition, exhaled NO was measured in 10 CF patients at the time of onset of an acute infective exacerbation and followed for 7 days during the treatment of the exacerbation in eight of the 10 patients. No significant differences were found in NO levels in patients with CF or bronchiectasis compared with normals (median 4.0, 5.5 and 4.4 parts per billion (ppb), respectively), but all were lower than in asthma patients (10.4 ppb). The NO levels in the CF patients at time of exacerbation were not increased and did not change during treatment. These data show that nitric oxide levels in the exhaled breath of patients with chronic suppurative lung diseases, in contrast to asthma, are not elevated, despite the presence of substantial airways inflammation. Possible explanations include poor diffusion of nitric oxide across increased and viscous airway secretions, removal of nitric oxide by reaction with reactive oxygen species in the inflamed environment and failure of upregulation of epithelial inducible nitric oxide synthase in chronic suppurative conditions.     

Individual differences in cardiovascular reactions to stress and cigarette smoking.

Examined the stability of cardiovascular (CDV) reactions to psychological stress and cigarette smoking and the extent to which CDV actions to stress were predictive of CDV reactions to smoking. 26 male Ss were given an initial test involving 2 repetitions of mental arithmetic stress and paced smoking while blood pressure and heart rate were measured. Ss were retested 2 mo later in the same paradigm. Large and stable individual differences were observed in CDV reactivity to both stress and smoking. For systolic and diastolic blood pressure, but not heart rate, reactions to stress were modestly correlated with reactions to cigarette smoking, suggesting that levels of reactivity to cigarette smoking may have significance for coronary heart disease and blood pressure. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Desire and efforts to quit smoking among cigarette smokers in Wisconsin

This research studied the desire and attempts of cigarette smokers in Wisconsin to quit smoking. Data were based on the 1993 Wisconsin Division of Health's Behavioral Risk Factor Surveillance System (BRFSS). Among the 23% of respondents who were current smokers, 79% said they wanted to quit smoking and 60% said they had quit smoking for a day or more in the preceding year. High rates of wanting to quit and having tried to quit were found in all demographic subgroups of smokers studied. Compared to lighter smokers, heavy cigarette smokers (20 or more cigarettes per day) were less likely to have tried quitting in the past year, but were almost as likely to want to quit. These results demonstrate the great demand for smoking cessation services among smokers in Wisconsin and support for efforts to increase the use and effectiveness of these interventions.     

Cytokine profiles differ in newly recruited and resident subsets of mucosal macrophages from inflammatory bowel disease

BACKGROUND & AIMS: Most macrophages in the normal intestinal mucosa have a mature phenotype. In inflammatory bowel disease (IBD), a monocyte-like subset (CD14+ L1+) accumulates. The aim of this study was to characterize its potential with regard to cytokines. METHODS: Lamina propria mononuclear cells were adherence-separated, with or without depletion of CD14+ cells, and production of cytokines was investigated by bioassay, enzyme-linked immunosorbent assay, or immunocytochemistry. RESULTS: Tumor necrosis factor alpha (TNF-alpha), interleukin 1beta (IL-1beta), and IL-1 receptor antagonist were found mainly in cells positive for myelomonocytic L1. In undepleted IBD cultures, TNF-alpha, IL-1alpha and beta, and IL-10 were markedly up-regulated by pokeweed mitogen stimulation; IL-1alpha and beta and IL-10 were also up-regulated by stimulation of interferon gamma and lipopolysaccharide in combination. The latter stimulation had no effect on normal control or CD14-depleted IBD cultures. Indomethacin caused a marked increase of TNF-alpha, particularly in undepleted IBD cultures, whereas IL-10 and IL-4 decreased TNF-alpha and IL-1beta in both CD14+ and CD14 macrophages. CONCLUSIONS: In IBD mucosa, macrophages with a monocyte-like phenotype are primed for production of TNF-alpha and IL-1alpha/beta and may therefore be of significant pathogenic importance [corrected]. However, this CD14+ subset, as well as the mucosal resident macrophages, have preserved responsiveness to several down-regulatory factors such as the macrophage deactivators IL-10 and IL-4.     

N-linked oligosaccharide processing is not necessary for glycoprotein secretion in plants

Mitochondria contain a potassium specific channel (mitoKATP channel) sensitive to ATP and antidiabetic sulfonylureas. The mitochondrial KATP channel plays an important role in the mitochondrial volume control and in regulation of the components of protonmotive force. This minireview describes the properties and current hypotheses concerning the function of mitoKATP channel.