Long-term prognosis in Crohn's disease: factors that affect quality of life

BACKGROUND: There are many studies investigating quality of life in recently diagnosed patients and following surgery for Crohn's disease, but there are none investigating quality of life changes with disease duration. The response shift model suggests quality of life improves with time following diagnosis. AIM: To assess how well the model applies to patients with Crohn's disease. METHODS: The Cardiff Crohn's disease database contains data on all patients diagnosed there since 1934. Three hundred and ninety four patients diagnosed before 1 January 1985 were traced and the mortality status on 31 December 2004 established. Two hundred and eleven still living were sent quality of life questionnaires. Two hundred and eighty five questionnaires were sent to patients with varying disease duration attending out-patient clinics in Leicester. RESULTS: Eighty-nine valid replies were received from Cardiff, 63 from Leicester patients diagnosed over 20 years, 69 from Leicester patients diagnosed <10 years. There was no difference in quality of life between newly diagnosed and established patients. Of greatest concern was possible need for ostomy, uncertain nature of disease, and lack of energy. Stepwise regression showed that increased disease severity, older age and smoking adversely affect quality of life. DISCUSSION: Quality of life is equally poor in patients with established disease as in those newly diagnosed, and directly correlates with disease severity. The response shift model may not be applicable in Crohn's disease.     

Modulation of the postprandial acid and bile pockets at the gastro-oesophageal junction by drugs that affect gastric motility

Background Previous studies have established the presence of a postprandial acid pocket at the gastro‐oesophageal junction. Aims To investigate whether altering gastric motility would affect the location and the extent of postprandial acid pockets in healthy volunteers and also to study the presence of bile in this pocket. Methods A total of 16 healthy volunteers underwent pH and Bilitec probe stepwise pull‐through to measure regional differences in pH and bile absorbance before and 10, 30 and 50 min after a liquid meal. At the start of the meal, saline, erythromycin or sumatriptan was administered. Results After saline, ingestion of a meal induced an acid pocket, with a mean pH drop of 2.26 (compared to 0.25 before the meal, P < 0.05) and a nadir pH of 2.71. The acid pocket persisted 30 and 50 min postprandially (pH drops 1.59 and 1.68 and nadir pH 3.17 and 2.52 respectively). Compared with saline, erythromycin significantly suppressed the pH drop and nadir pH (on average 0.66 and 3.4 at 10 min; comparable patterns at 30 and 50 min). After sumatriptan a significantly lower nadir pH was observed at 30 and 50 min (respectively 2.02 and 1.74, P < 0.05 compared with saline). A postprandial bile pocket was noted in 50% of pull‐throughs after saline, compared to 78% after erythromycin and 31% after sumatriptan. Conclusions The presence of a bile pocket in a subset of the subjects confirms the heterogeneity of postprandial intragastric contents. Erythromycin disrupts the acid pocket but increases the presence of bile, while sumatriptan has opposite effects.     

Pharmacokinetics in the aged: A review

Age-related differences in drug response have recently received increased attention in the medical literature. This report reviews those recent publications dealing with the study of pharmacokinetics in the aged population. The rate and extent of drug absorption do not appear to be altered to any appreciable degree in the elderly patient. However, drug disposition in the aged subject may be affected by a number of factors including alterations in protein binding, apparent volumes of distribution, and renal and/or extrarenal clearance of the drug.     

Role of the epithelium in the control of intestinal motility: implications for intestinal damage after anoxia and reoxygenation.

A vibration technique was used to dislocate the epithelium from the rat small intestine, in order to study the possible regulatory role of the epithelium on intestinal motility. Complete removal of the epithelium led to a slightly potentiated contraction of the longitudinal smooth muscle by the muscarinic agonist methacholine (pD2. 6.5 +/- 0.1 vs. 6.2 +/- 0.2). The maximal beta-adrenergic response expressed relative to the relaxation by 0.5 mM dibutyryl cyclic AMP increased from 55.9 +/- 9.0% to 72.6 +/- 9.1% by this treatment. Efforts were made to relate these observations to the endothelium-dependent relaxation in blood vessels, but no indication was found for a similar mechanism in the small intestine. Not only mechanical dislocation can be employed to affect the mucosal layer, but also intestinal ischemia has been reported to lead to mucosal damage. In this study we mimicked ischemia by applying in vitro anoxia and subsequent reoxygenation to isolated intestinal segments. When intestinal segments are isolated and kept in physiological buffer, xanthine dehydrogenase is converted slowly to xanthine oxidase, irrespective of whether the buffer is oxygenated or not. No evidence was found for oxygen radical damage after anoxia and reoxygenation. However, the intestinal mucosa was damaged both after normoxia, and after anoxia and reoxygenation. Anoxia and subsequent reoxygenation did not affect muscarinic contraction, but slightly increased the beta-adrenergic relaxation, which partly correlates with the effects of mechanical dislocation of the epithelium. The increased sensitivity of the smooth muscle after epithelial damage might be involved in motility changes during intestinal inflammatory diseases.     

Cannabinoids and intestinal motility: welcome to CB2 receptors

Delta(9)-tetrahydrocannabinol (the active ingredient of marijuana), as well as endogenous and synthetic cannabinoids, exert many biological functions by activating two types of cannabinoid receptors, CB(1) receptors (expressed by central and peripheral neurons) and CB(2) receptors (that occur mainly in immune cells). Convincing evidence has accumulated in recent years that cannabinoids inhibit gastric and intestinal motility through activation of enteric CB(1) receptors. However, a report in this issue of British Journal of Pharmacology has highlighted the possibility that CB(2) receptors in the rat intestine could contribute to reducing the increase of intestinal motility induced by an endotoxic inflammation. By minimizing the adverse psychotropic effects associated with brain cannabinoid receptors, the CB(2) receptor represents a new molecular target for the treatment of motility disorders associated with intestinal inflammation.     

Structure-activity relationships of anthraquinones in the decrease of intestinal motility

The effects of substituted anthraquinones on intestinal motility were evaluated in-vitro using rabbit small intestinal strips. This structure-activity relationship study revealed the critical requirement of a hydroxy group at R2 position. The intestinal motility was inhibited 50% (IC50) by emodine (8 microM), 2-hydroxy anthraquinone (20 microM), 2,6-dihydroxy anthraquinone (25 microM), 2,7-dihydroxy anthraquinone (10 microM), 1,2,4-trihydroxy anthraquinone (80 microM) and 1,2,5,8-tetra-hydroxyanthraquinone (9 microM). The presence of other polar groups at R2 position such as an amino, aldehyde and carboxylic acid group significantly reduced the activity (IC50 360-400 microM). The presence of a methyl group and esterification of the carboxylic acid at R2 position was found to abolish the activity. These data are useful for the future development of anthraquinones as laxative agents.     

Mechanism of inhibition of small intestinal motility by restraint stress differs from that with norepinephrine treatment in rats

We have previously reported that restraint stress inhibits small intestinal motility in rats, and that the adrenergic beta3-antagonist SR59230A administration recovered the inhibition. In the present study, we compared the effects of restraint stress and norepinephrine on small intestinal motility using alpha- and beta-adrenergic antagonists. SR59230A did not recover the norepinephrine-induced inhibition of small intestinal motility. The norepinephrine-induced inhibition of small intestinal motility was recovered after administration of the alpha2-antagonist yohimbine, but not by alpha1-, beta1-, and beta2-antagonists. Considering these results, it is reasonable to assume that the mechanisms of inhibition of small intestinal motility due to restraint stress and norepinephrine treatment are different.     

继发性小肠淋巴管扩张症一例并文献复习

目的加深小肠淋巴管扩张症（IL）的认识。方法报道1例具有完整临床和病理资料的继发性IL的患者,并结合文献复习进行分析。结果胶囊内镜提示小肠弥漫性黏膜白斑,结肠镜病理提示回肠黏膜组织中淋巴管明显扩张,小肠淋巴管扩张症诊断明确。结论IL是一种罕见病,临床表现缺乏特异性,临床上易误诊,对于以腹泻、浆膜腔积液及低蛋白血症为特点的患者应考虑IL的可能性。     

Exploring factors that affect public acceptance of establishing an urban environmental education and recycling center

The reduction of waste amounts, mainly Municipal Solid Waste (MSW), has not been successful in many parts of Southern Europe, including Greece. Looking ahead, much more needs to be done and Circular Economy (CE) can address this challenge. Nowadays, emerged from the growing interest to boost ‘green’ growth in EU, CE and, by extension, waste management – an inherent element of CE – are issues that have become one of the EU's and Greece's main policy priorities. In accelerating the transition towards CE, the present study focuses on building environmental awareness. Upon the latter, the establishment of the first Environmental Education and Recycling Center in Greece is illustrated here as a best practice, in an attempt to explore the factors affecting acceptance to establish an additional center in Megara Municipality, close to Athens. Based on the above, a quantitative survey was carried out collecting questionnaires from 209 respondents. Although not completely representative of total population, the sample offers a good basis in order to study the factors that influence environmental awareness. Statistical analysis indicates how the establishment of an Environmental Education and Recycling Center in Megara depends on the (i) demographic profile data (age, monthly income, employment status), (ii) environmental consciousness, (iii) recycling habits and (iv) financial incentives. The empirical findings of this study also show that acceptance levels will increase with emphasis on the local development, by improving urban infrastructure and creating new jobs. Finally, according to the questioned sample, the old Megara Railway Station (OSE) is considered the appropriate area for the proposed Environmental Education and Recycling Center.     

In vitro magnesium absorption and the role of intestinal motility.

Magnesium (Mg) is known as an inhibitor of spontaneously contracting muscular tissues. To increase extracellular Mg in vivo, high doses of Mg must be given orally. Therefore, we investigated the effect of different doses of Mg given from the mucosal side of the small intestine of rats. According to the model of Trendelenburg, a system for the perfusion of isolated small intestine was developed, which allows the simultaneous recording of absorption and muscle contractions. Increasing doses of Mg were applied serosally or intraluminally. Intramulinal Mg did not affect intestinal motility. In contrast, increasing concentrations of serosal Mg resulted in a 50% inhibition of motility at 2.9 mmol/l Mg. This indicates no influence on intestinal motility of high doses of Mg acting from the mucosal side. In further studies, the addition of citric acid or taurocholic acid did not alter Mg absorption. Serosally applied amiloride (1 mmol/l) inhibited absorption, but also resulted in complete loss of motility. Since in this model passive diffusion is the most important mechanism of Mg transport, a direct influence of amiloride on Mg absorption can be excluded. From these data, we conclude that intestinal motility influences absorption--also of ions in aqueous solution--and should therefore be taken into account in absorption studies.     

Architecture of enteric neural circuits involved in intestinal motility

This short review describes the conceptual development in the search for the enteric neural circuits with the initial identifications of the classes of enteric neurons on the bases of their morphology, neurochemistry, biophysical properties, projections and connectivity. The discovery of the presence of multiple neurochemicals in the same nerve cells in specific combinations led to the concept of "chemical coding" and of "plurichemical transmission". The proposal that enteric reflexes are largely responsible for the propulsion of contents led to investigations of polarised reflex pathways and how these may be activated to generate the coordinated propulsive behaviour of the intestine. The research over the past decades attempted to integrate information of chemical neuroanatomy with functional studies, with the development of methods combining anatomical, functional and pharmacological techniques. This multidisciplinary strategy led to a full accounting of all functional classes of enteric neurons in the guinea-pig, and advanced wiring diagrams of the enteric neural circuits have been proposed. In parallel, investigations of the actual behaviour of the intestine during physiological motor activity have advanced with the development of spatio-temporal analysis from video recordings. The relation between neural pathways, their activities and the generation of patterns of motor activity remain largely unexplained. The enteric neural circuits appear not set in rigid programs but respond to different physico-chemical contents in an adaptable way (neuromechanical hypothesis). The generation of the complex repertoire of motor patterns results from the interplay of myogenic and neuromechanical mechanisms with spontaneous generation of migratory motor activity by enteric circuits.     

Effects of curcumin on the intestinal motility of albino rats

Curcumin has been used in traditional medicine as a household remedy for various diseases including biliary diseases, cough, hepatic diseases, wound healing. For past few decades, extensive work has been done on biological activities of curcumin. This study was carried out to provide scientific basis for the use of curcumin in gastrointestinal disorders. Animals were divided into 5 groups (Group I--Group V), based on the time interval between administration of curcumin/vehicular fluid to administration of barium sulphate (Group I--1 hr, Group II--8 hrs, Group III--16 hrs, Group IV--24 hrs, Group V--48 hrs). Each group was further divided into two sub-groups, Group A (control) and Group B (experimental), containing 6 rats each. Rats in Group A were given vehicular fluid (0.9% NaCl) while the rats in Group B were administered curcumin intragastrically by the naso-gastric tube reaching up to the lower 1/3rd of esophagus, in the dose of 1 gm/kg body weight, suspended in normal saline. After the intra-gastric administration of single dose of curcumin, there was decrease in length of small intestine traversed by BaSO4 in all the experimental groups as compared to control groups. These data suggests that curcumin decreases intestinal motility in albino rats, and this may partly explain the traditional use of curcumin in different disorders like diarrhea, abdominal cramps and irritable bowel syndrome.     

Focus on: biologics that affect therapeutic agents in dermatology

Tumor necrosis factor (TNF)-alpha is one of the oldest known cytokines in human physiology. It is involved in both normal and pathologic states. Virtually every cell and organ in the body are affected by TNF-alpha. Though TNF-alpha is usually involved in inflammation as a normal host defense response, when overproduced, it can become pathologic and affect almost every organ system. In this article, we address the role of TNF-alpha in diseases such as rheumatoid arthritis, Crohn's disease, psoriasis, and ankylosing spondylitis as well as the drugs used to modulate TNF-alpha. Specifically, we look at the structure, mechanism of action, and clinical use for etanercept, infliximab, and adalimumab. Historically, we also review the drug lenercept, another TNF-alpha modulator. These drugs offer alternative effective treatments to rheumatologic and dermatologic diseases without as many of the toxic side effects of some of the traditional therapies. The traditional agents target TNF-alpha in addition to several other modes of action (disease modifying anti-rheumatic drugs [DMARDS] such as cyclosporine and methotrexate) (Table 1). Though TNF-alpha immunomodulation seems to be a very effective, promising treatment in several TNF-alpha mediated disease processes, long-term studies need to be performed to assess the risk-benefit ratio of using these drugs over an extended period of time.     

Hemopoietic growth factors: a review.

The hemopoietic growth factors are peptide hormones that are known to be responsible for the in vitro and in vivo proliferation of bone marrow progenitor cells into mature differentiated cells. These cytokines have had a major impact on the management of patients with cytopenias and have been extensively used as an adjunct to the management of patients with hematologic malignancies, with or without prior intensive chemotherapy. Other potential uses, being rigorously studied, include the potential mobilization of stem cells as well as recruitment phase-specific cells into the cell cycle, thus providing a more sensitive environment for targeting specific chemotherapeutic agents.