Homocysteine triggers mucosal microvascular activation in inflammatory bowel disease

OBJECTIVES: Increased homocysteine contributes to the pathophysiology of several chronic inflammatory diseases. Whether homocysteine could participate in mucosal inflammation in inflammatory bowel disease (IBD) has not been explored yet. Our aims were to study the levels of plasma and mucosal homocysteine in IBD patients and to assess whether homocysteine can trigger an inflammatory reaction on human intestinal microvascular endothelial cells (HIMECs). METHODS: Homocysteine was measured in the plasma, mucosal biopsy, and lamina propria mononuclear cell (LPMC) supernatants from normal and IBD subjects. HIMEC were cultured in presence of homocysteine, TNF-alpha, or folic acid, alone or in combination. Expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular cell adhesion molecule 1 was measured by flow cytometry and monocyte chemoattractant protein-1 (MCP-1) production by ELISA. Phosphorylation of p38 and p42/44 was assessed by immunoblot in HIMEC extracts. T-cell- and monocyte-HIMEC adhesion assays were used to evaluate the impact of homocysteine on leukocyte adhesion to intestinal endothelial cells. RESULTS: Patients with IBD displayed significantly higher homocysteine plasma and mucosal levels than control subjects. IBD-derived LPMC released higher homocysteine than control-derived LPMC. Treatment of HIMEC with homocysteine, and synergistically with the combination of TNF-alpha and homocysteine, triggered HIMEC inflammation, resulting in VCAM-1 up-regulation, MCP-1 production, and p38 phosphorylation. These events lead to an increased capacity of HIMEC to adhere T- and monocyte cells and were blocked by folic acid treatment. CONCLUSIONS: Homocysteine is increased in both the mucosa and plasma of patients with Crohn's disease and ulcerative colitis and contributes to the inflammatory state of the mucosal IBD endothelium. Therefore, homocysteine could play a proinflammatory role in IBD, which can be efficiently targeted by folic acid supplementation.     

Ethical implications of home telecare for older people: a framework derived from a multisited participative study

Context

Telecare and telehealth developments have recently attracted much attention in research and service development contexts, where their evaluation has predominantly concerned effectiveness and efficiency. Their social and ethical implications, in contrast, have received little scrutiny.

Objective

To develop an ethical framework for telecare systems based on analysis of observations of telecare‐in‐use and citizens’ panel deliberations.

Design

Ethnographic study (observation, work shadowing), interviews, older citizens’ panels and a participative conference.

Setting

Participants’ homes, workplaces and familiar community venues in England, Spain, the Netherlands and Norway 2008–2011.

Results

Older respondents expressed concerns that telecare might be used to replace face‐to‐face/hands‐on care to cut costs. Citizens’ panels strongly advocated ethical and social questions being considered in tandem with technical and policy developments. Older people are too often excluded from telecare system design, and installation is often wrongly seen as a one‐off event. Some systems enhance self‐care by increasing self‐awareness, while others shift agency away from the older person, introducing new forms of dependency.

Conclusions

Telecare has care limitations; it is not a solution, but a shift in networks of relations and responsibilities. Telecare cannot be meaningfully evaluated as an entity, but rather in the situated relations people and technologies create together. Characteristics of ethical telecare include on‐going user/carer engagement in decision making about systems: in‐home system evolution with feedback opportunities built into implementation. System design should be horizontal, ‘two‐way’/interactive rather than vertical or ‘one‐way’. An ethical framework for telecare has been developed from these conclusions (Table 1).     

Bile-Duct Hamartomas Presenting as Multiple Focal Lesions on Hepatic Ultrasonography

Multiple bile-duct hamartomas are usually diagnosed at autopsy as an incidental finding. We report a case of a 50-yr-old male in whom multiple bile-duct hamartomas were suspected in an abdominal ultrasonography and confirmed by an echo-guided needle liver biopsy. The ultrasonography disclosed multiple scattered hyperechoic lesions with a diameter of up to 1 cm, associated with some anechoic lesions of a larger size and a cystic appearance. Computed tomography demonstrated multiple hypodense lesions that were not modified by the administration of contrast. Bile-duct hamartomas should be included in the differential diagnosis of multiple focal hepatic lesions at ultrasonography or computed tomography.     

EUS-guided mucosectomy for gastrointestinal cancer.

INTRODUCTION: the only way of improving prognosis and survival in gastrointestinal cancer is early diagnosis, with intramucosal localization as confirmed by endoscopic ultrasonography (EUS) or 20-MHz miniprobes (MPs) (T1) being most appropriate. Endoscopic mucosal resection (EMR) has proven effective in the treatment of this sort of lesions. PATIENTS AND METHOD: in a group (18 cases) with 15 cases of superficial gastrointestinal cancer and 3 cases of severe gastric dysplasia, 9 cases (3 esophageal, 4 gastric, 2 rectal) underwent a classic EMR following EUS or a 7.5- and 20-MHz miniprobe exploration. RESULTS: ultrasonographic studies showed a T1 in all but one esophageal case (Tis), and in both gastric dysplasias, with no changed layer structure being demonstrated in the latter (T0). No complications arose with classic EMR, and all 9 patients are alive and free from local or metastatic recurrence, except for one esophageal case, which recurred distally to the esophageal lesion (metachronous). CONCLUSIONS: echoendoscopically-assisted EMR is a safe, effective technique in the endoscopic management of superficial gastrointestinal (esophageal, gastric, colorectal) cancer. Recurrence most likely depends upon cancer multiplicity.     

No effect of trait anxiety on differential fear conditioning or fear generalization

Previous studies have shown that individuals with anxiety disorders exhibit deficits in fear inhibition and excessive generalization of fear, but little data exist on individuals at risk from these disorders. The present study examined the role of trait anxiety in the acquisition and generalization of fear in 126 healthy participants selected on the basis of their trait-anxiety scores. Measures of conditioning included fear-potentiated startle, skin conductance response and online risk ratings for the unconditioned stimulus. Contrary to our hypotheses, trait anxiety did not have any effect either on the acquisition or the generalization of fear. Our results suggest that these fear conditioning processes are not impaired in individuals at risk from anxiety.     

Ultrastructure of the intrauterine eggs of the microphallid trematode Maritrema feliui: evidence of early embryonic development

Intrauterine embryonic development in the microphallid trematode Maritrema feliui is examined by means of transmission electron microscopy. Both fertilization and eggshell formation take place in the ootype. The eggshell is formed from a shell globule material derived from the vitelline cells combined with secretions of Mehlis' gland. The proximal uterus is packed with unembryonated eggs of the oligolecithal type, each composed of a fertilized oocyte and several vitelline cells, all surrounded by the shell. Intrauterine embryonic development of the egg is followed to the early stage of outer embryonic envelope formation, resulting in an embryo of ~20 blastomeres of three different types: macromeres, mesomeres and micromeres. The first equal cleavage division of the zygote produces two macromeres. The outer envelope is of cellular origin and formed by the cytoplasmic fusion of two macromeres, which become situated at opposite poles in the peripheral layer of the embryo just beneath the eggshell. Simultaneously, other blastomeres multiply and differentiate, whereas several micromeres exhibit clear signs of degeneration or apoptosis. These results show that the embryonic development of M. feliui starts in utero and represents an example of early stage ovoviviparity. A reduction in the number of blastomeres results from a continued degeneration of micromeres, which after autolysis and re-absorption, appear to represent an important source of nutritive reserves for the embryo. The embryonic development of this digenean is discussed in relation to its life cycle.