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.     

Influence of vitamin D on parathyroid function in the elderly.

The effect of age and vitamin D status on parathyroid function was studied in 129 healthy subjects between 20 and 89 yr old, with normal serum creatinine (less than 0.11 mmol/L), and living in Cordoba, Spain. Serum calcium and phosphorus as well as 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25-(OH)2D] decreased, whereas serum alkaline phosphatase increased, with age. Serum PTH also increased significantly with age when measured with either a carboxyl-terminal (cPTH) or an intact [PTH(1-84)] assay. The increase in cPTH, however, exceeded largely the increase in PTH(1-84) (+120% and +30% in subjects above 80 yr vs. young adults, respectively). Serum PTH(1-84) was negatively correlated with serum (ionized) calcium, 25OHD, and insulin-like growth factor I (IGF-I) but not with serum 1,25-(OH)2D. Serum 1,25-(OH)2D decreased with age and was highly correlated with serum 25OHD, cPTH, and IGF-I. In multiple regression analysis 50-60% of the variation of total and free 1,25-(OH)2D could be explained by serum 25OHD, PTH(1-84), and especially IGF-I, suggesting a possible role of decreasing GH and IGF-I concentrations in the mineral homeostasis of the elderly. Calcium infusion (1.5 mg/kg body weight over 10 min) decreased serum PTH(1-84) to below normal concentrations in young adults (nadir 14% of basal concentration), whereas the nadir in elderly subjects with secondary hyperparathyroidism was only 32% of basal concentration. The relative decrease was, however, identical in both age groups when simultaneous changes in ionized calcium were taken into account. Basal serum PTH(1-84) in selected elderly subjects (50 +/- 10 ng/L or 5 +/- 1 pmol/L, n = 10) decreased significantly (2.7 +/- 0.9 pmol/L, P less than 0.01) after 3 iv injections of 1,25-(OH)2D during 1 week without changes in serum (ionized) calcium. The PTH suppressibility after calcium infusion did not further improve. In conclusion: elderly patients with normal serum creatinine had a small (+30%) but significant increase in intact serum PTH concentration but the mean concentration still remained within the normal range. The PTH secretion remained normally suppressible by acute calcium infusion. Treatment with 1,25-(OH)2D decreased basal calcium-PTH setpoint without further additional effects during calcium infusion.     

Role of prostaglandins in mediating the renal effects of atrial natriuretic factor

The natriuretic response to the intrarenal administration of atrial natriuretic factor (ANF) is accompanied by an increase in the synthesis of prostaglandins and by a redistribution of renal blood flow from the superficial to the deep cortex. This study was undertaken to define whether prostaglandins mediate the ANF-induced redistribution of renal blood flow and if prostaglandins and renal blood flow redistribution contribute to the natriuretic actions of ANF. In anesthetized dogs, the intrarenal administration of indomethacin (10 micrograms/kg/min) or the intravenous administration of meclofenamate (5 mg/kg) completely prevented the sixfold and twofold increments in urinary prostaglandin E2 and 6-keto-prostaglandin F1 alpha excretion, respectively; it also abolished the redistribution of renal blood flow to the deep cortex. However, ANF induced a similar natriuresis before (from 53 +/- 17 to 281 +/- 48 microEq/min) and after (from 45 +/- 13 to 273 +/- 60 microEq/min) the administration of prostaglandin synthesis inhibitors. It is concluded that the ANF-induced redistribution of renal blood flow to the deep cortex is prostaglandin-mediated but that neither redistribution nor increased prostaglandin synthesis is an important mediator of ANF's natriuretic action.     

Functional Electrical Stimulation—A New Therapeutic Approach to Enhance Exercise Intensity in Chronic Obstructive Pulmonary Disease Patients: A Randomized,Controlled Crossover Trial

Objective

To evaluate the effect of quadriceps functional electrical stimulation (FES)-cycling on exertional oxygen uptake ($\dot{\text{V}}$o₂) compared with placebo FES-cycling in patients with chronic obstructive pulmonary disease (COPD).

A Review: Associations Between Attention-deficit/hyperactivity Disorder,Physical Activity,Medication Use,Eating Behaviors and Obesity in Children and Adolescents

In the past few years we have become increasingly aware of strong associations between obesity and ADHD. Both conditions are major public health issues, affecting children, adolescents and adults alike.

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).     

Partial blockage of the inferior vena cava. Results apropos of 110 cases]

Rheoplethysmography with occlusion (RPO) is useful in the diagnosis of deep venous thrombosis. Bilateral phlebography with cavography performed afterwards as an emergency gives information as to the embolic potential of the thrombosis and orientates treatment towards surgical interruption of the inferior vena cava. In the C.H.U. at Grenoble 83 clips, 25 umbrella filters and 2 ligatures were placed on the inferior vena cava from 1974 to 1977. Prevention of pulmonary emboli was achieved in 99% cases with lower limb embolic foci. Follow-up by RPO and isotopic phlebography showed that the course of venous thrombosis of the lower limbs seemed to be unchanged by partial interruption of the inferior vena cava, provided that elastic stockings and adequate anticoagulant therapy adapted to venous haemodynamics are used.     

Recombinant interferon gamma in hairy cell leukemia, multiple myeloma, and Waldenstrom's macroglobulinemia

Fifteen patients with multiple myeloma, five with hairy cell leukemia, and five with Waldenstrom's macroglobulinemia were treated with recombinant interferon gamma (rINF-gamma) to determine the antitumor activity of this agent. The rIFN-gamma was administered by daily intramuscular injection at doses ranging from 0.125 to 0.5 mg/m2. No responses were observed in patients with multiple myeloma, although in one patient the disease has remained stable for over 16 months. Minimal improvement in some hematologic indexes were observed in three of five patients with hairy cell leukemia. One partial remission and one minor response were documented in two of the five patients with Waldenstrom's macroglobulinemia. In five patients, an increase in normal serum immunoglobulins was observed. These results suggest that there is only minimal activity of rIFN-gamma as a single agent in neoplasms of B-cell origin.