The mitochondrion is a key organelle in the control of cell death. Nitric oxide (NO) inhibits complex IV in the respiratory chain and is reported to possess both proapoptotic and antiapoptotic actions. We investigated the effects of continuous inhibition of respiration by NO on mitochondrial energy status and cell viability. Serum-deprived human T cell leukemia (Jurkat) cells were exposed to NO at a concentration that caused continuous and complete (ϳ85%) inhibition of respiration. Serum deprivation caused progressive loss of mitochondrial membrane potential (⌬ m) and apoptotic cell death. In the presence of NO, ⌬m was maintained compared to controls, and cells were protected from apoptosis. Similar results were obtained by using staurosporin as the apoptotic stimulus. As exposure of serum-deprived cells to NO progressed (>5 h), however, ⌬m fell, correlating with the appearance of early apoptotic features and a decrease in cell viability. Glucose deprivation or iodoacetate treatment of cells in the presence of NO resulted in a collapse of ⌬m, demonstrating involvement of glycolytic ATP in its maintenance. Under these conditions cell viability also was decreased. Treatment with oligomycin and͞or bongkrekic acid indicated that the maintenance of ⌬ m during exposure to NO is caused by reversal of the ATP synthase and other electrogenic pumps. Thus, blockade of complex IV by NO initiates a protective action in the mitochondrion to maintain ⌬m; this results in prevention of apoptosis. It is likely that during cellular stress involving increased generation of NO this compound will trigger a similar sequence of events, depending on its concentration and duration of release. mitochondrial membrane potential ͉ apoptosis ͉ necrosis

The treatment with thiopurines and anti-TNF-α drugs does not seem to increase the risk of complications during pregnancy and does seem to be safe for the newborn.

For self-measurement of blood pressure to be useful, patient reporting of test results must be reliable and accurate. Until now no study directly measured the accuracy and reliability of patients' reporting of self-measured blood pressure values. Thirty hypertensive patients (69 +/- 11 years) were instructed to measure blood pressure at home over 14 days with the highly accurate Omron IC monitor and to keep a record of all readings in a patient logbook. To assess the reliability of the records, patients were not informed about the memory capacity of the device. We compared automatically stored blood pressure readings with the respective logbook entries to analyze deletion (under-reporting), addition (over-reporting), and precision of reporting of test results. The prevalent pattern was under-reporting, averaging 36% +/- 24% (3% to 89%), which occurred significantly more than over-reporting (9% +/- 11%; 0% to 38%). The precision of reporting (identical values at corresponding times) was 76% +/- 34% (0% to 100%). This observer error did not affect group comparisons of automatically stored values and logbook entries, although the estimated limits of agreement were wide. Blood pressure control, duration of hypertension, age, or previous use of self-measurement and patterns of logbook entries were not found to be predictive of the patients' reliability. Our results demonstrate a substantial observer error in the reporting of self-measured blood pressure values. This bias may be reduced by memory-equipped blood pressure devices.

1 The eect of prolonged exposure to nitric oxide on enzymes involved in cell metabolism was investigated in T lymphocyte-derived Jurkat and L929 ®broblast human cell lines using a constant concentration of nitric oxide (1.5 mM) released by the nitric oxide donor DETA-NO (0.5 mM). 2 Nitric oxide inhibited immediately the respiration of the cells acting reversibly at complex IV. With time, the inhibition became progressively persistent, i.e. not reversed by trapping of nitric oxide with oxyhaemoglobin, and was preceded by a decrease in the concentration of the intracellular reduced glutathione. This persistent eect of nitric oxide on respiration was due to inhibition of complex I activity which could be reversed by addition of reduced glutathione or by cold light, suggesting that it was due to S-nitrosylation of thiols necessary for the activity of the enzyme. 3 The activity of other enzymes also known to be susceptible to inhibition by S-nitrosylation, i.e. glyceraldehyde-3-phosphate dehydrogenase and glutathione reductase, was progressively decreased by exposure to nitric oxide with a similar time course to that observed for the inhibition of complex I. Furthermore, inhibition of these enzymes only occurred when the concentrations of reduced glutathione had previously fallen and could be prevented by increasing the intracellular concentrations of reduced glutathione. 4 Our results suggest that S-nitrosylation of dierent enzymes by nitric oxide may occur only if the reducing potential of the cells is impaired.

Oxidative stress during active CD depends on H(2)O(2) production. The inhibition of DeltaPsim suggests that this organelle is a source of ROS. CAT is permanently inhibited in CD, the biological significance of which is under study. The persistent oxidative damage detected may have implications for the evolution of the disease.

The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Primary culture rat astrocytes exposed to the long acting nitric oxide donor (Z)-1-[2-aminoethyl)-N-(2-ammonioethyl) amino]diazen-1-ium-1,2-diolate (DETA-NO) for 24 h approximately double their concentration of glutathione (GSH) and show no sign of cell death. In contrast, GSH was depleted by 48%, and significant loss of mitochondrial respiratory chain complex activity and cell death were observed in primary culture rat neurones subjected to DETA-NO for 18 h. Northern blot analysis suggested that mRNA amounts of both subunits of glutamate-cysteine ligase (GCL), the rate-limiting enzyme in GSH synthesis, were elevated in astrocytes following nitric oxide (NO) exposure. This correlated with an increase in astrocytic GCL activity. Neurones on the other hand did not exhibit increased GCL activity when exposed to NO. In addition, the rate of GSH efflux was doubled and c-glutamyltranspeptidase (c-GT) activity was increased by 42% in astrocytes treated with NO for 24 h. These results suggest that astrocytes, but not neurones, up-regulate GSH synthesis as a defence mechanism against excess NO. It is possible that the increased rate of GSH release and activity of c-GT in astrocytes may have important implications for neuroprotection in vivo by optimizing the supply of GSH precursors to neurones in close proximity.

Smoking is a major environmental factor that interferes in the establishment and clinical course of ulcerative colitis (UC). Firstly, the risk of smoking status impact in the development of UC is reviewed, showing that current smoking has a protective association with UC. Similarly, being a former smoker is associated with an increased risk of UC. The concept that smoking could have a role in determining the inflammatory bowel disease phenotype is also discussed. Gender may also be considered, as current smoking delays disease onset in men but not in women. No clear conclusions can be driven from the studies trying to clarify whether childhood passive smoking or prenatal smoke exposure have an influence on the development of UC, mainly due to methodology flaws. The influence of smoking on disease course is the second aspect analysed. Some studies show a disease course more benign in smokers that in non-smokers, with lower hospitalizations rates, less flare-ups, lower use of oral steroids and even less risk of proximal extension. This is not verified by some other studies. Similarly, the rate of colectomy does not seem to be determined by the smoking status of the patient. The third issue reviewed is the use of nicotine as a therapeutic agent. The place of nicotine in the treatment of UC is unclear, although it could be useful in selected cases, particularly in recent ex-smokers with moderate but refractory attacks of UC. Finally, the effect of smoking cessation in UC patients is summarised. Given that smoking represents a major worldwide cause of death, for inpatients with UC the risks of smoking far outweigh any possible benefit. Thus, physicians should advise, encourage and assist UC patients who smoke to quit.