Sleep disturbance is a classic sign of hepatic encephalopathy. However, there are limited data regarding its prevalence in cirrhotic patients without overt hepatic encephalopathy. We assessed the characteristics of sleep in cirrhosis using a sleep questionnaire (n ‫؍‬ 44) and actigraphy (n ‫؍‬ 20). The results were compared with those of subjects with chronic renal failure and those of healthy controls. Presence of subclinical hepatic encephalopathy, chronotypology profile, and individual's affective state were also analyzed. The questionnaire indicated an elevated number of cirrhotic patients (47.7%) and patients with chronic renal failure (38.6%) who complained of unsatisfactory sleep compared with healthy controls (4.5%, P F .01). Actigraphy corroborated the deterioration of sleep parameters in cirrhotic patients with unsatisfactory sleep. The sleep disturbance in cirrhosis was not associated with clinical parameters nor with cognitive impairment. Cirrhotic subjects and patients with chronic renal failure with unsatisfactory sleep showed higher scores for depression and anxiety, raising the possibility that the effects of chronic disease may underlie the pathogenesis of sleep disturbance. However, in contrast to chronic renal failure, unsatisfactory sleep in cirrhosis was associated with delayed bedtime, delayed wake-up time, and evening chronotypology. In conclusion, a sleep disturbance is frequent in cirrhotic patients without hepatic encephalopathy and may be related to abnormalities of the circadian timekeeping system. (HEPATOLOGY 1998;27:339-345.)A disturbance of sleep is recognized as one of the early signs of hepatic encephalopathy. 1 However, there are limited data regarding its prevalence in patients with cirrhosis without signs of overt hepatic encephalopathy. Results from a quality of life questionnaire indicated that disturbance in sleep was significantly higher in nonalcoholic cirrhotic patients compared with subjects with another chronic illness, such as Crohn' s disease. 2 In this survey and subsequent data, 3 up to 35% of cirrhotic individuals had difficulties in the area of sleep and rest.The mechanisms responsible for these findings are poorly understood. One possibility is that abnormalities in circadian function may underlie its pathogenesis. The sleep-wake cycle is one of the functions regulated by the circadian clock, the suprachiasmatic nucleus of the anterior hypothalamus, 4 which has efferent connections that influence a large array of biological functions including the secretion of melatonin from the pineal gland. Previous studies from our laboratory have shown that rats subjected to a portacaval anastomosis experience an alteration in the rhythm of circadian locomotor activity as well as the rhythm of pineal melatonin content. 5 In patients with cirrhosis, the diurnal plasma melatonin profile showed a significant delay in the onset of plasma melatonin increase and in its peak nocturnal level. 6 This displacement of the melatonin profile could be a reflection of an alteration in the ...

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We report a dual functional system for bacterial nitrate (NO3−) assimilation and nitric oxide (NO) detoxification. The assimilatory NO3− reductase (NasC) can generate nitric oxide (NO). Co-expression of an NO-detoxification system acts to counteract accumulation of cytotoxic NO during anaerobic NO3−-dependent growth.

Stanozolol (ST) is a 17alpha-alkyl anabolic-androgenic steroid (17alpha-AAS) often misused by athletes and bodybuilders. The use of anabolic-steroids by sportsmen and teenagers has increased dramatically, thus raising the question about their hepatotoxicity, specially those such as ST which are orally administered. Previously, we have reported diverse in vivo effects exerted by this steroid and published the existence of a highly specific ST-binding site in male rat liver microsomes. The existence of this binding site, the reported hepatic effects exerted in humans, and the very limited information about its potential hepatotoxicity led us to treat adult male rats acutely and chronically with ST and study different parameters that could indicate liver damage: serum levels of transaminases, concentration of monooxygenase enzymes in liver, liver membrane lipid peroxidation products, liver histopathology, and cell cycle/ploidy status of liver cells. In our study, no changes in serum transaminases or lipid peroxidation levels were obtained. However, acute stanozolol treatment significantly decreased the levels of cytochrome P450 (Cyt. P450) and cytochrome b5 (Cyt. b5) during the first 48 h of treatment, while subsequently, at 72 and 96 h, these microsomal enzymes underwent a significant increase in their levels. In sharp contrast with this response to acute treatment, the content of these two enzymes during chronic treatment showed an important decrease. Interestingly, acutely and chronically ST-treated livers showed slight to moderate inflammatory or degenerative lesions in centrilobular hepatocytes. Flow cytometric analysis demonstrated that both acute and chronic ST treatment were capable of increasing the percentage of S-phase fraction (%SPF) of liver cells. These findings taken together clearly show that this steroid is capable of altering the liver capacity for metabolizing xenobiotics and indicate that high doses of ST could exert a proliferative effect on liver cells. Such data should be considered in risk evaluations for this compound.

The powerful greenhouse gas, nitrous oxide (N2O) has a strong potential to drive climate change. Soils are the major source of N2O and microbial nitrification and denitrification the main processes involved. The soybean endosymbiont Bradyrhizobium diazoefficiens is considered a model to study rhizobial denitrification, which depends on the napEDABC, nirK, norCBQD, and nosRZDYFLX genes. In this bacterium, the role of the regulatory cascade FixLJ-FixK2-NnrR in the expression of napEDABC, nirK, and norCBQD genes involved in N2O synthesis has been previously unraveled. However, much remains to be discovered regarding the regulation of the respiratory N2O reductase (N2OR), the key enzyme that mitigates N2O emissions. In this work, we have demonstrated that nosRZDYFLX genes constitute an operon which is transcribed from a major promoter located upstream of the nosR gene. Low oxygen was shown to be the main inducer of expression of nosRZDYFLX genes and N2OR activity, FixK2 being the regulatory protein involved in such control. Further, by using an in vitro transcription assay with purified FixK2 protein and B. diazoefficiens RNA polymerase we were able to show that the nosRZDYFLX genes are direct targets of FixK2.

Background-Some cirrhotic patients with tense ascites who undergo paracentesis develop a circulatory dysfunction syndrome, manifested by an increase in plasma renin activity. Recently, a significant inverse correlation between postparacentesis changes in plasma renin activity and systemic vascular resistance has been demonstrated in these patients, suggesting that peripheral arterial vasodilatation could be responsible for this circulatory dysfunction, but the mechanisms by which tense ascites removal induces such changes are unknown Aim-To investigate the role of a decrease in intra-abdominal pressure (IAP) in the development of early postparacentesis haemodynamic changes Methods-Eleven cirrhotic patients with tense ascites received a large volume paracentesis. A specially designed pneumatic girdle was used to compress the abdomen to avoid a decrease in IAP during ascites removal. Haemodynamic studies were performed before paracentesis, one hour after ascites flow stopped, and 30 minutes after pneumatic girdle deflation Results-When IAP was maintained at its original level, no haemodynamic changes were observed, despite large volume paracentesis. However, a significant decrease in systemic vascular resistance was seen immediately after pneumatic girdle deflation Conclusions-Early haemodynamic changes after paracentesis are avoided if IAP is maintained at its original level. The abrupt decrease in IAP could be the trigger for the development of the initial haemodynamic changes that eventually produce postparacentesis circulatory dysfunction. (Gut 2001;48:384-389)

NO (nitric oxide) is a signal molecule involved in diverse physiological processes in cells which can become very toxic under certain conditions determined by its rate of production and diffusion. Several studies have clearly shown the production of NO in early stages of rhizobia-legume symbiosis and in mature nodules. In functioning nodules, it has been demonstrated that NO, which has been reported as a potent inhibitor of nitrogenase activity, can bind Lb (leghaemoglobin) to form LbNOs (nitrosyl-leghaemoglobin complexes). These observations have led to the question of how nodules overcome the toxicity of NO. On the bacterial side, one candidate for NO detoxification in nodules is the respiratory Nor (NO reductase) that catalyses the reduction of NO to nitrous oxide. In addition, rhizobial fHbs (flavohaemoglobins) and single-domain Hbs which dioxygenate NO to form nitrate are candidates to detoxify NO under free-living and symbiotic conditions. On the plant side, sHbs (symbiotic Hbs) (Lb) and nsHbs (non-symbiotic Hbs) have been proposed to play important roles as modulators of NO levels in the rhizobia-legume symbiosis. In the present review, current knowledge of NO detoxification by legume-associated endosymbiotic bacteria is summarized.