Cognitive parameters and morning and evening types: two decades of research (1990-2009).

An important area of study has examined cognitive aspects of morningness-eveningness orientation. Optimal times of efficiency in participants classified as Morning and Evening types are of great importance for understanding their cognitive abilities. The present review covers the last two decades (1990-2009), during which the important review by Tankova, Adan, and Buela-Casal appeared, and focuses particularly on attention, memory, and executive functions.

Decreased number of circulating endothelial progenitor cells in patients with Graves' hyperthyroidism.

OBJECTIVE: A relevant biological role of circulating endothelial progenitor cells (EPC) was recently demonstrated. EPC are generated in the bone marrow, and interact with damaged endothelium, restoring the integrity of the monolayer. Therefore, aim of the present study was to evaluate EPC in the blood of patients with untreated Graves' hyperthyroidism (GD), in whom an increased oxidative stress was observed. DESIGN AND METHODS: Twenty-three patients with untreated active GD and 18 matched normal controls (NC) were included in the study. Circulating EPC were isolated from peripheral blood. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots, and were identified by positive double staining after 7 days in culture. Circulating levels of C reactive protein, total antioxidant power, interleukin (IL)-6, IL- 18, monocyte chemoattractant protein-1, tumor necrosis facotr- α, soluble vascular cell adhesion molecule (VCAM) and intracellular adhesion molecule were evaluated by enzymelinked immunosorbent assay kit. EPC number was also evaluated in a subgroup of GD patients after restoration of euthyroidism. RESULTS: Systolic blood pressure resulted increased in GD patients compared with control subjects whereas diastolic blood pressure was not significantly different. Patients with GD showed an increase in circulating levels of IL-18 and VCAM-1 and a reduction of total antioxidant power (p<0.05) compared to NC. Moreover, a reduced number of EPC was observed in patients with GD compared to NC (p<0.05) which turned to NC values after restoring euthyroidism. CONCLUSION: Patients with GD showed a reduction in the physiological protective mechanisms against endothelial damage, probably induced by increased inflammation and oxidative stress.

Circulating adhesion molecules and carotid artery structural changes in patients with noninsulin-dependent diabetes mellitus.

Hypertension and non insulin-dependent diabetes mellitus (NIDDM) are well-known risk factors for atherosclerotic disease. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) may exert a relevant role in the pathogenesis of atherosclerosis; their prognostic relevance has been recently demonstrated. The aim of the study was to investigate possible inter-relation between circulating adhesion molecule levels, carotid artery structure and endothelial function in 15 patients with NIDDM, as well as in 15 patients with both NIDDM and essential hypertension (NIDDM+EH) compared with 15 normal subjects (NS) and 15 euglycaemic patients with EH, matched for age, sex and body weight. All subjects were submitted to a biopsy of the gluteal subcutaneous fat. Small arteries were dissected and mounted on a micromyograph, and the media-to-lumen (M/L) ratio was then calculated. Carotid artery structure was investigated by Doppler ultrasound. Endothelial function was evaluated by investigation of the flow-mediated dilatation (FMD) of the brachial artery. ICAM-1 and VCAM-1 plasma levels were measured by ELISA. ICAM-1 and VCAM-1 plasma levels were significantly greater and FMD smaller in EH, NIDDM and NIDDM+EH than in NS, but no difference was observed among the three pathological groups. Carotid artery structural changes were more pronounced in NIDDM+EH. No significant difference was observed among NIDDM, EH and NS. The M/L ratio of subcutaneous small resistance arteries was significantly greater in NIDDM+EH than in NIDDM or EH. NS had a smaller M/L ratio than the other groups. Significant correlations were observed between ICAM-1 plasma levels and indices of carotid artery structure in diabetic patients. However, the relations were close only in NIDDM+EH. In conclusion, our data suggest that NIDDM+EH may present more pronounced vascular structural alterations than NIDDM, and that adhesion molecules plasma levels are closely inter-related with carotid artery structural alterations, at least in NIDDM+EH, but not with M/L ratio of small resistance arteries.

Early effects of total paracentesis and albumin infusion on muscle sympathetic nerve activity in cirrhotic patients with tense ascites.

BACKGROUND/AIMS: Cirrhotic patients with ascites are characterized by a marked activation of the sympathetic and the renin-angiotensin-aldosterone system. Total paracentesis is associated with a short-lived suppression of the renin-angiotensin-aldosterone system. Little information exists as to whether this favourable effect is parallelled by sympathoinhibition. METHODS: In 16 Child C cirrhotic patients (age: 57.1+/-6.2 years, mean+/-SEM) with tense ascites we assessed the time course of the effects of total paracentesis followed by intravenous albumin (6-8 g/l of ascites) on beat-to-beat mean arterial pressure (Finapres), heart rate, plasma norepinephrine, epinephrine (high performance liquid chromatography) and muscle sympathetic nerve activity (microneurography, peroneal nerve). Measurements were obtained under baseline conditions, during staged removal of ascitic fluid (250 ml/min) and 24 h later. The patient remained supine throughout the study period. RESULTS: Total paracentesis (10.6+/-1.3 l) induced a decrease in mean arterial pressure (from 95.0+/-2.6 mmHg to 88.2+/-3.2 mmHg, p<0.01), in heart rate (from 82.5+/-3.3 beats/min to 77.1+/-2.8 beats/min, p<0.01) and a reduction in plasma norepinephrine values (from 782+/-133 pg/ml to 624+/-103 pg/ml, p<0.01), which were substantially maintained 24 h later. In eight patients muscle sympathetic nerve activity did not change during paracentesis (from 65+/-7.1 bursts/min to 65+/-7.4 bursts/min, p=NS), but a marked reduction was observed 24 h later (48.4+/-5.6 bursts/min, p<0.01). CONCLUSIONS: These data provide the first evidence that total paracentesis exerts an acute marked sympathoinhibitory effect. Whether this is a long-lasting phenomenon and to what extent plasma expansion with albumin contributes to this effects need to be further addressed.

Hepatic iron overload in patients with chronic viral hepatitis: role of HFE gene mutations.

Mild to moderate hepatic iron overload is frequent in patients with chronic viral hepatitis (CH). We evaluated the role of hemochromatosis (HFE) gene mutations and other acquired factors in the development of iron overload in these patients. We studied 110 patients with chronic B or C viral hepatitis (31 women, 79 men), including 20 with cirrhosis, and 139 controls. Hepatic iron was evaluated by semiquantitative analysis in all the patients, and hepatic iron concentration (HIC) was determined in 97 of them (26 women, 71 men). C282Y and H63D mutations were sought in all the subjects by a polymerase chain reaction-restriction assay. The frequency of HFE genotypes and alleles did not differ in patients and controls. No relation was detected between hepatic iron stores and HFE gene mutations in women. In men, all C282Y heterozygotes had iron overload, and the H63D mutation was significantly more frequent in patients with more marked hepatic siderosis than in those with mild or no siderosis (P = .0039) and in controls (P = .0008). Heavy alcohol intake and hepatic cirrhosis were also associated with increased hepatic iron stores in the men. In the 71 men in whom HIC was measured, multiple regression analysis showed that this variable was related independently only to alcohol intake and HFE gene mutations. We suggest that in patients with CH, iron accumulates in the liver as the result of an interplay between genetic and acquired factors, and that increased liver iron stores may influence progression toward liver fibrosis.

Evidence of functional and structural cardiac abnormalities in cirrhotic patients with and without ascites.

Cirrhosis is associated with cardiovascular abnormalities. Scanty information is available as to whether these include left ventricle diastolic dysfunction and wall thickness increase. To this aim in 27 cirrhotic patients with tense ascites, 17 cirrhotic patients with previous episodes of ascites (not actual), and 11 controls we investigated by echocardiography and echocolor Doppler left ventricle diastolic function (E wave, A wave, E/A ratio, deceleration time of E wave), systolic function (ejection fraction), and wall thickness (left ventricle posterior wall thickness + interventricular septum thickness) along with neurohumoral variables. All measurements (supine position) were repeated after total paracentesis (10.7 +/- 0.6 L of ascites) in ascitic patients. Both in patients with and without ascites E/A ratio was reduced as compared with controls (0.93 +/- 0.07 and 0.97 +/- 0.06 vs. 1.18 +/- 0.08, P < .05) while left ventricle wall thickness was increased (18.6 +/- 0.6 and 20.1 +/- 0.8 vs. 17.2 +/- 0.7, P < .05 and P < .01, respectively), irrespective of the postviral or alcoholic cause of liver disease. In all cirrhotics both right and left atrial and right ventricle diameters were significantly greater. Ejection fraction was slightly but significantly (P < .01) reduced in ascitic patients. Paracentesis induced a reduction of the highly increased basal plasma renin activity, aldosterone, norepinephrine (P < .01), and epinephrine (P < .05) and improved diastolic function (E/A, P < .05). Systolic function was unaffected. Thus, irrespective of ascites and cause, advanced cirrhosis is associated with left ventricle diastolic dysfunction and wall thickness increase. We can speculate that neurohumoral overactivity, known to stimulate cardiac tissue growth, may challenge the heart, promoting fibrosis and exerting a further hindrance to ventricular relaxation in patients with cirrhosis experiencing episodes of ascites.

Iron stores, response to alpha-interferon therapy, and effects of iron depletion in chronic hepatitis C.

We studied 81 patients with chronic hepatitis C to investigate the relationship between iron and alpha-interferon response. Sixty-one patients (group A) were given alpha-interferon irrespective of iron status, whereas 20 (group B) with iron overload, were iron depleted before alpha-interferon therapy. In group A, 21 patients responded to alpha-interferon and 40 were non-responders. Increased iron indices were significantly more frequent in non-responders than responders. Multivariate analysis showed that among the independent variables evaluated, only gamma-GT and liver iron concentration predicted therapy outcome. After phlebotomy treatment, serum alanine aminotransferase fell significantly both in patients of group B (196 +/- 122 IU/l vs 82 +/- 37 IU/l, p < 10(-6)) and in 12 non-responders of group A (198 +/- 89 IU/l vs 107 +/- 81 IU/l, p < 10(-6)). In 16 iron depleted patients, eight from each group, subsequent treatment with alpha-interferon produced a response in only one patient. These results suggest that increased liver iron is a negative prognostic factor for alpha-interferon response in chronic hepatitis C. Iron depletion had a beneficial effect on serum alanine aminotransferase in all the patients treated, but did not improve the response to alpha-interferon.

The ancestral hemochromatosis haplotype is associated with a severe phenotype expression in Italian patients.

We evaluate the relation between genotype and phenotype in 47 Italian male patients with homozygous genetic hemochromatosis (GH). Phenotype evaluation was based on the ratio of amount of iron removed (IR) by phlebotomy and age (IR/age). Patients were divided in two classes of phenotype expression: class I included 26 patients with less severe iron overload (IR/age <0.33) and class II included 21 patients with a more marked one (IR/age >0.33). Genetic variability was assessed by haplotype analysis combining alleles at HLA-B, D6S265, HLA-A, and D6S105 loci. A common ancestral haplotype carrying D6S265-1, HLA-A3, and D6S105-8 alleles was present in 13 of 52 (25%) chromosomes in class I and in 24 of 42 (57%) chromosomes in class II (P = .0027). Homozygotes and heterozygotes for the ancestral haplotype had higher iron indices than patients carrying two haplotypes other than the ancestral one. Seven of the eight patients homozygous for the ancestral haplotype were in class II, heterozygotes were equally distributed between the two classes, whereas 14 of 18 carriers of other haplotype combinations were in class I. Our results suggests that the gene defect linked to the ancestral haplotype is the result of a single, severe mutation. The high variability of phenotype expression in heterozygotes for the ancestral haplotype could be accounted for the contribution of the mutation carried by the second haplotype. Combination of different mutations could be responsible for the variable degrees of iron overload found in patients with GH.

Time course of circulatory and humoral effects of rapid total paracentesis in cirrhotic patients with tense, refractory ascites.

BACKGROUND/AIMS: Tense ascites of cirrhosis can be treated with total paracentesis; however, the short-term effects of this procedure are poorly defined. METHODS: The circulatory and humoral changes induced by total paracentesis (250 mL/min) were studied in 12 cirrhotics with tense, refractory ascites. Data were collected before, during, and after paracentesis and 24 hours later (after albumin infusion). Hormonal parameters were recorded again 48 hours and 6 days thereafter. RESULTS: Paracentesis (10.7 +/- 4.4 L; 64 +/- 20 minutes) caused marked reduction of intra-abdominal, intrathoracic, right atrial, and pulmonary pressures. Heart rate did not change. Cardiac output and heart volumes increased. Systemic vascular resistances and mean arterial pressure slightly decreased. Baseline plasma renin and aldosterone levels were markedly increased; a reduction was already evident during paracentesis with the lowest values at the end of the procedure. All changes were maintained 24 hours later. Hormones regained baseline levels 6 days later. CONCLUSIONS: Rapid total paracentesis is accompanied by marked cardiovascular and humoral changes. Some of these changes can be explained by mechanical factors that are directly or indirectly related to the relief of abdominal pressure. However, other changes (systemic vasodilatation, humoral deactivation) have a non-mechanical nature and may depend on reflexes originating from cardiac volume receptor stimulation. Most changes may beneficially (albeit transiently) influence the cardiovascular system of cirrhotic patients with tense ascites.