T. Barreca

Serum leptin levels in patients with viral chronic hepatitis or liver cirrhosis

BACKGROUND/AIM Serum levels of leptin, the adipocyte-derived hormone regulating food intake and energy expenditure in mammals, have been found to be increased in cirrhotic patients. The aim of the present study was to investigate leptin serum level in relation to anthropometric features and liver function in patients with viral chronic hepatitis or liver cirrhosis. METHODS Serum leptin levels were determined by radioimmunoassay in 30 male and 10 female patients with chronic hepatitis, in 42 male and 10 female patients with liver cirrhosis, and in four respective control groups. Liver function was evaluated by the monoethylglycinexylidide formation test. Body mass index and body fat mass were estimated by weight, height and skinfold thickness measurements. RESULTS Compared with controls, absolute serum leptin levels were significantly (p<0.01) lower in chronic hepatitis patients and similar in cirrhotic patients. Leptin serum levels were significantly (p<0.05) higher in cirrhotic than in chronic hepatitis patients. When expressed in relation to body fat mass, the above differences persisted; however, cirrhotic females showed significantly (p<0.05) higher serum leptin values than controls. Serum leptin values correlated negatively (p<0.01) with monoethylglycinexylidide serum values in all groups of patients. CONCLUSIONS In patients with chronic viral liver disease, serum leptin levels tend to increase as liver function worsens. This may reflect a decline in the ability to downregulate energy expenditure as an adaptation to anorexia and/or to defective substrate utilisation due to liver disease and may negatively influence body weight homeostasis in these patients.

Leptin as a Uremic Toxin Interferes with Neutrophil Chemotaxis

Leptin is a pleiotropic molecule involved in energy homeostasis, hematopoiesis, inflammation, and immunity. Hypoleptinemia characterizing starvation has been strictly related to increased susceptibility to infection secondary to malnutrition. Nevertheless, ESRD is characterized by high susceptibility to bacterial infection despite hyperleptinemia. Defects in neutrophils play a crucial role in the infectious morbidity, and several uremic toxins that are capable of depressing neutrophil functions have been identified. Only a few and contrasting reports about leptin and neutrophils are available. This study provides evidence that leptin inhibits neutrophil migration in response to classical chemoattractants. Moreover, serum from patients with ESRD inhibits migration of normal neutrophils in response to N-formyl-methionyl-leucyl-phenylalanine with a strict correlation between serum leptin levels and serum ability to suppress neutrophil locomotion. Finally, the serum inhibitory activity can be effectively prevented by immune depletion of leptin. The results also show, however, that leptin by itself is endowed with chemotactic activity toward neutrophils. The two activities-inhibition of the cell response to chemokines and stimulation of neutrophil migration-could be detected at similar concentrations. On the contrary, neutrophils exposed to leptin did not display detectable [Ca(2+)](i) mobilization, oxidant production, or beta(2)-integrin upregulation. The results demonstrate that leptin is a pure chemoattractant devoid of secretagogue properties that are capable of inhibiting neutrophil chemotaxis to classical neutrophilic chemoattractants. Taking into account the crucial role of neutrophils in host defense, the leptin-mediated ability of ERSD serum to inhibit neutrophil chemotaxis appears as a potential mechanism that contributes to the establishment of infections in ERSD.

Leptin has no role in determining severity of steatosis and fibrosis in patients with chronic hepatitis C.

OBJECTIVE:The presence of steatosis is a common histological finding in patients with chronic hepatitis C (CHC). The causes of the severity of this condition are not yet clear, although both metabolic and viral factors supposedly are involved. In this study our aim was to examine the possible influence that leptin levels, hepatitis C virus (HCV) RNA levels, and hepatitis G virus (HGV) infection have on the severity of steatosis and on the presence and degree of fibrosis in patients with CHC.METHODS:One hundred eighty-two CHC patients with histological findings of steatosis were chosen from among a cohort of patients referred to our center for staging of liver disease. Among them 48 CHC patients were accurately selected so as to rule out possible confounding factors for the presence of steatosis (diabetes mellitus, hyperlipemia, obesity, alcohol). Leptin levels, HCV RNA levels, and HCV genotype, and the presence of HGV RNA were assessed in these patients and related to histological findings.RESULTS:We found that leptin levels in CHC patients were similar to those in healthy subjects. No relationship was found between leptin levels and severity of steatosis. HCV RNA levels, HCV genotype, and the presence of HGV infection were no different among CHC patients with various degrees of steatosis. Leptin was not related to different degrees of fibrosis, whereas higher viral load was the only parameter associated to higher fibrosis scores.CONCLUSIONS:These findings suggest that the degree of steatosis in patients with CHC does not seem to depend on serum leptin levels or on viral factors, at least as far as HCV viremia and genotype and HGV infection are concerned. The severity of fibrosis does not seem to be influenced by leptin levels, whereas HCV viral load does seem to play some role.

Influence of β-endorphin on phytohemagglutinin-induced lymphocyte proliferation and on the expression of mononuclear cell surface antigens in vitro

Recent evidence suggests that opiates can modulate the immune responses. In particular it has been shown that beta-endorphin and morphine are able to depress some T lymphocyte functions in humans. In the present study, experiments were designed to evaluate the effect of beta-endorphin phytohemagglutinin-induced lymphocyte proliferation and determine the mechanism of this action. The ability of naloxone to block the effect of beta-endorphin was also investigated, and the influence of beta-endorphin on the expression of mononuclear cell surface antigens using the OKT3, OKT4, OKT8, anti-HLA-DR and anti-beta 2-microglobulin monoclonal antibodies was evaluated. Phytohemagglutinin-induced lymphocyte proliferation was significantly inhibited by beta-endorphin. This effect occurred when beta-endorphin was added to cells at the beginning of the culture period (30 min before, simultaneously or 30 min after phytohemagglutinin), but not when added after 48 h of incubation. The preincubation of cells with BEP for 1 h, 4 h or 24 h did not affect lymphocyte activation by phytohemagglutinin. A ten-fold excess of naloxone, added to cultures 30 min prior to beta-endorphin, did not block the inhibitory effect. Incubation with beta-endorphin had different effects on each surface antigen tested. The OKT8+ and beta 2-microglobulin+ cells did not show significant variations. The OKT4+ cells significantly decreased, after 4 h of incubation with beta-endorphin, both in mononuclear cell and in purified T lymphocyte cultures and, after 24 h, in mononuclear cell cultures only. The OKT3+ cells decreased, in mononuclear cell cultures only, after 24 h beta-endorphin incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

24-Hour Thyroid-Stimulating Hormone Secretory Pattern in Elderly Men

A chronobiological study was carried out in 10 elderly male subjects (78-83 years) to evaluate the 24-hour thyroid-stimulating hormone (TSH) secretory pattern. 10 young adult males (26-35 years) made up the control group. Hourly blood samples were drawn from each subject for a 24-hour period. TSH levels in elderly subjects showed blunted circadian fluctuations compared to those seen in young adult subjects. Mean 24-hour TSH values in elderly (3.1 +/- 0.3 microU/ml) and young adult subjects (3.5 +/- 0.1 microU/ml) did not differ statistically, but nighttime TSH values observed in elderly subjects (3.2 +/- 0.3 microU/ml) were lower (p less than 0.05) than those recorded in young adults (4.1 +/- 0.1 microU/ml).

Effects of ursodeoxycholic acid (UDCA) on serum liver damage indices in patients with chronic active hepatitis

SummaryThe effects of ursodeoxycholic acid (UDCA, 450 mg daily) in patients with histologically proven chronic active hepatitis (CAH) have been evaluated in a randomized, double-blind, placebo-controlled study. Twenty-six patients with serum alanine aminotransferase (ALT) values at least twice the normal upper limit in two of three pre-treatment tests received UDCA or a placebo for twelve weeks.In all UDCA-treated patients, serum aspartate aminotransferase (AST), ALT, gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (AP) fell significantly after 4 weeks of treatment. There was a further decrease at the end of therapy, as well as a small but significant fall in total serum bilirubin. Conversely, 4 weeks aftersuspension of therapy, serum enzyme levels had increased, reaching values not much lower than those recorded before treatment. Total serum protein, albumin and γ-globulin did not change after UDCA treatment. In the placebo group no significant variation in the test results were found.The results indicate that UDCA therapy in CAH, as has been observed in primary biliary cirrhosis and primary sclerosing cholangitis, is able to improve several indices of liver damage, without producing any toxic adverse effects.

Oxidative stress in subjects affected by celiac disease

In order to study the role of oxidative stress in celiac disease, protein carbonyl groups, thiobarbituric acid-reactive substance and pentosidine were evaluated in the plasma of nine patients with asymptomatic celiac disease and in a control group (n = 25). Plasma alpha-tocopherol, retinol and lipids were determined in the same samples. The levels of markers of oxidative stress derived from both protein (carbonyl groups) and lipids (thiobarbituric acid-reactive substances) were significantly higher in celiac disease patients, whereas lipoproteins and alpha-tocopherol were significantly lower. These data indicate that in celiac disease, even when asymptomatic, a redox imbalance persists; this is probably caused by an absorption deficiency, even if slight. Dietary supplementation with antioxidant molecules may offer some benefit and deserves further investigation.

The effects of sumatriptan on pituitary secretion in man

Sumatriptan, a new antimigraine drug with high affinity and selectivity for certain 5-hydroxytryptamine (5-HT1D) receptor subtypes, was administered to 12 normal subjects, in order to investigate the effects of 5-HT receptor activation on anterior pituitary secretion. Sumatriptan increased plasma growth hormone (GH) levels from 2.5 +/- 0.5 mIU/l in basal conditions to 17.3 +/- 2.6 mIU/l 30 min after administration of the drug. After pre-treatment with cyproheptadine, an anti-serotoninergic drug known to inhibit GH secretion, the mean integrated sumatriptan-induced GH response decreased from 14.8 +/- 3.9 muI/l*hr to 3.7 +/- 1.7 mIU/l*hr. Sumatriptan administration did not have any effect on the secretion of the other anterior pituitary hormones. It is concluded that sumatriptan selectively increases GH secretion in man, but the exact nature of the receptors involved is not yet known.

Plasma beta‐endorphin concentrations during suckling in lactating women

Summary. Beta‐endorphin appears to be involved in the hormonal response to suckling in some animals. The peripheral secretory patterns of β‐endorphin, prolactin and cortisol were investigated in serial venous blood samples taken during suckling from eight healthy women who were breast‐feeding on the third or fourth day of the puerperium. Plasma levels of prolactin and β‐endorphin increased significantly during suckling reaching a peak after 20 min, levels of cortisol remained unaffected. It is suggested that the increased β‐endorphin derives from an extra‐hypophyseal source.

Diurnal beta-endorphin changes in human cerebrospinal fluid

Plasma and cerebrospinal fluid (CSF) beta-endorphin levels were determined by a RIA method in seven hydrocephalic male patients. The samples were simultaneously collected every two hours from 8 AM to 12 midnight and every hour from 1 AM to 7 AM. In both plasma and CSF beta-endorphin levels showed significant time-related variations during the 24 hour period. These results suggest the existence of diurnal CSF beta-endorphin variations analogous to those observed in plasma.