Leptin in nonalcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition associated with obesity and insulin resistance (IR). Leptin plays a key role in the control of energy balance, and insulin sensitivity. In this study, we aimed to examine whether serum leptin levels correlate with insulin resistance, oxidative stress parameters and the severity of histological changes in NAFLD. METHODS: Fifty-two patients (M/F: 28/24) with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied. Serum leptin levels were measured by radioimmunoassay. HOMA (homeostasis model assessment) IR index was calculated. Comparisons between the patients with NAFLD and non-alcoholic steatohepatitis (NASH) were performed using the Student's t test. Multivariate regression analysis and the area under the receiver operating characteristic (ROC) curve were used to identify the independent predictors for NASH. RESULTS: We found no association between serum leptin, fasting insulin levels, and oxidative stress parameters. ROC curve and multiple regression analysis revealed no association between the severity of histological changes and serum leptin levels. During six months followed-up period only NASH group with elevated leptin levels had significant reductions of ALT and AST values (p = 0.03, and 0.005, respectively). CONCLUSION: Our findings show a preventive effect of leptin against progressive liver injury in NAFLD.

Serum YKL-40 levels and chitotriosidase activity as potential biomarkers in primary prostate cancer and benign prostatic hyperplasia.

BACKGROUND: YKL-40, also called human cartilage glycoprotein-39 (HC gp-39) and chitotriosidase are homologs of family 18 glycosyl hydrolases secreted by human macrophages. Although high levels of YKL-40 and chitotriosidase are associated with several diseases, the physiological functions of these enzymes are still unclear. YKL-40, a growth factor for connective tissue cells, a migration factor for endothelial and vascular smooth muscle cells, is expressed by several types of solid human carcinoma, including prostate carcinoma. PURPOSE: The purpose of this study was to compare serum YKL-40 levels and chitotriosidase activity both in benign prostatic hyperplasia and primary prostate cancer. METHODS: YKL-40 and chitotriosidase were determined in serum samples from 93 patients with primary prostate cancer and 61 patients with benign prostatic hyperplasia. Serum YKL-40 levels were measured by ELISA and chitotriosidase activity was determined by fluorometer. PSA levels were also measured by using an automated system. RESULTS: Serum YKL-40 levels were significantly higher (P < 0.001) in patients with prostate cancer compared with control group whereas there was no significant difference between BPH and control group. Serum chitotriosidase activities were significantly higher in carcinoma patients with high Gleason score than the control group (P < 0.001). No significant difference was observed in BPH patients (P > 0.05). Both YKL-40 and chitotriosidase were found statistically significant higher in primary prostate cancer and BPH. CONCLUSION: High serum YKL-40 levels in patients with primary prostate cancer indicate that YKL-40 may have a function in the progression of malignant diseases, whereas no significant elevation was observed in benign prostatic hyperplasia. Meanwhile, high serum chitotriosidase activity was observed only in patients with Gleason high grade, indicating possible macrophage involvement in cancer progression. Further studies are needed to elucidate the biologic role of YKL-40 in cancer aggressiveness and in progression of malignant diseases.

Serum chitotriosidase activity in patients with coronary artery disease.

BACKGROUND: Atherosclerosis is considered to be an inflammatory disease in which the initial process is augmented infiltration of monocytes into the vessel wall and their subsequent differentiation from macrophages into lipid-laden foam cells. Chitotriosidase is one of the most quantitative proteins secreted by activated macrophages, so the aim of this study was to investigate the association of the level of serum chitotriosidase activity with atherosclerotic coronary artery disease (CAD). METHODS AND RESULTS: A total of 200 subjects undergoing coronary angiography were divided into 4 subgroups according to the number of diseased vessels and their serum chitotriosidase activity levels were measured. Serum chitotriosidase activity in patients with CAD was significantly higher than in normal control subjects (p<0.001). Serum chitotriosidase activity was also significantly associated with the extent of CAD as defined by the number of stenosed vessels (p<0.001). CONCLUSION: Serum chitotriosidase activity can be considered a strong inflammatory marker of CAD. Moreover, plasma chitotriosidase activity may be also regarded as a quantitative indicator of disease extent, as well as being a marker of disease presence.

Effects of atorvastatin therapy on hypercholesterolemic rabbits with respect to oxidative stress, nitric oxide pathway and homocysteine.

Hypercholesterolemia is characterized with changes in lipid profile, nitric oxide pathway and oxidative stress markers. This study is designed to evaluate the effects of hypercholesterolemic diet and atorvastatin therapy on oxidative stress, lipid peroxide and thiobarbituric acid reactive substances (TBARS), NO pathway markers, nitric oxide(NO) and asymmetric dimethylarginine (ADMA), homocysteine, and paraoxonase activity (PON1) in rabbits. Twenty rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into 2 groups on the fourth week of the hypercholesterolemic diet. First group was fed with high-cholesterol diet alone, whereas the second group with the same cholesterol diet plus atorvastatin (0.3 mg/kg/day) for 4 weeks. High-cholesterol diet increased total cholesterol, low density lipoprotein (LDL-C), high density lipoprotein (HDL-C), ADMA, TBARS and lipid peroxide levels and reduced PON1 activity and NO levels in rabbits. Four weeks of atorvastatin therapy significantly increased HDL-C, PON1 activity and reduced LDL-C, TBARS and lipid peroxide concentrations. Atorvastatin therapy is beneficial in decreasing oxidative stress related with hypercholesterolemia, mainly affecting lipid profile and PON1 activity.

Dialysate CA125 levels in children on continuous peritoneal dialysis.

This prospective study was conducted to assess dialysate cancer antigen 125 (dCA125) levels in pediatric peritoneal dialysis (PD) patients and to investigate whether it exhibits any alterations during or after recovery from peritonitis, and also to analyze the relationships between dCA125 and age, duration of PD treatment, peritonitis incidence, time passed since the last episode of peritonitis, PD prescription parameters, and peritoneal transport parameters. Forty-seven standardized 4-h peritoneal equilibration tests (PET) were performed in 38 children (mean age 11.6+/-4.7 years) on PD (duration 20.9+/-14.3 months). Thirty-two of the patients were in stable condition at the time of PET (stable group). Six patients were included in the study only during a peritonitis episode, and two of the stable patients were reevaluated during a peritonitis episode afterwards (peritonitis group). Seven out of a total of eight patients with acute peritonitis were reexamined after recovery (recovery group). CA125 levels were measured in 188 samples at 0-, 1-, 2-, and 4-h dwells. Peritoneal appearance rates (AR) were calculated. Mean dCA125 (4 h) and AR CA125 values were 5.6+/-5.3 U/ml [median 4.15 U/ml/4 h (range 0.5-25.9)] and 50.1+/-45.6 U/min/1.73 m2[median 37.91 U/ml/1.73 m2 (range 3.61-223.39)]. AR CA125 levels did not correlate with age, PD duration, peritonitis incidence, time passed since the last peritonitis episode, exchange volume used per m2 per day, or peritoneal transport properties in the stable patients' group. Although stable patients using hypertonic PD solutions (n=16) had slightly lower AR CA125 levels (p=0.04), multivariate analysis showed no influence of hypertonic dextrose solutions on mesothelial CA125 secretion (p=0.4). During acute peritonitis, CA125 concentrations showed a reversible threefold increase [AR CA125: stable 37.9 vs. peritonitis 101.2 U/ml/1.73 m2 (p=0.001)]. No difference could be found between the stable group and the recovery group. We conclude that changes in the peritoneal mesothelial cell mass cannot be assessed by determining CA125 in a cross-sectional way and that longitudinal determinations could be more valuable in the follow-up of patients.

Effectiveness of morphine via thoracic epidural vs intravenous infusion on postthoracotomy pain and stress response in children.

BACKGROUND: Thoracotomy causes severe pain in the postoperative period. The aim was to evaluate effectiveness of two pain treatment methods with morphine on postthoracotomy pain and stress response. METHODS: Thirty-two children undergoing major thoracotomy for noncardiac thoracic surgery were allocated to receive either single dose of thoracic epidural morphine 0.1 mg x kg(-1) in 0.2 ml x kg(-1) saline (TEP group, n = 16) or morphine infusion at 0.02 mg x kg(-1) h(-1) (INF group, n = 16) following bolus dose of 0.05 mg x kg(-1) postinduction. Pain and sedation scores and incidence of complications were recorded for 24 h and cortisol, blood glucose, insulin and morphine serum levels were evaluated following induction, 1, 8, 12, and 24 h after initial morphine administration. RESULTS: Five patients in TEP and one in INF required rescue morphine. The cortisol, insulin and blood glucose increased during the study and returned to normal levels at 24th hour (P < 0.05), similarly in both groups (P > 0.05). The morphine levels were variable within and between groups (P < 0.05). A common complication was nausea and vomiting with both the techniques (P > 0.05). CONCLUSION: Single dose TEP morphine offers no advantage over INF for pain treatment for thoracotomy in children and neither technique provided suppression of stress hormones in the first 24 h postoperatively.

Effects of systemic and epidural morphine on antidiuretic hormone levels in children.

BACKGROUND: Although the use of opioids during general anaesthesia suppresses stress response to surgery and pain, the effects on antidiuretic hormone (ADH) are controversial. The aim of this study was to find the effects of morphine with either intravenous infusion or epidural route on ADH and other stress hormones. METHODS: Fifty children aging (1-15 years) undergoing major genito-urinary or abdominal operations were included in this study. The patients were allocated randomly to two groups receiving either a single dose of epidural morphine 0.1 mg.kg-1 (EP group, n = 25) postinduction or morphine infusion (INF group; n = 25) at 0.02 mg.kg-1.h-1 following 0.05 mg.kg-1 bolus. Blood samples were withdrawn for plasma ADH, osmolality, glucose, cortisol, insulin and morphine level analysis following induction and 1, 5, 12 and 24 h after initial morphine administration. RESULTS: The two groups were similar in demographic factors, pain scores, sedation scores, and incidence of nausea and vomiting. The amount of morphine received was different between groups and the changes in serum levels of morphine were statistically significant in EP group ( P < 0.05). The changes in cortisol, blood glucose and insulin levels were insignificant in both groups (P > 0.05). The changes of ADH levels were significant at time-points in both groups, reaching control levels at the 24th hour (P < 0.05). CONCLUSION: Despite the effective pain therapy and suppression of cortisol and insulin response to surgical stimulus, the increase in ADH secretion is not effected by systemic or epidural morphine administration.

Hypoxic initiation of pulmonary hypertension is mediated by serotonin secretion from neuroepithelial bodies in chemodenervated dogs.

The purpose of this study was to investigate the stimulatory effect of hypoxia on the secretion of serotonin by neuroepithelial bodies (NEB) as well as to determine the relation between its level and changes in pulmonary arterial pressure (PAP) and also to determinate the effect of serotonin antagonists (pizotifen and methysergide) on the responses of pulmonary and systemic arterial pressures. The experiments were carried out in peripheral chemoreceptor-denervated dogs anesthetized with Na penthabarbital (30 mg/kg i.v.). On the breathing of normoxic and hypoxic (7% O2-93% N2) gas mixtures and on the injection of KCN (80 microg/kg i.v.), PAP, systemic arterial blood pressure (BP), tidal volume (VT), respiratory frequency (f/min), ventilation minute volume (VE) were determined. Also PAP and BP were recorded before and after the injection of pizotifen (0.5 mg/kg i.v.) and methysergide (1 mg/kg i.v.) during normoxic or hypoxic gas mixture breathing. At the end of each experimantal phase, serotonin level, PaO2, PaCO2 and pHa values in blood samples obtained from left ventricle and femoral artery were determined. On the breathing of the hypoxic gas mixture of the chemodenervated dogs, VT, VE and BP significantly decreased (P < 0.001, P < 0.001, P < 0.01). The mean value of PAP and serotonin levels (ventricular and femoral) were found significantly increased when compared with the corresponding normoxic values (P < 0.001, P < 0.05). On the other hand, injection of KCN produced no significant changes in PAP, serotonin levels, BP and respiratory parameters. After the injection of pizotifen, PAP was significantly increased in hypoxia (P < 0.01). After the injection of methysergide, the response of PAP was completely abolished during the breathing of hypoxic gas mixture. The finding of the abolition of response of PAP to hypoxia after the injection of methysergide indicates that serotonin release from NEB may be responsible for the elevation of PAP in hypoxic hypoxia.