Pleiotropic effects of HDL subfractions and HDL-associated enzymes on protection against coronary artery disease.

OBJECTIVE: High-density lipoprotein cholesterol (HDL-C) levels are inversely related to the risk of coronary artery disease (CAD). Alterations in HDL-C subclass distribution and HDL-associated enzyme activities may be more important than total HDL levels for the progression of CAD. We intended to investigate the relationship of HDL-C subclass distribution and HDL-associated enzyme activities with CAD. METHOD AND RESULTS: Our study included 101 patients with stable coronary artery disease, and 64 healthy subjects. Serum levels of HDL lipoprotein-associated-phospholipase A2 (HDL-LpPLA2), paraoxonase 1 (PON1), and HDL subfraction distribution were measured. We found increased small HDL (sHDL) subfractions in patients with one-vessel disease (P < 0.001). We also found a reverse correlation between total HDL-C levels and affected vessel number (P < 0.05). Plasma HDL-Lp PLA2 enzyme level was higher in each vessel disease category compared to the control group (P < 0.001). However, PON1 enzyme activity in patients with CAD was not statically significant. Plasma sHDL, HDL-Lp PLA2 enzyme and Lp(a) were significantly different between subjects with CAD and control participants. CONCLUSIONS: We demonstrated decreased sHDL particles and a lower cardioprotective HDL-LpPLA, enzyme activity in all patient subgroups compared to controls. Measurement of total HDL-C level only may not be sufficient to predict CAD risk.

The effects of atorvastatin therapy on rheological characteristics of erythrocyte membrane, serum lipid profile and oxidative status in patients with dyslipidemia.

The statins, most commonly used in the treatment of hyperlipidemia, have certain beneficial effects including improved endothelial function, plaque stability and decreased oxidative stress and inflammation, beyond their lipid-lowering effect in plasma. We evaluated the pleiotropic impact of atorvastatin on erythrocyte structural/mechanical properties and lipid peroxidation in dyslipidemics. The study group included 44 patients with dyslipidemia and was divided into subgroups according to triglyceride and cholesterol levels as hypercholesterolemic (n = 29) and mixed-type hyperlipidemic (n = 15). Subjects were given 10 mg atorvastatin per day for 12 weeks. Changes in serum lipid composition, lipid contents, Na(+)/K(+)-ATPase activity and osmotic fragility in erythrocytes and oxidative stress parameters of erythrocytes and plasma were studied. Atorvastatin therapy improved the serum lipid profile of both subgroups. This alteration was accompanied by a decreased level of cholesterol in erythrocyte membranes. Moreover, enhanced activity of Na(+)/K(+)-ATPase in erythrocytes reflected the improvements in membrane lipids of both subgroups. However, a significant change was observed in osmotic fragility values of the mixed-typed dyslipidemic group. This treatment lowered the lipid peroxidation in plasma and erythrocytes and increased plasma total antioxidant capacity in all groups. The present study shows that the use of atorvastatin reversed the structural and functional features of erythrocyte membranes in dyslipidemic subjects. Also, hypolipidemic therapy had a beneficial impact on a balance between oxidant and antioxidant systems.

Evaluation of biological activities of Barbarea integrifolia and isolation of a new glucosinolate derivated compound.

The aim of the present study is to determine the potent biological activities and carry out isolation studies on Barbarea integrifolia. The antioxidant capacity of the species was evaluated by total phenolic content, FRAP, CUPRAC, and DPPH radical scavenging activity. Anticancer activity studies were performed by MTT assay in MDA-MB-231, MCF-7, Hep3B, PC-3, A549, HCT116, L-929 cell lines. It was observed that the remaining aqueous fraction has higher total phenolic content while higher activity in the CUPRAC and FRAP assays was displayed for the methanolic extract and chloroform fraction. The extracts showed anticancer activity as compared with vincristine. It was observed that chloroform fraction has the highest anticancer activity on MCF-7 cell line, while ethyl acetate fraction has the highest anticancer activity on Hep-3B and A549 cell lines. Methanolic extract has the highest anticancer activity on HCT116 and MDA-MB-23 cell lines. The isolation studies have been performed using several chromatographic methods. The chemical structures of compounds have been identified by means of 1H NMR, 13C NMR, 2D-NMR, and MS. Five major compounds, one steroid (ß-Sitosterol), one phenolic acid (Rosmarinic acid), one flavonol heteroside (kaempferol 7-O-α-l-rhamnoside-3-O-ß-d-(2-O-ß- d -glucosyl)-ß-d-glucoside), and two glucosinolates (Gluconasturtiin, Gluconasturtiin choline salt) have been isolated.

Protective effects of tumor necrosis factor alpha inhibitors on methotrexate-induced pancreatic toxicity.

BACKGROUND: Methotrexate (MTX), a folate antagonist, is commonly used in the treatment of many different types of cancer and inflammatory diseases, including pancreatic cancer, although its side effects on the pancreas have not yet been researched. The mechanism of MTX-induced toxicity is not well known, and it has been reported in high-dose toxicity studies that the pancreas is sensitive to toxic effects. OBJECTIVES: The aim of our study was to determine whether adalimumab (ADA) has a preventive effect on MTX-induced pancreas toxicity in rats. MATERIAL AND METHODS: The rats were equally and randomly divided into 3 groups (Group 1 comprised the healthy controls, Group 2 was the MTX group, and Group 3 was the MTX + ADA group). The rats in Groups 2 and 3 received an intraperitoneal (ip.) single-dose injection of MTX (20 mg/kg). A single dose of 5 mg/kg ADA (REMICADE®) was administered ip. to Group 3. All the rats were sacrificed under anesthesia 5 days after receiving the MTX injection. RESULTS: Significantly higher mean edema, necrotic cell, and inflammatory scores were recorded in Groups 2 and 3 compared to those recorded in Group 1. Significantly decreased edema, number of necrotic cells, and inflammatory scores were noted in Group 3 than in Group 2. A decrease in islets of Langerhans cell insulin and somatostatin-positive interneurons was demonstrated after the administration of MTX. An increase in insulin and somatostatin-positive cells in islets of Langerhans, as well as a remodeling of the structure of the pancreas, was shown following treatment with ADA. CONCLUSIONS: Adalimumab was demonstrated to have a protective effect against MTX-induced pancreatic injury in this study.

Reference values of cord blood transferrin, ceruloplasmin, alpha-1 antitrypsin, prealbumin, and alpha-2 macroglobulin concentrations in healthy term newborns.

Acute phase proteins are sensitive markers of tissue necrosis and inflammatory process. These markers may be especially useful in the neonatal period, in which mortality and morbidity rates are high, because fetus and baby are subjected to numerous metabolic, genetic, physiologic and environmental injuries such as neonatal asphyxia and septicemia. The purpose of the present study was to establish normal cord blood levels of some acute phase proteins in healthy term neonates. Umbilical cord blood was obtained at the time of vaginal delivery in 60 newborn infants (30 girls, 30 boys). Specific protein concentrations were measured by nephelometric assay. Transferrin, ceruloplasmin, alpha-1 antitrypsin, prealbumin, and alpha-2 macroglobulin concentrations [arithmetic mean (+/- SD)] were found to be 199.7 (+/- 34.6) mg/dl, 14.6 (+/- 4.0) mg/dl, 160.2 (+/- 23.6) mg/dl, 11.9 (+/- 2.2) mg/dl, and 284.6 (+/- 44.4) mg/dl, respectively. Prealbumin levels for girls [12.9 (+/- 2.2)] were found to be significantly higher than those of boys [10.9 (+/- 1.8)] (p < 0.001), while there were no significant differences between the other proteins. We conclude that these results may be used as reference values for the diagnosis of pathological conditions in newborns.

Effect of antiepileptic drugs on plasma lipids, lipoprotein (a), and liver enzymes.

We conducted a study to assess the effect of phenobarbital, carbamazepine, and valproate on serum lipid profiles and lipoprotein (a) in 64 children with epilepsy (aged between 1 and 15 years) admitted to the child neurology outpatient clinic between July 2000 and July 2002. The children were separated as group 1 (18 children), treated with phenobarbital, 5 mg/kg/day; group 2 (22 children), treated with carbamazepine, 10 to 15 mg/kg/day; and group 3 (24 children), treated with sodium valproate, 20 mg/kg/day. Plasma lipoprotein (a), total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, apolipoprotein A and apolipoprotein B levels, and liver enzymes alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and gamma-glutamyltransferase were determined before the initiation of the treatment and at 3, 6, and 12 months of the treatment period. The mean age of children in group 1 was significantly low compared with those in groups 2 and 3 (P <.05). The mean pretreatment lipid levels among the groups were not significantly increased. The mean lipoprotein (a) levels were significantly increased in all groups at 3, 6, and 12 months of the treatment period (P <.05). The increase in alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol at 3, 6, and 12 months was statistically significant in group 1 (P <.05). The higher levels in lipoprotein (a) (mean > 30 mg/dL) were observed only in carbamazepine-treated patients at 6 and 12 months. The percentage of children with lipoprotein (a) levels over 30 mg/dL was 44%, 63%, and 33% in the phenobarbital-, carbamazepine-, and valproate-treated children, respectively. Antiepileptic drugs significantly increase the level of lipoprotein (a), which is a major risk factor for atherosclerosis, and also have variable effects on other lipid parameters. Lipoprotein (a) levels should be closely followed in patients receiving antiepileptic drugs. (J Child Neurol 2006;21:70-74).

The effect of erythrocyte membranes from diabetic and hypercholesterolemic individuals on human carbonic anhydrase II activity.

CONTEXT: Erythrocyte membranes regulate many enzyme activities, including carbonic anhydrase II (CA II). Membrane fluidity is associated with alterations in protein function and protein-protein interactions. OBJECTIVE: The purpose of this study was to show the human CA II (hCA II) activity regulation by human erythrocyte membranes from diabetic and hypercholesterolemic subjects. MATERIALS AND METHODS: Erythrocyte membranes were obtained from diabetic, hypercholesterolemic, and healthy subjects. hCA II activity was measured using the electrometric method. RESULTS: hCA II activity was increased in vitro by membranes from both diabetic and hypercholesterolemic patients, with hypercholesterolemic membranes exhibiting a greater increase. CONCLUSION: Changes in membrane composition may affect the erythrocyte membranes' capacity to increase in vitro hCA II activity.

Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder.

BACKGROUND: The most commonly used medications for attention deficit hyperactivity disorder (ADHD) are the psychostimulants. There is, however, considerable awareness in alternative, nonstimulant therapies, because some patients respond poorly to stimulants or are unable to tolerate them. Some studies suggest that deficiency of zinc play a substantial role in the aetiopathogenesis of ADHD. Therefore, to assess the efficacy of zinc sulfate we conducted treatment trial. METHODS: Patients with a primary DSM-IV diagnosis of ADHD (N=400; 72 girls, 328 boys, mean age=9.61+/-1.7) were randomly assigned in a 1:1 ratio to 12 weeks of double-blind treatment with zinc sulfate (n=202) (150 mg/day) or placebo (n=198). Efficacy was assessed with the Attention Deficit Hyperactivity Disorder Scale (ADHDS), Conners Teacher Questionnaire, and DuPaul Parent Ratings of ADHD. Primary efficacy variables were differences from baseline to endpoint (last observation carried forward) in mean ADHDS and Conners Teacher Questionnaire scores between the zinc sulfate and the placebo groups. Safety evaluations included monitoring of adverse events, vital signs and clinical laboratory values. RESULTS: Zinc sulfate was statistically superior to placebo in reducing both hyperactive, impulsive and impaired socialization symptoms, but not in reducing attention deficiency symptoms, as assessed by ADHDS. However, full therapeutic response rates of the zinc and placebo groups remained 28.7% and 20%, respectively. It was determined that the hyperactivity, impulsivity and socialization scores displayed significant decrease in patients of older age and high BMI score with low zinc and free fatty acids (FFA) levels. Zinc sulfate was well tolerated and associated with a low rate of side effect. CONCLUSIONS: Zinc monotherapy was significantly superior to placebo in reducing symptoms of hyperactivity, impulsivity and impaired socialization in patients with ADHD. Although by themselves, these findings may not be sufficient, it may well be considered that zinc treatment appears to be an efficacious treatment for ADHD patients having older age and high BMI score with low zinc and FFA levels.

Ham's F-10 medium and Ham's F-10 medium plus vitamin E have protective effect against oxidative stress in human semen.

OBJECTIVES: To investigate possible protective effects of vitamin E and Ham's F-10 medium (HF-10) on lipid peroxidation, apoptosis, motility, and vitality of spermatozoa. METHODS: Normozoospermic semen samples were obtained from 35 volunteers. Normal saline solution, HF-10 only, or HF-10 with vitamin E were added to split semen samples (control, group 1, and group 2, respectively). Sperm motility and vitality were evaluated at the end of 1, 2, and 24 hours. Superoxide dismutase, catalase, and malondialdehyde levels were assessed at the end of the first hour. Flow cytometric DNA analysis was performed at the end of 24 hours. RESULTS: Superoxide dismutase, sperm motility, and vitality were not different among the groups. The catalase values decreased in group 1, but not in group 2. Malondialdehyde values in supernatants decreased in group 2 and apoptosis of spermatozoa decreased in groups 1 and 2. CONCLUSIONS: Our data suggest that vitamin E and HF-10 protect against the reactive oxygen species-mediated damage on spermatozoa.

Erythrocyte antioxidant enzyme activities and lipid peroxidation in patients with types IIb and IV hyperlipoproteinemias.

We measured lipid peroxidation and antioxidant enzymes in erythrocytes of types IIb and IV hyperlipoproteinemic (HLP) human subjects in comparison with age-matched controls. Thiobarbituric acid-reactive substances (TBARS), a measure of lipid peroxidation, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), glutathione reductase (GR), and catalase (CAT) were determined in erythrocytes. We also measured lipid parameters including triglycerides (TG), total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), apolipoprotein AI, and apolipoprotein B, and antioxidant related substances such as serum albumin, free iron, ferritin, ceruloplasmin. Thirty-two subjects (females 15, males 17) with type IIb (the mean age 45.6+/-8 [S.E.]), 34 with type IV (females 16, males 18) (the mean age 47+/-10 [S.E.]), and 36 normolipidemic voluntary subjects (females 18, males 18) (the mean age 46+/-8 [S.E.]) were included in the study. Erythrocytes were prepared by classical washing method (0.9% NaCl) from venous blood samples. The mean TBARS levels in plasma and erythrocyte suspensions were found to be significantly higher in both types IIb and IV hyperlipoproteinemics. Erythrocyte SOD and GSH-Px activities were decreased but erythrocyte GR activity did not change in both types IIb and IV hyperlipoproteinemics. Erythrocyte CAT activity was decreased in type IIb, but it was increased in type IV hyperlipoproteinemics. Erythrocyte SOD activity was negatively correlated with plasma TG level, whereas plasma free iron was positively correlated with plasma TBARS level in type IV hyperlipoproteinemics. These results suggest the presence of oxidative injury in patients with type IIb or IV hyperlipoproteinemia, and that the responses of erythrocyte antioxidant enzymes to oxidant stress are different in these conditions.