Paraoxonase 1 low activity and SYNTAX score may predict postoperative complications after coronary artery surgery.

OBJECTIVE: Coronary artery bypass grafting (CABG) seems to present a powerful trigger of oxidative stress (OS) and acute inflammatory response. This study aimed to estimate the effects of off-pump coronary artery bypass (OPCAB) grafting on the OS that is commonly observed in patients undergoing operation under cardiopulmonary bypass (CPB). Additionally, we aimed to examine the relationship between and paraoxonase 1 (PON1) activity and the degree of stenosis, severity and complexity of the atherosclerotic lesions, estimated by SYNTAX score (SS). PATIENTS AND METHODS: Study group of 107 patients scheduled for CABG were divided into CPB and OPCAB group. Blood samples for OS markers measurement were collected at six-time intervals: before skin incision (t1), immediately after surgery (t2), 6h (t3), 24h (t4), 48h (t5) and 96h after cessation of the operation and surgical trauma (t6). SS was calculated. RESULTS: A significant decrease in lipid hydroperoxides (LOOH) and advanced oxidation protein products (AOPP) levels after both types of surgeries were observed, whereas PON1 reduction was observed higher in the CPB than in the OPCAB group. A significant inverse correlation between SS values and PON1 activity, preoperatively and during the early postoperative hours after surgery [in t2, t3 time intervals (p<0.05 for all)] was found. ROC analysis showed that for CPB patients, Model with all OS parameters showed excellent accuracy (AUC=0.957, p<0.001) for prediction postoperative complications. CONCLUSIONS: Decrease in PON1 activity during the early post-operative phases was related to higher SS. This relationship was more convincing in CPB, compared with OPCAB patients. Moreover, integrated models of OS status parameters have the capability to predict the development of postoperative complications.

Pharmacogenomics: current applications and future prospects towards personalized therapeutics.

Personalized Medicine is more than just a metabolic activity of a person. Pharmacogenomics, pharmacogenetics, pharmacoproteomics, and metabolomics play an important role in the development of personalized medicines. Personalized medicine uses information about a person's genes, proteins, enzyme activities, and cellular environment to diagnose and treat disease, cancer included. A major problem of personalized medicine is the fact that there is no portable bedside and low-cost bioanalytical technology that can be used in close proximity to the patient. This technology could play a significant role in defining the dosage setting for subsets of the population. The success of the personalized therapy is possible through the application of technology, which can provide a bridge between metabolism status and an individual's response to a particular drug and therapeutic modality.

Alpha-tocopherol supplementation prevents the exercise-induced reduction of serum paraoxonase 1/arylesterase activities in healthy individuals.

OBJECTIVE: To investigate PON 1/Aryl activities in basketball players with or without alpha-T supplementation pre- and post-training. Vitamin E (alpha-tocopherol, alpha-T) reduces lipid peroxidation. Paraoxonase 1/arylesterase (PON 1/Aryl) activities are closely related to oxidation and atherogenesis. SUBJECT/METHODS: Blood was obtained from 10 players pre- (group A), post-exercise (group B) and after 1 month on alpha-T (200 mg per 24 h orally) supplementation pre- (group C) and post-exercise (group D). Lactate, pyruvate, muscle enzyme activities, creatine kinase, lactate dehydrogenase and total antioxidant status (TAS) were measured with commercial kits. Catecholamines and alpha-T were determined with high-performance liquid chromatography methods and PON 1/Aryl activities spectrophotometrically. RESULTS: Lactate, pyruvate, muscle enzyme activities and catecholamines were increased (P<0.001) in all groups post-training. Alpha-T levels remained unaltered pre- vs post-exercise. TAS was decreased in all the groups post training. PON 1/Aryl activities were significantly decreased post-exercise (group B) (PON1: 65+/-12 U min(-1) ml(-1), Aryl: 58+/-14 KU min(-1) ml(-1)) as compared to those pre-exercise (group A) (PON1: 142+/-16 U min(-1) ml(-1), Aryl: 114+/-12 KU min(-1) ml(-1), P<0.001). In contrast, the studied enzyme activities remained practically unaltered after alpha-T supplementation pre- vs post-training. Both enzyme activities positively correlated to TAS (r=0.60, P<0.001). CONCLUSIONS: Alpha-T supplementation may result in protection of the enzyme PON 1/Aryl activities from free radical production.

Maternal-neonatal retinol and alpha-tocopherol serum concentrations in Greeks and Albanians.

BACKGROUND: Vitamin A and E are required in physiological processes such as pregnancy and growth. AIM: To evaluate retinol and alpha-tocopherol serum levels in Greek and Albanian mothers and in their newborns. METHODS: Data concerned 1125 Greek and 898 Albanian mothers along with their newborns. Immediately after delivery, blood from the umbilical cord and from the mothers was collected into light-protected tubes. Retinol and alpha-tocopherol serum levels were measured with a reversed-phase HPLC method. A 60-d dietetic diary was kept by each woman during the last 2 mo of pregnancy. RESULTS: Retinol (1.3 +/- 0.1 micromol/l) and alpha-tocopherol (32.9 +/- 9.5 micromol/l) levels were estimated to be normal in Greek mothers and in most of their offspring (0.9 +/- 0.1 and 18.5 +/- 3.4 micromol/l, respectively). In contrast, in Albanian mothers, retinol concentration was found to be low (0.6 +/- 0.1 micromol/l), and in 1/3 significantly low (<0.45 micromol/l). Consequently, the vitamin was evaluated to be very low in their newborns (0.4 +/- 0.1 micromol/l), and in 1/2 extremely low. However, in 12% of the Albanian cord blood samples, retinol level was determined to be higher as compared with that of their mothers. alpha-Tocopherol was evaluated to be normal in most of the immigrant mothers (20.0 +/- 8.8 micromol/l) and low (<7.5 micromol/l) in 15% of their newborns. Vitamin A intake was found to be extremely low and vitamin E low (p < 0.05) in the Albanians. CONCLUSIONS: (a) The decreased vitamin A and vitamin E intake, and their low blood status in the Albanian mothers and in their newborns, could be due to their low socio-economic and nutritional status. (b) Immigrant Albanians, during their pregnancy, and their newborns should be "followed up", being at risk of developing symptoms from the very low levels of these lipid-soluble vitamins.

Maternal--neonatal serum selenium and copper levels in Greeks and Albanians.

AIM: To evaluate selenium (Se) and copper (Cu) concentrations in Greek and Albanian immigrant mothers and in the cord blood of their newborns. SUBJECTS AND METHODS: From 1118 Greek and 820 Albanian mothers and from the cord blood of their neonates blood was obtained for Se and Cu measurement. Se and Cu concentrations were determined in sera with graphite furnace atomic absorption spectroscopy (GFAAAS) and atomic absorption spectrometry, respectively. In all, 30 days' nutrient intakes were evaluated in both groups. RESULTS: Animal protein, Se and Cu intakes were poor in the Albanians vs the Greeks (P < 0.001). Se concentrations in the Greek mothers (68.3 +/- 8.5 microg/l) and in their newborns (37.02 +/- 8.9 microg/l) were found higher as compared with those in Albanian mothers (37.4 +/- 9.9 microg/l) and in their newborns (34.3 +/- 9.1 microg/l) (P < 0.001). Cu levels were also found higher (P < 0.001) in the Greek mothers (1687 +/- 353 microg/l) and in their neonates (449 +/- 87 microg/l) compared with those in the Albanian mothers (959 +/- 318 microg/l) and in their newborns (229 +/- 67 microg/l). Additionally, 31.5% of neonates born to Albanian women with Se concentrations less than 28 microg/l had higher Se levels (P < 0.01) than their mothers. CONCLUSIONS: The low Se and Cu levels evaluated in the Albanian mothers and their newborns could be related to their poor animal protein intake which could be the consequence of their low socioeconomic status. As an effective preventive measure, accurate dietetic strategies to assess the requirements of pregnant immigrant women for trace elements may be planned in Greece.

Effect of diet on plasma total antioxidant status in phenylketonuric patients.

BACKGROUND: Phenylketonuria (PKU), an inborn error of phenylalanine (Phe) metabolism, is treated with a low Phe lifelong diet, which is a vegetarian and contains many antioxidants. AIM: The aim of this study was to evaluate the effect of diet on plasma total antioxidant status in our PKU patients. METHODS, RESULTS: Twenty-two PKU patients on strict diet (group A), 24 PKU patients who did not accurately follow their dietary control (group B) and 40 healthy children (controls) of comparable age took part in this study. Nutrients, as well as blood levels of lipids, vitamin C, beta-carotene and alpha-tocopherol were evaluated in all groups. Vitamin C intake and its blood levels did not differ between the groups. However, the intake of beta-carotene, alpha-tocopherol (2211+/-116, 14+/-1.0 mg/24 h) and their blood levels (0.7+/-0.09, 34+/-0.9 micro mol/l) in group A were statistically significantly higher (P<0.001) as compared with those of group B (1352+/-118, 10+/-1.0 mg/24 h and 0.49+/-0.08, 22+/-0.6 micromol/l) and controls (1290+/-120, 9.0+/-0.9 mg/24 h and 0.40+/-0.09, 24+/-1.6 micromol/l). Lipid intakes and their blood levels were lower in patients on the strict diet. Plasma total antioxidant status was higher in the same group of patients (group A). Additionally, positive correlations were found between the antioxidant vitamin blood levels and the plasma total antioxidant status in the groups, especially in the group A. PKU patients of group A showed significantly higher antioxidant status (1.6+/-0.2 mmol/l) as compared with those of group B (1.0+/-0.19 mmol/l; P<0.001) and controls (1.01+/-0.2 mmol/l). CONCLUSIONS: The high plasma antioxidant status in patients with PKU, especially in those with a good compliance with their diet, is possibly due to the amounts of antioxidants which are present in their special low Phe vegetarian diet.

Homocysteine and other vascular risk factors in patients with phenylketonuria on a diet.

UNLABELLED: The aim of this study was to investigate the known risk factors, such as lipids, homocysteine and endothelin, for the development of coronary artery disease (CAD) in phenylketonuria (PKU) patients, depending on their diet. The PKU patients (n = 74) were divided into two groups. Group A (n = 34; mean age 6.78 +/- 1.5 y) adhered strictly to a diet and group B (n = 40; mean age 8.0 +/- 3.2 y) did not comply with the diet. The control group comprised 50 healthy non-PKU children. All groups were evaluated for blood levels of homocysteine and vitamin B6 by high-performance liquid chromatography, vitamin B12 and folate in serum by a radioassay, lipids by a routine method, and lipoprotein(a) and endothelin-1 with an immunoassay. Homocysteine levels (28.65 +/- 3.3 micromol l(-1)) were increased in group A compared with group B (6.86 +/- 1.6 micromol l(-1)) and the controls (6.9 +/- 2.0 micromol l(-1)) (p < 0.001). Vitamin B6 (10.7 +/- 10.9 nmol l(-1)), vitamin B12 (98.5 +/- 22.3 pmol l(-1)), folate (2.35 +/- 1.3 nmol l(-1)) and lipids were decreased in group A. The other vascular risk factors, which were not dependent on diet [lipoprotein(a) and endothelin-1], did not differ among the three groups. CONCLUSION: PKU patients on a strict diet had low vitamin B6, vitamin B12 and folate levels resulting in moderate hyperhomocysteinaemia. The evaluation of these vitamins at short intervals and their supplementation could be an early measure in the prevention of CAD.

Low serum biotinidase activity in children with valproic acid monotherapy.

PURPOSE: Valproic acid (VPA) is an effective antiepileptic drug (AED), which is associated with dose-related adverse reactions such as skin rash, hair loss (alopecia), etc. Profound as well as partial biotinidase deficiency causes dermatologic manifestations similar these. Therefore, it was of interest to evaluate serum biotinidase activity in patients receiving VPA monotherapy. METHODS: Seventy-five patients with seizures, mean age, 8.6 years (+/-1.9 years) were divided into three groups. Group A (n = 25) was treated with VPA 28.7 +/- 8.5 mg/kg/24 h, group B (n = 25) with 41.6 +/- 4.9 mg/kg/24 h, and group C with 54.5 +/- 5.8 mg/kg/24 h. Their "trough" VPA serum levels were 40.9 +/- 13.2, 86.25 +/- 11.5, and 137 +/- 14.5 microg/ml, respectively. Fifty healthy children were the controls. Patients and controls underwent clinical and laboratory evaluations including liver function data, complete blood counts, NH3, and so on, after 45 days of VPA treatment. Biotinidase serum levels were evaluated fluorometrically. RESULTS: Liver function data were found elevated in the groups B and C. On the contrary, biotinidase activity was significantly statistically lowered (p < 0.001) in groups B and C (1.22 +/- 1.11, 0.97 +/- 0.07 mmol/min/L respectively), as compared with controls (5.20 +/- 0.90 mmol/min/L). Strong inverse correlations were observed between liver enzymes and VPA blood levels with the activity of the enzyme. Additionally, no inhibitory effect on biotinidase activity was found, when the enzyme was incubated in vitro with high (1.2 mM) concentrations of the drug. Skin lesions (seborrheic rash, alopecia) were improved in our patients after biotin (10 mg/day) supplementation. CONCLUSIONS: It is suggested that VPA impairs the liver mitochondrial function, resulting in a low biotinidase activity and or biotin deficiency. Biotin supplementation could restore some of the side effects of the drug.

Evaluation of serum lipoprotein(a) levels in Greek schoolchildren.

UNLABELLED: This study aimed to provide associations of age and gender with serum lipoprotein(a) [Lp(a)] levels and percentile distribution data for Greek children. In total, 3298 children (1590M, 1708F, aged 6-14 y) participated in the study. Lp(a) levels were evaluated with an immunosorbent assay. Mean Lp(a) levels were 153-157 mg l(-1) for boys and 146-151 mg l(-1) for girls, and median levels 133-139 mg l(-1) for boys and 100-108 mg l(-1) for girls. CONCLUSION: The Lp(a) levels in these children were the lower ever reported. These results suggest that the young Greek population is not at high risk of developing coronary heart disease as a result of high Lp(a) levels.

Elevated plasma homocysteine levels in patients on isotretinoin therapy for cystic acne.

BACKGROUND: The use of Isotretinoin (Iso) for cystic acne (CA) therapy includes marked side-effects such as dyslipidemia, increased liver enzymes, and reduction of biotinidase activity. Moreover, Homocysteine (Hcy), an amino acid, is metabolized in the liver requiring folate, vitamin B6, vitamin B12, and the activity of enzymes, i.e. cystathionine-beta-synthase. Increased blood levels of Hcy are associated with premature occlusive vascular disease. OBJECTIVE: The aim of this study was the evaluation of Hcy levels and the responsible vitamins for its metabolism in patients with CA on Iso treatment. METHODS AND RESULTS: Twenty-eight patients with CA were submitted to laboratory examinations before (Value 1) and after (Value 2) 45 days on Iso (0.5 mg/kg/24 h) therapy. Blood levels of Hcy and vitamin B6 were evaluated by HPLC methods, and folate and vitamin B12 using a commercial Kit. Hcy levels (Value 1 = 7.86 +/- 1.6 micromol/L; Value 2 = 13.65 +/- 3.3 micromol/L; P < 0.001) were statistically significantly increased in patients on treatment. Vitamins were unaltered, and lipids and liver enzymes increased. Significant correlation between Hcy levels, vitamins, and liver enzymes was found. Methionine loading tests performed in nine patient-volunteers showed an abnormal response post-treatment. CONCLUSIONS: It is suggested that the elevated Hcy levels in patients after 45 days on Iso therapy could be due either to the 'inhibition' of cystathionine-beta-synthase by the drug and/or their liver dysfunction. Daily vitamin supplementation along with frequent evaluations of Hcy blood levels are recommended for the prevention of a premature occlusive vascular disease.

The effect of isotretinoin on biotinidase activity.

BACKGROUND: Among the reaction and effects of isotretinoin, mucocutaneous reactions, xerosis and erythema of the skin as well as elevation of liver enzymes and lipids except high density lipoprotein have been reported. OBJECTIVE: Since biotinidase is mainly produced in the liver and partial biotinidase deficiency causes dermatological manifestations, seborrheic dermatitis, alopecia etc., isotretinoin side effects in relation to biotinidase activity were studied. METHODS: Forty-two (n = 42) patients with severe cystic acne had liver function tests, lipid estimations, serum biotin as well as biotinidase activity evaluations before (value 1) and on the 30th day (value 2) of treatment with isotretinoin monotherapy (Roaccutane 0.5 mg/kg/24 h). The same laboratory tests were evaluated in 50 controls only once. Moreover, the effect of isotretinoin on a known plasma biotinidase activity was evaluated after incubation in vitro with various concentrations of the drug. RESULTS: A statistically significant elevation of liver enzymes and lipids, except high density lipoprotein, was observed at the end of this study. On the contrary, biotinidase activity was found to be significantly decreased as compared to the initial values (value 1 = 4.70 +/- 0.89 nmol/min/l, value 2 = 2.50 +/- 0.8 nmol/min/l, p < 0.001) and to controls (5.2 +/- 0.9 nmol/min/l vs. value 2 = 2.50 +/- 0.8 nmol/min/l, p < 0.001). Additionally, biotin levels showed no significant alterations and the in vitro incubation of the enzyme with various concentrations of the drug exhibited no effect on its activity. CONCLUSION: It is suggested that isotretinoin isomers-metabolites act in the liver, resulting in low biotinidase activity.

In vitro influence of phenylalanine on acetylcholinesterase activity and DNA.

Acetylcholinesterase (AChE) is a significant component of the membrane contributing to the permeability changes during synaptic transmission and conduction. Phenylketonuria is a group of metabolic disorders in which phenylalanine (Phe) is highly elevated in blood (up to 0.1 M) resulting in mental retardation etc. AChE activity was measured spectrophotometrically after incubation with various Phe concentrations. Phe interaction with DNA was evaluated with an established HPLC method. Phe was found to inhibit AChE almost 40%, at a concentration of 5 mM, whereas a 62.5% DNA peak exclusion (molecular interaction) was observed when Phe was incubated with DNA at a concentration of 3 mM. In addition the ratio of DNA: Phe determined the potency of the observed molecular effect.

Serum cholesterol and triglyceride distribution in 7767 school-aged Greek children.

OBJECTIVE: To elucidate associations of age and sex with serum cholesterol and triglyceride levels and to provide for the first time percentile distribution data for pediatric lipids. PARTICIPANTS AND METHODS: A high sample of 7767 (3980 boys, 3787 girls) fasting schoolchildren, 6 to 14 years of age, were studied in Athens, Greece. RESULTS: The mean cholesterol ranged from 157 to 174 mg/dL for boys and from 158 to 172 mg/dL for girls peaking at 9 years of age for both sexes. Triglyceride levels also tended to increase gradually and to peak at 11 years of age for both sexes. The high-density lipoprotein cholesterol levels were highest at 9 years of age for both sexes and the low-density lipoprotein cholesterol levels also tended to peak at 9 years of age for boys and at 8 years of age for girls. Atherogenic indices ranged from 1.54 to 1.68 for boys and 1. 51 to 1.85 for girls. CONCLUSION: According to these findings, it could be suggested that diet changes in the Greek population, especially in children and adolescents, living in big cities is significantly influencing their total cholesterol profiles throughout the last 10 years.

Pharmacological and phytochemical studies of Cephäelis axillaris.

The most significant effect, observed in the preliminary pharmacological evaluation of the whole ethanol extract and the alkaloidal fraction of Cephäelis axillaris, was the hyperemia of ears and external mucosas which was most probably due to an alpha-adrenergic blocking activity. In addition, both samples also induced a marked hypotension in normotensive as well as hypertensive (SHR) rats and inhibited the increases of blood pressure induced by i.v. administration of noradrenaline in pithed rats. The structures of the major alkaloidal components of the extract were elucidated on the basis of chemical characterization assays and IR, UV, 1H and 13C one and two-dimensional NMR analyses.

Constituents of the Stems of Arbutus unedo.

The dried stems of ARBUTUS UNEDO have been investigated for secondary metabolites. In addition to the previously reported lupeol, ursolic acid, monotropein, unedoside, and stilbericoside, the iridoids geniposide ( 2) and monotropein methyl ester ( 1) have been isolated for the first time from this source. Betulinic acid ( 4) has also been isolated for the first time from this plant.