George A. Karikas

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, β-carotene and α-tocopherol were evaluated in all groups. Vitamin C intake and its blood levels did not differ between the groups. However, the intake of β-carotene, α-tocopherol (2211±116, 14±1.0 mg/24 h) and their blood levels (0.7±0.09, 34±0.9 µmol/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 µmol/l) and controls (1290±120, 9.0±0.9 mg/24 h and 0.40±0.09, 24±1.6 µmol/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.

Low Serum Biotinidase Activity in Children with Valproic Acid Monotherapy

Summary:  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.

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

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 μmol 1‐1) were increased in group A compared with group B (6.86 ± 1.6 μmol 1‐1) and the controls (6.9 ± 2.0 μmol 1‐1) (p > 0.001). Vitamin B6 (10.7 ± 10.9 nmol 1‐1), vitamin B12 (98.5 ± 22.3 pmol 1‐1), folate (2.35 ± 1.3 nmol 1‐1) 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.

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

Abstract

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.

Serum homocysteine levels and paraoxonase 1 activity in preschool aged children in Greece

Abstract Background: Over the past decade, it has been well established that elevated total serum homocysteine (tHcy) in adults is associated with increased risk of cardiovascular and thromboembolic diseases. Since risk factors for such diseases are established at a young age, the aim of the present study was to measure serum tHcy levels in 134 (71 boys, 63 girls) randomly selected healthy preschool children aged 4–6years (mean 5.1), and to investigate possible correlation with paraoxonase 1 (PON1) activity, an antioxidant enzyme that contributes to the antiatherogenic properties of high-density lipoprotein (HDL). Methods: tHcy was determined using an IMX tHcy assay (FPIA). PON1 was measured by a spectrophotometric method at 412nm. Results: Mean serum tHcy was 7.71±2.35μmol/L. A relatively significant percentage (15.6%) of boys and girls had elevated serum tHcy levels (>10μmol/L). tHcy levels were slightly higher in girls compared to boys (8.20±2.80 vs. 7.29±1.79μmol/L, respectively; p<0.11). There was no significant interaction between age and tHcy levels. Mean PON1 activity was 124.86±66.62U/L. No statistical difference in enzyme activity was observed between boys and girls (126.81±69.99 vs. 121.74±64.78U/L) was observed. On the contrary, a weak negative relationship between tHcy concentration and PON1 activity was detected, with Pearsons correlation coefficient of r=−0.27. Conclusions: The significant percentage of elevated tHcy levels observed in healthy preschool cases and the negative tHcy correlation with PON1 activity are reported for the first time. Since children with a family history of cardiovascular disease have higher levels of serum Hcy, tHcy screening in children, even of this age, in relation to other parameters, such the protective PON1, might prove a useful prevention procedure for the genetic risk of premature atherosclerosis.

Early effects of sodium valproate monotherapy on serum paraoxonase/arylesterase activities

Objective. Valproic acid (VPA) treatment and paraoxonase1/arylesterase (PON1/Aryl) activities are related to the production of free radicals. Our aim was to study the PON1/Aryl activities in children on VPA therapy. Material and methods. Thirty‐two children with seizures and 30 healthy child volunteers took part. Ill children underwent the common laboratory tests, as well as total antioxidant status (TAS), total oxidant status (TOS), lipid profile, liver enzymes and PON1/Aryl activities pre‐ and post‐60 days on VPA therapy (30 mg/kg/24 h), whereas the healthy children were tested just once. Results. None of the studied biochemical parameters differed between volunteers and children with seizures pretreatment. Liver enzymes, lipids and TOS levels (124±30 versus 580±40 µmol/L; p<0.001) were significantly elevated, whereas the activities of PON1/Aryl (146±43 versus 118±40 U/mL/min 120±42 versus 98±38 KU/mL/min; p<0.01) and TAS levels (436±42 versus 288±39 µmol/L; p<0.001) were decreased in children after treatment. Additionally, strong negative correlations were found between PON1/Aryl activities, liver enzymes, TOS (r = −0.69) and VPA levels (r = −0.57), whereas PON1/Aryl activities correlated positively with TAS, HDL and Apo A‐I in all groups. Conclusions. Serum PON1/Aryl activities were decreased after 60 days on VPA treatment, probably due to liver dysfunction and free radicals production by VPA, without excluding the possibility of a direct action of the drug on the enzymes.

The effect of the mode of delivery on maternal-neonatal interleukin-6, biogenic amine and their precursor amino acid concentrations.

Abstract Background: Biogenic amine, adrenaline, noradrenaline, dopamine and 5-hydroxy-tryptamine (5-HT) levels are related to interleukin-6 (IL-6) plasma concentrations and endurance exercise. The aim of our study was to investigate the effect of the mode of delivery on maternal-neonatal IL-6, biogenic amine and their precursor amino acid levels. Methods: Some women with normal pregnancy (n=56) were divided into two groups: group A (n=26) with normal labor and vaginal delivery, and group B (n=30) with scheduled cesarean section. Blood was obtained from the mothers at the beginning of labor and immediately after delivery (pre- vs. post-delivery), as well as from the umbilical cord (CB). Total antioxidant status (TAS) and IL-6 levels were measured with commercial kits, the precursor amino acids, tyrosine and tryptophan with tandem mass spectrometry and the biogenic amine blood levels with HPLC methods, respectively. Results: TAS, IL-6, biogenic amine and their precursor amino acid blood levels were similar in the two groups of mothers pre-delivery. TAS levels were reduced, whereas the amino acids, the catecholamine, 5-HT and IL-6 levels were increased post-delivery and in the CB of group A and unaltered in group B at the same time of the study. Conclusions: During a vaginal delivery process, the low TAS, the increased levels of the studied amino acids, the catecholamines, 5-HT and IL-6 may be due to the activation of the neuroendocrine system and the participation of skeletal and uterine muscles. The mode of delivery may be taken into account when IL-6 plasma levels are evaluated as an anti-inflammatory index perinatally. Clin Chem Lab Med 2008;46:1624–30.

The effect of nutritional habits on maternal- neonatal lipid and lipoprotein serum levels in three different ethnic groups

Aim: To investigate the effect of nutritional habits on lipid profiles in mothers of three different ethnic groups and in their newborns. Subjects and Methods: Lipids and lipoproteins were determined in 7-day dietetic diaries of 9,134 mothers (Greeks n = 3,118, Albanians n = 3,050, Muslim Asians n = 2,966), in their sera and in the cord blood of their newborns with routine methods. Results: Monounsaturated fat intake (35 ± 12 g/day) was similar among the groups. Total fat, saturated fat and cholesterol intakes were significantly lower in Asians than those in Albanians and Greeks. Significantly lower lipid and lipoprotein concentrations (cholesterol 5.09 ± 0.85 mmol/l, triglyceride, TG, 2.38 ± 0.58 mmol/l, low-density lipoprotein cholesterol, LDL-C, 2.90 ± 0.78 mmol/l, very-low-density lipoprotein cholesterol, VLDL-C, 0.32 ± 0.11 mmol/l) were measured in the Muslim Asian mothers and in their newborns (cholesterol 1.06 ± 0.26 mmol/l, TG 0.52 ± 0.16 mmol/l, LDL-C 0.49 ± 0.10 mmol/l and VLDL-C 0.10 ± 0.02 mmol/l; p < 0.001). Higher levels of the mentioned biochemical parameters were found in Greek mothers versus their newborns (cholesterol 5.20 ± 0.98 mmol/l, TG 2.37 ± 0.62 mmol/l, LDL-C 3.40 ± 0.85 mmol/l and VLDL-C 0.48 ± 0.13 mmol/l vs. cholesterol 1.55 ± 0.31 mmol/l, TG 0.56 ± 0.20 mmol/l, LDL-C 0.65 ± 0.15 mmol/l and VLDL-C 0.12 ± 0.01 mmol/l; p < 0.001) and Albanian mothers versus their newborns (cholesterol 7.1 ± 0.78 mmol/l, TG 2.55 ± 0.60 mmol/l, LDL-C 4.1 ± 0.88 mmol/l and VLDL-C 0.52 ± 0.13 mmol/l vs. cholesterol 1.6 ± 0.40 mmol/l, TG 0.59 ± 0.15 mmol/l, LDL-C 0.70 ± 0.21 mmol/l and VLDL-C 0.12 ± 0.01 mmol/l; p < 0.001). The highest HDL-C levels were observed in the Asian mothers (1.60 ± 0.31 mmol/l vs. 1.4 ± 0.39 mmol/l in Greeks and 1.31 ± 0.39 mmol/l in Albanians; p < 0.001). Conclusion: The normal lipid profile in Greeks, the high one in Albanians and the low profile in Muslim Asians may be due to their nutritional habits and their socioeconomic status affecting those of their newborns.

Evaluation of serum lipoprotein(a) levels in Greek schoolchildren

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 l1 for boys and 100–108 mg l‐1 for girls.