Persistent coagulopathy during Escherichia coli sepsis in a previously healthy infant revealed undiagnosed tyrosinaemia type 1.

Hereditary tyrosinaemia type 1 (HT1) is caused by an enzymatic defect in tyrosine metabolism. It is an autosomal recessive disorder and affects both sexes equally. In young infants HT1 can present as severe liver involvement and in older infants as liver failure and renal tubular dysfunction together with growth failure and rickets. The authors report the case of a 5-month-old, previously healthy, male infant who presented with Escherichia coli sepsis and severe coagulopathy due to liver dysfunction. Despite the early diagnosis of HT1 and treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1, 3-cyclohexanedione (NTBC), the patient died from severe coagulopathy and multi-organ failure.

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.

Effect of L-carnitine administration on the modulated rat brain protein concentration, acetylcholinesterase, Na+K+-ATPase and Mg2+-ATPase activities induced by forced swimming.

BACKGROUND: Forced exercise produces free radicals and L-carnitine (L-C) administration reduces oxidative stress. AIM: To investigate whether short (2 hours) or prolonged (3 hours) forced swimming could modulate total antioxidant status (TAS), protein concentration and activities of acetylcholinesterase (AChE), Na(+)K(+)-ATPase and Mg(2+)-ATPase in rat brain following intraperitonal administration of L-C (300 mg/kg). METHODS: TAS, protein and enzyme activities were measured spectrophotometrically. RESULTS: TAS, protein concentration and AChE activity were reduced, whereas Na(+)K(+)-ATPase and Mg(2+)-ATPase were significantly increased after either 2 or 3 hours of training. L-C administration resulted in a profound restoration of TAS and protein concentration whereas AChE and Na(+)K(+)-ATPase were increased before exercise, followed by AChE restoration and Na(+)K(+)-ATPase reduction after exercise. Mg(2+)-ATPase remained unchanged. An in vitro study using L-C incubation of brain homogenates previously treated with L-C resulted in complete restoration of the modulated enzymes, whereas the enzyme activities from untreated animals remained unaltered. CONCLUSIONS: Short or prolonged swimming in rats may result in a reduction of brain TAS, protein concentration and AChE activity, and an activation of Na(+)K(+)-ATPase and Mg(2+)-ATPase. L-C administration may prevent reduction in TAS and protein concentration, and a decrease in AChE and Na(+)K(+)-ATPase activity; the latter reached pre-exercise values after L-C incubation.

Dramatic reduction of erythrocyte glucose-6-phosphate dehydrogenase activity in athletes participating in the ultradistance foot race "Spartathlon".

OBJECTIVE: To investigate the effect of a long-distance endurance exercise "Spartathlon" on erythrocyte glucose-6-phosphate dehydrogenase (G(6)PD) activity. MATERIAL AND METHODS: The study comprised 15 male runners, median age 36.5 years. Blood samples were obtained in the 15 min before the race and again within 15 min after the end of the race. Erythrocyte glutathione (GSH and GSSG) and plasma malonyldialdehyde were measured with HPLC methods, and total antioxidant capacity (TAC), total hyperoxides and G(6)PD activity with commercial kits. Lipids, uric acid and total bilirubin were determined with a clinical chemistry analyser. RESULTS: Total hyperoxides were found statistically reduced, whereas total bilirubin was measured elevated post-race. Interestingly, GSSG levels were found increased (167.3+/-12.0 versus 219.5+/-20.3 micromol/L; p<0.005) as well as GSSG/GSH ratio (16.0+/-1.3 versus 20.60+/-1.65; p<0.05) post-race. In contrast, G(6)PD activity was found remarkably decreased (8.72+/-3.10 versus 3.8+/-2.5 U/g Hb; p<0.0001) pre versus post the event. CONCLUSION: Red blood cell G(6)PD activity in athletes may be reduced post-race as a consequence of the modulation of NADP/NADPH levels and elevation of the erythrocyte GSSG, and especially GSSG/GSH ratio, resulting in an impairment of the hexose monophosphate shunt.

The effect of basketball training on the players' erythrocyte membrane acetylcholinesterase, (Na+,K+)-ATPase and Mg2+-ATPase activities.

The aim of this study was to investigate whether the activities of erythrocyte membrane acetylcholinesterase (AChE), (Na (+),K (+))-ATPase and Mg (2+)-ATPase are modulated by a basketball training. Blood was obtained from 10 basketball players pre- and postexercise. Total antioxidant status (TAS), lactate and pyruvate concentrations were determined with kits, while the enzyme activities were determined spectrophotometrically. Post-training blood lactate and pyruvate concentrations as well as AChE (2.90 +/- 0.05 vs. 3.98 +/- 0.09 Delta OD/min . mg protein, p < 0.01) and Na (+),K (+)-ATPase (0.58 +/- 0.04 vs. 1.27 +/- 0.12 micromol Pi/h . mg protein, p < 0.001) activities were remarkably increased, whereas TAS was significantly decreased. Mg (2+)-ATPase activity remained unaltered at the end of the training. In conclusion, the stimulation of AChE and Na (+),K (+)-ATPase by the training may be due to the rise of blood catecholamine oxidation contributing to TAS decrease and/or the increase of serotonin levels. This stress condition may modulate cholinergic and catecholaminergic/serotoninergic functions in players.

Serum paraoxonase/arylesterase activities in phenylketonuric patients on diet.

AIM: To compare serum paraoxonase/arylesterase (PON-aryl) activities in phenylketonuric (PKU) patients with high and low phenylalanine (Phe) blood concentration. PATIENTS AND METHODS: Seventeen poorly controlled PKU children (off diet) underwent clinical and laboratory examinations before and after 30 days adhering to their special diet (on diet), whereas controls (N=24) were examined once. Lipid, lipoprotein levels and paraoxonase (PON 1) activities were measured with the Bayer Advia 1650 Clinical Chemistry System. Apolipoprotein AI (Apo AI) levels were determined by the Dade Behring BN ProSpec nephelometer, whereas total antioxidant capacity (TAC), PON-aryl and Phe levels were measured spectrophotometrically. RESULTS: Phe significantly differed among the groups. Lipids and lipoproteins, except high-density-lipoprotein-cholesterol (HDL-C) and Apo AI, were higher when off diet than those on diet. HDL-C and Apo AI were similar in patients and controls. TAC (0.99+/-0.19 mmol/l) was significantly lower when the patients were off diet than when they adhered to diet and controls (1.71+/-0.20 and 1.81+/-0.20 mmol/l P<0.001 respectively). PON 1 and PON-aryl activities (68+/-2 U/min/ml, 88+/-26 KU (min/ml) in children with high Phe were reduced as compared with those with low blood Phe levels (152+/-41 U/min/ml, 107+/-23 KU/min/ml P<0.001) and controls (146+/-43 U/min/ml, 109+/-41 KU/min/ml P<0.001). The enzyme activities positively correlated with HDL-C and Apo AI when PKU patients were on diet and controls as well as with TAC in all the groups, whereas negatively correlated with Phe levels. CONCLUSIONS: PON-aryl activities are strongly related to the dietary control of PKU patients.

Effects of mode of delivery on maternal-neonatal plasma antioxidant status and on protein S100B serum concentrations.

OBJECTIVE: To investigate the effect of the mode of labour and delivery on total antioxidant status (TAS) and on the protein S100B serum concentrations in mothers and their newborns. MATERIAL AND METHODS: Sixty women with normal pregnancies were divided into three groups: Group A (n = 20) with normal labour and vaginal delivery (VG), group B (n = 18) with prolonged labour+VG and group C (n = 22) with scheduled caesarean section (CS). Blood was obtained at the beginning of the labour process and immediately after delivery (pre- and post-delivery) as well as from the umbilical cord (CB). TAS and creatine kinase (CK) were measured using commercial kits. Serum S100B levels were evaluated with the electrochemiluminescence immunoassay "ECLIA" on the ROCHE ELECSYS 2010 immunoassay analyser. RESULTS: Post-delivery, TAS levels were significantly decreased in group A and especially in group B. S100B levels were increased in group B (0.0712+/-0.02 microg/L) as compared with those of group A (0.0567+/-0.03 microg/L, p<0.01) and group C (0.038+/-0.03 microg/L, p<0.01), the levels in group C remaining practically unaltered (pre- versus post-delivery). In the newborns, S100B levels were almost 2-fold higher in group B (0.67+/-0.18 microg/L) than those in group A (0.40+/-0.05 microg/L p<0.001) and group C (0.31+/-0.04 microg/L p<0.001). A negative correlation was found between TAS and S100B protein (r = -0.61, p<0.001), the latter positively correlated to CK (r = 0.48, p<0.01). CONCLUSIONS: The increased S100B serum levels in the mothers of group B, post-delivery, may have been due to the long-lasting, oxidative and/or psychogenic stress. The observed remarkably high levels of S100B in the group B newborns may have been due to compressive conditions on the foetus brain during this mode of delivery.

The effect of L-cysteine and glutathione on inhibition of Na+, K+-ATPase activity by aspartame metabolites in human erythrocyte membrane.

BACKGROUND: Reports have implicated Aspartame (N-L-a-aspartyl-L-phenylalanine methyl ester, ASP) in neurological problems. AIM: To evaluate Na(+), K(+)-ATPase activities in human erythrocyte membranes after incubation with the ASP metabolites, phenylalanine (Phe), methanol (MeOH) and aspartic acid (Asp). METHODS: Erythrocyte membranes were obtained from 12 healthy individuals and were incubated at 37 degrees C for 1 h with the sum or each of the ASP metabolites separately, which are commonly measured in blood after ASP ingestion. Na(+), K(+)-ATPase and Mg(2+)-ATPase activities were measured spectrophotometrically. RESULTS: Membrane Mg(2+)-ATPase activity was not altered. The sum of ASP metabolite concentrations corresponding to 34, 150 or 200 mg/kg of the sweetener ingestion resulted in an inhibition of the membrane Na(+), K(+)-ATPase by -30, -40, -48%, respectively. MeOH concentrations of 0.14, 0.60 or 0.80 mM decreased the enzyme activity by -25, -38, -43%, respectively. Asp concentrations of 2.80, 7.60 or 10.0 mM inhibited membrane Na(+), K(+)-ATPase by -26, -40, -46%, respectively. Phe concentrations of 0.14, 0.35 or 0.50 mM reduced the enzyme activity by -24, -44, -48%, respectively. Preincubation with L-cysteine or reduced glutathione (GSH) completely or partially restored the inhibited membrane Na(+), K(+)-ATPase activity by high or toxic ASP metabolite concentrations. CONCLUSIONS: Low concentrations of ASP metabolites had no effect on Na(+), K(+)-ATPase activity. High or abuse concentrations of ASP hydrolysis products significantly decreased the membrane enzyme activity, which was completely or partially prevented by L-cysteine or reduced GSH.

The effect of MTHFR(C677T) genotype on plasma homocysteine concentrations in healthy children is influenced by gender.

OBJECTIVE: To explore the influence of gender, together with folate status, on the relation between the common methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma total homocysteine (tHcy) concentrations in healthy children. DESIGN: Cross-sectional study by face-to-face interview. SETTING AND SUBJECTS: A total of 186 sixth-grade students participated from twelve randomly selected primary schools in Volos, Greece. METHODS: Fasting tHcy, folate, and vitamin B(12) were measured in plasma. The MTHFR genotypes were determined. Anthropometric and dietary intake data by 24-h recall were collected. RESULTS: Geometric means for plasma tHcy, plasma folate and energy-adjusted dietary folate did not differ between females and males. The homozygous mutant TT genotype was associated with higher tHcy only in children with lower plasma folate concentrations (<19.9 nmol/l, P = 0.012). As a significant gender interaction was observed (P = 0.050), we stratified the lower plasma folate group by gender and found that the association between the genotype and tHcy was restricted to males (P = 0.026). Similar results were obtained when folate status was based on estimated dietary folate. Specifically, only TT males that reported lower dietary folate consumption (<37 microg/MJ/day) had tHcy that was significantly higher than tHcy levels of C-allele carriers (P = 0.001). CONCLUSIONS: Under conditions of lower folate status (as estimated by either plasma concentration or reported dietary consumption), gender modifies the association of the MTHFR(C677T) polymorphism with tHcy concentrations in healthy children. SPONSORSHIP: Kellog Europe.

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 folate and vitamin B12 serum concentrations in Greeks and in Albanian immigrants.

BACKGROUND: Low folate and vitamin B(12) concentrations during pregnancy are implicated with neural tube defects (NTD) and neurological manifestations in the neonates. AIM: To compare serum concentrations of folate and vitamin B(12) in 1025 Greek mothers, 908 immigrant Albanian mothers at delivery and in the cord blood of their neonates. METHODS: A 30 days food diary was kept from each mother. Folate and vitamin B(12) sera concentrations were measured with Bayer ADVIA Centaur System. RESULTS: Energy, carbohydrates and total fat intake were significantly higher in Albanian mothers when compared with those of Greek origin. On the contrary, total protein, and especially animal protein intake were higher in the Greek mothers. Folate intake was similar between the two ethnic groups whereas vitamin B(12) intake in Albanians was evaluated lower (1.8 +/- 0.13 microg day(-1)) when compared with that of Greeks (2.8 +/- 0.12 microg day(-1); P < 0.001). Folate serum concentrations in mothers and newborns were similar (17.7 +/- 9.1 and 26.5 +/- 15.2 nm versus 18.1 +/- 8.6 and 24.6 +/- 14.7 nm, respectively P > 0.05) in the two ethnic groups. In contrast, vitamin B(12) serum concentration was significantly lower (135.0 +/- 19.6 pm) in the Albanian mothers compared with that of Greeks (164.5 +/- 17.7 pm, P < 0.0001). Consequently, the vitamin concentrations was found lower in the newborns of Albanian origin (133.6 +/- 11.8 pm) compared with that of Greek neonates (213.3 +/- 11.4 pm, P < 0.0001). CONCLUSIONS: (a) Folate serum concentrations in Greek and Albanian mothers and in their neonates were similar, (b) vitamin B(12) serum concentrations, evaluated for first time in these ethnic groups, were significantly low in Albanians, both in mothers and newborns, (c) the low protein and especially the reduced animal protein intake from the Albanian mothers, possibly due to their low socio-economic status, may be responsible for their decreased vitamin B(12) serum concentrations and (d) vitamin B(12) supplementation along with an increase of animal protein intake might improve the vitamin serum status in the Albanians.

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.

Sanfilippo B syndrome: molecular defects in Greek patients.

Sanfilippo syndrome type B [mucopolysaccharidosis IIIB (MPS IIIB] is the most prevalent type of MPS III in Greece, accounting for 81% of all MPS III cases diagnosed at the Institute of Child Health (Athens) over the last 20 years. The majority of the patients originated from East Central/Central Greece, Thessaly, and Macedonia. We present the results of mutation analysis in 21 Greek patients from 18 different families, all of whom had the severe form of the disorder. Patients were initially screened for five previously known mutations by restriction enzyme digestion of polymerase chain reaction products. Unknown mutations were identified by single-strand conformation polymorphism analysis and DNA sequencing and were confirmed by restriction enzyme analysis. Seven previously described mutations (Y140C, R626X, 503-512del, H414R, G292R, 334del25, and E452K) and four novel mutations (P516L, L242P, E446K, and R482Q) were identified. Expression of the latter and H414R showed that they were all null activity mutations. Considerable genetic heterogeneity has been described in MPS IIIB patients of different origins. In our population, Y140C, H414R, and R626X account for approximately 70% of the studied alleles. Our findings, especially in combination with the origin of individual patients, can improve carrier detection and genetic counseling in affected families.

Gastrointestinal hormones and short-term nutritional schedules in critically ill patients.

BACKGROUND/AIMS: The purpose of the study is to evaluate the gastrointestinal hormone response in critically ill patients under different nutritional schedule (enteral vs. total parenteral) of short duration. METHODOLOGY: Twenty-one sedated and mechanically ventilated patients were nourished with continuous nasogastric schedule (Group A, 11 patients), or with total parenteral nutrition (Group B, 10 patients). Serum concentrations of gastrin, cholecystokinin, vasoactive intestinal peptide, neurotensin, and bombesin, were measured on the 2nd, 3rd and the 5th day of patients' admission, with radioimmunoassay methods. RESULTS: Changes of hormones concentrations were not significant either between the three measurements in each group or between the two groups at the same hospitalization day. CONCLUSIONS: The short-term parenteral nutrition in critically ill patients does not exert a different influence on the serum concentrations of gastrin, cholecystokinin, vasoactive intestinal peptide, neurotensin, and bombesin, compared to enteral nutrition. This conclusion is of clinical interest since the short-term administration of total parenteral nutrition is very often necessary during hospitalization in the intensive care unit.

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.

Reduced Mg2+-ATPase activity in the hypoglycemic adult rat brain.

The effects of different a-D-Glucose (Glu) concentrations (0-16 mM) on Na+, K+-ATPase and Mg2+-ATPase activities were investigated in homogenates of adult male rat whole brain at 37 degrees C. The enzyme activities were determined after 1 h preincubation with Glu. Brain Na+, K+-ATPase was not affected by Glu different concentrations. On the contrary, Mg2+-ATPase activity was considerably reduced with Glu concentrations lower than 4 mM. The enzyme was inhibited 40%, 50% or 80% with 3, 2 or 1 mM of Glu, respectively. The above results suggest: a) The various concentrations of Glu have no effect on brain Na+, K+-ATPase activity. b) The inhibited brain Mg2+-ATPase in hypoglycemia produces low intracellular Mg2+, which could modulate the activity of Mg2+-dependent enzymes and the rates of protein synthesis and growth of the cell.