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Biomedical subjects

I Elmadfa

Publications and source records attributed to I Elmadfa.

At least 19 recordsLinked to original sources

Acute hepatotoxicity of the polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphtaline (AHTN).

Synthetic musks are present in fine fragrances, cosmetics, soaps and laundry detergents. One of the most important synthetic musks is 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydro-naphthaline+ ++ (AHTN; annual production: about 1500 metric tons). An increasing number of studies show that AHTN accumulates in surface water and fish and can be detected in human adipose tissue, as well in human milk. In the present report it is shown that a single high dose of AHTN leads to acute hepatic damage in rats, characterized by single cell necrosis, inflammation, swelling of liver parenchymal cells, and the presence of cytoplasmic condensations in the hepatocytes, while at the ultrastructural level disorganization of the rough endoplasmic reticulum and mitochondria as well as focal cytolysis is evident. Furthermore, evidence is presented that AHTN is not genotoxic, does not induce peroxisome proliferation, and does not lead to the induction of drug-metabolizing enzymes as phenobarbital and 3-methylcholanthrene do.

Animals

Beneficial effects of protease inhibitors on body composition and energy expenditure: a comparison between HIV-infected and AIDS patients.

OBJECTIVES: (i) To investigate whether protease inhibitor (PI) (nelfinavir)-containing highly active antiretroviral therapy (HAART) affects body composition differently in HIV-infected and AIDS patients without wasting syndrome. (ii) To delineate the changes in resting energy expenditure (REE) under PI therapy, and to determine whether sustained reductions in HIV RNA would decrease REE. DESIGN: Prospective longitudinal cohort study with individually matched healthy controls. SETTING: Tertiary care centre at a University Hospital. METHODS: HIV-seropositive (n = 20) and AIDS patients (n = 17) with a plasma viral load of at least 10000 copies/ml and 37 healthy volunteers were enrolled. All participants were weight stable, free of acute opportunistic infections, and naive to PI therapy. Patients underwent testing of bioelectrical impedance analysis (BIA), indirect calorimetry and food intake, shortly before the initiation of HAART and 24 weeks thereafter. RESULTS: Both patient groups gained weight, body mass index (BMI), and fat-free mass (FFM) (P < 0.05 versus baseline), whereas only AIDS patients gained fat mass. Increases were more pronounced in the AIDS group. REE was elevated compared with corresponding controls at baseline, and decreased similarly in HIV and in AIDS patients during PI therapy (P < 0.05). The reduction in the viral burden preceded the decrease in REE by several weeks. CONCLUSION: Body composition and metabolic parameters improved during PI therapy in HIV-infected and AIDS patients without wasting. Although an early reduction in viral load as a result of HAART does not seem to influence REE directly, sustained viral load suppression may promote a decrease in energy expenditure.

Acquired Immunodeficiency Syndrome

Impact of diets with corn oil or olive/sunflower oils on DNA damage in healthy young men.

BACKGROUND: Plant fats and oils are major sources of mono- and polyunsaturated fatty acids as well as vitamin E, the major fat-soluble antioxidants in human nutrition. Dietary antioxidants are expected to reduce cancer risk by minimizing DNA damage. AIM OF THE STUDY: To compare the effects of gamma-tocopherol rich corn oil and the mixture of the alpha-tocopherol rich olive/sunflower oil on plasma concentration of tocopherols and on the frequency of sister chromatid exchange (SCE), an indicator of DNA damage. METHODS: This study had a double-blind, cross-over design and was conducted in 20 normal healthy non-smoking males aged 19-31 years. Design included a 2-week adjustment period and two 2-week test periods in which diets containing 30% energy as fat including either 80 g of corn oil (CO) (20 mg alpha-tocopherol, 100 mg gamma-tocopherol) or 80 g of olive/ sunflower oil (OSO) (24 mg alpha-tocopherol, 2.4 mg gamma-tocopherol), as the main fat-source, were given. Blood samples for analysis of SCE rate and content of tocopherols were collected at the beginning (T0), after adjustment (T1) and after the test period (T2) in intervals of 2 weeks. RESULTS: After two weeks of the corn oil diet, the plasma concentration of gamma-tocopherol increased but alpha-tocopherol decreased significantly compared to the olive/sunflower oil diet. The concentration of alpha-tocopherol increased (CO: 22.99 +/- 1.11 vs. OSO: 24.40 +/- 1.49 micromol/l) and that of gamma-tocopherol decreased (CO: 4.19 +/- 0.29 vs. OSO: 2.99 +/- 0.25 micromol/l) after the olive/sunflower oil diet. Intake of the corn oil diet was associated with reduced SCE rate and intensity, whereas there was no change in SCE after the olive/sunflower oil diet (CO: 7.66 +/- 0.25 vs. OSO: 8.06 +/- 0.47 mean SCE/cell) CONCLUSIONS: The combination of gamma-tocopherol with alpha-tocopherol in corn oil diet despite the lower alpha-tocopherol equivalents/diene acid equivalents ratio achieved better protection against DNA damage than alpha-tocopherol alone in the olive/sunflower oil diet.

Adult

Effects of multivitamin/mineral supplementation, at nutritional doses, on plasma antioxidant status and DNA damage estimated by sister chromatid exchanges in lymphocytes in pregnant women.

The purpose of this study was to evaluate the effect of multivitamin/mineral-supplementation during pregnancy on plasma levels of antioxidants and sister chromatid exchange (SCE) rate--an indicator of damage to DNA. A controlled, semi-randomized, prospective trial was performed comparing the supplement group, who received multivitamin/mineral tablet once daily for 10 weeks, to the control group. Plasma levels of antioxidants and SCE in lymphocytes were measured initially (20 wk gestation) and at the end of the intervention (34 wk gestation). In the control group, SCE rates increased significantly at 34 wk gestation compared to 20 wk gestation, whereas there was no change in the supplement group. Plasma retinol, beta-carotene and ascorbate decreased significantly in the control group. In the supplement group, a significant increase in plasma beta-carotene (55.6%), coenzyme Q10 (40.2%), folic acid (15.9%) and zinc (24.2%) was observed after 10 weeks of supplement. Increased plasma levels of antioxidants in the supplement group could not decrease SCE rates, however, they could prevent an increase in SCE rates which may be induced by reactive oxygen species generated from the enhanced steroid hormones in the last trimester, suggesting that multivitamin/mineral-supplement during pregnancy may prevent DNA damage due to the altered hormonal profile.

Adult

Status of lipidsoluble antioxidants and TRAP in patients with Crohn's disease and healthy controls.

OBJECTIVE: To assess the status of lipidsoluble antioxidants (carotenoids, tocopherols, ubiquinone), retinol and their correlation with TRAP (total radical-trapping antioxidant potential) in patients with Crohn's disease. DESIGN: Prospective case-control study. SETTING: Clinic of Internal Medicine IV/Department of Gastroenterology and Hepatology, University of Vienna Medical School. SUBJECTS/METHODS: Plasma antioxidant concentrations were determined in patients with Crohn's disease (n = 24) to evaluate the antioxidant capacity compared to healthy controls (n = 33). Additionally, plasma TRAP (total radical-trapping antioxidant potential) was measured in 13 patients and 22 controls. RESULTS: All investigated carotenoids (alpha-carotene, beta-carotene and cryptoxanthin) were significantly decreased in patients with Crohn's disease (10.2 +/- 9.3, 16.2 +/- 12.4 and 7.8 +/- 5.5 microg/dl) compared to controls (13.3 +/- 5.1, 34.7 +/- 18.8 and 48.5 +/- 38.4 microg/dl respectively), whereas gamma-tocopherol and ubiquinone were significantly elevated in patients (0.14 +/- 0.07 microg/dl and 82.3 +/- 41.5 microg/dl, controls: 0.09 +/- 0.04 microg/dl and 60.8 +/- 30.0 microg/dl, respectively). Retinol and alpha-tocopherol did not significantly differ from controls. The total radical-trapping antioxidant potential (TRAP) was significantly lower in patients (1.11 +/- 0.28 micromol/l) compared to controls (1.34 +/- 0.26 micromol/l). Antioxidants were neither related to duration or severity of disease nor to disease activity. CONCLUSIONS: In patients with Crohn's disease several plasma antioxidant parameters are altered and the total radical-trapping antioxidant potential is decreased.

Adult

Effects of intensified lifestyle modification on the need for further revascularization after coronary angioplasty.

BACKGROUND: In patients with coronary artery disease (CAD), a rate of restenosis as high as 50% is observed after percutaneous transluminal coronary angioplasty (PTCA). Frequently, this results in further revascularization procedures. Lifestyle intervention has been shown to slow the progression of CAD and to reduce cardiovascular events after myocardial infarction. However, no information exists whether such treatment influences the rate of restenosis in patients with CAD. The present study was performed to investigate the effects of an intensified lifestyle intervention on the need for further revascularization procedures in patients with established CAD after successful PTCA. DESIGN: A total of 60 patients were included and randomized to either conventional treatment by cardiologists and general practitioners or additional intensified lifestyle intervention in a diabetes and metabolism outpatient clinic for 12 months. The mean observation time after successful PTCA was 26 months. The primary outcome variable was the need for further revascularization procedures because of clinical restenosis. Secondary outcome variables were lifestyle-related measures. RESULTS: Intervention resulted in a reduction in body weight and blood pressure, and in increased physical activity. Furthermore, nutritional habits were changed towards less fat intake, and body composition changed towards a higher proportion of fat-free mass. The need for further revascularization procedures was reduced from a total of 14 out of 32 in the conventionally treated group to 3 out of 28 in the intervention group. This resulted in an event-free survival probability of 0.89 in the intervention group and 0.57 in the control group (P = 0.0055, log rank) with a resulting relative risk of 0.26 (95% CI 0.09-0.74). CONCLUSION: In conclusion, our data strongly suggest that intensified lifestyle modification is able to reduce the need for further revascularization procedures after PTCA in patients with CAD.

Angina Pectoris

Species and organ dependence of PCB contamination in fish, foxes, roe deer, and humans.

According to previous experimental results, PCBs are deposited in muscle fat in animals and in humans, although they also reach the brain, the liver, and the lungs. The aim of the present study was to determine the concentrations of the so-called "indicator PCBs" (PCB nos. 28, 52, 101, 138, 153, 180), as described by the German ordinance for maximum concentrations of contaminants in foodstuffs, in muscle tissue, liver, and brain of four different species: fish, fox, roe deer, and humans, all exposed to PCBs directly in their environment. Potential target organs for the accumulation of these congeners were also to be identified. Furthermore, the organs or tissues were to be identified in which PCBs are accumulated, and unusual patterns of accumulation or breakdown of particular PCBs, for example the "dioxin-like PCBs" (coplanar PCBs) determined. For humans, the lungs were also included in these studies. Statistical comparison of PCB concentrations in samples from wild animals and humans showed that in spite of its relatively high fat concentration, brain tissue in all of the species examined (with the exception of fish) appeared to be better protected against accumulation of PCB than liver or muscle tissue. This protection may be the result of the blood-brain barrier, as witnessed by the relatively uniform concentration of PCBs throughout the various organs of fish, since the blood-brain barrier of fish is considerably less efficient than that of mammals. No peculiarities were found in regard to distribution of the coplanar PCBs over the other congeners in this study. This applies to the brain and other organs or tissues of the four species that were examined. Accumulations of PCBs and coplanar PCBs in the liver were only found in fox and roe deer. In contrast, humans were found to have accumulations of the high-chlorinated biphenyls studied here as well as PCB no. 118 in muscle tissue fat and not in the liver. Unexpectedly, low-chlorinated biphenyls were found to accumulate in the human lung. The results of this study show that the lung represents a target organ for the accumulation of potentially metabolically activated low-chlorinated biphenyls, indicating that the possible biological effects of PCBs on the lungs will need to receive more attention in the future.

Adipose Tissue

[Carotenoids and vitamin A in fish].

Seven commercial salmon and six trout samples were investigated. Retinol and the carotenoids astaxanthin and canthaxanthin important for pigmentation of the muscle were determined by RP-HPLC. Vitamin A concentrations of raw salmon samples were 16-19 micrograms/100 g, of smoked salmon samples 9-19 micrograms/ 100 g; retinol values of salmon trout (raw) and trout (raw) reached 14-16 micrograms/100 g and 7-9 micrograms/100 g. Concentrations of astaxanthin the important carotenoid of pigmentation, ranged in samples of salmon from 310-465 micrograms/100 g. Samples of salmon trout showed astaxanthin values between 90 and 536 micrograms/100 g, trout samples only 67-85 micrograms/100 g. Concentrations of canthaxanthin were different in the examined samples and were not detectable in all samples. Highest values of canthaxanthin were found in salmon trout samples (113-226 micrograms/100 g), Irish smoked salmon and stremel-salmon (145-169 micrograms/100 g). Raw samples of salmon and of trout showed only low concentrations of canthaxanthin. Astaxanthin and canthaxanthin together reached values of 419-524 micrograms/100 g for salmon, 316-701 micrograms/100 g for salmon trout, and 72-91 micrograms/100 g for trout samples.

Animals

Mitochondrial oxygen consumption, lipid peroxidation and antioxidant enzyme systems in skeletal muscle of senile dystrophic mice.

To evaluate age-dependent abnormalities in mitochondrial redox metabolism specifically in dystrophic skeletal muscle, oxygen consumption, thiobarbituric acid reactivity (TBARS), free-radical scavengers and oxidative marker enzymes were measured in the skeletal muscle from adult and senile control (C57BL/10) and dystrophic (mdx/+) mice. Mitochondrial oxygen consumption in state 3 was significantly lowered with age in the senile dystrophic (-52%) and less markedly in the senile control (-30%) skeletal muscle. Compared with adult muscle, mitochondrial concentration of TBARS and cellular concentration of lipofuscin were significantly increased in senile control and dystrophic muscle. Enzymatic activity of glutathione peroxidase (GSH-Px) and concentration of alpha-tocopherol were significantly increased in the senile control (GSH-Px 43+/-5.7 vs 53+/-8.7 U/g protein, alpha-tocopherol 0.19+/-0. 09 vs 0.29+/-0.14 micromol/g total lipids), but significantly decreased in the senile dystrophic (GSH-Px 80+/-8.0 vs 53+/-12 U/g protein, alpha-tocopherol 0.45+/-0.13 vs 0.19+/-0.03 micromol/g total lipids) muscle. Selenium content was significantly decreased only in senile dystrophic muscle (1.37+/-0.42 vs 0.78+/-0.21 nmol/g wet muscle). In conclusion, the enzymatic adaptation to reactive oxygen species was limited in the dystrophic skeletal muscle, suggesting a higher need for antioxidants, especially alpha-tocopherol.

Aging

Effects of long-term oral beta-carotene supplementation on lipid peroxidation in patients with cystic fibrosis.

The aim of this study was to determine the efficacy of oral beta-carotene supplementation for the correction of an oxidant-antioxidant imbalance in cystic fibrosis (CF). We studied 24-patients with cystic fibrosis and 14 healthy controls. 13 CF-patients were allocated to a CF-supplementation group, which received 1 mg beta-carotene/kg BW/d up to a body weight (BW) of 50 kg, patients with a BW greater 50 kg received 50 mg beta-carotene/d for 12 weeks. For the following 12 weeks all patients of the CF-supplementation group were treated with 10 mg beta-carotene/d. Placebos with starch were applied to 11 CF-patients. Baseline plasma beta-carotene concentrations of CF patients (mean +/- SD, 0.08 +/- 0.04 mumol/l) were significantly lower than those of age-matched controls (o.3 +/- 0.1 mumol/l) (p < 0.001). beta-carotene concentrations of the CF-supplementation group increased rapidly and reached a value of 0.6 mumol/l after 12 weeks of supplementation. Normal values were measured for plasma ascorbate and alpha-tocopherol. Plasma retinol concentrations were in the lower normal range and did not increase during supplementation. Total antioxidative capacity in plasma of the CF-supplementation group increased after 12 weeks of supplementation at an extent of 12%. Positive influence was indicated by a decrease of plasma malondialdehyde. Thus oral beta-carotene supplementation is effective in normalizing status of beta-carotene and malondialdehyde in CF patients.

Adolescent

Increased sister chromatid exchanges in peripheral lymphocytes of patients with Crohn's disease.

A cytogenetic study was performed using Crohn's disease patients to determine whether the presence of chromosome instability is related to Crohn's disease, a chronic inflammatory bowel disease. Sister chromatid exchange (SCE) frequencies in peripheral blood lymphocyte cultures from 22 Crohn's disease patients and an equal number of healthy controls matched for sex and age were analyzed. The mean of SCE frequency in Crohn's disease patients was 11.64 +/- 0.42 (SEM) per cell, which was significantly higher than the value of 8.38 +/- 0.22 per cell in the matched controls (p < 0.0001). The Crohn's disease patients showed significantly increased high frequency cells (HFC) as compared to those among the matched controls. There was a significant correlation between HFC frequencies of the Crohn's disease patients and the severity of their disease as determined by the number of relapses per year and the degree of chronic activity after adjusting for the smoking status (r = 0.54, p = 0.011). In both smokers and non-smokers, the mean SCE and HFC frequencies of the patients were significantly higher than those of the controls. These results suggest that Crohn's disease is a condition with increased chromosome instability characterized by a high level of SCE frequencies which are associated with the inflammatory condition itself.

Adult

Antioxidant status in patients on chronic hemodialysis therapy: impact of parenteral selenium supplementation.

Reactive oxygen species may be involved in a broad pattern of tissue injury in patients on regular hemodialysis therapy and, in fact, increasing evidence suggests that the antioxidative system is compromized in these patients. One factor contributing to this reduction of antioxidative capacity is selenium deficiency. The present investigation was undertaken to further define the extent and type of impairment of the oxygen radical scavenger system in chronic hemodialysis patients and to evaluate the impact of selenium supplementation. Twelve non-wasted patients (6 male, 6 female, mean age of 58 years) on chronic hemodialysis for a minimum of 5 months (mean 46 months) were supplemented intravenously with 400 mg selenium (as sodium selenite) thrice weekly after each hemodialysis session over 8 weeks. Blood samples were taken before the start, at intervals of 2 weeks during, and 4 weeks after termination of supplementation. Concentrations were evaluated of selenium and alpha-tocopherol in plasma and erythrocytes, of retinol and ascorbic acid in plasma, of glutathione and the activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and, catalase (CAT) in erythrocytes. Lipid peroxidation endproducts were measured as malondialdehyde (MDA) in plasma. In patients on hemodialysis multiple alterations of the antioxidative system were present and the concentrations of selenium in plasma, of glutathione and the activity of GSH-Px in erythrocytes were profoundly decreased (p < 0.001). Selenium supplementation improved the selenium status of the patients, as indicated by an increase in selenium concentrations in plasma and erythrocytes and erythrocyte GSH-Px activity. Improvement in antioxidative capacity was further documented by an increase in alpha-tocopherol in erythrocytes. Plasma MDA showed a transient decrease after 6 weeks and increased activities of SOD and CAT were dampened. No effect was seen on plasma concentrations of ascorbic acid, a-tocopherol and retinol. We conclude that patients on chronic hemodialysis therapy manifest a profound depression in antioxidative potential and a selenium deficiency. Selenium supplementation improves the oxygen radical scavenger system and increases selenium concentrations in plasma and erythrocytes and the activity of selenium dependent glutathione peroxidase. Thus, selenium should also be considered for micronutrient supplementation in patients on chronic hemodialysis therapy.

Adult

[Reducing lipid peroxidation of stored frozen trout fillet by supplementing feed with vitamin E].

Rainbow trouts were fed a complete diet with 12 mg vitamin K3 and supplemented with 20, 200 or 2,000 mg all-rac-alpha-tocopheryl-acetate/kg for 18 weeks. The ratio of the vitamin E-supplementation was 1:10:100. Fillets were minced and stored at -18 degrees C. Concentrations of alpha-tocopherol and phylloquinone and parameters of lipid peroxidation were measured after 4, 6, and 8 months of storage. The effects of alpha-tocopherol incorporated into fillets on storage stability were assessed by measuring free fatty acids, peroxides, malondialdehyde and lipofuscin. Mean alpha-tocopherol-concentrations in fillets were 1.4, 2.7 and 16.3 mg/100 g, respectively representing ratios of 1:2:12. The increase in alpha-tocopherol concentration resulted in a significant improvement of storage stability. The phylloquinone concentration in fillet was reduced in treatments with > or = 200 mg vitamin E/kg; however, this did not affect the prothrombin time. No peroxides were detectable at any time. The concentrations of malondialdehyde significantly decreased with increasing supplementation of vitamin E. Lipofuscin concentrations were higher with low than with high vitamin E supplementation. The dose-related inhibition of lipid peroxidation became apparent in decreased concentrations of free fatty acids in the crude fat. These results confirm the effectiveness of alpha-tocopherol as antioxidant in fish flesh. In this study the incorporation of alpha-tocopherol from dietary supplementation improved the long-term storage quality of trout fillets due to the effective inhibition of the lipid peroxidation. A measurable improvement of the storage stability was achieved with a supplementation of 200 mg vitamin E/kg feed.

Animal Feed

Metabolic effect of sodium selenite: insulin-like inhibition of glucagon-stimulated glycogenolysis in the isolated perfused rat liver.

Selenium, an essential trace element, has been shown to decrease plasma glucose concentrations of diabetic rats. To study the short-term effects of selenium on hepatic carbohydrate metabolism, isolated perfused livers of fed Sprague-Dawley rats were continuously infused with sodium selenite for 90 minutes. This resulted in an immediate elevation of selenium in the effluent perfusate (3.3 +/- 0.1, 16.1 +/- 0.4, 30.3 +/- 1.6, and 118.9 +/- 0.8 mumol/L at infusion of 10, 50, 100, and 500 mumol/L sodium selenite, respectively). Basal hepatic glucose production decreased in a dose-dependent manner within 60 minutes of low-dose sodium selenite infusion (10: 0.60 +/- 0.20, 50: 0.21 +/- 0.40, and 100 mumol/L: 0.21 +/- 0.09 mumol.min-1.g-1 liver; P < .05 vs. zero time), while it was transiently increased by 500 mumol/L sodium selenite (1.11 +/- 0.18 mumol.min-1.g-1 liver; P < .05). Glucagon-stimulated glycogenolysis was suppressed by 50% (P < .05) at 1.8 nmol/L insulin and by 90% (P < .001) at 10 mumol/L sodium selenite. That selenium concentration did not affect glutathione peroxidase activities in liver and perfusate erythrocytes within 60 minutes. Toxic effects of high-dose selenite (500 mumol/L), but not of low-dose selenite (10 mumol/L) infusion, were indicated by increased hepatic glucose (P < .05), lactate (P < .01), and lactate dehydrogenase (P < .001) release as well as histologically by degeneration and necrosis of periportal hepatocytes. In conclusion, low-dose selenite exerts a potent insulinlike effect on hepatic glycogenolysis in vitro by counteracting glucagon action, whereas high-dose selenite may severely impair liver function.

Animals

Rapid HPLC assay for the assessment of vitamin K1, A, E and beta-carotene status in children (7-19 years).

The method presented allows the determination of plasma concentrations of the fat soluble vitamins K1, A, E and beta-carotene. After the extraction of the plasma, the only clean-up step required consisted of washing the hexane-layer with a methanol/water mixture. The RP-HPLC system contained a zinc-filled reduction post-column and after chromatographic separation the vitamin K was detected by fluorescence. Only 0.5-1 ml plasma was required for this procedure. 2',3'-Dihydrophylloquinone was added as an internal standard. For phylloquinone the limit of detection was estimated at 0.09 nmol/l (0.04 ng/ml). Investigating a plasma pool with a mean concentration of 0.75 nmol phylloquinone/l plasma, the all-over coefficient of variation was 5.6% for within-day (n = 11) and 7.1% from day to day (n = 8). The rate of recovery was found to be in the range of 92-104% (the same pool as for the precision test was used, and the added amounts were 0.13, 0.5, 2.0 ng phylloquinone). From an aliquot of hexane-extract, the vitamins A, E and beta-carotene were separated by RP-HPLC. The concentrations of vitamins A, E and beta-carotene were measured on the UV and visible detector respectively. Coefficients of variation for all vitamins were < 10%. In a group of 7 to 19 year-old healthy children (n = 298), the concentrations of vitamins A, E, K1 and beta-carotene ranged from 0.34-2.10 mumol/l, 12.0-80.8 mumol/l, 0.09-2.22 nmol/l and 0.23-3.92 mumol/l respectively, and the medians were 1.02 mumol/l, 21.3 mumol/l, 0.49 nmol/l and 0.56 mumol/l respectively.

Adolescent