The Use of Multi-parametric Biomarker Profiles May Increase the Accuracy of ASD Prediction.

Effective biomarkers are urgently needed to facilitate early diagnosis of autism spectrum disorder (ASD), permitting early intervention, and consequently improving prognosis. In this study, we evaluate the usefulness of nine biomarkers and their association (combination) in predicting ASD onset and development. Data were analyzed using multiple independent mathematical and statistical approaches to verify the suitability of obtained results as predictive parameters. All biomarkers tested appeared useful in predicting ASD, particularly vitamin E, glutathione-S-transferase, and dopamine. Combining biomarkers into profiles improved the accuracy of ASD prediction but still failed to distinguish between participants with severe versus mild or moderate ASD. Library-based identification was effective in predicting the occurrence of disease. Due to the small sample size and wide participant age variation in this study, we conclude that the use of multi-parametric biomarker profiles directly related to autism phenotype may help predict the disease occurrence more accurately, but studies using larger, more age-homogeneous populations are needed to corroborate our findings.

[Nutritional guidelines for healthy children aged 1-3 years - Polish Expert Group statement. Part I- energy and nutritional components demand]. / Normy zywienia zdrowych dzieci w 1-3. Rokuzycia . stanowisko polskiej grupy ekspertów.czesc i - zapotrzebowanie na energiei skladniki odzywcze.

Updating of the nutritional guidelines for the Polish population requires updates of the nutritional norms for children. We present the Polish Expert Group statement (2012) on intake of selected nutrients (protein, lipids, carbohydrates, vitamin D and E) essential in nutrition of children aged 1-3 years. For this purpose the Expert Group reviewed available scientific data: the recent guidelines, nutritional norms and recommendations, systematic reviews and expert opinions as well as original publications, in relation to the specific requirements of the Polish population.

Wear, bone density, functional outcome and survival in vitamin E-incorporated polyethylene cups in reversed hybrid total hip arthroplasty: design of a randomized controlled trial.

BACKGROUND: Aseptic loosening of total hip arthroplasties is generally caused by periprosthetic bone resorption due to tissue reactions on polyethylene wear particles. In vitro testing of polyethylene cups incorporated with vitamin E shows increased wear resistance. The objective of this study is to compare vitamin E-stabilized highly cross-linked polyethylene with conventional cross-linked polyethylene in "reversed hybrid" total hip arthroplasties (cemented all-polyethylene cups combined with uncemented femoral stems). We hypothesize that the adjunction of vitamin E leads to a decrease in polyethylene wear in the long-term. We also expect changes in bone mineral density, less osteolysis, equal functional scores and increased implant survival in polyethylene cemented cups incorporated with vitamin E in the long-term. DESIGN: A double-blinded randomized controlled trial will be conducted. Patients to be included are aged under 70, suffer from non-inflammatory degenerative joint disease of the hip and are scheduled for a primary total hip arthroplasty. The study group will receive a reversed hybrid total hip arthroplasty with a vitamin E-stabilized highly cross-linked polyethylene cemented cup. The control group will receive a reversed hybrid total hip arthroplasty with a conventional cross-linked polyethylene cemented cup. Radiological follow-up will be assessed at 6 weeks and at 1, 3, 5, 7 and 10 years postoperatively, to determine polyethylene wear and osteolysis. Patient-reported functional status (HOOS), physician-reported functional status (Harris Hip Score) and patients' physical activity behavior (SQUASH) will also be assessed at these intervals. Acetabular bone mineral density will be assessed by dual energy X-ray absorptiometry (DEXA) at 6 weeks and at 1 year and 2 years postoperatively. Implant survival will be determined at 10 years postoperatively. DISCUSSION: In vitro results of vitamin E-stabilized polyethylene are promising, showing increased wear resistance. However, controlled clinical follow-up data are not available at this moment.This randomized controlled trial has been designed to determine wear, bone mineral density, functional outcome and survival in reversed hybrid total hip arthroplasty comparing cemented vitamin E-stabilized highly cross-linked polyethylene cups with cemented conventional cross-linked polyethylene cups. TRIAL REGISTRATION: Dutch Trial Registry NTR3049.

Bioavailability study of berberine and the enhancing effects of TPGS on intestinal absorption in rats.

Berberine chloride (BBR) is a natural isoquinoline alkaloid extracted from medicinal herbs. It has been reported that the intestinal absorption of BBR is very low. In this study, the absolute bioavailability of BBR was studied, and the enhancing effects of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on intestinal absorption were investigated in rats. BBR injection was administrated via the femoral vein at a dose of 1.0 mg kg(-1) in intravenous group, and BBR oral formulations were administrated by oral gavage at a dose of 100 mg kg(-1) in BBR control (control) group and BBR-TPGS (test) group, respectively. The result showed that BBR had a very low absolute bioavailability of 0.68%, and TPGS could enhance intestinal absorption of BBR significantly. TPGS at a concentration of 2.5% could improve peak concentration (C(max)) and area under the curve (AUC(0-36)) of BBR by 2.9 and 1.9 times, respectively. The absorption enhancing ability of TPGS may be due to its ability to affect the biological activity of P-glycoprotein and thereby reduce the excretion of absorbed BBR into the intestinal lumen. This study indicated that absolute bioavailability of BBR was 0.68% in rats, and TPGS was a good absorption enhancer capable of enhancing intestinal absorption of BBR significantly.

Serum vitamin A and E analysis: comparison of methods between laboratories enrolled in an external quality assurance programme.

AIM: To survey laboratories enrolled in the Royal College of Pathologists of Australasia (RCPA) Chemical Pathology Quality Assurance Programme (QAP) for vitamin A and E testing to determine differences between methods of analysis. METHODS: A detailed questionnaire covering the major aspects of serum vitamin A and E analysis was sent to all participating laboratories in 2007. RESULTS: Thirteen out of the 22 laboratories completed the questionnaire. Methods between laboratories showed a great deal of commonality. All respondents performed a liquid extraction step, which included the addition of an internal standard, followed by high-performance liquid chromatography (C18 columns with predominantly methanol-based mobile phases) with spectrophotometric detection. Major inter-laboratory differences were whether the sample was protected from light, the extraction solvents and ratios used, the drying down temperature used post-liquid extraction and choice of calibrator. CONCLUSIONS: The questionnaire highlighted discrete methodological differences between laboratories. These findings provide direction to enable the Vitamins Working Party of the Australasian Association of Clinical Biochemists to further investigate the dispersion in results between participants of the RCPA QAP vitamin programme.

The value of measuring serum cholesterol-adjusted vitamin E in routine practice.

BACKGROUND: If the lipid concentration is not taken into account, then in certain situations the vitamin E status of a patient may be wrongly assigned based on serum measurement alone. In this study, the utility of using the calculated vitamin E:cholesterol ratio to determine vitamin E status was compared to the measurement of vitamin E alone. METHODS: The vitamin E:cholesterol ratio was measured in 457 patient samples received for routine vitamin E analysis. Serum vitamin E concentration was determined by high-performance liquid chromatography (HPLC) with UV detection and cholesterol concentration, using a Roche analyser and reagents. RESULTS: The mean vitamin E concentration and vitamin E:cholesterol ratio for the total study population was 22.0 micromol/L and 5.9 micromol/mmol, respectively. Of the 457 patient samples analysed, 57 (12.5%) were found to have a low vitamin E concentration, but only 25 (47%) of these patients had a low vitamin E:cholesterol ratio as well. Two patients both with cholestasis had a normal vitamin E concentration but low vitamin E:cholesterol ratio. CONCLUSION: The determination of vitamin E:cholesterol ratios can be used to better define the vitamin E status of patients with disease states or disorders likely to raise LDL cholesterol, for example cholestasis. For the majority of samples, measurement of serum vitamin E concentration alone is sufficient to establish patient vitamin E status.

[Tocopherol Succinate Reference Standard (Control 021) of National Institute of Health Sciences].

The raw material of tocopherol succinate was tested for the preparation of the "Tocopherol Succinate Reference Standard (Control 021)". Analytical data obtained were as follows: infrared spectrum, same as that of the Tocopherol Succinate Reference Standard (Control 981); specific absorbance, E1% 1 cm (286 nm) = 40.7; thin-layer chromatography, no impurities were detected until 50.0 micrograms; high-performance liquid chromatography (HPLC), four impurities were detected and the amount of tocopherol succinate was estimated to be 99.0%; loss on drying, 0.11%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 021).

Antioxidants: what role do they play in physical activity and health?

Exercise appears to increase reactive oxygen species, which can result in damage to cells. Exercise results in increased amounts of malondialdehyde in blood and pentane in breath; both serve as indirect indicators of lipid peroxidation. However, not all studies report increases; these equivocal results may be due to the large intersubject variability in response or the nonspecificity of the assays. Some studies have reported that supplementation with vitamins C and E, other antioxidants, or antioxidant mixtures can reduce symptoms or indicators of oxidative stress as a result of exercise. However, these supplements appear to have no beneficial effect on performance. Exercise training seems to reduce the oxidative stress of exercise, such that trained athletes show less evidence of lipid peroxidation for a given bout of exercise and an enhanced defense system in relation to untrained subjects. Whether the body's natural antioxidant defense system is sufficient to counteract the increase in reactive oxygen species with exercise or whether additional exogenous supplements are needed is not known, although trained athletes who received antioxidant supplements show evidence of reduced oxidative stress. Until research fully substantiates that the long-term use of antioxidants is safe and effective, the prudent recommendation for physically active individuals is to ingest a diet rich in antioxidants.

Vitamin E, vitamin C, and exercise.

Exercise increases the generation of oxygen free radicals and lipid peroxidation. Strenuous exercise in a person who is unconditioned or unaccustomed to exercise will induce oxidative damage and result in muscle injury. However, aerobic exercise training strengthens the antioxidant defense system by increasing superoxide dismutase. Vitamin C and, especially, vitamin E are shown to decrease the exercise-induced increase in the rate of lipid peroxidation. No ergogenic effects of either vitamin C or E have been shown. Vitamin E was shown to significantly increase circulating neutrophils in older, but not younger, subjects performing eccentric exercise that causes an increase in skeletal muscle damage. In addition to its effect in augmenting the neutrophil response to eccentric exercise, vitamin E causes a greater increase in circulating creatine kinase activity, perhaps indicating increased skeletal muscle repair. Increased vitamin E intake has been associated with enhanced glucose tolerance and insulin action as well as improved lipoprotein status. Future research should examine the combined effects of exercise training and vitamins E and C on these health-related outcomes.

Automated analysis of vitamin E isomers in vegetable oils by continuous membrane extraction and liquid chromatography-electrochemical detection.

A rapid and automated method for the analysis of alpha-, gamma- and delta-tocopherols in vegetable oils is reported. Continuous extraction of vitamin E isomers from oil samples dissolved in Triton X-114 in the presence of methanol-hexane is achieved and coupled on-line with the chromatographic system. Using an acetic acid/sodium acetate buffer in a methanol-water (97:3) solution as the mobile phase, a C18 stationary phase and electrochemical detection in the coulometric mode, alpha-, gamma- and delta-tocopherol isomers can be successfully analyzed within 17 min. Thirteen commercially available oils of olive, sunflower, corn and seed mixtures were analyzed using 2,2,5,7,8-pentamethyl-6-chromanol as internal standard. The results obtained using three methodologies, one of them including classical sample treatment for liposoluble vitamin analysis, were in good agreement. To validate the proposed method, analysis of the only BCR Reference Material available, with a certified content of alpha-tocopherol (margarine CRM 122), was carried out using the automated methodology, the results found being in agreement with the certified value.

[The oral vitamin E tolerance test--an attempt at standardization]. / Der orale Vitamin-E-Belastungstest--Versuch einer Standardisierung.

Chronic vitamin E deficiency causes various neurological symptoms such as cerebellar ataxia, hypoesthesia, areflexia, pigmentary retinopathy, nystagmus and muscle weakness. This is commonly caused by malabsorption of vitamin E, which is either a result of malabsorption of fat or occurs as an isolated vitamin E deficiency. The oral vitamin E tolerance test is suitable for the assessment of vitamin E reabsorption and elimination. However, standardised normal parameters have not yet been defined. We investigated 61 healthy individuals aged 18-70 years (mean age, 45.0 years). Each person involved in the trial received 100 IU of all-rac-alpha-tocopherol in 200 millilitres of whole milk. The vitamin E in the serum was then analysed 0, 3, 6, 9, 12, 24, 36, 48, 60, 72 hours after vitamin E was given, using high pressure liquid chromatography. The ratio of vitamin E to the sum of cholesterol and triglycerides was calculated. The 90% CI for the ratio of serum vitamin E to the sum of cholesterol plus triglycerides at the indicated time points was: t = 0 h: 2.0-6.3 micrograms/mg, t = 6 h: 4.2-15.3 micrograms/mg, t = 12 h: 3.0-13.0 micrograms/mg, t = 24 h: 3.8-14.4 micrograms/mg, t = 36 h: 2.9-10.5 micrograms/mg, t = 72 h: 2.1-8.7 micrograms/mg. The serum concentration of vitamin E correlated predominantly with the sum of cholesterol and triglycerides (r = 0.73). The ratio of these parameters is therefore most suitable for diagnosing vitamin E deficiency without relying on false normal serum vitamin E concentrations as a result of abnormally high serum lipid concentrations.

[Tocopherol Succinate Reference Standard (Control 981) of National Institute of Health Sciences].

The raw material of tocopherol succinate was tested for preparation of the "Tocopherol Succinate Reference Standard (Control 981)". The analytical data obtained were: infrared spectrum same as that of the Tocopherol Succinate Reference Standard (Control 8510); specific absorbance, E(1%)1 cm (286 nm) = 40.7; thin-layer chromatography, no impurities detected until 50.0 microgram; high-performance liquid chromatography (HPLC),three impurities detected and amount of tocopherol succinate estimated to be 98.2%, loss on drying, 0.19%, assay by HPLC, 101.7%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 981).

Quantitative subfemtomole analysis of alpha-tocopherol and deuterated isotopomers in plasma using tabletop GC/MS/MS.

A rapid, high-selectivity method with subfemtomole sensitivity is reported for quantification of alpha-tocopherol in plasma-based gas chromatography/tandem mass spectrometry (GC/MS/MS) using a tabletop quadrupole ion trap mass spectrometer. Sample workup is rapid, consisting of protein precipitation followed by liquid/liquid extraction and O-trimethylsilyl derivatization of alpha-tocopherol (alpha-T-TMS) and an internal standard, 2,2,5,7,8-pentamethyl-6-chromanol (PC-TMS). Rudimentary chromatography was carried out using an 8-m DB-5 capillary column resulting in an analyte retention time of 7.2 min. No interferences from the plasma matrix were observed. The assay has a detection limit of 178 amol (89.6 fg) and a lower limit of quantification of 700 amol (350 fg) of derivatized alpha-tocopherol in diluted plasma; < 30 pL of plasma is estimated to yield sufficient alpha-tocopherol for quantitative analysis at typical concentrations found in humans. A calibration curve constructed from National Institute of Standards and Technology serum standards was linear in the working range of 1.9-1073 ng/mL (0.95-0.54 ng). Within- and between-day precision averaged 5.8% and did not exceed 11.3% for three concentrations of quality control (QC) solutions. The overall accuracy for the QC samples was within 7.2%. Storage studies showed that, alpha-T-TMS and PC-TMS are stable under conditions that might be encountered during analyses. In a test study, plasma kinetic curves for alpha-tocopherol-d6 and alpha-tocopherol-d3 were obtained for a catheterized pregnant ewe and her fetus who were simultaneously given a bolus injection of alpha-tocopherol-d6, to the ewe and alpha-tocopherol-d3 to the fetus. These data show that a tabletop GC ion trap can determine alpha-T-TMS and its isotopomers quantitatively at high selectivity in a complex matrix.

[Tocopherol Acetate Reference Standard (Control 971) of National Institute of Health Sciences].

The raw material of tocopherol acetate was examined for the preparation of the "Tocopherol Acetate Reference Standard (Control 971)". Analytical data obtained were as follows: infrared spectrum, the same as that of the Tocopherol Acetate Reference Standard (Control 941); specific absorbance, E1 cm 1% (284 nm) = 43.0; thin-layer chromatography, no impurities were detected until 50.0 micrograms of the loaded raw material; high-performance liquid chromatography (HPLC), one impurity was detected and the amount was estimated to be about 0.68%; assay by HPLC, 100.2%. Based on the above results, the raw material was authorized as the Tocopherol Acetate Reference Standard (Control 971) of National Institute of Health Sciences.

Evaluation of multiple micronutrient supplementation in the management of oral submucous fibrosis in Karachi, Pakistan.

Oral submucous fibrosis (OSF) is an oral precancerous condition characterized by symptoms such as intolerance to spicy food, altered salivation, progressive difficulty in opening the mouth, and signs like vesiculation, ulceration, blanching, rigidity, and stiffening of the oral mucosa and depapillation and altered mobility of the tongue. It is seen mostly among people of Indian subcontinent origin. The major structural change is extensive fibroelastic scarring of the lamina propria and deeper connective tissues. A combination of micronutrients (vitamins A, B complex, C, D, and E) and minerals (iron, calcium, copper, zinc, magnesium, and others) was evaluated for its efficacy in controlling the symptoms and signs of OSF in 117 compliant subjects in Karachi, Pakistan, in a single-arm preliminary study. The subjects received supplementation for one to three years. Significant improvement in symptoms, notably intolerance to spicy food, burning sensation, and mouth opening, was observed at exit. The interincisor distance deteriorated in 11 subjects (10%) at exit; it was stable in 56 subjects (49%) and improved in 48 (41%). The mean interincisor distance was 19.1 +/- 10.8 (SD) mm at exit compared with 16.2 +/- 7.5 mm at baseline. A significant proportion of concomitant lesions like leukoplakia also regressed at exit. The major outcome from this study was a beneficial clinical response in subjects with OSF to multiple micronutrient intervention, which justifies its further evaluation in well-designed randomized controlled trials in other settings in South Asia.

Simultaneous determination of tissue tocopherols, tocotrienols, ubiquinols, and ubiquinones.

A tissue-specific distribution of the various vitamin E forms, tocotrienols and tocopherols, has been found, suggesting that these forms have unique roles in cellular functions. A sensitive procedure is described for the simultaneous determination of individual tocopherols, tocotrienols, ubiquinols, and ubiquinones using gradient high pressure liquid chromatography (HPLC) and electrochemical detection for vitamin E homologues and ubiquinols, and in-line UV detection for ubiquinones. Using this method, the lipophilic antioxidant complement of a variety of hairless mouse tissues was analyzed. Of the vitamin E forms, brain contained virtually only alpha-tocopherol (5.4 +/- 0.1 nmol/g; 99.8%) and no detectable tocotrienols were found. By contrast, skin contained nearly 15% tocotrienols and 1% gamma-tocopherol. In other tissues, the alpha-tocopherol content was higher (20 nmol/g), while each of the other forms represented about 1% of the total (gamma-tocopherol 0.2 to 0.4 nmol/g, alpha-tocotrienol 0.1, gamma-tocotrienol 0.2). Ubiquinol-9 concentrations were highest in kidney (81 nmol/g) and in liver (42 nmol/g), while the highest ubiquinone-9 concentrations were found in kidney (301 +/- 123 nmol/g) and heart (244 +/- 22 nmol/g). Liver contained nearly identical concentrations of each of the redox couple (ubiquinol-9 (41 +/- 16 nmol/g) and ubiquinone-9 (46 +/- 18 nmol/g). The unique distribution of these various antioxidants in the tissues measured suggests their distribution may be dependent upon selective mechanisms for maintaining antioxidant defenses in each tissue.

A new parameter for checking the suitability of alpha-tocopherol standards.

The quality of an alpha-tocopherol standard can be checked easily by measuring the UV absorbance at minimum (255 nm, Amin) and maximum (292 nm, Amax) wavelengths in n-hexane. If the quotient Amin/Amax exceeds 0.18, the standard contains less than 90% alpha-tocopherol and the determination at 292 nm will yield inaccurate results.

[Tocopherol Acetate Reference Standard (Control 941) of the National Institute of Health Sciences].

The raw material of tocopherol acetate was tested for the preparation of the "Tocopherol Acetate Reference Standard (Control 941)". Analytical data obtained were as follows: infrared spectrum, the same as that of the Tocopherol Acetate Reference Standard (Control 919); specific absorbance, E1(1%)cm (284nm) = 44.5; thin-layer chromatography, no impurities were detected until 50.0 micrograms; high-performance liquid chromatography (HPLC), 2-3 impurities were detected and the amount was estimated to be about 1%; assay by HPLC, 100.8%. Based on the above results, the raw material was authorized as the Japanese Pharmacopoeia Reference Standard (Control 941).