Vitamin E and C levels in infants during the first year of life.

The considerably lower vitamin E level found in cord blood and in newborns at birth than those found in the venous blood of mothers at delivery are not yet fully explained. In a group of 217 not selected newborns, we attempted to establish the relation between vitamin E and C levels at delivery and the changes during the first year of life. The mean serum vitamin E level rose from 0.37 mg/ml at 3 days to 0.80 mg/100 ml at 6 months and to 0.72 mg/100 ml at 12 months. On the other hand vitamin C mean levels lowered from 0.93 mg/100 ml in cord blood to 0.77 mg/100 ml at 6 months and to 0.73 mg/100 ml at 12 months. The rise of vitamin E values could be explained by the early use of infant solid foods with high vitamin and mineral content and by the increase of serum lipoproteins. Except at 3 days after delivery there were no individual values of serum vitamin E below the acceptable 0.35 mg/100 ml limit. However, serum vitamin C levels compatible with a moderate risk were very often observed, i.e., in 27.1% of infants at 6 months and in 30.5% at 1 year. Thus, vitamin E intake in infants was satisfactory with the usual diet but not vitamin C for which blood levels were not adequate. In view of these findings it appears necessary to evaluate periodically the vitamin E as well as vitamin C status in the infant population.

Nutrient intake patterns and nutritional status with regard to relative weight in early infancy.

To examine whether or not obesity in later life is related to feeding practice in early infancy, daily nutrient intake was studied in relation to relative weight in a cohort of 170 healthy infants from birth to 3 yr of age. Dietary records were made monthly for the first 6 months and at 3-monthly intervals thereafter, always covering the week preceding anthropometric measurements. The frequency distribution of relative weight varied according to age and sex; the infants did not remain in the same relative weight group during the observed period. When comparing the relative weight at 6 and 36 months, the coefficients of correlation were rather weak for both sexes (r = 0.33 and 0.35). There were no significant differences in the history of breast-feeding according to relative weight. The mean energy intake per kg of body weight was always lower in infants with relative weight above 105% of expected weight and fats and carbohydrates were consumed less in the same group. There were no differences in protein intake according to relative weight, although this intake was always higher than the recommended nutrient intake. Daily intake of zinc was comparable in all weight groups. Results indicate that the infants with above-average relative weights did not consume greater quantities of principal nutrients. The results, therefore, do not support the hypothesis that implicates overfeeding in early infancy as a major cause of obesity in later life.

Influence of exercise training on tissue chromium concentrations in the rat.

This study reports on the effects of exercise training on the chromium concentrations in the heart, liver, kidney, and gastrocnemius muscle of normal Sprague-Dawley rats. A pair-fed (to the trained rats' intake) and a preexperimental group were also studied in order to control food intake and to ascertain any age-related influence on tissue chromium levels, respectively. Four groups of animals were examined: exercise-trained, pair-fed, preexperimental, and sedentary control. Chromium determination was performed by flameless atomic absorption spectrophotometry. The results from this study show that exercise training increases while pair-feeding and normal aging both decrease chromium levels in tissues. It is suggested that the male Sprague-Dawley rat adapts to exercise training by enhancing tissue levels of chromium or by simply maintaining the high levels of the element found at a younger age.

Biochemical indices of nutritional status in maternal, cord, and early neonatal blood.

The nutritional status of 556 infants born in good health was measured by selected biochemical parameters in maternal venous blood, in mixed arteriovenous cord blood at delivery, and in infant's capillary blood collected at 5 days. The determinations indicating nutritional status were: Hb, hematocrit, protein, cholesterol, triglycerides, vitamins A, C, E, and folic acid, iron, calcium and magnesium. In maternal venous blood, a significant number of women were found to be deficient; 3.4% had Hb below 9.5 g/dl; 6.1% had hematocrit less than 30%; 4.0% had total protein below 5.5 g/dl; 7.0% had vitamin C below 0.20 mg/dl; 3.0% were deficient in iron (less than 40 microgram/dl), 3.6% in folic acid (less than 2.0 ng/ml) and 5.2% in calcium (less than 7.5 mg/dl). Significant correlations were more frequent between maternal and cord blood than in other comparisons. An influence of parity and maternal age was more evident for vitamin C in cord blood than in maternal venous blood. Iron in maternal and cord blood decreased in relation to parity.

Maternal cigarette smoking and fetal oxygen transport: a study of P50, 2,3-diphosphoglycerate, total hemoglobin, hematocrit, and type F hemoglobin in fetal blood.

The current study was undertaken to determine whether the O2 carrying capacity of newborns born to mothers who smoke can accommodate to carbon monoxide poisoning to compensate for the potential tissue hypoxia induced by CO. From a cohort of 1,222 women and newborn infants the total hemogloblin concentration, hematocrit, and carboxyhemoglobin (HbCO) were measured and analyzed with regard to the maternal HbCO level and the number of cigarettes smoked per day. Also, for 100 pairs of mothers, of whom 50 were smokers and 50 nonsmokers, and their newborns, measurements were made of the intraerythrocyte concentration of 2,3-diphosphoglycerate (2,3-DPG), the hemoglobin concentration, and the affinity of hemoglobin for oxygen by determination of O2 tension for 50% of Hb-O2 saturation (P50). The results showed no significant relationship between smoking habits of mothers and their levels of hemoglobin, P50, and 2,3-DPG; only the hematocrit was slightly increased in smoking mothers. However, in fetal blood a significant correlation was found between the number of cigarettes smoked per day and levels of hemoglobin, hematocrit, and P50. The P50 decreased in relationship to the increase in maternal HbCO. The P50 change was brought about by an increase in hemoglobin F found in the fetuses of mothers who smoked. Although all these changes were statistically significant, these mechanisms of acclimatization to CO poisoning appeared trivial in magnitude. It is concluded that the human fetus does not have a biologic capacity to accommodate to maternal cigarette smoking, and therefore the fetus is particularly susceptible to the adverse effects of cigarette smoking.

The measurement of Rivotril in whole blood by gas liquid chromatography.

Rivotril is extracted from blood into an organic solvent mixture, Mogadon, (Nitrazepam) is used as internal standard. The drugs are then back-extracted into acid which is heated to produce the corresponding benzophenones. These are extracted into benzene and separated by gas liquid chromatography with electron capture detection.

Single column high pressure liquid chromatographic determination of drugs in blood.

1. Analysis of anticonvulsants (phenobarbital, diphenylhydantoin and carbamazepine), theophylline and an antiarrhythmic agent (disopyramide) in blood using a simple high pressure liquid chromatography apparatus equipped with a reversed -- phase column is described. A simple extraction of plasma or serum with organic solvent is used to isolate the anticonvulsants and theophylline. Disopyramide is extracted with ether and is further purified by a back extraction into acid. 2. Hexanesulfonic acid -- methanol solutions are used for chromatography of the anticonvulsants and disopyramide while the mobile phase for theophylline is a NH4H2PO4 -- methanol mixture. Chromatographic analysis time for the drugs is approximately 15 minutes. The drugs are monitored by a UV detector at 254 nm except for theophylline which is measured at 280 nm. Quantitation is accomplished by comparison of peak heights with those of internal standards. Quantities of serum or plasma routinely used for analysis are: 200 ul for the anticonvulsants, 100 ul for theophylline and 0.5 ml for disopyramide. Detection limits are less than 1 ug/ml for these quantities.

Simple and rapid system for screening and identification of reducing sugars in urine.

As part of our screening programme for metabolic disorders we needed a rapid, simple, inexpensive means to detect reducing sugars in urine, with a simple but precise test for their identification. Our system comprises a bismuth reduction test for reducing sugars, with unidimensional thin layer chromatography on silica gel and color development with diphenylamine--aniline for definitive identification.

The measurement of volatile chromium in biological materials.

Chromium is an essential trace element in mammals since dietary chromium deficiency results in glucose intolerance due to decreased sensitivity to insulin. In humans, both adults and children with glucose intolerance have been improved by treatment with chromium. Furthermore, chromium deficiency has been implicated as a causative factor in hypercholesterolemia and atherosclerosis. However, little is known of the metabolism of chromium in humans, primarily because of analytical difficulties. The biologically active form of chromium is the "glucose tolerance factor" (GTF) which is a co-ordination complex of trivalent chromium with nicotinic acid and certain amino acids. At physiological pH, ionic chromium as a simple inorganic salt is insoluble in water, but trivalent chromium forms stable complexes with ascorbic acid, amino acids and other substances present in blood and tissue. Chromium is present in serum, bound to protein and also as dialysable or ultrafiltrable chromium (free chromium). The free chromium includes G.T.F. and other coordination complexes and represents the metabolically active form of the element; the ratio free/protein bound chromium in serum varies within the individual according to the diet and the metabolic state.

Hair chromium at delivery in relation to age and number of pregnancies.

To test the hypothesis that chromium deficiency may be cumulative with age and increasing parity, hair chromium levels were measured in 432 women at delivery. Although the levels in general were lower than those found in nonpregnant women there was no correlation between hair chromium level and age or number of pregnancies. Hair zinc levels were also measured to rule out zinc deficiency as a factor.

Studies on the role of taurine in Friedreich's ataxia.

New studies were undertaken to verify the previous findings of increased urinary excretion of taurine, in the basal state and after challenge with a taurine load, in Friedreich's disease. Particular attention was paid to possible causes of error such as weight, muscle mass, creatine and creatinine excretion, variability with time and appropriate control groups. Although the overall findings were confirmed, their interpretation is open to question because of all these factors of error. Many possibilities must still be further explored to account for the apparent taurine retention defect observed in many cases of Friedreich's disease.

Zinc and taurine in Friedreich's ataxia.

Zinc and taurine were measured in urine in the fasting state and following a 4mg/kg load of taurine in subjects with Friedreich's Ataxia (FA), and healthy controls (C), and subjects with Duchenne type muscular dystrophy (MD). Of the FA, 25% had increased fasting excretion of zinc, and 50% had increased excretion of zinc following the taurine load. The MD subjects all had increased zinc excretion at all times. The increased zinc excretion did not correlate with increased excretion of taurine. As an index of zinc deficiency, uptake of zinc by erythrocytes was measured in all subjects and in heterozygotes for FA. The pattern of uptake was abnormal for FA and heterozygotes. Hair analysis for zinc showed that 10 of the 12 FA subjects had low values. We conclude that significant abnormalities in zinc metabolism exist in some, but not all cases of FA. The evidence available does not permit definition of the cause of these abnormalities, whether zinc deficiency or abnormal zinc transport is the primary factor.

Glycosylated hemoglobins in Friedreich's ataxia.

In a study of glycosylated hemoglobins in Friedreich's Ataxia patients and in family members, the level was found to be higher in insulin dependent diabetics than in healthy non-diabetic control subjects (p < 0.01), but was similar to non-ataxic diabetic control subjects. Results for non-diabetic Friedreich's Ataxia patients and siblings were similar to those for non-diabetic control subjects while levels were slightly increased in the heterozygotes. It is concluded that in Friedreich's Ataxia patients and family members (apart from the insulin dependent diabetics), there was no hyperglycemia sufficient to be detected as an increase in glycosylated hemoglobins.

Taurine in cerebrospinal fluid in Friedreich's ataxia.

In a previous study we reported low values of taurine and aspartic acid in the CSF of patients with Friedreich's ataxia, when the results were compared to the literature. Further studies have revealed that unforetold difficulties with the advertised methodology of sequential multi-sample amino acid analysis were responsible for low values in the determination of these two amino acids in the small volumes necessary for CSF. A corrected method is presented. With the latter method the differences disappear for CSF taurine and aspartic acid, but they remain valid for the previously reported blood and urine values in Friedreich's ataxia. GABA levels are also normal in Friedreich's ataxia CSF.

Purine metabolism in Friedreich's ataxia.

In a detailed investigation of nucleotide synthesis, interconversion and degradation, no difference was found between subjects with Friedreich's Ataxia and normal controls. It appears improbable that this disorder is related to a primary defect in purine metabolism.

Glucose tolerance and erythrocyte insulin receptors in Friedreich's ataxia.

Detailed in vivo and in vitro studies of glucose and insulin metabolism in Friedreich's ataxia patients and unaffected family members have further defined the extent of the abnormalities in carbohydrate metabolism. The high incidence of glucose intolerance and a hyperinsulinemic response to a glucose challenge in a high percentage of Friedreich's ataxia patients has been confirmed. An increased incidence of glucose intolerance among heterozygotes is suggested, while the siblings show a more normal distribution of diabetes and a nearly normal insulin response to the glucose tolerance test. Human growth hormone patterns are normal for all groups. Preliminary studies of insulin binding to erythrocytes suggest a difference in the binding characteristics among diabetic Friedreich's ataxia patients, while the binding in the non-diabetic Friedreich's ataxia group is similar to that of non-diabetic controls. Results from a small group of non-diabetic siblings suggest a normal insulin binding, while a tendency toward increased binding at low insulin concentrations among diabetic family members is noted.

Erythrocyte membrane lipids in Friedreich's ataxia.

In a study of the lipid composition of erythrocyte membranes in Friedreich's ataxia, the concentration of the major membrane components (phospholipids, cholesterol and protein) in ataxic patients, family members, and control subjects were found to be the same. The total fatty acid distribution was also normal. However, an altered distribution of phospholipid classes in erythrocytes was noted (an increase of PI + PS and a decrease of PE in Friedreich's ataxia patients).

Oxygen transport in patients with Friedreich's ataxia.

The hypothesis is that an abnormal oxygen-hemoglobin dissociation curve is a primary or a secondary defect in patients with Friedreich's ataxia was investigated in 12 subjects with this disease. Hemoglobin and P50 were measured and compared with age and sex matched controls. The mean hemoglobin concentration was 14.2 g% and the P50 was 26.25 torr for the patients and 13.8 g% and 26.27 torr in the controls. These results indicate that the oxygen transport system is normal in this disease and likely exclude an abnormal oxygen dissociation curve as a primary or a secondary factor in the pathophysiology of the cardiomyopathy and the neuromyopathy found in this disease.

Clinical laboratory findings in Friedreich's ataxia.

All clinical laboratory tests carried out in 4 groups of patients with the diagnosis of typical or atypical Friedreich's ataxia have been found to be within the normal range. In this prospective study of 50 patients, a number of findings previously reported to be abnormal in the literature, have not been confirmed.

Amino acid metabolism in Friedreich's ataxia.

A study of amino acids determined by sequential Multi-sample Amino Acid Automatic Analyzer in plasma, urine and cerebrospinal fluid (CSF) in patients with Friedreich's ataxia and control subjects has revealed a number of mathematically significant variations from normal. Of practical physiological importance are the following: a high urinary excretion of alanine with slightly elevated plasma levels; a low plasma and CSF concentration of aspartic acid in the presence of normal urinary values and finally a low CSF concentration of taurine accompanied by normal plasma levels, but elevated urinary output and renal clearance rates. We postulate that the modifications in alanine and aspartic acid are less specific and probably secondary, but there could be a genetic defect in the membrane transport of taurine and the other beta-amino acids in Friedreich's ataxia.