The total fatty acid composition of the human retina was studied during early normal development and compared to that found in infancy and in adulthood. The retina of an infant undernourished prenatally and of two malnourished postnatally were also studied and compared to the normal values for the age. The fatty acid patterns of ethanolamine phosphoglycerides (EPG) and choline phosphoglycerides (CPG) were also studied. Total and ethanolamine plasmalogens (EP) were estimated by the aldehyde dimethyl acetal (DMA) content of total lipids and of EPG, respectively. After acid methanolysis, analyses of fatty acid methyl esters (FAME) and of DMA were effected by capillary GLC on a single 30 m long, SP-2330, capillary column. The main developmental fatty acid changes were an increase in 22:6 omega 3, 22:5 omega 3 and 20:3 omega 6 and a decrease in 20:4 omega 6. The 22:6 omega 3/20:4 omega 6 ratio increased in a very significant, parabolical way throughout development. In contrast to the brain, the proportion of ethanolamine plasmalogens decreased with maturation, whereas the ratio 18DMA/16DMA increased. The two postnatally malnourished infants had a very significant increase in retinal 22:5 omega 6, but only the child that had been fed on a very unbalanced omega 3/omega 6 diet since 25 weeks of gestation showed an important decrease in retinal 22:6 omega 3.

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The developmental changes in the fatty acid composition of ethanolamine phosphoglycerides (EPG) and choline phosphoglycerides (CPG) were studied in the liver and brain of 18 newborn infants with gestational ages ranging from 20 to 44 wk. A small group of five newborns receiving total parenteral nutrition (TPN) with high doses of linoleic acid (18:2 omega 6) was also studied and compared to controls of the same gestational age to look for effects on the developmental fatty acid patterns of liver and brain EPG and CPG. TPN with Intralipid 20% was given for 4-12 days, the total fat intake being 14.7-90 g (mean +/- S.D. = 47.1 +/- 29.8 g). The main developmental changes in the liver and brain of the control group were an increase in 22:6 omega 3 (docosahexaenoic acid) at the end of gestation and a linear decrease in 20:4 omega 6 (arachidonic acid) and 18:1 omega 9 (oleic acid) in EPG and CPG. A very good correlation in the percent values of these fatty acids in the brain and liver tissues was obtained. Very significant changes in the fatty acid composition of liver EPG and CPG could be found in the infants receiving TPN with Intralipid-mainly an increase in 18:2 omega 6, a decrease in the linoleate elongation/desaturation to longer members of the series and a decrease in the 22:6 omega 3 levels of liver EPG and CPG. In the brain, only an increase in the 18:2 omega 6 value of CPG, not accompanied by any increase in the longer omega 6 fatty acids, could be detected.(ABSTRACT TRUNCATED AT 250 WORDS)

The purpose of the study was to compare the polyunsaturated fatty acid (PUFA) status in patients with X-linked adrenoleukodystrophy or adrenomyeloneuropathy (X-ALD/AMN) with that in disorders of peroxisome biogenesis (PB). Total fatty acids and plasmalogens were quantified in plasma and red cells from 28 patients with X-ALD/AMN, 26 patients with generalized peroxisomal disorders, and 37 controls. Total fatty acid methyl esters and plasmalogen dimethyl acetals were obtained by direct transmethylation and separated by capillary column gas chromatography. The results confirm previous findings in that docosahexaenoic acid (DHA, 22:6n-3) was greatly decreased in both plasma and erythrocytes from patients with PB disorders. When nutritional conditions were adequate, patients with X-ALD/AMN had normal levels of DHA. A highly significant positive correlation was found between the levels of DHA and those of plasmalogens in peroxisomal patients. As in other tissues, the parent n-6 fatty acid, linoleic acid (LA, 18:2n-6) was significantly increased in red cells from PB patients, whereas arachidonic acid (20:4n-6) was virtually within normal limits. In clear contrast to red cells and other tissues, arachidonate was significantly lower in plasma from PB patients. The decrease in plasma arachidonate and the high tissue levels of LA suggest a defect of delta 6 desaturase and/or delta 5 desaturase in PB patients. The n-6 fatty acids were normal in X-ALD/AMN patients. The present data show that X-ALD/AMN patients do not have the profound PUFA alterations that PB patients have, at least in blood.

The biological effects of dihydrotestosterone (DHT) and testosterone (T) on cultured human fetal epiphyseal chondrocytes were assessed by studying the ability of these androgens to promote DNA synthesis. DNA synthesis was evaluated by measuring [3H]thymidine incorporation into DNA. After 48-h incubation in Ham's F-12 serum-free medium, chrondrocytes were incubated with or without DHT (10(-11)-10(-8) M) or T (10(-11)-10(-8) M) in MCDB-104 serum-free medium for a further 48 h, with the addition of [3H]thymidine (5 microCi/mL) for the last 24 h. In chondrocytes from five male fetuses (12-40 weeks' gestation) DHT and T significantly stimulated DNA synthesis. The maximum stimulatory effect was obtained for DHT at 10(-10) M (P less than 0.01) and for T at 10(-6) M (P less than 0.02). In chondrocytes from four female fetuses the stimulatory effect was significant only for DHT and was maximum at 10(-10) M (P less than 0.02), whereas no effect was observed for T. Cultured chondrocytes from both male and female fetuses show the presence of proteins with high affinity and limited binding capacity (Bmax) for DHT (male fetuses: Bmax, 4.9 +/- 1.9 x 10(-15) M/mg protein; Kd, 0.43 +/- 0.24 x 10(-9) M; female fetuses: Bmax, 4.8 +/- 1.6 x 10(-15) M/mg protein; Kd, 0.63 +/- 0.19 x 10(-9) M) with no significant differences between sexes. In conclusion, our results show that androgens elicit a biological response in cultured human fetal epiphyseal chondrocytes and that DHT-binding sites are present in these cells. DHT, rather than T, seems to be the active androgen. A sex difference in the degree of androgen action is also documented.

Skeletal growth and changes in body composition during growth present important variations; body mass index and lean body mass related to age show important gender differences. The process of ossification is developed in two different ways, endochondral and intramembraneous. The former is characterised by the formation of bone from growth cartilage. Intramembraneous ossification is characterised by the formation of bone from a mesenchymal structure, as occurs with the flat bones of the skull. During childhood and adolescence and up to the acquisition of adult stature, two phenomenons are produced simultaneously: the synthesis of new bone from growth cartilage due to the process of endochondral ossification, and modeling-remodeling of previously synthesized bone. Bone growth and mineralisation of its extracellular matrix are simultaneous phenomenons, the final result being the acquisition and maintenance of body bone mass. A positive calcium balance is necessary during adolescence in order to achieve the maximum peak of bone mass and even with the termination of longitudinal growth of bone, the process of mineralisation can last a further 4 years. Childhood and adolescence are the period of life in which the peak of bone mass must be achieved, and if during this time this does not happen there will be a greater risk for the later development of osteoporosis. Regulation of bone mass is a polygenic process and during recent years studies have been centred on the receptor genes of vitamin D and estrogens. A maximum calcium retention during adolescence may influence the achievement of a high peak of bone mass but at a certain level of calcium intake the calcium retention reaches a plateau. The expression of grams of hydroxyapatite per square centimetre has been used clinically, or expressed in volume as g/cm3. From birth until 3 years, the increase represents approximately 30% of the total increase, from 3 years until the beginning of pubertal development the increase is 20%. During pubertal development there is an increase of 30-40% and from the end of growth until the age of 21 years there is an increase of 15-20%. Both prepubertal boys and girls show a progressive increase of leptin levels during the years prior to the onset of puberty and until Tanner's stage 11 and higher levels are observed in girls in this period, possibly in relation to their earlier onset of puberty. This increase of leptin in girls during pubertal development suggests that leptin may be a link between adipose tissue and puberty.

ExtractThe fatty acids of total phosphoglycerides (TPG), ethanolamine phosphoglycerides (EPG), and choline phosphoglycerides (CPG) were obtained by mild alkaline transmethylation from lipid extracts of whole cerebrum and then analyzed by gas chromatography. A complete brain hemisphere from each of the 34 newborn infants reported previously was homogenized and its lipids extracted according to the procedure specified in that report. As the gestational age of the children went up, a statistically significant increase of the n-3/n-6 ratio and, especially, of the 22:4(n-6)/22:5(n-6) index was observed. Other ratios, such as the n-6/n-9 and the 18:0/18: 1 (n-9), were also studied in the fatty acid patterns of EPG and CPG. Both of them showed significant increases with the gestational age of the infants. The [22 :4(n-6) + 22 : 5(n-6)]/ 20:4(n-6) index, an indicator of the elongation process of arachidonic acid, on the other hand, did not show appreciable changes with maturation in T P G during this period of life. When ethanolamine and choline phosphoglycerides were analyzed separately, however, the elongation of arachidonic acid did rise with the gestational age in the former whereas it decreased in the latter.As intrauterine maturation of the human brain progresses, changes in the polyunsaturated fatty acid patterns, contrary to those observed in undernourished animals, take place. Among these changes, the increase of the n-3 family fatty acids and the decrease of the 22 : 5(n-6), reported in humans during the entire life span, can already be found in such early stages of life as selected for this study and within so narrow a range of gestational ages.

Sources of aluminium loading and exposure in preterm and full-term newborns were studied. Parenteral nutrition solutions were the main source of aluminium representing 88.7% of total aluminium intake. Blood and urine aluminium levels were followed over a 28-day period in a group of 26 preterm and 9 term infants while receiving parenteral nutrition (duration 15.6 +/- 8.7 days) and later when being formula fed. Urine levels were followed up to 13 weeks in a subgroup of the neonates. Serum aluminium levels (0.86 +/- 0.38 mumol/l) and urine aluminium/creatinine ratio (1.52 +/- 0.81 mumol/mmol) were increased when the infants were receiving parenteral nutrition compared with the control group (p < 0.001). The urine aluminium/creatinine ratio remained high up to 10 weeks following withdrawal of parenteral nutrition and suggested tissular loading. This was confirmed after high aluminium levels were found in post-mortem brain and bone samples from two preterm and one full-term infant. We conclude that both preterm and full-term neonates are susceptible to accumulation of aluminium in tissue while receiving parenteral nutrition.