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Biomedical subjects

P Mena

Publications and source records attributed to P Mena.

At least 19 recordsLinked to original sources

Essential fatty acid metabolism in the micropremie.

Lipids are structural components of all tissues and are indispensable for cell membrane synthesis. The brain, retina, and other neural tissues are particularly rich in LCPUFAs, affecting neural structural development and function. LCPUFAs serve also as specific precursors for eicosanoid production (prostaglandins, prostacyclins, thromboxanes, and leukotrienes). These autocrine and paracrine mediators are powerful regulators of numerous cell and tissue functions (e.g., thrombocyte aggregation, inflammatory reactions, and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction, uterine contraction). Dietary lipid intake affects cholesterol metabolism at an early age and is associated with cardiovascular morbidity and mortality in later life. Over recent years, the role of fatty acids in modulating signal transduction and regulating gene expression have been described, emphasizing the complex of fatty acid effects. Dietary fatty acids, especially LCPUFA, can have significant effects in the modulation of developmental processes affecting the clinical outcomes of extremely premature infants.

Fatty Acids, Essential↗

Essential fatty acids in early life: structural and functional role.

Essential fatty acids (EFA) are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LCPUFA). These fatty acids serve as specific precursors for eicosanoids that regulate numerous cell and organ functions. Results from animal and recent human studies support the essential nature of n-3 EFA in addition to the well-established role of n-6 EFA for human subjects, particularly in early life. The most significant effects relate to neural development and maturation of sensory systems. Recent studies using stable-isotope-labelled tracers demonstrate that even preterm infants are able to form arachidonic acid (AA) and docosahexaenoic acid (DHA), but that synthesis is extremely low. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation, and retinal and nervous system development. Regulation of gene expression by LCPUFA occurs at the transcriptional level and is mediated by nuclear transcription factors activated by fatty acids. These nuclear receptors are part of the steroid hormone receptor family. Two types of polyunsaturated fatty acid responsive transcription factors have been characterized, the peroxisome proliferator-activated receptor (PPAR) and the hepatic nuclear factor 4alpha. DHA also has significant effects on photoreceptor membranes involved in the signal transduction process, rhodopsin activation, and rod and cone development. Comprehensive clinical studies have shown that dietary supplementation with marine oil or single-cell oils, sources of LCPUFA, results in increased blood levels of DHA and AA, as well as an associated improvement in visual function in formula-fed premature infants to match that of human milk-fed infant. Recent clinical trials convincingly support LCPUFA supplementation of preterm infant formulations and possibly term formula to mimic human milk composition.

Animals↗

Long chain polyunsaturated fatty acid formation in neonates: effect of gestational age and intrauterine growth.

The present study was designed to evaluate the effect of gestational age and intrauterine growth on the long chain polyunsaturated fatty acid (LCP) synthesis from dietary precursors in neonates as reflected by plasma pools. These have been considered conditionally essential nutrients for normal growth, sensory maturation, and neurodevelopment. In vivo elongation/desaturation of deuterated d5-linoleic acid (d5-LA) to form arachidonic acid (AA), and d5-alpha-linolenic acid (d5-LNA) to form docosahexaenoic acid (DHA), was studied in 19 preterm appropriate-for-gestational-age (AGA) infants, 11 AGA term, and 11 intrauterine growth-retarded (IUGR) infants. They received a dose of 50 mg/kg body weight of d5-LA and d5-LNA enterally during the first days of life; d5-labeled derivatized fatty acids were determined in blood samples obtained at 24, 48, and 96 h after dosing. Lipids were extracted and fatty acids analyzed by gas chromatography and negative ion mass spectrometry. Mean concentrations, microg/mL, and d5/d0 for n-3 and n-6 precursor and products were computed at various times and were also integrated over the complete study period. Significantly higher time-integrated concentration of d5-AA and d5-DHA were observed in preterm infants relative to the other two groups. Time-integrated enrichment of DHA relative to LNA was 100-fold lower in preterms, 410-fold lower in term, and 27-fold lower in IUGR infants. Similar significant declines in product to precursor enrichments were noted for the n-6 series. A significant negative correlation of AA and DHA formation based on time-integrated d5/d0 ratios with gestational age was noted; product/ precursor enrichment versus gas chromatography for the n-6 series had an r of -0.5, p = 0.001, and for the n-3 series had an r of -0.6, p = 0.0001. Birth weight or weight adequacy did not add further strength to the relationship. We conclude that LCP formation from deuterated precursors occurs as early as 26 wk gestation, and in fact is more active at earlier gestational ages; growth retardation appears to slow down or diminish LCP formation. No quantitative estimates of LCP synthesis or nutritional sufficiency can be derived from these data.

Embryonic and Fetal Development↗

Essential fatty acids as determinants of lipid requirements in infants, children and adults.

Essential fatty acids (EFA) are the indispensable component of the lipid supply beyond the provision of energy as a fuel for oxidation. They serve as dietary precursors for the formation of prostanoids and other eicosanoids thus are of great significance in health and modulation of disease conditions. Eicosanoids are powerful autocrine and paracrine regulators of cell and tissue functions: thrombocyte aggregation, inflammatory reactions and leukocyte functions, vasoconstriction and vasodilatation, blood pressure, bronchial constriction, and uterine contraction. Recent attention has focused on the effect of n-3 and n-6 long chain EFAs in normal fetal development. Results from human infant studies suggest that n-3 fatty acids are needed for optimal development of visual and brain function. Human milk is the best and only time proven source of fat and dietary essential fatty acids for infant feeding. International recommendations for n-3 and n-6 EFA dietary intake are reviewed and suggested intakes for long chain EFAs are provided.

Adult↗

Requirements for long-chain polyunsaturated fatty acids in the preterm infant.

Dietary long-chain polyunsaturated fatty acids have demonstrable beneficial effects on early development. The effects on neural development are of particular interest. Human milk is the best and only time-proven source of fat and essential fatty acids in the infant diet. Technologic procedures based on chemical and physical separation of the unsaturated fatty acids have permitted the isolation of concentrated sources of docosahexaenoic acid and arachidonic acid for clinical use. Virtually all infant formulas in developed countries have increased the levels of gamma-linolenic acid, and several manufacturers in Europe and in Japan have added docosahexaenoic acid, or docosahexaenoic acid plus arachidonic acid, or have also included gamma-linolenic acid in formulas for preterm and term infants. The efficacy of this practice for preterm infants seems fairly well established. The use of stable isotope methods to evaluate biosynthesis of long-chain polyunsaturated fatty acids from dietary precursors may help to better define optimal amounts and relationships of fatty acids in infant formula.

Fatty Acids, Unsaturated↗

Sex ratio associated with timing of insemination and length of the follicular phase in planned and unplanned pregnancies during use of natural family planning.

This was a multicentred, prospective study of pregnancies among women using natural family planning. The women maintained natural family planning charts of the conception cycle, recording acts of intercourse and signs of ovulation (cervical mucus changes, including peak day and basal body temperature). Charts were used to assess the most probable day of insemination relative to the day of ovulation and length of the follicular phase of the cycle. The sex ratio (males per 100 females) for 947 singleton births was 101.5, not significantly different from the expected value of 105. The sex ratio did not vary consistently or significantly with the estimated timing of insemination relative to the day of ovulation, with the estimated length of the follicular phase or with the planned or unplanned status of the pregnancy. Although these findings may be affected by imprecision of the data, the study suggests that manipulation of the timing of insemination during the cycle cannot be used to affect the sex of offspring.

Family Planning Services↗

Adverse outcomes of planned and unplanned pregnancies among users of natural family planning: a prospective study.

OBJECTIVES: The purpose of this study was to determine prospectively whether unplanned pregnancies are associated with adverse pregnancy outcomes among users of natural family planning. METHODS: Women who became pregnant while using natural family planning were identified in five centers worldwide: there were 373 unplanned and 367 planned pregnancies in this cohort. The subjects were followed up at 16 and 32 weeks' gestation and after delivery. The risks of spontaneous abortion, low birth-weight, and preterm birth were estimated after adjustment by logistic regression. RESULTS: The women with unplanned pregnancies were more likely to be at the extremes of age, to report more medical problems before and during the index pregnancy, and to seek antenatal care later in gestation than the women with planned pregnancies. However, women with planned pregnancies reported a higher rate of spontaneous abortion in previous pregnancies (28.8%) than did women with unplanned pregnancies (12.9%). There were no significant differences in the rates of spontaneous abortion, low birthweight, or preterm birth between the two groups. CONCLUSIONS: No increased risk of adverse pregnancy outcomes was observed among women who experienced an unplanned pregnancy while using natural family planning.

Abortion, Spontaneous↗

Arachidonic and docosahexaenoic acids are biosynthesized from their 18-carbon precursors in human infants.

It is becoming clear that an adequate level of long-chain highly unsaturated fatty acids in the nervous system is required for optimal function and development; however, the ability of infants to biosynthesize long-chain fatty acids is unknown. This study explores the capacity of human infants to convert 18-carbon essential fatty acids to their elongated and desaturated forms, in vivo. A newly developed gas chromatography/negative chemical ionization/mass spectrometry method employing 2H-labeled essential fatty acids allowed assessment of this in vivo conversion with very high sensitivity and selectivity. Our results demonstrate that human infants have the capacity to convert dietary essential fatty acids administered enterally as 2H-labeled ethyl esters to their longer-chain derivatives, transport them to plasma, and incorporate them into membrane lipids. The in vivo conversion of linoleic acid (18:2n6) to arachidonic acid (20:4n6) is demonstrated in human beings. All elongases/desaturases necessary for the conversion of linolenic acid (18:3n3) to docosahexaenoic acid (22:6n3) are also active in the first week after birth. Although the absolute amounts of n-3 fatty acid metabolites accumulated in plasma are greater than those of the n-6 family, estimates of the endogenous pools of 18:2n6 and 18:3n3 indicate that n-6 fatty acid conversion rates are greater than those of the n-3 family. While these data clearly demonstrate the capability of infants to biosynthesize 22:6n3, a lipid that is required for optimal neural development, the amounts produced in vivo from 18:3n3 may be inadequate to support the 22:6n3 level observed in breast-fed infants.

Arachidonic Acid↗

Role of essential fatty acids in the function of the developing nervous system.

The basis for n-3 fatty acid essentially in humans includes not only biochemical evidence but functional measures associated with n-3 deficiency in human and nonhuman primates. Functional development of the retina and the occipital cortex are affected by alpha-linolenic acid deficiency and by a lack of docosahexaenoic acid (DHA) in preterm infant formulas and, as reported more recently, in term diets. Functional effects of n-3 supply on sleep-wake cycles and heart rate rhythms support the need for dietary n-3 fatty acids during early development. Our results indicate that n-3 long-chain polyunsaturated fatty acids should be considered provisionally essential for infant nutrition. DHA may also be required by individuals with inherited metabolic defects in elongation and desaturation activity, such as patients with peroxisomal disorders and some forms of retinitis pigmentosa.

Animals↗

Further evidence that infection is an infrequent cause of first trimester spontaneous abortion.

A previous cohort study found no clinical evidence that infection occurred more often in subjects experiencing pregnancy loss compared with those experiencing successful pregnancy [Simpson et al. (1996) Hum. Reprod., 11, 668-672]. Given these surprising findings, we conducted a similar analysis on another cohort also followed prospectively. Using couples practising natural family planning for conception or contraception, information on clinical evidence of infection was gathered beginning with week 5 of gestation. Information on fever and signs of overt infection was specifically sought by interview and physical examination. Frequencies of urinary, vaginal and other infections in subjects experiencing pregnancy loss were 11.1, 9.5 and 8.7% respectively, not significantly different from rates in subjects having liveborns (10.1, 10.2 and 10.3% respectively). Thus, no association between clinical infection and early pregnancy loss (< or = 16 weeks) was observed. Cohort studies utilizing biologically based assays are awaited because extant data do not provide evidence that clinically evident infections play major roles in first trimester pregnancy losses.

Abortion, Spontaneous↗

Changes in plasma enzyme activities in professional racing cyclists.

OBJECTIVE: To reports changes in plasma levels in professional racing cyclists. METHODS: Plasma levels of the intracellular enzymes aspartate aminotransferase, alanine aminotransferase, gamma glutamyl transpeptidase, lactate dehydrogenase, and alkaline phosphatase were measured resting and after exercise in professional cyclists participating in two road races: Vuelta Ciclista a Valencia (800 km, beginning of the cyclist season), and the top rank race Vuelta a España (2700 km, at the end of cyclist season). RESULTS: A significant increase in plasma aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase was observed at the end of the race over the corresponding paired start values (P < 0.05). The increase in plasma lactate dehydrogenase after the race was only statistically significant (P < 0.05) in the Vuelta a España. The longer the duration of the cycle tour race, the greater were the increases in aspartate aminotransferase and alanine aminotransferase levels. The high levels returned to their start values during the overnight resting period. CONCLUSIONS: The presence of these enzymes in the blood is probably due to mechanically damaged muscle cells leaking their contents into the interstitial fluid.

Alanine Transaminase↗

Hepatic and erythrocytic glutathione peroxidase activity in liver diseases.

Hepatic and erythrocytic glutathione peroxidase activity, together with malondialdehyde levels, were determined as indicators of peroxidation in 83 patients from whom liver biopsies had been taken for diagnostic purposes. On histological study, the patients were classified into groups as minimal changes (including normal liver), steatosis, alcoholic hepatitis, hepatic cirrhosis, light to moderately active chronic hepatitis, and severe chronic active hepatitis. The glutathione peroxidase activity in erythrocytes showed no significant changes in any liver disease group. In the hepatic study, an increased activity was observed in steatosis with respect to the minimal changes group, this increased activity induced by the toxic agent in the initial stages of the alcoholic hepatic disease declining as the hepatic damage progressed. There was a negative correlation between the levels of hepatic malondialdehyde and hepatic glutathione peroxidase in subjects with minimal changes. This suggested the existence of an oxidative equilibrium in this group. This equilibrium is broken in the liver disease groups as was manifest in a positive correlation between malondialdehyde and glutathione peroxidase activity.

Erythrocytes↗

Timing of conception and the risk of spontaneous abortion among pregnancies occurring during the use of natural family planning.

OBJECTIVE: Our purpose was to ascertain the effects of timing of conception on the risk of spontaneous abortion. STUDY DESIGN: To assess these effects, women who conceived while using natural family planning were identified in five centers worldwide between 1987 and 1993. Timing of conception was determined from 868 natural family planning charts that recorded day of intercourse and indices of ovulation (cervical mucus peak obtained according to the ovulation method and/or basal body temperature). Conceptions on days - 1 or 0 with respect to the natural family planning estimated day of ovulation were considered to be "optimally timed," and all other conceptions were considered as "non-optimally timed." The rate of spontaneous abortions per 100 pregnancies was examined in relation to timing of conception, ages, reproductive history, and other covariates with bivariate and multivariate statistical methods. RESULTS: There were 88 spontaneous abortions among 868 pregnancies (10.1%). The spontaneous abortion rate was similar for 361 optimally timed conceptions (9.1%) and 507 non-optimally timed conceptions (10.9%). However, among 171 women who had experienced a spontaneous abortion in a prior pregnancy, the rate of spontaneous abortion in the index pregnancy was significantly higher with non-optimally timed conceptions (22.6%) as compared with optimally timed conceptions (7.3%). This association was not observed among 697 women with no history of pregnancy loss. The adjusted relative risk of spontaneous abortion among women with non-optimally timed conceptions and a history of pregnancy loss was 2.35 (95% confidence intervals 1.42 to 3.89). The excess risk of spontaneous abortion was observed with both preovulatory and postovulatory conceptions. CONCLUSIONS: Overall, there is no excess risk of spontaneous abortion among the pregnancies conceived during natural family planning use. However, among women with a history of pregnancy loss, there is an increased risk of spontaneous abortion associated with preovulatory or postovulatory delayed conceptions.

Abortion, Spontaneous↗

Nutritional role of omega-3 fatty acids during the perinatal period.

There is now clear evidence that dietary supplementation of omega-3 fatty acid is essential for normal eye and brain development. Corn oil-based diets induce omega-3 deficiency in preterm infants, affecting retinal responses to light, cortical visual evoked potentials, and behavioral measures of visual acuity. Preterm infants require docosahexanoic acid (DHA) because they are unable to form sufficient quantities from precursors provided by soy oil-based formula products. Human milk provides an ideal source of essential fatty acids for premature infants. There is increasing evidence that premature infant formulas containing vegetable oils should be supplemented with long-chain EFAs to promote optimal retinal and cortical visual development.

Brain↗

HDL-cholesterol increase associated to triglycerides degradation in vitro.

The effect of muscle tissue from rats trained by swimming on the extracellular degradation of triglyceride (TG) rich particles has been studied in vitro. During incubation, there is a progressive decline of the TG concentration in the incubation medium. At the end of the incubation period (90 min), a significantly reduction in the TG levels (p < 0.05) is associated with a significant increase in the high-density lipoprotein (HDL) cholesterol level (p < 0.005). There are no significant changes in total cholesterol levels. The correlation of the TG decline with the HDL-cholesterol increase is significant (r = 0.695, p < 0.05, n = 25). The experimental model used here could be of great interest for the in vitro study of factors affecting lipid levels in plasma.

Adult↗

Urine excretion of androgen hormones in professional racing cyclists.

This study was performed on 16 professional racing cyclists to examine changes in urine concentrations of androgen hormones (testosterone, epitestosterone, androsterone, etiocholanolone, 11-hydroxy-androsterone and 11-hydroxy-etiocholanolone) and plasma sex hormone binding globulin (SHBG) after training and after competition. The urinary concentrations of androgen hormones decreased during the period of training and increased during competition, this being the reverse of what happened to SHBG plasma concentrations. These changes would suggest that physical activity may have an influence on the elimination of androgen hormones and on the synthesis of its transporting protein SHBG.

Androgens↗