Elevated plasma concentration of asymmetric dimethylarginine that is reduced by single dose testosterone administration in idiopathic hypogonadotropic hypogonadism patients

Our aim was to investigate whether plasma l-arginine and asymmetric dimethylarginine (ADMA) concentrations and nitric oxide (NO) production are altered in male idiopathic hypogonadotropic hypogonadism (IHH) patients in the hypogonadal state and after single dose testosterone administration compared with those in control subjects. Eighteen newly diagnosed male patients with IHH and 20 healthy volunteer controls matched by age and body mass index were enrolled in the study. Single dose testosterone was administrated im. Initially, pretreatment blood samples were collected after overnight fasting. Posttreatment blood samples were drawn 10 d after the injection. ADMA, l-arginine, and NO were measured in pre- and posttreatment blood samples. The pretreatment ADMA and l-arginine levels were significantly higher, and plasma nitrite plus nitrate (NOx) levels were lower than those in the control group. After 10 d of treatment, ADMA and l-arginine levels were significantly reduced, and NOx levels were significantly increased. There was a significant positive correlation (P < 0.01) between ADMA and l-arginine and a negative correlation between ADMA and NOx levels in patients and controls. In conclusion, the patients with IHH showed elevated plasma ADMA levels associated with a reduction in NO production. Single dose parenteral T administration lowered ADMA concentrations and increased NO production to the control group values.     

Plasma concentrations of nitric oxide and asymmetric dimethylarginine in human alcoholic cirrhosis

BACKGROUND/AIMS: The liver plays a prominent role in the metabolism of asymmetric dimethyl-l-arginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase. This study was designed to determine whether plasma levels of ADMA and NO production are altered in patients with compensated and decompensated alcoholic cirrhosis. METHODS: Plasma levels of l-arginine, ADMA, symmetric dimethylarginine (SDMA) and NO (nitrite plus nitrate, NOx) were measured in nine patients with compensated alcoholic cirrhosis (Child-Pugh A) and 11 patients with advanced cirrhosis (Child-Pugh B-C). Seven healthy volunteers served as controls. RESULTS: ADMA and NOx concentrations in decompensated cirrhosis were higher than in the compensated group and control group (ADMA: 1.12+/-0.08 vs. 0.58+/-0.05 and 0.58+/-0.07micromol/l, respectively; P<0.05; NOx 97.90+/-10.27 vs. 37.42+/-3.91 and 40.43+/-5.30micromol/l, respectively; P<0.05). There was a positive correlation between the clinical score of the patients and concentrations of ADMA (r(2)=0.547, P<0.01) and NOx (r(2)=0.689, P<0.01). SDMA and l-arginine levels were not significantly different between the three groups. CONCLUSIONS: The results suggest that hepatocellular damage is a main determinant of elevated ADMA concentration in advanced alcoholic cirrhosis. By inhibiting NO release from vascular endothelium, ADMA might oppose the peripheral vasodilation caused by excessive NO production in severe cirrhosis.     

Significance of asymmetric dimethylarginine (ADMA) concentrations during coronary circulation in patients with vasospastic angina.

The basal activity of nitric oxide (NO) is reduced in spastic arteries of patients with vasospastic angina (VSA). Elevated concentrations of ADMA are associated with reduced NO production and impaired endothelium-dependent vasodilatation. The aim of this study was to elucidate the role of ADMA and its relationship to NO end-products (NOx; nitrate + nitrite) during coronary circulation in patients with VSA. The plasma ADMA and NOx concentrations during coronary circulation were evaluated in 16 VSA and 16 control patients. Blood samples were obtained from the coronary sinus (V) and the ostium of the left coronary artery (A), and the (V-A) differences of ADMA and NOx were determined. The coronary sinus plasma ADMA concentration in patients with VSA was higher than that in the control. The coronary sinus - arterial (V-A) difference of NOx was negative in the VSA group and approximately zero in the control group (VSA group =-1.4 micromol/L, control group =-0.1 micromol/L, p=0.0005). Furthermore, in the VSA patients, there was a negative correlation between the (V-A) difference of NOx and the basal coronary artery tone at the site of spasm (r=-0.60, p=0.015). A significant negative correlation between the (V-A) differences of NOx and ADMA was observed in patients with VSA (r=-0.52, p<0.05), but not in those of the control. Higher ADMA concentrations might cause the reduced formation of NO that underlies the pathophysiology of coronary vasospasm.     

Presence of Melatonin in the Umbilical Cord Blood of Full-Term Human Newborns

The present study was designed to determine whether melatonin circulates in the umbilical cord blood of healthy human newborns and whether the concentrations of this hormone follow a circadian rhythm at birth. Umbilical cord blood was collected from full-term human newborns at the time of delivery. Serum melatonin was extracted with diethylether and determined by radioimmunoassay by using radioiodinated melatonin and rabbit antimelatonin antiserum. Significant amounts of melatonin were detected in the sera obtained from umbilical cord blood. When serum melatonin concentrations of human newborns were represented over 6-h periods or hour by hour over the 24 h of 1 d, similar hormone concentrations were found consistently. These results indicate that melatonin is present in quite high levels in the umbilical cord blood, which may be, at least in part, of maternal origin. Also, our results suggest the absence of a melatonin circadian rhythm in human newborns, which may reflect an immaturity of the components involved in melatonin synthesis.     

Leptin serum concentrations in healthy neonates within the first week of life: relation to insulin and growth hormone levels, skinfold thickness, body mass index and weight

BACKGROUND AND AIMS: Leptin, the ob gene product, plays a key role in the regulation of body fat mass and weight in adult life. The mechanisms by which maternal and fetal/neonatal weight are regulated during human pregnancy and in early postnatal life are poorly understood. High leptin levels are observed in women during gestation and in cord blood at term. We have hypothesized that high leptin levels at term could represent an important feed-back indicator of nutrient supply. Subsequently, leptin could signal adipose tissue status during late gestation and during early neonatal life. SUBJECTS AND METHODS: 51 healthy newborns were studied. Clinical and auxological data (birth length, weight, and iliac, subscapular, biceps and triceps skinfold thickness) were recorded using a standardized data sheet. Venous cord blood was obtained immediately after birth in all neonates. Subsequently, capillary blood was obtained from the heel from some of the newborns when blood had to be obtained because of signs or symptoms of particular problems such as hypoglycaemia or hyperbilirubinaemia, at the following time points: two to four hours after birth in 51 infants, 56-79 h after birth in 47 infants and 99-128 h after birth in 23 of the newborns. The ratio between the sexes (girls/boys) was similar at all time points. The infants that were included in the study were subsequently found to be normal and healthy after analysis of the clinical and biochemical data. A specific ultrasensitive radioimmunoassay was used to measure leptin, while growth hormone and insulin were measured using commercially available immunoassays. RESULTS: Gestational age was 38-42 weeks, maternal age was 21-42 years. Birth weights ranged from 2480 to 4400 g. All newborns and mothers were subsequently found to be healthy. Leptin levels in venous cord blood was 0.16-6.80 microg/l, median 3. 47 microg/l and in capillary blood shortly after birth 0.26-7.03 microg/l, median 3.89 microg/l. 56-79 h after birth leptin levels had fallen dramatically, range 0.02-1.69 microg/l, median 0.26 microg/l, while 99-128 h after birth, leptin concentrations in capillary blood (0.05-2.61 microg/l, median 0.59 microg/l) had significantly increased when compared to the levels at 56-79 h (P < 0.001). There was a significant correlation between leptin levels in umbilical vein and birth weight of the neonates (r = 0.57, P < 0.03). Multistep regression analysis revealed that weight and skinfold thickness accounted for approximately 35-70% of the variation of leptin levels. Insulin and growth hormone, and glucose and bilirubin however, had no major impact on leptin levels. CONCLUSION: High leptin levels are present in cord blood at birth and in capillary blood shortly after birth. Since leptin levels in cord blood correlate with birth weight it is tempting to speculate that in the fetus as in later life leptin is signalling expansion of fat stores. Most importantly, we now report that leptin levels are high in the fetus but decline rapidly and dramatically after birth in healthy neonates. This may be important for the stimulation of feeding behaviour and the acquisition of energy homeostasis in the neonate.     

Amelioration of vascular endothelial dysfunction in obstructive sleep apnea syndrome by nasal continuous positive airway pressure--possible involvement of nitric oxide and asymmetric NG, NG-dimethylarginine.

BACKGROUND: Asymmetric NG,NG-dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase and its plasma concentration is elevated in patients with cardiovascular risk factors, including hyperlipidemia, hypertension, diabetes, and hyperhomocysteinemia. Obstructive sleep apnea syndrome (OSAS) has been attracting attention as a risk factor for cardiovascular disorders because it often accompanies hypertension, obesity, glucose impairment, and dyslipidemia, all of which are factors in metabolic syndrome and risk factors for cardiovascular disease. METHODS AND RESULTS: In the present study, flow-mediated vasodilatation (FMD) of the brachial artery and plasma concentrations of ADMA were measured before and after nasal continuous positive airway pressure (nCPAP) therapy, which abrogates apnea, in 10 male patients aged 36-69 years old, who were given a diagnosis of OSAS by polysomnography. The percent FMD (%FMD) improved significantly from 3.3+/-0.3% to 5.8+/-0.4% (p<0.01) and 6.6+/-0.3% (p<0.01), before, 1 week, and 4 weeks after nCPAP, respectively. At the same time, the plasma NOx concentrations, metabolites of NO, tended to increase, but the plasma ADMA concentration decreased inversely to %FMD and NOx. A negative correlation between %FMD and plasma ADMA concentration, and a positive correlation between %FMD and plasma NOx concentrations were observed. CONCLUSION: Nasal CPAP improves endothelial function, in part by the decreasing ADMA concentration, thereby potentiating NO production.     

Salt loading on plasma asymmetrical dimethylarginine and the protective role of potassium supplement in normotensive salt-sensitive asians

Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase. Because endothelial NO pathway is compromised in patients with salt-sensitive hypertension, we investigated whether the plasma ADMA can be modulated by chronic salt loading in normotensive salt-sensitive persons and its relationship with NO, and we further determined whether or not dietary potassium supplementation can reverse them. Sixty normotensive subjects (aged 20 to 60 years) were selected from a rural community of Northern China. All of the people were sequentially maintained on a low-salt diet for 7 days (3 g/day, NaCl), then a high-salt diet for 7 days (18 g/day), and high-salt diet with potassium supplementation for another 7 days (4.5 g/day, KCl). After salt loading, the plasma ADMA concentrations increased significantly in salt-sensitive subjects (0.89+/-0.02 micromol/L versus 0.51+/-0.02 micromol/L; P<0.05), whereas the plasma NOx levels reduced considerably (41.8+/-2.1 micromol/L versus 63.5+/-2.1 micromol/L; P<0.01). All of the abnormalities normalized when dietary potassium were supplemented (0.52+/-0.03 micromol/L versus 0.89+/-0.02 micromol/L for ADMA and 58.1+/-0.9 micromol/L versus 41.8+/-2.1 micromol/L for NOx). Statistically significant correlations were found among plasma ADMA level, the mean blood pressure, and the level of NO after salt loading in normotensive salt sensitive individuals. Our study indicates that high dietary potassium intake reduces blood pressure and ADMA levels while increasing NO bioactivity in normotensive salt-sensitive but not salt-resistant Asian subjects after salt loading.     

Progesterone, 20 alpha-dihydroprogesterone and 20 beta-dihydroprogesterone in mother and child at birth.

In 14 healthy pregnant women at term progesterone (P) and 20 alpha-dihydroprogesterone (20 alpha-DHP) were determined by radioimmunoassay both in the maternal and foetal compartments. The average concentrations were as follows (ng/ml blood or ng/g wet weight tissue): peripheral maternal blood P 56 +/- 26, 20 alpha-DHP 16 +/- 8; placental tissue P 2514 +/- 1516, 20 alpha-DHP 429 +/- 412; placental blood P 365 +/- 160, 20 alpha-DHP 35 +/- 18; blood of the umbilical vein P 388 +/- 121, 20 alpha-DHP 33 +/- 15; blood of the umbilical arteries P 162 +/- 62, 20 alpha-DHP 28 +/- 10. In 5 healthy pregnant women at term progesterone (P), 20 alpha-dihydroprogesterone (20 alpha-DHP) and 20 beta-dihydroprogesterone (20 beta-DHP) were also determined by gas-liquid chromatography both in the maternal and foetal compartments. The average concentrations were as follows (ng/ml plasma or ng/g wet weight tissue): peripheral maternal plasma P 129 +/- 49, 20 alpha-DHP 15 +/- 15, 20 beta-DHP 1.7 +/- 0.9; placental tissue P 5060 +/- 1435, 20 alpha-DHP 230 +/- 158, 20 beta-DHP 38 +/- 30; placental plasma P 723 +/- 245, 20 alpha-DHP 24 +/- 13, 20 beta-DHP 1.0 +/- 0.1; plasma of the umbilical vein P 740 +/- 227, 20 alpha-DHP 17 +/- 3, 20 beta-DHP 1.2 +/- 0.3; plasma of the umbilical arteries P 324 +/- 94, 20 alpha-DHP 17 +/- 5, 20 beta-DHP 2.6 +/- 2.1. These results show that, contrary to the progesterone concentrations, no significant difference exists in the concentrations of 20 alpha-DHP and 20 beta-DHP between the blood from the umbilical vein and arteries. Furthermore, no significant difference could be found in the concentrations of P and 20 alpha-DHP between the sexes in either the blood from the umbilical vein or from the umbilical arteries.     

Plasma markers of NO synthase activity in women after ovarian hyperstimulation: influence of estradiol on ADMA

The beneficial effects of estrogen on vasculature are partially explained by an estrogen-induced increase in nitric oxide (NO) synthesis. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of NO synthase. In the present study, the effect of 17beta-estradiol (E2) on ADMA and NO synthesis was investigated both in vivo and in vitro. Plasma NO and ADMA levels were measured in healthy women at a low menstrual estrogenic stage (E2 < 100 pg/ml) and in women who were undergoing ovarian hyperstimulation (E2 > 2000 pg/ml) before in vitro fertilization embryo transfer. Primary human umbilical vein endothelial cell (HUVEC) cultures were incubated with and without 100 nM E2 for 24 hours and the NO and ADMA levels of the media were measured. A nitric oxide analyzer was used for the detection of NO metabolites. ADMA and L-arginine were measured by high-performance liquid chromatography after precolumn derivatization with o-phthaldialdehyde. The IVF patients with high plasma E2 concentrations had significantly lower (48%, n = 12) plasma ADMA and higher (56%, n = 14) NO levels than the women at a low estrogenic stage. The incubation of HUVEC cultures with estradiol resulted in a significant decrease (47%, n = 10) in ADMA and an increase (46%, n = 10) in NO concentration in the culture media. Estradiol, by reducing ADMA, may therefore facilitate NO synthesis in endothelial cells. The protective effects of estradiol on vasculature may partly be related to a reduction in ADMA levels.     

Altered metabolisms of mediators controlling vascular function and enhanced oxidative stress in asymptomatic children with congenital portosystemic venous shunt

Children with congenital portosystemic venous shunt (PSVS) are at risk for developing pulmonary hypertension, irrespective of the severity of portal hypertension or liver damage. Altered metabolisms of nitric oxide (NO) and endothelin-1 (ET-1), which are linked with oxidative stress and control vascular tone, might contribute to the vascular disturbance. This study examined 14 children (aged 1-5 years) with congenital PSVS lacking major liver damage and portal hypertension. Serum levels of nitrite/nitrate (NOx) as stable metabolites of NO, and of asymmetric dimethylarginine (ADMA) as an endogenous NO synthase inhibitor were determined, along with the plasma level of ET-1. Oxidative stress, which might affect the production of such mediators, was also examined using specific urinary and blood markers. The NOx levels were significantly lower in affected children than in the age-matched control group, although ET-1 levels were significantly higher than the control levels. In the affected children, the ADMA levels and ADMA/NOx ratios were higher, respectively, by 30% and 130% and showed significant positive correlations with the shunt ratios. Oxidative stress markers, including plasma thiobarbiturate reactive substances and urinary acrolein-lysine and 8-hydroxy-2′-deoxyguanosine, were significantly higher in affected children than in the control group, consistent with them being subjected to enhanced oxidative stress. These results suggest the presence of altered metabolisms of vascular mediators and enhanced oxidative stress in asymptomatic preschool children with congenital PSVS.     

Circulating tissue factor, tissue factor pathway inhibitor and D-dimer in umbilical cord blood of normal term neonates and adult plasma.

The investigation of many hemostatic defects in newborns is restricted by the lack of normal reference values. The coagulation system of the neonate differs in many ways from that of the adult. The present study was designed to compare the concentrations of tissue factor (TF), tissue factor pathway inhibitor (TFPI) and D-dimer (DD) in the umbilical cord blood of healthy newborns and in adult plasma. TF antigen was quantified using an in-house enzyme-linked immunosorbent assay, whereas TFPI and DD levels were measured with commercial kits. The mean TF level in cord blood (mean standard deviation, 183.94 103.63 pg/ml) was significantly higher ( = 0.008) than that in adults (136.64 65.09 pg/ml). Cord blood exhibited enhanced fibrinolysis, as was reflected by a significantly higher level of DD (924.57 733.87 ng/ml, 0.001) than that in adults (45.57 17.21 ng/ml). Conversely, cord blood (30.88 10.16 ng/ml) demonstrated significantly lower ( 0.001) TFPI levels than that in adults (55.77 21.16 ng/ml). However, no significant differences of these three hemostatic markers were noted between both gender groups in newborns and adults. Our findings indicate that an active and dynamic state of hemostasis exists in cord blood, as the fluidity of cord blood remains preserved in the presence of birth injury.     

Adiponectin in human cord blood: relation to fetal birth weight and gender

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The aim of this study was to examine whether adiponectin is present in human fetal blood, to define its association with fetal birth weight, and to evaluate whether dynamic changes in adiponectin levels occur during the early neonatal period. Cord blood adiponectin levels were extremely high (71.0 +/- 21.0 microg/ml; n = 51) compared with serum levels in children and adults and positively correlated with fetal birth weights (r = 0.4; P < 0.01). No significant differences in adiponectin levels were found between female and male neonates. In addition, there was no correlation between cord adiponectin levels and maternal body mass index, cord leptin, or insulin levels. Cord adiponectin levels were significantly higher compared with maternal levels at birth (61.1 +/- 19.0 vs. 17.6 +/- 4.9 microg/ml; P < 0.001; n = 17), and no correlation was found between cord and maternal adiponectin levels. There were no significant differences between adiponectin levels at birth and 4 d postpartum (61.1 +/- 19.0 vs. 63.8 +/- 22.0 microg/ml; n = 17). These findings indicate that adiponectin in cord blood is derived from fetal and not from placental or maternal tissues. The high adiponectin levels in newborns compared with adults may be due to lack of negative feedback on adiponectin production resulting from lack of adipocyte hypertrophy, low percentage of body fat, or a different distribution of fat depots in the newborns.     

Plasma adiponectin levels in newborns are higher than those in adults and positively correlated with birth weight

OBJECTIVE: The aim of this study was to examine plasma adiponectin concentrations during perinatal the period and their correlations with fetal anthropometric parameters and other hormones. DESIGN: Venous cord blood samples were obtained from 59 full-term healthy newborns (36 males and 23 females, gestational age 37.0-41.4 weeks, birth weight 2,146-4,326 g, birth length 44.0-54.5 cm). The blood samples were also obtained from 15 neonates (postnatal day 3-7) whose cord blood had already been collected and the changes in adiponectin concentrations were examined. MEASUREMENTS: The adiponectin concentration was determined by enzyme-linked immunosorbent assay. The leptin concentration was determined by radioimmunoassay. Insulin, GH and IGF-1 concentrations were determined by immunoradiometric assays. RESULTS: The plasma adiponectin concentrations in cord blood ranged from 6.0 to 55.8 microg/ml (median 22.4 microg/ml), which were much higher than those in normal-weight adults (P < 0.0001). In contrast to the findings in adults, these values were positively correlated with birth weight (r = 0.43, P = 0.0005), body mass index (r = 0.44, P = 0.0005), birth weight/birth length ratio (r = 0.46, P = 0.0002) and the leptin concentrations (r = 0.39, P = 0.004). When the effects of fat mass-related anthropometric parameters such as the birth weight/birth length ratio were controlled, plasma adiponectin concentrations had a significant inverse correlation with insulin concentrations (r = -0.35, P = 0.01). There was no significant gender difference in adiponectin concentrations among newborns. The adiponectin concentrations in neonates (postnatal day 3-7) did not change significantly compared with those in cord blood. CONCLUSIONS: In contrast to the findings in adults, these results suggest that the adiponectin concentration increases with the mass of fetal fat.     

T-cell receptor repertoire and function in umbilical cord blood lymphocytes from newborns of type 1 diabetic mothers

Abstract Recent observations show that the development of the human fetal immune system is susceptible to conditions of the maternal immune system and vice versa. To investigate the impact of type 1 diabetes mellitus in pregnant women on the maturation of the immune system of their newborn infants, the umbilical cord blood (UCB) T-cell repertoire at birth was analysed for clonal or oligoclonal expansions and TCRBV gene usage. Quantitative PCR using TCRBV family-specific probes and the spectratyping method were used. The extent of oligoclonal expansions observed in cord blood was markedly lower than in peripheral blood of the diabetic mothers and healthy adults. Functional analysis revealed that UCB T cells from newborns of both type 1 diabetic and gestational diabetic mothers are mature and can be readily stimulated by superantigens and phytohemagglutinin in vitro. No significant differences of the clonal contingent and the TCRBV usage were found in newborns of type 1 diabetic mothers when compared to newborns of gestational diabetic mothers, independent from the presence or absence of islet autoantigens. Our findings indicate that the immune system of type 1 diabetic mothers has no major effects on the TCR repertoire of the newborn infants. In that respect, no evidence was found for superantigen-activated T cells, nor was chronic hyperglycaemia per se found to alter either T-cell repertoire or functional activity.     

Relationships between placental GH concentration and maternal smoking, newborn gender, and maternal leptin: possible implications for birth weight

The control of fetal growth depends on multiple hormones, including both IGF-I and placental GH (PGH) in the mother, and IGF-I rather than pituitary GH (pitGH) in the fetus. Leptin, which is produced by adipocytes and syncitiotrophoblast cells, has also been thought to influence fetal growth by an as yet unknown mechanism. This study assessed the relationships between the GH-IGF-I axis in mothers and newborns, and maternal smoking, neonate gender, and maternal and fetal leptin. We collected blood in 87 mothers at the onset of labor and cord blood immediately after birth in their 87 healthy full-term newborns. GH concentrations were log(10) transformed, and data were expressed as the geometric mean (-1, +1 tolerance factor). PGH was lower in the 30 smoking mothers, as compared with the 57 nonsmoking mothers [18.2 (11.5; 28.6) vs. 27.0 (15.1; 48.2) microg/liter, P < 0.01]. Cord blood IGF-I was lower in neonates from smoking mothers (90 +/- 44 vs. 135 +/- 65 microg/liter, mean +/- SD, P < 0.01), consistent with their lower birth weight percentile (P < 0.01). A gender effect was observed for PGH, which was higher when the newborn was female, and for newborn pitGH and newborn leptin, which were, respectively, lower and higher in females, even after adjustment for birth weight and maternal smoking category (P < 0.05 for all comparisons). Multiple regression analyses identified maternal leptin as a negative predictor of PGH (P < 0.05) and newborn leptin as a positive predictor of newborn IGF-I (P < 0.05). Maternal smoking is associated to decreased maternal PGH and cord blood IGF-I concentrations. A sexual dimorphism for PGH, newborn pitGH, and newborn leptin exists at the time of birth, but its physiological significance remains to be studied. The relationships between maternal leptin and PGH and between cord blood leptin and IGF-I are consistent with the hypothesis that leptin could contribute to the control of fetal growth.     

Cardioprotective effect of a biofermented nutraceutical on endothelial function in healthy middle-aged subjects

We tested a biofermented nutraceutical (FPP) that has been previously shown to positively modulate nitric oxide (NO). Forty-two healthy middle-aged subjects were given 3 grams of FPP three times a day for 6 weeks, and tests were repeated at 3 and 6 weeks; the control group was given a placebo. Flow-mediated dilation (FMD) was measured together with NO compounds (nitrogen oxides [NOx]: NO(2)(-)+NO(3)(-)) plasma levels and asymmetrical dimethylarginine (ADMA). In the interventional group, overall FMD significantly increased from 4.2% to 7.3% (p<0.05 vs. placebo). A significant increase in plasma NO and a decrease in ADMA were detected after consumption of FPP (p<0.01). Although larger studies are awaited, it appears that, at least in healthy individuals, such nutraceutical intervention by positively acting on significant cardiovascular parameters can be considered in the armamentarium of a proactive age-management strategy.     

Reversible sequestration of nitric oxide by hemoglobin during hemodialysis in end-stage renal disease

BACKGROUND: During hemodialysis, patients whose plasma concentrations of nitric oxide (NO) products increase reportedly experience hypotension. Therefore, whether NO bound to hemoglobin (Hb) could contribute to various clinical and laboratory changes during hemodialysis was explored in patients with end-stage renal disease (ESRD). METHODS: Ten patients were studied during 3 hemodialysis treatments with samples of blood analyzed for RBC nitrosyl Hb (HbNO), L-arginine, asymmetric dimethylarginine (ADMA), plasma nitrite+nitrate (NOx), and buffy coat NO synthase (NOS) activities. RESULTS: HbNO before and during hemodialysis varied considerably. Those with higher predialysis levels had lower HbNO values during dialysis, whereas HbNO levels in those with lower levels before dialysis increased. Plasma NOx did not correlate with HbNO, but change in HbNO in the first hour and change in NOx in the first 2 hours correlated with drop in diastolic and systolic blood pressures (BP), respectively. HbNO concentrations increased in patients with >35% drop in systolic BP, whereas in those with <35% drop, HbNO concentrations decreased. HbNO levels adjusted by the hematocrit showed a drop in HbNO for the <35% group and a >3-fold increase in the >35% group. HbNO levels were higher in men than in women, and levels and changes correlated with the hematocrit, skin temperatures, plasma ADMA, arginine, and buffy coat NOS. CONCLUSIONS: In patients with >35% drop in systolic BP, NO was scavenged by Hb in the circulating RBCs, undoubtedly attenuating the degree of hypotension. These data indicate that the amount of NO that is scavenged or released by Hb in the circulating RBCS during dialysis is highly variable and reversible. Various predialysis factors relate to the concentration of HbNO before and during dialysis, which in turn influence clinical findings that occur during the interdialytic period.     

Adrenocorticotropic hormone and catecholamines in maternal, umbilical and neonatal plasma in relation to vaginal delivery

The aim of this study was to evaluate the effect of vaginal delivery on both ACTH and catecholamines (DA, NE, E) secretion in the mother, the fetus (umbilical artery) and the newborn. Blood samples were obtained from 19 normal pregnant women and the corresponding umbilical cords, and from the newborns. Seventeen normal nonpregnant women, matched for age and parity, were also included in the study as "nonpregnant controls". The results demonstrate that in the mother, plasma catecholamines (CA) concentrations during labor and delivery are elevated above the values reported for normal nonpregnant women and there is a predominant E response. The concentrations of CA in umbilical arteries are very high compared to those in the corresponding mother and they fall rapidly after birth. Unlike that in the mother, the predominant CA response to parturition in the fetus and newborn infant is NE. The extraction rate of DA, NE and E from placenta is approximately 60%. The peripheral plasma levels of ACTH in pregnant women during labor are twice and 10 times as high as those observed in the corresponding umbilical arteries and in nonpregnant women respectively. At delivery they increase further. No significant differences are found between the values measured in the arterial cord blood and those in the venous cord blood and in the newborns. A way of explaining the prevalence of E and the higher ACTH/E ratio found in the mother in comparison with the fetus could be that in the mother the stress response to parturition is regulated mainly by the pituitary-adrenal axis, whereas in the fetus there is a prevalent stimulation of the sympathetic nervous system.     

Cord blood leptin concentrations in relation to intrauterine growth

OBJECTIVE: Leptin, a hormone that signals the amount of energy stores to the brain, has recently been shown to play a role in the regulation of several hypothalamic pituitary axes, including the growth hormone axis. To investigate a potential association between cord blood leptin concentrations and intrauterine growth we measured leptin concentrations in the cord blood of small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) healthy newborns. PATIENTS AND MEASUREMENTS: Cord blood leptin concentrations were evaluated in 25 SGA, 100 AGA, and 45 LGA, neonates. RESULTS: Leptin was detectable in all newborns in concentrations comparable with those found in adults. Moreover, SGA newborns had lower leptin concentrations (3.70 +/- 1.81 micrograms/l) than AGA (5.65 +/- 4.98 micrograms/l) and LGA newborns (11.99 +/- 7.06 micrograms/ l)(P < 0.01). Cord blood leptin concentrations were significantly associated with ponderal index, cord blood insulin concentrations, placental weight and maternal serum leptin concentrations. Importantly, the association between cord blood leptin concentrations and intrauterine growth status persisted after adjusting for adiposity, placental weight, maternal serum leptin concentrations and cord blood insulin concentrations. CONCLUSIONS: Cord blood leptin concentrations are independently associated with intrauterine growth. Future studies are needed to elucidate the underlying mechanism and clarify the role of leptin in regulating growth and controlling appetite in newborns.     

Maternal-fetal transfer of melatonin in pregnant women near term

Abstract: Our objective was to evaluate the maternal-fetal transfer of melatonin in pregnant women. Serum melatonin concentration was measured by high-performance liquid chromatography with electrochemical detection in a maternal vein and in the umbilical artery and umbilical vein at the time of birth. Blood samples were obtained from 12 women who had spontaneously delivered vaginally at night. A single oral dose of melatonin was administered to each of 33 patients who underwent a cesarean section, and. blood samples were taken at 1,2, 3, or 4 hr after the administration of melatonin at delivery. Cesarean section was performed between 1300 and 1500 hr. The mean melatonin concentrations of melatonin in maternal peripheral venous blood and umbilical arterial and umbilical venous blood did not differ significantly, and positive correlations in the serum levels of melatonin were observed between the three sources of blood. The oral administration of 3 mg of melatonin to pregnant women led to marked increases in the serum levels of melatonin, with maximum levels observed 2 hr (21.84 ± 2.09 ng/ml) after drug administration. Changes in serum levels of melatonin in the umbilical vein and artery resembled those found in the maternal vein. Serum melatonin concentrations did not differ significantly between the maternal vein and the umbilical veins. Serum levels of melatonin in the umbilical vein after the administration of melatonin were significantly and closely correlated with those in the maternal vein (r = 0.924, ( P < 0.001). These results suggest that, in humans, melatonin is transferred from the maternal to the fetal circulation both easily and rapidly. A potential for the therapeutic use of melatonin as an antioxidant exists in the patients with preeclampsia.