RESUMEN
Objective: Reports relating to maternal-fetal transport kinetics of chromium, an essential trace element in the human pregnancies are scanty. Hence, we thought it interesting to investigate the transport kinetics of this trace element in the human placenta in late gestation in vitro. Methods: Human placentae were collected immediately after delivery from normal uncomplicated pregnancies. Chromium chloride solution (GFS Chem Inc, Ohio, USA) at 10 times the physiological concentrations and antipyrine (Sigma Chem Co., St. Louis, USA) as internal reference marker was injected as a single bolus (100 µl) into the maternal arterial circulation of perfused placental lobules and perfusate samples were collected from maternal and fetal circulations over a study period of 5 minutes. National culture and Tissue collection medium, diluted with Earle's buffered salt solution was used as the perfusate. Serial perfusate samples were collected from fetal venous perfusate for a period of 30 minutes. Chromium concentration in perfusate samples was determined using atomic absorption spectrophotometry and the concentration of reference marker, antipyrine was measured by spectrophotometry. Transport kinetics and transport parameters of study and reference markers were assessed using well-established parameters. Results: Differential transport rates of chromium and antipyrine in 10 perfusions differed significantly for 10 and 50% efflux fractions (ANOVA test, p < .05) while those of 25, 75, and 90% efflux fractions were not significantly different between the study and reference substances. Chromium transport fraction (TF) averaged 54.9% of bolus dose in 10 perfusions while that of antipyrine averaged 89% of bolus dose, representing 61.80% of reference marker TF. The difference observed in TF values of chromium and antipyrine was statistically significant (Student's t-test, p < .05). Pharmacokinetic parameters such as area under the curve, clearance, absorption rate, elimination rate of chromium compared to reference marker was significantly different (ANOVA test, p < .05) between the study and reference substances. Conclusions: Our studies report for the first time maternal-fetal transport kinetics of chromium in human placenta in vitro. Considering the restricted transfer of this essential trace element from maternal to fetal circulation despite its small molecular weight, we hypothesize an active transport of chromium across the human placental membrane. Further studies relating to placental transport kinetics of this trace element in various pregnancy-related disease states are in progress.
Asunto(s)
Cromo/metabolismo , Intercambio Materno-Fetal/fisiología , Placenta/química , Adulto , Antipirina/administración & dosificación , Transporte Biológico/fisiología , Femenino , Humanos , Placenta/metabolismo , EmbarazoRESUMEN
OBJECTIVE: Folate antagonists are widely used in the treatment of various cancerous states. Paucity of data on effect of administration of one such widely used drug, methotrexate (MTX), on the status of essential trace elements and antioxidant enzymes in pregnant women or in pregnant animals prompted us to undertake this study. METHODS: MTX at a concentration of 5 mg/kg body weight was administered intraperitoneally as single dose to pregnant Sprague-Dawley rats for three consequitive days from day 17 of pregnancy. Control group of pregnant rats received single dose of saline instead of the anti-cancer drug on all the 3 days. After receiving the third dose of drug, the treated rats and control group rats were sacrificed, 1 h after intraperitoneal injection of a cocktail of essential trace elements namely, Cu, Se and Zn administered as a single bolus dose. Blood samples were collected 30 min of trace element cocktail injection, after decapitation and concentrations of trace elements in serum samples were determined by atomic absorption spectrophotometry. Concentrations of antioxidant enzymes, such as superoxide dismutase, glutathione peroxidase and total antioxidant status were determined by specific analytical kits, using spectrophotometry. RESULTS: In control group(n = 6), serum concentrations of Cu, Se and Zn averaged 2330.5, 614.8 and 2773.2 microg/l, while in study group (n = 6) the concentrations of trace elements averaged 2294, 596 and 2713 microg/l, respectively. Student's t-test did not show any statistical significance (p > 0.05) between various trace element concentrations in control and treated groups. Cu:Zn ratios of control and treated group of rats did not vary significantly as well. Concentrations of superoxide dismutase, glutathione peroxidase in whole blood samples in control rats averaged 165 and 43,260 U/ml, respectively, while in MTX-treated group of animals the corresponding antioxidant enzymes averaged 330.6 and 67,101 U/ml respectively. SOD and GPX values were significantly higher in drug-treated animals compared to controls (Student's t-test, p < 0.05) However, total antioxidant activity was shown to be significantly lower (Student's t-test; p < 0.05) in the drug-treated group compared to control. CONCLUSIONS: We report for the first time that effect of MTX administration in pregnancy is not associated with significant alteration in disposition of essential trace elements. However, the effect of drug administration on antioxidant enzyme status in pregnant women cannot be excluded while using the drug in clinical states.
Asunto(s)
Antioxidantes/metabolismo , Metotrexato/administración & dosificación , Oligoelementos/sangre , Análisis de Varianza , Animales , Recuento de Células Sanguíneas , Glucemia/metabolismo , Cobre/sangre , Femenino , Antagonistas del Ácido Fólico/administración & dosificación , Glutatión Peroxidasa/sangre , Embarazo , Ratas , Ratas Sprague-Dawley , Selenio/sangre , Espectrofotometría Atómica , Superóxido Dismutasa/sangre , Zinc/sangreRESUMEN
Obesity is well known to be a contributory risk factor for several disease states, including diabetes mellitus. Paucity of data on maternal-foetal status of essential trace elements in obese diabetic pregnancies prompted us to undertake this study. Maternal venous and umbilical arterial and venous blood samples were collected from obese gestational diabetic patients (Body Mass Index (BMI) >30) and control obese pregnant women (BMI>30) at time of spontaneous delivery or caesarean sections and concentrations of essential trace elements such as Cu, Fe, Mo, Se and Zn were determined in various samples by atomic absorption spectrophotometry. Activities of antioxidant enzymes, superoxide dismutase (SOD), glutathione peroxidase (GPX) and total antioxidant (TAO) in maternal and umbilical blood were assessed using appropriate reagent kits. Maternal-foetal disposition and exchange parameters of elements studied were assessed using established criteria. Concentrations of Cu, Fe, Mo, Se and Zn in serum of control obese pregnant women (n=10) averaged 2404, 2663, 11.0, 89.0 and 666 microg/l respectively, while in the obese diabetic group (n=11), the corresponding values averaged 2441, 2580, 13.3, 85.1 and 610 microg/l respectively. Activities of antioxidant enzymes such as SOD, GPX and TAO were not significantly different in maternal veins of control and diabetic groups. Varying differences were noted in the case of antioxidant enzyme activities in umbilical blood samples of control and study groups. We conclude that obesity is not associated with significant alterations in antioxidant enzyme status in gestational diabetes and only with relatively minor alterations in status of some essential trace elements.
Asunto(s)
Cobre/sangre , Diabetes Gestacional/metabolismo , Hierro/sangre , Intercambio Materno-Fetal , Molibdeno/sangre , Obesidad/metabolismo , Complicaciones del Embarazo/metabolismo , Selenio/sangre , Zinc/sangre , Adulto , Puntaje de Apgar , Femenino , Edad Gestacional , Humanos , Recién Nacido , Obesidad/complicaciones , Paridad , EmbarazoRESUMEN
The effect of hyperglycaemic loads on L-leucine transport in the maternal-foetal direction has been investigated in human placenta in vitro, using perfusion of isolated placental lobules. National Culture and Tissue Collection medium diluted with Earle's buffered salt solution was used as the perfusate. (14)C-labelled L-leucine along with tritiated water as reference were injected as a 100-microl bolus into the maternal circulation and serial perfusate samples were collected over a 5-min study period. In 6 successful perfusions, the differential transport rate of leucine for 10, 25, 50, 75 and 90% of efflux in the foetal vein averaged 1.26, 1.10, 1.19, 1.10 and 1.04 times respectively that of reference in the control euglycaemic phase. In the experimental hyperglycaemic phases of 27.8 and 55.6 mM/l, leucine transport for the corresponding efflux periods averaged 1.37, 1.33, 1.28, 1.22 and 1.26 times and 1.16, 0.97, 1.08, 1.08 and 1.08 times respectively that of the reference marker. Analysis of variance (ANOVA) test showed that the difference between the three groups was not statistically significant. In the control euglycaemic phase, leucine transport fraction (TF) averaged 40.90+/-3.51% of corresponding water TF while in experimental hyperglycaemic phases, TF of the amino acid averaged 37.80+/-4.82% and 35.61+/-3.21% of water TF respectively. The difference between the control and hyperglycaemic perfusion phases was not statistically significant. Further, no statistical difference could be shown between the two hyperglycaemic perfusion series themselves. Similarly, kinetic parameters such as absorption rate, elimination rate and absorption rate:elimination rate ratio were not significantly different in the hyperglycaemic perfusion phases compared to control phase. Our studies seem to indicate that leucine transport kinetics in in vitro conditions are not altered significantly in placentas exposed to hyperglycaemic loads.
Asunto(s)
Hiperglucemia/metabolismo , Leucina/farmacocinética , Intercambio Materno-Fetal/fisiología , Placenta/metabolismo , Área Bajo la Curva , Transporte Biológico , Femenino , Humanos , Cinética , Perfusión , Embarazo , Embarazo en Diabéticas/metabolismo , Técnicas de Cultivo de TejidosRESUMEN
OBJECTIVE: Paucity of data relating to transport of amino acids in gestational diabetic pregnancies prompted us to undertake this study. Transport kinetics of a model amino acid, L-leucine was investigated in gestational diabetic pregnancies in vitro, using perfusion of isolated placental lobules. METHODS: Placentae from diabetic and control pregnant women were collected post-partum. Suitable placental lobules were then perfused, using National Culture and Tissue Collection (NCTC) medium, diluted with Earle's buffered salt solution as perfusate. 14C-labelled L-leucine along with tritiated water as reference were injected as a 100 ul bolus into the maternal circulation and serial perfusate samples collected over a 5-minute study period. RESULTS: In 6 successful perfusions, differential transport rate of L-leucine for 10, 25, 50, 75 and 90% of efflux in the fetal vein averaged 1.17, 1.12, 1.22, 1.20 and 1.17 times respectively that of reference in the diabetic group. In the control group (n=6), leucine transport indices for the corresponding efflux periods averaged 1.13, 1.15, 1.18, 1.17 and 1.16 times respectively that of the reference marker. Student's 't' test showed that the difference between the two groups was not statistically significant (p > 0.05) for all the efflux fractions studied. In the diabetic series, leucine transport fraction (TF) averaged 41.2 +/- 4.5% of corresponding water TF while in control group, the amino acid TF averaged 46.5 +/- 6.5% of water TF. The difference between the two series, however was not statistically significant (p > 0.05). Similarly, kinetic parameters as area under the curve, clearance, elimination constant, time for maximum response, absorption rate, and elimination rate in the diabetic and control groups, were not significantly different (p > 0.05) as well. CONCLUSION: Our study seems to indicate that transport kinetics of leucine under in vitro conditions, do not differ significantly in placentae of gestational diabetic women compared to controls.
Asunto(s)
Diabetes Gestacional/sangre , Leucina/metabolismo , Intercambio Materno-Fetal/fisiología , Adulto , Transporte Biológico , Peso al Nacer , Peso Corporal , Femenino , Humanos , Recién Nacido , Cinética , Leucina/sangre , Embarazo , Valores de Referencia , Aumento de PesoRESUMEN
OBJECTIVE: The status of the essential trace elements copper (Cu), iron (Fe), zinc (Zn), selenium (Se) and molybdenum (Mo) has been investigated in maternal and umbilical cord blood in control, uncomplicated pregnancies at term, and the possibility assessed of a relationship between blood levels of these trace elements and newborn weight and placental weight. Fetal-maternal ratios of the elements were also computed to establish baseline values for the Kuwaiti obstetric population. METHODS: Blood samples were collected from a maternal vein, the umbilical artery and umbilical vein of normal pregnant women at the time of spontaneous delivery or Cesarean section, and the concentrations of various trace elements determined by atomic absorption spectrophotometry. RESULTS: The concentration of Cu, Fe, Mo, Se and Zn averaged 2406.1, 3252.1, 11.6, 107.3 and 696.2 microg/l, respectively, in maternal venous blood in the pregnant women (n=39) at term. Umbilical venous/maternal venous ratios of Cu, Fe, Mo, Se and Zn averaged 0.32, 1.96, 1.03, 0.83 and 1.55, respectively. Neonatal birth weight did not correlate with maternal blood levels of the trace elements (p>0.05) in the mother-child pairs studied. However, neonatal weight correlated negatively (p<0.05) with umbilical venous Cu level. Placental weight correlated positively (p<0.05) with Fe and Mo levels and negatively with Zn level in umbilical venous blood. CONCLUSIONS: Our results indicate an active placental transport for Fe and Zn, while Cu, Mo and Se appear to be exchanged passively between mother and fetus. Evaluation of Fe, Mo, Se and Zn levels in maternal and umbilical cord blood does not appear to be useful in the assessment of fetal growth.
Asunto(s)
Peso al Nacer , Sangre Fetal/química , Placentación , Oligoelementos/sangre , Adulto , Femenino , Humanos , Modelos Lineales , Tamaño de los Órganos , Embarazo , Espectrofotometría AtómicaRESUMEN
OBJECTIVE: The status of essential trace elements such as copper, iron, zinc, selenium and molybdenum was investigated in gestational diabetic pregnancies at term, and data were compared to control pregnancies. Fetal/maternal ratios of the elements and copper/zinc ratio were also computed in control and study populations. METHODS: Samples from maternal venous, umbilical artery and umbilical vein were collected from gestational diabetic and control pregnant women, at the time of spontaneous delivery or Cesarean section, and concentrations of various trace elements were determined by atomic absorption spectrophotometry. RESULTS: The concentrations of copper, iron, molybdenum, selenium and zinc averaged 2156.2 microg/l, 2020.1 microg/l, 13.1 microg/l, 102.3 microg/l and 656.2 microg/l, respectively, in maternal venous blood in control pregnant women at term (n=15) while in the corresponding gestational diabetic group (n=15), concentrations of the trace elements averaged 2345.8 microg/l, 2061.6 microg/l, 15.0 microg/l, 75.2 microg/l and 610.3 microg/l, respectively. Student's t test showed that the selenium concentration was significantly lower (p<0.05)in the diabetic group compared to controls. Values of other elements were not significantly different. Umbilical blood/maternal blood ratios of the trace elements showed varying differences. The Cu/Zn ratio was found to be significantly different between umbilical and maternal samples of control and study groups, indicating a possibility of compromised antioxidant function in diabetic pregnancies. CONCLUSIONS: We speculate that altered maternal-fetal status of some essential trace elements in gestational diabetes patients could have deleterious influences on the health of the mother as well as the fetus and newborn.
Asunto(s)
Diabetes Gestacional/sangre , Sangre Fetal/química , Oligoelementos/sangre , Adulto , Antioxidantes/análisis , Femenino , Humanos , Embarazo , Estadísticas no Paramétricas , Oligoelementos/análisisRESUMEN
Transport characteristics of essential trace elements as zinc, copper, selenium and iron have been studied in maternal-fetal direction in normal pregnancies, using in vitro perfusion of human placental lobules. Solutions of trace elements corresponding to twice the physiological concentrations were injected (100 microl bolus) into the maternal arterial perfusate. Serial perfusate samples were collected every 30 sec from venous outflows for a study period of 5 min. Concentrations of these trace elements and their transport kinetics were determined. Transport fractions (TF) of zinc, copper, selenium and iron averaged 0.21, 0.49, 0.55 and 0.10% of maternal load respectively. Other parameters such as area under the curve, clearance, elimination constant, absorption and elimination rates showed some significant differences between the various elements. Copper and selenium appear to be transported passively in maternal-fetal direction, while for iron and zinc, role of active transport for transfer across the human placental membrane cannot be discounted. We speculate that alterations in copper: zinc TR50 (transport rate for 50% efflux) and TF ratios could serve as useful indicators for assessing placental transport status of these essential elements in complicated pregnancy states.
Asunto(s)
Cobre/farmacocinética , Hierro/farmacocinética , Placenta/metabolismo , Selenio/farmacocinética , Zinc/farmacocinética , Femenino , Humanos , EmbarazoRESUMEN
Placental Na(+)/H(+) exchanger (NHE-1), which plays an important role in maintaining fetal and maternal Na+ and H+ homeostasis, is uniquely regulated. However, the role of this protein in type-2 diabetic placentas, and the molecular basis for its unique regulation in normal placenta remain poorly understood. To address these issues, a C-terminus regulatory domain of NHE-1 was cloned and sequenced from normal human placentas, and was used to prepare a GST-fusion protein for raising polyclonal antibodies. For this study, age-matched type 2 diabetic (n=8) and normal (n=8) pregnant women were recruited to investigate the effects of controlled hyperglycemia on the expression of placental NHE-1 at term delivery. The C-terminal sequence in the normal human placental isoform was identical to that reported for other tissues. The antibodies reacted selectively with a 110 kD protein. The level of NHE-1 protein was decreased significantly ( p<0.05) in diabetic placentas, whereas beta-actin, an internal control, remained unaltered. Yield of placental crude microsomes was significantly higher from diabetic placentas. Interestingly, the levels of NHE-1 mRNA and beta-actin mRNA did not change in diabetic pregnancies. Blood pressure values of the mothers in both groups were also normal. The placental mass and weight of babies were slightly increased, whereas the gestational age was lower in diabetic pregnancies. These results suggest that the unique regulation of placental NHE-1 is not due to differences in its C-terminus structure. Lack of a significant correlation between the suppression of NHE-1 and gestational age, placental mass or birth weight in the diabetic pregnancies suggests that suppression is independent of these parameters, and is regulated post-transcriptionally. This change in NHE-1 may contribute to an adequate provision of electrolytes and nutrients to the fetus.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Placenta/metabolismo , Embarazo en Diabéticas/metabolismo , Intercambiadores de Sodio-Hidrógeno/antagonistas & inhibidores , Adulto , Secuencia de Aminoácidos/genética , Secuencia de Bases/genética , Femenino , Humanos , Datos de Secuencia Molecular , Embarazo , Estructura Terciaria de Proteína/genética , ARN Mensajero/metabolismo , Intercambiadores de Sodio-Hidrógeno/genéticaRESUMEN
OBJECTIVE: To evaluate the incidence of hyperemesis gravidarum among pregnant women in Kuwait and the status of HCG, TSH, Total T4 and Free T4 in the serum of patients with hyperemesis gravidarum compared with a control group of women. METHODOLOGY: During a 6-month period all patients admitted to Maternity Hospital with features of hyperemesis gravidarum (excessive vomiting and ketonuria) were enlisted into the study. In fifty of these patients and their fifty normal controls, the status of serum total (beta)hCG, TSH, total T4 and freeT4 were evaluated with AXSYM micro particle enzyme immunoassay. RESULTS: The incidence of hyperemesis in the maternity population was 45 per 1000 deliveries. Total (beta)hCG and Total T4 and FreeT4 were significantly higher in the hyperemesis patients than in the normal controls (p<0.0001, p=0.004 and p=0.01 respectively). TSH levels were significantly lower in hyperemesis patients than in their normal controls (p<0.0001). There was a strong positive correlation between the total (beta)hCG and the gestational age (r=0.8). CONCLUSION: There is a high incidence of hyperemesis gravidarum in the Kuwaiti population. Total (beta)hCG, Total T4 and Free T4 titers were significantly higher in patients with hyperemesis gravidarum, but none of the patients showed signs of hyperthyroidism.
Asunto(s)
Hormonas/sangre , Hiperemesis Gravídica/sangre , Hiperemesis Gravídica/epidemiología , Adulto , Estudios de Casos y Controles , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Femenino , Edad Gestacional , Humanos , Hiperemesis Gravídica/etiología , Incidencia , Kuwait/epidemiología , Embarazo , Primer Trimestre del Embarazo , Tirotropina/sangre , Tiroxina/sangreRESUMEN
The role of hyperglycemia on modulation of maternal-fetal transport of amino acids in humans is little understood. Hence, we have explored the effect of increased glucose load on transport kinetics of a model non-metabolizable amino acid, alpha-aminoisobutyric acid (AIB), in the human placenta in vitro. Transport kinetics of AIB in maternal-fetal direction was studied using perfusion of isolated human placental lobules. NCTC (National Culture and Tissue Collection)-135 medium, diluted with Earle's buffered salt solution was used as the perfusate and tritiated water was used as the reference marker. Effect of increased glucose load on transport kinetics of study and reference substances was studied in normal term placentae (n=5; gestational age, 38.5 +/- 0.5 weeks) in succeeding experimental phases, after a control perfusion phase with physiological glucose concentration. AIB transport fraction (TF), relative to tritiated water TF, averaged 54.8% in control euglycemic phase while in hyperglycemic concentration phases of 27.8 and 55.6 mM, the AIB TF index averaged 42.4% and 38.2%, respectively. Analysis of variance revealed that the difference was statistically significant. Similarly, absorption rate index of the amino acid was also significantly lower in the hyperglycemic perfusion phases compared to control euglycemic phase. We conclude that hyperglycemia may play a deleterious role in limiting maternal-fetal transport of A-type amino acids in the in vivo state.
Asunto(s)
Ácidos Aminoisobutíricos/farmacocinética , Glucosa/administración & dosificación , Intercambio Materno-Fetal/efectos de los fármacos , Placenta/metabolismo , Transporte Biológico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Glucosa/farmacología , Humanos , Técnicas In Vitro , Perfusión , EmbarazoRESUMEN
Transport characteristics of certain inorganic elements such as copper, magnesium, selenium and iron have been studied in maternal-fetal direction in normal pregnancies, using in vitro perfusion of isolated placental lobules. Copper, selenium, magnesium and iron salts corresponding to twice physiological concentrations were injected as a 100 microl bolus, into the maternal arterial perfusate. Serial perfusate samples were collected from venous outflows for a study period of 5 min. Concentrations of various inorganic elements and their transport kinetics were determined. Transport fractions of copper, selenium, magnesium and iron averaged 0.14, 0.19, 0.06 and 0.23% of maternal load respectively. The pharmacokinetic parameters such as area under the curve, clearance, elimination constant, and time for maximum response showed some significant differences between the various elements. We speculate that copper and selenium share the same transport pathway along a concentration gradient in maternal-fetal direction, while for iron and magnesium, active transport plays a predominant role for element transfer across the human placental membrane.
Asunto(s)
Cobre/metabolismo , Hierro/metabolismo , Magnesio/metabolismo , Intercambio Materno-Fetal , Placenta/metabolismo , Selenio/metabolismo , Transporte Biológico , Femenino , Humanos , Cinética , Perfusión , EmbarazoRESUMEN
BACKGROUND: The limited data available on the role of insulin on maternal-fetal transport of amino acids prompted us to undertake this study. METHODS: Transport kinetics of a model amino acid, alpha-aminoisobutyric acid (AIB) was investigated in perfusion of isolated human placental lobules in vitro in non steady-state conditions and the effect of therapeutic dose of insulin was assessed in parallel series of perfusions. National Culture and Tissue Collection medium diluted with Earle's buffered salt solution was used as the perfusate and tritiated water was used as the reference marker for comparison. RESULTS: In five successful perfusions with insulin, differential transport rate indices of AIB for 10, 25, 50, 75 and 90% of efflux fractions in the fetal venous outflow averaged 0.76, 1.03, 1.02, 1.09, 1.04 and 1.03 times those of reference values, respectively. The indices differed significantly than in controls for 10, 25 and 50% efflux fractions, but not in the case of 75 and 90% efflux values. The AIB transport fraction (TF), expressed as percentage of injected maternal dose, averaged 29.4 +/- 5.4% and 38.7 +/- 6.2% of the corresponding reference marker value in control and insulin series, respectively. With regards to the pharmacokinetic transport parameters, the absorption and elimination rates of the amino acid were significantly higher in the study group than in the control. CONCLUSION: We conclude that insulin, in physiological and therapeutic doses, stimulates maternal-fetal AIB transport in vitro, in the perfused human placental lobule.
Asunto(s)
Ácidos Aminoisobutíricos/farmacocinética , Hipoglucemiantes/farmacología , Insulina/farmacología , Intercambio Materno-Fetal/efectos de los fármacos , Placenta/metabolismo , Femenino , Humanos , Técnicas In Vitro , Intercambio Materno-Fetal/fisiología , Perfusión , Embarazo , Valores de Referencia , Volumetría , Agua/farmacologíaRESUMEN
BACKGROUND: The paucity of data relating to transport kinetics of free fatty acids (FFA) in pregnant diabetic women prompted the undertaking of the present study. METHODS: Transport kinetics of a model FFA, palmitic acid, have been investigated in Type I diabetic pregnancies, using in vitro perfusion of isolated placental lobules. National Cancer Tissue Culture medium diluted with Earle's buffered salt solution was used as the perfusate and control placental lobules were perfused for comparison. RESULTS: In five Type I diabetic women, the palmitic acid transport fraction (TF) averaged 5.6 +/- 0.42% of injected maternal bolus dose, representing 11.8 +/- 2.1% that of tritiated water used as reference. In control perfusions (n = 5), the palmitic acid TF represented 10.2 +/- 1.3% of tritiated water TF. Differential transport rates of palmitic acid for 10, 25, 50, 75 and 90% of efflux in fetal veins differed significantly from the corresponding values for tritiated water in both study and control series. However, palmitic acid transport rates for the various efflux fractions in the two series were not significantly different. For kinetic parameters, such as area under the curve, clearance, elimination constant, time for maximum response, absorption rate and elimination rate, the values for palmitic acid in the diabetic and control series also did not differ significantly. CONCLUSION: Transport kinetics of palmitic acid in Type I human diabetic pregnancies in in vitro conditions do not differ significantly from those observed in normal pregnancies.
Asunto(s)
Diabetes Mellitus Tipo 1/metabolismo , Ácido Palmítico/farmacocinética , Embarazo en Diabéticas/metabolismo , Transporte Biológico , Diabetes Mellitus Tipo 1/complicaciones , Femenino , Humanos , Técnicas In Vitro , Masculino , EmbarazoRESUMEN
1. A paucity of data relating to free fatty acid (FFA) transport in the human placenta in non-steady state conditions prompted us to undertake the present study. 2. The transport kinetics of palmitic acid in non-steady state conditions have been investigated in vitro using human perfused placental lobules. The effects of varying glucose concentrations on maternal-foetal transport of the FFA were also investigated to mimic the hyperglycaemic states of human diabetic pregnancies. 3. National Cancer Tissue Culture medium diluted with Earle's buffered salt solution was used as the perfusate. [14C]-Palmitic acid, along with tritiated water as a reference, was injected as a bolus into the maternal arterial perfusate and perfusate samples were collected from the venous outflow for a period of 5 min. 4. The transport fraction (TF) of palmitic acid, expressed as percentage of the injected bolus, averaged 3.45 +/- 0.15% in five perfusions, representing 9.2 +/- 1.3% of the corresponding reference marker TF. Kinetic parameters, as well as TF indices of palmitic acid expressed in relation to the reference substance, did not differ significantly between perfusions with a physiological glucose load and those with hyperglycaemic concentrations of glucose of 27.8 and 55.6 mmol/L. 5. The present study shows that hyperglycaemia per se does not significantly alter palmitic acid transport kinetics in vitro in the human perfused placental lobule.
Asunto(s)
Glucosa/farmacología , Intercambio Materno-Fetal/efectos de los fármacos , Ácido Palmítico/farmacocinética , Placenta/efectos de los fármacos , Femenino , Humanos , Intercambio Materno-Fetal/fisiología , Placenta/fisiología , EmbarazoRESUMEN
The sodium hydrogen exchanger isoform, NHE-1 plays an important role in electrolyte and water homeostasis. These functions are compromised in pregnancies complicated with preeclampsia. At present it is not known whether NHE-1 expression is altered during preeclampsia. In the present study the placental level of NHE-1 protein was measured using immunoblotting. Since prostaglandins regulate the secretory and absorptive functions, the levels of prostaglandin E-2 as well as the expression of cyclooxygenase-1 and -2 were also estimated. The amount of NHE-1 protein and cyclooxygenase-2 was reduced in preeclamptic placentas, whereas the level of cyclooxygenase-1 remained unaltered. In contrast, prostaglandin E-2 concentration was higher in preeclampsia. Suppression of NHE-1 might render the placenta with impaired uptake of water and electrolytes and therefore may be involved in the pathogenesis of preeclampsia. While prostaglandin E-2 may play a role in preeclampsia, these findings discount the induction of cyclooxygenase-genes for this increase.
Asunto(s)
Placenta/metabolismo , Preeclampsia/etiología , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Intercambiadores de Sodio-Hidrógeno/biosíntesis , Adulto , Femenino , Humanos , Placenta/enzimología , Embarazo , Isoformas de ProteínasRESUMEN
BACKGROUND: There have been no reports to date on glucose transport kinetics and the effect of graded hyperglycemia in the human placenta in non-steady-state conditions. METHODS: The transport kinetics of D-glucose in the human placenta was investigated in non-steady state conditions in vitro using perfusion of isolated placental lobules. National Cancer Tissue Culture (NCTC) 135 culture medium, diluted with Earle's buffered salt solution was used as the perfusate. 14C-Labeled D-glucose and water as reference were injected as a single bolus into the maternal arterial perfusate. Perfusate samples were collected and analyzed from the maternal and fetal venous outflows. RESULTS: In four successful perfusions, differential transport rates of glucose in the maternal-fetal direction averaged 1.03, 1.02, 1.09, 1.04 and 1.03 times those of corresponding tritiated water transport rates for 10, 25, 50, 75 and 90% of efflux fractions, respectively. Glucose transport fraction, expressed as percentage of injected maternal dose averaged 84 +/- 3.1% of water transport fraction in the four perfusions. Glucose kinetic parameters expressed as area under the curve, elimination constant (Kel), clearance, time for maximum response, absorption rate and elimination rate averaged 0.25, 0.29, 3.96, 1.02, 0.25 and 0.18 times that of the corresponding tritiated water value, respectively. Neither the different kinetic parameters nor the transport fraction indices differed significantly when glucose concentrations in the same perfusions were raised successively from 5.56 to 27.80 and then to 55.6 mmol/L. CONCLUSIONS: We speculate that within physiological limits, hyperglycemia per se plays no significant part in altering glucose transport kinetics across the human placenta in the maternal-fetal direction.
Asunto(s)
Glucosa/farmacocinética , Placenta/metabolismo , Femenino , Humanos , Técnicas In Vitro , Intercambio Materno-Fetal/fisiología , EmbarazoRESUMEN
Changes in the rostral ventrolateral medullary neurotransmitter levels and associated cardiovascular functions in response to local administration of brain natriuretic peptide were investigated in urethane-anesthetized Sprague-Dawley rats. Unilateral injections of various doses of brain natriuretic peptide into the rostral ventrolateral medulla region led to significant reductions in both blood pressure and heart rate. To identify the changes occurring in the extracellular neurochemical profile, brain natriuretic peptide was perfused at the rate of 1.5 microliters/min for a period of 1 h through a microdialysis probe implanted stereotaxically into the rostral ventrolateral medulla area and the dialysate was assayed every 15 min for both catechols and indoleamine. Both norepinephrine and epinephrine concentrations were significantly reduced. Dihydroxyphenylacetic acid concentration showed no significant change in response to brain natriuretic peptide perfusion. On the other hand, serotonin turnover estimated by the measurement of its metabolite (5-hydroxyindoleacetic acid) concentration increased during the perfusion of brain natriuretic peptide. Blood pressure and heart rate also showed significant reduction during the perfusion of brain natriuretic peptide. These results suggest that brain natriuretic peptide may be relevant in the central regulation of cardiovascular functions by modulating monoamine neurotransmitters.
Asunto(s)
Factor Neurotrófico Derivado del Encéfalo/farmacología , Espacio Extracelular/metabolismo , Bulbo Raquídeo/metabolismo , Neurotransmisores/metabolismo , Animales , Presión Sanguínea/efectos de los fármacos , Epinefrina/metabolismo , Espacio Extracelular/efectos de los fármacos , Frecuencia Cardíaca/efectos de los fármacos , Ácido Hidroxiindolacético/metabolismo , Inyecciones , Masculino , Bulbo Raquídeo/efectos de los fármacos , Norepinefrina/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
Transfer of cyclosporine A (CsA) in the human placenta has been studied in vitro using a dual perfusion technique of isolated placental lobules. Antipyrine was used as a reference marker for comparison. Our studies showed a negligible transfer of CsA from the maternal to the fetal circulation, representing less than 5% of the maternal drug load. These results are in agreement with that reported earlier in an in vivo study in a pregnant woman. We conclude that the low placental transfer of CsA is attributable mainly to the drug's relatively high molecular weight.
Asunto(s)
Ciclosporinas/farmacocinética , Intercambio Materno-Fetal , Placenta/metabolismo , Antipirina/farmacocinética , Femenino , Humanos , Peso Molecular , EmbarazoRESUMEN
Pregnant Sherman rats were given propranolol (a) per os (50 mg X kg-1, twice a day) on days 17-19 of gestation, (b) by constant rate infusion: osmotic minipumps (6 mg X kg-1 X day-1) from day 13 of gestation. On day 20 (a-treated) or 21 (b-treated), [14C]-AIB + [3H]-H2O were injected intravenously; plasma and tissue samples were collected at different times up to 4 h (a-treated) or at 2 h (b-treated) for radioactivity measurements. Whatever the treatment, no difference was found between control and treated animals for all parameters studied (number of fetuses; weight, protein; DNA; [14C]-AIB or [3H]-H2O tissue levels) except in propranolol-treated mothers where maternal heart [14C]-AIB uptake was decreased and where fetal plasma and tissue [3H]-H2O levels where higher than control at 5 min. Another set of experiments were performed in a-treated rats. On day 20, each mother was anesthetized with ether and injected as above; maternal plasma sample and one feto-placental unit were collected at different times within 15 min after injection. For this period, [14C]-AIB uptake and mainly [3H]-H2O diffusion were increased in placentae and fetuses of propranolol-treated dams. Arterial blood pressure did not change throughout the experiment in propranolol-treated animals, but decreased in controls. Heart rate was slowed down in the former compared to controls. Thus, in our experimental conditions, propranolol treatment: does not modify fetal weight; has no effect on AIB placental transfer and tissue uptake, and could protect towards the stress of anesthesia and surgical injuries, since H2O transfer was impaired in control but not in treated animals.