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.

Body composition, fasting leptin, and sex steroid administration determine GH sensitivity in peripubertal short children.

Serum IGF-I levels in GH-treated subjects demonstrate a wide range of responsiveness to GH. However, the factors influencing GH sensitivity are not well known. The aim of this work was 1) to test whether body composition (determined by dual energy x-ray absorptiometry) or factors related to body composition (fasting blood glucose, FFA, C-peptide, leptin, and insulin sensitivity determined by an insulin tolerance test) influence GH sensitivity; and 2) to study the effect of sex steroid priming on GH sensitivity. We measured serum IGF-I at baseline and 24 h after a single administration of GH (2 mg/m(2)) in 60 healthy prepubertal and early pubertal children (height, -2.1 +/- 1.0 SD score). GH sensitivity, as estimated by the increase in serum IGF-I after GH administration (difference between stimulated and baseline serum IGF-I = delta IGF-I), was also determined after a short-term administration of oral ethinyl E2 in girls and im T in boys. The serum IGF-I concentration was 297 +/- 114 microg/liter at baseline and increased to 429 +/- 160 microg/liter, corresponding to a 46 +/- 29% increase over the baseline value (P < 0.0001, stimulated vs. baseline serum IGF-I). delta IGF-I was not different between gender or pubertal stage. There were positive correlations (P < 0.001) between delta IGF-I and adiposity (total body fat, r = 0.62; trunk fat, r = 0.62), fasting leptin (r = 0.64), and C-peptide (r = 0.54), and a negative correlation with fasting FFA (r = -0.33; P < 0.05) even after adjustment for age, gender, and pubertal stage. These factors remained significant independent predictors of the absolute as well as the percent increase in serum IGF-I in multiple regression analyses. Priming with T and ethinyl E2 had a similar stimulating effect on the serum GH peak in response to the insulin tolerance test. In boys, serum baseline IGF-I increased by 60%, and delta IGF-I was similar after vs. before T administration. By contrast, in girls, serum baseline IGF-I was similar, and delta IGF-I was 60% less after vs. before ethinyl E2 administration. This study indicates that 1) GH sensitivity is determined by fat mass, serum fasting leptin, C-peptide, and FFA; and 2) oral ethinyl E2 and im T have divergent effects on the IGF-I response to a single administration of GH.

[Assay of serum elastase 1 in adenocarcinoma of the pancreas: diagnostic value, compared and combined study with serum CEA and CA 19-9]. / Dosage sérique de l'élastase 1 dans l'adénocarcinome du pancréas: intérêt diagnostique, étude comparée et combinée avec l'ACE et le CA 19-9 sériques.

Serum elastase 1, CEA and, CA 19-9 titers were determined by radioimmunoassay in 113 patients with benign non pancreatic digestive disease, 88 patients with non pancreatic carcinoma, 25 patients with chronic pancreatitis and 40 patients with pancreatic carcinoma (of whom 34 were classified according to Fortner's staging classification), respectively: a) to evaluate the diagnostic value of elastase in pancreatic carcinoma, b) to compare and to study the value of its association with CEA and CA 19-9 for earlier detection of this type of cancer. The specificity of serum elastase (greater than 500 ng/dl) was greater than that of CA 19-9 (greater than 37 U/ml), (93.3 p. 100 vs 64.6 p. 100, p less than 0.01), but its sensitivity was significantly lower than that of CA 19-9 (27.5 p. 100 vs 82.5 p. 100; p less than 0.001). The sensitivity of CA 19-9 (greater than 37 U/ml) and/or elastase (greater than 500 ng/dl) was 85.2 p. 100 (greater, but not significantly, than CA 19-9 alone) and 91.6 p. 100 in Fortner stage I or II tumors (greater, but not significantly, than Fortner stage III tumors which were at 83.6 p. 100). The specificity of the combined test was 62 p. 100, lower (but not significantly) than CA 19-9 alone. As serum CEA (greater than 5 ng/ml) alone and in association with CA 19-9 was disappointing, it might be replaced by the elastase assay. The combined CA 19-9-elastase assay coupled with morphologic investigations could represent an attractive approach for earlier detection of this cancer.

[Automatic microdetermination of serotinin in capillary blood]. / Microdosage automatique de la sérotonine sur sang capillaire

The authors describe an automatic fluorimetric micromethod based on the reaction of condensation of serotonin with orthophthaldialdehyde forming a fluorescent compound. This precise and sensitive method permits estimation of serotonin on microsamples. The results obtained on capillary blood are identical to those obtained on venous blood.

[Serum alkaline phosphatase levels in pregnancy]. / Taux sérique gravidique des phosphatases alcalines.

Serum levels of total alkaline phosphatase increase during pregnancy but the presently available methods are not very precise. We used the CHEM 1 Bayer Diagnostic test in all the consecutive patients admitted to our unit between June 1 and October 16, 1990. Exclusion criteria were twin pregnancies, pruritus, liver disease or parasitosis. A multifactorial analysis was used to discriminate between general, obstetric, pathologic and drug parameters. There were 373 serum samples, 91% were obtained during the last three months of pregnancy. The mean serum alkaline phosphatase level was 68.2 U/l and 75.9 U/l during the first two trimesters respectively and rose to 126.7, 178.8 and 234 U/l during the last three months respectively. The elevation was greater in cases of vomiting during the first trimester, alpha-methyldopa intake. It was less after hypodroxyapatite intake and was positively correlated with weight gain. Age, parity, pregestational weight, neonatal weight, other pathologies and other drug intake did not affect the results. Knowledge of these physiological levels will be useful for evaluating most liver diseases occurring during pregnancy. Assay of the enzyme fractions would be ordered secondarily.

[Ethyl alcohol levels in the expiratory air vs blood alcohol levels. 204 cases in an emergency unit]. / Ethylométrie dans l'air expiré versus ethanolémie. 204 cas dans un service d'accueil et d'urgence.

OBJECTIVES: Twenty to forty percent of all patients admitted to the emergency ward are positive for blood alcohol. Devices which measure alcohol in expired breath have been increasingly used in these units. This study was conducted to compare the results of breath alcohol analyzers with the classical laboratory methods based on enzyme assay and gas phase chromatography. METHODS: All patients with suspected acute ethanol intoxication at admission to the emergency room were included if blood alcohol had been ordered (enzyme assay and gas phase chromatography). RESULTS: There were 204 patients (151 men (74%) and 53 women (26%); mean age 43 +/- 12.7 years, range 14-80). The coefficient of correlation between blood alcohol level determined by gas phase chromatography (GC) and breath alcohol was 0.96 (r2 = 0.92, p < 10(-4)). The coefficient of correlation between breath alcohol and blood alcohol level determined by enzyme assay was 0.96 (r2 = 0.92, p < 10(-4)). Comparing the coefficients of correlation GC/blood (r2 = 0.92) versus GC/enzyme assay (r2 = 0.96) demonstrated a statistically significant difference (p < 10(-3)). CONCLUSION: In our 204 patients, the breath alcohol analyzer gave 3 false positives and 3 false negatives (2.94%). Even though breath alcohol levels are 21.1% lower than the levels given by gas phase chromatography, it is an instantaneous nonaggressive method well correlated with classical blood tests. Nevertheless, this method could not be used in 19.6% of emergency patients due to physical impossibility or refusal, justifying laboratory tests.

Immobilized-enzyme membrane sandwich reactor used in automated micro-scale assay of plasma uric acid.

We describe the automated microassay of plasma uric acid by use of an immobilized uricase-membrane sandwich reactor. Hydrogen peroxide, formed when uric acid is oxidized, oxidatively couples two molecules of p-hydroxyphenylacetic acid in the presence of peroxidase to produce a highly fluorescent compound. The specificity of the uricase reaction is coupled with a significantly lower cost of analysis.

Serotonin in experimental histidinemia.

An experimental histidinemia was obtained in rats by in vivo administration of nitromethane, a histidase inhibitor. The magnitude of increase in plasma histidine in the nitromethane-treated rats was in the same range as that in the histidinemic subjects. No modifications were observed in the serotonin concentrations in blood or in various areas of brain between the nitromethane-treated rats and the control rats. No dramatic modifications of serotonin metabolism seem to be implicated in histidinemia, unlike phenylketonuria.

Long-term administration of PGE1 increases liver fibrosis and collateral blood flow in bile-duct-ligated rats.

BACKGROUND/AIMS: The aim of this study was to assess the effect of early and chronic administration of a prostaglandin E1 analogue (misoprostol) in the prevention of liver fibrosis and portal hypertension. METHODS: Liver fibrosis was induced by bile duct ligation. Controls had a sham operation. Bile-duct-ligated rats were divided into two groups: placebo (vehicle only) and misoprostol (10 microg/d by gavage) for 4 weeks after surgery. Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline content and serum hyaluronate. Systemic and splanchnic hemodynamics were evaluated including spleno-renal shunt blood flow by the transit-time ultrasound technique. RESULTS: Mean arterial pressure was significantly lower in the misoprostol group (p<0.01). There was an unexpected increase in fibrosis parameters in the misoprostol group compared to the placebo group, e.g. area of fibrosis: 9.5+/-4.0 vs 15.0+/-8.1% (p<0.05). Spleno-renal shunt blood flow was significantly higher in the misoprostol group than in the placebo group (4.6+/-3.7 vs 2.2+/-2.0 ml/min, p<0.05) while portal pressure was unchanged. CONCLUSIONS: The early and chronic administration of misoprostol enhances porto-collateral circulation blood flow and the development of liver fibrosis in bile-duct-ligated rats.

Effects of long-term administration of interferon alpha in two models of liver fibrosis in rats.

BACKGROUND/AIMS: The aim of this study was to assess the effect of the early and chronic administration of interferon alpha in the prevention of hepatic fibrosis and portal hypertension. METHODS: Rats with liver fibrosis due to bile duct ligation or CCl4 were divided into three groups: sham, placebo and interferon alpha2a 100,000 UI/day. Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and mRNA (fibronectin, procollagen alpha2(I)) contents, and serum hyaluronate. Systemic and splanchnic hemodynamics were also evaluated. RESULTS: Interferon alpha significantly decreased fibrosis in the CCl4 model only: area of fibrosis: 13.9+/-3.7 vs 10.5+/-3.3% (p<0.05), hydroxyproline: 1.8+/-0.6 vs 1.2+/-0.2 mg/g wet liver (p<0.001), respectively placebo vs interferon alpha. There was a significant correlation between the area of fibrosis and hydroxyproline liver content (r=0.77 in the biliary model and r=0.87 in the CCl4 model, p<0.0001). Interferon decreased spleno-renal shunt blood flow (2.0+/-1.8 vs 0.9+/-0.7 ml/min; p<0.05) but not portal pressure in the CCl4 model. No significant effects were observed in rats with biliary fibrosis. CONCLUSIONS: The early and chronic administration of interferon alpha prevents the development of liver fibrosis and porto-collateral circulation in the CCl4 model but not in the biliary model. However, the antifibrotic effects of interferon need to be confirmed in further studies.

Prevention of portal hypertension by propranolol and spironolactone in rats with bile duct ligation.

BACKGROUND/AIMS: It has been suggested that the early administration of propranolol (PR) and a low sodium diet may prevent the development of portosystemic shunts in animals with presinusoidal portal hypertension. Our aim was to study the hemodynamic effects of the early and chronic administration of PR and spironolactone (SPN), alone or in combination, in a model of hepatic fibrosis and sinusoidal portal hypertension induced in rats by bile duct ligation. METHODS: A blind study was performed in 40 Sprague-Dawley rats divided into four groups: placebo (PL), PR (75 mg/kg per day), SPN (100 mg/kg per day), and PR+SPN at the same doses. Drugs were administered by daily gavage over a 4-week period as soon as bile duct ligation was performed. At day 28, the splanchnic and systemic hemodynamics (radiolabeled microspheres) were evaluated. RESULTS: a) Systemic hemodynamics: PR significantly reduced cardiac index and increased vascular resistance, SPN had no significant effect and PR+SPN significantly decreased mean arterial pressure. b) Splanchnic hemodynamics: portal venous pressure (PL: 15.5 +/- 1.5, PR: 14.8 +/- 1.0, SPN: 13.5 +/- 2.1, PR+SPN: 15.0 +/- 1.3 mmHg, p < 0.05) and portosystemic shunts (PL: 30 +/- 31, PR: 13 +/- 14, SPN: 5 +/- 4, PR+SPN: 29 +/- 33%, p < 0.05) were significantly reduced in the SPN group; other hemodynamic parameters were not significantly altered. In multivariate analysis, the only determinant of portosystemic shunts was portal pressure but with a low R2 (0.2). CONCLUSIONS: In this model, the early administration of PR, alone or in combination with SPN, had no beneficial hemodynamic effects. On the other hand, SPN alone decreased portal pressure and prevented portosystemic shunts. Therefore, this drug may have beneficial effects in patients with early portal hypertension.

Antifibrotic and hemodynamic effects of the early and chronic administration of octreotide in two models of liver fibrosis in rats.

The aim of this study was to assess the effect of the early and chronic administration of octreotide in the prevention of hepatic fibrosis and portal hypertension (PHT). Two experimental models of liver fibrosis caused by bile duct ligation (BDL) or CCl4 were divided into 4 rat groups: sham, placebo, and octreotide (10 and 100 micrograms/kg twice daily, subcutaneously). Liver fibrosis was assessed by the area of fibrosis (image analysis), liver hydroxyproline and fibronectin mRNA contents, and serum hyaluronate. Systemic and splanchnic hemodynamic changes were also evaluated, including the splenorenal shunt blood flow by the transit-time ultrasound (TTU) technique. In both models, splenorenal shunt blood flow was significantly lower in the octreotide groups than in the placebo group (P <.05), while portal pressure was not significantly decreased. There was a significant decrease in fibrosis by octreotide in the CCl4 model only: area of fibrosis: 13.9% +/- 3.7% vs. 9.8% +/- 2.5% (P <.01), hydroxyproline: 1.8 +/- 0.6 vs. 1.3 +/- 0.4 mg/g wet liver (P <.05), respectively, placebo vs. octreotide 10 micrograms/kg. There was a significant correlation between the area of fibrosis and hydroxyproline liver content (r =.87 in the biliary model and r =.91 in the CCl4 model; P <.0001). The early and chronic administration of octreotide prevents the development of portocollateral blood flow without reducing portal pressure in two models of liver fibrosis and the development of liver fibrosis in the CCl4 model.