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PubMed1986

Detection and characterization of peaks and estimation of instantaneous secretory rate for episodic pulsatile hormone secretion.

We have developed a new computer program for detection of "peaks" in sequential hormone measurements in longitudinal studies of episodic hormone secretion. The program provides: (a) several statistically based approaches to the estimation of the random measurement error as a function of hormone level; (b) peak detection based on analysis of first derivatives with logic that has been optimized for asymmetrical peaks with exponential decays; (c) several approaches to the estimation of tolerances for the first and second derivatives; (d) a sensitive curve-fitting approach, to distinguish between upstrokes, exponential decays, and flat baselines; (e) ability to detect multiple overlapping peaks; (f) analysis of "robustness" by systematically varying the threshold around the most-likely value; (g) superimposition of detected peaks, to evaluate "average peak shape"; (h) analysis of the "decay rate," to obtain an estimate of the disappearance rate constant and half-life; (i) use of a "discrete deconvolution" approach, to solve for the apparent instantaneous rate of secretion, and provision of an error analysis to obtain estimates of the precision of these derived values; and (j) correlation with other relevant series as a means of cross validating. The program has been tested extensively on real and synthetic data, and appears to perform well. The frequency of "false positive" peaks can be held at any desired low level, and can be prevented from increasing as sampling frequency increases. The number of arbitrary assumptions, approximations, or thresholds is held to an absolute minimum. These methods are natural, logical, and follow from first principles of statistics.

Biometry↗
PubMed1977

Uptake of K+ by frog gastric mucosa from submucosal side and acid secretory rate.

The K+ content in frog gastric mucosa (K+) was measured as a function of the submucosal K+ concentration ([K+sm]) in the absence of K+ on the mucosal side. The (K+) in HCO3- buffer with 95% O2-5% CO2 gas showed that the removal of external K+ induced a 27% K+ loss from the control value of 5 mM K+sm, that there was no linear relation between (K+) and [K+sm, and that the change in the (K+) versus the [K+sm] was hyperbolic, indicating that there are two different types of K+ in the mucosa: bound and free K+.

Animals↗
PubMed1994

Impact of metabolism by extragastrointestinal tissues on secretory rate of milk proteins.

This paper reviews the current state of knowledge about the postabsorptive utilization of AA. Data on the duodenal entry of AA and the projected output of these same AA as milk protein demonstrate significant losses. Within the essential AA, these losses range from 70% for Thr to 40% for Met and Lys. For Val, almost half of the loss is due to its use for nonsecretory purposes by the mammary gland; values decrease to 0% for other AA. The liver is the other major organ, apart from the portal-drained viscera, that is responsible for significant AA disposal. Interactions of Met metabolism with other methyl sources and gluconeogenic precursors that can alter the Met requirement also are discussed. Data on the transhepatic and transsplanchnic AA balance in lactating cows, and the coordinated use of these balances with duodenal flow and mammary balance, are needed. Further research also is needed into the functionality of use of AA for purposes other than milk protein synthesis to determine whether excess catabolism of AA occurs; assuming it does, more efforts are needed to identify regulation of AA disposal in the crucial tissues.

Amino Acids↗
PubMed1978

Endoscopic measurement of pancreatic juice secretory flow rates and pancreatic secretory pressures after secretin administration in human controls and in patients with acute relapsing pancreatitis, chronic pancreatitis, and pancreatic cancer.

Secretory flow rates were measured inside the main pancreatic duct during endoscopic retrograde cholangiopancreatography (ERCP) in patients with acute relapsing pancreatitis, chronic pancreatitis, and pancreatic cancer and in controls after intravenous administration of secretin. Peak secretory flow rates in these groups were 5.04 +/- 1.74, 0.71 +/-1.28, 0.60 +/- 1.37, and 4.13 +/- 0.88 ml/min, respectively. Peak secretory pressures were also measured intraductally in patients with acute relapsing pancreatitis and pancreatic cancer and in controls and were 402 +/- 69, 75 +/- 161, and 403 +/- 99 mm pancreatic juice, respectively. Peak secretory flow rates and pressures measured in controls during constant administration of secretin were similar to those measured when secretin was administered as a bolus.

Endoscopy↗
PubMed2005

Pubertal alterations in growth and body composition: IX. Altered spontaneous secretion and metabolic clearance of growth hormone in overweight youth.

Deconvolution analysis was used to determine 12-hour spontaneous nocturnal growth hormone (GH) secretion and GH half-life in lean (body mass index, <85th percentile; n = 39) and overweight (body mass index, > or =85th percentile; n = 18) youth. The integrated GH concentration, GH burst mass, and half-life were lower (P < .05) in overweight than in lean youth. For each unit increase in percentage of body fat, integrated serum GH concentrations, secretory burst mass, and half-life declined by 83.6 microg/L per minute (r = -0.39, P < .01), 0.22 microg/L (r = -0.28, P < .05), and 0.2 minute (r = -0.38, P < .01), respectively. The effect of overweight on GH secretion was independent of pubertal status. Hierarchical regression models tested the hypothesis that altered GH secretion in youth is more related to total adiposity than abdominal visceral fat. When age, sex, fat-free mass, testosterone, and estradiol were held constant, the sequential addition of abdominal visceral fat did not increase R2 for any GH secretion variable. Sequential addition of percentage of body fat increased R2 (P < .05) for integrated GH concentration, total secretory rate, secretory burst mass, and pulsatile production rate. We conclude that serum GH concentrations are reduced in overweight youth primarily because of reduced GH burst mass with no change in the number of secretory events and secondarily to reduced GH half-life. Based on the model that GH-releasing hormone predominantly increases GH pulse amplitude whereas somatostatin primarily controls GH pulse frequency, these results suggest that overweight in youth diminishes GH-releasing hormone stimulation resulting in truncated GH bursts but does not alter the number of somatostatin withdrawal intervals so that GH burst frequency is conserved.

Abdomen↗
PubMed1995

Enhanced biliary excretion of canalicular membrane enzymes in ethynylestradiol-induced cholestasis. Effects of ursodeoxycholic acid administration.

Cholestasis is associated with a marked increase in the release of canalicular membrane enzymes into bile. This phenomenon has been related to an increased lability of these canalicular membrane integral proteins to the solubilizing effects of secreted bile salts. To further characterize the effects of oral ursodeoxycholic acid (UDCA) administration on ethynylestradiol (EE)-induced cholestasis, the influence of this bile acid on changes in biliary excretion of membrane-bound enzymes was investigated. Bile flow, basal bile salt and biliary lipid secretory rates, the maximum secretory rate of taurocholate (TC SRm), and the biliary excretion of the canalicular membrane-bound ectoenzymes alkaline phosphatase (ALP) and gamma-glutamyl transpeptidase (GGT) were measured in rats after EE and/or UDCA administration. The activities of ALP, GGT and Na+,K(+)-ATPase in purified isolated canalicular and sinusoidal membrane fractions and the ultrastructure of hepatic acinus, including histochemical studies of ALP distribution, were also examined. EE significantly reduced bile flow, bile salt and biliary lipid secretory rates, and TC SRm, and caused dilatation and loss of microvilli at the canalicular pole of hepatocytes. Biliary excretion of ALP increased 2-fold, whereas biliary excretion of GGT was unchanged. The relationship between biliary excretion of ALP or GGT and bile salt secretion (units of enzyme activity secreted per nanomole of bile salt) was greater in EE-treated rats compared with controls (2.1- and 1.5-fold greater for ALP and GGT, respectively), indicating that in EE-induced cholestasis more enzyme was released into bile per nanomole of bile salt. Na+,K(+)-ATPase activity in sinusoidal membrane fraction was reduced significantly, whereas ALP activity increased in both membrane fractions in EE-treated rats. The histochemical distribution of ALP in the acinus showed a strong reaction in acinar zone 3 and at both the canalicular and sinusoidal membranes. Oral administration of UDCA prevented EE-induced bile secretory failure by normalizing bile flow, bile salt and biliary phospholipid secretory rates, and TC SRm. UDCA also prevented the EE-induced changes in the biliary excretion of enzymes. On the contrary, UDCA did not modify either the enzyme activity in isolated membrane fractions or the morphological or ALP histochemical changes associated with EE administration. These data indicate that in EE-induced cholestasis changes occur at the canalicular membrane, enabling this portion of the plasma membrane to be more susceptible to the solubilizing effect of bile salt, and that oral administration of UDCA prevents bile secretory failure and changes in the biliary excretion of ALP and GGT in EE-treated rats.

Alkaline Phosphatase↗
PubMed1987

Kinetics of bicarbonate transport in the early proximal convoluted tubule.

Bicarbonate permeability and bicarbonate transport kinetics in the S1 segment of the proximal convoluted tubule (PCT) have not been previously studied. In vivo microperfusion at a rate of 30 nl/min was performed in early and late PCT of Munich-Wistar rats. Bicarbonate permeability was first defined, using a bicarbonate-free, acetazolamide-containing perfusate, and was over fourfold higher in the early compared with the late PCT (20.4 +/- 1.8 vs. 4.6 +/- 0.4 X 10(-7) cm2/s, P less than 0.001). Net bicarbonate absorption was then measured using perfusate bicarbonate concentrations of 15, 25, 40, and 100 mM at 30 nl/min perfusion rate. Proton secretory rate was calculated for each group by subtracting the passive bicarbonate transport component from the net flux. Saturation kinetics of acidification were observed in both the early and late PCT. The maximal proton secretory rate at the highest luminal bicarbonate concentration (Vmax) in the early PCT was about twice that in the late PCT (504 +/- 37 vs. 265 +/- 15 peq.mm-1.min-1, P less than 0.001). However, the luminal bicarbonate concentration eliciting half-maximal proton secretion (apparent Km) was approximately the same (11 mM) in the early and late PCT. In conclusion, the early PCT has a higher bicarbonate permeability and proton secretory capacity than the late PCT. Increased Vmax but axial constancy of Km suggests that there is amplification of similar transport mechanism(s) affecting bicarbonate absorption in S1 compared with S2 cells.

Absorption↗
PubMed1979

Foetal-maternal production and transfer of cortisol during the last days of gestation in the guinea-pig.

The metabolism and the rate of transfer of cortisol across the placenta in pregnant guinea-pigs and foetuses were studied by constant intravenous infusions of tritium-labelled cortisol. Estimates of endogenous and radioactive plasma cortisol levels were used to calculate the following parameters at four stages before parturition (days 62, 64, 66 and 67; parturition occurring at day 68): metabolic clearance rate; production rate; adrenal secretory rate; transfer rate from mother to foetus and from foetus to mother; irreversible removal rate; the fraction of cortisol derived from the other in the foetal and maternal vascular compartments; the fraction of secreted and recycled cortisol involved in the transfer. The metabolic clearance rate and the rates of production and secretion of cortisol were higher in the mother than in the foetus between days 62 and 67 of gestation. About 90% of the foetal cortisol was of maternal origin. The fraction of maternal cortisol of foetal origin increased in the last days of gestation.

Anesthesia↗
PubMed1996

The effect of beta andrenoceptor stimulation of canine stomach on pentagastrin-stimulated histamine release.

The effect of beta adrenergic agonist isoproterenol, infused directly into the gastrosplenic artery in anesthetized mixed-breed dogs, on pentagastrin-stimulated gastric histamine release was examined to clarify the potential mechanisms by which beta adrenoceptor stimulation results in gastric acid inhibition. Two doses of isoproterenol (3 and 10 ng/kg/min) were infused with pentagastrin; histamine and n(tau)-methyl-histamine concentrations were measured in arterial and gastric venous samples, and their gastric secretory rates were calculated. Both doses of isoproterenol decreased histamine-secretory rate to pentagastrin from a peak of 234 +/- 51.5 ng/min with vehicle to 17.7 +/- 4.2 ng/min with the 3 ng/kg/min dose of isoproterenol and to 8.6 +/- 2.9 ng/min with the 10 nk/kg/min dose of isoproterenol. The change in N(tau)-methyl-histamine-secretory rate paralleled the histamine-secretory rate. Concomitantly with the histamine-secretory rate, the effect of beta adrenoceptor agonist on gastric somatostatin secretion was also examined. The lower dose of isoproterenol stimulated somatostatin-secretory rate from 4.0 +/- 1.8 to 31.8 +/- 10.3 ng/min, and the higher dose of isoproterenol increased somatostatin-secretory rate from 6.0 +/- 3.1 to 61.5 +/- 21.5 ng/min, whereas isoproterenol potentiated pentagastrin-stimulated gastric somatostatin release. These data demonstrate that isoproterenol is a potent inhibitor of pentagastrin-stimulated gastric histamine release, and the mechanism may be related to the concomitant somatostatin release. Thus, the most likely mechanism by which beta adrenoceptor stimulation results in inhibition of gastric acid secretion is through down-regulation of gastric histamine release.

Animals↗
PubMed1993

Postcholestatic alkaline phosphatase activity after relief of bile duct obstruction in the rat.

The effects of obstructive cholestasis on the activity of alkaline phosphatase have been extensively studied in serum and liver tissue. However, very little is known about the activity of this enzyme in the postcholestatic condition after relief of the biliary obstruction. The purpose of this study has been to characterize alkaline phosphatase activity in serum, liver and bile in the postcholestatic period and to relate it to changes in bile acid secretory rate. Serum activity and biliary secretory rates of alkaline phosphatase were markedly increased in rats subjected to a reversible obstructive cholestasis for 24 hr or 48 hr and progressively declined along the postcholestatic period to values not significantly different from those of control rats within 48 hr. A significant direct linear relationship between the biliary secretory rates of enzyme activity and bile salts was apparent both in cholestatic groups and in the control groups. The slope of the regression line (units of alkaline phosphatase secreted per micromole of bile salts) was 1.5-fold to 3-fold higher in cholestatic animals. Remarkably, a positive y-intercept of regression lines suggested that a significant fraction of the enzyme was secreted independently of bile salts; this fraction was 18-fold and 34-fold greater in 24-hr and 48 hr cholestatic rats, respectively, compared with that in controls. Sodium taurocholate administered intravenously, either as a bolus or as an infusion at increasing submaximal rates, resulted in parallel increases of bile salt and alkaline phosphatase secretory rates into bile. The enzyme activity secreted per micromole of taurocholate was significantly greater in cholestatic than in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMedDate not supplied

Effects of taurocholate infusion on biliary excretion in isolated perfused rat livers. Decreased biliary excretion of dibromosulfophthalein in pregnancy.

A crossover experimental design was used to examine the effects of saline (SAL) vs. taurocholate (TC) infusion on hepatic excretory function in isolated perfused livers from pregnant (19-21 days gestation) and nonpregnant female rats. Bile flow, bile acid concentration, bile acid secretory rate, dibromosulfophthalein (DBSP) concentration in bile, and DBSP secretory rates were determined in livers infused continuously with DBSP and initially with SAL (1 ml/hr, 45 min), followed by TC (60 mumol/hr, 1 ml/hr; 75 min) or initially with TC (45 min) followed by SAL (75 min). The order of infusion (SAL-TC vs. TC-SAL) had no significant effect. TC infusion significantly increased all measures in livers from both nonpregnant and pregnant rats. Two-way analysis of variance followed by the Tukey-Kramer test showed that bile flow (microliter/min/g liver) and DBSP concentration in bile (mumol/ml) were significantly decreased during SAL infusions in pregnancy. These two measures plus bile acid and DBSP secretory rates (nmol/min/g liver) were also significantly decreased during TC infusion in pregnancy. Pregnancy had no effect on bile acid concentration in the presence of SAL or TC infusions. When bile flow, bile acid, and DBSP secretory rates were calculated per whole liver, only the DBSP secretory rate was significantly decreased in pregnancy. These data indicate that bile flow and bile acid secretion do not increase in proportion to the increase in liver weight in pregnancy so that these measures are decreased when expressed per g liver. Pregnancy appears to have a real inhibitory effect on DBSP since its secretion is depressed when activity is expressed per g liver or per whole organ.

Animals↗
PubMed1980

Quantitative electron microscopic studies on rat ileal Paneth cells under various physiological and experimental conditions.

The Paneth cells of the rat ileum were studied with quantitative electron microscopical methods. Estimations were made of the average volume of the cells and the nucleus, and the mean diameter and volume density of the secretory granules. Six groups of rats, each comprising 6-7 animals, were investigated: the rats in the first group were fasted controls, those in the second group non-fasted controls. In the third group the rats were given pilocarpine and in the fourth atropine. In the fifth group the rats were chemically sympathectomized, and the rats in the sixth group were subjected to partial removal of the small intestine. The secretory granules remained unchanged in all groups, except for the atropinized rats which contained significantly increased amounts, presumably indicating a low secretory rate. Moreover, the secretory granules were smaller in the rats treated with pilocarpine and in those operated on; this probably reflects a high secretory rate.

Animals↗