Endogenous estrogen modulates phenothiazine stimulated prolactin secretion

The role of endogenous estrogen in the regulation of serum prolactin concentration in man is controversial. To evaluate the possible effect of endogenous fluctuations in serum estrogen on the regulation of prolactin secretion, the authors determined phenothiazine stimulated prolactin secretion in 12 women in the early follicular phase of the menstrual cycle when estrogen levels were low (mean +/- SE E1 + E2 = 82 +/- 7 pg/ml) and compared it to the response during the late follicular phase when estrogen levels were higher (mean E1 + E2 = 320 +/- 63 pg/ml). Mean basal serum prolactin concentrations were similar in the early and late follicular phases of the cylcle (17 +/- 4 and 20 +/- 2 ng/ml, respectively). The integrated prolactin response following phenothiazine administration was significantly higher at mid-cycle (402 +/- 46 ng-hr/ml) than in the early follicular phase (317 +/0 46 ng-hr/ml, P less than .02). Thus, these studies suggest that endogenous estrogen secretion may play a role in the regulation of serum prolactin concentration in man.     

A pancreatic extract-enriched diet corrects ileal mucosa atrophy in endotoxemic aged rats

An altered adaptive response of the pancreas and small intestine to nutritional stress has an adverse impact upon nutritional status in elderly humans or senescent rats. We evaluated the effects of a pancreatic extract nutritional supplement on intestinal mucosa adaptation in LPS-treated aged rats. Endotoxemic rats were starved for 48 hr and then refed ad libitum for four days with a standard diet. Afterwards they received, over one week, the standard diet enriched with either pancreatic extract (PE) (2.4 g/day) or casein (isonitrogenous to PE supplement). Healthy aged rats fed ad libitum with a standard diet were studied in parallel. Whereas no changes occurred in the jejunal segment, an adaptive villus hyperplasia was observed in the proximal ileum of rats receiving PE without an increase in the brush border hydrolase activities. Our results indicate that oral PE supplementation exerts a trophic effect on the ileal mucosa of aged rats in response to nutritional stress.     

Fibrinolytic components in nasal mucosa and nasal secretion

Effects of a newly synthesized antiulcer agent, YJA20379-4, on gastric proton pump (H+/K+-ATPase) activity, Helicobacter pylori (H. pylori) growth, gastric acid secretion, and gastro-duodenal lesions, were examined in comparison with those of omeprazole. YJA20379-4 markedly inhibited the H+/K+-ATPase activity in a concentration-dependent manner and the inhibitory effect was increased under a weak acidic condition; the IC50 values were 32 and 81 microM at pH 6.4 and 7.4, respectively. The inhibition was completely antagonized by 0.5 mM dithiothreitol (DTT). In addition, YJA20379-4 showed a significant anti-H. pylori activity determined by the agar dilution method. The value of minimum inhibitory concentration (MIC, 3.9-11.7 microg/ml) was at least 3 times more potent than that of omeprazole. In pylorus ligated rats, YJA20379-4 inhibited basal gastric acid secretion when administered by the intraduodenal route (ED50: 23.6 mg/kg). In experimental ulcer models, YJA20379-4 administered by the oral route dose-dependently prevented the development of gastro-duodenal lesions in rats. Moreover, repeated administration of YJA20379-4 promoted the healing of gastric ulcers induced by acetic acid. On the basis of the data obtained, it is suggested that YJA20379-4 has a wide spectrum of antiulcer activities, and its mode of antiulcer actions is dependent on the inhibition of H+/K+-ATPase activity and H. pylori growth and the enhancement of a mucosal defense. Thus, YJA20379-4 might prove to be a beneficial therapy for gastritis and peptic ulcer diseases.     

Oragnotypic culture of the rabbit gastric mucosa

A case is reported in which obstetric management resulted in 52 minutes elapsing between the induction of anaesthesia and delivery by Caesarean section. The mother was induced and maintained on Althesin and minimal methoxyflurane throughout this period without detriment to the neonate.     

Effect of histamine on intestinal fluid secretion in the dog

Intra-arterial infusion of histamine into the small intestine caused about a onefold increase of blood flow, edema of the intestinal tissues and mesentery, and produced a copious secretion of fluid. The jejunal secretions had an ionic composition similar to that of plasma, whereas ileal secretions contained high concentrations of HCO3 with relative low concentrations of Cl. The secretions contained protein (1.5 +/- .2 g/100 ml, range 0.5-2.4) with a similar electrophoretic pattern of plasma protein. When lissamine green was present in the blood, it also appeared in the secretion to a considerable concentration. It is inferred from these findings that a major mechanism of fluid secretion by the action of histamine involves a filtration process across the mucosal epithelium by the incrreased tissue fluid pressure due to extensive capillary leak.     

Hepatic secretion of VLDL fatty acids during stimulated lipogenesis in men

Fatty acids (FA) that are utilized for triglyceride (TG) synthesis in the liver and principally from two sources: FA synthesized de novo in the liver and preformed FA. We have measured the contribution from the two sources to very low density lipoprotein (VLDL) TG synthesis individually for palmitate, oleate, stearate, and linoleate (approximately 98% of the total FA of VLDL TG (VLDL TGFA)) by isotopomer analysis. Five healthy men were studied in the basal state, and 1 (day 1) and 4 days (day 4) after the start of a hypercaloric carbohydrate-enriched diet (approximately 2.5 times energy expenditure). The secretion of de novo palmitate was increased 15- and 43-fold after 1 and 4 days of hyperalimentation (2.6+/-1.2 (basal state), 40.8+/-20.0 (day 1), and 113.3+/-42.0 micromol/kg per d (day 4)). Even though 4 days of hyperalimentation increased the secretion of de novo stearate 43-fold and de novo oleate 70-fold (stearate; 0.2+/-0.2 (basal), 8.6+/-3.3 micromol/kg per d (day 4), oleate; 0.4+/-0.4 (basal), 28.2+/-12.7 micromol/kg per d (day 4)), palmitate accounted for 75-85% of all the de novo VLDL TGFA. One day of carbohydrate hyperalimentation tended to decrease the secretion while 4 days increased the secretion of all preformed FA in VLDL TG. The rate of secretion of preformed palmitate and oleate were almost identical (palmitate; 80.2+/-22.2 (basal), 45.1+/-23.8 (day 1), and 256.2+/-74.1 micromol/kg per d (day 4), oleate; 95.2+/-22.8 (basal), 46.2+/-24.2 (day 1), and 356.8+/-74.1 micromol/kg per d (day 4)) and collectively these two FA accounted for 80-90% of the secretion from the preformed source. Palmitate is the predominant product of acute and prolonged carbohydrate mediated lipogenesis in the human liver. The pathway of further elongation and subsequent desaturation of de novo synthesized palmitate to generate stearate and oleate is inducible but, quantitatively, of minor significance in hepatic lipogenesis.     

Inhibition of stimulated amylase secretion by adrenomedullin in rat pancreatic acini

Adrenomedullin is a novel hypotensive peptide originally isolated from human pheochromocytoma and recently localized to PP cells of the pancreatic islets of Langerhans. Based on the pancreatic islet-acinar axis model, we investigated the effect of adrenomedullin on regulated exocytosis of exocrine pancreas. Using rat [125I]-adrenomedullin, specific binding sites were localized to rat pancreatic acini. We next examined the effect of adrenomedullin on 100 pM cholecystokinin (CCK)-stimulated amylase release from pancreatic acini. Adrenomedullin inhibited amylase secretion in a dose-dependent manner by approximately 50% at maximum, and the IC50 was 1.1 pM. However, adrenomedullin did not affect rat [125I]CCK binding to isolated acini or reduce the intracellular free Ca2+ concentration increased by CCK. Adrenomedullin also inhibited amylase secretion induced by 1 microM calcium ionophore A23187, suggesting that adrenomedullin inhibits stimulated amylase secretion by functioning at a step(s) distal to the ligand-receptor binding system and intracellular calcium mobilizing mechanism. In streptolysin-O permeabilized acini, 10 nM adrenomedullin shifted the calcium dose-response curve to the right, indicating that adrenomedullin inhibits calcium-induced amylase secretion by reducing calcium sensitivity of the pancreatic exocytotic machinery. In addition, pretreatment of pancreatic acini with pertussis toxin abolished the inhibitory effect of adrenomedullin on CCK-stimulated amylase secretion. These results indicate that adrenomedullin inhibits stimulated amylase secretion by reducing the calcium sensitivity of the exocytotic machinery of the pancreatic acini. A pertussis toxin-sensitive GTP-binding protein(s) is also involved in this mechanism.     

Topological photoaffinity labeling of the rabbit ileal Na+/bile-salt-cotransport system

For the investigation of the topology of the rabbit ileal Na+/bile-salt-cotransport system, composed of a 93-kDa integral membrane protein and a peripheral 14-kDa bile-acid-binding protein (ILBP), we have synthesized photolabile dimeric bile-salt-transport inhibitors (photoblockers), G1-X-G2, where two bile acid moieties (G1 and G2) are tethered together via a spacer, X, and where one of the two bile acid moieties carries a photoactivatable group. These photoblockers specifically interact with the ileal Na+/bile-salt-cotransport system as demonstrated by a concentration-dependent inhibition of [3H]cholyltaurine uptake by rabbit ileal brush-border membrane vesicles and by inhibition of photolabeling of the 93-kDa and 14-kDa bile-salt-binding proteins by 7,7-azo and 3,3-azo derivatives of cholyltaurine. Ileal bile-salt uptake was specifically inhibited by the photoblockers, which were not taken up themselves by the small intestine as demonstrated by in vivo ileal perfusion. Dependent on the photoblocker used several polypeptides in the molecular-mass range of 14-130 kDa were labeled. The cytoplasmically attached 14-kDa ILBP was significantly labeled only by inhibitors that are photoactivatable in bile acid moiety G1, suggesting that during binding and translocation of a bile-salt molecule by the ileal bile-salt-transport system the steroid nucleus gets access to the cytoplasmic site of the ileal brush-border membrane first. Photoaffinity labeling in the frozen state with the transportable 3,3-azo and 7,7-azo derivatives of cholyltaurine revealed a time-dependent increase in the extent of labeling of the 14-kDa and 93-kDa proteins, suggesting a labeling of these proteins from the cytoplasmic site of the ileal brush-border membrane. By photoaffinity labeling in the frozen state with the various photoblockers time-dependent changes in the extent of photoaffinity labeling of bile-salt-binding proteins were observed, demonstrating the possibility of topological analysis of the rabbit ileal Na+/bile-salt-cotransport system.     

Effect of histamine on technetium-99m excretion by gastric mucosa

The ability of histamine to increase excretion of 99mtechnetium by gastric mucosa was investigated in dogs with Heidenhain pouches and denervated antral pouches. Histamine increased Heidenhain pouch 99mtechnetium output in a dose-related manner, and 99mtechnetium output was related linearly to acid output. Antral pouch 99mtechnetium output was unchanged by increasing doses of histamine. The study suggests that concomitant use of histamine may improve the accuracy of 99mtechnetium scanning in the clinical diagnosis of conditions caused by ectopic gastric mucosa.     

Mechanisms by which histamine stimulates rapidly adapting receptors in dog lungs

The relative amounts of folate compounds having 1--3--, 4--, 5-- and 6--glutamic acid residues in the molecule were measured in red blood cells. The results were expressed in relation to methyltetrahydrofolate pentaglutamate (5-glutamic acid residues) which is the analogue present in highest concentration. When the concentration of pentaglutamate is given a value of 100 the relative concentration of folates with 1--3--, 4--, 5-- and 6--glutamic acid residues in control subjects are 48, 48, 100 and 50 respectively. In folate deficiency there is a fall in the relative amount of the short chain glutamic acid chain compounds in addition to having an overall fall in the amount of folate present, the values for 1--3, 4, 5 and 6 chain folates being 16, 14, 100 and 39. By contrast, in untreated pernicious anaemia there is an accumulation of the short chain folates as well as an overall fall in polyglutamate concentration and the relative concentrations were 72, 44, 100 and 30. Folate polyglutamate appears to be the active coenzyme and the reltive amounts of glutamic acid residues may serve to regulate the rate of enzyme activity. In pernicious anaemia the amount of enzyme is reduced and on this hypothesis the regulatory function impaired.     

Glucagon-like peptide-1 7-36 amide and peptide YY from the L-cell of the ileal mucosa are potent inhibitors of vagally induced gastric acid secretion in man

The level of noise at washer and pouring system stations was estimated in 12 dairy plants in 7 regions of the country (voivodships). dB(A) and dB(Lin) were measured and the octave analysis performed within the range of 31.5-8000 Hz. The examined premises were found to be a source of hazard to hearing in workers. Mean value of the sound level expressed in dB(A) accounted for 90.61 dB at the washer station and 90.22 dB at the pouring system station.     

Ion transport across isolated antral mucosa of the rabbit

Isotopic fluxes of Na, Cl, and K were measured across isolated antral mucosa under short-circuit conditions. HCO3 fluxes were also measured with either isotopic and/or pH-stat methods. Net secretion of all four ions was observed. HCO3 secretion is due to a transmural process requiring metabolic energy. Secretion of endogenous HCO3 was not observed, and the unidirectional mucosal-to-serosal flux of HCO3 was negligible. There appears to be a close relationship between HCO3 secretion and the unidirectional mucosal-to-serosal Cl flux, but not relationships were observed between the unidirectional serosal-to-mucosal flux or either unidirectional Na flux. The bulk of HCO3 secretion is independent of the unidirectional Cl fluxes, but there is a fraction of HCO3 transport that is dependent on unidirectional Cl transport. However, HCO3 transport is not measurably influenced by inhibition of net Cl (and Na) transport per se.     

Mechanisms of secretion of toxic organic anions in mammalian kidneys

This short review considers the mechanisms of organic anion secretion in renal proximal tubules. Particular attention is given to the energy coupling of p-aminohippurate transport to inorganic anion gradients generated across both basolateral and brush-border membranes. The coupling is considered to be a consequence of the combined operation of the co-transport and anion-exchange mechanisms. A possible coexistence of several organic anion pathways with overlapping substrate specificity and/or energetic dependence of the total ion gradient are suggested. The problem of identification of transporters involved in organic anion secretion is discussed.     

Identification of gamma delta T lymphocyte subsets that populate calf ileal mucosa after birth

Ileal intraepithelial and lamina propria lymphocytes from newborn, 1.5-week-old, and 3-week-old calves were compared to determine to what extent the mucosa becomes populated after birth. Single and dual fluorescence flow cytometry were used with monoclonal antibodies to bovine (Bo) CD molecules to identify lymphocyte subpopulations. Few ileal mucosal lymphocytes were present in calves at birth. However, by 1.5 weeks of age, the villi were populated with large numbers of lymphocytes, and by 3 weeks of age, the numbers had increased further. These included a prominent subpopulation of gamma delta T cells. Several subsets of gamma delta T cells populated ileal mucosa after birth. The predominant subset coexpressed BoCD2, and a smaller subset coexpressed BoCD8. WC1+ gamma delta T cells comprised the smallest subset. All gamma delta T cell subsets coexpressed ACT2, a molecule expressed on activated WC1+ and WC1- gamma delta T cells from cattle.     

Mechanisms determining the time course of secretion in neuroendocrine cells

Transmitter release from chromaffin cells differs from that in synapses in that it persists for a longer time after Ca2+ entry has stopped. This prolonged secretion is not due to a delay between vesicle fusion and transmitter release, nor to slow detection of released substance: step increases in capacitance due to single vesicle fusion precede the release detected by amperometry by only a few milliseconds. The persistence of secretion after a depolarization is reduced by addition of mobile calcium buffer. This suggests that most of the delay is due to diffusion of Ca2+ between channels and release sites, implying that Ca2+ channels and secretory vesicles are not colocalized in chromaffin cells, in contrast to presynaptic active zones.     

Expression of rabbit ileal N3 Na+/nucleoside cotransport activity in Xenopus laevis oocytes

OBJECTIVES: Our goal was to provide the range of cost savings associated with various catheter reuse strategies. BACKGROUND: Percutaneous transluminal coronary angioplasty catheters are commonly reused in several countries outside the United States. However, the cost-effectiveness of such reuse strategies has not been evaluated. METHODS: Three theoretical models of catheter reuse were constructed using the actual costs for treating patients with coronary angioplasty at the Cleveland Clinic. Costs were calculated based on the number of balloon catheters, the amount of contrast agent used and the rates for urgent revascularization that were observed in a prospective Canadian study on catheter reuse. RESULTS: The median cost to treat a lesion by means of coronary angioplasty using new catheters was $8,800 per patient. In reuse models, the potential to reduce cost depended on the number of balloon catheters used and the rates of urgent revascularization. The "best care" scenario offered a potential savings of $480 (5.5% of total in-hospital cost), whereas the "worst case" scenario resulted in an increased cost of $1,075 (12.2% of total in-hospital cost) compared with the single-use strategy. Cost of the "likely case" scenario was similar to that of the single-use strategy. Sensitivity analyses identified the different rates of revascularization and cost of balloon catheters required to offset potential savings in each strategy. CONCLUSIONS: Although reusing coronary angioplasty catheters may reduce total in-hospital costs, even a modest increase in complications requiring urgent revascularization may offset any potential savings. However, if an increase in complications and procedure time can be avoided, the reuse strategy has significant economic potential and, ultimately, may be extended to other percutaneous coronary interventional equipment.