Effect of portal hypertension on in vivo bile acid-mediated small intestinal mucosal injury in the rat.

This study's purpose was to determine whether portal hypertension adversely affects small intestinal mucosal injury. Portal hypertension was produced in male Sprague-Dawley rats by two-stage ligation of the portal vein. Sham-operated rats were used as controls. Two weeks later, intestinal injury was produced by in vivo perfusion with 5 mM chenodeoxycholic acid for 30 min. Intestinal injury was assessed by quantitative morphometry and by measuring intestinal water and mannitol absorption. Portal hypertension resulted in more injury in the distal perfused intestine as manifested by increased villus tip denudation [portal hypertensive 52.5 +/- 9.6 (SEM) vs controls 28.1 +/- 5.7 microns, P = 0.05). Additionally there was a significant decrease in the unperfused duodenal villus height in portal hypertensive rats (portal hypertensive 755 +/- 22 vs controls 848 +/- 28 microns, P less than 0.02). Portal hypertension had no significant effect on the increase in mannitol absorption or water secretion caused by chenodeoxycholic acid perfusion. This study suggests that portal hypertension alters small intestinal mucosa and increases susceptibility to injury.

Regulation of rat ileal water absorption by central alpha 2 adrenergic receptors.

This study examined the role of central adrenergic receptors in the regulation of water absorption by the rat ileum. Clonidine, an alpha 2-adrenergic receptor agonist, increased water absorption in vivo following intracerebroventricular but not intravenous injection. Intracerebroventricular injection of prazosin, an alpha 1-adrenergic receptor antagonist, did not alter basal water absorption. Prazosin did not prevent the clonidine effect. In contrast, the alpha 2-adrenergic receptor antagonist, yohimbine, reduced basal absorption and prevented the intracerebroventricular clonidine effect. Treatment with reserpine reduced ileal norepinephrine content by 98%, reduced basal water absorption consistent with a loss of sympathetic outflow to the mucosa, but did not prevent the increase in water absorption due to intracerebroventricular clonidine. These results suggest that central alpha 2 receptors regulate water absorption by the rat ileum. The clonidine-induced increase in water absorption is not mediated by the sympathetic nerves innervating the intestine.

Permeation of water through the polymeric components of boil-in-bag laminates.

Diffusion coefficients and equilibrium uptake have been measured for water and 3% acetic acid in film of PETP, lldpe, nylon 6 and nylon 66, and also in some isocyanate adhesives. These materials are used in the construction of boil-in-bags for food. The three methods of measurement used were permeation from a bag, mass uptake, and the use of a novel technique using isotopically labelled water. The principal temperature of investigation has been 100 degrees C. Differences in the permeation parameters for water and 3% acetic acid were small for PETP, but surprisingly large for an inert material such as lldpe. With the nylons differences could readily be ascribed to the fact that these materials are bases. When immersed in boiling water there was no change in the degree of crystallinity of PETP, but lldpe and nylon 66 showed small increases.

Neural blockade in basal and postreceptor-stimulated intestinal transport.

Postreceptor protein stimulation significantly alters the transport state of the ex vivo small intestine. This study investigated the effects of neural blockade on basal and stimulated ionic transport. Rabbit ileal segments (n = 46) were arterially perfused with an oxygenated sanguinous buffered electrolyte solution. The lumen was perfused with an isotonic solution containing [14C]polyethylene glycol as a nonabsorbable marker. Net fluxes of H2O, Na+, and Cl- were calculated. Tetrodotoxin (TTX) was used to block enteric neural transmission. Forskolin (FOR) was used to activate adenylate cyclase, and phorbol 12,13-dibutyrate (PDB) served to activate protein kinase C. Two groups were studied. Group A preparations had no TTX pretreatment, while group B preparations were pretreated with TTX. In the Group A preparations, TTX at 10(-6) M and PDB at 10(-5) M caused significant proabsorptive effects with a delta FH2O of +20 +/- 7 and +15 +/- 2 microliters/min, respectively (P less than 0.05), while FOR stimulated significant secretion with a delta FH2O of -14 +/- 3 microliter/min (P less than 0.05). In the Group B TTX-pretreated preparations, FOR did not cause secretion and PDB maintained an absorptive state. These results indicate that neural blockade with TTX reverses basal secretion in the ex vivo intestine, suggesting that an intact enteric nervous system maintains the secretory status of the intestine. FOR-induced adenylate cyclase-activated secretion does not occur in the presence of TTX, implying that intact neural transmission is required for the FOR effect. PDB-induced protein kinase C-activated absorption occurs despite neural blockade, suggesting that the PDB-induced proabsorptive effect is mediated without neural intermediaries.

Shed snake skin and hairless mouse skin as model membranes for human skin during permeation studies.

Difficulties in obtaining and using human skin have tempted many workers to employ animal membranes for percutaneous absorption studies. We have investigated the suitability of two species of snake (Elaphe obsoleta, Python molurus) for this purpose and compared our in vitro experimental results for human skin and for hairless mouse, a currently popular model. The effects of long-term hydration on the membranes were investigated over 8 d using tritiated water as a model permeant. The initial permeability coefficients of all the membranes were similar (0.74-2.2 X 10(-3) cm 2h-1). Although the human and squamate skins did not change significantly over the test period, the permeability of hairless mouse skin increased 37 times. The actions of typical enhancers on the permeabilities of the membranes to a model penetrant 5-fluorouracil (5-FU) were tested using 3% Azone in Tween 20/saline, propylene glycol (PG), 2% Azone in PG, and 5% oleic acid in PG. While the data from snake membranes tended to underestimate the enhancer effects, those from hairless mouse skin greatly overestimated the changes. None of the membranes was a completely reliable model for assessing human percutaneous absorption as modified by accelerants. Pretreatment with acetone did not significantly change the permeability of human or squamate skins to 5-FU, although that of hairless mouse increased twentyfold. An overall conclusion is that, wherever possible, human skin should be used in absorption studies and not hairless mouse or snake skin; otherwise, misleading results may be obtained.

Apical membrane vesicles of ADH-stimulated toad bladder are highly water permeable.

Antidiuretic hormone (ADH) stimulation of the toad urinary bladder causes intracellular vesicles called aggrephores to fuse with the apical plasma membrane of granular cells. Aggrephore membranes contain particle aggregates. Particle aggregates are believed to be water channels that cause large increases in the water permeability (PF) of the granular cell apical membrane. Removal of ADH causes the retrieval of particle aggregate-containing apical membrane via endocytosis and a decline in PF. We have previously shown that fluid phase markers are sequestered in these particle aggregate-containing vesicles during retrieval of the apical membrane and that these vesicles can be recovered in cell homogenates. We have now loaded these vesicles with the self-quenching fluorophore carboxyfluorescein (CF) to measure and compare their PF with that of CF-loaded resealed human erythrocyte ghosts. The membranes of these retrieved vesicles have a very high water permeability. The minimum PF of 99% of these vesicles is 4.5 X 10(-2) cm/s. This PF is comparable with that of erythrocyte ghosts (5.4 X 10(-2) cm/s) measured under identical conditions. We conclude that these vesicles are highly permeable to water, and this is consistent with their postulated function of retrieving water channels that have been inserted into the apical membrane in response to ADH.

Effects of hypertonicity on ADH-stimulated water permeability in rat inner medullary collecting duct.

To assess the effects of increased tonicity on water reabsorption (Jv) in inner medullary collecting ducts (IMCD), antidiuretic hormone (ADH)-stimulated Jv and water permeability (PF) were determined in microperfused IMCD dissected from the inner medulla of rat kidney. In IMCD exposed to a 150-mosmol/kgH2O gradient in isotonic bath, ADH-stimulated PF averaged 719 +/- 93 microns/s. Symmetric addition of 75 mM NaCl to perfusate and bath resulted in a significant augmentation of ADH-stimulated PF (56%) that was reversible when initial solutions were restored. Despite the increase in PF, JV did not change but would have decreased by 16% (P less than 0.01) had PF not increased, because of the greater absolute axial increase in luminal tonicity that occurs with more hypertonic luminal solutions. When 150 mM mannitol was used to increase tonicity, similar effects were observed. However, 150 mM urea had no effect on ADH-stimulated PF. In IMCD exposed to 8-para-(chlorophenylthio)-adenosine 3',5'-cyclic monophosphate, addition of 75 mM NaCl to both and perfusate also resulted in a 76% increase in PF. These results are the first to demonstrate directly that increased effective tonicity augments ADH-stimulated PF in rat IMCD at a site distal to adenosine 3',5'-cyclic monophosphate generation. This effect may contribute to maintenance of medullary interstitial tonicity during antidiuresis by ensuring that most water reabsorption occurs more proximally within the IMCD.

Effect of low mole fraction of trehalose dicorynomycolate from Corynebacterium diphtheriae on water permeability and electrical capacitance of lipid bilayer membranes.

The effect of incorporation of different proportions of trehalose dicorynomycolates (TDC) into lecithin bilayer membranes was studied. It was found that TDC, induces a 14% decrease of water osmotic permeability (42.6 +/- 3.9 to 36.8 +/- 2.7 microns/s) at 1.6 mole%, suggesting that this substance leads to an increase of the degree of packing of the constituent lipid molecules. A condensing effect of TDC was also apparent from membrane electrical capacitance (Cm) measurement. By incorporating TDC into bilayer membranes, the value of Cm experienced a decrease of 29% at 1.6% mole fraction. This finding was taken to reflect an increase in membrane thickness, known in many examples, to be related to the condensing effect.

Lung vascular permeability changes in lambs with hyaline membrane disease.

To investigate the mechanism of pulmonary edema in hyaline membrane disease (HMD), lymph from the efferent duct of the mediastinal lymph node was collected in premature lambs before and after delivery by cesarean section. Mean lymph flow in 7 lambs with histologically verified HMD increased progressively over 4 h after delivery to 3 times the fetal value, while lymph flow in 7 lambs without HMD increased to 3.5 times at 1 h and decreased thereafter. At 4 h after birth, lung lymph flow was significantly higher in lambs with HMD than in lambs without HMD (0.70 +/- 0.15 (SEM) vs 0.43 +/- 0.07 ml.h-1.kg-1). Lymph/plasma concentration ratio for small endogenous protein fractions (effective molecular radius, 3.6 and 3.8 nm) was significantly higher in lambs with HMD than in lambs without HMD at 2-4 h. Postmortem extravascular lung water was significantly higher in lambs with HMD (6.1 +/- 0.5 vs 4.3 +/- 0.3 ml/g dry lung weight). It is concluded that lung water is high in lambs with HMD, which appears to be a result both of delayed absorption of fetal lung liquid and increased permeability of the pulmonary exchange vessels.

[The effect of external gamma-irradiation on the distribution of deuterium oxide in the rat body]. / Vliianie vneshnego gamma-izlucheniia na raspredelenie okisi deiteriia v organizme krys.

External gamma-irradiation (7.74 and 15.48 x 10(-2) C/kg) does not influence the distribution of deuterium oxide within a rat body: it is distributed uniformly among the organs and tissues as it is observed in nonirradiated animals. The effect of external irradiation favors the retention of deuterium oxide within the organs and tissues. The delayed excretion of deuterium oxide from the body can enhance the biological effect. This should be taken into account in standardizing the combined radiation effects.

On mechanisms of water nuclear magnetic relaxation in protein solutions.

To describe water nuclear magnetic relaxation in protein solutions a new modification of two-state model has been advanced. It is assumed that the hydration water molecules take part in two type rotation motions: fast anisotropic and slow isotropic ones, each of them can be characterized by a single correlation time. A transition of water molecule from bound state into bulk water is considered as defect arousing and is described by defect diffusion model. The model advanced allows one to describe both frequency and temperature dependences of water spin-lattice relaxation times in protein solutions and to get an information on microdynamic parameters of hydration water molecules such as life time, fraction, hindrance of local motion, etc.

Dynamics and compartmentation of water in certain biosystems.

Investigation performed by nuclear magnetic resonance and by deuteration on the dynamics of water molecules in mammalian blood cells and in amphibian oocytes, muscles and nerves allowed to reveal several populations of cell water molecules. Following up relaxation and exchange processes in cell suspensions, packed cell pellets and in isolated tissues, characteristics of water dynamics and compartmentation in various biosystems are compared.

Hydration forces involved in cellular interactions.

Cellular physical interactions are determinant in many and various biological processes: aggregation, adhesion, segregation, contact inhibition, fusion, etc. A real advance concerning the understanding of cellular interactions from a physical point of view has been performed of late, but a great many problems still remain to be clarified. Thus, DLVO theory extrapolated to cell-cell interactions, is unable to describe cellular interactions at very short distances of separation, where other forces play an important role. A sketch of the original form of DLVO theory, its criticism along with the nature and mechanism of the short range repulsive forces (hydration forces) are presented and discussed.

Root parenchyma cells in water transport.

In experiments with the "sleeves" and the whole roots of Zea mays seedings, the idea of the complicated nature of root pressure and an active part of parenchyma cells in water pumping by roots has been confirmed. It has been shown that root pumping activity is summarized by two, principally different constituents--metabolic and osmotic. The metabolic constituent functions exclusively at the expense of the parenchyma cells activity.

Thermodynamic network modelling of transfer across the perfused guinea-pig placenta, using SPICE.

The response of the dually perfused guinea pig placenta to bolus inputs of the marker substances 125I-albumin and tritiated water is used to model vascular placental topology and membrane characteristics. This is accomplished by generating a thermodynamic network containing ten adjustable variables describing flow and transfer quantitatively. After translation of the network into an electronic circuit the parameter values are determined with the use of the SPICE program. The results are then used to estimate unknown physiological variables like shunted flow, membrane permeabilities, etc. This model has potential usefulness in the study of those areas of placental physiology in which transient analysis is required.

Effect of cecectomy on water and nutrient absorption of birds.

The effect of the removal of the avian digestive ceca on osmoregulation and on absorption of certain nutrients is reviewed. While data indicate that the ceca have the potential for absorption of a significant quantity of water, several studies have demonstrated that effects of cecectomy on water intake and output are transitory and that compensatory adjustments made within 2 to 3 weeks postsurgery allow cecectomized birds to eat and gain weight normally. However, cecectomized great horned owls exposed to 27 degrees C turned over their body water 1.6 times faster than intact owls under the same conditions, suggesting that the ceca do have a vital role in water balance of thermally stressed horned owls. Cecectomy resulted in slightly lower metabolizability of food, lower digestibility of crude fiber in low fiber diets, and greater loss of certain amino acids in cecectomized birds that were fasted or fed a protein-free diet. The latter suggests that the ceca are important in recovery of amino acids endogenous protein degradation. Loss of cecal function also resulted in higher energy intake and excretion in Japanese quail, amounting to 5.7% of the total daily energy requirement.

Effect of chronic vanadate ingestion on amino acid and water absorption in rat intestine.

Chronic administration of a relatively low concentration of vanadate to rats causes inhibition of water, alpha-aminoisobutyric acid (AIB) and L-alanine absorption. The mechanism responsible for this inhibition was tested by studying the uptake of alanine in isolated rat intestinal cells. The studies suggest that the vanadate inhibition of amino acid transport is primarily caused by a decreased activity of the Na+-K+ pump, an action that is similar to what is observed when the rat intestine is acutely exposed to vanadate. Vanadate appeared to have no direct effect on the entry of amino acids into the intestinal cell. This was evident by the fact that amino acid uptake by enterocytes of control rats was not different from the uptake by cells of vanadate-treated animals that have an inwardly directed Na gradient artificially created across them. Furthermore, 86RB influx and efflux into and out of intestinal tissues of the vanadate-treated animals were, respectively, decreased and increased as compared to normal control tissues and they were similar to what is observed when the intestine is acutely exposed to ouabain, a known specific inhibitor of the Na+-K+ pump.

[Estimation of absorbed dose of beta radiation into the critical tissues by a single injection of tritiated water].

The biological effects of tritium in humans need to be clarified, because the chances of humans becoming exposed to tritium beta radiation may increase with the development of the nuclear fusion reactor. To evaluate the biological effects of tritium, it is necessary to estimate exactly the absorbed dose from the tritium beta rays in the tissue. In many reports, the absorbed dose of HTO in the tissues is estimated from the tritium content in body fluid and dose calculations are customarily based upon the water content of soft tissues, which is taken to be 0.7 to 0.8. However, these methods may not show the exact absorbed dose in the organs. In the present study, the radioactivity of the critical tissues was measured directly using a sample oxidizer and the absorbed dose was calculated from the radioactivity of tritium in the tissues. Details on the method for calculation of the absorbed dose in tissues of the mouse is shown in this report. The results suggest that the absorbed dose should be obtained from the radioactivity in the tissues.