Intestinal anion exchange in teleost water balance

Simultaneous measurements of all major electrolytes including HCO3(-) and H+ as well as water demonstrated that fluids absorbed by the anterior intestine of the marine gulf toadfish under in vivo-like conditions on an overall net basis are hypertonic at 380 mOsm and acidic ([H+] = 27 mM). This unusual composition of fluids absorbed across the intestinal epithelium is due to the unusual intestinal fluid chemistry resulting from seawater ingestion and selective ion and water absorption along the gastro-intestinal tract. Measurement under near symmetrical conditions with high NaCl concentrations and low MgSO4 concentrations revealed absorption of iso-osmotic and much less acidic fluids by the intestinal epithelium, a situation resembling that of other water absorbing leaky vertebrate epithelia. Reduced luminal NaCl concentrations seen in vivo results in lower absolute water absorption rates but higher Cl-/HCO3(-) exchange rates which are associated with higher net H+ absorption rates. It appears that apical anion exchange is important for net Cl- uptake by the marine teleost intestine especially when luminal NaCl concentrations are low and/or when MgSO4 concentrations are high. Observations indicate that fluid absorption from solutions of low NaCl but high MgSO4 concentrations is energetically more demanding than absorption from NaCl rich solutions at the level of the intestinal epithelium. Furthermore, the high luminal MgSO4 concentration which is an unavoidable consequence of seawater ingestion projects a demand for renal and branchial compensation for intestinal MgSO4 uptake and absorption of hypertonic and acidic fluid by the intestine.     

Gastrointestinal nitric oxide generation in germ-free and conventional rats

Nitric oxide (NO) is a central mediator of various physiological events in the gastrointestinal tract. The influence of the intestinal microflora for NO production in the gut is unknown. Bacteria could contribute to this production either by stimulating the mucosa to produce NO, or they could generate NO themselves. Using germ-free and conventional rats, we measured gaseous NO directly in the gastrointestinal tract and from the luminal contents using a chemiluminescence technique. Mucosal NO production was studied by using an NO synthase (NOS) inhibitor, and to evaluate microbial contribution to the NO generation, nitrate was given to the animals. In conventional rats, luminal NO differed profoundly along the gastrointestinal tract with the greatest concentrations in the stomach [>4,000 parts per billion (ppb)] and cecum (approximately 200 ppb) and lower concentrations in the small intestine and colon (< or =20 ppb). Cecal NO correlated with the levels in incubated luminal contents. NOS inhibition lowered NO levels in the colon, without affecting NO in the stomach and in the cecum. Gastric NO increased greatly after a nitrate load, proving it to be a substrate for NO generation. In germ-free rats, NO was low (< or =30 ppb) throughout the gastrointestinal tract and absent in the incubated luminal contents. NO also remained low after a nitrate load. Our results demonstrate a pivotal role of the intestinal microflora in gastrointestinal NO generation. Distinctly compartmentalized qualitative and quantitative NO levels in conventional and germ-free rats reflect complex host microbial cross talks, possibly making NO a regulator of the intestinal eco system.     

Transfer of functional immunoglobulin G (IgG) antibody into the gastrointestinal tract accounts for IgG clearance in calves.

The transfer of circulating immunoglobulin G1 (IgG1) antibody to the gastrointestinal tract in young calves was quantified by using bovine anti-dinitrophenol IgG1 antibody labeled with 125I. The antibody was administered to newborn calves by intravenous injection, and transfer of the labeled IgG1 to the gastrointestinal tract occurred as demonstrated by excretion of protein-bound label in the feces and by the presence of the labeled IgG1 antibody in the gastrointestinal tract lumen at necropsy. Sixty-eight percent of the [125I]IgG1 clearance occurred by transfer to the gastrointestinal tract. Protein-bound 125I in the gastrointestinal tract lumen retained 65% of the specific dinitrophenol-binding ability of the labeled antibody originally administered. These results show that (i) transfer to the intestinal lumen is the major means of IgG1 clearance in calves, and (ii) this transfer results in antigen-binding antibody in the intestinal tract lumen. The potential contribution to enteric immunity of IgG1 reaching the intestinal lumen from circulation remains to be determined.     

The prevention of the fluid-electrolyte "problem" by simple means

Proper fluid balance may be maintained in patients after operation by the employment of simple, inexpensive procedures which may be carried out even in the smallest hospitals. Daily weighing of patients, measurement of fluid intake and output, and knowledge of the probable electrolyte content of fluid losses are adequate guides for replacement of fluids and electrolytes. An increase in body weight is a warning of overhydration.The content of the solution used for replacement is dictated by the route of fluid output-whether from the gastrointestinal tract, the skin, or the kidneys. Insensible losses (by perspiration and respiration) are fairly static. Except to replace extrarenal losses, parenteral administration of normal saline solution in the immediate postoperative period is contraindicated. Mistakes in replacement methods, especially those causing overhydration, are particularly hazardous for elderly patients.     

Gastrointestinal somatostatin: distribution, secretion and physiological significance

Somatostatin-like immunoreactivity (SLI) has been found throughout the gastrointestinal tract in all species examined. In the stomach it is mainly present in endocrine-type D-cells whereas in the intestine there is also an extensive distribution in enteric neurones. In all regions of the gastrointestinal tract multiple forms of somatostatin exist. A precursor (prosomatostatin) has been partially sequenced, three forms with 20 (SS-20), 25 (SS-25) and 28 (SS-28) amino acids completely sequenced, and somatostatin-14 (SS-14) demonstrated by radioimmunoassay. Both SS-14 and SS-28 exert a wide range of actions on the gastrointestinal tract and there is strong supportive evidence for a role in the regulation of gastric acid and gastrin secretion, gastrointestinal motility and intestinal transport. Both in vivo and in vitro studies on the secretion of gastric SLI into the vasculature have shown that nutrients initiate the process but that subsequent events are regulated by a complex interplay between hormonal and neuronal pathways. GIP is one of the most potent hormonal secretagogues. In the stomach, acetylcholine, opioid peptides and substance P are probably involved in parasympathetic inhibitory pathways and gastrin releasing peptide in stimulatory pathways. The sympathetic nerves are also stimulatory. Regulation of secretion of intestinal SLI has not been so extensively studied. Although SLI is also found in the gastrointestinal lumen the significance is unclear. Despite these advances the exact route of delivery of somatostatin to its target organs is uncertain and paracrine, endocrine and neural pathways may all be involved.     

PREVENTION OF THE FLUID-ELECTROLYTE “PROBLEM” BY SIMPLE MEANS

Proper fluid balance may be maintained in patients after operation by the employment of simple, inexpensive procedures which may be carried out even in the smallest hospitals.Daily weighing of patients, measurement of fluid intake and output, and knowledge of the probable electrolyte content of fluid losses are adequate guides for replacement of fluids and electrolytes. An increase in body weight is a warning of overhydration.The content of the solution used for replacement is dictated by the route of fluid output—whether from the gastrointestinal tract, the skin, or the kidneys. Insensible losses (by perspiration and respiration) are fairly static.Except to replace extrarenal losses, parenteral administration of normal saline solution in the immediate postoperative period is contraindicated.Mistakes in replacement methods, especially those causing overhydration, are particularly hazardous for elderly patients.     

Gastrointestinal assimilation of Cu during digestion of a single meal in the freshwater rainbow trout (Oncorhynchus mykiss)

Gastrointestinal processing and assimilation of Cu in vivo was investigated by sequential chyme analysis over a 72 h period following ingestion of a single satiation meal (3% body weight) of commercial trout food (Cu content=0.42 micromol g(-1)) by adult rainbow trout. Leaded glass ballotini beads incorporated into the food and detected by X-ray radiography were employed as an inert marker in order to quantify net Cu absorption or secretion in various parts of the tract. Cu concentrations in the supernatant (fluid phase) fell from about 0.06 micromol mL(-1) (63 microM) in the stomach at 2 h to about 0.003 micromol mL(-1) (3 microM) in the posterior intestine at 72 h. Cu concentrations in the solid phase were 10 to 30-fold higher than in the fluid phase, and increased about 4-fold from the stomach at 2 h to the posterior intestine at 72 h. By reference to the inert marker, overall net Cu absorption from the ingested food by 72 h was about 50%. The mid-intestine, and posterior intestine emerged as important sites of net Cu and water absorption and a potential role for the stomach in this process was also indicated. The anterior intestine was a site of large net Cu addition to the chyme, probably due to large net additions of Cu-containing fluids in the form of bile and other secretions in this segment. The results provide valuable information about sites of Cu absorption and realistic concentrations of Cu in chyme fluid for future in vitro mechanistic studies on Cu transport in the trout gastrointestinal tract.     

Oral bioavailability and drug/carrier particulate systems

The oral route remains the preferred route of administration to ensure patient satisfaction and compliance. However, new chemical entities may exhibit low bioavailability after oral administration because of poor stability within the gastrointestinal tract, poor solubility in gastrointestinal fluids, low mucosal permeability, and/or extensive first-pass metabolism. Consequently, these new drug substances cannot be further developed using conventional oral formulations. This issue is addressed by an innovative approach based on the entrapment of drug molecules in drug/carrier assembling systems. The carrier materials are lipids, naturally occurring polymers or synthetic polymers, which are considered as nontoxic and biocompatible materials. Drug entrapment is intended to protect drug substances against degradation by gastrointestinal fluids. Fine drug/carrier particle size ensures increased drug dissolution rates. Carriers and particle supramolecular organization can be designed to enhance drug absorption through the intestinal epithelium and lymphatic transport. Promising preclinical results have been obtained with model drugs like paclitaxel, insulin, calcitonin, or cyclosporin. Attention has focused on mucoadhesive carriers like chitosan that favor an intimate and extended contact between drugs and intestinal cells, thus enhancing absorption. Addition of ligands such as lectins improves intestinal drug absorption through specific binding of the carrier to intestinal cell carbohydrates. In conclusion, drug/carrier particulate systems are an attractive and exciting drug delivery strategy for highly potent drug substances unsuitable for oral use. Further evidence will determine whether this approach has marked therapeutic benefits over conventional drug formulations and is compatible with large-scale industrial production and stringent registration requirements. Producing highly effective particulate systems requiring low-complexity manufacturing processes is therefore an ongoing challenge.     

Qualitative and quantitative comparison of gut bacterial colonization in enterally and parenterally fed neonatal pigs

Total parenteral nutrition (TPN) has been associated with mucosal atrophy, impaired gut barrier function, and translocation of luminal bacteria with resultant sepsis in preterm human infants. Currently, we examined the effects of enteral (ENT) or TPN treatments on translocation events in neonatal pigs and on colonization and composition of microbiota in the neonatal gut. Newborn, colostrum-deprived pigs (<24 hours old) were fitted with intravenous catheters and were fed either ENT (n = 13) or TPN (n = 13) for 7 days. After 7 days of treatment, pigs were euthanized and samples were collected for bacterial culture from the blood, intestinal tract and organs. ENT pigs had increased numbers of bacterial genera isolated, higher concentrations of bacteria (CFU/g), and increased colonization of all segments of the intestinal tract compared to the TPN pigs. Translocation of bacteria from the intestinal tract to tissues or blood was similar (8 of 13) for both groups. The ENT group had 1/13 positive for Clostridium difficile toxin A whereas the TPN group had 5/13. We concluded that ENT favored increased bacterial concentrations comprised of more speciation in the gastrointestinal tract compared to TPN, and that TPN-treated piglets were at higher risk of colonization by toxin-expressing strains of C. difficile.     

Digestive proteinases of larvae of the corn earworm, Heliothis zea: characterization, distribution, and dietary relationships.

Proteinases and peptidases from the intestinal tract of fifth-instar larvae of Heliothis (= Helicoverpa) zea (Boddie) (Lepidoptera:Noctuidae) were characterized based on their substrate specificity, tissue of origin, and pH optimum. Activity corresponding to trypsin, chymotrypsin, carboxypeptidases A and B, and leucine aminopeptidase was detected in regurgitated fluids, midgut contents, and midgut wall. High levels of proteinase activity were detected in whole midgut homogenates, with much lower levels being observed in foregut and salivary gland homogenates. In addition, enzyme levels were determined from midgut lumen contents, midgut wall homogenates, and regurgitated fluids. Proteinase activities were highest in the regurgitated fluids and midgut lumen contents, with the exception of leucine aminopeptidase activity, which was found primarily in the midgut wall. Larvae fed their natural diet of soybean leaves had digestive proteinase levels that were similar to those of larvae fed artificial diet. No major differences in midgut proteinase activity were detected between larvae reared under axenic or xenic conditions, indicating that the larvae are capable of digesting proteins in the absence of gut microorganisms. The effect of pH on the activity of each proteinase was studied. The pH optima for the major proteinases were determined to be pH 8.0-8.5 for trypsin, when tosyl-L-arginine methyl ester was used as the substrate; and pH 7.5-8.0 for chymotrypsin, when benzoyl-L-tyrosine ethyl ester was used as the substrate.     

The familial syndromes of intestinal pseudoobstruction

Ten reported families with chronic intestinal pseudoobstruction were reviewed. Although clinical manifestations and gastrointestinal contrast roentgenograms are similar in these families, the pathology and inheritance are quite different. Five families have degeneration and fibrosis of the gastrointestinal tract and urinary bladder, three have normal intestinal morphology, and one has degeneration of the myenteric plexus throughout the gastrointestinal tract. Four families are consistent with dominant inheritance, three are consistent with X-linked dominant transmission, and three are compatible with recessive inheritance. Patients in these families have a wide spectrum and degree of chronic and/or intermittent gastrointestinal symptoms. As many as 20% of the family cases discovered are asymptomatic. Operative procedures to drain or resect short dilated intestinal segments may help to relieve symptoms.     

Degradation of insulin-like growth factors in small intestine of suckling rats

Insulin-like growth factors (IFGs), IGF-I and IGF-II, present in mammalian milk, play an important role during gastrointestinal tract development. In this study we identified and localized the activities of the common intestinal proteolytic enzymes and investigated their degradation effect on IGFs. Results indicated that the enzymatic activities of chymotrypsin, trypsin, and elastase progressed from the lowest in the duodenum, to the highest in the midjejunum, and declined in the ileum. Chymotrypsin exhibited the greatest IGFs degradation activities in neonatal intestinal lumen followed by elastase. These data furnish a potential strategic design to supplement IGFs into milk formulas.     

Distinct distributions of D-erythro-neopterin in arteries and veins and its recovery by an enterohepatic circulation.

Large amounts of D-erythro-neopterin, a pteridine derivative, are formed from guanosine triphosphate (GTP) by human macrophages upon stimulation with interferon-gamma. In addition, in humans a basal neopterin level in all body fluids is evident also in absence of immunological stimuli. Extremely high concentrations of D-erythro-neopterin were detected in biliary fluid. We therefore investigated, if an enterohepatic circulation might exist for this substance. We quantified concentrations of pteridines in serum obtained from various vessels and in biliary fluid. Samples were collected during surgery of five patients with duodenal ulcer or adenocarcinoma of the stomach. Our data clearly demonstrate the existence of an enterohepatic circulation for the recovery of neopterin which seems to be specific for this substance. The relative distributions of neopterin concentrations in the gastrointestinal tract and vessels were seen invariably in all patients and were consistent with findings in five corpses examined post mortem. In addition, significantly higher neopterin concentrations, were found in arteries than in veins. The data indicate that neopterin derivatives are consumed in the peripheral capillary system and an enterohepatic circulation is established to maintain constant blood levels of neopterin derivatives. Furthermore, we suppose that the liver is the source of constitutive neopterin concentrations.     

The amount of secreted IgA may not determine the secretory IgA coating ratio of gastrointestinal bacteria

It is reported that some, but not all, bacteria in human faeces are coated with secretory immunoglobulin A (S-IgA). We evaluated the proportion of S-IgA-coated bacteria to total intestinal bacteria (S-IgA coating ratio) in the gastrointestinal tract of two different strains of mice supplied by two different suppliers. The S-IgA coating ratio was significantly different in each gastrointestinal segment and between mouse suppliers. The amount of non-bacteria-bound IgA (free IgA) in each gastrointestinal segment indicated that this difference in the S-IgA coating ratio might not be due to the amount of secreted IgA. Furthermore, immunoblotting analysis revealed that only a small amount of IgA (<5% to free-IgA) was used for the coating. This indicates that, although sufficient S-IgA was secreted to coat the entire intestinal population of bacteria, only some part of the bacteria were coated with S-IgA. This study suggests that the amount of luminal S-IgA may not determine the S-IgA coating ratio, and that the amount of IgA coating intestinal commensal bacteria is very small.     

Osmoregulation and epithelial water transport: lessons from the intestine of marine teleost fish

For teleost fish living in seawater, drinking the surrounding medium is necessary to avoid dehydration. This is a key component of their osmoregulatory strategy presenting the challenge of excreting excess salts while achieving a net retention of water. The intestine has an established role in osmoregulation, and its ability to effectively absorb fluid is crucial to compensating for water losses to the hyperosmotic environment. Despite this, the potential for the teleost intestine to serve as a comparative model for detailed, integrative experimental studies on epithelial water transport has so far gone largely untapped. The following review aims to present an assessment of the teleost intestine as a fluid-transporting epithelium. Beginning with a brief overview of marine teleost osmoregulation, emphasis shifts to the processing of ingested seawater by the gastrointestinal tract and the characteristics of intestinal ion and fluid transport. Particular attention is given to acid–base transfers by the intestine, specifically bicarbonate secretion, which creates the distinctly alkaline gut fluids responsible for the formation of solid calcium carbonate precipitates. The respective contributions of these unique features to intestinal fluid absorption, alongside other recognised ion transport processes, are then subsequently considered within the wider context of the classic physiological problem of epithelial water transport.     

Transferrin degradation by gastrointestinal fluids of suckling and weanling rats

Dietary transferrins are postulated to play a number of biological roles in the developing gastrointestinal tract. A prerequisite for such roles is survival in the gastrointestinal lumen. To evaluate luminal transferrin digestion during development, 125I-transferrin was incubated in vitro with luminal fluid from the stomach and small intestine of 12-day old suckling and 31-day old weanling rats, followed by analysis of degradation products. At both ages, the rate of degradation to trichloroacetic acid soluble material was maximum in the mid-jejunum and lowest in the stomach. Transferrin hydrolysis by weanling fluid was 2-10 times greater than suckling depending upon the particular segment. Chromatography of small intestinal reaction mixtures on Sephacryl S-200 revealed label eluting between intact transferrin and free iodine: two such peaks were generated with suckling fluid and one with weanling. Electrophoresis on SDS-polyacrylamide gels showed two major bands of Mr 69K and 20K; the former was the predominant reaction product with suckling intestinal fluid and the latter with weanling. Both methods showed small amounts of apparently intact transferrin. Results indicate substantial yet incomplete luminal degradation of transferrin which is more pronounced in the weanling than in the suckling. This survival is compatible with potential biological functioning of dietary transferrin or one of its breakdown products within the gastrointestinal tract.     

草鱼肠道酸碱度的研究

胃肠道是一个复杂的消化系统, 每一部分都具有独特的生理特征。酸碱度(pH)是消化道重要的生理指标之一, 其对营养物质的消化、吸收和肠道微生物的生长等具有重要影响。为了研究草鱼在食物消化过程中, 肠道的酸碱度变化, 测定了草鱼肠道食物糜、肠液和黏膜的pH。结果显示, 随着食物的消化, 它们的pH都有下降的趋势。肠道食物糜pH在6.86±0.24到8.43±0.10之间, 肠液pH在7.14±0.22到8.63±0.02之间, 相同时间点相同肠段两者之间的pH差异很小, 并且在实验期间两者的pH变化趋势相同。黏膜pH在6.23±0.04到6.7±0.13之间, 为弱酸性。除了时间点12h外, 相同时间点和相同肠道部位黏膜的pH与食物糜、肠液的pH相比均有显著性差异(P<0.05)。分析发现草鱼摄食食物的pH与上述三相的pH之间均有显著性差异(P<0.05), 研究结果为草鱼消化生理及营养学研究提供了基础资料。     

缬沙坦对动脉粥样硬化兔血清IL-8和TNF-α水平的影响

目的：研究缬沙坦对动脉粥样硬化兔血清IL-8和TNF-α水平的影响。方法：将30只实验兔随机分为3组,每组10只,即正常对照组：喂以普通饲料;高脂饮食组：喂以高脂饮食（含15%蛋黄粉,0.5%胆固醇和5%猪油的饲料）6周,后给予10 ml/d生理盐水4周;药物干预组：喂以高脂饮食6周,后给予缬沙坦（10 mg/kg/d）治疗4周。饲养6周和10周时分别经兔耳缘静脉取血,通过酶联免疫法检测各组兔血清中IL-8和TNF-α的水平。结果：饲养第6周时,高脂饮食组和药物干预组兔血清TNF-α和IL-8水平均较正常对照组明显升高,差异均具有统计学意义（P〈0.05）,而高脂饮食组与药物干预组比较差异无统计学意义（P〉0.05）。饲养第10周时,即缬沙坦干预4周后,药物干预组与建模6周时比较,血清TNF-α及IL-8水平均明显下降,差异具有统计学意义（P〈0.05）,且与高脂饮食组比较,血清TNF-α及IL-8水平亦明显下降,差异具有统计学意义（P〈0.05）。结论：动脉粥样硬化时,血清IL-8和TNF-α升高,缬沙坦能明显降低动脉粥样硬化中IL-8和TNF-α水平,从而发挥抗动脉粥样硬化作用。     

Effect of misoprostol in preventing stress-induced intestinal fluid secretion in rats

Psychological stress may alter gastrointestinal function by central nervous system controlled alteration of local intestinal mediators. Prostaglandins have been shown to prevent epithelial damage to various noxious stimuli. The purpose of this study was to determine (a) if wrap restraint stress altered in vivo intestinal fluid absorption in rats, and (b) if the prostaglandin E1 analogue, misoprostol, could correct observed fluid malabsorption. In vivo loop studies demonstrated net fluid secretion in the ileum and colon of cold wrap restraint stressed rats. In cold wrap restraint stressed rats, misoprostol reversed net secretion to absorption, but it had no effect on fluid absorption in controls. Mild wrap restraint stress did not alter in vivo fluid absorption. We conclude that cold wrap restraint stress is accompanied by net intestinal fluid secretion that can be effectively reversed with misoprostol.     

Sodium and potassium concentrations in the intestinal fluids of the fowl, Gallus domesticus

1. Na and K concentrations in the luminal fluids on the jejunum, ileum and colon were measured in domestic fowl on diets containing different amounts of Na and K. 2. Physiological adjustments of the Na and K content of these fluids were observed to occur in all three intestinal segments. 3. Regulation of gastrointestinal losses of Na and K appears to be initiated in the anterior regions of the intestines of the domestic fowl and is maintained or amplified as the ingesta moves posteriorly.