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PubMed2001

Muc13, a novel human cell surface mucin expressed by epithelial and hemopoietic cells.

Transmembrane mucins are glycoproteins involved in barrier function in epithelial tissues. To identify novel transmembrane mucin genes, we performed a tblastn search of the GenBanktrade mark EST data bases with a serine/threonine-rich search string, and a rodent gene expressed in bone marrow was identified. We determined the cDNA sequence of the human orthologue of this gene, MUC13, which localizes to chromosome band 3q13.3 and generates 3.2-kilobase pair transcripts encoding a 512-amino acid protein comprised of an N-terminal mucin repeat domain, three epidermal growth factor-like sequences, a SEA module, a transmembrane domain, and a cytoplasmic tail (GenBanktrade mark accession no. ). MUC13 mRNA is expressed most highly in the large intestine and trachea, and at moderate levels in the kidney, small intestine, appendix, and stomach. In situ hybridization in murine tissues revealed expression in intestinal epithelial and lymphoid cells. Immunohistochemistry demonstrated the human MUC13 protein on the apical membrane of both columnar and goblet cells in the gastrointestinal tract, as well as within goblet cell thecae, indicative of secretion in addition to presence on the cell surface. MUC13 is cleaved, and the beta-subunit containing the cytoplasmic tail undergoes homodimerization. Including MUC13, there are at least five cell surface mucins expressed in the gastrointestinal tract.

Amino Acid Sequence↗

PubMed1999

Expression and regulation of the human beta-defensins hBD-1 and hBD-2 in intestinal epithelium.

The intestinal epithelium forms a physical barrier to limit access of enteric microbes to the host and contributes to innate host defense by producing effector molecules against luminal microbes. To further define the role of the intestinal epithelium in antimicrobial host defense, we analyzed the expression, regulation, and production of two antimicrobial peptides, human defensins hBD-1 and hBD-2, by human intestinal epithelial cells in vitro and in vivo. The human colon epithelial cell lines HT-29 and Caco-2 constitutively express hBD-1 mRNA and protein but not hBD-2. However, hBD-2 expression is rapidly induced by IL-1alpha stimulation or infection of those cells with enteroinvasive bacteria. Moreover, hBD-2 functions as a NF-kappaB target gene in the intestinal epithelium as blocking NF-kappaB activation inhibits the up-regulated expression of hBD-2 in response to IL-1alpha stimulation or bacterial infection. Caco-2 cells produce two hBD-1 isoforms and a hBD-2 peptide larger in size than previously described hBD-2 isoforms. Paralleling the in vitro findings, human fetal intestinal xenografts constitutively express hBD-1, but not hBD-2, and hBD-2 expression, but not hBD-1, is up-regulated in xenografts infected intraluminally with Salmonella. hBD-1 is expressed by the epithelium of normal human colon and small intestine, with a similar pattern of expression in inflamed colon. In contrast, there is little hBD-2 expression by the epithelium of normal colon, but abundant hBD-2 expression by the epithelium of inflamed colon. hBD-1 and hBD-2 may be integral components of epithelial innate immunity in the intestine, with each occupying a distinct functional niche in intestinal mucosal defense.

Anti-Bacterial Agents↗

PubMed2004

[Heterogeneity of small intestinal microcirculation].

INTRODUCTION: Microcirculatory disorders play important roles in the impairment of the mucosal barrier of the small intestine. Circulatory failures may increase the heterogeneity of microvascular perfusion, however, conventional methods are inadequate to describe an evolving heterogeneity in time or space. The authors aims were to examine and characterize the microcirculatory reactions in the mucosa and longitudinal muscle of the small intestine in clinically relevant experimental models of circulatory disorders. METHODS: Intravital videomicroscopy with orthogonal polarization spectral imaging technique was used to visualize the microcirculation. A mathematical approach was applied to describe the temporal variability in perfusion based on the calculation of average red blood cell velocity from the relative time periods of observed velocity, while spatial heterogeneity was calculated as a function of the perfused area. The authors' experiments were performed after 1. sham operation, 2. during hemorrhagic shock and crystalloid resuscitation, 3. during 2-hr endotoxin infusion, 4. in response to nitric oxide synthesis inhibition, and 5. after superior mesenteric artery occlusion and reperfusion. RESULTS: During hemorrhagic shock a fluctuating flow pattern appeared in the mucosa, the average red blood cell velocity decreased by 40% in the villi and by 60% in the muscle. Ischemia caused 20% flow reduction in both layers, while endotoxin caused a temporary 20% decrease in the mucosa, and a persistent, over 25% decrease in the muscle layer. Nitric oxide synthesis inhibition resulted in a 40% decrease in both structures. CONCLUSIONS: Heterogeneity of microcirculatory perfusion may appeared both spatially (between or within anatomical layers) and in time (periodically) after the insults. A redistribution of blood flow favouring the mucosa evolves in the small intestine after systemic circulatory disorders. Heterogenous perfusion-related microcirculatory changes can be characterized with mathematical approaches, and these calculations should be taken into account during the comparison of the consequences of distinct circulatory failures involving the small intestine.

Animals↗

PubMed2004

Improvement of barrier function and stimulation of colonic epithelial anion secretion by Menoease Pills.

AIM: Menoease Pills (MP), a Chinese medicine-based new formula for postmenopausal women, has been shown to modulate the endocrine and immune systems. The present study investigated the effects of MP and one of its active ingredients, ligustrazine, on epithelial barrier and ion transport function in a human colonic cell line, T84. METHODS: Colonic transepithelial electrophysiological characteristics and colonic anion secretion were studied using the short circuit current (ISC) technique. RT-PCR was used to examine the expression of cytoplasmic proteins associated with the tight junctions, ZO-1 (zonula occludens-1) and ZO-2 (zonula occludens-2). RESULTS: Pretreatment of T84 cells with MP (15 microg/mL) for 72 h significantly increased basal potential difference, transepithelial resistance and basal ISC. RT-PCR results showed that the expressions of ZO-1 and ZO-2 were significantly increased after MP treatment, consistent with improved epithelial barrier function. Results of acute stimulation showed that apical addition of MP produced a concentration-dependent (10-5,000 microg/mL, EC50 = 293.9 microg/mL) increase in ISC. MP-induced ISC was inhibited by basolateral treatment with bumetanide (100 micromol/L), an inhibitor of the Na+-K+-2Cl- cotransporter, apical addition of Cl- channel blockers, diphenylamine-2, 2'-dicarboxylic acid (1 mmol/L) or glibenclamide (1 mmol/L), but not 4, 4'-diisothiocyanostilbene-2, 2'-disulfonic acid or epithelial Na+ channel blocker, amiloride. The effect of MP on ZO-1 and ZO-2 was mimicked by Ligustrazine and the ligustrazine-induced ISC was also blocked by basolateral application of bumetanide and apical addition of diphenylamine-2, 2'-dicarboxylic acid or glibenclamide, and reduced by a removal of extracellular Cl-. CONCLUSION: The results of the present study suggest that MP and lligustrazine may improve epithelial barrier function and exert a stimulatory effect on colonic anion secretion, indicating the potential use of MP and its active ingredients for improvement of GI tract host defense and alleviation of constipation often seen in the elderly.

Adrenergic beta-Agonists↗

PubMed2005

Evolution of the ATP-binding cassette (ABC) transporter superfamily in vertebrates.

The ATP-binding cassette (ABC) superfamily of genes encode membrane proteins that transport a diverse set of substrates across membranes. Mutations in ABC transporters cause or contribute to many different Mendelian and complex disorders including adrenoleukodystrophy, cystic fibrosis, retinal degeneration, hypercholesterolemia, and cholestasis. The genes play important roles in protecting organisms from xenobiotics and transport compounds across the intestine, blood-brain barrier, and the placenta. There are 48 ABC genes in the human genome divided into seven subfamilies based on amino acid sequence similarities and phylogeny. These seven subfamilies are represented in all eukaryotic genomes and are therefore of ancient origin. Sequencing the genomes of numerous vertebrate organisms has allowed the complement of ABC transporters to be characterized and the evolution of the genes to be assessed. Most ABC transporters are conserved in all vertebrates, but there are also several examples of recent duplication and gene loss. For genes with a conserved ortholog, animal models have been identified or developed that can be used to probe the function and regulation of selected genes. Genes that are restricted to a specific group of animals may represent specialized functions that could provide insight into unique biological properties of that organism. Further characterization of all ABC transporters from the human genome and from model organisms will lead to additional insights into normal physiology and human disease.

ATP-Binding Cassette Transporters↗

PubMed1985

[Microbial ecology of the colon].

It has been known for a long time that the human gastrointestinal tract contains 10(14) micro-organisms, which are predominantly anaerobic. Recent research has provided a better understanding of the functions and the equilibrium of the intestinal ecosystem in which the intestinal mucosa and the microbial flora which it supports interact. Any modification in one or other of the constituents of this ecosystem is likely to disturb the normal ecological equilibrium, resulting in a variety of gastro-intestinal diseases. Today, the intestinal ecosystem can be considered to be a system of defence and equilibrium or, conversely, as a reservoir of infection, which is confirmed by the study of certain faecal bacterial profiles with a high risk of infection. In gastrointestinal surgery and paediatrics, the correlation between antibiotic therapy, intestinal microbial proliferation and the development of septicaemia confers a fundamental role of the defence barriers of the gastrointestinal tract in the control or potentially pathogenic endogenous micro-organisms.

Colon↗

PubMed1992

Thrombus with infection in total artificial heart animals.

From January 1980 to December 1990, several types of total artificial hearts were implanted into 378 animals. In a retrospective study of these animals, 147 (39%) were found to have thrombus with infection (T&I). The criteria for diagnosis was thrombus formation in the artificial heart and a positive blood culture. The most common pathogen isolated from T&I animals was Pseudomonas species. Concurrent skin lesions and contamination from the pressure lines may be the primary sources of infection, but bacterial translocation from the intestine is another possible route. The main pathological findings at necropsies of artificial heart animals with T&I were associated with sepsis, congestive heart failure, infected thrombus, thromboembolism, and multiple organ infarctions. Most thrombi appeared to have originated from valve junctions and connectors. On the basis of these observations, a possible mechanism for pathogenesis of T&I has been proposed. The results suggest that design improvements and surface modifications to reduce thrombosis are important factors that should be carefully considered. Similarly, it is important to eliminate the route of entry of pathogenic microorganisms. These findings imply that bacterial interaction with thrombus, device related bacterial colonization, and host immunomodulation and gut barrier function following artificial heart implantation need further investigation.

Animals↗

PubMed1991

Dosimetric estimates for clinical positron emission tomographic scanning after injection of [18F]-6-fluorodopamine.

Positron emission tomographic (PET) scanning after systemic i.v. injection of fluorine-18-6-fluorodopamine ([18F]-6F-DA) is a method for visualizing and measuring regional sympathetic nervous system innervation and function. Based on results of preclinical studies of rats and dogs and on previous literature about the fate of injected tracer-labeled catecholamines, dosimetric estimates for clinical studies are presented here. After injection of 1 mCi of [18F]-F-DA, the radiation dose would be highest to the wall of the urinary bladder (1.40 rem/mCi), due to accumulation of radioactive metabolites of [18F]-F-DA in urine. Radioactivity also would accumulate in bile. Organs receiving the next highest dose would be the kidneys (0.9 rem/mCi) and small intestine (0.2 rem/mCi). The parenchymal radiation dose would be lowest in the brain, since there is an effective blood-brain barrier for circulating catecholamines. Radiation doses to all organs after administration of 1 mCi of [18F]-F-DA to humans would be less than 3 rem and, therefore, within current FDA guidelines.

Animals↗

PubMed1997

Antigen sampling by epithelial tissues: implication for vaccine design.

Mucosal surfaces of the respiratory, digestive and urogenital tracts are covered by a specialized epithelium which constitutes an efficient physical barrier against environmental pathogens. These surfaces differ greatly in their cellular organisation and in antigen sampling. In stratified epithelia, professional antigen-presenting cells, the dendritic cells or Langerhans cells, are intimately associated with the epithelial barrier and take up samples of foreign material from the external environment which they transport to local or distant organized lymphoid tissues. In simple epithelia highly specialised cells, the so-called M cells, sample foreign material and microorganisms and deliver them by transepithelial transport from the lumen to the underlying organized lymphoid tissue (MALT). The interaction of lymphocytes with the follicle-associated epithelium (FAE) is responsible for the loss of digestive functions and the acquisition of transepithelial transport activity. The three way interaction of epithelium, lymphoid cells, and microorganisms seen in the FAE which controls the formation of MALT provides a dramatic demonstration of the phenotypic plasticity of the intestinal epithelium and probably of all simple epithelia. We have shown that all mucosal surfaces, covered by stratified or simple epithelia are able to sample and transport live recombinant bacterial vaccines, which elicit systemic and local immune responses against the carrier and the foreign antigen. In gut and nasal-associated lymphoid tissue, Salmonella are taken up by dendritic cells which form a dense cellular network in the dome regions of MALT. Targeting bacterial vaccine candidates to dendritic or M cells is likely to facilitate their sampling by epithelial tissues and to contribute to strong mucosal and systemic immune responses.

Animals↗

PubMedDate not supplied

The influence of celomic membranes and a tunnel between celomic cavities on cancer metastasis in poultry.

The roles of celomic membranes and celomic structures in preventing cancer metastasis were examined. The relationship between a tunnel in the peritoneal cavity of hens and the cancer metastasis was also investigated. A tunnel between the right and left dorsal hepatic cavities was found in almost half of healthy hens. The tunnel was also found in 17% of hens with cancer. Neoplastic cells were detected in the ascitic fluid of 79% of hens with effusions. Metastasis was most severe in the intestinal peritoneal and left dorsal hepatic cavities, whereas the right dorsal hepatic cavity showed the least involvement. Severe inflammatory responses were found within the metastatic membranes, resulting in an increase in their thickness. In tumor-bearing hens, crevasse-like splits were present within the membranes at the layers of loose connective tissues. It appears that the splits prevent further invasion by the cancer cells. There were no successful lesions on the inner surfaces of air sacs. It is suggested that the tunnel in the peritoneal cavity enhances cancer metastasis. We also conclude that the celomic membranes and their structure in hens retard the spread of cancer by functioning as a barrier against direct spread of the cancer cells.

Animals↗

PubMed1994

[An intestinal neosphincter attained by circumscribed muscle proliferation. Technical development and functional evaluation in the dog].

In an experimental study an intestinal neosphincter (INS) was constructed by modifying the principle of the ileocolic nipple-valve anastomosis by means of ultrasonic tissue fragmentation of the contacting serosa of the ileum and the corresponding mucosa of the ileum and colon. The healing of the muscle layers was studied histologically. The function of the INS was investigated in six dogs and compared intraindividually with that of the ileocecal valve and conventional end-to-end anastomosis. Morphologically the neospincters healed within 3 months without major fibrosis. The reference values of the aerobic and anaerobic bacterial counts in the terminal ileum were more than 2 logs lower than in the colon with the normal ileocecal valve, and after ileo-colonic end-to-end-anastomosis bacterial colonization of the terminal ileum was found both qualitatively and quantitatively. Subsequent interposition of the INS led to bacterial clearance of the terminal ileum. The median aerobic bacterial counts were lower by six logs and the an aerobic bacterial counts by 3 logs than in the colon. However, differences were not statistically significant owing to the wide variation in the individual values. Nevertheless, the demonstrable clearance of the terminal ileum could be explained by the orthograde passage with absolutely no stagnation and the relative competence of the INS in resisting retrograde pressure competence. In conclusion, ultrasonic fragmentation of the serosa and mucosa of the bowel allows construction of an INS from three muscle layers, which acts as a bacteriological barrier. Before it is introduced into the clinical setting its integration into the intestinal motility should be evaluated by further studies.

Anastomosis, Surgical↗

PubMedDate not supplied

The effects of sodium deoxycholate, lactulose and glutamine on bacterial translocation in common bile duct ligated rats.

BACKGROUND/AIMS: Sepsis is a major cause of post-operative morbidity and mortality in obstructive jaundice as a result of bacterial translocation from the gut. This study was conducted to investigate the effects of glutamine, lactulose, and the bile salt Na deoxycholate in preventing bacterial translocation in an animal model where obstructive jaundice was developed by common bile duct ligation. METHODOLOGY: Fifty Wistar albino rats were divided into 5 groups of 10 animals each. The animals in groups I-IV underwent common bile duct ligation and received, respectively, either saline, Na deoxycholate, lactulose or glutamine, orally. Group V had sham ligation and received saline orally. The animals were sacrificed at the end of the 7th day, and serum concentrations of bilirubin, aspartate aminotransferase (ALT), alanine aminotransferase (ALT), and alkaline phosphatase (AP) were measured. In addition, mesenteric lymph nodes were removed and cultured together with cecal content. Histopathologic examination of terminal ileum specimens was made. RESULTS: Na deoxycholate, lactulose and glutamine all reduced bacterial translocation rates to mesenteric lymph nodes (p<0.05), with glutamine causing the greatest effect. Na deoxycholate and lactulose prevented bacterial translocation by causing a decrease in cecal intraluminal bacterial content (p<0.001), while glutamine exerted its effect by preserving intestinal mucosal integrity. CONCLUSIONS: The integrity of the intestinal mucosal barrier is of paramount importance in preventing bacterial translocation, and the measures taken to protect mucosal integrity reduce bacterial translocation to a greater extent than those taken to decrease the number of bacteria in the gut.

Animals↗

PubMed1998

Interactions of the bacterial pathogen Listeria monocytogenes with mammalian cells: bacterial factors, cellular ligands, and signaling.

Listeria monocytogenes is a food borne pathogen which has the very unique property of crossing three barriers during infection eliciting meningitis, meningo-encephalitis and abortions with a mortality rate of about 30%. Indeed, after crossing the intestinal barrier, Listeria disseminates via the lymph and the blood, to the brain and/or the placenta after crossing the brain-blood barrier and/or the placental barrier. During disease, this organism infects a variety of tissues and cell types in which it is mostly intracellular due to its capacity to induce its own phagocytosis into cells which are normally nonphagocytic. The strategies used by Listeria to enter cells are different from those used by other well known invasive pathogens. Listeria thus appears as a fine model to study the molecular and cellular basis of bacterial invasion. In addition, not only during entry into cells but also during intra- and intercellular movement, Listeria exploits mammalian cell functions and is thus a novel tool for elucidating some unsolved fundamental aspects of cell biology, such as ligand receptor signaling and actin cytoskeleton rearrangements. In this review, the molecular and cellular basis of entry of Listeria into cells and of its intracellular motility will be discussed.

Animals↗

PubMed1996

Epithelial exposure to hypoxia modulates neutrophil transepithelial migration.

Polymorphonuclear leukocytes (PMN) are central to the pathogenesis of a number of intestinal diseases. PMN-induced damage to the protective epithelium occurs in hemorrhagic shock, necrotizing enterocolitis and conditions resulting in intestinal reperfusion injury. In such diseases, tissue hypoxia has been implicated as a pathophysiologic mediator. Thus, we hypothesized that exposure of intestinal epithelia to hypoxia may modulate PMN-epithelial interactions. In this study, T84 cell monolayers, a human intestinal crypt cell line, and isolated human PMN were used to examine the influence of hypoxia/reoxygenation (H/R) on PMN transepithelial migration. Confluent T84 cell monolayers were exposed to hypoxia (range 2-21% O2 for 0-72 h) and reoxygenated with buffer containing PMN. Transmigration of PMN (basolateral to apical orientation) was driven by a transepithelial gradient of the chemotactic peptide tMLP. In response to hypoxia/reoxygenation (H/R), transmigration into, and across epithelial monolayer was increased in a dose- (EC50 approximately 7% O2) and time-dependent fashion (3.5 +/- 0.3-fold increase at 2% O2 for 48 h, P < 0.001). Such conditions of H/R were not toxic to epithelia and did not influence epithelial barrier function. The influence of H/R on PMN transmigration was protein synthesis-dependent (> 80% decreased in the presence of cycloheximide) and could be inhibited by addition of functionally inhibitory antibodies to the PMN beta 2 integrin CD11b/18 (> 80% attenuated) and to CD47 (> 90% decreased compared to control). Hypoxia induced epithelial production and basolateral release of the PMN activating chemokine interleukin-8 (IL-8, nearly sixfold increase over normoxic control) which remained avidly associated with the epithelial matrix. Treatment of epithelial cells with IL-8 antisense oligonucleotides resulted in decreased monolayer-associated PMN but did not influence PMN transmigration, suggesting that epithelial IL-8 production may serve as a recruitment signal for PMN to the basal surface of polarized epithelia. The present observations indicate that H/R provides a relevant stimulus for novel biochemical crosstalk between epithelia and PMN.

Animals↗

PubMed2006

ATP-binding cassette transporters are required for efficient RNA interference in Caenorhabditis elegans.

RNA interference (RNAi) is a conserved gene-silencing phenomenon that can be triggered by delivery of double-stranded RNA (dsRNA) to cells and is a widely exploited technology in analyses of gene function. Although a number of proteins that facilitate RNAi have been identified, current descriptions of RNAi and interrelated mechanisms are far from complete. Here, we report that the Caenorhabditis elegans gene haf-6 is required for efficient RNAi. HAF-6 is a member of the ATP-binding cassette (ABC) transporter gene superfamily. ABC transporters use ATP to translocate small molecule substrates across the membranes in which they reside, often against a steep concentration gradient. Collectively, ABC transporters are involved in a variety of activities, including protective or barrier mechanisms that export drugs or toxins from cells, organellar biogenesis, and mechanisms that protect against viral infection. HAF-6 is expressed predominantly in the intestine and germline and is localized to intracellular reticular organelles. We further demonstrate that eight additional ABC genes from diverse subfamilies are each required for efficient RNAi in C. elegans. Thus, the ability to mount a robust RNAi response to dsRNA depends upon the deployment of two ancient systems that respond to environmental assaults: RNAi mechanisms and membrane transport systems that use ABC proteins.

ATP-Binding Cassette Transporters↗

PubMedDate not supplied

Total parenteral nutrition supplemented with L-alanyl-L-glutamine and gut structure and protein metabolism in septic rats.

The effects of administering total parenteral nutrition (TPN) supplemented with the dipeptide of L-alanyl-L-glutamine (Ala-Gln) on gut structure, barrier function, and protein metabolism were investigated in septic rats. Sepsis was induced by the continuous intraperitoneal administration of endotoxin via a miniosmotic pump. Twenty-three rats were divided into two groups and fed parenterally for 5 days. The Ala-Gln group (n = 11) received a conventional TPN solution supplemented with 2% Ala-Gln, whereas the control group (n = 12) received conventional TPN solution alone. One rat in each group died of endotoxemia. The groups showed similar nitrogen balance, urinary excretion of 3-methylhistidine, and plasma concentration of endotoxin in the portal vein. The groups showed similar incidence of bacterial translocation from the gut to the mesenteric lymph nodes. The intestinal mucosal weight and villous height were significantly greater in the Ala-Gln group than in the control group. Pathological derangement of the mucosal structure was more marked in the control group than in the Ala-Gln group. These results suggest that TPN supplemented with Ala-Gln preserves the gut structure without decreasing the nitrogen balance under septic conditions.

Animals↗

PubMed2003

Adrenomedullin is increased in the portal circulation during chronic sepsis in rats.

BACKGROUND: A clinical hallmark of sepsis is an early, hyperdynamic cardiac phase (increased cardiac output) that degrades to a hypodynamic phase, which results in poor gut perfusion and subsequent gastrointestinal (GI) hypoxemia, tissue ischemia, necrosis and loss of gut barrier function. Studies in rat cecal-ligation and puncture suggest that the potent vasodilator adrenomedullin (AM) might initiate or maintain the hypodynamic phase. We hypothesize that AM expression is increased in acute Escherichia coli bacteremia and chronic E coli-Bacteroides fragilis sepsis. METHODS: Acute bacteremia: male Sprague-Dawley rats were anesthetized (urethane/alpha-chloralose), tracheotomized, and cannulated for monitoring blood pressure (MABP) and heart rate (HR) and for infusion of E coli (10(9) colony-forming units [CFU] E coli per 1 mL normal saline) and blood sampling. Arterial blood was withdrawn for arterial blood gas (ABG) measurements every 60 minutes. After 6 hours, we harvested lung, liver, kidney, spleen, and small intestine tissue samples and drew arterial and portal blood for AM enzyme-linked immunosorbent assay (ELISA). Chronic sepsis: a sterile gauze pad was implanted and animals recovered for 5 days. Twenty-four hours (10(9) CFU E coli and 10(9) CFU B fragilis per 1 mL normal saline; 1 injection) or 72 hours (2 injections) after the inoculation of the back sponge, rats were anesthetized, intubated, and cannulated as above. MABP, HR, and ABG were measured for 1 hour before tissue and serum harvest for AM ELISA. RESULTS: Sepsis increased HR and MABP in all groups. Acute sepsis caused a respiratory alkalosis and pH was also elevated in chronic sepsis. Serum AM levels were increased in all groups compared with baseline and remained elevated at every time point, but were not different between saline controls and septic animals at any time point, except for the portal serum from the 72-hour chronic sepsis, which was elevated. CONCLUSIONS: These data suggest that surgical manipulation alone is sufficient to stimulate AM secretion, most probably from endothelial cells. While the AM levels were decreasing at 72 hours compared with 6 hours or 24 hours in the arterial blood and the saline control portal blood, it remained elevated in the septic portal samples, suggesting that the sepsis-induced increase of AM was derived from the gut by a different mechanism than that which elevated arterial serum levels.

Acute Disease↗

PubMed1983

[Comparative study on the effect of the dopamine receptor blockers metoclopramide and domperidone on stomach emptying and the visualization of the small intestine in monocontrast].

The effects of a new dopamine receptor blocking agent, domperidone are compared pharmacoradiographically with the well-know action of metoclopramide. The investigated parameters were pyloric muscle function, passage time through the small intestine and, in correction with this, an evaluation of barium filling of the small intestine. Our investigations show that domperidone at dosages of 0.1 mg/kg and 0.2 mg/kg body weight does not accelerate intestinal junction as markedly as 0.3 mg/kg metoclopramide. Nevertheless, domperidone is as well suited as metoclopramide for pharmacoradiography of gastric emptying and for radiological examination of the small intestine. Hence, it can be concluded that the stimulation of the pyloric muscle as the leading pace maker of propulsion is achieved satisfactorily. Contrary to the findings with metoclopramide, domperidone shows no central nervous side effects. It appears that domperidone, at therapeutic dosages, does not pass the blood-brain barrier. Hence, this pharmaceutical preparation should prove of particular value in paediatrics.

Adult↗