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1.
Compounds that prevent chloride transport in membrane vesicles have been tested for in vivo activity against the effects of intestinal secretory agents. Chloride channel blockers including diphenylamine-2-carboxylate, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonate, 5-nitro-2-(2-phenylethylamino)benzoic acid, and alpha-phenylcinnamic acid were tested for effects on jejunal or ileal secretion in weanling pigs. Secretion was studied in ligated intestinal loops in a control state, during exposure to secretory concentrations of theophylline, and after prior treatment with cholera toxin. Increases in net fluid flux induced by either theophylline or cholera toxin were not prevented by adding chloride channel blockers into the intestinal lumen. Channel blocker concentrations that reduced chloride transport by greater than 50% in pig jejunal brush border vesicles did not cause significant changes in unidirectional blood to lumen chloride flux measured in situ. Several routes of administration of the specific chloride channel blocker alpha-phenylcinnamate failed to reduce fluid secretion induced by theophylline. Chloride channel blocker effectiveness appears to be significantly different between in vitro and in vivo experimental models. In contrast to the chloride channel blockers, loperamide significantly reduced net fluid and chloride flux in ileal loops secreting fluid in response to theophylline. Antagonism of the production or actions of second messenger by loperamide was more effective than the chloride channel blockers in reducing conductive chloride transport associated with intestinal secretion.  相似文献   

2.
Acute, isolated loops of proximal and distal jejunum of weanling swine were exposed to either heat stable porcine Escherichia coli enterotoxin, heat labile porcine Escherichia coli enterotoxin, cholera toxin or theophylline. Unidirectional sodium fluxes in response to heat stable in the proximal jejunum were dependent on the length of time that the intestinal mucosae was exposed to the enterotoxin. Net water, sodium and chloride and unidirectional sodium and chloride flux measurements in the proximal jejunum in response to each agent uniformly indicated that net secretion of fluid and electrolytes was the result of increased unidirectional sodium secretion or blood-to-lumen flux and decreased unidirectional chloride absorption or lumen-to-blood flux. In addition heat stable cholera toxin and theophylline but not heat labile decreased unidirectional chloride secretion a small but significant amount in the proximal jejunum.

Sodium and chloride flux measurements in the distal jejunum demonstrated that all four secretory agents could stimulate net secretion of water, sodium and chloride in that region. The response to these secretory agents as measured by sodium and chloride unidirectional flux rates was not similar to changes observed in the proximal jejunum. In the distal small intestine, whereas heat labile cholera toxin and theophylline induced similar qualitative changes in unidirectional sodium and chloride fluxes, that induced by heat stable differed.

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3.
Glucose, l-alanine, l-aspartate, l-methionine and glycine enhanced net fluid and electrolyte absorption in acute isolated loops of the proximal jejunum of weanling swine. The effect of glucose on intestinal secretion induced by heat stable and heat labile Escherichia coli entero-toxin, cholera toxin and theophylline was examined in both the proximal and distal jejunum of weanling swine. In the proximal jejunum glucose enhanced the rate of net fluid and electrolyte absorption. This increase was accompanied by an increase in unidirectional dosium absorption. In loops exposed to either heat stable or heat labile enterotoxins, glucose significantly decreased the rate of net fluid and electrolyte secretion. The magnitude of glucose enhancement in loops exposed to heat stable and heat labile enterotoxins was similar to adjacent control loops. However, glucose enhancement did not occur in loops exposed previously to cholera toxin or concurrently to theophylline. Therefore, cholera toxin and theophylline may inhibit substrate dependent sodium absorption in the proximal jejunum. In the distal jejunum glucose enhancement did occur but the rate of enhancement was less than in the proximal jejunum. In this region glucose enhancement was not evident in loops exposed to either theophylline, heat stable, heat labile or cholera toxin.  相似文献   

4.
The use of nicotinic acid for preventing intestinal secretion caused by cholera toxin and by the heat-stable enterotoxin of Escherichia coli has been investigated in the weanling pig. Secretory effects were measured in ligated jejunal loops of halothane-anesthetized pigs by dilution of a nonabsorbable marker added to the loop fluid. Different routes of administration and different initial pH values for nicotinate solutions were studied to determine optimal conditions for secretory inhibition. The neutral sodium salt of nicotinic acid had no significant antisecretory activity under any conditions used in these trials. Inhibition of secretion was most effective with partly neutralized nicotinic acid at pH 4.5 added directly to loops containing enterotoxin. Net fluid secretion induced by cholera toxin or heat-stable enterotoxin of E. coli was prevented by this treatment. Reversal of secretion was not accompanied by any measurable changes in cyclic nucleotide concentration in intestinal mucosa. Nicotinic acid antagonism of a secretory step common to cholera toxin and heat-stable enterotoxin of E. coli but subsequent to cyclic nucleotide involvement is indicated by these data.  相似文献   

5.
The effect of heat stable and heat labile Escherichia coli enterotoxins or cholera toxin in combination with theophylline on net water, sodium and chloride and unidirectional sodium and chloride fluxes was examined in acute isolated loops of jejunum of weanling swine. The effect of heat stable enterotoxin in combination with theophylline was determined in loops located in the proximal jejunum, while combinations of theophylline and either heat labile enterotoxin or cholera toxin were studied in the distal jejunum. In each situation the addition of theophylline resulted in an additive rather than a synergistic increment of intestinal secretory activity. This study implies that the intestinal adenyl cyclase system and enterotoxin induced intestinal secretion may not be directly related in the swine small intestine.  相似文献   

6.
The effect of the cyclooxygenase and prostaglandin E2 (PGE2) synthesis inhibitor, indomethacin, on the secretory responses induced by Salmonella serotype Typhimurium (ST) and cholera toxin (CT), in the porcine small intestine was investigated. ST (10(10) colony-forming units) and CT (56 micrograms) were instilled in tied-off intestinal loops in young anaesthetized pigs receiving intravenous indomethacin in a total dose of 7.5 mg/kg, or saline. The accumulated fluid in the loops and the luminal content of endogenous secretagogues PGE2 and 5-hydroxytryptamine (5-HT) were measured. ST induced fluid accumulation in the jejunum, whereas CT induced fluid accumulation in the jejunum and ileum. Indomethacin had no effect on the secretory responses. Indomethacin had a significant effect on the luminal content of PGE2 in jejunal ST and CT loops, whereas no effect of indomethacin was observed on the luminal content of 5-HT in ST and CT loops. In ST and CT loops, an increased content of PGE2 and 5-HT compared with test loops infused with Ringer's solution was observed. These results indicate that the porcine jejunal secretory response to ST and CT does not involve prostaglandins although indomethacin has an influence on the luminal release of PGE2 but not of 5-HT.  相似文献   

7.
The effect of cholera toxin, heat labile and heat stable Escherichia coli enterotoxin on mucosal cyclic AMP concentrations was determined on the proximal jejunum of weanling pigs and young rabbits. Ligated loops were injected with solutions containing no enterotoxin for control and either cholera toxin, heat labile or heat stable E. coli enterotoxin. The loops were drained after either two, four or six hours incubation at which time accumulated fluid was recorded and mucosal samples removed for determination of cyclic AMP concentration. In the rabbit, cholera toxin and heat labile, but not heat stable E. coli enterotoxin stimulated intestinal secretion while in the pig all three enterotoxins induced net fluid accumulation. Cholera toxin and heat labile, but not heat stable E. coli enterotoxin elevated rabbit mucosal cyclic AMP concentrations. In the pig these enterotoxins had no significant effect on mucosal cyclic AMP concentrations. The results are inconsistent with the hypothesis that the adenyl cyclase system is an essential step for enterotoxin induced intestinal secretion. The activation of intestinal adenyl cyclase by bacterial enterotoxins may only be an associated and not a necessary event for the stimulation of intestinal secretion.  相似文献   

8.
The effect of a heat-stable enterotoxin of Escherichia coli was compared with that of theophylline on ion transport in the pig jejunum, using both in vivo and in vitro techniques. The maximal electrical response to heat-stable enterotoxin was only one-half that of theophylline even though the magnitude of the net secretory response was similar. A net, active secretion of HCO3 was partially responsible for the secretory response induced by heat-stable enterotoxin, whereas theophylline induced an active secretion of chlorine which could account for the entire secretory response. Heat-stable enterotoxin elevated tissue cyclic guanosine monophosphate levels, whereas theophylline elevated both cyclic adenosine monophosphate and cyclic guanosine monophosphate. Cyclic guanosine monophosphate levels induced by heat-stable enterotoxin were markedly potentiated by theophylline. Results suggest that HCO3 secretion in the pig jejunum may be controlled by the cyclic guanosine monophosphate system and this system also activates a neutral secretory process which at high heat-stable enterotoxin doses accounts for the bulk of the net secretion observed. Conversely, the chlorine secretion elicited by theophylline is entirely electrogenic and is consistent with results obtained in other species.  相似文献   

9.
In contrast to cholera enterotoxin and other Escherichia coli enterotoxins, a pig-specific, heat-stable E. coli enterotoxin (STb) causes morphologic lesions (loss of villous epithelial cells and partial villous atrophy). These lesions reflect a loss of absorptive cells and thus suggest that STb causes impaired absorption as well as inducing net secretion. The present studies assess functional significance of morphologic changes induced by STb. Net fluid movement, mucosal surface area, sucrase activity and the electrical response induced by alanine were measured in swine jejunal loops exposed to E. coli culture filtrates with and without STb. Net fluid secretion (-11.1±1.1 ml) occurred in some STb loops (secretors) and net absorption (2.7±0.3 ml) in others (nonsecretors), but net absorption occurred in all control loops (4.9±0.2 ml). The mucosal surface area of Stb loops was about 20% less than that of controls (P<0.01). Sucrase activity was also lower (about 15%) in STb loops than in control loops (P<0.01). The electrical response induced by alanine in mucosa from nonsecreting STb loops did not differ from that induced in mucosa from control loops. However, the response to alanine in mucosa from secreting STb loops was reduced about 70% from that in mucosa from nonsecreting STb loops or from control loops (P<0.05). It is concluded that reduced sucrase activity is a functional correlate to villous atrophy induced by STb, that STb impairs alanine absorption in some loops (secretors), and that the impaired alanine absorption is independent of the decreased surface area caused by Stb. Because the impaired alanine absorption occurred independent of the decreases in surface area, it is suggested that the secretory response to STb is associated with an impairment of active absorption of alanine.  相似文献   

10.
OBJECTIVE: To evaluate the morphologic and physiologic changes induced by Clostridium perfringens type A (alpha toxin in the ileum and colon of sheep. SAMPLE POPULATION: 16 ligated intestinal loops in 4 Merino lambs and 18 explants of ileum and colon from slaughtered lambs. PROCEDURE: alpha Toxin-induced fluid accumulation was evaluated in ligated ileal and colonic loops of sheep. Tissues were evaluated morphologically by use of gross and histologic examination. Effects of toxin on in vitro intestinal net water transport were tested in modified Ussing chambers. RESULTS: Ovine ileal and colonic loops incubated with C perfringens type A alpha toxin retained more fluid than control loops. Histologically, in the ileum of lambs inoculated with 300 LD50 of alpha toxin/mL, there was a mild to moderate multifocal infiltration of neutrophils in the lamina propria and submucosa. The colonic loops of lambs inoculated with 30 or 300 LD50 of alpha toxin/mL had excessive mucus in the lumen, a moderate amount of neutrophils mixed with mucus in the intestinal lumen, and moderate multifocal infiltration of the lamina propria and submucosa with neutrophils; the blood vessels of these layers were engorged with neutrophils. In vitro measurements of water transport also revealed inhibition of net epithelial water absorption in ileum and colon incubated with alpha toxin on the mucosal side. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that alpha toxin induces alterations in sheep intestine. Clostridium perfringens type A organisms that produce alpha toxin could be responsible for diseases of intestinal origin in some ruminants.  相似文献   

11.
Net electrolyte and water transport and unidirectional Na+ fluxes were examined in ligated colonic loops of clinically normal pigs and in pigs with swine dysentery (etiologic agent Treponema hyodysenteriae) in the presence or absence of theophylline. In normal pigs, theophylline abolished net Na+ absorption via a reduction in the lumen-to-blood flux, decreased Cl- absorption, and increased HCO3- accumulation in the lumen. In infected pigs, all net ion transport was abolished, with the addition of theophylline producing little effect. The absence of net Na+ absorption in infected pigs was also the result of a decreased lumen-to-blood flux. Seemingly, colonic malabsorption may be the primary transport alteration in swine dysentery. Concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in samples of colonic mucosa from normal and infected pigs after in vitro exposure to a Ringer's solution containing 0 or 20 mM theophylline. Basal values of cAMP or cGMP did not increase in infected colonic mucosa. There was a diminished capacity of the infected mucosa to respond to theophylline. Alterations in ion transport in conjunction with measurements of cAMP and cGMP indicated that the pathogenic mechanism(s) in swine dysentery were not similar to those of Salmonella, Shigella, Vibrio cholerae, or Escherichia coli diarrhea.  相似文献   

12.
Villous atrophy and crypt hyperplasia were induced in the jejunal epithelium of thirteen 3-week-old pigs by inoculation with transmissible gastroenteritis virus. The responses (changes in net fluid movement) induced in ligated intestinal loops of these pigs by intraloop injections of prostaglandin E1 (PGE1) or Escherichia coli broth culture filtrates containing either or both E coli heat-stable enterotoxins (STa and STb) were compared with the responses induced by these preparations in littermates not inoculated with virus. Villous atrophy was associated with a marked decrease in response to preparations containing STa, STb, or STa + STb, but the response to PGE1 was undiminished. These results were consistent with the reports of others that the response to cyclic adenosine monophosphate-mediated secretogogues (PGE1) is a function of crypt epithelium; however, the present results also suggest that the secretory response to STa and to STb is dependent on the integrity of the villous epithelium. In the present study, loss of villous epithelium was associated with loss of response to STa and STb, but not to PGE1.  相似文献   

13.
The Escherichia coli heat-stable enterotoxin (STb) is the most prevalent toxin associated with diarrheagenic E coli isolates of porcine origin. Unequivocal biological activity of this toxin has been observed only in swine intestine. In this study, when endogenous protease activity was blocked with soybean trypsin inhibitor, intestinal secretion was stimulated by STb in jejunal loops of rats, mice, calves, and rabbits. Compared with pigs, rats, mice, and calves, rabbits were relatively insensitive to STb. These data demonstrate that the activity of STb is not a species-specific toxic activity; there is species variation in sensitivity to STb, and some common laboratory animals may have potential to be used to measure biological activity of STb.  相似文献   

14.
Responses of jejunal transcapillary and transmucosal fluid fluxes to IV infusion of crystalloid or colloid solutions were evaluated in 12 dogs. One isolated intestinal segment in each dog was used as the control segment, and 2 segments were distended to a intraluminal hydrostatic pressure of 10 cm of H2O. The artery supplying 1 of the 2 distended (autoperfused) segments was cannulated and perfused with blood from the femoral artery. One of the 2 distended segments was autoperfused from the femoral artery. Intraluminal pressure was increased in the autoperfused segment and in 1 other segment for three, 20-minute periods after administration of the crystalloid or colloid solution. Net transmucosal fluid flux was estimated, using a volume recovery method. In each autoperfused segment, blood flow, capillary pressure, lymph flow, and plasma protein and lymph protein concentrations were measured during each 20-minute distention period. Systemic arterial pressure was monitored throughout the procedure. Plasma and tissue oncotic pressures were calculated from the plasma protein and lymph protein concentrations. Total vascular resistance and precapillary and postcapillary resistances were determined. Capillary pressure increased after infusion with colloids and crystalloids, with the effects being more prolonged in the colloid group. Plasma oncotic pressure transiently increased after infusion with colloids and decreased after infusion with crystalloids. Lymph flow increased only in crystalloid-treated dogs. Due to alterations in transcapillary fluid filtration, crystalloids induced a net loss of fluid into the intestinal lumen, whereas the fluid absorptive capacity of the jejunum was unaltered by colloid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

15.
The involvement of Ca++ ions as secretory mediators in pig jejunal epithelia has been investigated with an in vitro system. Omission of Ca++ from the Ringer-HCO3 bathing media on both sides of the tissue had minor effects on the basal electrical activity of pig jejunal mucosa. There were only slight decreases in transepithelial potential difference and increases in conductance with Ca++ free media. Low EGTA concentrations which reversibly blocked potential difference responses to secretory agents also had minimal effects on basal electrical activity. The in vitro secretory responses to A23187, to theophylline, and to Escherichia coli heat-stable enterotoxin were all eliminated by Ca++ depletion and restored by replacing normal Ca++ concentrations in the bathing media. Dantrolene prevented the secretory response but not the potential difference increases caused by heat-stable enterotoxin and A23187, suggesting that intracellular Ca++ stores may be reservoirs of secretory signal agent. Verapamil only blocked the secretory response to heat-stable enterotoxin. Chlorpromazine had negligible effects on basal conditions, but totally blocked both the secretory response and the Ca++-dependent effects of A23187 and heat-stable enterotoxin on potential difference. The response to theophylline was only partially inhibited by chlorpromazine, implying some involvement of both cAMP and Ca++ as secretory signals for theophylline. Cytoplasmic Ca++ concentrations appear to be at least as important as cyclic nucleotides in regulating the secretory effects of pig jejunum.  相似文献   

16.
Isolated segments of left dorsal colon and a side-to-side colocolostomy (between the left ventral colon and left dorsal colon) were surgically created in 6 adult ponies. Four segments, each separated by an empty segment, were inoculated (20 ml) with 1 of the following 4 solutions: phosphate buffered saline solution (PBSS)/1% polyethylene glycol (PEG); purified cholera toxin in PBSS/1% PEG (5 micrograms cholera toxin/ml of PBSS/1% PEG); lyophilized Salmonella typhimurium UCD 1755 culture lysate, reconstituted in PBSS/1% PEG; and viable S typhimurium UCD 1755 (10(8) organisms/ml of PBSS/1% PEG). Twenty hours following inoculation of the treatment solutions into the isolated colon segments, the ponies were reanesthetized. Fluid accumulation in the isolated segments was measured, and tissue samples from isolated segments were taken for examination by light microscopy and electron microscopy, and for measurement of mucosal cyclic adenosine monophosphate levels. There was fluid accumulation in segments inoculated with cholera toxin in 4 ponies (29.5 +/- 12.7 ml), and in segments inoculated with S typhimurium UCD 1755 culture lysate in 3 ponies (14.0 +/- 8.7 ml). There was no fluid accumulation in segments inoculated with either the control solution (PBSS/1% PEG) or viable S typhimurium UCD 1755. There was significantly (P less than 0.05) less cyclic adenosine monophosphate in segments inoculated with cholera toxin, Salmonella lysate, and viable Salmonella, compared with control segments. Histologically, there were minimal changes in control segments, consisting of mild to moderate submucosal edema and capillary congestion.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

17.
The intestinal loop technique was used to evaluate the response of three week old piglets to the heat labile (LT) and the heat stable (ST) enterotoxins produced by Escherichia coli F11(P155). The serum anti-LT activity and the lipase, amylase and trypsin activities in the jejunal lumen of these pigs were determined. Piglets responded independently ti each toxin and no relationship between these responses and serum anti-LT activity or the enzyme activities of the jejunal content could be demonstrated.  相似文献   

18.
EAST1 (EnteroAggregative heat-Stable Toxin 1) is a 4.1 kDa toxin that was first detected in the enteroaggregative Escherichia coli (EAEC) strain 17-2 (O3:H2) isolated from the stools of a Chilean child with diarrhoea. Accordingly, EAST1 is thought to play a role in the pathogenicity of EAEC. The goal of this study was to obtain purified biologically active forms of two EAST1 variants (17-2 and O 42). Purified toxin samples were treated with protein disulfide isomerase (PDI) to ascertain the integrity of the disulfide bridges. Since EAST1 is often compared to STa (heat-Stable Toxin a), both purified EAST1 variants were tested for biological activity using the suckling mouse assay, the reference test for STa. A positive gut to body (G/B) weight ratio was not observed for any of the EAST1 preparations tested, although STa was active. Exposure of the purified toxins to T84 cell monolayers, an epithelial cell line derived from a human colon carcinoma, in modified Ussing flux chambers resulted in a rapidly attained and prolonged increase in short circuit current, a sensitive measure of net ion transport. Responses to 17-2 and O 42 variants were comparable in magnitude and inhibitable by bumetanide and DASU-02, indicating net anion secretion. The results demonstrate that EAST1 toxin stimulates anion secretion by T84 cell monolayers and it is sustained for the duration of toxin exposure.  相似文献   

19.
Effective oral adjuvants are needed to improve the intestinal immune responses to oral vaccines that are based on relatively low molecular weight antigens refined from veterinary pathogens. Liposomes prepared by different methods and composed of phospholipids of varying transition temperature were used to entrap cholera toxin (CT) and fed to mice. No significant increase in the intestinal antibody nor the serum IgA antibody response was detected but levels of serum IgG anti-CT antibody were significantly elevated in the group fed CT in phosphatidylcholine-based liposomes. Levels of antibody were significantly reduced in the groups fed CT in dipalmitoylphosphatidylcholine liposomes. Escherichia coli wall extract (ECWE) entrapped in certain liposome types and fed to mice elicited significantly increased serum anti-ECWE antibody responses but intestinal antibody responses were insignificantly different from the controls. These results suggest that orally administered liposomes fail to act as potent intestinal adjuvants for the entrapped antigens of bacterial origin used in this study.  相似文献   

20.
The objective of this study was to determine whether exposure of swine jejunum to crude culture filtrates containing Escherichia coli pig-specific, mouse-negative, heat-stable enterotoxin (STb) induces structural alterations in the jejunal mucosa of pigs. Two ligated intestinal loops in each of twelve 3-week-old pigs were exposed for 2 hours to sterile E coli culture filtrates from each of the following strains: 431 (STa-producing), 1261 (STa and STb-producing), and 1790 (STb-producing); recombinant strain HB101-pRAS-1 (STb-producing); the nontoxigenic K-12 variant HB101; or trypticase soy broth. Formalin-fixed sections from these loops were examined for sloughed cells around villi, and a lesion score was determined, indicating a change in villous epithelium from columnar to cuboidal or squamous cell types or to discontinuous epithelium. Villous lengths and crypt depths also were determined. For loops exposed to culture filtrates containing STa and STb or containing only STb, lesion scores and numbers of sloughed cells were greater (P less than 0.05) and villous length was shorter (P less than 0.01) than in loops not exposed to toxin. For loops exposed to culture filtrates containing STa, lesion scores, villus lengths, and numbers of sloughed cells were not different from those of loops not exposed to toxin. Therefore, exposure of swine jejunum to STb induced structural alterations in intestinal mucosa (ie, loss of villous absorptive cells and partial atrophy of villi) that were consistent with those causing compromised absorptive capacity.  相似文献   

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