Biomedical subjects

R A Argenzio

Publications and source records attributed to R A Argenzio.

At least 19 recordsLinked to original sources

PubMed2004

Arginine stimulates intestinal cell migration through a focal adhesion kinase dependent mechanism.

BACKGROUND: L-Arginine is a nutritional supplement that may be useful for promoting intestinal repair. Arginine is metabolised by the oxidative deiminase pathway to form nitric oxide (NO) and by the arginase pathway to yield ornithine and polyamines. AIMS: To determine if arginine stimulates restitution via activation of NO synthesis and/or polyamine synthesis. METHODS: We determined the effects of arginine on cultured intestinal cell migration, NO production, polyamine levels, and activation of focal adhesion kinase, a key mediator of cell migration. RESULTS: Arginine increased the rate of cell migration in a dose dependent biphasic manner, and was additive with bovine serum concentrate (BSC). Arginine and an NO donor activated focal adhesion kinase (a tyrosine kinase which localises to cell matrix contacts and mediates beta1 integrin signalling) after wounding. Arginine stimulated cell migration was dependent on focal adhesion kinase (FAK) signalling, as demonstrated using adenovirus mediated transfection with a kinase negative mutant of FAK. Arginine stimulated migration was dependent on NO production and was blocked by NO synthase inhibitors. Arginine dependent migration required synthesis of polyamines but elevating extracellular arginine concentration above 0.4 mM did not enhance cellular polyamine levels. CONCLUSIONS: These results showed that L-arginine stimulates cell migration through NO and FAK dependent pathways and that combination therapy with arginine and BSC may enhance intestinal restitution via separate and convergent pathways.

Animals↗

PubMed2004

Physiological responses in swine treated with water containing sodium bicarbonate as a prophylactic for gastric ulcers.

Maintenance of gastric pH above 4.0 aids the prevention of bile acid-mediated ulcerative damage to the pars esophageal tissue in pigs. One means of doing so is the addition of buffering compounds, such as sodium bicarbonate, to the water supply; however, any potential physiological effect of buffer consumption has yet to be determined. Experiment 1 tested the acute effects of buffer addition to the water supply on systemic acid-base and electrolyte balance in swine (BW 40.7 +/- 3.0 kg). Consumption of water calculated to a 200 mOsm solution with sodium bicarbonate for 24 h increased (P < 0.05) blood Na+, HCO3(-), and pCO2, although these effects were all within physiologically tolerable levels. Urine pH and Na+ excretion increased (P < 0.001) following the consumption of NaHCO3, with Na+ concentration almost threefold higher in treated pigs compared with controls. Experiment 2 determined the chronic systemic effects of buffer consumption by measuring blood and urine variables, with pigs consuming NaHCO3-treated water throughout. Water consumption increased (P < 0.001) during buffer consumption, although intake levels remained within normal ranges. Blood pH levels were not affected by long-term consumption of dietary buffer; however, blood HCO3(-) (P < 0.05), Na+, and pCO2 (P < 0.01) increased. Urine pH and urine Na+ concentration increased (P < 0.01) in buffer-treated compared with control animals. Results indicate that sodium bicarbonate can safely be added to the water supply for pigs, with no clinically relevant alterations in acid-base balance because the animals readily compensate for buffer intake.

Acid-Base Equilibrium↗

PubMed2002

Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2.

BACKGROUND: We have previously shown that the non-selective cyclooxygenase (COX) inhibitor indomethacin retards recovery of intestinal barrier function in ischaemic injured porcine ileum. However, the relative role of COX-1 and COX-2 elaborated prostaglandins in this process is unclear. AIMS: To assess the role of COX-1 and COX-2 elaborated prostaglandins in the recovery of intestinal barrier function by evaluating the effects of selective COX-1 and COX-2 inhibitors on mucosal recovery and eicosanoid production. METHODS: Porcine ileal mucosa subjected to 45 minutes of ischaemia was mounted in Ussing chambers, and transepithelial electrical resistance was used as an indicator of mucosal recovery. Prostaglandins E1 and E2 (PGE) and 6-keto-PGF1alpha (the stable metabolite of prostaglandin I2 (PGI2)) were measured using ELISA. Thromboxane B2 (TXB2, the stable metabolite of TXA2) was measured as a likely indicator of COX-1 activity. RESULTS: Ischaemic injured tissues recovered to control levels of resistance within three hours whereas tissues treated with indomethacin (5x10(-6) M) failed to fully recover, associated with inhibition of eicosanoid production. Injured tissues treated with the selective COX-1 inhibitor SC-560 (5x10(-6) M) or the COX-2 inhibitor NS-398 (5x10(-6) M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1alpha compared with untreated tissues. However, SC-560 significantly inhibited TXB2 production whereas NS-398 had no effect on this eicosanoid, indicating differential actions of these inhibitors related to their COX selectivity. CONCLUSIONS: The results suggest that recovery of resistance is triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2.

Animals↗

PubMed2000

Glutamine metabolism stimulates intestinal cell MAPKs by a cAMP-inhibitable, Raf-independent mechanism.

BACKGROUND & AIMS: Infectious diarrhea caused by viruses plus enterotoxigenic bacteria is often more severe than diarrhea induced by either pathogen alone. We postulated that the increased cell adenosine 3',5'-cyclic monophosphate (cAMP) concentration observed during infection by enterotoxigenic organisms retards the intestinal repair process by blocking activation of mitogen-activated protein kinases (MAPKs) in proliferating intestinal cells. METHODS: We evaluated the effects of glutamine on MAPK activity, thymidine incorporation, and cell number in glutamine-starved and -sufficient rat intestinal crypt cells (IEC-6). RESULTS: In glutamine-starved cells, 10 mmol/L glutamine in the absence of serum stimulated [(3)H]thymidine incorporation 8-fold. This effect was inhibited by 60% with 8-(4-chlorophenylthio) (8-CPT)-cAMP (100 micromol/L) + isobutyl methylxanthine (100 micromol/L). In cells not starved of glutamine, glutamine stimulated thymidine incorporation by 3-fold, and 8-CPT-cAMP completely blocked the mitogenic effect. Inhibition of proliferation by cAMP persisted for at least 68 hours after cAMP removal. In vitro kinase assays showed that glutamine signaling requires an intact ERK (extracellular signal-related kinase) pathway in unstarved cells. In starved cells, at least one other pathway (JNK) was activated by glutamine, and the mitogenic inhibition by 8-CPT-cAMP was incomplete. Other intestinal fuels (glucose and acetate) were not mitogenic. CONCLUSIONS: Increased levels of intracellular cAMP inhibit ERKs but only partially reduce glutamine-stimulated proliferation in enterocytes adapted to low glutamine.

Cell Division↗

PubMed2000

Low endogenous prostaglandin E2 predisposes to relapsing inflammation in experimental rat enterocolitis.

Intramural injection of peptidoglycan-polysaccharide (PG-PS) induces acute enterocolitis that spontaneously relapses in Lewis but not Fischer rats. Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) induce prostaglandin E2 (PGE2) secretion, which inhibits secretion of these cytokines by macrophages, suggesting an inhibitory feedback mechanism. We postulate that Lewis rat susceptibility to relapse is due to an imbalance between protective prostaglandins and cytokines. Female Fischer and Lewis rats were injected with PG-PS (37.5 microg/g) or human serum albumin intramurally. Tissue IL-1alpha and PGE2 immunoreactivities and myeloperoxidase (MPO) activity were determined. Relapsing rats had lower PGE2 and PGE2/IL-1alpha ratios than nonrelapsing rats (P < 0.05). In Fischer rats, 2 mg/kg/day of indomethacin potentiated cecal MPO and IL-1alpha concentrations above PG-PS alone (P < 0.05). Misoprostol treatment blocked PG-PS induced IL-1alpha and MPO and inhibited the potentiating effect of indomethacin on MPO and IL-1alpha (P < 0.05). In conclusion, increased endogenous PG may be protective against relapsing inflammation in PG-PS induced enterocolitis, at least partially via inhibition of proinflammatory cytokines. Imbalance between protective prostaglandins and proinflammatory cytokines may be involved in the pathogenesis of chronic relapsing inflammation in genetically susceptible hosts.

Animals↗

PubMed2000

Genistein augments prostaglandin-induced recovery of barrier function in ischemia-injured porcine ileum.

We have previously shown that PGE(2) enhances recovery of transmucosal resistance (R) in ischemia-injured porcine ileum via a mechanism involving chloride secretion. Because the tyrosine kinase inhibitor genistein amplifies cAMP-induced Cl(-) secretion, we postulated that genistein would augment PGE(2)-induced recovery of R. Porcine ileum subjected to 45 min of ischemia was mounted in Ussing chambers, and R and mucosal-to-serosal fluxes of [(3)H]N-formyl-methionyl-leucyl phenylalanine (FMLP) and [(3)H]mannitol were monitored as indicators of recovery of barrier function. Treatment with genistein (10(-4) M) and PGE(2) (10(-6) M) resulted in synergistic elevations in R and additive reductions in mucosal-to-serosal fluxes of [(3)H]FMLP and [(3)H]mannitol, whereas treatment with genistein alone had no effect. Treatment of injured tissues with genistein and either 8-bromo-cAMP (10(-4) M) or cGMP (10(-4) M) resulted in synergistic increases in R. However, treatment of tissues with genistein and the protein kinase C (PKC) agonist phorbol myristate acetate (10(-5)-10(-6) M) had no effect on R. Genistein augments recovery of R in the presence of cAMP or cGMP but not in the presence of PKC agonists.

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed2000

Evaluation of intestinal permeability and gluten sensitivity in Soft-Coated Wheaten Terriers with familial protein-losing enteropathy, protein-losing nephropathy, or both.

OBJECTIVE: To evaluate intestinal permeability and gluten sensitivity in a family of Soft-Coated Wheaten Terriers (SCWT) affected with protein-losing enteropathy (PLE), protein-losing nephropathy (PLN), or both. ANIMALS: 6 affected adult dogs. PROCEDURE: Intestinal biopsy specimens, urine protein-to-creatinine ratio, serum concentrations of albumin and globulin, and concentration of alpha1-protease inhibitor in feces were evaluated before, during, and 13 weeks after daily administration of 10 g of gluten for 7 weeks. Eosinophils and lymphocytes-plasmacytes were enumerated in intestinal biopsy specimens. Intestinal permeability was evaluated before and during the sixth week of gluten administration via cellobiose-mannitol and chromium-EDTA absorption tests. RESULTS: Serum globulin concentration decreased significantly after prolonged administration of gluten. Although not significant, there was an increase in lymphocytes-plasmacytes and a decrease in eosinophils in intestinal biopsy specimens. Furthermore, these counts were greater than those reported for clinically normal dogs. Gluten administration did not increase intestinal permeability. CONCLUSIONS AND CLINICAL RELEVANCE: Daily administration of gluten was associated with a significant decrease in serum globulin concentration in SCWT affected with PLE or PLN, but other variables remained unchanged. Although enhanced wheat-gluten sensitivity may be one factor involved in the pathogenesis of PLE or PLN in SCWT, this syndrome does not appear to be the result of a specific sensitivity to gluten.

Animals↗

PubMed2000

Evaluation of diet as a cause of gastric ulcers in horses.

OBJECTIVE: To measure pH, volatile fatty acid (VFA) concentrations, and lactate concentrations in stomach contents and determine number and severity of gastric lesions in horses fed bromegrass hay and alfalfa hay-grain diets. ANIMALS: Six 7-year-old horses. PROCEDURE: A gastric cannula was inserted in each horse. Horses were fed each diet, using a randomized crossover design. Stomach contents were collected immediately after feeding and 1, 2, 3, 4, 5, 6, 7, 8, 10, 12, and 24 hours after feeding on day 14. The pH and VFA and lactate concentrations were measured in gastric juice Number and severity of gastric lesions were scored during endoscopic examinations. RESULTS: The alfalfa hay-grain diet caused significantly higher pH in gastric juice during the first 5 hours after feeding, compared with that for bromegrass hay. Concentrations of acetic, propionic, and isovaleric acid were significantly higher in gastric juice, and number and severity of nonglandular squamous gastric lesions were significantly lower in horses fed alfalfa hay-grain. Valeric acid, butyric acid, and propionic acid concentrations and pH were useful in predicting severity of nonglandular squamous gastric lesions in horses fed alfalfa hay-grain, whereas valeric acid concentrations and butyric acid were useful in predicting severity of those lesions in horses fed bromegrass hay. CONCLUSIONS AND CLINICAL RELEVANCE: An alfalfa hay-grain diet induced significantly higher pH and VFA concentrations in gastric juice than did bromegrass hay. However, number and severity of nonglandular squamous gastric lesions were significantly lower in horses fed alfalfa hay-grain. An alfalfa hay-grain diet may buffer stomach acid in horses.

Animal Feed↗

PubMed2000

Effects of feed physical form and buffering solutes on water disappearance and proximal stomach pH in swine.

The effects of the physical form of feed on water disappearance and the effects of buffered water on proximal stomach pH in swine were determined in two experiments. In Exp. 1, 32 barrows were used to evaluate the water disappearance in pigs fed a finely ground and pelleted diet vs those fed a coarsely ground and mashed diet for ad libitum consumption over a 2-wk interval. There were four replicates with eight pigs per replicate. Average daily water and feed disappearance did not differ (P = 0.06 and P = 0.10, respectively). However, average daily water to feed ratio was higher for pigs on the pelleted diet (4.21+/-0.31 L/kg vs 3.04+/-0.33 L/kg; P = 0.02). The higher ratio for the pelleted diet indicated that this may be the cause of a more fluid digesta allowing reflux of irritants from the distal stomach to damage the pars esophageal region of the proximal stomach. In Exp. 2, four barrows (25+/-2 kg) had gastric cannulas surgically implanted into the proximal region of the stomach. Pigs were given ad libitum access to a finely ground and pelleted diet. The experimental design was a Latin square. Water treatments included water (control), 200 mOsm NaHCO3, 250 mOsm NaHCO3, and 250 mOsm mono-dibasic sodium phosphate. Pigs were given a 4-d adjustment period, and pH measurements began on the morning of the 5th d and continued for 24 h under normal feeding conditions. Feed was removed and measurements were continued for 16 h. Buffered water raised the pH of the proximal region of the stomach compared to the control (P < 0.001). Average pH while consuming the water treatments was 3.65+/-0.11 (n = 4) for water control, 4.86+/-0.11 (n = 4) for the 200 mOsm NaHCO3, 4.63+/-0.11 (n = 4) for the 250 mOsm NaHCO3, and 4.59+/-0.14 (n = 3) for the 250 mOsm mono-dibasic sodium phosphate. Buffers also raised the pH of the proximal region of the stomach for the fed (P < 0.001) and the feed restriction (P < 0.01) phases of the trial. Water disappearance rates in pigs given NaHCO3 were higher than in the control (P < 0.01). Average daily water disappearance for the treatments was 9.13+/-0.74 L for the control, 13.56+/-0.74 L for 200 mOsm NaHCO3, 13.77+/-0.74 L for the 250 mOsm NaHCO3, and 10.33+/-0.95 L for the phosphate buffer. The proximal pH of the stomach was increased by adding buffers to the water supply. Addition of NaHCO3 buffers also caused increased water disappearance.

Animal Feed↗

PubMed1999

Low endogenous prostaglandin E2 predisposes to relapsing inflammation in experimental rat enterocolitis.

Intramural injection of peptidoglycan-polysaccharide (PG-PS) induces acute enterocolitis that spontaneously relapses in Lewis but not Fischer rats. Interleukin-1 (IL-1) and tumor-necrosis factor-alpha (TNF-alpha) induce prostaglandin E2 (PGE2) secretion, which inhibits secretion of these cytokines by macrophages, suggesting an inhibitory feedback mechanism. We postulate that Lewis rat susceptibility to relapse is due to an imbalance between protective prostaglandins and cytokines. Female Fischer and Lewis rats were injected with PG-PS (37.5 microg/g) or human serum albumin intramurally. Tissue IL-1alpha and PGE2 immunoreactivities and myeloperoxidase (MPO) activity were determined. Relapsing rats had lower PGE2 and PGE2:IL-1alpha ratios than nonrelapsing rats (P < 0.05). In Fischer rats, 2 mg/kg/day indomethacin potentiated cecal MPO and IL-1alpha concentrations above PG-PS alone (P < 0.05). Misoprostol treatment blocked PG-PS-induced IL-1alpha and MPO and inhibited the potentiating effect of indomethacin on MPO and IL-1alpha (P < 0.05). In conclusion, increased endogenous PG may be protective against relapsing inflammation in PG-PS induced enterocolitis, at least partially via inhibition of proinflammatory cytokines. An imbalance between protective prostaglandins and proinflammatory cytokines may be involved in the pathogenesis of chronic relapsing inflammation in genetically susceptible hosts.

Animals↗

PubMed1999

The characteristics of intestinal injury peripheral to strangulating obstruction lesions in the equine small intestine.

Recent studies suggest that horses requiring surgical correction of strangulating intestinal obstruction may develop post operative complications as a result of ischaemia/reperfusion injury. Therefore, the mucosal and serosal margins of resected small intestine from 9 horses with small intestinal strangulating lesions were examined for evidence of ischaemia/reperfusion injury. Severe mucosal injury and marked elevations in myeloperoxidase activity were detected at ileal resection margins (n = 4), whereas the mucosa from proximal jejunal (n = 9) and distal jejunal (n = 5) resection margins was normal. However, the serosa from jejunal resection margins had evidence of haemorrhage and oedema, and the proximal jejunal serosa had significantly increased numbers of neutrophils. Histological injury in ileal stumps is indicative of the inability fully to resect the ileum in horses with distal small intestinal strangulations. One of 4 horses subjected to ileal resection was subjected to euthanasia and found to have a necrotic ileal stump. Evidence of serosal injury and neutrophil infiltration in the proximal jejunal resection margins may predispose horses to post operative adhesions. Four of 8 horses discharged from the hospital suffered from recurrent colic in the post operative period.

Anastomosis, Surgical↗

PubMed1999

Comparative pathophysiology of nonglandular ulcer disease: a review of experimental studies.

Ulceration of the nonglandular, stratified squamous mucosa of the equine and porcine stomach is a common event in both species, although in pigs the fatality rate is significant and it is an economically important disease. Because the barrier function of this mucosa in horses and pigs appears similar, it is probable that similar pathophysiological mechanisms may be responsible for the initiating lesions and reparative events. Recent studies of ulcer pathogenesis in the pig have shown that feed preparation or prolonged fasting can result in disruption of the normal stratification of gastric contents, thereby allowing high concentrations of HCl, pepsin and refluxed bile to mix in the proximal stomach. Conditions simulating those found in vivo have been shown to damage this mucosa in vitro and indicate that luminal products, such as short chain fatty acids and bile salts, which act in synergy with HCl, probably are necessary to induce significant damage to this mucosa. Studies of the equine stomach have shown a similar proximal to distal pH gradient in the fed stomach, a significant duodenal-gastric reflux, and induction of squamous ulcers with fasting, thereby illustrating that similar conditions may be responsible for damage to the equine nonglandular mucosa.

Animal Feed↗

PubMed1999

Prostaglandin-induced recovery of barrier function in porcine ileum is triggered by chloride secretion.

We have previously shown that PGI2 and PGE2 have a synergistic role in restoring electrical transepithelial resistance (R) in ischemia-injured porcine ileum via the second messengers Ca2+ and cAMP. Because Ca2+ and cAMP stimulate Cl- secretion, we assessed the role of PG-induced Cl- secretion in recovery of R. Mucosa from porcine ileum subjected to ischemia for 45 min was mounted in Ussing chambers and bathed in indomethacin and Ringer solution. Addition of PGs stimulated a twofold increase in R, which was preceded by elevations in short-circuit current (increase of 25 microA/cm2). The PG-induced effect on R was partially inhibited with bumetanide, an inhibitor of Cl- secretion. The remaining elevations in R were similar in magnitude to those induced in ischemic tissues by amiloride, an inhibitor of Na+ absorption. Treatment with 10(-4) M 8-bromo-cGMP or 300 mosM mucosal urea resulted in elevations in R similar to those attained with PG treatment. PGs signal recovery of R via induction of Cl- secretion and inhibition of Na+ absorption, possibly by establishing a transmucosal osmotic gradient.

16,16-Dimethylprostaglandin E2↗

PubMed1999

Effects of diet and housing density on growth and stomach morphology in pigs.

Two experiments were conducted to evaluate the impact of housing density on the stomach morphology of growing pigs and determine whether there was an interaction between housing density and diet. All diets were corn-soybean meal based. In Exp. 1, 42 barrows (41.0+/-.95 kg BW) were allotted either individually or three pigs per pen to evaluate the effects of crowding on stomach lesions. Pen space per pig was 1.54 and .51 m2, respectively. All pigs were fed a finely ground and pelleted diet (610 microm) for 6 wk. The ADG decreased (P<.05) for the pigs housed three per pen during wk 4 to 6 only. There was no effect of housing density on feed intake or gain/feed ratio. Neither visual nor histological ulcer score differed between the two treatment groups. No stomachs were graded as normal. In Exp. 2, 80 barrows (39.8+/-.9 kg BW) were allotted either two or four pigs per pen. Pen space per pig was .77 and .39 m2, respectively. Half of the pigs in each housing situation were fed a coarse meal diet (1,050 microm), and half of the pigs were fed a finely ground and pelleted diet (577 microm) throughout the 49-d experimental period. Throughout the trial, pigs housed two per pen gained at a greater rate (P<.05) than pigs housed four per pen. From d 14 to the end of the trial, pigs consuming the finely ground and pelleted diet gained at a greater rate (P<.05) than pigs fed the coarse meal diet. The differences in ADG were reflected in final body weight. Stomach weight as a percentage of body weight was higher for animals on the coarse meal diet. Visual and histological ulcer scores were similar, and both were higher (P<.001) on the finely ground and pelleted diet, indicating greater damage. There was no effect of space restriction on stomach morphology. These data show the major effect of diet type on stomach lesions with no interaction with space restriction.

Animals↗

PubMed1999

Effects of diets differing in propensity to promote gastric lesions on defense systems in gastric mucosae.

The objectives were to characterize biochemical changes, focusing on the antioxidant defense system, in stratified squamous and oxyntic mucosae in pigs fed diets with differing propensity to promote gastric lesions. Barrows (n = 24; 48.7+/-1.0 kg BW) housed in individual pens were used in the experiment. Barrows were fed a corn-soybean meal diet. Half of the animals were fed the diet as a coarsely ground meal (CGM; average particle size = 886 microm), and half were fed the diet as a finely ground pelleted (FGP; average particle size = 528 microm) feed. Initiation and termination of the experiment were staggered over a 3-wk period. Diets were fed for 6 wk. Visual evaluation of the stratified squamous mucosa of the proximal stomach showed increased (P<.001) damage in animals fed the FGP diet. These results were supported by histological evaluation. Thiobarbituric acid-reacting substances (TBARS), indicative of peroxide generation, relative to amount of protein were higher (P<.001) in stratified squamous than in oxyntic mucosa, and, per unit of tissue, TBARS were highest in stratified squamous mucosa of animals fed the FGP diet. Glutathione peroxidase activity followed a pattern similar to that of peroxides. Prostaglandin E2 was higher (P<.004) in stratified squamous than in oxyntic mucosa. In contrast, the activity of catalase was higher (P<.001) in oxyntic mucosa and was not affected by diet. The data show differences in the production of peroxides, the antioxidant defense system, and PGE2 between stratified squamous and oxyntic mucosae. Generation of prooxidants and the antioxidant defense system may play a role in the predilection of ulcers for the stratified squamous mucosal region of the pig stomach.

Animals↗

PubMed1999

Changes in gastric contents in pigs fed a finely ground and pelleted or coarsely ground meal diet.

The objective was to characterize the change in stomach contents in relation to time after feeding between pigs consuming a restricted amount of a finely ground and pelleted (FGP) or coarsely ground meal (CGM) diet. Particular interest was placed on the concentration of organic acids and ammonia, the products of microbial fermentation. Thirty barrows were ranked by weight and assigned to a postfeeding time of 2, 4, 6, 8, or 12 h and either the FGP or CGM diet. Initiation and termination of the experiment were staggered over a 2-wk period. The treatment period was 42 d. Percentage of dry matter was higher (P<.01) in the stomach contents of pigs on the CGM diet. Concentrations of pepsin and protein were higher (P<.05) and ammonia tended to be higher (P = .10) in the proximal stomach of pigs fed the FGP diet. In contrast, concentrations of acetate and L-lactate were higher (P<.05) in the proximal stomach of pigs fed the CGM diet. All pigs on the CGM diet had stomachs that graded as normal on visual inspection. There was variable damage to the stomachs of pigs on the FGP diet. Measurement of chromium concentration in the stomach after an oral dose of Cr-EDTA clearly demonstrated the mixing that occurs between the proximal and distal stomach by 2 h after feeding in pigs consuming the FGP diet, whereas a gradient was maintained in pigs consuming the CGM diet. Thus, components normally secreted in the distal stomach return to the proximal stomach. These data show that components secreted in the distal region, such as acid and pepsin, may play a role in initiating damage to the stratified squamous mucosa. High concentrations of organic acids in the stomach of pigs on the CGM diet were not associated with damage to the stratified squamous mucosa in the esophageal region.

Ammonia↗

PubMed1999

Glutamine and transforming growth factor-alpha stimulate extracellular regulated kinases and enhance recovery of villous surface area in porcine ischemic-injured intestine.

BACKGROUND: Epidermal growth factor (EGF) signals enterocyte proliferation via extracellular regulated kinases (ERKs). Because glutamine is required for EGF-stimulated proliferation and stimulates ERKs in intestinal cell culture, we hypothesized that glutamine and the EGF-related peptide transforming growth factor-alpha (TGF-alpha) would synergistically enhance repair associated with stimulation of ERKs. METHODS: Thiry-Vella loops were created in juvenile pigs. One half of the loop was subjected to 2 hours of ischemia, and the other half served as control. Loops were infused daily with Ringer's solution containing 140 mmol/L glucose, 140 mmol/L glutamine, 140 mmol/L glucose plus 60 micrograms/L TGF-alpha, or 140 mmol/L glutamine plus 60 micrograms/L TGF-alpha. RESULTS: After 2 hours of ischemia, complete villous epithelial sloughing was present. By 18 hours, villous epithelium had fully restituted, but villi remained stunted until 144 hours after injury. Glutamine + TGF-alpha triggered sustained increases in ERK activity compared with glucose-treated tissues (maximal at 18 hours), whereas glutamine alone or glucose + TGF-alpha caused only transient elevations in ERK activity. By 72 hours, villous surface area had increased to normal values with glutamine plus TGF-alpha treatment, whereas villi remained stunted with glucose alone, glutamine alone, or glucose plus TGF-alpha. CONCLUSIONS: Glutamine plus TGF-alpha treatment restored mucosal architecture within 72 hours of severe ischemic injury associated with sustained elevations in ERK activity.

Animals↗

PubMed1998

Production of gastroesophageal erosions and ulcers (GEU) in gnotobiotic swine monoinfected with fermentative commensal bacteria and fed high-carbohydrate diet.

Erosions and gastroesophageal ulcers (GEU) were produced in the pars esophagea of young gnotobiotic swine fed a carbohydrate-enriched liquid diet and monoinfected with two different fermentative commensal bacteria, Lactobacillus and Bacillus sp. In contrast, piglets, fed a similar diet and inoculated with Gastrospirillum sp. (Helicobacter heilmannii), a helicobacter species that colonizes the gastric mucosa, did not develop GEU. Experimental GEU likely develops secondary to epithelial damage mediated by microbial-origin acids whose production is potentiated by high dietary carbohydrate and parietal cell-origin hydrochloric acid.

Animals↗