Biomedical subjects

A Barbul

Publications and source records attributed to A Barbul.

At least 37 records · Page 2Linked to original sources

PubMed1999

Inhibition of nitric oxide synthesis in wounds: pharmacology and effect on accumulation of collagen in wounds in mice.

OBJECTIVE: To investigate the effect of systemic inhibition of nitric oxide (NO) synthesis in wounds on collagen accumulation. DESIGN: Randomised experimental study. SETTING: Teaching hospital, USA. MATERIAL: 240 Balb/C mice divided into groups of 10 animals each. INTERVENTIONS: Polyvinyl alcohol sponges were inserted subcutaneously through a dorsal skin incision. Beginning on the day of wounding, N omega-nitro-L-arginine-methylester (L-NAME), NG-L-monomethyl-arginine (L-NMMA), aminoguanidine hemisulphate (AGU), and S-methyl isothiouronium (MITU) were given orally or intraperitoneally. The mice were killed 10 days later. MAIN OUTCOME MEASURES: Nitrite and nitrate concentrations, both stable end products of NO, were measured in wound fluid. Sponge hydroxyproline content was assayed as an index of reparative collagen deposition. RESULTS: NOS inhibitors given orally in the drinking water or by daily intraperitoneal injection had no effect on wound nitrite/nitrate concentrations or deposition of collagen in wounds. When given continuously through intraperitoneally-placed osmotic pumps, AGU (500 mg/kg/day) (p < 0.001) and MITU (p < 0.01) significantly reduced wound fluid nitrite/nitrate concentrations in a dose dependent manner. Inhibition of wound nitric oxide synthase by 500 mg AGU/kg/day and 100 mg MITU/kg/day was paralleled by lowered accumulation of collagen in wounds (p < 0.01). CONCLUSION: NO is beneficial in wound healing.

Analysis of Variance↗

PubMed1998

Enhanced collagen accumulation following direct transfection of the inducible nitric oxide synthase gene in cutaneous wounds.

Inducible nitric oxide synthase (iNOS) is expressed during cutaneous wound repair. Mounting evidence suggests that wound nitric oxide (NO) augments collagen accumulation. We hypothesized that in vivo transfection of wound cells with the iNOS gene would increase physiological wound NO levels and thus augment collagen accumulation. Polyvinyl alcohol sponges were instilled with a mammalian expression plasmid (pMP6) containing either the chloramphenicol acetyl transferase (CAT) reporter or murine iNOS gene driven by a CMV immediate-early promoter. Plasmid DNA was injected alone or in complex with cationic liposomes, and the sponges were placed subcutaneously in male Sprague-Dawley rats which had received a longitudinal dorsal midline incision. Animals were sacrificed at different time points post-wounding and the sponges assayed for CAT activity, transfected iNOS mRNA, total nitrate and nitrite concentration (NOx) (as an index of wound NO synthesis), and hydroxyproline content (as an index of sponge collagen accumulation). The results demonstrate that wound cells were more efficiently transfected by naked DNA than by liposome mediated transfection and that maximal expression of both iNOS and CAT occurred at 48 hrs with a rapid decline after this time point. After 7 days, iNOS transfected sponges had accumulated significantly more collagen than those transfected with CAT. We conclude that cutaneous wounds can be successfully transfected by direct injection of naked DNA and that increased iNOS expression precedes an increase in collagen synthesis.

Animals↗

PubMed1998

Lymphocyte function in wound healing and following injury.

BACKGROUND: Injury activates a cascade of local and systemic immune responses. METHODS: A literature review was undertaken of lymphocyte function in wound healing and following injury. RESULTS: Lymphocytes are not required for the initiation of wound healing, but an intact cellular immune response is essential for a normal outcome of tissue repair. Injury affects lymphocyte immune mechanisms leading to generalized immunosuppression which, in turn, increases host susceptibility to infection and sepsis. Although the exact origin of post-traumatic immunosuppression remains unknown, stress hormones and immunosuppressive factors, such as inflammatory cytokines, prostaglandin E2 and nitric oxide, affect lymphocyte function adversely. Post-traumatic impairment of T lymphocyte immune function is reflected in decreased lymphocyte numbers, as well as altered T cell phenotype and activity. Antibody-producing B lymphocytes are variably affected by injury, probably secondary to alterations of T lymphocyte function, as a result of their close interaction with helper T cells. Therapeutic modulation of the host immune response may include non-specific and specific interventions to improve overall defence mechanisms. CONCLUSION: Early resuscitation to restore lymphocyte function after injury is important for tissue repair and the prevention of immunosuppression.

Animals↗

PubMed1998

Modulation of inflammation and immunity by arginine supplements.

Arginine holds a key position in the cellular functions and interactions that occur during inflammation and immune responses. The competition for arginine as a substrate between nitric oxide synthase and arginase appears to be at the core of the regulation of the inflammatory process. This review examines some of the recently defined effects of arginine on various inflammatory processes and immune cell functions.

Animals↗

PubMed1998

Metalloproteinase inhibitors and wound healing: a novel enhancer of wound strength.

BACKGROUND: Wound strength is a balance between collagen synthesis and degradation. The role of collagen breakdown in wound healing is still not well understood. We investigated the role of collagenases (metalloproteinases [MMPs]) in wound healing in using GM6001, a novel inhibitor of MMPs. METHODS: We used the dorsal skin incision model with implantation of polyvinyl alcohol sponges. Twenty male Sprague-Dawley rats were randomly assigned to receive either GM6001 (10 mg/kg body weight) or 2 mL saline subcutaneously. Ten days after operation the animals were killed and fresh wound breaking strength, scar and sponge hydroxyproline content, and collagen type I gene expression in sponges were assayed. In addition, the inflammatory response and the wound fluid cytokine (tumor necrosis factor-alpha [TNF-alpha] and transforming growth factor-beta 1 [TGF-beta 1]) profile were studied. RESULTS: GM6001 significantly increased wound strength (422 +/- 59 vs 302 +/- 33 g, P < .05), whereas scar collagen content did not differ. In the sponge granulomas the inflammatory infiltrate, the collagen content, and the collagen type I gene expression were all significantly decreased by GM6001. CONCLUSIONS: Inhibition of MMP activity during acute wound healing enhances wound strength even though new collagen synthesis and the inflammatory response are significantly decreased. This could be achieved by decreasing collagen turnover or increasing collagen maturation and crosslinking, or both.

Animals↗

PubMed1997

Nitric oxide metabolism in wounds.

Arginine can be metabolized in wounds to nitric oxide and citrulline by nitric oxide synthase or to urea and ornithine by arginase. We investigated the expression of these arginine metabolic pathways over a 3-week period. Groups of 8-10 male Balb/C mice underwent a dorsal skin incision and subcutaneous polyvinyl alcohol sponge implantation. The animals were sacrificed at various times, and sponges were harvested to obtain wound fluid and wound cells. Cells or whole sponges were incubated with L-[2,3-(3)H]arginine, with or without N(G)-L-monomethyl-arginine (NMMA, a competitive inhibitor of nitric oxide synthase). Nitrite and nitrate (both stable end products of nitric oxide metabolism) and amino acids were measured in wound fluid and wound cell culture supernatants. Increasing concentrations of nitrite and nitrate were noted in wound fluid and in whole sponge cultures until the second week postwounding, indicating sustained wound nitric oxide synthesis. In wound fluid arginine levels were undetectable at all times, suggesting sustained utilization. Wound fluid citrulline levels showed an early peak and then a gradual decrease, suggesting that recycling for continued nitric oxide production may occur. Wound fluid ornithine levels increased until Day 10 and remained elevated, indicative of continued arginase activity. In vitro production of nitrite/nitrate and citrulline by cells and whole sponges was inhibitable by NMMA. Inducible nitric oxide synthase expression was confirmed by immunoblotting, while immunohistochemistry demonstrated that macrophages are a major source of wound nitric oxide. The data show that nitric oxide synthesis occurs for prolonged periods after injury and macrophages appear to be a major cellular source.

Animals↗

PubMed1997

Nitric oxide, an autocrine regulator of wound fibroblast synthetic function.

Nitric oxide (NO) is synthesized in wounds, but its exact role and cellular source are not known. Wound fibroblasts (WF) are phenotypically characterized by increased collagen synthesis and contractility. We hypothesized that WF may be also phenotypically altered during wound healing to synthesize NO. WF were isolated from polyvinyl alcohol sponges implanted in male Lewis rats and harvested 10 days later. Proliferation in response to 10% fetal bovine serum was assessed by [3H]thymidine incorporation in a microculture system. A fibroblast-populated collagen lattice was used for assaying contractility. Collagen synthesis was determined by measuring the collagenase-sensitive fraction of protein-incorporated [3H]proline. Fibroblasts were incubated in the presence or the absence of 0.5 mM S-methyl-isothio-uronium or 0.5 mM N-monomethyl-L-arginine, both competitive inhibitors of NO synthase. WF spontaneously synthesize and release NO (4.60 +/- 0.29 nmol nitrite/microg DNA/48 h). Normal dermal fibroblasts do not synthesize NO. WF NO synthesis was limited to the first and second passages postharvest and was inhibitable by S-methyl-isothio-uronium (96%) and N-monomethyl-L-arginine (84%). In vivo iNOS expression by WF was confirmed by in situ hybridization and immunohistochemistry. Inhibition of endogenous NO synthesis had no effect on fibroblast proliferation. However, fibroblast-mediated collagen contraction was enhanced (p < 0.01), and collagen synthesis was significantly decreased (p < 0.05) by inhibiting NO synthase. The data show that WF are phenotypically altered during the healing process to synthesize NO, which, in turn, regulates their collagen synthetic and contractile activities.

Animals↗

PubMed1997

Sepsis impairs anastomotic collagen gene expression and synthesis: a possible role for nitric oxide.

Although intra-abdominal sepsis is known to impair colon healing by inhibiting anastomotic collagen synthesis, the effect of systemic sepsis on this process is unknown. Endotoxins and cytokines associated with sepsis induce nitric oxide synthesis both systemically and locally within colonic tissue. We hypothesized that systemic sepsis impairs colonic healing and examined a possible correlation with nitric oxide expression. Male Sprague-Dawley rats received intraperitoneal injections of either saline (sham group) or Escherichia coli endotoxin (lipopolysaccharide 1 mg/100 g body weight) at Times -24 and -12 hr (LPS group). All animals underwent laparotomy and left colonic anastomosis at Time 0. At 24 and 96 hr postlaparotomy rats were sacrificed, the anastomoses excised, and [3H]-proline incorporation into protein measured as an index of total new protein synthesis (TNP). Digestion with purified collagenase yielded incorporation into the collagen fraction (CDP). Additional sham and LPS-treated rats were sacrificed at 24, 72, and 120 hr, the anastomoses excised, and nitric oxide synthase activity in the tissue measured by the conversion of [3H]-arginine to [3H]citrulline in an ex vivo culture system. Finally, sham and LPS rats were sacrificed at 120 hr for measurement of colon anastomotic bursting pressure. Systemic sepsis significantly impaired new collagen synthesis in anastomotic tissue at 24 hr compared to control samples (P < 0.02). No difference was noted at 96 hr. TNP synthesis was similar in both groups at 24 or 96 hr. Northern blot analysis confirmed a significant decrease in Type I and Type III collagen mRNA expression at 24 hr in septic rats. Anastomotic bursting pressure was also decreased in the septic group (P < 0.003). Sepsis elevated nitric oxide synthase activity in anastomotic tissue 24 hr postanastomosis, when compared to sham tissue (P < 0.0001). These data suggest that systemic endotoxin induces nitric oxide synthesis at the anastomotic site. The simultaneous dysregulation of collagen gene expression and synthesis with decreased anastomotic strength suggests a possible regulatory role for nitric oxide in gastrointestinal healing.

Anastomosis, Surgical↗

PubMed1997

Diabetes-impaired healing and reduced wound nitric oxide synthesis: a possible pathophysiologic correlation.

BACKGROUND: Nitric oxide (NO) is synthesized in wounds, but its role in the healing process is not fully understood. The inhibition of NO production during wound healing is accompanied by decreased wound reparative collagen deposition. To further define the role of NO in reparative collagen accumulation, we studied its production during diabetes-induced wound healing impairment. METHODS: Male Sprague-Dawley rats (290 to 310 gm) were rendered diabetic by intraperitoneal streptozotocin administration. Seven days after induction of diabetes (blood glucose greater than 300 mg/dl), the rats underwent dorsal skin incision and subcutaneous implantation of polyvinyl alcohol sponges. Beginning on the day of wounding, 21 diabetic animals were treated with 3 units/day insulin via intraperitoneally implanted miniosmotic pumps. Ten days after injury, wound breaking strength was determined, and wound collagen accumulation and types I and III collagen gene expression were measured in subcutaneously implanted polyvinyl alcohol sponges. NO-synthesis, as measured by nitrite/nitrate accumulation, was determined in wound fluid and in supernatants of wound cell cultures. RESULTS: Streptozotocin-induced diabetes markedly impaired wound breaking strength and collagen deposition. A parallel decrease occurred in wound NO synthesis as reflected by decreased nitrite/nitrate concentration in wound fluid and in diminished ex vivo NO production by wound cells. Insulin treatment partially but significantly improved wound mechanical strength (p < 0.01) and collagen accumulation (p < 0.001). Decreased wound NO accumulation and ex vivo NO production by wound cells were also partially restored by insulin treatment. CONCLUSIONS: Impaired diabetic wound healing is paralleled by decreased wound NO synthesis, supporting the hypothesis that NO plays a significant role in wound reparative collagen accumulation.

Animals↗

PubMed1997

General principles of wound healing.

Wound healing is a complex process involving different biologic and immunologic systems. Despite improvements in diagnostics and therapy, wound failures remain a clinical problem. The approach to a nonhealed wound is an interdisciplinary challenge that should not be underestimated. Better understanding of the complex wound-healing cascade helps our approach to wound healing and its possible failure. Manipulations of the involved immunologic features offer future therapeutic strategies.

Cell Division↗

PubMed1997

Healing in the gastrointestinal tract.

Healing in the GI tract is rapid when free of complications: Unlike cutaneous healing, in which progress can be observed on a daily basis and intervention instituted early if necessary, healing of the intestinal anastomosis is anatomically obscured from inspection, allowing the surgeon only the patient's parameters of general well-being to judge the success of the operation. For the same reason, complications usually require re-operation, with the associated morbidity of a laparotomy and additional general anesthetic. This places a great responsibility on the surgeon to be cognizant of all the preoperative, intraoperative, and postoperative factors relating to anastomotic healing that might compromise the healing process. Bearing these in mind, along with attention to technical detail, should limit complications to an acceptable level. Patients most at risk are (1) those who perioperatively develop physiologic problems that lead to shock, hypoxia, and resultant anastomotic ischemia, (2) those with radiation-induced tissue injury, (3) those with sepsis, and (4) those with preoperative bowel obstruction. Malnourishment, malignancy, diabetes, steroids, and age also influence outcome to varying degrees. Future advancement in the field of GI healing lies in our ability to manipulate the early struggle between collagen synthesis and collagen breakdown. A profound understanding of the molecular and biochemical pathways and the factors that control them will bring us closer to this goal. Clinically, this may be accomplished by the introduction of wound healing enhancers into the anastomotic site, possibly by incorporating them into suture materials, biofragmentable anastomotic rings, or staple materials. Already much is known about the influence of different cytokines and growth factors on collagen regulation, knowledge that will help resolve many of the long-standing problems associated with GI surgery.

Anastomosis, Surgical↗

PubMed1997

Stimulation of fibroblast proliferation and matrix contraction by wound fluid.

Fibroblast proliferation and fibroblast-mediated matrix contraction are critical to wound healing. Different cytokines have been shown to modulate fibroblast functions but little is known about the physiological role of these soluble factors during wound repair. In these experiments we characterized a fibroblast stimulating factor in wound fluid. Wound fluid was obtained from subcutaneously implanted polyvinyl alcohol sponges harvested 10 days post-wounding (pool of 100 Lewis rats). Normal dermal fibroblasts were obtained from Lewis rats by an explant technique, while wound fibroblasts were isolated from sponges harvested 10 days post-wounding. Proliferation in response to 0.5% and 10% fetal bovine serum was assessed by [3H]-thymidine incorporation. A fibroblast-populated collagen lattice was used for assaying contractile properties. Wound fibroblasts demonstrated markedly diminished proliferative and enhanced contractile properties compared to normal dermal fibroblasts. 10% wound fluid (v/v) stimulated proliferation of normal dermal fibroblasts (119%, p < 0.001) and wound fibroblasts (103%, p < 0.001). Wound fluid also stimulated collagen gel contraction by normal dermal fibroblasts (24% at 24 hr and 16% at 72 hr, p < 0.01), but not by wound fibroblasts. Separation by Sephadex G-100 gel filtration identified the active factor in wound fluid to have a molecular weight of about 100 kDa. Characterization of the soluble factor showed it to be a protein (ammonium sulfate precipitation), sensitive to trypsin digestion, heat resistant (56 degrees C, 30 min), and neuraminidase resistant. The isoelectric point appeared to be 7.0, as determined by ion exchange chromatography. Mitogenic proliferation of thymic lymphocytes was not affected by the active factor, suggesting cell target specificity. These data demonstrate that the wound environment contains high molecular weight protein(s) that promote fibroblast functions, essential for the healing process.

Animals↗

PubMed1997

Acute protein-calorie malnutrition impairs wound healing: a possible role of decreased wound nitric oxide synthesis.

BACKGROUND: Nitric oxide is synthesized in wounds. Systemic inhibition of wound nitric oxide synthesis decreases wound collagen accumulation and wound mechanical strength. The role of nitric oxide during impaired healing is not known. In a model of impaired wound healing induced by acute protein-calorie malnutrition, we correlated wound healing parameters with wound nitric oxide synthesis. STUDY DESIGN: One group of Sprague-Dawley rats was rendered acutely malnourished by restricting its food intake to 50 percent of the food intake of an ad libitum-fed control group. Wound collagen accumulation and types I and III collagen gene expression were measured 10 days postwounding in subcutaneously implanted polyvinyl alcohol sponges. Nitric oxide synthesis was determined in wound fluid and in supernatants of wound cell cultures. RESULTS: Animals with acute protein-calorie malnutrition lost 10.4 +/- 0.8 percent, while controls gained 17.5 +/- 1.2 percent of their original body weight. Protein-calorie malnutrition reduced sponge hydroxyproline contents (995 +/- 84 compared with 1,580 +/- 109 micrograms/100 mg sponge, p < .001), indicating diminished wound collagen accumulation. Gene expression of type III, but not type I, collagen was decreased in wounds of protein-calorie malnutrition animals. Nitrite/nitrate and citrulline concentrations in wound fluid (p < .01) and in wound cell supernatants (p < .001) were also lower in protein-calorie malnutrition animals, indicating a net decrease in nitric oxide production. CONCLUSIONS: Impaired wound collagen accumulation caused by protein-calorie malnutrition may be a reflection of reduced nitric oxide synthesis within the wound.

Acute Disease↗

PubMed1997

Wound healing in sepsis and trauma.

Wound healing represents a dynamic and immediate response of the body to tissue injury with the purpose of restoring anatomical continuity, structure and function. Success or failure of this complex cascade of events is determined largely by competence of the host's immune system. Sepsis represents one of the most formidable threats to successful wound healing. It can present as a local bacterial colonization of the injury site with minimal systemic reaction or the "systemic inflammatory response syndrome," a primary cause of mortality among critically ill patients. Trauma also predisposes patients to wound complications especially as a result of post-traumatic immunosuppression. This phenomenon exposes the patient to the risk of microbial infection and ultimately the sepsis syndrome. The immune system, therefore, represents a vulnerable gateway through which trauma and sepsis exert their deleterious effect on the wound healing process resulting in increased morbidity and mortality for the surgical patient.

Humans↗

PubMed1996

Nitric oxide regulates wound healing.

Nitric oxide (NO) synthesis occurs during wound healing, but its role has not been defined. To study the effect of NO on wound repair, S-methyl isothiouronium (MITU, a competitive inhibitor of NO synthase) was administered at a dose of 10, 50, and 100 mg/kg body weight/day, using intraperitoneally implanted miniosmotic pumps. Groups of 10 male Balb/C mice underwent a dorsal skin incision and polyvinyl alcohol sponges were inserted subcutaneously. The animals were sacrificed 10 days postwounding and wound breaking strength and hydroxyproline content of sponges, an index of reparative collagen deposition, were determined. Some sponges were used to harvest wound fluid and infiltrating cells, which were then incubated overnight with or without 1 mM MITU. Nitrite and nitrate, stable end products of NO, were measured in wound fluid and in wound cell culture supernatants. Continuous intraperitoneal infusion of MITU significantly decreased wound fluid nitrite/nitrate concentrations in a dose dependent manner (P < 0.01). Inhibition of wound NO synthesis by 100 mg MITU/kg/day was paralleled by lowered wound collagen accumulation (P < 0.01) and wound breaking strength (P < 0.01). In vitro NO synthesis by wound cells obtained from animals treated with 100 mg MITU/kg/day was not significantly different from controls (12.6 +/- 1.2 vs 10.7 +/- 0.6 nmole NO2 + NO3/microgram DNA), reflecting the reversible inhibition of NO synthase by MITU. However, NO production was equally inhibited in wound infiltrating cells by the in vitro addition of MITU (83% vs 85%, respectively). These data suggest that nitric oxide synthesis is critical to wound collagen accumulation and acquisition of mechanical strength.

Animals↗

PubMed1996

Intra-abdominal sepsis impairs colonic reparative collagen synthesis.

BACKGROUND: Intra-abdominal infection is generally considered a contraindication to primary colon anastomosis. In order to elucidate the mechanisms by which sepsis affects colonic healing, we studied anastomotic new collagen and protein synthesis and collagen gene expression in a relevant animal model. METHODS: Forty male Sprague-Dawley rats (240 to 260 g) underwent sham laparotomy (SHAM, n = 18) or cecal ligation and single puncture (CLP, n = 22). After 24 hours, animals underwent single-layer left colon anastomosis. Animals were sacrificed either 1 or 4 days postanastomosis. Anastomotic segments of colon were excised, minced, and incubated with 4.5 muCi 3H-proline. After 3 hours, tissue 3H-proline incorporation was quantitated as an index of total new protein synthesis. The protein fraction was then digested with purified collagenase enzyme to determine 3H-proline incorporation into collagenase-digestible protein, an index of new collagen synthesis. Total RNA was extracted from anastomotic tissue samples and subjected to Northern blot analysis for type I and type III collagen genes. RESULTS: Intra-abdominal sepsis resulted in markedly less new collagen synthesis 1 day postanastomosis (9,163 +/- 1,234 versus 3,744 +/- 444 disintegrates per minute 3H-proline/mg of protein, P < 0.0001) and 4 days postanastomosis (8,462 +/- 956 versus 5,708 +/- 802 dpm/mg of protein P < 0.05). Noncollagenous protein synthesis was also impaired in anastomotic tissue from CLP rats on postanastomosis day 1 (37,497 +/- 3,740 versus 18,593 +/- 2,695 dpm/mg of of protein, P < 0.001) and postanastomosis day 4 (28,238 +/- 834 versus 17,784 +/- 1,415 dpm/mg of of protein, P < 0.0001). The expression of type I and type III collagen was altered relative to the normal temporal sequence observed in SHAM animals. CONCLUSION: Intra-abdominal infection impairs colonic reparative collagen and protein synthesis. In addition, regulation of type I and type III collagen genes is altered by intra-abdominal sepsis, and the alteration likely contributes to impaired new collagen synthesis and decreased colonic mechanical strength.

Abdomen↗

PubMed1995

Reduced intestinal absorption of arginine during sepsis.

OBJECTIVE: To investigate the effect of sepsis on the intestinal absorption of arginine. DESIGN: Controlled, nonintervention study. SETTING: Surgical research laboratories of Sinai Hospital of Baltimore. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Experimental sepsis induced by cecal ligation and puncture or intraperitoneal injection of lipopolysaccharide. MEASUREMENTS AND MAIN RESULTS: Sepsis assessed by peritoneal and blood cultures. Intestinal absorption estimated by measuring the transfer of 3H-arginine by everted jejunal sacs prepared from septic and control animals (n = 6 per group) at multiple time points after the induction of sepsis (6, 12, 24, 48, and 72 hrs after cecal ligation and puncture; 6 and 12 hrs after intraperitoneal injection of lipopolysaccharide). Induction of peritonitis in the rat by cecal ligation and puncture significantly reduced the in vitro uptake of arginine by everted jejunal sacs at 12, 24, and 48 hrs after laparotomy. Arginine transfer by everted jejunal sacs was also significantly reduced in rats as early as 6 hrs after intraperitoneal injection of endotoxin (endotoxin 273 +/- 14; saline 377 +/- 14 nmol/sac/hr). Data are expressed as mean +/- SEM. Recovery from sepsis was associated with normalization of arginine transfer by intestinal sacs. CONCLUSIONS: Experimental sepsis, induced by either cecal ligation and puncture or intraperitoneal injection of lipopolysaccharide, resulted in impaired intestinal amino acid uptake. Impaired intestinal arginine absorption may explain the lack of benefit of enteral, compared with parenteral, arginine therapy on survival from a septic insult.

Animals↗

PubMed1995

Colitis and colonic mucosal barrier dysfunction.

Trauma, infection, neoplasia, and inflammation can all disrupt the intact intestinal mucosal barrier to intraluminal bacteria and bacterial antigens. This study investigated the relation between colonic inflammation and colonic mucosal barrier function in three experimental models of colitis. There were significantly increased systemic endotoxin concentrations in rats with acetic acid (7.5 (1.7-119.5) pg/ml), ethanol (13.7 (0-111.2) pg/ml), and hapten induced (14.4 (5-31.1) pg/ml) colitis compared with saline controls (3.3 (0-13.7) pg/ml). Data expressed as median (range). There were significant correlations between the systemic endotoxin concentration and both the severity of colitis and of illness in acetic acid induced colitis. A significant increase in colonic permeability to 14C-polyethylene glycol was shown in rats with acetic acid (3.42 (1.36-5.63)%) and hapten induced colitis (2.86 (1.03-8.10)%) compared with saline controls (1.20 (0.67-1.36)%). Data expressed as median (range) of percentage of the intracolonic bolus excreted in urine. There was a significant positive correlation between the severity of colitis and % colonic permeability to 14C-polyethylene glycol. This and other studies provide evidence that mucosal barrier dysfunction is a feature of colitis irrespective of aetiology or species. Such barrier dysfunction may be responsible for the systemic inflammatory response and complications seen in patients with inflammatory bowel disease.

Acetates↗