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Biomedical subjects

A Barbul

Publications and source records attributed to A Barbul.

At least 55 records · Page 3Linked to original sources
PubMed1995

Failure of intestinal amino acid absorptive mechanisms in sepsis.

BACKGROUND: Sepsis has been shown to impair the barrier function and metabolism of the intestine. This study was done to investigate the effect of sepsis on intestinal absorption of proline, leucine, glutamic acid, and aminoisobutyric acid. STUDY DESIGN: Rats (six per group) were studied 24 hours after cecal ligation and puncture (CLP) or six hours after intraperitoneal injection of lipopolysaccharide (LPS). Controls underwent sham laparotomy or saline solution injection. Four 7-cm everted proximal jejunal sacs were prepared from each rat and filled with 800 microL Krebs' bicarbonate buffer containing 100 mumol/L of amino acid. Paired sacs (septic and control) were incubated at 37 degrees C in flasks containing the same solution trace labeled with 3H containing the same solution trace labeled with 3H amino acid. Sac contents were aspirated 60 minutes later and amino acid uptake was determined by scintillation counting. RESULTS: Twenty-four hours after CLP and six hours after LPS administration there was significant impairment in the intestinal absorption of all amino acids studied. Absorption of glutamic acid was the least affected, followed by leucine, aminoisobutyric acid, and proline. CONCLUSIONS: Sepsis impairs the intestinal absorption of amino acids. The magnitude of this defect in absorption differed with the amino acid studied, suggesting that not all transport systems were affected equally. This differential response of transport systems to sepsis appears to be the inverse of what is observed after a period of starvation.

Amino Acids↗
PubMed1995

Immune involvement in wound healing.

Both in vitro and in vivo studies have demonstrated that the presence of both macrophages and T lymphocytes at the wound site is essential in order for the normal healing process to occur. Both macrophages and T lymphocytes possess the capacity to regulate essential steps in the process of wound healing. The presence of macrophages is essential for the initiation and maintenance of wound fibroblast activity. T cells do not appear to be required for the initiation of the healing process, and healing can progress in the absence of T lymphocytes, but the presence of an intact T-cell immune system is essential for a normal outcome, indicating that the T cells probably exert a regulatory influence over macrophage-induced activities. Further research is still required into the interaction of these immune cells, their secretory products, and other wound elements before our understanding of the mechanism of wound healing is complete.

Animals↗
PubMed1994

Loss of colonic structural collagen impairs healing during intra-abdominal sepsis.

OBJECTIVE: To investigate colon anastomotic healing in an experimental model of sepsis. DESIGN: Prospective, randomized, experimental trial. SETTING: Experimental surgical laboratory of a large community hospital. STUDY PARTICIPANTS: Twenty-eight male Sprague-Dawley rats weighing 310 to 380 g. INTERVENTIONS: On day 0, the rats underwent either sham laparotomy or cecal ligation and puncture. The next day, the rats underwent left colon resection and single-layer inverted anastomosis. Colon-bursting pressure was determined 5 days after surgery at which time the anastomosis and a segment of colon 3 cm proximal to the anastomosis were excised. MAIN OUTCOME MEASURES: Colon-bursting pressure, colonic hydroxyproline concentration (index of collagen content), and total protein concentration measured as alpha-amino nitrogen. RESULTS: Sepsis resulted in decreased anastomotic bursting pressure and collagen concentration in all colon segments that were analyzed in the animals that underwent cecal ligation and puncture compared with control animals. CONCLUSIONS: Sepsis impairs healing of the colon, reflected by decreased bursting pressure and collagen concentration. The decrease in bowel wall structural collagen may affect the ability of the gut to hold sutures and thus may lead to more anastomotic failure.

Anastomosis, Surgical↗
PubMed1994

Peritonitis impairs intestinal absorption of proline and leucine in the rat.

Systemic sepsis is associated with reduced mesenteric blood flow and impairment of metabolic and barrier functions of the small intestine. A study was performed in the rat to investigate the effect of sepsis induced by caecal ligation and double puncture on intestinal absorption of leucine and proline in vivo. Absorption was studied 24 h after caecal ligation and puncture by measuring intestinal disappearance and circulatory appearance of intraluminal 3H-labelled amino acid over a 60-min study period. Peritonitis resulted in a significant increase relative to controls in the mean (s.e.m.) percentage of leucine (67.2(3.6) versus 18.0(3.5), P < 0.001) and proline (64.7(6.0) versus 15.1(3.7), P < 0.001) remaining within the small intestine. There were significant decreases in portal venous and femoral arterial concentrations of leucine and proline in animals with sepsis. Intestinal amino acid absorption is impaired in this model.

Animals↗
PubMed1994

Clinical benefits of an immune-enhancing diet for early postinjury enteral feeding.

In this multicenter prospective controlled trial, 98 evaluable patients sustaining major torso trauma were randomized to receive early enteral nutrition with a new "immune-enhancing" diet (study: n = 51) or a standard stress enteral formula (control: n = 47). At baseline, both groups had comparable demographics and Injury Severity Scores. After 7 days of feeding, the groups had equivalent increases in serum total protein, albumin, and transferrin concentrations. Patients receiving the "immune-enhancing" diet, however, experienced significantly greater increases in total lymphocyte (p = 0.014), T lymphocyte (p = 0.04), and T-helper (p = 0.004) cell numbers. Additionally, these patients had significantly fewer intraabdominal abscesses (study, 0% vs. control, 11%; p = 0.023) and significantly less multiple organ failure (study, 0% vs. control, 11%; p = 0.023). In conclusion, this multicenter trial suggests this "immune-enhancing" enteral diet offers clinical benefits in stressed surgical patients.

Abdominal Injuries↗
PubMed1993

Sepsis impairs gut amino acid absorption.

Sepsis has been shown to adversely affect the barrier and metabolic functions of the small intestine as well as to reduce mesenteric blood flow and cause histologic damage. However, the effect of sepsis on gut absorptive function has been largely ignored. In this study, intestinal absorption of arginine and an amino acid analogue, aminoisobutyric acid, was studied using in vivo and in vitro techniques in an experimental model of sepsis. In vivo studies showed a significant impairment in the absorption of both amino acids from the intestinal lumen 24 and 72 hours after cecal ligation and puncture. Uptake of these amino acids by everted gut sacs prepared from septic animals was also significantly reduced. This reduction in absorptive capacity of the gut may limit the ability of enteral feeding alone to supply nutritional requirements during sepsis and may also contribute to the associated morbidity and mortality.

Aminoisobutyric Acids↗
PubMed1993

Arginine stimulates wound healing and immune function in elderly human beings.

BACKGROUND: Experimentally, arginine enhances immune function and promotes wound healing. In this randomized double-blind study we investigated the effect of oral arginine supplementation on wound healing and T-cell function in elderly human beings (more than 65 years of age). METHODS: Thirty elderly, healthy, human volunteers (15 men and 15 women) received daily supplements of 30 gm arginine aspartate (17 gm free arginine). Fifteen volunteers (nine men and six women) received a placebo syrup. Fibroplastic wound responses were assessed by inserting a polytetrafluoroethylene catheter subcutaneously into the right deltoid region. Epithelialization was examined by creating a 2 x 2 cm split thickness wound on the lateral aspect of the upper thigh. Mitogenic response of peripheral blood lymphocytes to concanavalin A, phytohemagglutinin, pokeweed mitogen, and allogeneic stimuli was assayed at the beginning and end of supplementation. Polytetrafluoroethylene catheters were analyzed for alpha-amino nitrogen (assessment of total protein accumulation), hydroxyproline (index of reparative collagen synthesis), and DNA accumulation (index of cellular infiltration). RESULTS: Arginine supplementation for 2 weeks significantly enhanced wound catheter hydroxyproline accumulation (26.49 +/- 2.39 nmol/cm vs 17.41 +/- 2.04 nmol/cm) and total protein content (43.47 +/- 3.85 micrograms/cm vs 21.95 +/- 2.5 micrograms/cm). Arginine did not influence the DNA content of the catheters or the rate of epithelialization of the skin defect. Peripheral blood lymphocyte responses to mitogenic and allogenic stimulation were greater in the arginine supplemented group. Serum insulin-like growth factor-1 levels were significantly elevated in the arginine group. CONCLUSIONS: The data suggest that arginine supplementation may improve wound healing and immune responses in the elderly.

Aged↗
PubMed1993

Tumor necrosis factor-alpha inhibits in vivo collagen synthesis.

In this study we sought to determine the in vivo role of tumor necrosis factor-alpha (TNF-alpha) at the wound-healing site. In vivo abrogation of endogenous TNF-alpha activity in experimental wounds by administration of anti-murine TNF-alpha rabbit serum resulted in a significant 77.5% increase in wound collagen deposition, as assessed by wound sponge granuloma hydroxyproline content. Administration of pharmacologic doses of recombinant murine TNF-alpha into subcutaneously inserted polyvinyl alcohol sponges resulted in an increase in collagen deposition (1594 +/- 117 vs 1014 +/- 49 and 1588 +/- 135 vs 1014 +/- 49 micrograms/100 mg sponge, for TNF-alpha in situ administration at a dose of 0.05 and 0.5 micrograms, respectively). This effect could be abolished by the simultaneous systemic treatment of the animals with the antiinflammatory drug indomethacin. The data suggest that the enhanced collagen deposition after TNF-alpha administration is a consequence of a nonspecific inflammatory activity that indirectly promotes collagen synthesis. The data also support the hypothesis that endogenous wound TNF-alpha down-regulates collagen synthesis during normal wound healing.

Animals↗
PubMed1992

The effect of hemorrhagic shock on intestinal amino acid absorption in vivo.

Hemorrhagic shock causes a disproportionate decrease in portal blood flow which may adversely affect the barrier and absorptive functions of the intestine. The absorptive capacity of the small intestine was studied during shock induced by mild and severe hemorrhage in the rat by measurement of the uptake of a radiolabelled amino acid analog (aminoisobutyric acid: AIB). Hemorrhage resulted in a significant reduction in systemic blood pressure, portal blood flow, and the absorption of AIB from the small intestine. Resuscitation restored both blood pressure and portal blood flow. But a significant reduction in absorption of AIB persisted. This suggests that hemorrhage results in an inhibition of amino acid intestinal active transport which is not dependent on the mesenteric circulation. The reduced intestinal absorptive function has important implications for the route of administration of nutrition following hemorrhage and trauma.

Aminoisobutyric Acids↗
PubMed1992

Effect of age on wound healing in healthy human beings.

BACKGROUND: Although the elderly clinically have a higher rate of wound complications, the physiologic effect of age on wound healing in human beings is unknown. METHODS: Healthy young (18 to 55 years of age) and elderly (more than 65 years of age) human volunteers had a 2 x 2 cm, superficial, split-thickness wound created on the anterior aspect of the thigh, and the rate of epithelialization was assessed. For studies of fibroplasia, similar groups underwent subcutaneous implantation of polytetrafluoroethylene catheters, which were removed after 14 days. Biochemical analyses of the catheters included determinations of hydroxyproline, total alpha-amino nitrogen, and DNA. RESULTS: The elderly volunteers had a significant delay of 1.9 days in epithelialization. Analyses of the subcutaneously implanted catheters showed no difference in DNA content or hydroxyproline-accumulation; however, the young volunteers had a significantly higher amount of total alpha-amino nitrogen. CONCLUSIONS: In healthy humans, aging leads to delayed epithelialization. No effect of age on collagen synthesis was noted, although accumulation of wound noncollagenous protein was decreased. This decrease may impair the mechanical properties of scarring in aged human beings.

Adolescent↗
PubMed1991

The wound environment as a regulator of fibroblast phenotype.

Fibroblasts are fundamental to successful wound healing. We hypothesized that the induction and regulation of various fibroblast functions (proliferation, collagen synthesis, and remodeling) are determined by the wound environment. We examined the effect of wound fluid (WF), as a reflection of the wound environment, on the phenotypic expression of normal dermal (NF) and wound-harvested fibroblasts (WHF). WF and WHF were obtained from implanted polyvinyl alcohol sponges in 10-day-old wounds. NF and WHF were used between one and three passages. Proliferative function was assayed in a microculture system using serum stimulation (n = 12). The proliferative response of both NF and WHF to serum was significantly reduced by the addition of 20% WF (17,261 +/- 1231 cpm vs 2704 +/- 1215 cpm for NF, P less than 0.05; and 15,391 +/- 3735 cpm vs 1701 +/- 816 cpm for WHF, P less than 0.05 in serum and WF, respectively). Total protein synthesis (measured by [3H]proline incorporation) was equal in both fibroblast types; however, the relative collagen synthesis (collagenase-digestible fraction) was markedly different (2.2 +/- 0.9% for NF vs 11.4 +/- 2% for WHF, P less than 0.05). Addition of WF markedly enhanced NF collagen synthesis to 9.4 +/- 2%, but had no effect on WHF. Mechanical and remodeling functions were assayed using fibroblast-populated collagen lattices. In serum, WHF contracted the lattices faster than NF (499 +/- 14 mm2 vs 770 +/- 30 mm2 at 24 hr, P less than 0.05, and 301 +/- 18 mm2 vs 540 +/- 21 mm2 at 72 hr, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Nitric oxide generation from L-arginine is required for optimal human peripheral blood lymphocyte DNA synthesis.

We examined whether L-arginine is a substrate for nitric oxide (NO) production by peripheral blood mononuclear cells (MNC) in vitro. Minimal extracellular arginine (0.04 mmol/L) is required for maximal lymphocyte proliferation after phytohemagglutinin stimulation. In the absence of arginine, proliferation was 41% of normal without loss of viability. In contrast, MNC total protein synthesis (as assessed by tritiated leucine incorporation) or lymphokine synthesis (interleukin-2, as assessed by cytotoxic lymphoid line (CTLL) proliferation) were not affected by the absence or presence of arginine in the medium. Exogenous nitric oxide provided as sodium nitroprusside could replace L-arginine for maximal blastogenic proliferation. The addition of NG-monomethyl-L-arginine (NMMA; 0.1 mmol/L), a specific inhibitor of the NO synthetic pathway, significantly reduced DNA synthesis both at 0 and 0.1 mmol/L arginine concentrations; this effect was reversed to 91% of normal by excess arginine (1.0 mmol/L). Homoarginine (0.1 mmol/L; a known substrate for NO production) partially substituted for arginine, and this effect was also abrogated by NMMA. Nitrite levels (an end product of NO metabolism) were reduced when L-arginine was absent or NMMA was added to L-arginine-containing media. Cytosol from phytohemagglutinin-stimulated MNC-enhanced cyclic guanosine monophosphate production in the presence of L-arginine as substrate. The data suggest that the inductive effects of L-arginine on MNC DNA synthesis are not related to its nutrient requirement for protein synthesis, but rather caused by its role as a substrate for NO production. MNC actively synthesize NO during mitogenic proliferation. NO appears to be a promoter of MNC DNA synthesis, probably by its well-known effect as an activator of guanylate cyclase, which increases cyclic guanosine monophosphate levels.

Arginine↗
PubMed1990

Cloned murine T lymphocytes synthesize a molecule with the biological characteristics of nitric oxide.

Recently, activated neutrophils and macrophages have been shown to synthesize nitric oxide (NO) exclusively from L-arginine. We searched for the presence of this pathway in murine T cell clones. Using a platelet aggregation bioassay sensitive to NO, we demonstrate that IL2-stimulated CTLL and HT2 cells inhibit platelet aggregation, whereas unstimulated lymphocytes do not. This action can be inhibited by the specific NO synthase competitor NG-mono-methyl arginine, and only the L form of arginine or its analogue L-homoarginine are capable of providing substrate for NO synthesis.

Animals↗
PubMed1990

Wound healing and T-lymphocytes.

T-cell depletion leads to impaired wound healing. We studied the effect of combined T-helper and T-suppressor lymphocyte depletion on wound healing and compared it with the effect of all T-cell depletion. Groups of 10 male balb/c mice, 8 weeks old, underwent a 2.5-cm skin incision and subcutaneous implantation of polyvinyl alcohol sponges. Twenty-four hours prior to wounding one group was treated with 3OH12, a rat anti-mouse monoclonal antibody against the Thy-1.2 antigen present on all T-cells (1 mg); another group received 1 mg each of GK1.5 (anti-L3T4, CD4; anti-helper/effector subset) and 2.43 (anti-Lyt 2.1, CD8; anti-suppressor/cytotoxic subset). All monoclonal antibodies are cytotoxic in vivo. Controls received 1 mg of nonspecific rat IgG. Treatments were repeated weekly. Animals were sacrificed at 2 and 4 weeks postwounding. Equal depletion of all T- and Th- and Ts-subsets in peripheral blood and spleens was noted in the two experimental groups at sacrifice. Depleting Thy-1.2 cells (all T-cells) impaired wound healing as assessed by wound breaking strength and collagen synthesis. Combined anti-T-helper/effector and T-suppressor/cytotoxic depletion resulted in improved wound-healing parameters. This suggests that there is a Thy-1.2+, L3T4-, Lyt2- subpopulation of T lymphocytes which normally stimulates wound healing.

Animals↗
PubMed1990

Immune aspects of wound repair.

During the past few years, it has become evident that the cellular immune system plays a major role in the regulation of various phases of wound healing. Although there is much to learn about the interaction of the immune system with the healing wound, the explosion of knowledge in the field of growth factors and of monokines and lymphokines has generated information that greatly increases our understanding of the wound healing phenomenon. This discussion of the cellular immune system is restricted to macrophages and T lymphocytes.

Biological Factors↗
PubMed1990

Arginine enhances wound healing and lymphocyte immune responses in humans.

Arginine has been shown to enhance wound healing and T-cell-mediated immune function in rodents. In this study the effect of oral arginine supplementation on human collagen synthesis and T-cell function was studied in 36 healthy, nonsmoking human volunteers. While volunteers were under local anesthesia, a 5 cm segment of expanded polytetrafluoroethylene tubing (1 mm outer diameter, 90 mu pore size) was inserted subcutaneously into the right deltoid region. The volunteers were then randomized into three groups that were given the following substances: (1) daily supplements of 30 gm arginine hydrochloride (24.8 gm free arginine); (2) 30 gm arginine aspartate (17 gm free arginine) daily; or (3) placebo. The supplements were given orally for 2 weeks; dietary intake was not controlled. Mitogenic responses of peripheral blood lymphocytes to phytohemagglutinin and concanavalin A were assayed at the start of study and at 1 and 2 weeks after supplementation. At 2 weeks the catheters were removed, and the amount of hydroxyproline was determined as an index of new collagen synthesis and deposition. Arginine supplementation significantly enhanced the amount of collagen deposited into a standardized wound as assessed by the amount of hydroxyproline present (10.1 +/- 2.32 nmol/cm graft in controls vs 17.57 +/- 2.16 nmol/cm in the arginine aspartate group, [p = 0.028] and vs 23.85 +/- 2.16 nmol/cm in the arginine hydrochloride group [p less than 0.001]). In parallel, arginine supplementation at both doses increased lymphocyte mitogenesis in response to phytohemagglutinin and concanavalin A. The data suggest that arginine may be of clinical benefit in improving wound healing and immune responses.

Adult↗