PubMed Health⌕ Search

Biomedical subjects

A Barbul

Publications and source records attributed to A Barbul.

At least 19 recordsLinked to original sources
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↗
PubMed1989

The wound is a possible source of posttraumatic immunosuppression.

Wound fluid from 10-day-old healing wounds in rats inhibits lymphocyte immune responses. Since severe injury is frequently complicated by immunosuppression as manifested by sepsis, we hypothesized that the wound may be a source of factors that impair host immune responses. Therefore, we studied the effect of systemic wound fluid administration on the survival of rats subjected to an acute peritonitis model. Male Sprague-Dawley rats, fitted with internal jugular catheters 48 hours previously, underwent cecal ligation and puncture with a 23-gauge needle. Immediately after the operation, rats were treated intravenously every 12 hours with either wound fluid obtained from 10-day-old healing wounds and adjusted to 10 mg of protein per milliliter or rat serum. In vitro testing of the wound fluid showed it to be highly inhibitory of thymic lymphocyte mitogenesis. Rats treated with wound fluid had significantly higher mortality after peritonitis than did control rats. The data show that the wound contains factors that can impair host immune responses to sepsis. This suggests that the wound may be the source of posttraumatic host immunosuppression.

Animals↗
PubMed1989

The effect of in vivo T helper and T suppressor lymphocyte depletion on wound healing.

The role of T lymphocytes in wound healing is still not well-defined. Because it had been previously shown that in vivo depletion of T cells leads to impaired wound healing, the effect of depleting T cell subsets on subsequent fibroplasia was studied. T helper/effector cells were depleted by the use of the monoclonal antibody GK1.5, reactive against the L3T4 antigen (CD4). T suppressor/cytotoxic lymphocytes were depleted by using the 2.43 monoclonal antibody reactive against the Lyt 2 antigen (CD8). In the first experiment, Balb/c mice were treated with the antibodies starting at 24 hours before wounding was performed, and weekly thereafter. Depletion of the T helper/effector cells had no effect on wound-breaking strength or hydroxyproline deposition in sponge granulomas, whereas depletion of T suppressor/cytotoxic cells significantly enhanced both of these healing parameters. In a second experiment, T cell subset depletion was started on Days 0, 3, 7, 10, and 14 postwounding, and treatments were continued weekly thereafter. Once again, depletion of T helper/effector cells had no effect on wound healing, whereas depletion of T suppressor/cytotoxic cells markedly increased both wound-breaking strength and collagen synthesis. In conclusion, the data show that T suppressor/cytotoxic cells have a counter-regulatory role in wound healing, whereas the T cell subset responsible for up-regulating wound healing remains to be identified.

Animals↗
PubMed1989

Wound healing in nude mice: a study on the regulatory role of lymphocytes in fibroplasia.

In order to understand the role of T cells in postinjury fibroplasia, we have studied wound healing in congenitally athymic nude mice that lack a normally developed T cell system. Healing of incisional wounds, as assessed by wound breaking strength, was significantly stronger in nude mice compared with normal thymus-bearing animals. This was accompanied by a marked increase in the amount of reparative collagen synthesized at the wound site, as assessed by the hydroxyproline content of subcutaneously implanted sponges. Because nude mice have some extrathymic T cell maturation, we used an anti-Thy-1.2 (30H12) monoclonal antibody to selectively deplete T cells in vivo. Although such treatments impaired wound healing in normal mice, they had no effect on any wound healing parameter in nude mice. In a separate experiment, T cell reconstitution of nude mice, sufficient to significantly enhance in vivo delayed hypersensitivity responses, led to a decrease in both wound breaking strength and hydroxyproline deposition in subcutaneously implanted polyvinyl sponges. The data suggest that T cells play a dual role in wound healing: an early stimulatory role on macrophages, endothelial cells, and fibroblasts, and a late counterregulatory role, which may be responsible for the orderly completion of wound repair.

Animals↗
PubMed1989

Inhibition of wound repair by thymic hormones.

To further define the role of the thymus in wound healing, we studied the effects of two thymic hormones on fibroplasia in normal euthymic and in nude athymic mice. Groups of 10 mice underwent a 2.5 cm dorsal skin incision with subcutaneous placement of polyvinyl alcohol sponges. Starting on the day of wounding, the following daily injections were given: (1) thymopentin (TP5), an active synthetic pentapeptide of thymopoietin, a naturally occurring thymic hormone (1 microgram/day/IM); (2) thymulin or facteur thymique serique (FTS), a naturally occurring circulating thymic hormone (0.2 microgram/day/IM); (3) control saline solution (0.1 ml/day/IM). All mice were killed 4 weeks after wounding, and wound breaking strength and hydroxyproline content of the sponge granulomas were measured. The results show that both thymic hormones impaired wound breaking strength and reparative collagen synthesis in normal and athymic mice. The magnitude of the wound healing impairment induced by the two hormones was equal in the thymus-bearing and in the nude mice. The data support previous findings, which suggested that the thymus has an inhibitory effect on wound healing.

Animals↗
PubMed1988

Generation of an anti-interleukin 2 factor in healing wounds.

Previously we have noted that fluid obtained from ten-day-old healing wounds noncytotoxically inhibits the blastogenesis of lymphocytes in response to mitogens or antigens. Since these lymphocytic responses are interleukin 2 (IL-2)-mediated, we looked for a specific IL-2 inhibitor in wound fluid. We have found that wound fluid blocks the response of thymic lymphocytes and of two cloned T-helper cell lines (D10 and HT2) to exogenous human recombinant IL-2. The wound fluid enhances fibroblast proliferation, thus demonstrating that its proliferative inhibitory activity is specific for lymphocytes. The findings suggest that wound fluid contains a factor that impairs lymphocyte response to IL-2, probably at the receptor or postreceptor level.

Animals↗
PubMed1988

Stimulation of T cell immunity by arginine enhances survival in peritonitis.

T cell-mediated immunity may play a role in host responses to infection. Arginine is a known thymic and T cell stimulator which enhances host allogenic, mitogenic, and anti-tumor responses. We, therefore, examined the effect of arginine on the survival of rats with severe and lethal peritonitis induced by cecal ligation and double-needle puncture (CLP). In Experiment 1, arginine HCl (100 mg) was given bid by gavage starting immediately after CLP. In Experiment 2, the same dose of arginine was given by gavage bid for 3 days pre-CLP and continued thereafter. In Experiment 3, arginine was administered iv post-CLP (100 mg tid). Arginine had no effect on overall survival in Experiment 1. In Experiments 2 and 3, arginine therapy significantly increased survival at all times. A separate experiment was carried out to determine the reason for the differential response to arginine administered via gavage or iv post-CLP (Experiments 1 and 3). Nonseptic rats showed a 400% increase in plasma arginine 30 min after gavage with 100 mg arginine (P less than 0.001). No rise in plasma arginine was noted when arginine was administered by gavage post-CLP. The impaired intestinal absorption or markedly increased utilization of arginine in this septic model may explain why no improved survival was seen in Experiment 1. The mechanism for the improved survival with arginine therapy seen in Experiments 2 and 3 may be related to its known thymic and T cell immunostimulatory effects.

Animals↗
PubMed1988

Suppressor cell generation during normal wound healing.

We have previously shown that 10 day healing wounds in rats contain wound mononuclear cells (WMNC) which inhibit normal lymphocyte mitogenic and allogeneic responses. In the present study we sought to further characterize the WMNC and define their mechanism of action. Polyvinyl alcohol sponges implanted in wounds were harvested and processed 10 days postwounding. The resultant WMNC suspension contained less than 15% macrophages. By FACS analysis, 69.5 +/- 11.4% (mean +/- SD of eight separate experiments) of the cells expressed the all T cell marker (W3/13), while 47.7 +/- 11.9% stained with the T helper/effector marker (W3/25) and 49.5 +/- 18.8% expressed the T suppressor/cytotoxic phenotype (OX8) (Th/Ts ratio = 0.96 +/- 0.13). When various numbers of WMNC were cocultured with 5 X 10(5) PHA-stimulated rat thymic lymphocytes, as few as 500 WMNC inhibit normal blastogenesis. Long-term (72 or 144 hr) culture of WMNC revealed that they maintain their suppressive activity. Furthermore, the conditioned media of long-term cultures also significantly suppressed thymic lymphocyte PHA blastogenesis, suggesting that the WMNC secrete suppressive cytokines. Large doses of human recombinant IL-2 or indomethacin did not abrogate the inhibitory effect of WMNC. We conclude that the healing wound is normally infiltrated by suppressor lymphocytes which generate immune inhibitory cytokines.

Animals↗
PubMed1988

Arginine metabolism in wounds.

Arginine metabolism in wounds was investigated in the rat in 1) lambda-carrageenan-wounded skeletal muscle, 2) Schilling chambers, and 3) subcutaneous polyvinyl alcohol sponges. All showed decreased arginine and elevated ornithine contents and high arginase activity. Arginase could be brought to the wound by macrophages, which were found to contain arginase activity. However, arginase was expressed by macrophages only after cell lysis and no arginase was released by viable macrophages in vitro. Thus the extracellular arginase of wounds may derive from dead macrophages within the injured tissue. Wound and peritoneal macrophages exhibited arginase deiminase activity as demonstrated by the conversion of [guanido-14C]arginine to radiolabeled citrulline during culture, the inhibition of this reaction by formamidinium acetate, and the lack of prokaryotic contamination of the cultures. These findings and the known metabolic fates of the products of arginase and arginine deiminase in the cellular populations of the wound suggest the possibility of cooperativity among cells for the production of substrates for collagen synthesis.

Amino Acids↗