PubMed Health⌕ Search

Biomedical subjects

M C Regan

Publications and source records attributed to M C Regan.

30 records · Page 2Linked to original sources
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↗
PubMedDate not supplied

Arginine enhances T-cell responses in athymic nude mice.

Supplemental L-arginine has been shown to enhance thymic and T-cell responses in rodents. We examined the ability of supplemental dietary L-arginine to induce T-cell function in athymic nude mice that lack a normally developed T-cell system. Groups of male nude (nu/nu) mice (Balb/c background) 7 to 8 weeks old were given for 2 weeks 1.2% arginine hydrochloride solution for drinking, whereas controls received acidified tap water. All mice ingested a standard laboratory chow. In the first experiment, the arginine-supplemented animals had significantly greater number of T cells in the spleen (assessed by the number of Thy 1.2-positive lymphocytes) and these cells had enhanced mitogenic responses to mitogenic stimulation (phytohemagglutinin and concanavalin A). In vivo delayed-type hypersensitivity responses to 2,4-dinitro-1-difluorobenzene were also significantly increased after the 2 weeks of arginine supplementation. In a second experiment, mice maintained under the same conditions were skin grafted with rat tail skin. Animals were observed for 100 days for rejection but no significant difference was noted in skin graft survival. We conclude that dietary arginine can increase extrathymic T-cell maturation and function, but cannot induce in vivo allogeneic graft recognition in athymic nude mice.

Animals↗
PubMedDate not supplied

Metabolic effects of arginine in a healthy elderly population.

Recently there has been much interest in the use of arginine to stimulate immune responses and to promote wound healing. In the present study, the effect of an oral supplementation with arginine on the metabolism of 45 healthy, nonsmoking, elderly volunteers was investigated. Subjects were divided into two groups that received either arginine aspartate (17 g free arginine) (n = 30) or a placebo (n = 15). The supplements were taken for a period of 14 days. Dietary intake of food was not controlled. Blood chemistry, lipid profiles, and as an index of nutritional status, serum insulin-like growth factor-1 levels and nitrogen balance were compared before and after supplementation. Two weeks of arginine supplementation led to a significant elevation of serum insulin-like growth factor concentrations and an improved and positive nitrogen balance (2.0 +/- 0.41 g N) when compared with controls (0.11 +/- 0.47 g N; p = 0.0114). In addition the arginine-supplemented group demonstrated a decreased total serum cholesterol with a reduction in the low-density lipoprotein but not the high-density lipoprotein fraction resulting in a increase in the ratio of low- to high-density lipoprotein fraction. No adverse effects were observed at this dosage of arginine. The data suggest that oral arginine supplementation may be used safely in elderly humans.

Aged↗