Search PubMed⌕ Search

Biomedical subjects

A Barbul

Publications and source records attributed to A Barbul.

104 records · Page 6Linked to original sources
PubMedDate not supplied

Inhibition of tumor necrosis factor-alpha attenuates wound breaking strength in rats.

Exogenous administration of tumor necrosis factor-alpha has been shown to both enhance and attenuate cutaneous healing in a dose-dependent manner. We examined the effects of tumor necrosis factor inhibition in the healing wound by both systemic and local administration of tumor necrosis factor-binding protein. Male Balb/C mice underwent dorsal skin incision with subcutaneous implantation of 20 mg polyvinyl alcohol sponges (4 per animal). In Experiment I, one group (n = 20) received intraperitoneal injections of tumor necrosis factor-binding protein (3 mg/kg) at the time of wounding, while another group (n = 20) received saline. Four animals from each group were euthanized on days 1, 3, 5, 7, and 14 postwounding. In Experiment II, one group (n = 10) received an intraperitoneal injection of tumor necrosis factor-binding protein (3 mg/kg) at the time of wounding and every third day thereafter. Another group (n = 10) received an intraperitoneal injection of saline at the time of wounding and every third day thereafter. In Experiment III, one group received a single intraperitoneal injection of tumor necrosis factor-binding protein (3 mg/kg) at the time of wounding (n = 7), or on postwounding day 4 (n = 7), or day 7 (n = 7). Another group received saline injections at the time of wounding (n = 7), or on postwounding days 4 or 7 (n = 7, respectively). All animals in Experiments II and III were killed at postwounding day 14. Wound breaking strengths were assessed using a tensiometer. Wound fluid collected from the implanted sponges was assayed for tumor necrosis factor-alpha and tumor necrosis factor-binding protein levels using a biological assay and enzyme-linked immunosorbent assay, respectively. Collagen gene expression in sponge granulomata was assessed by Northern analysis. Collagen deposition in sponges was quantified by measuring hydroxyproline content. Wounds were significantly weaker in the animals that received repeated injections of tumor necrosis factor-binding protein with a mean wound breaking strength of 93.1 g vs. 186.6 g in controls (p < 0.05). Wound breaking strength in groups that received a single injection of tumor necrosis factor-binding protein on either day 0, 4, or 7 postwounding were no different than their respective controls. There was no difference in the mean hydroxyproline content of sponges between any of the tumor necrosis factor-binding protein groups and their respective controls. Northern analysis for collagen I and III expression also revealed no differences. These data indicate that continued systemic administration of tumor necrosis factor-binding protein resulted in significantly weaker wounds with no corresponding differences in wound collagen content, and collagen gene expression. This suggests that tumor necrosis factor-alpha inhibition throughout healing leads to a qualitatively impaired wound without a quantitative alteration in collagen deposition.

Analysis of Variance↗
PubMedDate not supplied

Supplemental arginine increases thymic cellularity in normal and murine sarcoma virus-inoculated mice and increases the resistance to murine sarcoma virus tumor.

Arginine supplements were given to 6 week old CBA mice beginning 3 days prior to inoculation with a murine sarcoma virus, the Moloney Sarcoma Virus (MSV). Although the basal diet contained 1.8% arginine and was therefore not arginine-deficient, supplementation of the diet and the drinking water with 0.5% arginine HCl reduced tumor incidence, lengthened the latency period, decreased tumor size, and hastened tumor regression. Arginine also increased thymic weight and cellularity in normal and in MSV-inoculated mice. The antitumor action of arginine may be related to its effect on the thymus.

Adrenal Glands↗
PubMedDate not supplied

Thymic stimulatory actions of arginine.

Various arginine HCl supplements (0.5-3%), half added to a basal commercial rodent chow (1.8% arginine) and half to the drinking water, were given to 8- to 9-week-old male CBA/J mice for 6 days. Control animals were fed the basal chow and drank tap water. All mice ate and drank ad libitum. Weight gain and food intake were similar in all groups. All arginine supplements increased significantly: thymic weight (average 22%), thymic lymphocyte content (average 45%), and the in vitro reactivity of thymic lymphocytes judged by the incorporation of 3H-leucine into the TCA-precipitable protein fraction in response to stimulation by phytohemagglutinin and concanavalin A. All these thymic effects resulted from the 0.5% arginine hydrochloride supplement; further increases in arginine supplementation did not increase these effects. These data suggest that supplemental arginine may improve host defence mechanisms and thereby may play an important role in the care of severely injured or ill patients, since it is well established that their defense mechanisms are reduced.

Animals↗
PubMedDate not supplied

Arginine stimulates thymic immune function and ameliorates the obesity and the hyperglycemia of genetically obese mice.

The effect of 6-day dietary arginine supplementation on the weight gain, blood glucose, thymus weight, thymic lymphocyte content, and in vitro thymic lymphocyte immune reactivity was studied in obese (C57BL/6J-OB/)B) and heterozygous lean mice. Control mice were fed a commercial laboratory chow (1.8% arginine content) and drank tap water, while supplemented mice were given 0.5% arginine in the chow and 0.5% arginine solution for drinking. All mice ate and drank ad libitum. Supplemental arginine significantly decreased the weight gain (1.2 g vs. 2.2 g, p less than 0.01) and blood glucose levels (303 mg% vs 236 mg%, p less than 0.02) of the OB/OB mice; no such effects were noted in the lean heterozygotes, all of which had normal blood glucose levels. OB/OB mice had thymus glands which weighed less and contained significantly fewer lymphocytes than their lean littermates. In vitro mitogen-stimulated thymic lymphocyte protein synthetic rates were equal in chow-fed lean and OB/OB mice. In both groups, supplemental arginine significantly increased thymus weight, the number of thymic lymphocytes per gland, and thymic lymphocyte immunoreactivity in vitro. The hormonal secretagogue activity of arginine on the pituitary may explain its beneficial effects on the rate of weight gain, hyperglycemia, and depressed thymic immune function of OB/OB mice.

Animals↗
PubMedDate not supplied

Optimal levels of arginine in maintenance intravenous hyperalimentation.

The optimal levels of arginine (Arg) for growth and immunity were studied in mildly depleted, noninjured rats maintained on intravenous hyperalimentation. Three groups of S-D rats (eight/group, weighing 275-300 g) underwent catheter insertion, 1 day of fasting, and then 7 days of intravenous hyperalimentation consisting of 20% dextrose, adequate minerals and vitamins, and three amino acid regimens: (1) FreAmine II (1.55 g Arg/liter); (2) FreAmine III (4.05 g Arg/liter); (3) experimental (7.5 g Arg/liter). The increase in arginine levels was achieved by lowering the glycine levels. There were no differences among the groups in terms of body weight gain (6.9 vs 8.3 vs 10.0 g) or in cumulative N balance (574 vs 660 vs 642 mg). Liver, spleen, and adrenal weights did not differ. Thymus weight was greater in groups B and C: (A) 345 +/- 27 mg vs (B) 445 +/- 34 mg, p less than 0.05, vs (C) 438 +/- 26 mg, p less than 0.05) as were the total number of lymphocytes/thymus (X 10(-9) (A) 0.93 +/- 0.12 vs (B) 1.37 +/- 0.18, p less than 0.05, vs (C) 1.46 +/- 0.15, p less than 0.05). Mitogen-induced thymocyte blastogenesis (cpm) was greatest in group C in response to phytohemagglutinin: (A) 9.558 +/- 3,799 vs (B) 20,088 +/- 5,890, NS, vs (C) 37,234 +/- 6,209, p less than 0.01 vs A and p less than 0.05 vs B) and Concanavalin A: (A) 71,035 +/- 15,228 vs (B) 111,734 +/- 15,021, NS, vs (C) 172,967 +/- 19,861, p less than 0.01 vs A and p less than 0.05 vs B). In the intravenous hyperalimentation-maintained noninjured rat ARG concentrations more than 1.55 g/liter do not enhance N retention or growth. Larger doses of ARG have strong thymic immunostimulatory effects without any toxicity or growth reduction.

Amino Acids↗
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

Intestinal amino acid absorption during sepsis.

Sepsis has been shown to cause a decrease in mesenteric blood flow in association with ultrastructural changes in the small intestine and impaired immune, barrier, and metabolic functions of the gut. These impairments in the structure and function of the gastrointestinal tract may have a detrimental effect on the morbidity and mortality of sepsis. Two recent studies have shown that the ability of the small intestine to absorb amino acids is also impaired during sepsis, but the systemic and cellular mechanisms of this impairment are not known. Release of cytokines induced by systemic bacteria or endotoxin may lead to a reduction in the synthesis of transporter proteins by the enterocyte at a time when there is reduced availability of both luminal (because of anorexia) and circulating (because of reduced mesenteric blood flow) substrates. Future research needs to investigate the systemic and local mediation of the sepsis-induced reduction in intestinal amino acid absorption and the possibility of correcting the defect by the administration of enteral nutrients, hormones, or drugs.

Amino Acids↗
PubMedDate not supplied

The role of the imino transporter protein in sepsis-impaired intestinal proline absorption.

Recently, sepsis has been shown to impair intestinal amino acid absorption in addition to gut metabolic and barrier functions. We investigated intestinal proline absorption in a rabbit model of sepsis. Twelve hours after intraperitoneal injection of lipopolysaccharide, proline uptake by everted jejunal sacs prepared from septic animals (480.4 +/- 67.4 nmol per sac per hour) was significantly reduced compared with controls (846.8 +/- 73.5 nmol per sac per hour) (p < .001 by t test). We next investigated whether reduced expression of transporter proteins contributed to the impaired intestinal proline uptake during sepsis. The proline (imino) carrier of rabbit jejunum is covalently bound by fluorescein isothiocyanate (FITC) and/or phenylisothiocyanate with irreversible inhibition of proline uptake. This binding and inhibition is prevented by sodium chloride and L-proline. Single-cell suspensions of rabbit enterocytes were prepared 12 hours after intraperitoneal injection of lipopolysaccharide/saline or saline alone. Enterocytes were incubated for 30 minutes in tris(hydroxymethyl)aminomethane/ethylenediaminetetraacetate (Tris/EDTA) buffer; buffer with 1 mM phenylisothiocyanate; or buffer with 10 mM proline, 100 mM sodium chloride, and 1 mM phenylisothiocyanate. After incubation with 10 microM FITC in Tris/EDTA buffer for 15 minutes, the percent positivity and fluorescent intensity of FITC binding to enterocytes were determined by using flow cytometry. Sepsis significantly reduced the percentage of enterocytes binding FITC and the fluorescent intensity of FITC binding of proline/sodium chloride-pretreated or untreated cells. This suggests that sepsis depresses the expression of imino transporters by rabbit enterocytes, which may explain the reduced intestinal proline absorption.

Amino Acid Transport Systems, Neutral↗
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↗
PubMedDate not supplied

The route of nutrition support affects the early phase of wound healing.

BACKGROUND: Nutrition support via the enteral route has been shown to be superior to parenteral administration in maintaining immune function, decreasing septic complications, and increasing survival after severe trauma and surgical injury. Whether the route of nutrition support affects wound healing, another important determinant of outcome following injury, is not known. METHODS: Forty-nine Sprague-Dawley rats, 290 to 360 g body wt, underwent identical surgical manipulation consisting of central venous catheterization, fashioning of gastrostomy and dorsal skin incision, and placement of polyvinyl alcohol sponges into subcutaneous pockets. Identical infusates of 25% dextrose, 4.25% amino acids, and vitamins were given, half the animals receiving the infusion via the gastrostomy and the other half via the venous catheter. Animals were killed on day 5, 7, or 10. Wound breaking strength, sponge hydroxyproline content (an index of wound collagen deposition), and types I and III collagen gene expression were measured. RESULTS: There were no nutritional differences between the two groups in terms of energy intake, body weight gain, and plasma levels of albumin, total protein, or urea nitrogen. On day 5 wound breaking strength was significantly higher in the enterally supported group (89.3 +/- 90.7 vs 64.9 +/- 40.2 g for the parenteral group, p < .05). This was paralleled by enhanced wound collagen accumulation (182 +/- 19 vs 132 +/- 13 microg, p < .05). Gene expression of type I, but not type III, collagen also was increased in the enterally fed group. There were no differences noted between the two groups in wound healing parameters 7 and 10 days after injury. CONCLUSIONS: The data demonstrate that the route of nutrition administration can influence wound healing. The beneficial effect of the enteral feeding route is limited to the early phases of healing.

Amino Acids↗