PubMed Health⌕ Search

Biomedical subjects

A M Aquino

Publications and source records attributed to A M Aquino.

8 recordsLinked to original sources

Sustained microgravity reduces intrinsic wound healing and growth factor responses in the rat.

Spaceflight is known to diminish bone mass and reduce immune function, suggesting that repair of connective tissue might be impaired in a microgravity environment. Fisher 344 rats were used to test wound healing responses in the orbiting Space Shuttle Endeavour by preflight implantation of polyvinyl acetal sponge disks in which pellets were placed to release either platelet-derived growth factor (PDGF-BB), basic fibroblast growth factor (bFGF), or placebo. Control groups on the ground included a matched environment group in similar housing modules and temperature control groups in cages at 22 degreesC and 28 degreesC. After 12 days of implantation and 10 days in orbit, the removed sponges were analyzed for histological and biochemical responses. Growth factor responses were histologically evident after release of PDGF-BB and bFGF in ground controls, whereas only immediate-release bFGF and delayed-release PDGF-BB showed significant responses in microgravity. Biochemical data confirmed that cellularity was increased by both factors in ground sponges; however, this response was significantly blunted in flight sponges (P<0.005, ANOVA), irrespective timing of factor release. Collagen content was 62% lower in sponges from animals with 10 days of microgravity exposure (P<0.01, ANOVA) and further reduced by bFGF. These data suggest that orbital exposure retards the capacity of wounds to heal and respond to exogenous stimuli.

Animals↗

Hyaluronate derivatives and their application to wound healing: preliminary observations.

Hyaluronic acid and its derivatives show promise as biomaterials in wound healing applications. Studies of cutaneous wound repair were carried out in two animal models to compare the biological effects of hyaluronic acid and hyaluronic acid ethyl ester, a new semisynthetic derivative. The two compounds were tested in partial-thickness excisional wounds in 40-kg pigs and full-thickness excisional wounds in the rabbit ear as 0.2% (w/w) formulations in a neutral Na alginate vehicle. All compounds were administered daily under an occlusive, polyurethane dressing. Neither hyaluronic acid nor the hyaluronic acid ethyl ester showed toxic or inflammatory influences over the observation period of about 2 weeks. Morphometric analysis of porcine wounds revealed small differences among treatment groups which may have been masked by the effect of the vehicle. The rabbit ear model data suggested a very slight inhibition of wound closure. Biochemical analysis of ear wounds showed this injury model to be a sensitive system for evaluation of vulnerary agents. The hyaluronate-treated wounds tended to accumulate collagen more slowly, which may reflect the capacity of these compounds to modify the scarring process. Given the ability to fabricate hyaluronate esters into films and fibers, these data suggest that such biomaterials will not, by themselves, exert a negative influence on the repair process and may improve healing, either alone or in combination with other soluble agents.

Animals↗

Monospecific antibodies implicate basic fibroblast growth factor in normal wound repair.

Exogenous polypeptide growth factors influence the rate of wound healing and other biological processes, but there is no direct evidence that these peptides have an intrinsic role. To test whether basic fibroblast growth factor is involved in wound repair, rats were implanted with subcutaneous polyvinyl alcohol sponges containing slow-release pellets releasing either a polyclonal neutralizing antiserum directed against basic fibroblast growth factor, preimmune IgG, or nothing. Histological and biochemical evaluation of the granulation tissue that infiltrated the sponges showed anti-basic fibroblast growth factor to cause significant reductions in DNA, protein, and collagen content when compared with either preimmune IgG or placebo at the early stages of wound repair.

Animals↗

Recombinant basic fibroblast growth factor accelerates wound healing.

Basic fibroblast growth factor (bFGF) stimulates extracellular matrix metabolism, growth, and movement of mesodermally derived cells. We have previously shown that collagen content in polyvinyl alcohol sponges increased after bFGF treatment. We hypothesized that bFGF-treated incisional wounds would heal more rapidly. After intraperitoneal pentobarbital anesthesia, male, 200- to 250-g, Sprague-Dawley rats (n = 27) each underwent two sets of paired, transverse, dorsal incisions closed with steel sutures. On Day 3 postwounding, 0.4 ml of bFGF (recombinant, 400 ng. Synergen) or normal saline was injected into one of each paired incisions. Animals were killed with ether on postwounding Days 5, 6, and 7 and their dorsal pelts were excised. Fresh or formalin-fixed wound strips were subjected to tensile strength measurements using a tensiometer. Breaking energy was calculated. Wound collagen content (hydroxyproline) was measured in wound-edge samples following hydrolysis using high-performance liquid chromatography. There was an overall significant increase in fresh wound tensile strength (13.7 +/- 1.06 vs 19.1 +/- 1.99 g/mm, P less than 0.01) and wound breaking energy (476 +/- 47 vs 747 +/- 76 mm2, P less than 0.001) in bFGF-treated incisions. There was an increase in wound collagen content which was not statistically significant and there was no difference in fixed incisional tensile strength. Histologic examination showed better organization and maturation in bFGF wounds. Recombinant bFGF accelerates normal rat wound healing. This may be due to earlier accumulation of collagen and fibroblasts and/or to greater collagen crosslinking in bFGF-treated wounds.

Animals↗

Growth factors bFGF and TGB beta accelerate the rate of wound repair in normal and in diabetic rats.

The effects of basic fibroblast growth factor (bFGF) and transforming growth factor beta (TGF beta) on the rate of wound repair in both normal and streptozotocin-induced diabetic rats were investigated using two model systems of wound repair, namely incisional wounding and subcutaneous implantation of polyvinyl alcohol (PVA) sponges. Both models showed the expected wound-healing defects of the diabetic rats. Granulation tissue collected from the implanted PVA sponges showed that the diabetic rats had reduced amounts of collagen, DNA and protein present at the wound site at two time points tested (7 and 9 days post-implantation). Fresh tensile strength of the incisional wounds, a measure of the collagen organization in a wound, was reduced to 53% of normal in diabetic rats on day 7 post-wounding, and was only 29% of normal by day 21. Formalin-fixed tensile strength, a measure of collagen content of the wound, was 41% of normal on day 7, and 78% of normal by day 21, giving evidence that while the collagen concentration of the diabetic wounds approached that of normal wounds, it did not undergo the normal maturation process. A single injection of 2 micrograms of TGF beta directly into the incision three days after wounding resulted in little difference in the fresh and fixed tensile strength of diabetic wounds when tested at 7, 14 and 21 days post-wounding. Normal rats, however, responded well, resulting in a greater than 30% increase in both fresh and fixed tensile strength.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Asymmetrical distribution of noradrenaline in the neocortex, hippocampus and adrenal glands of rats and changes with chronic activity restriction].

The norepinephrine content of neocortex, hippocampus, and adrenals of adult male Wistar rats was estimated. In normal rats an asymmetrical right-left-distribution of the norepinephrine content was found. Neocortex and hippocampus showed a contralateral, neocortex and adrenals an ipsilateral ratio. Chronic stress cancelled this right-left asymmetry of norepinephrine distribution. In brain the levelling appeared earlier than in adrenals.

Adrenal Glands↗

[Behavior of thyroid hormones, corticosterone, adrenocorticotropic hormone and insulin in the plasma of the rat under stress conditions].

In male Wistar rats the behaviour of the plasma concentrations of thyroid hormones, corticosterone, adrenocorticotrophic hormone and insulin was examined in the course of a hypokinase stress of 6 weeks duration. Blood was taken after a stress of 1, 3 and 6 weeks. In these cases in thyroid hormones a decrease of the thyroxine (T4) and an increase of the triiodothyronine (T3) appeared. In an increased need of energy of the organism apparently a more rapid peripheral conversion of T4 to the more active metabolic T3 takes place. Only after a longer stress the deficit of thyroid hormone is equalized via the regulating circle hypothalamus-hypophysis-thyroid gland. The hormones ACTH and corticosterone which are connected together in the regulation system hypothalamus-hypophysis-adrenal cortex, after one week slightly increase in the plasma of rats and clearly decrease after a stress of 3 weeks. This shows that in a longer stress load apparently an exhaustion of the bioenergetic reserves of the organism develops. At last under long-term stress a significant decrease of the plasma insulin level was found. The decrease of insulin might be conditioned by an endogenic liberation of catecholamine.

Adrenocorticotropic Hormone↗

The diabetic rat as an impaired wound healing model: stimulatory effects of transforming growth factor-beta and basic fibroblast growth factor.

Two models of wound repair compared the effect of defined, recombinant growth factors on the rate of wound repair in both normal and streptozotocin-induced diabetic rats: subcutaneous implantation of polyvinyl alcohol sponges and incisional wounding. Transverse incisional wounds were made on the dorsal surface of rats and closed with steel sutures. Three days postwounding the rats received a single injection of either transforming growth factor-beta or vehicle alone directly into the wound site. Animals were sacrificed 7, 14, and 21 days postwounding, and fresh and formalin-fixed wound tensile strength were measured. Diabetic rats had expected defects in wound repair, including decreased granulation tissue and reduced amounts of collagen, protein, and DNA. Fresh tensile strength of the diabetic incisions was 53% of normal on Day 7 (p < or = .01) and 29% of normal on Day 21. Fixed tensile strength was 41% of normal on Day 7 (p < or = .01) and fell to 78% of normal by Day 21 (p < or = .01), suggesting that collagen concentrations of diabetic wounds increased towards normal but did not undergo maturation. TGF beta produced a moderate increase in tensile strength of fresh and fixed wounds of diabetic rats, but not to the levels of wounds in untreated normal rats. Sponges fill with granulation tissue, their reproducible rate of organization being measured by histological and biochemical methods. A single injection into sponges 3 days postimplantation of basic fibroblast growth factor, transforming growth factor-beta, or vehicle only, was evaluated at 7 and 9 days postimplantation. In the sponge model, bFGF and TGF beta were each able to induce significant increases in the accumulation of granulation tissue in both diabetic and normal rats. TGF beta increased the collagen content of sponges by 136% in sponges from diabetic animals (p < or = .001), thereby raising the collagen content to that of normal control wounds, while stimulating a 49% (p < or = .02) increase in sponges from normal animals on Day 9. By contrast, the response to bFGF was predominantly an increase in the protein and DNA content of the sponges. These results emphasize the differential effects of the two cytokines in accelerating healing under conditions of defective wound repair.

Animals↗