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Biomedical subjects

J M Davidson

Publications and source records attributed to J M Davidson.

248 records · Page 14Linked to original sources
PubMedDate not supplied

Low-energy helium-neon laser irradiation and the tensile strength of incisional wounds in the rat.

Low-level laser energy has been reported to modulate the wound healing process in some but not all studies. To examine this hypothesis, we investigated incisional wounds made on the dorsal pelt of rats for changes in the healing produced by low-level irradiation with a helium-neon laser. The incisions were made with a scalpel and closed with sutures. The rats were irradiated daily for 12 days with four levels of laser light (0.0, 0.47, 0.93, and 1.73 J/cm(2)). Analysis of wound tensile strength indicated a possible strengthening of fresh wounds at the highest levels of irradiation (1.73 J/cm(2)). No change was observed in the tensile strength of formalin-fixed wounds. The distribution of measured tensile strengths did not follow normal statistics; instead they showed a platykurtic distribution. Using resampling statistics, where no assumption is made as to the nature of the distribution, we found that the results were contrary to other studies: no biostimulatory effect was seen.

Journal Article↗
PubMedDate not supplied

Reversal of the wound healing deficit in diabetic rats by combined basic fibroblast growth factor and transforming growth factor-beta1 therapy.

Wound healing is impaired in the diabetic state because of, at least in part, low expression of growth factors. Individual growth factors can partially activate healing, yet the actual wound environment presents a dynamic continuum of multiple cellular signals. Complex interactions among growth factors and target cells can have synergistic effects, and several examples of combinatorial, in vivo activity are evident in the literature. In this study, the implantation of a combination of basic fibroblast growth factor and transforming growth factor-beta in rats induced fivefold to sevenfold increases in granulation tissue formation in comparison with implantation of each growth factor alone. Diabetes was induced in adult, male Sprague-Dawley rats with streptozotocin. Incisional wounds and sponge granulation tissue were produced in separate groups and then treated with an injection of 2 microg transforming growth factor-beta1 combined with 10 microg basic fibroblast growth factor on day 3. DNA, collagen, and protein were analyzed in granulation tissue on days 7 and 9, and biomechanical properties of incisions were tested on days 7, 14, and 21. The combination of transforming growth factor-beta1 and basic fibroblast growth factor had marked, positive effects on biochemical parameters of wound healing and reversed the tensile strength deficit of diabetic wounds. Nonradioactive in situ hybridization showed increased expression of messenger RNA for type I and III procollagen and transforming growth factor-beta1 in normal and diabetic wounds, whereas ultrastructural examination showed a marked reorganization of collagen fibrils. These findings reinforce the concept that appropriate mixtures of cytokines rather than individual cytokines may more adequately stimulate tissues in cases of impaired wound healing.

Journal Article↗
PubMedDate not supplied

Boosting epidermal growth factor receptor expression by gene gun transfection stimulates epidermal growth in vivo.

Expression constructs encoding a full-length cDNA encoding the human epidermal growth factor receptor, or reporter gene for green fluorescent protein or luciferase were coated onto gold particles and driven into porcine skin using a gene gun delivery system. Strategies for epidermal growth factor receptor boosting were tested in two types of wounds. For grafted wounds, intact porcine skin was pretreated by the introduction of the epidermal growth factor receptor expression construct 24 hours before its harvesting as a split-thickness skin graft. Partial-thickness excisional wound beds (donor sites) were transfected at the time of their creation. Wound healing parameters were subsequently tested in the presence or absence of excess epidermal growth factor ligand. Initial distributions of gene gun delivered gold particles as well as luciferase expression levels suggested that optimal skin penetrations and expression levels were achieved at 500 psi for intact epidermis and 300 psi for exposed wound beds. At 2 days after gene delivery, visualization of green fluorescent protein by fluorescence microscopy showed focal expression of green fluorescent protein at the advancing epithelial outgrowths found at wound edges or surviving epithelial remnants. Green fluorescent protein expression appeared transient since no green fluorescent protein was noted in specimens removed at 4 days after injury. Northern blot analysis on mRNA isolated from wounds 2 days after introduction of epidermal growth factor receptor coated gold particles by gene gun confirmed the expression of the human epidermal growth factor receptor transgene in both skin grafts and excisional wounds. Skin grafts showed subsequent biological responses to the introduction of excessive epidermal growth factor receptor as well as expression of the human epidermal growth factor receptor construct within healing epidermis. While control autografts (reporter gene treated, epidermal growth factor alone, placebo formula, no treatment) showed few 5'-bromodeoxyuridine-labeled cells, epidermal growth factor receptor autografts showed 5'-bromodeoxyuridine labeling of nearly every basal cell. Favorable wound healing outcomes were also shown within excisional wounds following in vivo boosting of epidermal growth factor receptor. Four days after receiving epidermal growth factor receptor particle growth factor receptor transgene. Application of topical epidermal growth factor ligand resulted in the highest percentage of resurfacing. Maximal re-epithelialization was noted in wound beds receiving both receptor boosting and excessive daily epidermal growth factor ligand. A modest increase in the thickness of the granulation tissue followed gene therapy with epidermal growth factor receptor. In summary these in vivo data suggest that it is possible to boost in vivo expression of a tyrosine kinase receptor during wound repair. Increased epidermal growth factor receptor expression has an integral impact on cell proliferation, rates of resurfacing and dermal components and merits consideration as a possible therapeutic agent.

Animals↗
PubMedDate not supplied

Particle-mediated gene therapy of wounds.

Gene therapy is becoming a reality, and it is a particularly attractive approach for wound healing, because the wound site is often exposed, the treatment and condition should be transient, and gene products such as growth factors and cytokines suffer from problems with bioavailability and stability. Among the techniques for gene delivery to the wound site, particle-mediated bombardment with a device called the gene gun has become an important developmental tool. This instrument has been used in numerous examples of wound gene therapy with growth factors or their receptors in the last decade. Among the advantages of particle-mediated bombardment are ease and speed of preparation of the delivery vehicle, the stability of the DNA preparation, the absence of (viral) antigens, the ability to target the projectiles to different tissue depths and areas, and the rapid shedding of both particles and DNA if they are targeted to the epidermis. Clinical application of the technology remains limited by the relatively low efficiency of the method, the potential tissue damage created by impact of the particles, and the coverage area. The gene gun can also be used to facilitate the discovery and validation of gene products as wound healing agents.

Drug Carriers↗
PubMedDate not supplied

Delayed wound healing in aged rats is associated with increased collagen gel remodeling and contraction by skin fibroblasts, not with differences in apoptotic or myofibroblast cell populations.

Aging has been anecdotally reported to result in prolonged wound healing. Measurement of punch biopsy wound closure in young (4 month old) and old (36 month old) rats indicated there was a significant delay in wound closure by old rats during the early phase of repair, after which closure rates were equivalent. The delay in granulation tissue accumulation in older animals could involve premature programmed cell death (apoptosis); however, apoptotic fibroblasts in sponge granulation tissue and tissue culture were less abundant in samples from old rats relative to young rats. Myofibroblasts express alpha-smooth muscle actin, and they are believed to be important in wound contraction. There were no significant differences in overall abundance or distribution of alpha-smooth muscle actin containing myofibroblasts in granulation tissue and in cultured granulation tissue fibroblasts regardless of the age of the donor rat. The spatial distribution of myofibroblasts and apoptotic cells was distinct. Fibroblasts from granulation tissue and skin explants were placed in a collagen gel contraction assay prior to the 5th passage to determine their in vitro contractility. While granulation tissue fibroblasts from young and old rats showed similar collagen gel contractility, skin fibroblasts from old rats displayed greater collagen gel contractile behavior than young skin fibroblasts. Greater gel contractility of fibroblasts from old rats appeared to result, in large part, from the ability of those cells to cause generalized gel degradation. Gelatin zymography indicated a greater abundance of matrix metalloproteinase-2 in supernatants from gels containing skin fibroblasts from old rats. Taken together, these results suggest that the age-associated healing delay in the rat may not be related to the appearance or abundance of distinct myofibroblast or apoptotic cell populations. Proteolysis may have a significant role in delayed wound healing in aged animals.

Age Factors↗
PubMedDate not supplied

Induction of increased collagen and elastin biosynthesis in copper-deficient pig aorta.

Young pigs raised on a copper-deficient diet develop severe abnormalities of connective tissue due to defective cross-linking of collagen and elastin. They eventually succumb to anemia and cardiovascular damage, the latter apparently due to the defective connective tissue metabolism. We evaluated the effects of nutritional copper deficiency upon collagen and elastin synthesis using short-term explant cultures of the medial portion of four successive segments of the descending aorta from 110-day-old pigs raised on a copper-deficient diet. Collagen synthesis was evaluated by collagenase susceptibility, and elastin synthesis was quantified by immunoprecipitation with an antiporcine-elastin antiserum. In the normal developing aorta, elastin synthesis was maximal in the upper thoracic aorta, while levels of collagen synthesis were highest in the lower abdominal aorta. Both activities subsided by 110 days postpartum. Compared with controls, the copper-deficient group showed: 1) histopathologic changes confined to the luminal half of the thoracic aorta; 2) a 1.3- to 1.6-fold increase in cellularity along the entire length of the organ; 3) a 1.3- to 2.4-fold increase in relative collagen synthesis, the greatest change occurring in the thoracic portion; 4) a 3- to 4-fold increase of relative elastin synthesis in the thoracic aorta, the abdominal aorta remaining unchanged; 5) 4- to 10-fold increases in collagen production; and 6) a greater than 15-fold increase in elastin production by the tissue of the thoracic aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Posterior resin-based composite: review of the literature.

The use of direct posterior resin-based composite has increased primarily due to patient esthetic desires and product improvements. Other factors (substantiated or not) contributing to increased use of resin-based composite are environmental and health concerns with dental amalgam. New visible light cured resin-based composite products are introduced yearly, as manufacturers continue to improve this tooth-colored restorative material. This paper will characterize current posterior resin-based composite materials (hybrid, microfill, flowable, and packable), review recent in vitro and clinical research, and recommend indications for these materials. In addition, the literature on compomers will be reviewed and recommendation made for their use. The data indicates that composite resin is a technique sensitive restorative material that can be used in large preparations if proper manipulation and isolation can be maintained. Compomers may also be used as an esthetic posterior restorative if proper isolation is provided.

Bicuspid↗
PubMedDate not supplied

A long-term, prospective study of the physiologic and behavioral effects of hormone replacement in untreated hypogonadal men.

This study describes sexual activity, nocturnal penile erections, and mood states as a function of serum levels of androgens in previously untreated hypogonadal men before and during hormone replacement, selected infertile men (elevated serum follicle-stimulating hormone levels), and normal men. Nocturnal penile tumescence and rigidity were measured with a portable monitor, and sexual activity and mood were assessed by prospective, self-reported written forms. Nocturnal erections were absent or of very low amplitude and duration in the untreated hypogonadal men compared to the infertile and normal men. Nocturnal erections increased steadily during hormone replacement and were in the normal range within 6 to 12 months of treatment. In contrast, serum testosterone concentration rapidly reached the upper range of normal. During treatment, the hypogonadal men reported increases in several aspects of sexual activity, including sexual interest and the number of spontaneous erections. On mood inventories, the untreated hypogonadal men scored significantly higher in ratings of depression, anger, fatigue, and confusion than did infertile and normal men. During hormonal replacement therapy these scores decreased, although the hypogonadal men continued to score higher in "depression" than did infertile and normal men. In most instances, the men with infertility and the normal men were statistically indistinguishable in nocturnal penile tumescence and rigidity parameters, self-reported sexual activity, and mood state. These data support the hypothesis that androgen treatment increases nocturnal and spontaneous erections, and sexual interest, and has some capacity to improve mood.

Adult↗
PubMedDate not supplied

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↗