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Biomedical subjects

S E Lynch

Publications and source records attributed to S E Lynch.

35 records · Page 2Linked to original sources
PubMed1993

Expression of growth factor and receptor mRNAs in skin epithelial cells following acute cutaneous injury.

We report that acute injury induces the expression of selective growth factor and growth factor receptors in the epithelial cells of the wounded tissue. In situ hybridization analysis of skin biopsy specimens obtained after cutaneous injury in swine demonstrated the induction of the expression of transforming growth factor-alpha, its receptor, epidermal growth factor-R, acidic fibroblast growth factor, and basic fibroblast growth factor messenger RNAs in the skin epithelial cells of the wounded tissue. There was no significant expression in the epithelial cells of control, uninjured tissues. The expression levels were maximal during the period of active tissue repair (1 to 5 days after injury) and were totally suppressed upon the healing of the wounded tissues. In contrast, insulinlike growth factor-I, (IGF-I), IGF-I receptor, and IGF-II receptor messenger RNAs were expressed in the epithelial cells of both the control, uninjured tissues and in tissue specimens obtained after injury. There was no significant expression of IGF-II messenger RNA in the epithelial cells before or after injury. It seems that injury induces the coordinated expression of selective growth factor and growth factor receptor genes whose products contribute to the regulation of the complex processes involved in tissue repair and remodeling.

Animals↗
PubMed1992

A comparison of ePTFE membranes alone or in combination with platelet-derived growth factors and insulin-like growth factor-I or demineralized freeze-dried bone in promoting bone formation around immediate extraction socket implants.

The purpose of this study was to compare bone promotion around implants which were augmented with ePTFE membranes alone or in combination with cortical demineralized freeze-dried bone (DFDB) or the combination of platelet derived growth factor-BB (PDGF) and insulin like growth factor I (PDGF/IGF-I). Membranes were placed over titanium implants which had been inserted into fresh extraction sockets with large buccal dehiscences. Twenty-four implants were placed in 4 dogs. At 18 weeks clinical bone height measurements were taken, the animals were sacrificed, and all specimens retrieved for histologic evaluation. Clinically, a significant gain in bone levels was present in both the ePTFE membrane alone group (P < 0.005) and PTFE plus PDGF/IGF-I group (P < 0.01), but not in the PTFE plus DFDB group. Results from histometric measurements revealed an approximately 2-fold increase in the percentage of implant surface in contact with bone, area of bone adjacent to the implant surface, and in the total length of the implant surface in contact with bone in the dehiscence defects treated with ePTFE plus PDGF/IGF-I compared to the defects receiving ePTFE membranes alone (each P < 0.05). The response to the DFDB was highly variable and it did not significantly improve the efficacy of the PTFE membranes for any parameter measured. The distance from the outer surface of the new bone to the implant surface was statistically significant for ePTFE membranes alone and membranes plus PDGF/IGF-I. The results demonstrated that clinically, ePTFE membranes alone or ePTFE membranes with PDGF/IGF-I were equally effective in promoting bone growth around the implants. Histologic measurements demonstrated that sites treated with ePTFE membranes plus PDGF/IGF-I had the highest bone density compared with sites which received ePTFE membranes alone or with ePTFE membranes and DFDB. The results of this study question the use of DFDB and support the use of ePTFE membranes alone or with PDG-F-BB/IGF-I as potential methods of promoting bone formation around dental implants.

Alveolar Bone Loss↗
PubMed1992

Methods for evaluation of regenerative procedures.

A multitude of new procedures and materials are being tested for their ability to promote periodontal wound healing. This review provides an overview of the most well-accepted methods for evaluating periodontal wound healing procedures/materials. Topics discussed include appropriate patient selection, general principles in non-surgical and surgical therapy as they relate to wound healing trials, clinical soft and hard tissue measurements which are generally obtained, an overview of radiographic assessments, and a discussion of the methods and role of histological evaluations in clinical trials. The advantages and disadvantages of the various methodologies are presented. The review concludes with the potential endpoints which can be used in periodontal wound healing studies.

Bone Regeneration↗
PubMed1991

Injury induces in vivo expression of platelet-derived growth factor (PDGF) and PDGF receptor mRNAs in skin epithelial cells and PDGF mRNA in connective tissue fibroblasts.

Platelet-derived growth factor (PDGF) stimulates many of the processes important in tissue repair, including proliferation of fibroblasts and synthesis of extracellular matrices. In this study we have demonstrated with in situ hybridization and immunocytochemistry the reversible expression of c-sis/PDGF-2 and PDGF receptor (PDGF-R) b mRNAs and their respective protein products in epithelial cells and fibroblasts following cutaneous injury in pigs. Epithelial cells in control, unwounded skin did not express c-sis and PDGF-R mRNAs, and fibroblasts expressed only PDGF-R mRNA. The expression levels in the injured site were correlated with the stage of tissue repair, being highest during the initial stages of the repair process and declining at the time of complete re-epithelialization and tissue remodeling. It is suggested that the controlled, reversible expression of a potent mitogen and its receptor induced by injury may function in an autocrine/paracrine manner on both epithelial cells and fibroblasts to bring about their sustained proliferation during the normal healing process. These studies provide a molecular basis for understanding the mechanisms contributing to normal tissue repair. We suggest the possibility that a defect in these mechanisms may be associated with defective wound healing. It is also conceivable that "chronic" injury may induce irreversible gene expression leading to pathologic, unregulated cell growth.

Animals↗
PubMed1991

Effects of the platelet-derived growth factor/insulin-like growth factor-I combination on bone regeneration around titanium dental implants. Results of a pilot study in beagle dogs.

The purpose of this study was to evaluate the early wound healing events of bone around press-fit titanium implants inserted with and without the concurrent application of a combination of platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF-I). Nine months prior to implant placement all mandibular premolar teeth were extracted in 8 beagle dogs. Subsequently, 40 specially manufactured titanium implants with 2 transverse holes in the apical section were press fit into precise recipient sites in the dogs' mandibles. The dogs were sacrificed at 7 and 21 days following implant placement yielding 12 PDGF-B/IGF-I treated and 8 control (placebo gel or non-treated) implants for each observation period. Coded undecalcified sections were analyzed for: 1) percentage of implant surface in contact with new bone; 2) percentage of peri-implant space filled with new bone; and 3) percentage of implant hole filled with new bone. An analysis of variance was used to determine significant differences among the treatment groups. At 7 days, the percentage of bone fill in the peri-implant spaces and the percentage of implant surface in contact with new bone were both significantly increased in PDGF-B/IGF-I treated sites (P less than 0.01 for both groups). There was less than 1.5% fill of the implant holes in both treated and control sites (no significant differences). At 21 days the percentage of bone fill in the peri-implant spaces was significantly increased in the PDGF-B/IGF-I treated sites (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1991

The effects of short-term application of a combination of platelet-derived and insulin-like growth factors on periodontal wound healing.

Polypeptide growth factors are a class of potent natural biologic mediators which regulate many of the activities of wound healing including cell proliferation, migration, and metabolism. Platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I) have been shown to regulate DNA and protein synthesis in bone cells in vitro and to interact synergistically to enhance soft tissue wound healing in vivo. We have hypothesized that the combination of PDGF and IGF-I may, therefore, enhance regeneration of both the soft and hard tissue components of the periodontium. To test this hypothesis we performed conventional periodontal surgery on all 4 quadrants of the mouth of 13 beagle dogs with naturally occurring periodontal disease. Following flap reflection, degranulation, and root planing, all premolar teeth in 2 quadrants of each dog received a combination of 3 micrograms of recombinant PDGF-B and IGF-I in a methylcellulose gel, while the premolar teeth in the contralateral quadrants received the gel alone. Teeth in 4 additional animals also received 125I-PDGF or 125I-IGF-I in the treated sites. The clearance rate of the 125I-labeled protein, changes in local bone metabolism, and amount of new bone and cementum with inserting collagen fibers were measured. The clearance studies revealed that the half-life of the factors at the site of application was 3.0 hours for IGF-I and to 4.2 hours for PDGF-B. Greater than 96% of the radio-labeled proteins was cleared by 96 hours and no radioactivity was detected 2 weeks after application. There was a significant (P less than 0.01) 2-fold increase in uptake of the bone-seeking radiopharmaceutical Technetium 99-MDP at 2 and 4 weeks in growth factor treated sites compared to controls, indicating that there was increased metabolic activity within the bone at these sites. Computer-aided histologic analyses of biopsies obtained at 2 and 5 weeks post-operatively revealed a significant (P less than 0.01), 5 to 10 fold increase in new bone and cementum in PDGF-B/IGF-I treated sites at both time points compared to controls receiving the placebo gel. The height and total area of new bone continued to increase from 2 to 5 weeks. The new bone underwent a normal maturation process as judged by histologic appearance. A physiologic periodontal ligament space was also formed between the new bone and new cementum. There was no increase in ankylosis in the treated sites.(ABSTRACT TRUNCATED AT 400 WORDS)

Alveolar Bone Loss↗
PubMed1990

Topical nonsteroidal agents and corneal wound healing.

The effects on corneal wound healing of two topical nonsteroidal anti-inflammatory agents, flurbiprofen sodium (0.03%) and diclofenac sodium (0.1%), and the topical corticosteroid, prednisolone sodium phosphate (1%), were evaluated in masked, controlled rabbit studies. Healing of epithelial scrape wounds was significantly retarded in all three treatment groups for the first 3 days after wounding. There was no difference in the epithelial healing rate between the two nonsteroidal or corticosteroid treatment groups. Clinical grading of epithelial quality, conjunctival hyperemia, keratitis, stromal edema, and corneal haze were similar in all groups. There was a significant early decrease in the iritis score in the diclofenac treatment group. The strength of 2-mm central penetrating corneal trephination wounds and the collagen content of these wounds were similar in all groups. Both the topical nonsteroidal anti-inflammatory agents and the corticosteroid used in the preparations and dosages investigated in this study decreased early epithelialization of scrape wounds but had no apparent effect on corneal stromal healing. No toxic effects of the various drugs were found.

Administration, Topical↗
PubMed1989

A combination of platelet-derived and insulin-like growth factors enhances periodontal regeneration.

The combination of platelet-derived growth factor (PDGF) and insulin-like growth factor one (IGF-1) has previously been shown to enhance repair of soft tissue wounds. Here we report initial observations following application of PDGF and IGF-1 to periodontitis-affected teeth in beagle dogs. 1 micrograms of PDGF and IGF-1 in an aqueous gel was applied to the root surfaces of test teeth following open flap debridement. Control sites received the gel alone. Block biopsies of the teeth and surrounding bone were taken 2 weeks after treatment. Histologic analyses of control specimens revealed a long junctional epithelial attachment, and no new bone or cementum formation. In contrast, growth factor treated sites exhibited significant amounts of new bone and cementum formation. A nearly continuous layer of osteoblasts lined the newly formed bone, and there was a dense cellular "front" at the coronal extent of the new bone. These preliminary results suggest that in vivo application of the combination of PDGF and IGF-1 may enhance regeneration of the periodontal structures.

Alveolar Process↗
PubMed1989

Growth factors in wound healing. Single and synergistic effects on partial thickness porcine skin wounds.

Several growth factors are potential mediators of wound healing, although their actual roles, interactions, and therapeutic use are not established. Six well-characterized human growth factors were chosen for detailed investigation by topical application to standardized skin wounds in swine: epidermal growth factor (EGF), transforming growth factors alpha and beta (TGF-alpha and TGF-beta), fibroblast growth factor (FGF), insulin-like growth factor-I (IGF-I), and platelet-derived growth factor (PDGF). When applied singly in doses up to 1,500 ng, only TGF-beta produced a marked tissue response, as demonstrated by an increase in the new connective tissue volume, the collagen content and maturity, and increased angiogenesis. However, TGF-beta enhanced inflammation and caused abnormal epithelial differentiation and decreased epithelial volume, the last reversed by addition of IGF-I. Recombinant PDGF-2 homodimer, if given in combination with recombinant IGF-I, caused a similar increase in the new connective tissue volume and collagen content and maturity, but without increased inflammation. In addition, this combination stimulated increased amounts of epithelium with normal differentiation. The synergy of PDGF-2 and IGF-I was optimal at a ratio of 2:1 by weight. Of the six individual factors and nine combinations tested, the combinations of PDGF-2 and IGF-I or PDGF-2 and TGF-alpha were the most potent stimulators of healing in the absence of increased inflammation.

Animals↗
PubMed1987

Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors.

Platelet-derived growth factor (PDGF) in vitro stimulates DNA synthesis and chemotaxis of fibroblasts and smooth muscle cells and stimulates collagen, glycosaminoglycan, and collagenase production by fibroblasts. These in vitro properties suggest that PDGF, delivered by platelets to the site of injury in vivo, may play an important role in the initiation of the wound repair process. Studies presented here show that the addition of pure PDGF to a wound site involving the epidermis and dermis has little effect on the morphology or biochemistry of the healing wound. In contrast, the addition of partially purified PDGF resulted in significant dose-dependent increases in the width of the newly synthesized connective tissue and epidermal layers. Autoradiography using [3H]thymidine revealed increased numbers of labeled cells in the new connective tissue and epithelial layers. Furthermore, addition of partially purified PDGF resulted in significant increases in the rate of protein and DNA synthesis and the total content of these components in biopsies taken from the wound site. Similar effects were obtained when insulin-like growth factor I was added in combination with pure PDGF. This combination of factors caused a 2.4-fold increase in the width of the newly formed connective tissue layer and a 95% increase in epidermal thickness compared with controls. Insulin-like growth factor I alone caused no significant morphologic changes. Epidermal growth factor alone or in combination with PDGF resulted in a thickening only of the epidermis. These results indicate that the synergistic actions of other factors with PDGF are important in the modulation of the wound healing process.

Animals↗
PubMed1985

Detection of gram-negative bacteremia by limulus amebocyte lysate assay: evaluation in a rat model of peritonitis.

A spectrophotometric Limulus amebocyte lysate assay using lysis filtration and centrifugation has been developed for the detection of gram-negative bacteria in blood. The assay is directed at detection of endotoxin in viable and nonviable bacteria present in the blood-stream and not detection of free endotoxin in plasma. The assay was evaluated in a model of peritonitis in which rats were challenged with an inoculum consisting of sterilized human feces, barium sulfate, and one of eight species of bacteria. This assay was able to detect gram-negative bacteremia due to Escherichia coli, Pseudomonas aeruginosa, Serratia marcescens, Proteus mirabilis, and Klebsiella pneumoniae in the rat model when compared with sham-inoculated uninfected rats. The assay failed to detect bacteremia due to Bacteroides fragilis or Staphylococcus aureus, nor was there a significant rise in absorbance when a pellet containing sterilized feces was implanted in the rat.

Animals↗
PubMedDate not supplied

Combination of platelet-derived growth factor-BB and insulin-like growth factor-I is more effective than platelet-derived growth factor-BB alone in stimulating complete healing of full-thickness wounds in "older" diabetic mice.

Platelet-derived growth factor and insulin-like growth factor-I have been shown to interact synergistically to enhance repair of skin wounds in normal healing swine. Platelet-derived growth factor alone has shown promise in treating human chronic ulcers. The objective of this study was to compare the wound healing effects of platelet-derived growth factor-BB alone with those of a combination of platelet-derived growth factor-BB and insulin-like growth factor-I in an improved model with the use of "older" animals with diabetes. Older diabetic (db/db) mice (>15 weeks of age) have less elevated insulin levels compared with young db/db mice. The serum insulin levels in the older animals is 1.0 to 2.5 times that of the nondiabetic animals, a similar increase to that which occurs in human patients with type II diabetes. Healing was evaluated in two studies involving a total of 104 animals. Treatment groups included the following: 4.0 microg/cm(2) of platelet-derived growth factor-BB, 40.0 microg/cm(2) of platelet-derived growth factor-BB, 4.0 microg/cm(2) of both platelet-derived growth factor-BB and insulin-like growth factor-I or vehicle. All growth factors were applied topically in a methylcellulose vehicle to full-thickness wounds every other day for 24 days. Efficacy end points were median and mean time to complete healing and rate of wound closure. The median time to complete healing for animals receiving the platelet-derived growth factor-BB/insulin-like growth factor-I combination was 38% and 33% faster (p < 0.001) than animals receiving 4.0 microg/cm(2) and 40.0 microg/cm(2) of platelet-derived growth factor-BB, respectively. The mean time to complete healing for platelet-derived growth factor/insulin-like growth factor-I treated animals was 31% and 29% faster (p < 0.001) than 4.0 microg/cm(2) and 40.0 microg/cm(2) platelet-derived growth factor-BB treated animals, respectively. Wounds treated with 4.0 microg/cm(2) platelet-derived growth factor-BB/insulin-like growth factor-I healed, on average, in 22 days compared with 31 days for 40.0 microg/cm(2) platelet-derived growth factor-BB alone and 38 days for vehicle. Also, platelet-derived growth factor-BB/insulin-like growth factor-I significantly improved the rate of wound closure throughout the duration of the studies compared with either dose of platelet-derived growth factor-BB alone (p < 0.005) or vehicle (p < 0.001). In conclusion, the data show that the combination of platelet-derived growth factor-BB and insulin-like growth factor-I is more effective than platelet-derived growth factor-BB alone at the doses tested or vehicle treatment in stimulating cutaneous wound healing in older, diabetic mice.

Journal Article↗
PubMedDate not supplied

Eighteen-month radiographic and histologic evaluation of sinus grafting with anorganic bovine bone in the chimpanzee.

Maxillary sinus grafting procedures are currently the treatment of choice when the alveolar crest of the posterior maxilla is in close approximation to the maxillary sinus. The short-term histologic and radiographic healing following sinus grafting with natural bone mineral (Bio-Oss) in the chimpanzee has been evaluated. We have previously shown by histomorphometric and radiographic analysis that the percentage of vital bone area, the vertical height, and the density of new bone in the maxillary sinus was significantly greater with anorganic bovine bone compared to bovine Type I collagen matrix. The purpose of this in vivo study was to determine the bone mineral density (BMD) of the sinus grafts, the vertical height stability, the vital bone area, and the extent of anorganic bovine bone replacement 18 months postoperatively in 4 maxillary sinuses from 4 different animals. Radiographic analysis of computed tomographic scans taken at 1.5 years revealed an average BMD of 658 mg/mL, which was not significantly different from the values found at 6.5 months. The radiographic vertical height was maintained between the 6.5- and 18-month time points. On average, the grafts were found to have a height of 14 mm. Lateral wall biopsy specimens at 7.5 months were compared to those at 18 months. With the anorganic bovine bone treatment, the percentage of vital bone area increased from 62 +/- 3% to 70 +/- 7% and the percentage of natural bone mineral area decreased from 19 +/- 14% to 6 +/- 3%. The bovine Type I collagen matrix vital bone percentage at 7.5 months was 34 +/- 21%. These results demonstrate that sinus grafting with anorganic bovine bone maintains radiographic evidence of density and height stability of 1.5 years. In addition, histologic evidence supports the hypothesis that anorganic bovine bone is replaced by vital bone.

Animals↗