When cultured in a hypoxic environment similar to that found in the center of a wound, macrophages secreted active angiogenesis factor into the medium. Under conditions similar to those of well-oxygenated tissue, macrophages did not secrete active angiogenesis factor. Macrophages that secreted the factor at hypoxic conditions stopped secreting it when returned to room air. Thus the control of angiogenesis in wound healing may be the result of macrophages responding to tissue oxygen tension without the necessity of interacting with other cell types or biochemical signals.
Anti-inflammatory corticosteroids significantly impair wound healing. Retinoids partially, but significantly, reverse this effect. Little is known about the mechanism of steroid retardation or retinoid reversal. We hypothesized that corticosteroids lower transforming growth factor- (TGF-) and insulinlike growth factor-I (IGF-I) levels and tissue deposition in wounds and that retinoids stimulate corticosteroid-impaired TGF- and IGF-I release and collagen production.
The object of this animal study was to examine and further develop the expanded polytetrafluoroethylene wound healing model. The goal was to increase its potential for assessing wound healing by increasing yield, reducing variability, establishing the elements of a standard technique, and further testing its ability to detect variations of healing which have clinical significance. Expanded polytetrafluoroethylene implants of various dimensions and fabrications and several implantation and sterilization techniques were compared in rats. Hydroxyproline, DNA, and protein deposition into the expanded polytetrafluoroethylene implants as parameters for wound healing were assessed. Additionally, a 4 cm skin incision for tensile strength assessment was created. Wound healing was assessed under normal and corticosteroid-impaired healing conditions. The highest yield of collagen was found in the stiffer fabrication of expanded polytetrafluoroethylene with the larger pore size and after the more traumatic implantation technique of incisional placement. Variability was unaffected by fabrication, implantation technique, indexing by various geometric dimensions of the implant, sterilization, or sampling techniques. Variability was the same in the individual animals as in groups of animals. The expanded polytetrafluoroethylene method also detects the influence of antiinflammatory corticosteroids and reflects the tensile strength of incisional wounds made in other sites in the same animal.
C orticosteroids are used to reduce inflammation in systemic disease, local tendinitis, myositis, and other soft tissues (39). While these drugs are most often taken orally, they have also been a p plied transcutaneously by rubbing, injection, electrical current, o r ultrasound.Ultrasound is commonly used by physical therapists to treat musculoskeletal injuries, wounds, and chronic inflammatory conditions (1). Approximately one-third of the ultrasound treatments performed in 35 US Army physical therapy clinics include transcutaneous drugs (38). These drugs are usuallv added to treatment to relieve local capsular, muscular, tendinous, o r ligamentous inflammation o r pain (2,9,22, 35.47.52).In general, transcutaneous drug delivery is easy to control in terms of dosage, application, and concentration at the site of delivery (3,4,5). It also has the advantage of bypassing the liver, avoiding first-pass metabolism and directly accessing the circulatory system (2 1). Transcutaneous drug delivery is one of the fastest ways to distribute the drug into the system once it diffuses through the outermost layer of the skin, the stratum corneum, which is the primary rate-limiting factor (3). OnceAlthough physical therapists and physicians often treat patients with local musculoskeletal inflammation using topically applied steroids enhanced with ultrasound, there is a paucity of research confirming that phonophoresis significantly enhances drug diffusion. The purpose of this study was to determine if ultrasound enhances the diffusion of transdermally applied corticosteroids.Diffusion was measured secondarily in terms of collagen deposition [estimated by levels of hydroxyproline in polytetrafluroethylene (ePJFE) tubing] and cellular activity (measured by levels of DNA). Sixteen pieces of ePTFE tubing were subcutaneously implanted on the dorsum of five mini Yucatan pigs. Pairs of tubing were randomly assigned to sham control or treatment groups. Over the paired ePJFE tubes in the treatment groups, a single transdermal application of hydrocortisone acetate (HC) or dexamethasone (DX) was applied to the skin by rubbing, sonating with the drug mixed in the acoustic gel (1.5 W/cm2, 1 MHz, 5 minutes), or injecting the drug into the tubing. Four additional ePJFE tubes were threaded in the extremities, two submuscularly and two subtendinourly, with random assignment to a sham control or a DX sonation treatment group. At the end of a week, the mean hydroxyproline levels in the swine were lower than expected F= 9.3 pg/cm compared to an expected y= 22.2 pglcm). Comparing the control and skin-applied groups with the injected and sonated treatment groups, the hydroxyproline was found to be 50?!0 lower in the DX-injected, DXsonated, and HC-injected sites. However, statistically there were no significant differences in DNA or hydroxyproline levels between the HC subcutaneous control and treatment groups or the DX submuscular and subtendinous groups. There was a significant main effect of group on hydroxyproline levels in the group of DX-treat...
Since morphine has been shown to inhibit potassium-stimulated oxygen uptake of rat brain slices incubated in calcium-free Ringer’s solution experiments were done to clarify this finding. We found that altering conditions to favor morphine uptake resulted in inhibition of stimulated oxygen uptake by morphine when the slices were incubated in conventional Ringer’s solution. These alterations consisted of (a) incubation of slices in 0.01 M morphine, (b) incubation of slices in 0.01 M KC1, or (c) pretreatment with 100 mg/kg morphine 30 min prior to sacrifice. The data suggest that permeability of the cell membrane is an important factor in the effect of morphine on the oxygen uptake of rat brain slices.
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