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Biomedical subjects

S C Davis

Publications and source records attributed to S C Davis.

At least 19 recordsLinked to original sources

An octyl-2-cyanoacrylate formulation speeds healing of partial-thickness wounds.

BACKGROUND: Occlusive dressings have been known to accelerate the rate of healing. Every year new dressings are being introduced in the marketplace. OBJECTIVE: The purpose of this study was to evaluate the effect of a new octyl-2-cyanoacrylate liquid dressing as compared to two over-the-counter bandages on partial-thickness wounds. Performance parameters were epithelialization, erythema, scab formation, material adherence, hemostasis, and infection. METHOD: Eight pigs with a total of 645 partial-thickness wounds were assigned to one of the following treatments: liquid dressing, standard bandage, hydrocolloid bandage, or untreated air exposed. RESULT: The liquid bandage enhanced the rate of epithelialization and was the only treatment to provide complete hemostasis, reduced scab formation, and did not induce an irritant response (erythema) or infection. CONCLUSION: The liquid bandage is an easy to use material that stops bleeding (instantaneous hemostasis) while enhancing healing of partial-thickness wounds.

Animals↗

Supersonic molecular beam-hyperthermal surface ionisation coupled with time-of-flight mass spectrometry applied to trace level detection of polynuclear aromatic hydrocarbons in drinking water for reduced sample preparation and analysis time.

Analysis of sub-ppb levels of polynuclear aromatic hydrocarbons (PAHs) in drinking water by high performance liquid chromatography (HPLC) fluorescence detection typically requires large water samples and lengthy extraction procedures. The detection itself, although selective, does not give compound identity confirmation. Benchtop gas chromatography/mass spectrometry (GC/MS) systems operating in the more sensitive selected ion monitoring (SIM) acquisition mode discard spectral information and, when operating in scanning mode, are less sensitive and scan too slowly. The selectivity of hyperthermal surface ionisation (HSI), the high column flow rate capacity of the supersonic molecular beam (SMB) GC/MS interface, and the high acquisition rate of time-of-flight (TOF) mass analysis, are combined here to facilitate a rapid, specific and sensitive technique for the analysis of trace levels of PAHs in water. This work reports the advantages gained by using the GC/HSI-TOF system over the HPLC fluorescence method, and discusses in some detail the nature of the instrumentation used.

Chromatography, High Pressure Liquid↗

The evaluation of a cadexomer iodine wound dressing on methicillin resistant Staphylococcus aureus (MRSA) in acute wounds.

BACKGROUND: Many bacteria have become resistant to commonly-used antibiotics. OBJECTIVE: The purpose of this study was to examine the effect of a cadexomer iodine wound dressing on methicillin resistant Staphylococcus aureus (MRSA). METHOD: Partial thickness wounds were made on the backs of three pigs and inoculated with a known amount of MRSA. Wounds were treated with either cadexomer iodine dressing or vehicle dressing (without iodine), or they were left untreated. Three wounds from each treatment group per animal were cultured using quantitative scrub techniques after 24, 48, or 72 hours of treatment. CONCLUSIONS: The cadexomer iodine dressing significantly reduced MRSA and total bacteria in the wounds as compared to both the no treatment control and vehicle. No significant differences were observed in the number of bacteria recovered between the no treatment control and cadexomer (vehicle) treated wounds. Cadexomer iodine may be an effective agent for preventing proliferation of MRSA in wounds.

Animals↗

Histological comparison of postoperative wound care regimens for laser resurfacing in a porcine model.

BACKGROUND: The use of short-pulsed CO2 lasers for skin resurfacing is routinely performed, but few studies have examined postsurgical care. OBJECTIVE: To determine which postoperative treatments are most beneficial in promoting optimal healing after laser resurfacing. METHODS: Four pigs received laser resurfacing. The laser sites were randomly left untreated or treated with petroleum-based ointment or dressed with 1 of the following occlusive dressings: hydrocolloid, hydrogel or foam. Biopsies were taken from each treatment group on Days 2, 3, 4, 5, 8, 12, and 19. All samples were stained with hematoxylin and eosin. Each histological slide was evaluated by a blinded investigator. RESULTS: Differences were observed between treatment groups in the amount of cellular infiltrate, presence of necrotic tissue, progression of the epidermal sheet, maturation of the epidermis, presence of rete ridges, and appearance of new collagen. CONCLUSION: Postoperative treatments after laser resurfacing vary in their ability to influence the quality of healing.

Animals↗

Glu-320 and Asp-323 are determinants of the CYP4A1 hydroxylation regiospecificity and resistance to inactivation by 1-aminobenzotriazole.

Little information is available on the active site structure of the CYP4A family of enzymes or the mechanism by which their omega-hydroxylation regiospecificity is enforced. We report here that the E320A, D323E, and E320/D323E mutations decrease the catalytic rate of CYP4A1 approximately 5-fold and cause up to a 10-fold shift from omega- to (omega-1)-hydroxylation. The decreased catalytic rate is due to an increase in the uncoupled reduction of molecular oxygen. Tighter binding of 1- and 4-substituted imidazoles to the double mutant than to the other proteins suggests that its active site is less constrained. The reaction of these proteins with phenyldiazene causes heme degradation without the detectable formation of a phenyl-iron complex. CYP4A1 and its E320A mutant are not inactivated by 1-aminobenzotriazole (1-ABT), but the D323E and E320A/D323E mutants are inactivated. The resistance of purified CYP4A1 to inactivation by 1-ABT is surprising in view of the fact that 1-ABT causes the loss of the omega-hydroxylase activity both in microsomal preparations and in vivo. Collectively, the results establish that Glu-320, and particularly Asp-323, help to define the active site dimensions, the degree of coupled versus uncoupled versus uncoupled turnover, the omega-versus (omega-1)-hydroxylation regiospecificity, and the susceptibility to inactivation by mechanism-based inhibitors. Furthermore, they provide experimental evidence for a structural analogy between the CYP4A1 and P450BM-3 active sites.

Amino Acid Substitution↗

Medial prefrontal cortical injections of c-fos antisense oligonucleotides transiently lower c-Fos protein and mimic amphetamine withdrawal behaviours.

Prefrontal cerebral cortical areas display decreased expression of several transcription factor/immediate-early genes, including c-fos, during amphetamine withdrawal. Antisense strategies can help to test possible roles for this prefrontal c-fos down-regulation in the behavioural correlates of amphetamine withdrawal. Medial prefrontal cortical injections delivering 1.7 nmoles of anti c-fos oligonucleotides revealed an approximately 3 h half-life for phosphothioate and a 15 min half-life for phosphodiester oligonucleotides. Antisense phosphothioates complementary to the c-fos translational start site reduced levels of c-Fos protein, while exerting modest and variable effects on c-fos messenger RNA levels. Neither missense phosphorothioate nor antisense phosphodiester oligonucleotides significantly reduced levels of either c-fos messenger RNA or protein. Animals injected with anti c-fos phosphothioate oligonucleotides into the medial prefrontal cortex displayed marked reductions in linear locomotor activity and repetitive movements measured in a novel environment, effects not seen when missense oligonucleotides were used or when animals were accustomed to the activity monitor prior to antisense oligonucleotide injection. Behavioural changes produced by prefrontal cortical injections of c-fos antisense oligonucleotides closely mimic alterations recorded during amphetamine withdrawal. Prefrontal c-fos could thus conceivably play roles in the neurobiological underpinnings of psychostimulant withdrawal and of responses to stressors such as exposure to novel environments.

Amphetamine↗

Oxidation of omega-oxo fatty acids by cytochrome P450BM-3 (CYP102).

Cytochrome P450 enzymes oxidize aldehydes either to the corresponding acid or, via a decarboxylation mechanism, to an olefin one carbon shorter than the parent substrate. To explore the factors that control partitioning between these two pathways, we have examined the cytochrome P450BM-3 (CYP102)-catalyzed oxidation of fatty acids with a terminal aldehyde group. P450BM-3 oxidizes 18-oxooctadecanoic, 16-oxohexadecanoic, 14-oxotetradecanoic, and 12-oxododecanoic acids exclusively to the corresponding alpha,omega-diacids. The rates of these oxidations decrease in the order C16 > C18 approximately = C14 > C12. No kinetic isotope effect is observed nor is the catalytic outcome altered when the aldehyde hydrogen is replaced by a deuterium in 16-oxohexadecanoic acid. The only product observed with 16-oxohexadecanoic acid is the diacid even when a 13,14-double bond or 15-methyl groups, substitutions that should stabilize the proposed radical intermediate generated by decarboxylation, are present. The oxidation of 16-oxohexadecanoic acid is not supported by H2O2. The results demonstrate that aldehyde oxidation by cytochrome P450BM-3 is insensitive to changes in substrate structure expected to stabilize the transition state for decarboxylation. Decarboxylation, in contrast to the oxidation of aldehydes to acids, depends on specific substrate-protein interactions and is enzyme-specific.

Aldehydes↗

Effects of cytochrome P450 inhibitors on EDHF-mediated relaxation in the rat hepatic artery.

1. The possibility that the endothelium-derived hyperpolarising factor (EDHF) in the rat hepatic artery is a cytochrome P450 mono-oxygenase metabolite of arachidonic acid was examined in the present study. In this preparation, acetylcholine elicits EDHF-mediated relaxations in the presence of the nitric oxide (NO) synthase and cyclo-oxygenase inhibitors N omega-nitro-L-arginine (L-NOARG) and indomethacin, respectively. 2. 17-Octadecynoic acid (17-ODYA, 50 microM), a suicide-substrate inhibitor of the cytochrome P450 mono-oxygenases responsible for the production of 5,6-, 8,9-, 11,12- and 14,15-epoxyeicosatrienoic acids (EETs), had no effect on acetylcholine-induced relaxations in the presence of L-NOARG (0.3 mM) plus indomethacin (10 microM). Furthermore, 5,6-, 8,9-, 11,12- and 14,15- EETs failed to relax arteries without endothelium in the presence of L-NOARG plus indomethacin. 3. Proadifen and clotrimazole, which are inhibitors of several isoforms of cytochrome P450 mono-oxygenases, inhibited acetylcholine-induced relaxations in the presence of L-NOARG plus indomethacin. The concentration of acetylcholine which caused half-maximal relaxation was about 3 and 30 times higher in the presence than in the absence of clotrimazole (3 microM) and proadifen (10 microM), respectively. The maximal relaxation was reduced by proadifen but not by clotrimazole. Proadifen (10 microM) also inhibited acetylcholine-induced hyperpolarization in the presence of L-NOARG plus indomethacin. 4. In the presence of 30 mM K+ plus indomethacin (10 microM), acetylcholine induced an L-NOARG-sensitive relaxation mediated via release of NO. Under these conditions, proadifen (10 microM) shifted the acetylcholine concentration-response curve 6 fold to the right without affecting the maximal relaxation. Clotrimazole (3 microM) was without effect on these responses. The relaxant actions of the NO donor, 3-morpholino-sydnonimine, were unaffected by proadifen (10 microM). 5. The relaxant effects of the opener of ATP-sensitive potassium channels, levcromakalim, were abolished by proadifen (10 microM) and strongly attenuated by clotrimazole (3 microM). Proadifen (10 microM) also abolished the hyperpolarization induced by levcromakalim (1 microM). 6. The lack of effect of 17-ODYA on relaxations mediated by EDHF, together with the failure of extracellularly-applied EETs to produce relaxation, collectively suggest that EDHF is not an EET in the rat hepatic artery. It seems likely that inhibition of ion channels in the smooth muscle rather than reduced EDHF formation in the endothelium offers a better explanation for the actions of the cytochrome P450 inhibitors proadifen and clotrimazole.

Acetylcholine↗

Incorporation of the yeast mitochondrial ribosomal protein Mrp2 into ribosomal subunits requires the mitochondrially encoded Var1 protein.

Mrp2 is a protein component of the small subunit of mitochondrial ribosomes in the yeast Saccharomyces cerevisiae. We have examined the expression of Mrp2 in yeast mutants lacking mitochondrial DNA and found that the steady-state level of Mrp2 is dramatically decreased relative to wild type. These data suggest that the accumulation of Mrp2 depends on the expression of one or more mitochondrial gene products. The mitochondrial genome of S. cerevisiae encodes two components of the small ribosomal subunit, 15S rRNA and the Var1 protein, both of which are necessary for the formation of mature 37S subunits. Several studies have shown that in the absence of Var1 incomplete subunits accumulate, which lack a limited number of ribosomal proteins. Here, we show that Mrp2 is one of the proteins absent from subunits lacking Var1, indicating that Var1 plays an important role in the incorporation of Mrp2 into mitochondrial ribosomal subunits.

DNA, Mitochondrial↗

Magnetic resonance imaging of nalbuphine-induced myocutaneous sclerosis.

Myocutaneous sclerosis is a known complication of intramuscular and subcutaneous injection of narcotics. We have described the MRI findings of this entity with superimposed infection in a patient addicted to intramuscular and subcutaneously administered nalbuphine. The clinical and imaging features of this disorder are sufficiently characteristic to allow confident diagnosis. This is the first report of this disorder due to nalbuphine.

Adult↗

Electrical stimulation and ultrasound in wound healing.

The events that lead to tissue repair are very complex. Because our understanding of these processes is increasing in scope, the use of nontraditional treatment therapies should be considered. Evidence is reported in the literature that both electrical stimulation and ultrasound therapies may be beneficial in certain circumstances to heal various wound types. Owing to clinicians' unfamiliarity with the current research and general understanding of such therapies, many patients receive only traditional treatment and remain unexposed to the potential benefits of the nontraditional. With continued research to better define optimal treatment parameters, improved wound healing will result.

Electric Stimulation Therapy↗

Characterization of a yeast mitochondrial ribosomal protein structurally related to the mammalian 68-kDa high affinity laminin receptor.

We have cloned the nuclear gene MRP4 coding for a mitochondrial ribosomal protein of the yeast, Saccharomyces cerevisiae. The gene was isolated by complementation of a respiratory-deficient mutant with a pleiotropic defect in mitochondrial gene expression. The nucleotide sequence of MRP4 revealed that it has sequence similarity with Escherichia coli ribosomal protein S2 and related proteins of chloroplast ribosomes from different plants. Further characterization of the MRP4 protein revealed that it is a component of the 37 S subunit of mitochondrial ribosomes. Moreover, the phenotype of cells carrying a disrupted copy of MRP4 is consistent with the MRP4 protein being an essential component of the mitochondrial protein synthetic machinery. Finally, we note that the MRP4 protein and other members of the S2 family of ribosomal proteins have regions of sequence similarity with the mammalian 68-kDa high affinity laminin receptor.

Amino Acid Sequence↗

Second-degree burn healing: the effect of occlusive dressings and a cream.

Because occlusive dressings and some creams have been found to speed epithelialization of blade-induced wounds, we studied the effect of two occlusive dressings and a polyglycerylmethacrylate cream containing low concentration of fibronectin on epithelialization in second-degree burn wounds. Cylindrical brass rods were heated in a boiling water bath, removed, wiped dry, and placed (6 sec) on the skin of domestic pigs. The burned epidermis was removed and each burn wound was assigned to one of the following treatment groups: (1) air-exposed, (2) DuoDERM (hydrocolloid dressing; Squibb Co., New Jersey), (3) Opsite (polyurethane dressing; Smith & Nephew, New Jersey), or (4) experimental cream. Several burn wounds were excised from each treatment group on Days 6 to 14 after wounding. The excised burn wounds were incubated in 0.5 M NaBr for 24 hr which allowed separation of the epidermis from the dermis. The epidermis was examined macroscopically for defects in the area of the burn. Specimens were considered healed when a defect was not present. Neither of the occlusive dressings changed the rate of epithelialization as compared to air exposure. Wounds which were treated with the experimental cream epithelialized faster than the air-exposed wounds (P less than 0.025).

Administration, Topical↗

Interleukin-1 enhances epidermal wound healing.

Previous in vitro studies suggest that the interleukin-1 (IL-1) proteins may be important for skin function. Keratinocytes are known to synthesize IL-1 in response to injury and IL-1 has been shown to stimulate fibroblast and keratinocyte growth, collagen synthesis by fibroblasts, and chemotaxis of keratinocytes. In order to evaluate the ability of IL-1 to enhance wound healing, recombinant human IL-1 alpha was applied topically in a water-miscible cream to partial thickness wounds made on the backs of pathogen-free adult pigs. The wounded site was excised at various times for assessment of epidermal regeneration. This study shows a statistically significant enhancement of healing of the IL-1-treated wounds compared with either air-exposed or vehicle-treated wounds. Histologic examination of biopsies from IL-1-treated wounds indicated complete and architecturally normal epidermal regeneration. Porcine keratinocytes and membranes prepared from porcine skin were found to possess high affinity receptors for human IL-1 alpha. This study suggests that topical administration of IL-1 may be useful for the promotion of wound healing.

Administration, Cutaneous↗