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Biomedical subjects

E Robb

Publications and source records attributed to E Robb.

13 recordsLinked to original sources
PubMed2005

Penetration of ceftiofur into sterile vs. Mannheimia haemolytica-infected tissue chambers in beef calves after subcutaneous administration of ceftiofur crystalline free acid sterile suspension in the ear pinna.

The effect of Mannheimia haemolytica infection on the penetration of ceftiofur and desfuroylceftiofur metabolites into tissue chambers was studied in cattle after subcutaneous administration of ceftiofur crystalline free acid sterile suspension (CCFA-SS). Four tissue chambers were implanted subcutaneously in each of 12 calves. Approximately 45 days after implantation, two chambers were inoculated with M. haemolytica (10(6) colony-forming units per chamber) while the remaining two chambers were inoculated with sterile phosphate-buffered saline. Twenty-four hours after inoculation, CCFA-SS was administered subcutaneously in the middle third of the caudal ear pinna of each calf. Chamber fluid and blood samples were collected at predetermined times for 10 days following dosing and analyzed for ceftiofur and desfuroylceftiofur metabolites by high-performance liquid chromatography. Concentrations of ceftiofur and desfuroylceftiofur metabolites in plasma and tissue chamber fluid remained above a threshold of 0.2 microg/mL for at least 8 days. Infected tissue chamber fluid concentrations of ceftiofur and desfuroylceftiofur metabolites were significantly higher than those in non-infected tissue chamber fluid, which correlated with significantly higher total protein concentration in infected tissue chambers. These results indicate that single subcutaneous administration of CCFA-SS at 6.6 mg/kg can be expected to provide effective therapy of susceptible bacterial infections for a period of at least 1 week.

Animals↗
PubMed1998

Antimicrobial mixtures used by tissue banks for harvested skin: comparative in vitro activity.

The activities of antimicrobial combinations from three geographically diverse skin/tissue banks used in the processing of skin/ tissue were compared using bacteria and yeast isolated from burn patients. All formulations showed 90% or more effectiveness against bacteria generally susceptible to antibiotics but were less effective (60-80%) when tested against bacteria resistant to specific antimicrobials. Anti-yeast activity was present when an appropriate antifungal agent was included in the combination. All formulations were stable for at least six weeks. Results of this study raise certain questions about the use of these antimicrobial combinations in contemporary skin/tissue banking and point the way toward areas for future study.

Anti-Bacterial Agents↗
PubMed1997

The expression of cytokines, growth factors and ICAM-1 in the healing of human cutaneous xenografts on nude mice.

We postulate that wound healing is an orderly process mediated by a programmed expression of cytokines and growth factors. We suggest that these factors are produced in a consistent sequence, in regulated quantities and eliminated when their function is complete. We report here the results of studies on several cytokines, growth factors and the intercellular adhesion molecule expressed during the healing of grafts were visible clinically around 3-5 days post-graft and were completed by 4 weeks post-graft. During the 1st 2 weeks, we observed the following. (i) K-14 keratin was prominent throughout the entire epidermis. Thereafter it was limited to basal cell layers. (ii) Langerhans cells were not detectable with anti-human CD1a antibodies during the first week of healing but were clearly detectable 2 weeks post-graft. (iii) DOPA (dihydroxy phenylalanine) positive melanocytes gradually increased with time. The epidermis 21 to 28 days post-graft clinically and histologically seemed to be morphologically intact. Interleukin-1 (IL-1) was clearly detected in some basal cells of the epidermis, especially in melanocytes and some keratinocytes during the early stage of healing. Transforming growth factor-alpha (TGF-alpha) was detected in epidermis first in melanocytes and some keratinocytes shortly after grafting and again in the late stage of healing. It was also found in some dermal cells. Its expression coincided with keratinocyte proliferation and melanocyte migration. TGF-beta was strongly expressed in the epidermis and dermis after the first week post graft. (iv) ICAM-1 was transiently expressed only at the onset of healing. We previously reported that pro-opiomelanocortin and its derivatives MSH/ ACTH are expressed strongly during the healing of human xenografts. The 4 additional molecules which are the subject of this report all are expressed in healing human skin in a predictable sequence and quantity (intensity of stain). Together these data support our hypothesis that healing is a highly regulated process mediated by numerous cytokines.

Animals↗
PubMed1996

Hyperpigmentation of human skin grafted on to athymic nude mice: immunohistochemical study.

Human skin grafted on to athymic nude mice (BALB/C-nu/nu) spontaneously hyperpigments. We wished to identify the morphological and molecular bases for the hyperpigmentation for this phenomenon. We present data on the relationship of healing, regeneration of melanocytes and production of some melanogenic stimuli. Biopsies were taken at preset times post-graft and studied by histological and immunohistochemical methods. DOPA-positive melanocytes first became visible 120 h post-graft and melanin deposition became visible along the basal cell layer 2 weeks post-graft and increased in quantity with time. By immunochemical stains the quantity of three melanocyte specific enzymes, i.e. tyrosinase, tyrosinase-related protein-1 (TRP-1) and DOPA-chrome tautomerase (TRP-2), was markedly enhanced 1 week after grafting and persisted until 4 weeks post-graft. alpha-Melanocyte-stimulating hormone and adrenocorticotrophic hormone were clearly detected in the epidermis soon after grafting. They were still strongly detected in the epidermis and in the dermis 2-4 weeks post-graft. We conclude that hyperpigmentation in the grafted skin accompanies a marked increase in the quantity of melanogenic enzymes and melanogenic peptides. The neuropeptides might be one of many factors which stimulate melanogenesis.

Adrenocorticotropic Hormone↗
PubMed1995

Isolation of a unique melanogenic inhibitor from human skin xenografts: initial in vitro and in vivo characterization.

Previously, split-thickness human skin grafted onto athymic mice has been shown to become markedly hyperpigmented, but the factor(s) responsible for this hyperpigmentation had not been isolated. The present study describes the isolation and characterization of a potent melanogenic inhibitor from grafted human skin. Extracts from grafted skin inhibited, in a concentration-dependent manner, tyrosinase activity of normal human melanocytes and of Cloudman S91 murine melanoma in culture. Sodium dodecylsulfate-polyacrylamide gel electrophoresis analysis of extracts from pre- and post-grafted skin demonstrated the presence of a protein doublet of approximately 14 kD exclusively in the post-grafted skin. This protein inhibited both tyrosinase activity and cellular proliferation in a concentration-dependent manner. The inhibition of tyrosinase activity in normal human melanocytes was 53% at 0.5 microgram/ml concentration, whereas this inhibition was almost complete in murine melanoma cultures at 1.0 microgram/ml. The protein did not inhibit either cellular proliferation or protein synthesis in normal human fibroblast cultures, and therefore may act specifically on melanocytes. Injections of the inhibitor corresponded with a delay and reduction in the quantity of pigment in human skin 2 weeks after grafting. Multiple injections of the inhibitor into the hyperpigmented xenografts (20 weeks after grafting) reversed the hyperpigmentation with no observable inflammatory or toxic responses. The results indicate that hyperpigmented human skin xenografts contain a potent inhibitor of melanogenesis and melanocyte proliferation.

Animals↗
PubMed1993

Histological, biochemical, and ultrastructural studies on hyperpigmented human skin xenografts.

The mechanisms for hyperpigmentation observed in human cutaneous xenografts placed on athymic nude mice was investigated. Histologic, biochemical, histochemical, and ultrastructural examinations were performed on human skin prior to grafting and at various times ranging from 2 weeks to 30 weeks post-grafting (PG). Hyperpigmentation was macroscopically visible on the graft as early as 4-6 weeks. The number of Dopa-positive melanocytes per unit area was increased at 2 weeks PG and remained elevated until 20 weeks PG. The surface area of the melanocytes, a measure of the activity of the cells, also increased significantly and remained above the pre-grafting size throughout the study. Western blot analysis using tyrosinase specific antibody (alpha Ty-SP) revealed the presence of tyrosinase exclusively in the grafted skin from 2 weeks to 12 weeks PG tested. Histological and ultrastructural observations revealed the presence of numerous dendritic melanocytes, indeterminant clear cells suggestive of Langerhans cells, and dermal melanophages. The results of this study suggest that the observed hyperpigmentation in grafted tissue is caused by an increase in the number of Dopa-positive melanocytes and probably from enhanced melanin production. Extracts of proteins from the xenografts exhibited prominent differences in low and high molecular proteins between pre- and post-grafted skin. Among them, the exclusive appearance of a protein doublet with apparent mw approximately 14 kDa was found in grafted skin, and subsequent studies indicate it has potent effects on melanocyte function.

Animals↗
PubMed1987

Effect of transfusion on immune function in a traumatized animal model. II. Effect on mortality rate following septic challenge.

It is well established that transfusions given prior to transplantation diminish rejection, and recent reports suggest that transfused patients having surgery for cancer developed more metastases than those who did not receive transfusions. To our knowledge, however, there are no studies evaluating whether transfusions result in increased rates of infections. To investigate this, 295 Lewis rats were subjected to a 25% total body surface area burn and were given either 3 mL of Lewis blood, 3 mL of A'Solagoft Cancer Institute rat blood, or 9 mL of lactated Ringers' solution intravenously on day 1 before burn or on the day of burn. One additional group received 1-mL transfusions on days 9, 7, and 5 before burn. The burns were painted with 1 X 10(8) Pseudomonas aeruginosa lot No. 1244 on postburn days 0, 1, or 2. All rats were followed up for 28 days and survival and mean survival times were recorded. Transfusion of A'Solagoft Cancer Institute blood increased mortality unless given within 24 hours prior to Pseudomonas challenge, when it diminished mortality. Transfusion with syngenic Lewis blood had no effect. We conclude that transfusions may adversely affect survival when given before bacterial challenge, possibly due to immunosuppression from exposure to non-self-histocompatibility antigens.

Animals↗
PubMed1986

The effect of the thromboxane synthetase inhibitor Dazmegrel (UK-38,485) on wound healing, dermal ink perfusion and skin blood flow measurements in deep partial thickness burns.

A guinea-pig model was used to evaluate the effect of Dazmegrel (UK-38,485), a new highly selective inhibitor of thromboxane synthetase, on burn wound healing. Dazmegrel had a beneficial effect on wound healing when given systemically at a dosage of 3.4 mg kg-1 day-1 but higher doses had no effect. There was no change in dermal perfusion measured by India ink injection or by 133Xe injection in any of the groups receiving parenteral Dazmegrel. Neither was the number of hair follicles in the healing burn wound significantly different between the treated and control animals. When Dazmegrel was applied topically, it inhibited wound healing. These findings are consistent with previous reports from different laboratories that prostaglandin inhibitors impair healing of the burn wound when applied topically but improve wound healing when given parenterally. The present study further suggested that the improvement in wound healing in this model was not mediated by improved dermal perfusion.

Administration, Topical↗
PubMedDate not supplied

Evaluation of the effect of topical steroids on human scar contracture using a nude mouse model.

Adult nude mice had 1.5 to 1.0 meshed split-thickness human skin applied to an excised area of their back. The animals were then randomized into two groups, one of which had a steroid cream applied to their graft on alternate days. The other group had no ointment applied and served as a control. The wounds were measured on a weekly basis and the rate of wound contracture was found to be identical. Topical steroids would thus appear to offer no benefit in the prevention of scar contracture.

Animals↗
PubMedDate not supplied

Antimicrobial mixtures used to store harvested skin: antimicrobial activities tested at refrigerator (4 degrees C) temperatures.

Tissue culture media used by skin and tissue banks to store tissue were tested, with and without antimicrobial mixtures, for their ability to inhibit the growth of bacteria during incubation at refrigerator temperatures. Reductions in bacterial load were found after incubation at 4 degrees C in both the basal tissue culture media with and without the addition of antimicrobial mixtures. The presence of antimicrobials enhanced the degree and rapidity of reduction. Variations occurred among the different formulations, with or without added antimicrobials. No one formulation for either the basal tissue culture medium or antimicrobial mixture was ideal. Methods described in this study can be used to establish optimum basal medium and antimicrobial mixture formulations for general use by skin and tissue banks.

Anti-Bacterial Agents↗