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Biomedical subjects

G R Elliott

Publications and source records attributed to G R Elliott.

At least 37 records · Page 2Linked to original sources
PubMed1995

Maintenance of donor phenotype after full-thickness skin transplantation from mice with chronic proliferative dermatitis (cpdm/cpdm) to C57BL/Ka and nude mice and vice versa.

Chronic proliferative dermatitis is a spontaneous mutation in C57BL/Ka mice (cpdm/cpdm) and is characterized by epithelial hyperproliferation, infiltration by eosinophils and macrophages, and vascular dilatation. To elucidate whether these pathologic features are the result of a local (skin) process or a consequence of a systemic disorder, transplantations were performed of full-thickness grafts of affected skin from cpdm/cpdm mice and normal skin from control (C57BL/Ka) mice on the back of cpdm/cpdm, C57BL/Ka and athymic nude mice. After 3 months, the grafts maintained the histologic phenotype of the donor animal. Intercellular adhesion molecule-1 continued to be expressed by basal keratinocytes of the cpdm/cpdm grafts after transplantation. In contrast, the basal keratinocytes of the C57BL/Ka grafts onto cpdm/cpdm mice remained negative for intercellular adhesion molecule-1 3 months after transplantation. An increased number of proliferating keratinocytes was present in the cpdm/cpdm skin-graft transplanted to nudes or to C57BL/Ka mice based on short-term bromodeoxyuridine labeling. The bromodeoxyuridine incorporation in the keratinocytes of the control C57BL/Ka skin grafts transplanted to cpdm/cpdm, nude, or C57BL/Ka mice was the same as in the keratinocytes of normal C57BL/Ka mice. This study demonstrates that the pathologic features found in the cpdm/cpdm mice are the result of a disorder in the epidermis or dermis and not due to a systemic defect.

Animals↗
PubMed1994

The rate of percutaneous permeation of xylene, measured using the "perfused pig ear" model, is dependent on the effective protein concentration in the perfusing medium.

In order to study the dermal permeation of compounds through the skin, an in vitro model was developed which utilized pig ears perfused with autologous pig blood (de Lange, J., van Eck, P., Elliott, G. R., de Kort, W. L. A. M., and Wolthuis, O. L. (1992). J. Pharmacol. Toxicol. Methods 27, 71-77). In the present article we investigated to what extent the rate of permeation of xylene through pig ear skin is dependent on the perfusion medium used. Pig ears were exposed to xylene (10 cm2 area) for a 4-hr period (30 degrees C, relative humidity of 40-60%) and the perfusate was analyzed for xylene using gas chromatography. The rates of permeation of xylene for whole blood, blood depleted of white blood cells, and a buffer containing 4.5% albumin were similar (+/- 300 ng/min/cm2). The rate of penetration was fivefold higher when pig plasma was used and ninefold lower when albumin was excluded from the buffer. Using the buffer, we found that the rate of permeation of xylene was proportional to flow (constant protein concentration) and protein concentration (constant flow). Our data demonstrate that the measured permeation rate for xylene is, to a large degree, dependent on the effective protein concentration (mg/min) passing through the ear. Differences in this parameter could explain the variations in rates of permeation found using the different perfusion media. To avoid problems associated with the choice of receptor fluid for permeation experiments, we suggest that full blood remains the vehicle of choice, although the practical perfusion period is limited to about 6 hr. If longer perfusion periods are required, then it should be possible to reproduce results obtained with whole blood by choosing an appropriate buffer.

Animals↗
PubMed1994

Effects of short- and long-term feeding of L-carnitine and congeners on the production of eicosanoids from rat peritoneal leucocytes.

The effect of short- and long-term feeding with L-carnitine, L-acetyl carnitine and L-propionyl carnitine on the production of eicosanoids from in vitro stimulated carrageenan-induced rat peritoneal macrophages was investigated. Both young (4 weeks) and old (18 months) rats were used. A lower number of cells was isolated from the peritonea of treated than control young rats after 4 d feeding, but after 60 d no differences were observed. A similar reduction in cell number was found when old animals were given L-acetyl carnitine or L-propionyl carnitine (acutely) or L-acetyl carnitine or L-carnitine (chronically). Plasma carnitine levels were higher in young rats given carnitine both chronically and acutely. Carnitine derivatives were without effect. In contrast, levels of total carnitine in the plasma of old rats given L-carnitine and L-acetyl carnitine for 4 d and 60 d were higher than in controls. There was no correlation between total plasma carnitine level and effects on prostaglandin, thromboxane and leukotriene B4 (LTB4) production. In young rats the most important changes were observed in relation to the production of prostacyclin (PGI2), measured as 6 keto-prostaglandin F1 alpha. Prostacyclin production was higher in the groups given carnitine or its derivatives. The net result of the changes in PGI2 was that the 6 keto-prostaglandin F1 alpha: thromboxane B2 and the 6-keto-prostaglandin F1 alpha: LTB4 ratios tended to be higher in cells from young animals following short-term feeding with L-carnitine.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Interleukin-1 alpha-stimulated fibroblast eicosanoid synthesis is not mediated by interleukin-6.

Adherent human dermal fibroblasts secreted interleukin-6, prostaglandin E2, prostaglandin I2 and 15-hydroxyeicosatetraenoic acid (assayed by radioimmunoassay) during a 3 h incubation period. Although human dermal fibroblasts did not secrete interleukin-1 alpha or interleukin-1 beta, human recombinant interleukin-1 alpha stimulated arachidonic acid metabolism and interleukin-6 synthesis. This effect was, at least partly, dependent on de novo protein synthesis. In contrast, human recombinant interleukin-6 had no effect on the synthesis and release of the eicosanoids measured. Human recombinant interleukin-1 alpha also stimulated the metabolism of [14C]arachidonic acid, but only if fibroblast were pre-incubated with the cytokine for three hours. Our data indicate that (a) fibroblasts secrete interleukin-6 but not interleukin-1, (b) interleukin-1 alpha, but not interleukin-6, stimulates fibroblast arachidonic acid metabolism and (c) the mechanisms involved in the metabolism of endogenous arachidonic acid are more sensitive to human recombinant interleukin-1 alpha than those involved in metabolism of the exogenous substrate.

Arachidonic Acid↗
PubMed1992

The isolated blood-perfused pig ear: an inexpensive and animal-saving model for skin penetration studies.

To overcome most of the disadvantages of current models to investigate percutaneous penetration of drugs or toxic substances, a model is proposed here based on the isolated pig ear, which is obtained at the slaughterhouse, and perfused with oxygenated blood from the same pig. To determine the viability of the preparations, we measured glucose consumption and lactate production as metabolic parameters, Na+ and K+ ions, as well as lactate dehydrogenase activity in blood as markers for cell damage, whereas vasomotor reactivity was assessed by administering noradrenaline and isoxsuprine. After 60 min of equilibration, only insignificant changes in these parameters were observed during the subsequent 3-hr test period (longer periods were not tested). A slight weight increase was noted during the total period 4 hr, presumably due to slight edema formation. On the basis of several types of measurements, such as in vivo blood flow and ear temperature and in vitro glucose metabolism, standard procedures were developed. It is concluded that this technique offers an easy to handle, cost-efficient, and animal-saving model for skin penetration studies that lacks most of the disadvantages of existing models.

Animal Testing Alternatives↗
PubMed1990

The effect of acute feeding of carnitine, acetyl carnitine and propionyl carnitine on basal and A23187-stimulated eicosanoid release from rat carrageenan-elicited peritoneal macrophages.

Little is known about the ability of carnitine to modulate cell functions. As carnitine plays an important role in lipid metabolism we investigated the acute effect of L-carnitine, L-acetyl carnitine and L-propionyl carnitine (300 mg/kg per d; 4 d) on the basal and calcium-ionophore (A23187)-stimulated release of arachidonic acid metabolites from rat carrageenan-elicited peritoneal macrophages. A decrease in the number of peritoneal carrageenan-elicited macrophages was observed after feeding all three compounds. The basal release of prostaglandin E2, 6 keto-prostaglandin F1 alpha and leukotriene B4 was stimulated by all treatments. In contrast, thromboxane B2 production was diminished by feeding carnitine and acetyl carnitine. A23187-stimulated synthesis of 6 keto-prostaglandin F1 alpha and leukotriene B4 was further enhanced by all three compounds. Acetyl carnitine and propionyl carnitine also enhanced thromboxane B2 synthesis. However, no effects on prostaglandin E2 formation were detected. The 6 keto-prostaglandin F1 alpha:thromboxane B2 ratio, calculated from the basal and A23187-stimulated values, was increased by carnitine treatment. In the presence of A23187 there was also an increase in the 6 keto-prostaglandin F1 alpha:leukotriene B4 ratio. We conclude that carnitine, and possibly some of its derivatives, could modify the macrophage component of an inflammation in vivo.

6-Ketoprostaglandin F1 alpha↗
PubMed1990

Reduction of sputum Pseudomonas aeruginosa density by antibiotics improves lung function in cystic fibrosis more than do bronchodilators and chest physiotherapy alone.

We evaluated patients with cystic fibrosis (CF) and moderate obstructive lung disease in pulmonary exacerbation in a double-blind placebo-controlled trial to determine the contribution of antibiotic-mediated reduction in sputum bacterial density to clinical improvement. For the first 4 days of study, all patients received bronchodilating aerosols and chest physiotherapy but no antibiotics. During this time, the patients showed significant improvement in mean FVC, FEV1, and maximal midexpiratory flow rate (FEF25-75). In 12 of 13 trials, the patients showed no significant increases in the density of Pseudomonas aeruginosa during these first 4 days. In these 12 trials, the patients were stratified by their initial FVC and randomized to receive either parenteral tobramycin and ticarcillin (n = 7) or placebo (n = 5), in addition to continued aerosol and chest physiotherapy. In the remaining trial, the patient had a significant rise in the density of P. aeruginosa and was assigned to the antibiotic group. During the next 14 days of therapy, the antibiotic group showed significantly (p less than 0.01) greater reductions in log10 colony-forming units (cfu) of P. aeruginosa per gram of sputum and greater increases in FVC, FEV1, and FEF25-75 than did the placebo group. The degree of decrease in log10 cfu P. aeruginosa/g sputum correlated significantly (p less than 0.001) with the degree of improvement in FVC, FEV1, and FEF25-75.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Prostaglandin E2 enhances, and leukotriene C4 inhibits, interleukin-1 inhibition of WEHI-3B cell growth.

Human recombinant interleukin-1 (HrIL-1) inhibited WEHI-3B cell growth in a dose-related manner (10-10,000 U/ml). Prostaglandin E2 at high concentrations (1000 ng/ml) also inhibited cell growth. When added together, HrIL-1 and prostaglandin E2 inhibited WEHI-3B growth in a synergistic manner (HrIL-1 concentrations of 10-10,000 U/ml and prostaglandin E2 concentrations of 10-1000 ng/ml). In contrast to the effects of the cyclooxygenase metabolite of arachidonic acid leukotriene C4, a lipoxygenase metabolite, reversed the cytostatic action of HrIL-1.

Adjuvants, Immunologic↗
PubMed1989

Endogenous lipoxygenase metabolites mediate A23187 induced macrophage cytostasis towards P815 tumor cells in vitro.

The calcium ionophore A23187 stimulated cytostatic activity of peritoneal macrophages towards P815 tumor cells in coculture served as a model for macrophage activation. A macrophage enriched preparation, separated on the basis of cell size in a discontinuous fetal calf serum gradient column, expressed cytostatic activity when stimulated by A23187. This was inhibited dose-dependently, by AA-861 but not by nordihydroguaiaretic acid (NDGA). AA-861 inhibited the 5-lipoxygenase specifically, NDGA inhibited both lipoxygenase- and cyclooxygenase activity: The ratio cyclooxygenase/lipoxygenase products increased with AA-861 but not with NDGA. These results show that lipoxygenase products are necessary for expression of cytostatic activity of these arachidonic acid metabolite producing macrophages and that the ratio of cyclooxygenase/lipoxygenase metabolites plays an important role in macrophage activation.

Animals↗
PubMed1989

Cardiovascular effects of desipramine in children.

The effect of desipramine hydrochloride was studied in children who were treated for eating disorders (5), attention deficit disorder (13), or affective disturbance (3). Serial heart rate, blood pressure, ECG, and 24-hour ambulatory monitoring were recorded before treatment and at 4 and 8 weeks during treatment. Maximum dose of desipramine was 5 mg/kg/day, average 4.25. A 21% increase in heart rate and 2.5% increase in QTc at 4 weeks were sustained at 8 weeks. No dysrhythmias or clinically significant changes in blood pressure occurred. Desipramine is safe in children who have normal cardiovascular examinations and ECGs when used within the limits of the study design. The cardiovascular effects of desipramine should be kept in mind and monitored when patients are starting tricyclic antidepressant therapy such as desipramine.

Arrhythmias, Cardiac↗