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D Soucy

Publications and source records attributed to D Soucy.

8 recordsLinked to original sources

Effect of methotrexate on cell cycle and DNA synthesis of astrocytes in primary culture: flow cytometric studies.

Relatively pure population of astrocytes in primary culture were examined by flow cytometry at various time intervals after exposure to 1, 10 and 100 microM of methotrexate (MTX). The percentage population of cells in different phases of the cell cycle was determined using propidium iodide (PI) to measure cellular DNA content. DNA synthesis was assessed by measuring the fluorescence intensity of FITC-conjugated antibody to bromodeoxyuridine (BrdUrd). The two parameters were correlated to determine the location of BrdUrd-incorporating cells within the cell cycle. Exposure of astrocytes to MTX caused a consistent increase in number of cells in S-phase which correlated with the increase in BrdUrd incorporation. These studies provide supportive evidence that the astrogliosis seen in MTX encephalopathy may be due to a primary involvement of astrocytes.

Animals↗

Effects of methotrexate on astrocytes in primary culture: light and electron microscopic studies.

Recent studies on the animal model suggest that astrocytes may be a primary target for methotrexate (MTX) toxicity. To establish whether the astroglial alterations are due to a direct toxic effect of the drug, we studied the morphologic alterations, mitotic index, viability and growth rate of astrocytes in primary culture after exposure to varying concentrations of MTX in the absence or presence of dibutyryl cyclic AMP (dBcAMP). Dense bodies and cellular debris were noted by light and electron microscopy, and became more prominent with increasing doses and greater frequency of treatment. Degenerating cells and areas of necrosis were seen at higher concentrations. These changes became less conspicuous when MTX was given concurrently with dBcAMP. Large reactive-like astrocytes were also seen after MTX administration both in the absence or presence of dBcAMP. Mitotic rate inhibition was noted at all concentrations but was not dose-related. Cell viability was reduced and remained low up to 48 h after withdrawal of MTX and correlated well with drug concentration, although growth rate did not vary significantly from the control. Our findings show that pure populations of astrocytes can be adversely affected by MTX especially in the absence of bBcAMP, while also causing reactive-like changes in some cells. This report provides further evidence that astrocytes may be a primary target for MTX toxicity and suggests that the gliosis seen in MTX encephalopathy may in part be related to MTX-induced astrocytic injury.

Animals↗

Effect of iron and liver injury on the pathogenesis of Vibrio vulnificus.

Noncholera vibrio species can cause necrotizing soft tissue infections and cellulitis in addition to gastroenteritis. Cellulitis and necrotizing soft tissue infections frequently occur in people with liver disease or in people who are in some way a compromised host. We studied the effect of Vibrio vulnificus on the mortality of mice treated with carbon tetrachloride, an agent that causes liver damage, Desferal, an iron-chelating agent, or iron. The LD50 of V. vulnificus is approximately 2.5 X 10(6) CFU. In mice, desferal lowered the LD50 to less than 100 CFU, and carbon tetrachloride lowered the LD50 to approximately 1000 CFU. Twenty percent of the mice that survived had necrosis of the skin overlying the injection site. These studies demonstrate that liver damage and iron chelating agents increase mortality and necrotizing soft tissue infections caused by V. vulnificus.

Animals↗

Murine neutrophil migration during the course of an intra-abdominal abscess.

Studies of neutrophil migration in heterogeneous groups of septic patients have reported elevated, normal, and depressed neutrophil mobility. This experiment, conducted in a standardized murine population, measured neutrophil migration under agarose during the course of a chronic intra-abdominal abscess initiated by cecal ligation. Compared with both control (unoperated) and sham celiotomy mice, those mice with an abdominal abscess showed elevations of 22% and 14% of directed and random migration, respectively, at 48 hours. They had 30% to 40% decreases in these functions at days 4 through 10. Murine neutrophil migratory response during the course of an intra-abdominal abscess consisted therefore of an early elevation followed by a prolonged depression. Such a biphasic response could underlie the variable findings of neutrophil studies in septic patients. This model could be further applied to the study of the effects of chemotherapy and immunologic adjuvants on abscess course and neutrophil function, as well as to the study of the mechanisms of neutrophil response to sepsis.

Abdomen↗

Topical antimicrobial toxicity.

Three topical antibiotics and four antiseptics (1% povidone-iodine, 0.25% acetic acid, 3% hydrogen peroxide, and 0.5% sodium hypochlorite) were directly applied to cultured human fibroblasts to quantitatively assess their cytotoxicity. The four antiseptics were found to be cytotoxic; all of the cytotoxic agents except hydrogen peroxide were subsequently found to adversely affect wound healing in an animal model. Comparison of bactericidal and cytotoxic effects of serial dilutions of these four topical agents indicated the cellular toxicity of hydrogen peroxide and acetic acid exceeded their bactericidal potency. Bactericidal noncytotoxic dilutions of povidone-iodine and sodium hypochlorite were identified. These experiments provide evidence that 1% povidone-iodine, 3% hydrogen peroxide, 0.5% sodium hypochlorite, and 0.25% acetic acid are unsuitable for use in wound care. This sequence of experiments could be used to identify bactericidal, noncytotoxic agents prior to their clinical use.

Acetates↗

Cellular and bacterial toxicities of topical antimicrobials.

Cellular and bacterial toxicities of four commonly used topical antimicrobials (1% povidone-iodine, 3% hydrogen peroxide, 0.25% acetic acid, and 0.5% sodium hypochlorite) were assayed in vitro using cultures of human fibroblasts and Staphylococcus aureus. All agents tested at full strength killed 100 percent of exposed fibroblasts. Fibroblast toxicity exceeded bacterial toxicity with serial dilutions of hydrogen peroxide and acetic acid. Dilutions of povidone-iodine (1:1000) and sodium hypochlorite (1:100) were identified where no fibroblast toxicity occurred while full bactericidal activity persisted.

Acetates↗