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Biomedical subjects

C Fournier

Publications and source records attributed to C Fournier.

At least 127 records · Page 7Linked to original sources
PubMed1994

[Oslerosis of the dog: diagnostic and therapeutic status].

Oslerus osleri is a metastrongle whose first-stage larvae are expectorated by the bitch, and which are infecting for pups; few cases are described from France. The biological features of this parasite, diagnosis and therapy are described in a first bibliographic part. 29 of 66 dogs examined were infected with Oslerus osleri. We investigated the cause of their chronic coughing, which was not cured by routine therapies. Several diagnostic methods were used, of which endoscopy was the best. The following drugs were used to treat infection with Oslerus osleri: ivermectin, levamisole, oxfendazole and fenbendazole. The last-mentioned two drugs are safe for dogs and very effective against this parasite.

Animals↗
PubMed1993

Synthesis and antitumor properties of an anthraquinone bisubstituted by the copper chelating peptide Gly-Gly-L-His.

A new molecule 4 [(GGH-DAE)2DHQ] associating the 1,4,5,8-tetrahydroxyanthraquinone ring (DHQ) of the antitumor drug mitoxantrone (2), two diaminoethylene chains (DAE), and the metal-chelating peptide Gly-Gly-His (GGH) has been synthesized. Such a molecule presents characteristics able to induce antitumor activity: compound 4 intercalates into DNA as measured by delta Tm, fluorescence quenching, and viscometry; ESR studies demonstrate that several types of Cu complexes are formed depending on pH; and the production of free radicals, as evidenced by spin-trapping, is enhanced by 4. In vitro, in leukemia cells L1210 and mammary cells MCF7, 4 is slightly less cytostatic than mitoxantrone, but substantially less toxic. In vivo, in leukemia P388 on mice, a T/C value of 230 is obtained at 25 mg/kg, higher than the one of mitoxantrone, which is toxic at the same dose.

Animals↗
PubMed1993

Interleukin-1-mediated phospholipid breakdown and arachidonic acid release in human synovial cells.

OBJECTIVE: Interleukin-1 (IL-1), an important mediator contributing to joint destruction in rheumatoid arthritis, is known to stimulate the release of arachidonic acid (AA) and prostaglandin E2 (PGE2) from adherent synoviocytes. To study the intracellular pathways involved in these functions, we stimulated cultures of human synovial cells with recombinant IL-1 beta. METHODS: AA liberation was measured after labeling synovial cells with 3H-AA, and PGE2 levels were determined by high performance liquid chromatography or radioimmunoassay. Identification of 3H-AA-labeled phospholipids was performed by thin layer chromatography. Cell-associated phospholipase A2 (PLA2) enzymatic activity was determined by an assay with cell-free systems and exogenous substrates. RESULTS: Stimulation of synovial cells with recombinant IL-1 beta induced a decrease in phosphatidylcholine (PC), phosphatidylinositol (PI), and phosphatidylethanolamine (PE), and a marked increase in cell-associated PLA2 activity as compared with controls. In the presence of either quinacrine, an inhibitor of PLA2 pathway activation, or neomycin, which binds to PI mono- and biphosphate thus blocking their degradation by phospholipases, AA and PGE2 secretion were reduced in a dose-dependent manner. Kinetic studies revealed that quinacrine had little blocking activity on the IL-1-mediated AA release after 1 hour of stimulation but completely abolished it after 5 or 8 hours. In contrast, neomycin exerted a partial but significant inhibitory effect from the first hour of stimulation onward. Addition of quinacrine was also demonstrated to abolish the IL-1-induced hydrolysis of PC and PE but not PI, indicating that PC and PE are the preferred substrates for PLA2 enzymatic activity in human synovial cells. CONCLUSION: Our findings strongly suggest that AA and PGE2 production by IL-1-triggered synoviocytes are largely dependent upon PLA2-mediated hydrolysis of PC and PE and to a lesser extent upon the earlier degradation of PI.

Arachidonic Acids↗
PubMed1993

T cell regulation of collagen-induced arthritis in mice. II. Immunomodulation of arthritis by cytotoxic T cell hybridomas specific for type II collagen.

Injection of native type II collagen (CII) to susceptible strains of mice (H-2q) induces a rheumatoid arthritis-like disease. To study the role of CD8+ T cells in the collagen-induced arthritis (CIA), we generated CII-specific T cell hybridomas by fusion of cells from arthritic C3H. Q mice and an AKR thymoma. Two hybrid clones (P3G8 and P2D9) were selected for their ability to lyse syngeneic CII-pulsed macrophages and recognize different antigenic epitopes in association with Kq molecules. When these T cell clones were irradiated and inoculated into (C3H.Q x AKR)F1 mice 21 days prior to priming with native CII/complete Freund's adjuvant, the incidence and the duration of CIA were significantly reduced in comparison to groups receiving saline or control T cell hybridoma. Furthermore, both anti-CII T cell hybridomas were able to attenuate CIA in highly susceptible inbred strains of mice and this suppression was antigen and disease specific. The protective activity seems to require intact cells as neither membrane fractions nor cytosolic preparations of the hybridoma T cells retained the vaccinating activity. Most importantly, one of the hybrid clones (P3G8) had a therapeutic effect on CIA since its administration to arthritic DBA/1 mice on day 30 after priming down-regulated the ongoing disease. Taken together, these findings suggest that anti-CII cytotoxic T cell clones can vaccinate against CIA and even reverse the disease.

Adjuvants, Immunologic↗
PubMed1993

Plasma insulin-like growth factor-1 (IGF-1) concentrations in human breast cancer.

Insulin-like growth factor-1 (IGF-1) is capable of stimulating breast cancer cell growth in vitro and the presence of IGF-1 receptors has been demonstrated in primary breast cancers. We determined plasma IGF-1 in a primary breast cancer population and in a control population. Radioimmunoassays were performed either directly on plasma, IGF-1 (NE), or after an acid-ethanol extraction of the plasma, IGF-1 (E). We demonstrated an inverse correlation between age and IGF-1: for this reason, only results obtained in females of the same age range (> 35 years) were compared. Median concentrations of IGF-1 were significantly higher in primary breast cancers [IGF-1 (E) = 152 ng/ml, IGF-1 (NE) = 26 ng/ml, n = 44] than in controls [IGF-1 (E) = 115 ng/ml, IGF-1 (NE) = 20 ng/ml, n = 92]. To our knowledge such a growth factor increase has never been described in breast cancer. We conclude that IGF-1 could be an important factor involved in the development of breast cancer and that treatment reducing IGF-1 levels could be beneficial for patients.

Adult↗
PubMed1993

[Serodiagnosis of Pseudomonas aeruginosa infections in mucoviscidosis: comparative study of Western blotting, ELISA exotoxin A and ELISA phospholipase C].

Anti-Pseudomonas aeruginosa antibodies were studied by Western Blot, ELISA-exotoxin A and ELISA-phospholipase C for 91 serums from 31 patients with cystic fibrosis. More, for the two enzyme-linked immunosorbent assays, 44 serums from 44 healthy individuals were studied as controls. The study of these three parameters revealed the followings: with no infection by Pseudomonas aeruginosa all the results were negative, at the beginning of the infection, anti-exotoxin A antibodies appeared in first, followed in some cases by the reactions of Western Blot, anti-phospholipase C antibodies became positive at last and went on a par with the installation of the chronic characteristic of the infection, as soon as the chronicity were indisputable, the three methods revealed elevated serum antibodies amounts. Generally there was a correlation between detected antibodies and Pseudomonas aeruginosa isolation in sputum. Among these three methods, ELISA-exotoxin A appeared to be the most interesting because of its good reproducibility and its early positivity, before the others methods and sometimes before Pseudomonas aeruginosa isolation. It would be a significant argument to establish as soon as possible an antimicrobial therapy.

ADP Ribose Transferases↗
PubMed1993

[Technetium TC 99m pyrophosphate myocardial scintigraphy in amyloidosis. Correlations with Doppler echocardiography].

Technetium 99m cardiac scintigraphy as practiced at present for diagnosing amyloisodid only provides a visual semi-quantitative assessment of uptake of the isotope. To improve the diagnostic accuracy of the method, the authors evaluated prospectively a personal technique of scintigraphy quantification based on early images obtained at the 20th minute in 15 patients with neuropathic amyloidosis. Doppler echocardiographic studies indicated that 9 patients had cardiac involvement whilst 6 were free of cardiac amyloidosis. The index of isotopic uptake (ratio of cardiac/abdominal uptake) was 0.44 to 1.58 in the first group and 0.09 to 0.31 in the second group. The correlation between the scintigraphic index and interventricular septal or posterior wall thickness measured by echocardiography was poor. These results obtained in 15 patients with neuropathic amyloidosis suggest that the scintigraphic index measured at the 20th minute is discriminatory and allows identification of those patients with cardiac involvement. On the other hand, the correlations with echocardiographic wall thickness are poor. Technetium 99m cardiac scintigraphy with this technique of quantification is a useful tool for diagnosing cardiac amyloidosis, especially when echocardiography is difficult to interpret.

Adult↗
PubMed1992

Biological activity and molecular interaction of a netropsin-acridine hybrid ligand with chromatin and topoisomerase II.

A hybrid molecule, which combines an anilinoacridine chromophore related to the antitumour drug amsacrine (m-AMSA) and a bispyrrole moiety analogous to the antiviral agent netropsin, has been examined for its ability to bind chromatin and to modulate the activity of topoisomerase II. The results show that the presence of histones does not alter the bimodal DNA binding process. Intercalation of the acridine and groove binding of the netropsin part of the drug are both observed with chromatin preparations. Moreover, the hybrid has a clear topoisomerase II-DNA cleavable complex-inducing activity close to that of m-AMSA. The role of the two parts of the hybrid ligand is discussed in relation to ternary complex formation. Two cell lines (L1210 leukemia and MCF7 mammary carcinoma) were compared in their sensitivity to the tested ligand. The drug, which appears to be an efficient growth inhibitor of leukemic cells in vitro, reveals moderate activity against P388 leukemia in vivo. The biological activity of the hybrid may derive from a mechanism that involves DNA binding and topoisomerase II inhibition. This study demonstrates that agents which intercalate and bind to the minor groove of DNA simultaneously represent a new class of drugs interfering with topoisomerase II and provide opportunities for the development of new antitumour agents.

Amsacrine↗
PubMed1992

Modification of the physicochemical and pharmacological properties of anticancer platinum compounds by commercial 5-fluorouracil formulations: a comparative study using cisplatin and carboplatin.

The influence of a commercial formulation of 5-fluorouracil (5-FU) on the stability and pharmacological properties of two platinum derivatives, cisplatin and carboplatin, was studied to determine whether the drugs could be mixed in containers or intravenous lines. When cisplatin was incubated in a French commercial formulation of 5-FU (Fluoro-uracile, Roche, France), high-performance liquid chromatographic (HPLC) studies demonstrated a rapid disappearance of the parent platinum compound, the extent of the degradation being 75% after 3.5 h. These studies also revealed that the degradation was not caused by a reaction between 5-FU and cisplatin but rather resulted from an interaction between cisplatin and trometamol, the excipient used in the French 5-FU formulation to buffer the solution at pH 8.2. The sole presence of trometamol in a cisplatin solution for 24 h at 30 degrees C resulted in the complete inhibition of both the ability of cisplatin to bind in vitro to human serum albumin and the antitumor activity of the cytostatic agent against P388 leukemia in mice (T/C% = 88% for cisplatin+trometamol vs greater than 333% for cisplatin). When cisplatin was incubated at the same pH in trometamol-free sodium hydroxide solutions (the excipient used in 5-FU formulations in several countries, including the United States and the United Kingdom), the parent compound was transformed into reactive species that were toxic to mice (T/C% = 40% in P388 leukemia). The degradation determined for a carboplatin-trometamol admixture using HPLC was similar to that found for cisplatin but occurred at a slower rate (0 after 3.5 h incubation and 55% after 24 h). The antitumor activity of carboplatin in P388-bearing mice was not significantly altered by a 24-h period of preincubation in the presence of trometamol (T/C% = 209% vs 241% for treatment with carboplatin in the absence of trometamol). As in the case of cisplatin, incubation of carboplatin for 24 h in a sodium hydroxide solution resulted in a toxic effect (T/C% = 64%). Our results thus demonstrate the incompatibility of both cisplatin and carboplatin with commercial formulations of 5-FU.

Animals↗
PubMed1992

Variations in the glycoforms of serum alpha 1-antichymotrypsin in liver diseases and after liver transplantation.

1. Using crossed immunoaffinity electrophoresis with free concanavalin A in the first dimension, we studied the microheterogeneity of alpha 1-antichymotrypsin due to various glycoforms in sera from patients with various liver diseases and after liver transplantation. 2. Studies by isoelectric focusing and immunoblotting and by crossed immunoelectrophoresis without concanavalin A in the first dimension allowed us to show that there is no dramatic variation in electrophoretic heterogeneity of alpha 1-antichymotrypsin in the serum of patients with liver diseases or after liver transplantation when compared with that of normal subjects. Therefore the heterogeneity observed in crossed immunoaffinity electrophoresis is due to various interactions with concanavalin A. 3. The results were expressed as the ratio of concanavalin A non-reactive glycoforms plus concanavalin A weakly reactive glycoforms to concanavalin A reactive glycoforms, called R alpha 1-ACT. R alpha 1-ACT was significantly higher in patients with cirrhosis (n = 53) when compared with normal subjects (n = 30). The median R alpha 1-ACT was 1 (range 0.72-1.25) in normal subjects. It was 1.6 (range 1.18-3.02), 1.45 (range 0.65-4.12) and 2.24 (range 1.03-19) in cirrhosis of Child's grade A, B and C, respectively. There was a dramatic decrease in glycoforms with mostly biantennary glycans in some patients with Child's grade C cirrhosis. Serum levels of alpha 1-antichymotrypsin were lower than normal only in some patients with Child's grade C cirrhosis. 4. Among the patients with acute viral hepatitis studied (n = 17), five were studied longitudinally.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Combination of cyclosporine A and calcitriol in the treatment of adjuvant arthritis.

We investigated combination treatment with cyclosporine A (CsA) and calcitriol (CT), 2 immunomodulatory agents, in vivo in the adjuvant arthritis (AA) model in rats. Treatment initiated at priming with complete Freund's adjuvant consisted of daily administration of CsA and CT during the prearthritic phase (14 days). CsA given alone delayed the onset of the disease, whereas the severity was either not affected or paradoxically enhanced. Injection of CT alone reduced the severity of arthritis. The association of low doses of CsA (5 mg/kg) and CT (0.2 micrograms/kg) further delayed the onset of AA and abolished the aggravating effect. Our findings suggest that low doses of CsA and CT in association exhibit the additive beneficial effects of either agent alone.

Administration, Oral↗
PubMed1992

Protective effects of ciprofloxacin against type II collagen induced arthritis in rats.

Ciprofloxacin, a new fluoroquinolone antibiotic, inhibits the in vitro production of interleukin 1 beta and tumor necrosis factor alpha by monocytes. We investigated its activity against type II collagen induced arthritis in rats. It exerted a dose dependent preventive effect at 50 and 75 mg/kg/day against clinical and histologic features of collagen induced arthritis without any influence on the production of anticollagen antibodies and alpha 1-acid glycoprotein. This effect was reversible after early removal of the treatment. Ciprofloxacin did not inhibit collagen induced arthritis in adrenalectomized rats but rather caused an exacerbation of the disease. Its effect was not modified by the simultaneous administration of an antiglucocorticoid, RU 40555.

Adrenal Cortex Hormones↗
PubMed1991

Experimental studies and preliminary clinical trial of vinorelbine-loaded polymeric bioresorbable implants for the local treatment of solid tumors.

Vinorelbine is a new 5' nor Vinca alkaloid, active by i.v. route, in various types of cancer disease such as non-small cell lung cancer and advanced breast cancer. In order to evaluate the possibility of using this drug for local treatment of cancer, Vinorelbine-loaded bioresorbable polymeric implants were prepared using a copolymer of D,L-lactic and glycolic acids (PLA 37.5 GA 25). According to the manufacturing process, the 1.2-mm-diameter cylindrical rods obtained had a drug content of 1, 5, or 20% (w/w) and released half of their content within about 6 days in vitro. In vivo release in rats was slower, half of the drug being released after about 14 days. A dose-dependent antitumoral effect was observed in mice (solid P388 leukemia model) when implants were administered into or in contact with the tumor. At highest drug loads and when administered soon after tumor implantation, Vinorelbine implants were more effective than i.v. administration (median survival time of treated animals related to untreated controls, greater than 360 versus 188). In dogs, results of toxicity experiments revealed that administration of implants in vital organs must be avoided. On the contrary, s.c. administration was well tolerated. A transient local necrosis was observed in the days following implantation, but normal skin was recovered after about 10 weeks. Thus, a clinical trial was conducted on patients with head and neck cancer; implantation of 20% loaded polymeric implants into the tumor sites succeeded in 8 of 9 patients. The sole failure was attributed to the unusual hardness of the tumor tissue. Except for a local transient inflammatory reaction (easily treated with nonsteroidal antiinflammatory agents), no other sign of toxicity was detected, and patients tolerated the device well. Fourteen days after implantation, patients underwent their planned surgery, and the implants were recovered. Residual drug content varied from 24 to 55%. In all cases, there was a clearly delimited necrotic area around the implant, ranging from 0.5 to 3.5 cm in diameter. In the smallest tumors, necrosis was also observed in the normal tissue inside this area. These results invite further studies to evaluate such drug-loaded polymeric implants.

Adult↗
PubMed1991

Therapy against murine collagen-induced arthritis with T cell receptor V beta-specific antibodies.

Immunization with native type II collagen (CII) of susceptible strains of mice (H-2q) induces a rheumatoid arthritis-like disease. Collagen-induced arthritis (CIA) is an experimental model for T cell-mediated autoimmune disease. To investigate the T cell receptor (TcR) repertoire involved in the pathogenesis of CIA, CII-primed DBA/1 mice were treated with various TcR V beta-specific monoclonal antibodies (mAb) using a protocol resulting in a long-term elimination of the target T cells. In vivo treatment with anti-CD4 mAb led to nearly complete protection against CIA. Mice injected with anti-V beta 8.1, 2 or anti-V beta 5.1, 2 mAb had a reduced incidence of arthritis (respectively 28.6% and 50% vs 84.6% for the control group). Administration of anti-V beta 2 mAb delayed the onset of the disease whereas injection of anti-V beta 6 or anti-V beta 11 mAb did not alter CIA. Moreover, the combined treatment with anti-V beta 2 and anti-V beta 5 mAb efficiently reduced the development of CIA. The humoral response to CII was down-regulated only in the groups of mice that were improved by the treatment. In vitro proliferative response to CII of lymph node cells from primed DBA/1 was partially blocked by addition of several anti-V beta mAb. Thus, our findings suggest that the overall T cell response to CII may be polyclonal while the T cell clones involved in the pathogenesis of CIA express a limited number of V beta chains.

Animals↗
PubMed1991

Modification of inflammatory processes by phenobarbital in rats.

Enzyme-inducing drugs such as phenobarbital (PB) increase serum concentrations of an acute-phase protein, alpha 1-acid glycoprotein (AGP), in man, dogs, and rats via an unknown mechanism. We studied the effects of PB on components of an acute inflammatory reaction in rats in order to determine if PB acts only on this biological marker of inflammation or is capable of altering the clinical course of inflammatory processes. Local carrageenan injection induces a similar time-dependent plantar edema and increases serum AGP levels in Sprague-Dawley (SD) and Dark Agouti (DA) rats. Pretreatment with PB for seven days modified neither parameter in SD rats while plantar edema was aggravated and serum AGP levels were increased in DA rats. The sedative-hypnotic properties of PB were not involved, since a single administration of this drug had no action in DA rats. On the other hand, chronic PB administration reduced the severity of an autoimmune disease, type II collagen-induced arthritis, in DA rats. These data indicate that PB, a potent inducer a cytochrome P-450-dependent enzymes, modifies the course of the inflammatory process. Preliminary results with macrophage transfer experiments suggest that this response to PB could be mediated by stimulated macrophages.

Acute Disease↗