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Biomedical subjects

P Lefevre

Publications and source records attributed to P Lefevre.

At least 37 records · Page 2Linked to original sources

Benzodiazepine-withdrawal-induced gastric emptying disturbances in rats: evidence for serotonin receptor involvement.

This study was performed in rats to determine if serotonin and its receptors are involved in the increase of gastric emptying (GE) induced by benzodiazepine (BZ) withdrawal. GE was measured with a test meal (2 ml) containing 1 microCi/ml of 51Cr sodium chromate administered in rats, either previously receiving injections with diazepam (15 mg/kg/day i.p.) or with DMSO (0.9 ml/day i.p.) during 7 days. On the 8th day, animals received the different serotonin (5-HT) agonists or antagonists, and flumazenil (BZ antagonist; 15 mg/kg i.p.) 30 and 15 min, respectively, before the test meal. Methiotepin (5-HT1 antagonist) either i.p. (0.1-1 mg/kg) or intracerebroventricularly (10 micrograms/kg) had no effect on the increase of GE induced by precipitated-withdrawal. 8-OH-DPAT (5-HT1A agonist) administered i.c.v. (1-10 micrograms/kg) dose dependently reduced GE increase. Administered i.p. (0.1 mg/kg), it blocked GE increase in control and diazepam-withdrawn rats. Ritanserin (5-HT2 antagonist) antagonized GE increase only when administered i.p. (0.1 mg/kg). Granisetron (5-HT3 antagonist) was active both i.p. (0.01-0.1 mg/kg) and intracerebroventricularly (1-10 micrograms/kg). Administered intracerebroventricularly (1 microgram/kg) in diazepam-treated rats, 5-HTP mimicked the effect of flumazenil. It is concluded that diazepam-withdrawal increases GE by stimulating central release of 5-HT and/or central activation of 5-HT neurons. At least central 5-HT3 receptors, and in less extend, peripheral 5-HT2 receptors are involved in this mechanism.

5-Hydroxytryptophan↗

Direct observation of substance P-induced internalization of neurokinin 1 (NK1) receptors at sites of inflammation.

Substance P (SP) can cause plasma leakage at sites of inflammation by binding to neurokinin type 1 (NK1) receptors on the surface of endothelial cells. Internalization after ligand binding could reduce the number of NK1 receptors on the cell surface and thus participate in the desensitization and resensitization of the inflammatory response to SP. By using an antibody to the receptor, we directly observed SP-induced internalization of NK1 receptors into endosomes in endothelial cells of postcapillary venules in the rat tracheal mucosa. In the absence of SP, an average of 15 immunoreactive endosomes were present per endothelial cell. After an intravenous injection of SP, the number of immunoreactive endosomes peaked at 107 per cell at 3 min and gradually returned to the baseline by 120 min. In parallel experiments we observed that when cultured cells transfected with the NK1 receptor were exposed to rhodamine-SP and an antibody to an extracellular Flag epitope of the NK1 receptor, the SP was internalized with the receptor antibody. Both in the cultured cells and in the endothelial cells of intact animals, the prompt SP-induced internalization was accompanied by rapid, long-lasting desensitization to SP. These studies suggest that internalization of NK1 receptors by endothelial cells may be one of the mechanisms that limit the amount of plasma leakage at sites of inflammation.

Animals↗

Long-term results of therapy with interferon alpha for cryoglobulinemia associated with hepatitis C virus infection.

We describe the long term results of treatment with interferon (IFN) in two patients with cryoglobulinemia and chronic hepatitis related to Hepatitis C virus (HCV). Our results suggest that interferon may induce long remission in cryoglobulinemia associated with HCV infection and that the effect of IFN is not dependent on the effect on liver function, but results of its antiviral activity.

Aged↗

Accelerated hypertension and nephroangiosclerosis associated with antiphospholipid syndrome. Report of two cases and review of the literature.

We describe two patients with the primary antiphospholipid syndrome who presented with severe hypertension. Renal biopsy specimen provided histologic evidence of intra-renal vascular disease with intravascular microthrombosis and nephrosclerosis, without feature of proliferative glomerulopathy. Accelerated hypertension and nephroangiosclerosis might indeed be one of the complications associated with anticardiolipin antibodies. The mechanism responsible might be the interaction of anticardiolipin antibodies, platelets and endothelial cell leading to microthrombi formation and increased local mitogenic activity that attract and stimulate neighbouring smooth muscle cell and fibroblast proliferation.

Adult↗

Identification of cytotoxic T cell epitopes on the VP3 and VP6 rotavirus proteins.

It has been shown previously that the viral glycoprotein VP7 is a major target of cytotoxic T lymphocytes (CTLs) induced by bovine rotavirus RF in C57BL/6 mice. Here we show that these RF-specific CTLs recognize target cells infected with a recombinant vaccinia virus (rVV) expressing the SA11 (simian rotavirus) VP6 but not those infected with rVVs that express RF VP1, VP2 or VP3 core proteins. After immunization of mice with insect cells infected with recombinant baculoviruses that express the corresponding RF proteins a strong specific CTL response was generated against target cells infected with VP6 rVV and VP3 rVV, a weak one against the VP2 rVV but none against the VP1 rVV. Kb-restricted CTL epitopes were identified on VP6 and VP3 using allele-specific motifs. When peptides corresponding to these epitopes were used to restimulate in vitro the spleen cells from RF-immunized mice, CTLs specific for each peptide and its corresponding rVV were induced.

Animals↗

[Peroperative use of Cell Saver in elective surgery on the abdominal aorta].

In order to determine the impact of intraoperative autotransfusion on vascular surgical care, data related to 200 abdominal aortic surgical operations performed over a 20 months period were prospectively analysed. Volumes of blood salvaged and transfused during and after each operation were considered. One hundred and twenty one patients had an intraoperative autologous transfusion at a mean volume of 616 +/- 410 ml. Among them, 36 patients (43%) had only their own autotransfused blood and no other homologous blood components were required. Rapid autotransfusion was associated neither with significant haemolysis, nor with coagulopathy. Neither mortality nor morbidity was related to intraoperative autotransfusion. These data suggest that intraoperative autotransfusion is a safe replacement method in major vascular surgery. The procedure should be used in conjunction with preoperative donations when feasible.

Aged↗