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P Devillier

Publications and source records attributed to P Devillier.

At least 73 records · Page 4Linked to original sources

[Recombinant vaccine and extracting vaccine against hepatitis B in patients with kidney insufficiency: comparative immunogenicity].

OBJECTIVES: Patients with chronic renal failure respond rather poorly to hepatitis B vaccines. A better response could be expected from recombinant vaccines including both the S and the pre-S2 antigens. We therefore prospectively compared the immunogenicity of plasma-derived Hevac B vaccine (H) with that of recombinant GenHevac B vaccine (G). METHODS: Vaccinations were performed in 120 non-dialyzed patients with chronic renal failure. The patients were randomly divided into two groups. Group G included 60 patients (24 males, mean age 58 +/- 16 years, mean creatinine clearance 25.3 +/- 12.6 ml/min) who were given the Hevac B vaccine at the dose of 5 micrograms. Group H included 60 patients (31 males, mean age 60 +/- 15 years, mean creatinine clearance 24.4 +/- 11.1 ml/min) who were given GenHevac B vaccine at the dose of 20 micrograms. All vaccinations were repeated at 0, 1, 2, 4 and 12 months. RESULTS: Following the fourth injection, seroconversion (anti-Hbs > or = 2 mlU/ml) was observed in 50/59 (85%) of the patients in group G versus 38/58 (67%) in group H (p < 0.02). Seroprotection (> or = 10 mlU/ml) was obtained in 42/59 (71%) vs 34/58 (59%), (NS) in the two groups respectively with a geometric mean titer of 112 versus 229 mlU/ml (NS) in responders. Following the booster injection at the 12th month, seroconversion was achieved in 48/51 (94%) vs 40/53 (76%) (p < 0.01) and seroprotection in 84% vs 70% (p = 0.053) respectively. The mean geometric titers were 879 and 1001 mlU/ml. CONCLUSIONS: Recombinant GenHevac B vaccine elicits seroconversion and seroprotection in a higher proportion of patients with chronic renal failure than the plasma-derived Hevac B vaccine, with comparably high antibody titers in responders. Therefore, GenHevac B vaccine should be recommended for vaccinating patients with chronic renal failure against hepatitis B.

Adult↗

Immunogenicity of the recombinant GenHevac B Pasteur vaccine against hepatitis B in chronic uremic patients.

Immunogenicity of the recombinant GenHevac B vaccine (G), containing both the S and the preS2 antigen, was compared with that of the plasma-derived Hevac B (H) vaccine in 120 chronic uremic predialysis patients. Sixty received 20 micrograms/dose of G and 60 received 5 micrograms/dose of H at 0, 1, 2, 4, and 12 months. Two months after the fourth injection, seroconversion (antibody to hepatitis B surface antigen [HBs], > or = 2 mIU/mL) was seen in 85% of group G and 67% of group H patients (P < .02); seroprotection (anti-HBs, > or = 10 mIU/mL) was seen in 71% and 59%, respectively. The geometric mean titers (GMT) of anti-HBs in responders were 112 and 229 mIU/mL, respectively. After booster injection at month 12, seroconversion occurred in 94% and 76% and seroprotection in 84% and 70%, with anti-HBs GMTs of 879 and 1001 mIU/mL in groups G and H, respectively. The recombinant GenHevac B vaccine elicited seroconversion and seroprotection in a higher proportion of chronic uremic patients, with comparably high anti-HBs antibody titers in responders.

Adult↗

[Neurokinins and the skin].

Neurokinins are a family of peptides which are released from sensory nerves. This family involves substance P, neurokinin A and B which stimulate neurokinin-NK1, -NK2 and -NK3 receptors respectively. The neurokinins as well as C.G.R.P. (calcitonin gene related peptide) and V.I.P. (vasoactive intestinal peptide) are the mediators of the non adrenergic non cholinergic (N.A.N.C.) nervous system. All these peptides can be released by nerve fibres innervating the skin. They are mainly inflammatory mediators. At skin level, the neurokinin induce itch, wheal and flare. Itch and flare are partly due to histamine release from mast cells in response to substance P.

Amino Acid Sequence↗

Influence of benzodiazepines on the response of the guinea-pig isolated trachea to the contractile action of adenosine.

The effects of diazepam and other agonists of central or peripheral benzodiazepine receptors were studied on the contractile action of adenosine, 2-chloroadenosine and R-PIA (N6-(L-2-phenylisopropyl)-adenosine) on the guinea-pig isolated trachea. These effects were compared to those of dipyridamole. Diazepam 10(-7) to 10(-5) M potentiated the efficacy of adenosine; the maximal contractile effect of adenosine (% vs. acetylcholine 10(-3) M) was 20.4 +/- 4.2 (n = 21) in control conditions and 45.5 +/- 3.7 (n = 6; P less than 0.001) in the presence of diazepam 10(-5) M. Ro5-4864 (10(-7) to 10(-5) M) or alpidem (10(-7) to 10(-5) M), both agonists of peripheral benzodiazepine receptors, potentiated the contractile effects of adenosine to the same extent as diazepam. Clonazepam and zopiclone, both agonists of central benzodiazepine receptors, did not modify these effects. Antagonists of central (flumazenil) or peripheral (RP 52028) benzodiazepine receptors had no influence on the interaction between diazepam or Ro5-4864 and adenosine. Conversely, dipyridamole significantly reduced (10(-7) M) or suppressed (10(-6) M) the contractile effects of adenosine. The contractile effects of 2-chloroadenosine and R-PIA were weakly affected in presence of high concentrations of diazepam and dipyridamole. Epithelium removal potentiated the contractile effect of adenosine on the guinea-pig isolated trachea and increased the potentiating effect of diazepam. It is concluded that benzodiazepines and related compounds can potentiate the contractile effect of adenosine on the guinea-pig isolated trachea through the activation of a peripheral receptor for the benzodiazepines and the resulting inhibition of adenosine uptake.

2-Chloroadenosine↗

Contractile effect of alpha,beta-methylene ATP on the guinea-pig isolated trachea.

The effects of alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-methylene ATP), 2-chloroadenosine and R-PIA (N6-(L-2-phenylisopropyl)-adenosine) and their interaction with dipyridamole, indomethacin, 8-phenyl-theophylline, diazepam and other agonists of central or peripheral benzodiazepine receptors were studied on the guinea-pig isolated trachea. alpha,beta-methylene ATP exerted contractile effects on the guinea-pig isolated trachea; - log EC50 and E(max) values were 8.86 +/- 0.19 and 31.3 +/- 2.3 (n = 31) (% vs acetylcholine 10(-3) M) respectively. In comparison with other purinergic receptor agonists, the rank order of potency was: alpha,beta-methylene ATP greater than 2-chloroadenosine greater than R-PIA. alpha,beta-methylene ATP and 2-chloroadenosine had significantly (P less than 0.05) greater efficacy (E(max)) than R-PIA. Indomethacin (3 x 10(-6) M) and 8-phenyltheophylline (10(-7) to 10(-5) M) significantly reduced the contractile effect of 2-chloroadenosine and R-PIA but did not affect alpha,beta-methylene ATP-induced contraction. Conversely, dipyridamole significantly reduced (10(-7) M) or suppressed (10(-6) M) the contractile effects of alpha,beta-methylene ATP whereas it only partially reduced (10(-6) M) the contractile effects of high concentrations of 2-chloroadenosine or R-PIA. Diazepam potentiated the efficacy of alpha,beta-methylene ATP. The E(max) (% vs acetylcholine 10(-3) M) values were 26.1 +/- 2.0 (n = 10) in control conditions and 45.9 +/- 4.6 (n = 5; P less than 0.05) in the presence of diazepam 10(-5) M. Diazepam did not modify the contractile effects of 2-chloroadenosine or R-PIA. Ro5-4864 (10(-7) to 10(-5) M), an agonist of peripheral benzodiazepine receptors, potentiated the contractile effects of alpha,beta-methylene ATP to the same extent as diazepam. Clonazepam, an agonist of central benzodiazepine receptors, did not modify these effects. Antagonists of central (flumazenil) or peripheral (RP 52028) benzodiazepine receptors had no influence on the interaction between diazepam or Ro-4864 and alpha,beta-methylene ATP. In conclusion, alpha,beta-methylene ATP exerts on guinea-pig isolated trachea a contractile effect which is not modified by indomethacin and 8-phenyltheophylline, but is reduced by dipyridamole. It is suggested that this effect might involve P2 chi receptor stimulation.

2-Chloroadenosine↗

Activation of an epithelial neurokinin NK-1 receptor induces relaxation of rat trachea through release of prostaglandin E2.

We studied the type of neurokinin (NK) receptor involved in the epithelium-dependent substance P (SP)-induced relaxation of rat trachea precontracted with serotonin (5-HT). We first compared the relaxant effects of different agonists to the three NK receptors on rat trachea in the presence (E+) and absence (E-) of the epithelium. The three agonists to the NK-1 receptor, SP, SP-O-methylester and [beta Ala4, Sar9, Met(O2)] SP(4-11), at a concentration of 1 microM induced a relaxation of 40 +/- 5, 33 +/- 4 and 31 +/- 6%, respectively in E+ segments. They had weak and nonsignificant effects in E- segments. In addition, (+/-)CP-96,345 (1 microM), the NK-1-selective non-peptide antagonist, inhibited the SP-induced relaxation by 45%. Conversely, the three NK-2 receptor agonists, NKA, NKA(4-10) and [Nle10]NKA(4-10), and the two NK-3 receptor agonists, neurokinin B (NKB) and [MePhe7]NKB(4-10), had no effect on E+ or E- tracheal segments. The N-terminal SP fragment SP(1-9) was also inactive. These results suggest that SP-induced relaxation is mediated through activation of epithelial NK-1 receptors. Preincubation with the cyclooxygenase inhibitor, indomethacin (2.8 microM), abrogated the relaxant effect of the three NK-1 receptor agonists on E+ tracheas. We measured in additional experiments prostaglandin E2 (PGE2), PGF2 alpha, 6-keto PGF1 alpha and thromboxane B2. SP (1 microM) induced a 6.1-fold increase in PGE2 production (from 13 pg after 5-HT to 78 pg) in E+ segments, whereas only a 1.5-fold increase occurred in E- preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗

Immunogenicity and safety in newborns of a new recombinant hepatitis B vaccine containing the S and pre-S2 antigens.

A study to evaluate the safety and immunogenicity of a recombinant hepatitis B vaccine containing the S and pre-S2 antigens (GenHevac B Pasteur) was conducted in healthy newborn infants. All infants received 20 micrograms of vaccine within 24 h of birth and at 1 and 2 months with a booster injection at month 12. The vaccine was administered alone in 19 infants born to low risk mothers, i.e. surface antigen (HBsAg)-negative and antibody to the core antigen (Anti-HBc)-positive mothers. The vaccine was administered in combination with 100 IU hepatitis B immune globulin (HBIg) at birth and 1 month in 18 infants born to high risk mothers, i.e. HBsAg positive mothers. In the group not receiving HBIg, the anti-HBs seroconversion rate at the 10 mIU ml-1 threshold was 50% 1 month after the first injection. In both groups, the anti-HBs seroconversion rates were 100% 1 month after the third injection and greater than 85% 1 month after the second injection. After the booster injection greater than 90% of the infants had an anti-HBs titre greater than 1000 mIU ml-1 which will probably provide them with adequate protection for several years. The kinetics of the anti-pre-S2 response was similar to that of the anti-HBs response and 100% of infants in both groups had seroconverted 1 month after the second injection of the vaccine. The side effects were scarce, all mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation↗

Effect of atrial natriuretic peptide and on atriopeptins on the human isolated bronchus. Comparison with the reactivity of the guinea-pig isolated trachea.

ANF, ANF7-28 and atriopeptins (AP1, AP2 and AP3) (10(-11) to 3 x 10(-7) M) induce a relaxant response on the guinea-pig isolated trachea, which is partially potentiated by the enkephalinase inhibitor thiorphan 10(-5) M but is unmodified by epithelium removal. Conversely, these drugs were found to be without any significant relaxant effect on the isolated human bronchus. Several hypotheses, such as the activation of ANF receptors not located on airway smooth muscle or an indirect effect of ANF in vivo are suggested to explain the discrepancy between these in vitro results and those of clinical trials in asthmatic subjects.

Amino Acid Sequence↗

Influence of diazepam, alpidem, zolpidem and zopiclone, on the response to adenosine of the guinea pig isolated trachea.

It has been reported that dipyridamole and some benzodiazepines potentiate the responses to adenosine in peripheral organs and in particular in the guinea pig isolated atria or trachea by inhibition of adenosine uptake and/or metabolism. In this study, we have examined the sensitization of guinea pig isolated trachea to relaxant responses to adenosine produced by dipyridamole, diazepam and 3 compounds chemically unrelated to benzodiazepines but which display selective agonistic activity towards the central (zolpidem and zopiclone) or peripheral (alpidem) type benzodiazpine receptors. In preparations under spontaneous tone and in the absence of adenosine, dipyridamole (10(-5) M) and diazepam (10(-5)-10(-4) M), alpidem (3 x 10(-6) M-10(-5) M) and zopiclone (10(-6)-10(-4) M) induced a relaxation of the airway smooth muscle. In addition, dazepam (10(-4) M) attenuated the phasic response to histamine (10(-5) M). Dipyridamole (10(-5) M) and diazepam (10(-4) M) respectively produced a 56.2 and 32.4-fold potentiation of adenosine relaxant effects. Alpidem (10(-6)-10(-5) M), zolpidem (10(-6)-10(-4) M) and zopiclone (10(-6)-10(-4) M) were without any significant effect on the adenosine concentration-response curves. Moreover, alpidem, zolpidem, and zopiclone did not modify the 2-chloroadenosine dose-response curves nor the diazepam induced sensitization of adenosine-induced relaxation. In conclusion, adenosine sensitization of the guinea pig isolated trachea caused by diazepam might involve a peripheral benzodiazpine receptor subtype coupled to a nucleoside transporter system which is different from those recognized by compounds derived from the imidazopyridine series.

2-Chloroadenosine↗

[Immunogenicity and harmlessness in the newborn of a vaccine (GenHevac B) containing the antigens S and pre-S2].

A study to evaluate the safety and immunogenicity of a recombinant hepatitis B vaccine containing the S and pre-S2 antigens (GenHevac B Pasteur) was conducted in healthy newborn infants. All infants received 20 micrograms of vaccine within 24 hours after birth, at 1 and 2 months with a booster injection at month 12. The vaccine was administered alone in 19 infants born to low risk mothers, i.e. surface antigen (HBsAg)-negative and antibody to the core antigen (Anti-HBc)-positive mothers. The vaccine was administered in combination with 100 IU hepatitis B immune globulin (HBIg) at birth and one month in 18 infants born to high risk mothers, i.e. HBsAg positive mothers. In the group not receiving HBIg, the anti-HBs seroconversion rate at the 10 mlU/ml threshold was 50% one month after the first injection. In both groups, the anti-HBs seroconversion rates were 100% one month after the third injection and above 85% one month after the second injection. After booster injection, more than 90% of the infants had an anti-HBs titre above 1,000 mlU/ml that will probably provide them with adequate protection for several years. The kinetics of the anti-pre-S2 response was similar to those of the anti-HBs response and 100% infants in both groups had seroconverted one month after the second injection of the vaccine. The side effects were scarce, all mild and transient. Given the protective role of the anti-pre-S2 antibodies, the precocity of the response to pre-S2 antigen may therefore increase the effectiveness of hepatitis vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗

Peripheral type benzodiazepine receptors and response to adenosine on the guinea-pig isolated trachea.

It has been reported that dipyridamole, an adenosine uptake inhibitor, and some benzodiazepines potentiate the responses to adenosine in peripheral organs and in particular, on guinea-pig isolated atria. In this paper, we have examined the potentiation of responses to adenosine produced by dipyridamole, diazepam and four compounds with selective agonistic activity towards the central (clonazepam) or peripheral (Ro5-4864) type benzodiazepine receptors or antagonistic activity towards the central (flumazenil) or peripheral (PK 11195) benzodiazepine receptors in guinea-pig trachea in vitro. In preparations under basal tone and in the absence of adenosine, dipyridamole (10(-5) M) and benzodiazepines (10(-4) M) with the exception of flumazenil induced a relaxation of the airway smooth muscle. In addition, diazepam (10(-4) M) attenuated the phasic response to histamine (10(-5) M). Dipyridamole, and the benzodiazepine agonists diazepam, Ro5-4864 and clonazepam (10(-5) to 10(-4) M) produced potentiation of the tracheal response to adenosine, the rank order of potency being dipyridamole (pKi = 7.77 +/- 0.12, n = 8) greater than Ro5-4864 (pKi = 5.43 +/- 0.18, n = 6) greater than or equal to diazepam greater than clonazepam (pKi = 4.84 +/- 0.11, n = 6). The two benzodiazepine receptor antagonists, flumazenil and PK 11195, gave a significant but small potentiation to adenosine only at 10(-4) M. In the presence of dipyridamole (10(-5) M), diazepam (10(-4) M) did not cause any further potentiation to adenosine. Additionally, the potentiation produced by diazepam was not antagonised by flumazenil, whereas it was potently antagonised by PK 11195. Similarly, PK 11195 potently inhibited the adenosine potentiation produced by Ro5-4864.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Inhibition of human and rabbit platelet activation by Ketotifen.

The effects of Ketotifen and disodium cromoglycate were investigated on human and rabbit platelet activation. Ketotifen inhibited dose-dependently human and rabbit platelet aggregation. The paf-acether pathway was the most markedly influenced by Ketotifen in human and rabbit platelets (IC50 = 38.8 +/- 7.7 microM and 7.2 +/- 4.5 microM respectively) as compared to adenosine diphosphate (IC50 greater than 100 microM and 79 +/- 19 microM) and to arachidonic acid (IC50 greater than 100 microM and 98 +/- 28 microM). Similar concentrations of Ketotifen inhibited the ATP release from human platelets induced by paf-acether. Disodium cromoglycate up to 5 x 10(-4) M did not inhibit platelet aggregation induced by paf-acether, adenosine diphosphate and arachidonic acid.

Adenosine Triphosphate↗

Role of the N-terminal arginine in the histamine-releasing activity of substance P, bradykinin and related peptides.

A series of substance P (SP)- and bradykinin (BK)-related peptides have been compared for their histamine-releasing activities on rat peritoneal mast cells. Some of these peptides only differed in the N-acetylation of the N-terminal arginine residue or by the removal of charged residue at the N-terminal. The aim was to examine the role of the N-terminal positive charges in the histamine-releasing activity of compounds that are selective for the SP receptor (named NK-1) or for the B2 type bradykinin receptor. Only compounds with positive charges at the N-terminal caused non-cytotoxic histamine release from rat mast cells. It is suggested that SP- and BK-related peptides caused histamine release by a mechanism which appeared to be non-specific and not related to the activation of mast cell NK-1 or B2 receptors, respectively. Our results show that NK-1 agonists or B2 antagonists devoid of histamine-releasing activity, which could be of potential use in the clinic, can be obtained by removing the positively charged N-terminal aminoacids or by N-acetylation of the N-terminal arginine.

Animals↗

Characterisation of enkephalinase (EC 3.4.24.11) activity on various leukemic cells expressing the common acute lymphocytic leukemia antigen (CALLA).

The deduced amino acid sequences of CALLA, a cell surface marker of human acute lymphocytic leukemia, and human enkephalinase (neutral endopeptidase, EC 3.4.24.11) were recently reported to be almost identical. We show that membranes of CALLA+ cells of the REH lymphoblastic cell line as well as blast cells derived from the blood or bone marrow of patients with acute lymphocytic leukemia display high enkephalinase activity. This activity was abrogated by several enkephalinase inhibitors at concentrations closely similar to those required to inhibit pure human enkephalinase. However, these compounds did not significantly modify the rate of REH cell proliferation in vitro. Hence, the functional role, if any, of the high peptidase activity in lymphoblastic cells remains to be established.

Antigens, Differentiation↗

Histamine-releasing activity of endogenous peptides on mast cells derived from different sites and species.

We have examined the cytological and functional characteristics of mast cells grown in tissue culture from the bone marrow of mice and rats and compared them with mast cells isolated from the peritoneal cavity of these animals. In both species, bone marrow-derived mast cells (considered to be a model of mucosal mast cells) have fewer cytoplasmic granules and lower histamine content than peritoneal mast cells. Sprague-Dawley rat peritoneal mast cells were responsive to various endogenous peptides and to compound 48/80. However, peritoneal mast cells isolated from BDF1 mice (a strain widely used to obtain bone marrow-derived mast cells) were not responsive to the same secretagogues. Rat and mouse bone marrow-derived mast cells obtained from Sprague-Dawley rats and BDFI1 mice were also hyporesponsive to calcium ionophore as compared to peritoneal mast cells and unresponsive to compound 48/80 and peptides. Despite the similarity of the functional characteristics of mouse and rat bone marrow-derived mast cells, mouse bone marrow-derived mast cells could not be used as a model of responsiveness to peptides for rat mucosal mast cells because of the differences in responsiveness between the peritoneal mast cells in the two species. Obtention of homogeneous rat bone marrow-derived mast cells may provide a useful tool to study the functional heterogeneity in an intraspecies system since most of our knowledge on mast cell physiology and pharmacology is derived from studies on rat peritoneal mast cells.

Animals↗