European Society of Anaesthesiology.

No abstract

A study on malaria transmission, prevalence of infection and anti-sporozoite antibodies was carried out in Burkina Faso (West Africa). The prevalence and the levels of antibodies to (NANP)3 were found to be related to the entomological sporozoite inoculation rates measured at the same time in a defined area. The major inducer of anti-(NANP)3 antibody production under field conditions is sporozoite inoculation by infected mosquitoes. Levels of antibodies to (NANP)3 vary considerably with age and transmission season. High levels of anti-(NANP)3 antibodies raised under field conditions might offer protection against small inocula of sporozoites.

The lentivirus feline immunodeficiency virus (FIV) is a widespread pathogen of the domestic cat that is mainly transmitted through bites, although other means of transmission are also possible. Its prevalence ranges from 1 to 10% in different cat populations throughout the world, thus representing a large reservoir of naturally infected animals. FIV resembles the human immunodeficiency virus (HIV) in many respects. Similarities include the structural features of the virion, the general organization and great variability of the genome, the life cycle in the infected host, and most importantly, the pathogenic potential. Infection is associated with laboratory signs of immunosuppression as well as with a large variety of superinfections, tumors, and neurological manifestations. Our understanding of FIV is steadily improving and is providing important clues to the pathogenesis of immunodeficiency-inducing lentiviruses. The cellular receptor for FIV is different from the feline equivalent of the human CD4 molecule used by HIV; nevertheless, the major hallmark of infection is a progressive loss of CD4+ T lymphocytes as in HIV infection. The mechanisms by which FIV escapes the host's immune responses are being actively investigated. FIV causes lysis of infected T cells and also appears to predispose these cells to apoptosis. Infection of macrophages and other cell types has also been documented. For reasons yet to be understood, antibody-mediated neutralization of fresh FIV isolates is very inefficient both in vitro and in vivo. Vaccination studies have provided some encouraging results, but the difficulties encountered appear to match those met in HIV vaccine development. FIV susceptibility to antiviral agents is similar to that of HIV, thus providing a valuable system for in vivo preclinical evaluation of therapies. It is concluded that in many respects FIV is an ideal model for AIDS studies.

Objectives Microparticles are membrane vesicles shed by cells upon activation and apoptosis. Agonists capable of inducing microparticle generation include cytokines, bacterial products, P-selectin, histamine. Cigarette smoke extract has also been recognized as an agonist involved in microparticle generation with an apoptosis-dependent mechanism. We investigated the possibility that cigarette smoke extract induces the rapid generation of proinflammatory microparticles by human mononuclear cells with a calcium-dependent mechanism. Materials and methods Human mononuclear cells were exposed to cigarette smoke extract. [Ca 2? ] i mobilization was assessed with the fluorescent probe Fluo-4 NW. Microparticles were quantified with a prothrombinase assay and by flow cytometry. Normal human bronchial epithelial cells and A549 alveolar cells were incubated with cigarette smoke extract-induced microparticles and the generation of ICAM-1, IL-8, and MCP-1 was assessed by ELISA.Results Exposure to cigarette smoke extract induced a rapid increase in [Ca 2? ] i mobilization. Microparticle generation was also increased. EGTA, verapamil and the calmodulin inhibitor, W-7, inhibited microparticle generation. Incubation of lung epithelial cells with cigarette smoke extract-induced microparticles increased the expression of proinflammatory mediators. Conclusions Exposure of mononuclear cells to cigarette smoke extract causes a rapid shedding of microparticles with a proinflammatory potential that might add to the mechanisms of disease from tobacco use.

Sixty-six 20- to 23-amino-acid synthetic peptides, partially overlapping by 10-12 amino acids, spanning the entire sequence of the envelope SU and TM glycoproteins of the Petaluma isolate of FIV, have been used to investigate the Env domains involved in viral infection. Peptides 5 to 7, spanning amino acids 225E-P264 located in a conserved region of the SU protein, and peptides 58 to 61, spanning amino acids 767N-P806 and encompassing hypervariable region 8 of TM protein, exhibited a remarkable and specific antiviral effect against the homologous and one heterologous isolate, as judged by inhibition of FIV-induced syncytium formation and p25 production in CrFK cells. Peptides 5 and 7, but not peptides 58 and 59, also inhibited viral replication of a fresh FIV isolate on nontransformed lymphoid cells. By flow cytometry, peptides 5, 7, 58, and 59 were shown to bind the surface of FIV permissive cells. The antiviral activity of peptides 5 and 7, however, was time-dependent, as inhibition of FIV replication was seen when the peptides were administered before or within 3 hr after virus inoculation; in contrast, TM peptides 58 and 59 exerted a potent inhibitory effect when added up to 24 hr after virus inoculation. Circular dychroism analysis showed that peptide 5 folds to a helical conformation in the presence of a hydrophobic environment. Although the basis for the antiviral action of the peptides is not understood, our data suggest that the inhibitory peptides may act by interacting with cell-surface molecules involved in viral infection.

Synthetic peptides have been used to map linear B-cell epitopes of the third variable (V3) region of the feline immunodeficiency virus (FMI) external membrane glycoprotein gpl20. The analysis of sera from naturally and experimentally FlV-infected cats by Pepscan and enzyme immunoassay with four partially overlapping peptides evidenced three antibody-binding domains, two of which mapped in the carboxyl-terminal half of V3.

Specific-pathogen-free cats, immunized with a 22-amino-acid synthetic peptide designated V3.3 and derived from the third variable region of the envelope glycoprotein of the Petaluma isolate of feline immunodeficiency virus (FIV), developed high antibody titers to the V3.3 peptide and to purified virus, as assayed by enzymelinked immunoassays, as well as neutralizing antibodies, as assayed by the inhibition of syncytium formation in Crandell feline kidney cells. V3.3-immunized animals and control cats were challenged with FIV and then monitored for 12 months; V3.3 immunization failed to prevent FIV infection, as shown by virus isolation, anti-whole virus and anti-p24 immunoglobulin G antibody responses, and positive PCRs for gag and env gene fragments. Sequence analysis of the V3 region showed no evidence for the emergence of escape mutants that might have contributed to the lack of protection. The sera of the V3.3-hyperimmunized cats and two anti-V3.3 monoclonal antibodies neutralized FIV infectivity for Crandell feline kidney cells at high antibody dilutions but paradoxically failed to completely neutralize FIV infectivity at low dilutions. Moreover, following FIV challenge, V3.3-immunized animals developed a faster and higher antiviral antibody response than control cats. This was probably due to enhanced virus replication, as also suggested by quantitative PCR data.