-The body's early defence in response to trauma, inflammation or infection, the acute phase response, is a complex set of systemic reactions seen shortly after exposure to a triggering event. One of the many components is an acute phase protein response in which increased hepatic synthesis leads to increased serum concentration of positive acute phase proteins. The serum concentration of these acute phase proteins returns to base levels when the triggering factor is no longer present. This paper provides a review of the acute phase proteins haptoglobin, C-reactive protein and serum amyloid A and their possible use as non-specific indicators of health in large animal veterinary medicine such as in the health status surveillance of pigs at the herd level, for the detection of mastitis in dairy cattle and for the prognosis of respiratory diseases in horses.

Alternatives to traditional antibiotics and to antiviral and anti-inflammatory drugs are much in need and the molecular design and development of anti-infective compounds constitute a pivotal area in modern medicinal research. Dendrimers are a relatively new class of structurally well-defined, i.e. monodisperse, synthetic polymers with hyperbranched structures which enable a given molecular motif to be presented in a highly multivalent fashion. Several types of dendrimers with various structural elements and molecular dimensions are commercially available at an affordable price. The surface of dendrimers can be modified relatively easily and, depending on the surface motif, the pharmacological properties of the dendrimer such as cytotoxicity, bacteriocidal and virucidal effect, biodistribution and biopermeability may be modulated to fit a specific medicinal purpose. Dendrimers are thus highly suitable tools in drug discovery and they allow the synthesis of molecules with high and specific binding affinities to a wide variety of receptors, viruses and bacteria. Hence the use of dendrimers for the development of antiviral or antibacterial drugs, destroying the infective agent or disrupting multivalent binding interactions between the infective agent and cells of the host organism has become a highly active research field. The wide range of applications reported for the use of dendrimers as anti-infective and anti-inflammatory drugs in the patent literature demonstrates the general applicability of these molecules as drug candidates. The present review will briefly treat the intrinsic properties of dendrimers in biological systems, as well as general concerns regarding the treatment of infective diseases. The use of dendrimers as anti-infective and anti-inflammatory drugs will be based on a thorough review of the recent patent literature.

A biotinylated peptide covering a sequence of 21 amino acids (aa) from the erythrocyte binding antigen (EBA-175) of Plasmodium falciparum bound to human glycophorin A, an erythrocyte receptor for merozoites, as demonstrated by enzyme-linked immunosorbent assay (ELISA) and to erythrocytes as demonstrated by flow cytometry analysis. The peptide, EBA(aa1076-96), also bound to desialylated glycophorin A and glycophorin B when tested by ELISA. The peptide blocked parasite multiplication in vitro. The glycophorin A binding sequence was further delineated to a 12-aa sequence, EBA(aa1085-96), by testing the binding of a range of truncated peptides to immobilized glycophorin A. Our data indicate that EBA(aa1085-96) is part of a ligand on the merozoite for binding to erythrocyte receptors. This binding suggests that the EBA(aa1085-96) peptide is involved in a second binding step, independent of sialic acid. Antibody recognition of this peptide sequence may protect against merozoite invasion, but only a small proportion of sera from adults from different areas of malaria transmission showed antibody reactivities to the EBA(aa1076-96) peptide, indicating that this sequence is only weakly immunogenic during P. falciparum infections in humans. However, Tanzanian children with acute clinical malaria showed high immunoglobulin G reactivity to the EBA(aa1076-96) peptide compared to children with asymptomatic P. falciparum infections. The EBA(aa1076-96) peptide sequence from EBA-175 induced antibody formation in mice after conjugation of the peptide with purified protein derivative. These murine sera inhibited EBA(aa1076-96) peptide binding to glycophorin A.

The V3 domain is highly variable and induces HIV neutralizing antibodies (NA). Here we addressed the issues of 1) the participation of mutations in V3 in generation of neutralization resistant escape virus in vivo and 2) the applicability of synthetic V3 peptides corresponding to field isolates to induce neutralizing immune sera. Seven peptides corresponding to the V3 region of primary and escape virus from 3 HIV-1 infected patients were synthesized and used for antibody (Abs) studies and immunizations. The anti-V3 Abs titre in patient serum was generally low against peptides corresponding to autologous virus isolated later than the serum sample in contrast to the titre against peptides corresponding to virus isolated earlier than the serum sample. Furthermore, neutralizing anti-V3 monoclonal antibodies (MAbs) raised against V3 peptides from laboratory strains of HIV-1 showed distinct binding patterns against V3 peptides corresponding to sequential primary and escape field isolates, with the strongest reactivity against late isolated escape virus. These observations suggest that the neutralization epitope was influenced by the appearance of mutations. When used as immunogen in rabbits, V3 peptides corresponding to field isolates were highly immunogenic but failed to induce neutralizing or gp120-precipitating Abs. On the contrary, V3 peptide corresponding to the laboratory strain HXB2 induced HIV neutralizing, gp120-precipitating immune serum. In conclusion, these data suggest a participation of the V3 domain in the immunoselection of escape virus, and that V3 on early field virus is less accessible to NA than that on laboratory strains.

BackgroundPorcine circovirus type 2 (PCV2) and Lawsonia intracellularis infections can cause enteritis in pigs. A Danish study showed a significantly higher probability of detecting PCV2 without concurrent L. intracellularis infection, indicating that one of these pathogens has an impact on the dynamics of the other. Therefore, a delayed co-infection model was set up, initially aiming at investigating the interaction between PCV2 and L. intracellularis in pigs challenged with PCV2 and 2 weeks later with L. intracellularis. But due to PCV2 contamination of the L. intracellularis inoculum the aim was revisited to describing the infection dynamics and pathogenesis of pigs infected with PCV2 followed by delayed simultaneous exposure to PCV2 and L. intracellularis. Twenty-four high-health piglets were divided into three groups of eight pigs (A, B, C) and inoculated at experimental day (EXD) 0 with mock (groups A and B) or PCV2 (group C), and at EXD 14 with mock (group A) or L. intracellularis/PCV2 (groups B and C). The pigs underwent daily clinical examination, and were necropsied at EXD 51–52. Furthermore, histology, immunohistochemistry, serology and PCR for PCV2 and L. intracellularis, and measurement of C-reactive protein were carried out.ResultsGroup A remained negative for PCV2 and L. intracellularis. Following inoculation with L. intracellularis/PCV2, no significant differences were observed between group B and C, however pigs already infected with PCV2 (group C) showed milder clinical signs and exhibited milder intestinal lesions, less shedding of L. intracellularis and developed higher L. intracellularis antibody titers than the pigs in group B that only received the combined infection. Though the differences between group B and C were non-significant, all results pointed in the same direction, indicating that the pigs in group B were more affected by the L. intracellularis infection compared to the pigs in group C.ConclusionsPrevious exposure to PCV2 had limited impact on the subsequent exposure to a combined L. intracellularis/PCV2 inoculation. However, there was a tendency that the infection dynamics of PCV2 and development of antibodies to PCV2 and L. intracellularis were altered in pigs previously exposed to PCV2. These differences should be confirmed in further experimental trials.