Synergistic effect of azithromycin on the phagocytic killing ofStaphylococcus aureus by human polymorphonuclear leukocytes

Many macrolides have been shown to affect the interaction between bacteria and various immune defense mechanisms, such as chemotaxis, accumulation, and bioactivity within phagocytic cells. The interaction of azithromycin with human polymorphonuclear leukocytes (PMNs) was studied in vitro and compared with the interactions between other macrolides and PMNs. The opsonophagocytic killing ofStaphylococcus aureus was synergistically enhanced by azithromycin at concentrations below and above the minimal inhibitory concentration, with a reduction of up to 2.82 log₁₀ cfu/ml with 2 mg/ml of azithromycin. Other macrolides were effective only at subinhibitory concentrations. The beneficial azithromycin-leukocyte interaction may explain azithromycin's efficacy against intracellular pathogens.     

Analysis of the Equalization of Inverted Repeats and Neurovirulence Using a Pseudorabies Virus Mutant Strain Altered at the Ul/Ir Junction

A recombinant pseudorabies (Aujeszky’s disease) virus (PrV) designated as vE16lac was constructed by deleting a 3-kbp DNA segment spanning the junction of long and short components of the viral genome, and by replacing the deleted segment with a lacZ-expression cassette. The aim of constructing this mutant was (a) to determine whether the terminal repeat (Tr) can serve as a template for the regeneration of the internal repeat (Ir), and (b) whether this deletion causes a reduction in the neuroinvasiveness of the virus. To analyze the mechanism of equalization, revertant viruses were selected and structurally characterized from vE16lac infection of PK-15 cells, mice and pigs. Because all revertants acquired Ir sequences identical to that of the wild-type virus, the equalization process occurred using the Tr as a template to reconstitute the Ir. We also found that the recombinant virus vE16lac was virulent in both pigs and mice. The data are discussed in view of studies performed with similar PrV mutants by other authors (Rall et al., 1992, Dean and Cheung, 1995 and Dean et al., 1996). This revised version was published online in July 2006 with corrections to the Cover Date.     

The experimental receptivity ofHelicella (Helicella) itala andCepaea nemoralis (Mollusca,Helicidae) to larvae ofMuellerius sp. andNeostrongylus linearis (Nematoda,Protostrongylidae) from chamois (Rupicapra rupicapra)

Two batches ofHelicella (H.) itala (adult specimens) and two ofCepaea nemoralis (adult and young specimens) were experimentally infected with larvae I (L-I) ofMuellerius sp. andNeostrongylus linearis obtained from the lungs and faeces ofRupicapra rupicapra. In assess larval development, the number and percentage of the total number of larvae (L-I+L-II+L-III) per mollusc were studied, together with the number and percentage of L-III per snail and the days on which the different larval stages were reached. The development ofMuellerius sp. andN. linearis was greater in larvae from faeces. For both species of molluscs, the values for the percentages of the total number of larvae and L-III were higher inN. linearis than inMuellerius sp., but there were no notable differences in the days on which the various larval stages were reached. Both nematodes achieved a greater degree of development in young specimens ofC. nemoralis than in adults. Whether the larvae came from facces or the lungs,H. (H.) itala was a better intermediate host thanC. nemoralis forMuellerius sp. andN. linearis.     

Evaluation of the mutagenic and cytotoxic effects of mercurous chloride by the micronuclei technique in golden Syrian hamsters

The aims of this study were to evaluate the mutagenic and cytotoxic activity of mercurous chloride by the micronucleus technique in vivo on the bone marrow of golden Syrian hamsters after a single i.p. drug administration. Forty male golden Syrian hamsters were classified into eight groups: negative control, positive control and six groups treated with different doses of mercurous chloride (1.25, 2.5, 5, 10, 20 and 40 mg/kg). The negative control was injected with physiological saline i.p. and the positive control with cyclophosphamide at a dose of 80 mg/kg i.p. With respect to mutagenic effect, the average number of micronucleated polychromatic erythrocytes (MPE) in hamsters treated with different doses of mercurous chloride was not significant compared with the negative control. With respect to cytotoxic effect, the average polychromatic erythrocyte/red blood cell ratio showed a significant decrease when the doses were higher than the 2.5 mg/kg dose compared with the negative control. In conclusion, this preliminary study shows a cytotoxic effect but not a mutagenic effect of calomel in vivo at one time point (24 h).     

Heat-shock protein (HSP70-2) allelic frequencies in three distinct Mexican populations

The major histocompatibility complex (MHC) genes are highly polymorphic and therefore have been useful in population genetics and disease association studies. We analyzed restriction fragment length polymorphism of HSP70-2 alleles in healthy unrelated Mestizo, Mazatecan and Nahua populations. Both Indian groups, Mazatecans and Nahuas, were in Hardy-Weinberg equilibrium, while Mestizos were in disequilibrium (chi 2 = 0.399; P < 0.05). The Mazatecan Indians presented a high frequency of BB homozygosity (17.35%) compared to Mestizos (5%) (P = 0.01). Mexican ethnic groups present differences in distribution of BB genotype. The low frequency of BB genotype in Mestizos may be the result of a negative selection process.     

Herpes Simplex Virus Type 1 (HSV-1) Strain HSZP Host Shutoff Gene: Nucleotide Sequence and Comparison with HSV-1 Strains Differing in Early Shutoff of Host Protein Synthesis

The UL41 gene of the HSZP strain of herpes simplex virus type 1 (HSV-1) defective with respect to the early shutoff of host protein synthesis was sequenced and compared with the corresponding HSV-1 strain KOS and 17 gene sequences. In comparison with strain 17, nine mutations (base changes) were HSZP specific, five KOS specific and four were common for both strains. Nine mutations caused codon changes. Three of these mapped to the nonconserved regions and the others to the conserved regions of the functional map of UL4l gene. One KOS specific mutation mapped to the region responsible for the binding of the virion host shutoff (vhs) protein to the alpha-transinducing factor (VP16). The possible relationship between mutations and host shutoff function is discussed. The nucleotide sequence data of the UL41 gene of HSZP and KOS have been submitted to the Genbank nucleotide database and have been assigned the accesion numbers Z72337 and Z72338. This revised version was published online in July 2006 with corrections to the Cover Date.     

Heterogeneity in the plasma levels of two acute-phase proteins in mice from inbred strains infected withTrypanosoma cruzi

We analyzed the variations observed in the plasma levels of both alpha-macroglobulins (AM) and serum amyloid P (SAP) in mice from three different inbred strains (C3H, Balb/C and C57black/6) acutely infected withTrypanosoma cruzi. SAP levels increased in C57black/6 and Balb/C mice but not C3H mice. AM levels increased in all C3H mice but not in C57black/6 mice and rose slightly in only 43% of the Balb/C mice. AM and SAP levels are differently modulated in patterns that may be strain-determined.     

Hyaluronan-related limited concentration by the immature kidney

The limited renal concentration performance by the immature kidney traditionally is thought to be attributed to blunted renal response to arginine vasopressin (AVP) and medullary hypotonicity. The diminished AVP-dependent osmotic water permeability of the collecting duct is the result of decreased AVP binding and adenylate cyclase activation, and low expression of aquaporin-2 (AQP2) mRNA and low levels of AQP2 protein. Moreover, the immature kidney fails to establish deep cortico-papillary osmotic gradient because of structural immaturity, limited solute transport and increased medullary blood flow. Based on indirect clinical and experimental evidences this article puts forward a hypothesis that during perinatal period the abundant hyaluronan (HA) content in the renomedullary interstitium has a primary role in antagonizing water reabsorption and limiting concentration performance. Hydration-related alterations in renal HA appears to be mediated by antidiuretic hormone.The concept of HA-mediated renal water transport may imply that interfering selectively with renal HA metabolism may provide a new therapeutic approach to promote diuresis or antidiuresis, respectively, according to the elevation or reduction in renomedullary HA.     

CD4 and CD8 act as co-receptors during thymic selection of the T cell repertoire

The selection of T cell receptor specificities must logically not only involve the alpha beta-TCR but, also the CD4 and CD8 molecules, as antigen recognition by the alpha beta-TCR on mature T cells is facilitated by the CD4 and CD8 co-receptors. In this review, the studies that provided key advances in our understanding of the possible role of CD4 and CD8 in T cell development will be discussed.