The novel anti-inflammatory agent VA694, endowed with both NO-releasing and COX2-selective inhibiting properties, exhibits NO-mediated positive effects on blood pressure, coronary flow and endothelium in an experimental model of hypertension and endothelial dysfunction.

Selective cyclooxygenase 2 (COX2) inhibitors (COXIBs) are effective anti-inflammatory and analgesic drugs with improved gastrointestinal (GI) safety compared to nonselective nonsteroidal anti-inflammatory drugs known as traditional (tNSAIDs). However, their use is associated with a cardiovascular (CV) hazard (i.e. increased incidence of thrombotic events and hypertension) due to the inhibition of COX2-dependent vascular prostacyclin. Aiming to design COX2-selective inhibitors with improved CV safety, new NO-releasing COXIBs (NO-COXIBs) have been developed. In these hybrid drugs, the NO-mediated CV effects are expected to compensate for the COXIB-mediated inhibition of prostacyclin. This study evaluates the potential CV beneficial effects of VA694, a promising NO-COXIB, the anti-inflammatory effects of which have been previously characterized in several in vitro and in vivo experimental models. When incubated in hepatic homogenate, VA694 acted as a slow NO-donor. Moreover, it caused NO-mediated relaxant effects in the vascular smooth muscle. The chronic oral administration of VA694 to young spontaneously hypertensive rats (SHRs) significantly slowed down the age-related development of hypertension and was associated with increased plasma levels of nitrates, stable end-metabolites of NO. Furthermore, a significant improvement of coronary flow and a significant reduction of endothelial dysfunction were observed in SHRs submitted to chronic administration of VA694. In conclusion, VA694 is a promising COX2-inhibiting hybrid drug, showing NO releasing properties which may mitigate the CV deleterious effects associated with the COX2-inhibition.

More experience on the microagglutination test in the diagnosis of Legionella pneumophila infection.

The sensitivity of the indirect immunofluorescence (IFA) test in Legionella pneumophila infection is said to be maximal when a plyimmunoglobulin conjugate is used. However commercially available non-class-specific fluorescent antisera are not always sensitive enough to detect IgM antibodies as class-specific conjugates do. IFA test's drawback is its inability to detect early stages of infection. We routinely performed the microagglutination (MA) test in order to check the reliability of this test alone in screening diagnostic work for L. pneumophila group 1 infections. The 252 sera tested were from suspected or confirmed legionellosis cases. Five-hundred and thirty sera from healthy-people, 49 sera from patients with serologically confirmed chlamydia, coxiella and mycoplasma pneumonia, and ten sera from patients with Pseudomonas aeruginosa infection were used as controls. There was a good agreement between IFA and MA tests, the MA proving almost as specific as, and in some cases more sensitive than the IFA test. This was particularly evident in early stages of infection. For these reasons, together with its low cost and the ease to perform, it appears that the MA test can be a useful screening test for presumptive cases of legionellosis even on a single serum specimen.

Upper limit of normal titer for Legionella pneumophila group 1 by indirect immunofluorescence and microagglutination tests in healthy population in Italy.

The background prevalence of antibody to Legionella pneumophila group 1 in two groups of healthy population of the areas of Milano and Roma, Italy, was determined by testing single serum specimens from 530 blood donors by indirect immunofluorescence (IFA) test and by microagglutination (MA). The upper limit of normal (ULN) titer was found to be 16 by IFA and 8 by MA. There was little difference in the prevalence of titers in the two geographic regions. Of the 486 subjects from whom data were available titers above the ULN value did not vary significantly with age or sex. Considering the possibility of an equivocal area IFA titers greater than 64 and MA titers greater than 16 in single serum specimens can be considered as presumptive of infection.

Comparison of phenol- and heat-killed antigens in the indirect immunofluorescence test for serodiagnosis of Legionella pneumophila group 1 infections.

An antigen prepared with agar-grown Legionella pneumophila group 1 killed by 0.5% phenol and suspended in 0.5% yolk sac was examined for use in the indirect immunofluorescence test for legionellosis and compared with a heat-killed antigen. The serological results of the two antigens for single and paired sera agreed well. Morphological and staining characteristics were better for phenol-treated organisms. Electron microscopy observation showed an apparently well-preserved cell surface. The background antibody level among a healthy control population was very low (3.4% with titers of greater than or equal to 16). Sera of patients with gram-negative bacteria infections (Yersinia enterocolytica, Campylobacter jejuni, Salmonella typhimurium, Escherichia coli, Brucella melitensis, Pseudomonas aeruginosa, Mycoplasma pneumoniae, Coxiella burnetti, and Chlamydia psittaci) showed no cross-reactions with the phenol-killed antigen. The data suggest that phenol-killed antigen is sensitive and specific. This antigen is stable for at least 1 year.