Efficiency of Monoclonal Antibodies to Detect Respiratory Virus Antigens in Clinical Specimens

The development of specific antiviral therapy has increased the need for rapid viral diagnosis and necessitates a better understanding of viral epidemiology. The purposes of this study were to determine the efficiency of immunofluorescent assay employing monoclonal antibodies from commercial sources to detect respiratory virus antigens in clinical specimens and to define the epidemiology of respiratory viruses in Bismarck, North Dakota. Throat swab, nasopharyngeal swabs and nasopharyngeal washes were excellent specimens for studying viral epidemiology; virus isolation rates were 7.7%, 33.2%, and 39.7%, respectively. Yearly epidemics of respiratory syncytial virus and influenza were observed. In contrast, parainfluenza and adenovirus infections occurred endemically throughout the study period. Children less than 6 years of age and adults greater than 50 years of age had the highest viral morbidity. Respiratory syncytial and influenza were the most frequently isolated viruses. Nasopharyngeal swab and nasopharyngeal wash specimens were evaluated for the ability to harvest ciliated epithelial cells from the upper respiratory tract. Overall, 8.7% of the specimens were unsuitable for immunofluorescent assay. The probability of specimen rejection was source- and patient age-dependent. The rejection rate for NPW specimens was more than twice that for NPS specimens and the rejection rate for specimens from patients greater than 7 years of age was approximately 5 times higher than the rate for specimens obtained from patients less than 6 years of age. Immunofluorescent assay was a sensitive and specific method for rapid diagnosis of respiratory viral infections in cell cultures. The Bartels indirect fluorescent antibody reagents exhibited acceptable levels of sensitivity (overall 84.6%, range 33.3-100%) and specificity (overall 83.3%, range 87.3-100%). The Whittaker direct fluorescent antibody reagents had poor sensitivity (overall 50%, range 18.2-94.1%) and high specificity (overall 91.5%, range 93.8-100%). The highly efficient Bartels reagents for respiratory syncytical virus and influenza A virus could be used as acceptable alternatives to culture for these viruses. The specificity of the influenza B, parainfluenza 3 and adenovirus reagents allowed for rapid presumptive diagnosis but were not sufficiently sensitive to replace culture. Shell vial assays using HEp-2 and A549 cells offered no diagnostic advantage over immunofluorescent assay or conventional tube cell culture for the identification of respiratory viruses. Immunofluorescent assay using commercial monoclonal antibodies was a sensitive and specific method for rapid diagnosis of respiratory virus infections and has the potential to replace expensive and laborious conventional culture methods

Digitale geometrische Daten 2 Teilergebnisses der Voruntersuchung zum Aufbau eines statistischen Informationssystems zur Bodennutzung

TIB Hannover: RN 9417(35) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

Novel bipharmacophoric inhibitors of the cholinesterases with affinity to the muscarinic receptors M1 and M2

A set of hybrid compounds composed of the fragment of allosteric modulators of the muscarinic receptor, i.e. W84 and naphmethonium, and the well-known AChE inhibitor tacrine on the one hand, and the skeletons of the orthosteric muscarinic agonists, iperoxo and isox, on the other hand, were synthesized. The two molecular moieties were connected via a polymethylene linker of varying length. These bipharmacophoric compounds were investigated for inhibition of AChE (from electric eel) and BChE (from equine serum) as well as human ChEs in vitro and compared to previously synthesized dimeric inhibitors. Among the studied hybrids, compound 10-C10, characterized by a 10 carbon alkylene linker connecting tacrine and iperoxo, proved to be the most potent inhibitor with the highest pIC50 values of 9.81 (AChE from electric eel) and 8.75 (BChE from equine serum). Docking experiments with compounds 10-C10, 7b-C10, and 7a-C10 helped to interpret the experimental inhibitory power against AChE, which is affected by the nature of the allosteric molecular moiety, with the tacrine-containing hybrid being much more active than the naphthalimido- and phthalimido-containing analogs. Furthermore, the most active AChE inhibitors were found to have affinity to M1 and M2 muscarinic receptors. Since 10-C10 showed almost no cytotoxicity, it emerged as a promising lead structure for the development of an anti-Alzheimer drug