Determination of Cell Proliferation and Apoptosis in Placentas of Chronically Stressed Rats

Chronic stress during gestation can alter several mechanisms that maintain homeostasis in the placenta. The aim of this study was to determine both effects of chronic stress on the apoptotic and cell proliferation processes in placentas of rats, during the second half of pregnancy and the immunolocalization of apoptotic and proliferating marked nuclei in the different placental zones. Stress by immobilization was applied to rats from the 4th day of pregnancy until their sacrifice on days 12, 17 or 21. Placental sections were immunolabeled with anti-BrdU and TUNEL. The apoptotic index did not present significant differences between control and stress groups. The gestational day influenced significantly on the apoptotic index, which showed a significant decrease on day 17 of gestation and significant increase on day 21. The proliferating index presented significant differences between gestational stages studied, which showed a significant increase at day 17 and then a significant decrease at day 21. Moreover, the stress treatment applied highly influenced on the proliferation index. In conclusion, chronic stress by immobilization did not produce effects on apoptotic process. However it produces an increase in cellular proliferation index in the three gestation days analyzed, which could generate a deleterious environment for the fetus developmentFil: Cots, Debora Soledad. Universidad Nacional de Rio Cuarto. Facultad de Agronomia y Veterinaria. Departamento de Anatomia Animal. Laboratorio de Biología Cecular y Embriologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Rolando, Alicia Nelida. Universidad Nacional de Rio Cuarto. Facultad de Agronomia y Veterinaria. Departamento de Anatomia Animal. Laboratorio de Biología Cecular y Embriologia; ArgentinaFil: Mugnaini, Maria Teresa. Universidad Nacional de Rio Cuarto. Facultad de Agronomia y Veterinaria. Departamento de Anatomia Animal. Laboratorio de Biología Cecular y Embriologia; ArgentinaFil: Soñez, Carlos Alberto. Universidad Nacional de Rio Cuarto. Facultad de Agronomia y Veterinaria. Departamento de Anatomia Animal. Laboratorio de Biología Cecular y Embriologia; ArgentinaFil: Bozzo, Aida Andrea. Universidad Nacional de Rio Cuarto. Facultad de Agronomia y Veterinaria. Departamento de Anatomia Animal. Laboratorio de Biología Cecular y Embriologia; ArgentinaFil: Borghi, Damiana. Universidad Nacional de Rio Cuarto. Facultad de Agronomia y Veterinaria. Departamento de Anatomia Animal. Laboratorio de Biología Cecular y Embriologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba; ArgentinaFil: Gauana, Hector Fernando. Universidad Nacional de Rio Cuarto. Facultad de Agronomia y Veterinaria. Departamento de Anatomia Animal. Laboratorio de Biología Cecular y Embriologia; ArgentinaFil: Romanini, María Cristina. Universidad Nacional de Rio Cuarto. Facultad de Agronomia y Veterinaria. Departamento de Anatomia Animal. Laboratorio de Biología Cecular y Embriologia; Argentin

Screen of Unfocused Libraries Identified Compounds with Direct or Synergistic Antibacterial Activity

Antibiotic resistance is an increasingly important global public health issue, as major opportunistic pathogens are evolving toward multidrug- and pan-drug resistance phenotypes. New antibiotics are thus needed to maintain our ability to treat bacterial infections. According to the WHO, carbapenem-resistant Acinetobacter, Enterobactericaeae, and Pseudo- monas are the most critical targets for the development of new antibacterial drugs. An automated phenotypic screen was implemented to screen 634 synthetic compounds obtained in-house for both their direct-acting and synergistic activity. Fourteen percent and 10% of the compounds showed growth inhibition against tested Gram-positive and Gram-negative bacteria, respectively. The most active direct-acting compounds showed a broad- spectrum antibacterial activity, including on some multidrug-resistant clinical isolates. In addition, 47 compounds were identified for their ability to potentiate the activity of other antibiotics. Compounds of three different scaffolds (2-quinolones, phenols, and pyrazoles) showed a strong potentiation of colistin, some being able to revert colistin resistance in Acinetobacter baumannii

Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 3. Synthesis, Structure-Affinity Relationships, and Pharmacological Characterization of 6-Substituted 4-Quinolone-3-carboxamides as Highly Selective Cannabinoid-2 Receptor Ligands

A set of quinolone-3-carboxamides 2 bearing diverse substituents at position 1, 3, and 6 of the bicyclic nucleus was prepared. Except for six compounds exhibiting Ki >100 nM, all the quinolone-3- carboxamides 2 proved to be high affinity CB2 ligands, with Ki values ranging from 73.2 to 0.7 nM and selectivity [SI=Ki(CB1)/Ki(CB2)] varying from >14285 to 1.9, with only 2ah exhibiting a reverse selectivity (SI<1). In the formalin test of peripheral acute and inflammatory pain in mice, 2ae showed analgesic activity that was antagonized by a selective CB2 antagonist. By contrast, 2e was inactive per se and antagonized the effect of a selective CB2 agonist. Finally, 2g and 2p exhibited CB2 inverse agonistlike behavior in this in vivo test. However, two different functional assays carried out in vitro on 2e and 2g indicated for both compounds an overall inverse agonist activity at CB2 receptors