Furvina (G-1) in vitro effectiveness on microorganisms isolated from skin infections in dogs

Los objetivos del presente estudio consistieron en aislar microorganismos de la piel de caninos con piodermitis de la ciudad de Santa Clara, Cuba, y evaluar la actividad in vitro de la furvina frente a los microorganismos aislados. La resistencia a los agentes antibacterianos se determinó mediante el método de difusión en agar y la actividad in vitro se evaluó cuantitativamente mediante macrodilución en caldo según procedimientos internacionales. Se identificaron 50 cepas multirresistentes, siendo 47 del género Staphylococcus y 3 del género Pseudomonas. El test exacto de Fisher demostró sensibilidad altamente significativa de los microorganismos del género Staphylococcus para la ciprofloxacina. Todas las cepas fueron resistentes al menos a tres de los antibacterianos enfrentados. Las muestras evaluadas mostraron una Concentración Inhibitoria Mínima (CIM) entre 2-16 g/ml frente a furvina, destacándose que el 83.2% de las cepas osciló entre 4 y 8 g/ml, y una Concentración Bactericida Mínima (CBM) entre 4-32 g/ml, resaltando que el 86.2% de los aislados osciló entre 8 y 16 g/ml. Todas las cepas evaluadas mostraron una CIM50 frente a furvina de 5.59 g/ml (4.70-6.48) y una CBM50 de 11.8 g/ml (10.0-13.6). Los resultados permiten inferir que furvina posee una actividad bactericida in vitro frente a las cepas sensibles y resistentes aisladas de lesiones en la piel de caninos.The aim of this study was to evaluate the in vitro activity of furvina against microorganisms isolated from the skin of canines with piodermatitis in of Santa Clara, Cuba. Resistance to antibacterial agents was assessed by the diffusion method in agar and the in vitro activity was evaluated quantitatively by the broth macrodilution method according to international clinical laboratory standards. Fifty multiresistant strains were identified, 47 from the genus Staphylococcus and 3 from Pseudomonas. The Fisher’s exact test showed highly significant sensibility of microorganisms of the genus Staphylococcus to ciprofloxacin. All strains were resistant to at least three antimicrobials. The Minimum Inhibitory Concentration (MIC) for furvina ranged from 2-16 mg/ml where 83.2% of the strains having a MIC of 4-8 mg/mL. The Minimum Bactericidal Concentration (MBC) ranged from 4-32 mg/ml where 86.2% of the isolates oscillating between 8 and 16 mg/ml. All strains showed a MIC50 against furvina of 5.59 μg/ml (4.70-6.48) and a MBC50 of 11.8 μg/ml (10.0-13.6). These results may infer that furvina exhibits an in vitro bactericidal activity against sensitive and resistant bacteria from canine skin lesions

3-Alkoxy-1-Benzyl-5-Nitroindazole Derivatives Are Potent Antileishmanial Compounds

Indazoles have previously been identified as molecules with antiprotozoal activity. In this study, we evaluate the in vitro activity of thirteen 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) against L. amazonensis, L. infantum, and L. mexicana. In vitro, cytotoxicity against mouse peritoneal macrophages and growth inhibitory activity in promastigotes were evaluated for all compounds, and those showing adequate activity and selectivity were tested against intracellular amastigotes. Transmission and scanning electron microscopy were employed to study the effects of 3-alkoxy-1-benzyl-5-nitroindazole and 2-benzyl-5-nitroindazolin-3-one derivatives on promastigotes of L. amazonensis. Compounds NV6 and NV8 were active in the two life stages of the three species, with the latter showing the best indicators of activity and selectivity. 3-alkoxy-1-benzyl-5-nitroindazole derivatives (series D) showed in vitro activity comparable to that of amphotericin B against the promastigote stage of Leishmania spp. Two compounds were also found to be active the amastigote stage. Electron microscopy studies confirmed the antileishmanial activity of the indazole derivatives studied and support future research on this family of compounds as antileishmanial agents

DISTRIBUCIÓN Y ABUNDANCIA DE GASTRÓPODOS FLUVIALES Y TERRESTRES CON VARIABLES METEOROLÓGICAS MEDIANTE LA MODELACIÓN MATEMÁTICA. SANTA CLARA, VILLA CLARA, CUBA

Los moluscos son un grupo altamente diverso en apariencia, anatomía, fisiología y ecología y representa el segundo mayor grupo de invertebrados. El objetivo del presente trabajo consistió en confeccionar un modelo matemático en función de variables meteorológicas, que permita predecir la distribución y abundancia de los gasterópodos fluviales y terrestres en el municipio Santa Clara, Cuba. Para ello se analizaron las cinco áreas de salud del municipio, en el período comprendido entre marzo y julio del 2019. Se colectaron especímenes en los ecosistemas con uso humano de estas áreas de salud, así como datos meteorológicos de la estación que mantiene vigilancia sobre ellas. En el desarrollo del modelo predictivo se empleó la Modelación Objetiva Regresiva (ROR). El área de salud con una mayor abundancia y diversidad de gasterópodos fue Capitán Roberto Fleites, la especie fluvial con una mayor distribución resultó ser Physella acuta (Draparnaud, 1805) y la más abundante, Tarebia granifera (Lamarck, 1816). En el caso de las especies terrestres ambos valores correspondieron a Praticolella griseola (Pfeiffer, 1841). Las variables meteorológicas con mayor influencia sobre los gasterópodos fueron las temperaturas y las precipitaciones; a medida que estas aumentan, disminuyen las cantidades de gasterópodos. El modelo de predicción introdujo a la temperatura mínima y la humedad relativa mínima como variables directamente proporcionales a la cantidad de gasterópodos; por otra parte, introdujo a la precipitación y la presión atmosférica como variables inversamente proporcionales. La influencia predicha del anticiclón del Atlántico resultó ser inversamente proporcional a la cantidad de gasterópodos esperada

Measuring the Performance of Computer Vision Systems in Malaria Studies

Digital image processing-computer vision (DIP-CV) systems are used to automate malaria diagnosis through microscopy analysis of thin blood smears. Some variability is observed in the experimental design to evaluate the statistical measures of performance (SMP) of such systems. The objective of this work is assessing good practices when using SMP to evaluate DIP-CV systems for malaria diagnosis. A mathematical model was built to characterize diagnosis using DIP-CV systems and used to obtain curve families showing the relationships among various SMP of these systems, both using theoretical equations and computer simulation. Curve families showing (a) the relationships among the minimum number of positive erythrocytes (RBCs) to be observed, the per object (RBC) sensitivity and the probability to detect at least one positive, (b) per specimen sensitivity vs. total number of RBCs observed for a typical per object sensitivity and a range of parasite densities (c) per object positive predictive value vs. per object specificity for a typical per object sensitivity and various parasite densities. When determining the per specimen sensitivity, the parasite density p showed to have more influence on the number of RBCs that must be analyzed than the per object sensitivity. Measuring p accurately depends heavily upon the per object positive predictive value of the classifier. For low p values, this would require very high per object specificity and a high enough value of observed RBCs to measure this accurately

Measuring the Performance of Computer Vision Systems in Malaria Studies

Digital image processing-computer vision (DIP-CV) systems are used to automate malaria diagnosis through microscopy analysis of thin blood smears. Some variability is observed in the experimental design to evaluate the statistical measures of performance (SMP) of such systems. The objective of this work is assessing good practices when using SMP to evaluate DIP-CV systems for malaria diagnosis. A mathematical model was built to characterize diagnosis using DIP-CV systems and used to obtain curve families showing the relationships among various SMP of these systems, both using theoretical equations and computer simulation. Curve families showing (a) the relationships among the minimum number of positive erythrocytes (RBCs) to be observed, the per object (RBC) sensitivity and the probability to detect at least one positive, (b) per specimen sensitivity vs. total number of RBCs observed for a typical per object sensitivity and a range of parasite densities (c) per object positive predictive value vs. per object specificity for a typical per object sensitivity and various parasite densities. When determining the per specimen sensitivity, the parasite density p showed to have more influence on the number of RBCs that must be analyzed than the per object sensitivity. Measuring p accurately depends heavily upon the per object positive predictive value of the classifier. For low p values, this would require very high per object specificity and a high enough value of observed RBCs to measure this accurately

Synthesis and in vitro and in vivo biological evaluation of substituted nitroquinoxalin-2-ones and 2,3-diones as novel trichomonacidal agents

Two series of ten novel 7-nitroquinoxalin-2-ones and ten 6-nitroquinoxaline-2,3-diones with diverse substituents at positions 1 and 4 were synthesized and evaluated against the sexually transmitted parasite Trichomonas vaginalis. Furthermore, diverse molecular and drug-likeness properties were analyzed to predict the oral bioavailability following the Lipinski's rule of five. 7-Nitroquinoxalin-2-one derivatives displayed moderate to high in vitro activity while the efficiency of most nitroquinoxaline-2,3-diones was rather low; both kinds of compounds did not show cytotoxic effects in mammalian cells. 7-Nitro-4-(3-piperidinopropyl)quinoxalin-2-one 9 achieved the highest trichomonacidal activity (IC50 = 18.26 μM) and was subsequently assayed in vivo in a murine model of trichomonosis. A 46.13% and a 50.70% reduction of pathogenic injuries were observed in the experimental groups treated orally during 7 days with 50 mg/kg and 100 mg/kg doses. The results obtained in the biological assays against T. vaginalis indicate that compounds with ω-(dialkylamino)alkyl substituents and a keto group at positions 4 and 2 of quinoxaline ring, respectively, provide interesting structural cores to develop novel prototypes to enhance the nitroquinoxalinones activity as trichomonacidal agents with interesting ADME properties according to virtual screening analysis.Peer Reviewe

A sequential procedure for rapid and accurate identification of putative trichomonacidal agents

In the current report, a sequential step-wise methodology based on in silico, in vitro and in vivo experimental procedures for the prompt detection of potential trichomonacidal drugs is proposed. A combinatorial of 12 QSAR (Quantitative Structure-Activity Relationship) models based on Linear Discrimination Analysis (LDA) are suggested for the rational identification of new trichomonacidal drugs from virtual screening of in house chemical libraries and drug databases. Subsequently, compounds selected as potential anti-trichomonas are screened in vitro against Trichomonas vaginalis. Finally, molecules with specific trichomonacidal activity are evaluated in vivo. Herein, different molecules were exposed to the proposed methodology. Firstly, the agents were virtually screened and two of the eight molecules (G-1 and dimetridazole) were classified as trichomonacidals by the 12 models. Subsequently both drugs were proved in vitro and in vivo following the workflow procedure. Although a remarkable in vitro activity was observed in both cases, dimetridazole achieved higher MIC100 activity than metronidazole against the resistant isolate. Furthermore, the in vivo models showed a remarkable reduction of lesions of more than 55% in both compounds. These observations support the current flowchart screening and suggest the use of dimetridazole as a promising drug-like scaffold for novel therapeutic alternatives against T. vaginalis resistant infections.Peer Reviewe