RESUMEN
Florfenicol, a structural analog of thiamphenicol, has broad-spectrum antibacterial activity against gram-negative and gram-positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic-pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK-PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC50 (8 µg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time-killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC24 hr , AUC0-∞ , Tmax , T1/2 , Cmax , CLb, and Ke were 49.83, 52.33 µg*h/ml, 1.32, 10.58 hr, 9.12 µg/ml, 0.50 L/hr*kg, 0.24 hr-1 and 134.45, 138.71 µg*hr/ml, 2.05, 13.01 hr, 16.57 µg/ml, 0.18 L/hr*kg, 0.14 hr-1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 µg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 µg/ml) for clinical use, but these predicted data should be validated in the clinical practice.
Asunto(s)
Antibacterianos/uso terapéutico , Infecciones por Escherichia coli/veterinaria , Escherichia coli/efectos de los fármacos , Tianfenicol/análogos & derivados , Animales , Antibacterianos/administración & dosificación , Antibacterianos/sangre , Infecciones por Escherichia coli/tratamiento farmacológico , Femenino , Masculino , Pruebas de Sensibilidad Microbiana/veterinaria , Método de Montecarlo , Porcinos , Enfermedades de los Porcinos/tratamiento farmacológico , Enfermedades de los Porcinos/microbiología , Tianfenicol/administración & dosificación , Tianfenicol/sangre , Tianfenicol/uso terapéuticoRESUMEN
Arctigenin (ACT) is a phenylpropanoid dibenzylbutyrolactone lignan extracted from the traditional herb Arctium lappa L. (Compositae) with anti-viral and anti-inflammatory effects. Here, we investigated the antiviral activity of ACT found in traditional Chinese medicine on porcine circovirus type 2 (PCV2) in vitro and in vivo. Results showed that dosing of 15.6-62.5µg/mL ACT could significantly inhibit the PCV2 proliferation in PK-15 cells (P<0.01). Dosing of 62.5µg/mL ACT 0, 4 or 8h after challenge inoculation significantly inhibited the proliferation of 1MOI and 10MOI in PK-15 cells (P<0.01), and the inhibitory effect of ACT dosing 4h or 8h post-inoculation was greater than 0h after dosing (P<0.01). In vivo test with mice challenge against PCV2 infection demonstrated that intraperitoneal injection of 200µg/kg ACT significantly inhibited PCV2 proliferation in the lungs, spleens and inguinal lymph nodes, with an effect similar to ribavirin, demonstrating the effectiveness of ACT as an antiviral agent against PCV2 in vitro and in vivo. This compound, therefore, may have the potential to serve as a drug for protection of pigs against the infection of PCV2.
Asunto(s)
Antivirales/farmacología , Infecciones por Circoviridae/veterinaria , Circovirus/efectos de los fármacos , Furanos/farmacología , Lignanos/farmacología , Enfermedades de los Porcinos/prevención & control , Animales , Arctium/química , Infecciones por Circoviridae/prevención & control , Infecciones por Circoviridae/virología , Circovirus/fisiología , Femenino , Inyecciones Intraperitoneales , Medicina Tradicional China , Ratones , Ratones Endogámicos BALB C , Distribución Aleatoria , Porcinos , Enfermedades de los Porcinos/virologíaRESUMEN
The surface glycoproteins of coronaviruses play an important role in receptor binding and cell entry. Different coronaviruses interact with their specific receptors to enter host cells. Lentiviruses pseudotyped with their spike proteins (S) were compared to analyze the entry efficiency of various coronaviruses. Our results indicated that S proteins from different coronaviruses displayed varied abilities to mediate pseudotyped virus infection. Furthermore, the cell tropisms of porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) have been characterized by live and pseudotyped viruses. Both live and pseudoviruses could infected Vero- CCL-81 (monkey kidney), Huh-7 (human liver), and PK-15 (pig kidney) cells efficiently. CCL94 (cat kidney) cells could be infected efficiently by TGEV but not PEDV. Overall, our study provides new insights into the mechanisms of viral entry and forms a basis for antiviral drug screening.