RESUMEN
Dengue (DEN) is the most common cause of mosquito-borne endemic viral diseases in the tropical and subtropical countries. DEN outbreaks associated with multiple dengue virus (DV) serotypes have been regularly reported in different parts of India. This study was done during DEN outbreaks in 2015 to 2016 in UP and Bihar where DEN-2 was found as the only prevalent serotype. DV-2 was the only serotype amplified in serotype-specific reverse-transcription polymerase chain reaction from sera of 210 (65.21%) out of 322 DV NS1 antigen-positive patients. Further genetic analysis based on full-length envelope (E) protein sequence derived from patient's sera as well as DV isolate showed the circulation of lineages I and III of DV-2 cosmopolitan genotype during 2015 and lineage II during 2016. Finally, the phylogenetic analysis using the E gene sequence revealed that these DV-2 strains have a close genetic relationship with the recently reported DV-2 genotypes from DEN outbreaks reported from different parts of north India. These results showed the circulation of cosmopolitan genotype of DV-2 in eastern Uttar Pradesh and western Bihar, India. The genetic database generated on circulating DV strains in this study will be useful as reference for disease surveillance and strengthening laboratory diagnosis protocols.
Asunto(s)
Virus del Dengue/clasificación , Virus del Dengue/genética , Dengue/virología , Brotes de Enfermedades , Genotipo , Serogrupo , Dengue Grave/epidemiología , Dengue/epidemiología , Humanos , India/epidemiología , Filogenia , ARN Viral/genética , Dengue Grave/virologíaRESUMEN
Tigecycline, a novel glycylcycline antibiotic, shows atypical nonlinear plasma-protein-binding behavior using ultrafiltration and ultracentrifugation techniques. The mechanism of such counterintuitive behavior is currently unknown. Ultrafiltration and ultracentrifugation cause fractional change in protein concentration and therefore may influence plasma-protein binding. Microdialysis (MD), a novel technique, can sample unbound drugs without any change in fractional protein concentration. To determine whether the atypical nonlinear plasma-protein-binding behavior is not related to measurement technique, the plasma-protein binding of tigecycline was determined using MD. A sensitive liquid chromatography-mass spectrometry method was developed and validated for the bioanalysis of tigecycline in the dialysate. The probe recoveries and plasma-protein binding of tigecycline at four different concentration levels 0.1, 1, 10, and 100 µg/mL were determined. Similar to ultracentrifugation and ultrafiltration, MD also showed atypical nonlinear plasma-protein-binding behavior of tigecycline up to 10 µg/mL, but unbound fraction increased at 100 µg/mL indicating saturation of mechanism responsible for atypical nonlinear behavior. This study concludes that the atypical nonlinear binding behavior of tigecycline is not technique-dependent, rather it is a true behavior of tigecycline. Further investigations are necessary to elucidate the mechanism.