Antibacterial and Sporicidal Activity Evaluation of Theaflavin-3,3'-digallate.

Theaflavin-3,3'-digallate (TFDG), a polyphenol derived from the leaves of Camellia sinensis, is known to have many health benefits. In this study, the antibacterial effect of TFDG against nine bacteria and the sporicidal activities on spore-forming Bacillus spp. have been investigated. Microplate assay, colony-forming unit, BacTiter-GloTM, and Live/Dead Assays showed that 250 µg/mL TFDG was able to inhibit bacterial growth up to 99.97%, while 625 µg/mL TFDG was able to inhibit up to 99.92% of the spores from germinating after a one-hour treatment. Binding analysis revealed the favorable binding affinity of two germination-associated proteins, GPR and Lgt (GerF), to TFDG, ranging from -7.6 to -10.3 kcal/mol. Semi-quantitative RT-PCR showed that TFDG treatment lowered the expression of gpr, ranging from 0.20 to 0.39 compared to the control in both Bacillus spp. The results suggest that TFDG not only inhibits the growth of vegetative cells but also prevents the germination of bacterial spores. This report indicates that TFDG is a promising broad-spectrum antibacterial and anti-spore agent against Gram-positive, Gram-negative, acid-fast bacteria, and endospores. The potential anti-germination mechanism has also been elucidated.

Spatiotemporal perturbations in paced finger tapping suggest a common mechanism for the processing of time errors.

Paced finger tapping is a sensorimotor synchronization task where a subject has to keep pace with a metronome while the time differences (asynchronies) between each stimulus and its response are recorded. A usual way to study the underlying error correction mechanism is to perform unexpected temporal perturbations to the stimuli sequence. An overlooked issue is that at the moment of a temporal perturbation two things change: the stimuli period (a parameter) and the asynchrony (a variable). In terms of experimental manipulation, it would be desirable to have separate, independent control of parameter and variable values. In this work we perform paced finger tapping experiments combining simple temporal perturbations (tempo step change) and spatial perturbations with temporal effect (raised or lowered point of contact). In this way we decouple the parameter-and-variable confounding, performing novel perturbations where either the parameter or the variable changes. Our results show nonlinear features like asymmetry and are compatible with a common error correction mechanism for all types of asynchronies. We suggest taking this confounding into account when analyzing perturbations of any kind in finger tapping tasks but also in other areas of sensorimotor synchronization, like music performance experiments and paced walking in gait coordination studies.

Apnea del recién nacido pretérmino / Apnea of premat urity

La apnea del recién nacido pretérmino es una condición con alto riesgo de morbimortalidad es este grupo etario, es por ello que pediatras, neonatólogos, enfermeras, terapeutas y personal en general quienes identifican y de una u otra manera intervienen en la prevención y manejo de esta patología, se ven en la necesidad de permanecer en continua actualización. Se hace una revisión de la literatura acerca de la definición, diagnóstico y tratamiento actual que se puede y debe ofrecer al recién nacido pretérmino con apnea...

Apnea in premature infants is a problem associated with high risk of morbidity and mortality in this age group. For this reason, pediatricians, neonatologists, nurses, care givers and pediatric general staff who identify, and in a way or another, intervene in preventing and managing this condition, need to continuously update. A literature review concerning, definition, diagnosis and available current treatment that must be offered to the premature infants with apnea was conducted.

Vocal caricatures reveal signatures of speaker identity.

What are the features that impersonators select to elicit a speaker's identity? We built a voice database of public figures (targets) and imitations produced by professional impersonators. They produced one imitation based on their memory of the target (caricature) and another one after listening to the target audio (replica). A set of naive participants then judged identity and similarity of pairs of voices. Identity was better evoked by the caricatures and replicas were perceived to be closer to the targets in terms of voice similarity. We used this data to map relevant acoustic dimensions for each task. Our results indicate that speaker identity is mainly associated with vocal tract features, while perception of voice similarity is related to vocal folds parameters. We therefore show the way in which acoustic caricatures emphasize identity features at the cost of loosing similarity, which allows drawing an analogy with caricatures in the visual space.

Farmacocinética de la ulamina administrada en perros como prueba aguda intravenosa e intramuscular / Pharmacokinetic disposition of ulamina in dogs administered as intravenous and intramuscular acute test

Se realizó una investigación con el objeto de describir la disposición farmacocinética del antimonial pentavalente genérico ulamina en 8 perros sanos, como prueba aguda intravenosa e intramuscular, después de administrar una dosis de 25 mg/kg. Las curvas obtenidas para ambas vías muestran un descenso de las concentraciones plasmáticas de 184,91± 86,06 μg/mL a 86,06±39,24 μg/mL y 164,61 ± 23,80 μg/mL a 100,94 ± 45,3 μg/mL, hasta la hora 4,0 para las vía IV e IM, respectivamente, que corresponden a la fase alfa de distribución. Seguidamente se aprecia un descenso lento, con antimonio detectable más allá de la hora 24 para ambas vías, denominada fase beta o de eliminación. La droga se absorbe rápidamente y mostró alta biodisponibilidad. La vida media (t1/2β) IV fue de 8,1 horas y t1/2 β IM fue 13,35 horas. El volumen de distribución (Vd) IV fue de 0,17 L/Kg e IM fue de 0,23 L/Kg. No se encontraron diferencias significativas al comparar AUC y t1/2β, después de administrar ulamina IV e IM, proponiéndose esta última como ruta de administración por resultar más práctica y segura. La ulamina constituiría una opción terapéutica para el tratamiento de la leishmaniasis humana y canina, por lo que se sugiere la aplicación de ensayos con dosis múltiples para evaluar la fase de eliminación y determinar si hay acumulación de antimonio, lo cual justificaría una disminución de la dosis.

A study was carried out to describe the pharmacokinetic disposition of pentavalent antimony generic ulamina in 8 healthy dogs in acute intravenous and intramuscular test after a dose of 25mg/Kg. The curves obtained for both routes show a decrease in plasma concentrations of 184.91 ± 86.06 μ g / mL to 86.06 ± 39.24 μ g / mL and 164.61 ± 23.80 μ g / mL to 100.94 ± 45.3, μ g / mL to 4.0 hours for the IM and IV, respectively, corresponding to the alpha phase distribution. There was a decrease slowly, with antimony detectable beyond 24.0 hours for both routes, called beta or disposal. The drug is rapidly absorbed and showed high bioavailability. The half life (t1/2β) IV was 8.1 hours and t1/2β IM was 13.35 hours. The volume of distribution (Vd) IV was 0.17 L /Kg and MI was 0.23 L /Kg. No significant differences were found when comparing AUC, and t1/2β, after IV and IM administration ulamina, proposing the latter as a more practical and safe administration route. The ulamina may be a therapeutic option for the treatment of human and canine leishmaniasis, as it is suggested by the application of multiple dose trials to evaluate the phase of removal and to determine if there is an accumulation of antimony, which would warrant a dose reduction.

Structural and photophysical properties of visible- and near-IR-emitting tris lanthanide(III) complexes formed with the enantiomers of N,N'-bis(1-phenylethyl)-2,6-pyridinedicarboxamide.

The enantiomers of N,N'-bis(1-phenylethyl)-2,6-pyridinedicarboxamide (L), namely, (R,R)-1, and (S,S)-1, react with Ln(III) ions to give stable [LnL(3)](3+) complexes in an anhydrous acetonitrile solution and in the solid state, as evidenced by electrospray ionization mass spectrometry, NMR, luminescence titrations, and their X-ray crystal structures, respectively. All [LnL(3)](3+) complexes [Ln(III) = Eu, Gd, Tb, and Yb; L = (R,R)-1 and (S,S)-1] are isostructural and crystallize in the cubic space group I23. Although the small quantum yields of the Ln(III)-centered luminescence clearly point to the poor efficiency of the luminescence sensitization by the ligand and the intersystem crossing and ligand-to-metal energy transfers, the ligand triplet-excited-state energy seems relatively well suited to sensitize many Ln(III) ion's emission for instance, in the visible (Eu and Tb), near-IR (Nd and Yb), or both regions (Pr, Sm, Dy, Er, and Tm).

Disposición farmacocinética de las especies de antimonio en perros después de una dosis de antimoniato de meglumina (Glucantime®) / Pharmacokinetic disposition of antimony species in dogs after a dose of meglumine antimonite (Glucantime®)

Se estudiaron los parámetros farmacocinéticos de las especies de antimonio (pentavalente y trivalente) presentes en el antimoniato de meglumina (Glucantime®), en cuatro perros sanos, después de la administración subcutánea de una dosis única de 90 mg/kg-1. Las muestras sanguíneas fueron analizadas por espectroscopia de absorción atómica. Después de la administración de Glucantime®, el antimonio pentavalente mostró un decaimiento en dos fases, la vida media de eliminación fue de 13,18 h, el volumen aparente de distribución de 30,65 Lkg-1, el área bajo la curva (0-24h) 48,25 μg. h mL-1 y el área bajo la curva (0-∞) μg.h mL-1. Mientras que el antimonio trivalente mostró una fase bien distinguida, con una vida media de eliminación de 16,10 h, un volumen aparente de distribución de 126,5 Lkg-1, valores de el área bajo la curva (0-24h) 10,35 μg.h L-1 y el área bajo la curva (0-∞) 7,35 μg.h mL-1. El porcentaje de conversión sistémica de antimonio pentavalente hacia antimonio trivalente a las 24 horas fue de 23,62%. A pesar del reducido tamaño de la muestra, los resultados obtenidos presentan desigualdad en la farmacocinética de las especies de antimonio en perros, estas podrían explicar, al menos parcialmente, las diferencias en la eficacia terapéutica atribuidas a las especies por separado.

Pharmacokinetics of experimental pentavalent antimony after intramuscular administration in adult volunteers.

BACKGROUND: Pentavalent antimony (SbV) has demonstrated therapeuticeffectiveness against clinical manifestations of leishmaniasis, an infection caused by Leishmania, a genus of flagellate protozoa comprising parasites of worldwide distribution. Approximately 1.8 million new cases are reported annually. OBJECTIVE: The aim of this study was to assess the pharmacokinetics of the investigational generic SbV, Ulamina (pentachloride of antimony + N-methylglucamine), in healthy adult volunteers. METHODS: In this study, SbV was administered IM as a single 5-mg/kg dose.Blood samples were collected at 0.25, 0.75, 1, 2, 4, 8, 12, and 24 hours after administration; urine samples were collected at 6-hour intervals during the 24-hour postadministration period. Determination of trivalent antimony, SbV, and total antimony concentrations in blood and urine samples was carried out using atomic absorption spectrometry. Clinical history was reviewed and the subjects were monitored before and after administration of SbV using physical examination, weight, and hepatic- and renal-function studies. The pharmacokinetic parameters calculated were Cmax, Tmax, absorption constant (Ka), elimination constant (Kel), AUC2-24h, AUC0-∞, elimination phase (t½ß), volume of distribution (Vd), and urinary excretion rate. RESULTS: Five subjects (3 men, 2 women; mean age, 28 years [range, 18-34 years]) were included in the study. One hour after drug administration the following values were obtained: Cmax, 1.1 µg/mL; Tmax, 1.3 hours; Ka, 1.87 hours; Kel, 0.043 hours; AUC0-24h, 12.26 µg/mL · h; AUC0-∞, 19.84 µg/mL · h; t½ß, 17.45 hours; Vd, 6.6 L/kg; and urinary excretion rate, 2.8 µg/h; these were mean values for the entire study group. The single dose was well tolerated by all subjects. CONCLUSIONS: The investigational generic SbV, Ulamina, was associated with linearelimination after IM administration of a single 5-mg/kg dose. A 2-compartment pharmacokinetic model was observed in these volunteers; the mean t½ß, was 17.45 hours and the mean Vd was 6.6 L/kg.