Multitarget neuroprotection by quercetin: Changes in gene expression in two perinatal asphyxia models.

Hypoxic-ischemic encephalopathy (HIE) causes mortality and long-term neurologic morbidities in newborns, affecting pathways related to energy failure, excitotoxicity and oxidative stress that often lead to cell death. The whole process of HIE injury is coupled to changes in the expression of a great array of proteins. A nanoliposomal preparation of the flavonoid quercetin has been shown to exert neuroprotective effects in perinatal asphyxia models. This study aimed to identify neonatal HIE markers and explore the effect of quercetin administration in two perinatal asphyxia models: newborn rats and piglets. In the rat model, nanoliposomal quercetin administration reduced mortality after asphyxia. In the piglet model, quercetin partially overrode the reduction of HIF-1α mRNA levels in the cortex induced by asphyxia. Quercetin administration also reduced increased level of HO-1 mRNA in asphyctic piglets. These results suggest that quercetin neuroprotection might be involved in the regulation of HIF-1α, HO-1 and their targets. A proteomic approach revealed that the glycolytic pathway is strongly regulated by quercetin in both species. We also identified a set of proteins differentially expressed that could be further considered as markers. In piglets, this set includes Acidic Leucine-rich nuclear phosphoprotein 32 (ANP32A), associated with nervous system differentiation, proteins related with death pathways and alpha-enolase which can be converted to neuron-specific enolase, a glycolytic enzyme that may promote neuroprotection. In newborn rats, other promising proteins associated with neurogenesis and neuroprotection emerged, such as dihydropyrimidinase-related proteins, catalytic and regulatory subunits of phosphatases and heterogeneous nuclear ribonucleoprotein K (hnRNPK). Our results show that a nanoliposomal preparation of quercetin, with protective effect in two HIE mammal models, modulates the expression of proteins involved in energy metabolism and other putative neuroprotective signals in the cortex. Identification of these signals could reveal potential molecular pathways involved in disease onset and the novel quercetin neuroprotective strategy.

New Approach For Simvastatin As An Antibacterial: Synergistic Effect With Bio-Synthesized Silver Nanoparticles Against Multidrug-Resistant Bacteria.

BACKGROUND: Multidrug-resistant bacteria such as extended-spectrum beta-lactamase (ESBL), Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus (MRSA) pose a challenge to the human health care system. MRSA is among the major causes of hospital-acquired and community infections. METHODS: Therefore, in the present study, we evaluated the antibacterial activity of silver nanoparticles synthesized by Fusarium oxysporum (AgNPbio) in combination with simvastatin against reference and multidrug-resistant bacterial strains. RESULTS: Simvastatin showed a minimal inhibitory concentration (MIC) ranging from 0.062 to 0.25 mg mL-1 against MRSA. AgNPbio with a size of 77.68± 33.95 nm and zeta potential -34.6 ± 12.7 mV showed an MIC of 0.212 mg mL-1 against S. aureus including MRSA strains. The checkerboard assay and time-kill curves exhibited a synergistic effect of the simvastatin-AgNPbio combination on antibacterial activity against MRSA strains. The combination of simvastatin and AgNPbio demonstrated antibacterial activity against Escherichia coli producing ESBL. Scanning electron microscopy showed the formation of cell surface protrusions after treatment with AgNPbio and the formation of a large amorphous mass after treatment with simvastatin, both in MRSA. CONCLUSION: Our results indicate that the combination of AgNPbio and simvastatin could be a great future alternative in the control of bacterial infections, where, when combined with simvastatin, smaller doses of AgNPbio are required, with the same antibacterial activity.

Diarrea aguda: Epidemiología, concepto, clasificación, clínica, diagnóstico, vacuna contra rotavirus

La enfermedad diarreica es la segunda causa de muerte en menores de cinco años. Desde la incorporación de la vacuna contra Rotavirus, se ha observado una reducción de la mortalidad por diarreas. En Venezuela, es la primera causa de consulta y hospitalización, la mortalidad disminuyó en los últimos 20 años, a más del 50%. La OMS/OPS definen la diarrea aguda como tres o más evacuaciones liquidas o semilíquidas en 24 horas o de al menos una con presencia de elementos anormales (moco, sangre, pus), durante un máximo de dos semanas. Se clasifica según: duración en aguda, persistente y crónica; etiología en infecciosa y no infecciosa; síndromes clínicos en diarreico coleriforme y diarreico disenteriforme; fisiopatológicamente en osmótica, secretora, y por alteración de la motilidad. La evaluación del paciente con diarrea debe incluir: duración, presencia de sangre, de vómito, número de deposiciones y vómitos en las primeras 24 horas, capacidad de beber, presencia e intensidad de la sed, presencia de diuresis en las últimas seis horas, medicamentos que se le han dado en el actual episodio. La diarrea con deshidratación leve a moderada no requieren estudios de laboratorio, el examen coprológico, leucocitos fecales, coproantígenos son de ayuda diagnóstica, el coprocultivo no debe ser realizado de rutina. Existe en el país dos vacunas contra Rotavirus. Se recomienda su uso a partir de los 2 meses de vida, La edad mínima para la primera dosis es 6 semanas; y la edad máxima para la primera dosis es 14 semanas y 6 días.

Diarrheal disease is the second leading cause of death in children under five years of age. Since the introduction of Rotavirus vaccine, there has been a worldwide reduction of mortality by diarrhea. In Venezuela, it is the leading cause of consultation and hospitalization. Mortality caused by diarrhea declined in the past 20 years, more than 50%. WHO/PAHO define acute diarrhea as three or more liquid or semi-liquid evacuations within 24 hours or at least one with the presence of abnormal elements (mucus, blood, pus), for a maximum of two weeks duration. Diarrhea is classified according to duration in acute, persistent and chronic; according to etiology in infectious and non-infectious; clinical syndromes are classified in choleriform and disenteriform diarrhea; pathogenesis may be osmotic, secretory or by disruption of motility. Patient evaluation should include assessment of duration, presence of blood, presence of vomiting, number of bowel movements in the first 24 hours, ability to drink, presence and intensity of thirst, presence of urinary output in the last six hours, drugs that have been given during the current episode. Mild to moderate diarrhea with dehydration do not require laboratory studies, stool test, fecal leukocytes, coproantigens are diagnostic aids. Stool culture should not be of routine practice. There are two Rotavirus vaccines in the country. They are recommended after 2 months of age. The minimum age for the first dose is 6 weeks; and the maximum age for the first dose is 14 weeks and 6 days.