RESUMEN

Polycyclic aromatic hydrocarbons (PAHs), such as phenanthrene (PHE), are common pollutants found in coastal areas where shrimp farming is developed. Even though PAHs can have adverse effects on physiology, shrimp can detoxify and metabolize toxic compounds and neutralize the reactive oxygen species (ROS) produced during this process. This requires the activation of multiple antioxidant enzymes, including peroxiredoxin 6 (Prx6). Prx6 uses glutathione (GSH) to reduce phospholipid hydroperoxides, a function shared with GSH peroxidase 4 (GPx4). Prx6 has been scarcely studied in crustaceans exposed to pollutants. Herein, we report a novel Prx6 from the shrimp Penaeus vannamei that is abundantly expressed in gills and hepatopancreas. To elucidate the involvement of Prx6 in response to PAHs, we analyzed its expression in the hepatopancreas of shrimp sub-lethally exposed to PHE (3.3 µg/L) and acetone (control) for 24, 48, 72, and 96 h, along with GPx4 expression, GSH-dependent peroxidase activity, and lipid peroxidation (indicated by TBARS). We found that GPx4 expression is not affected by PHE, but Prx6 expression and peroxidase activity decreased during the trial. This might contribute to the rise of TBARS found at 48 h of exposure. However, maintaining GPx4 expression could aid to minimize lipid damage during longer periods of exposure to PHE.

Asunto(s)

Glutatión Peroxidasa , Peroxidación de Lípido , Penaeidae , Peroxiredoxina VI , Fenantrenos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Animales , Fenantrenos/toxicidad , Peroxidación de Lípido/efectos de los fármacos , Penaeidae/metabolismo , Penaeidae/efectos de los fármacos , Penaeidae/genética , Penaeidae/enzimología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Peroxiredoxina VI/metabolismo , Peroxiredoxina VI/genética , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/genética , Contaminantes Químicos del Agua/toxicidad , Hepatopáncreas/metabolismo , Hepatopáncreas/efectos de los fármacos , Branquias/metabolismo , Branquias/efectos de los fármacos , Proteínas de Artrópodos/metabolismo , Proteínas de Artrópodos/genética

RESUMEN

OBJECTIVE: This work aims to present a Quality-by-Design (QbD) step-by-step methodology to formulate anti-ulcer and gastro-protective oral suspensions. METHODS: Sucralfate was used as a drug model. The Quality Target Product Profile was established early during preformulation. Viscosity, resuspendability, pH, and density were assessed through the screening of several suspension platforms based on different prototype compositions. A compatibility study between the active pharmaceutical ingredient and the excipients was performed by thermal analysis and infrared spectroscopy. An Ishikawa fishbone diagram and Failure Mode and Effect Analysis were employed to identify the Critical Material Attributes (CMAs), Critical Process Parameters (CPPs), and Critical Quality Attributes (CQAs). CMAs' and CPPs' impact on identified CQAs was further assessed through a 22 full factorial experimental design at normal conditions after manufacture and one month at super-accelerated stress conditions. Results: The lead prototype exhibited no physicochemical incompatibilities. The risk assessment tools revealed that the concentration of the wetting agent and the total concentration of thickening agents represented critical factors for the quality profile of the preparation in terms of viscosity. The optimized formulation comprising 1.125 w/v% total concentration of Natrosol 250 HX and Avicel RC 591 exhibited an enhanced performance according to the established profile. CONCLUSIONS: The analytical and physicochemical tests showed the robustness and compliance of the final preparation with the quality profile. The proposed step-by-step methodology based on QbD, Design of Experiments, and Quality Risk Management presented in our research holds practical implications for local industries and formulation scientists involved in the development of oral suspensions.

Asunto(s)

Antiulcerosos , Química Farmacéutica , Composición de Medicamentos , Excipientes , Sucralfato , Suspensiones , Antiulcerosos/administración & dosificación , Antiulcerosos/química , Viscosidad , Excipientes/química , Sucralfato/administración & dosificación , Sucralfato/química , Administración Oral , Composición de Medicamentos/métodos , Química Farmacéutica/métodos , Concentración de Iones de Hidrógeno

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) are persistent organic pollutants ubiquitous in coastal ecosystems. The white shrimp Penaeus vannamei naturally inhabits in coastal areas and is cultivated in farms located nearby the oceans. PAHs can damage shrimp health, endanger natural populations, and lower shrimp aquaculture productivity. However, crustaceans have enzymes capable of metabolizing organic xenobiotics as PAHs and to neutralize reactive oxygen species (ROS) produced during xenobiotics metabolism. An important superfamily of xenobiotic-metabolizing and antioxidant enzymes are glutathione S-transferases (GSTs). In white shrimp, some GSTs are known, but they have been scarcely studied in response to PAHs. In this study we report the molecular cloning and bioinformatic characterization of two novel nucleotide sequences corresponding to cytosolic GSTs belonging the Delta and Theta classes (GSTD and GSTT). Both proteins genes have tissue-specific patterns of expression under normal conditions, that do not necessarily relate to GST activity and glutathione content. The expression of the GSTD and GSTT, GST activity and glutathione content was analyzed in juvenile P. vannamei exposed to two PAHs, naphthalene (NAP) and phenanthrene (PHE) in sub-lethal concentrations for 96 h. GSTD expression was up-regulated by the two PAHs, while GSTT expression was only induced by NAP. In contrast, GST activity towards CDNB was only up-regulated by PHE, suggesting differential effects of PAHs at gene and protein level. On the other hand, lower reduced glutathione content (GSH) caused by PAHs indicates its utilization for detoxification or antioxidant defenses. However, the GSH/GSSG did not change by PAHs treatment, indicating that shrimp can maintain redox balance during short-term sub-lethal exposure to NAP and PHE. Despite the variations in the responses to NAP and PHE, all these results suggest that the GSTD and GSTT genes could be useful biomarkers for PAH exposure in P. vannamei.

Asunto(s)

Glutatión Transferasa , Glutatión , Naftalenos , Penaeidae , Fenantrenos , Contaminantes Químicos del Agua , Animales , Penaeidae/genética , Penaeidae/efectos de los fármacos , Fenantrenos/toxicidad , Glutatión Transferasa/genética , Glutatión Transferasa/metabolismo , Contaminantes Químicos del Agua/toxicidad , Naftalenos/toxicidad , Glutatión/metabolismo , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Secuencia de Aminoácidos

RESUMEN

The white shrimp Penaeus (Litopenaeus) vannamei is the most cultivated shrimp worldwide. Compared to other shrimp species, it has higher resistance to adverse conditions. During hypoxia, the shrimp reduces oxygen consumption and adjusts energy metabolism via anaerobic glycolysis, among other strategies. Hexokinase (HK) is the first enzyme of glycolysis and a key regulation point. In mammals and other vertebrates, there are several tissue-specific HK isoforms with differences in expression and enzyme activity. In contrast, crustacean HKs have been relatively little studied. We studied the P. vannamei HK isoforms during hypoxia and reoxygenation. We cloned two HK1 sequences named HK1-long (1455 bp) and HK1-short (1302 bp), and one HK2 (1344 bp). In normoxia, total HK1 expression is higher in hepatopancreas, while HK2 is higher in gills. Severe hypoxia (1 mg/L of DO) after 12 h exposure and 1 h of reoxygenation increased HK1 expression in both organs, but HK2 expression changed differentially. In hepatopancreas, HK2 expression increased in 6 and 12 h of hypoxia but diminished to normoxia levels after reoxygenation. In gills, HK2 expression decreased after 12 h of hypoxia. HK activity increased in hepatopancreas after 12 h hypoxia, opposite to gills. These results indicate that shrimp HK isoforms respond to hypoxia and reoxygenation in a tissue-specific manner. Intracellular glucose levels did not change in any case, showing the shrimp ability to maintain glucose homeostasis during hypoxia.

Asunto(s)

Penaeidae , Animales , Penaeidae/metabolismo , Hexoquinasa/genética , Hexoquinasa/metabolismo , Secuencia de Aminoácidos , Hipoxia/metabolismo , Oxígeno/metabolismo , Isoformas de Proteínas/metabolismo , Glucosa/metabolismo , Hepatopáncreas/metabolismo , Mamíferos/metabolismo

RESUMEN

Cell models are indispensable tools in biotechnology when investigating the functional properties of organic compounds. The emergence of various additives designed to enhance animal production has introduced the need for in-depth evaluations, which are often hindered by the complexities of in vivo testing. In this study, we harnessed cell-based models to scrutinize the impact of Solergy as a regulator of cellular metabolism with a particular focus on its modulation of glycogen and antioxidant effects. Our experiment was designed to include assessments of the influence of Solergy on the viability of both terrestrial and aquatic vertebrate cell models, which revealed the benign nature of Solergy and its lack of adverse effects. Furthermore, we examined the capacity of Solergy to modulate intracellular ATP concentrations and enhance glycogen accumulation. Notably, the antioxidant potential of Solergy and its ability to mitigate cellular aging were evaluated within the same cellular frameworks. The outcomes of our investigation suggest that Solergy is a potent metabolic regulator that elevates cellular activity while exerting an antioxidant effect. Importantly, our study demonstrates that Solergy does not induce changes in membrane oxidation. These findings indicate the potential of using Solergy to regulate glycogen synthesis, intracellular ATP concentrations, and oxidative stress in production animals. The multifaceted effects of this additive, which acts as both a metabolism enhancer and an antioxidant, open doors to the creation of custom diets tailored to meet specific production needs while maintaining stable production parameters.

RESUMEN

OBJETIVO: Estimar la prevalencia e identificar determinantes de la infección por el virus del papiloma humano (VPH) en mujeres jóvenes (18-25 años). Material y métodos. Se analizaron datos de 5 871 mujeres sexualmente activas a quienes se les realizó una entrevista y toma de muestras cervicouterinas para detección de VPH y citología durante la visita de reclutamiento del Ensayo de Vacunación contra VPH16/18 en Costa Rica. Se calculó la prevalencia total para cualquier tipo de VPH y tipos oncogénicos, no oncogénicos y específicos, con intervalos de confianza al 95% (IC95%). Se utilizó regresión logística múltiple paso-a-paso para identificar determinantes asociados con la infección. RESULTADOS: La prevalencia total de VPH fue 50.0% (IC95% 48.8,51.3) y por tipos oncogénicos fue 33.8% (IC95% 32.6,35.0). El VPH-16 fue el tipo más prevalente (8.3%, IC95% 7.6,9.0). Los determinantes asociados con un alto riesgo de infección prevalente por VPH oncogénicos fueron no estar casada/unión libre, >1 compañero sexual, infección concomitante por Chlamydia trachomatis, y entre aquéllas con un único compañero sexual en su vida, un compañero con antecedente de múltiples compañeras sexuales. Conclusión. Se confirma la asociación de las infecciones por VPH oncogénicos con el comportamiento sexual de la mujer y se destacan los comportamientos del compañero sexual.

RESUMEN

Glutathione peroxidases (GPxs) are important antioxidant enzymes that act at distinct levels of the antioxidant defense. In vertebrates, there are several glutathione peroxidase (GPx) isoforms with different cellular and tissue distribution, but little is known about their interrelationships. The shrimp Litopenaeus vannamei is the main crustacean cultivated worldwide. It is affected by environmental stressors, including hypoxia and reoxygenation that cause reactive oxygen species accumulation. Thus, the antioxidant response modulation is key for shrimp resilience. Recently, several GPx isoforms genes were identified in the L. vannamei genome sequence, but their functions are just beginning to be studied. As in vertebrates, shrimp GPx isoforms can present differences in their antioxidant responses. Also, there could be interrelationships among the isoforms that may influence their responses. We evaluated shrimp GPx2 and GPx4 expressions during hypoxia, reoxygenation, and GPx4 knock-down using RNAi for silencing, as well as the enzymatic activity of total GPx and GPx4. Also, glutathione content in hepatopancreas was evaluated. GPx2 and GPx4 presented similar expression patterns during hypoxia and reoxygenation. Their expressions decreased during hypoxia and were reestablished in reoxygenation at 6 h in non-silenced shrimp. GPx2 expression was down-regulated by GPx4 knock-down, suggesting that GPx4 affects GPx2 expression. Total GPx activity changed in hypoxia and reoxygenation at 6 h but not at 12 h, while GPx4 activity was not affected by any stressor. The GSH/GSSG ratio in hepatopancreas indicated that at early hours, the redox status remains well-modulated but at 12 h it is impaired by hypoxia and reoxygenation.

Asunto(s)

Antioxidantes , Oxígeno , Animales , Antioxidantes/metabolismo , Oxígeno/metabolismo , Hipoxia/genética , Hipoxia/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Glutatión , Isoformas de Proteínas

RESUMEN

The white shrimp Litopenaeus vannamei is exposed to hypoxic conditions in natural habitats and in shrimp farms. Hypoxia can retard growth, development and affect survival in shrimp. The hypoxia-inducible factor 1 (HIF-1) regulates many genes involved in glucose metabolism, antioxidant proteins, including metallothionein (MT) and apoptosis. In previous studies we found that the L. vannamei MT gene expression changed during hypoxia, and MT silencing altered cell apoptosis; in this study we investigated whether the silencing of HIF-1 affected MT expression and apoptosis. Double-stranded RNA (dsRNA) was used to silence HIF-1α and HIF-1ß under normoxia, hypoxia, and hypoxia plus reoxygenation. Expression of HIF-1α, HIF-1ß and MT, and apoptosis in hemocytes or caspase-3 expression in gills, were measured at 0, 3, 24 and 48 h of hypoxia and hypoxia followed by 1 h of reoxygenation. The results showed that hemocytes HIF-1α expression was induced during hypoxia and reoxygenation at 3 h, while HIF-1ß decreased at 24 and 48 h. In normoxia, HIF-1 silencing in hemocytes increased apoptosis at 3 h and decreased at 48 h; while in gills, caspase-3 increased at 3, 24 and 48 h. In hypoxia, HIF-1 silencing decreased apoptosis in hemocytes at 3 h, but caspase-3 increased in gills. During reoxygenation, apoptosis in hemocytes and caspase-3 in gills increased. During normoxia in hemocytes, silencing of HIF-1 decreased MT expression, but in gills, MT increased. During hypoxia and reoxygenation, silencing induced MT in hemocytes and gills. These results indicate HIF-1 differential participation in MT expression regulation and apoptosis during different oxygen conditions.

Asunto(s)

Apoptosis , Translocador Nuclear del Receptor de Aril Hidrocarburo/metabolismo , Proteínas de Peces/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hipoxia/metabolismo , Metalotioneína/metabolismo , Oxígeno/metabolismo , Penaeidae/metabolismo , Animales , Translocador Nuclear del Receptor de Aril Hidrocarburo/genética , Proteínas de Peces/genética , Regulación de la Expresión Génica , Branquias/metabolismo , Branquias/patología , Hemocitos/metabolismo , Hemocitos/patología , Hipoxia/genética , Hipoxia/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Metalotioneína/genética , Penaeidae/genética , Especies Reactivas de Oxígeno/metabolismo

RESUMEN

The white shrimp Penaeus (Litopenaeus) vannamei is the most economically important crustacean species cultivated in the Western Hemisphere. This crustacean shifts its metabolism to survive under extreme environmental conditions such as hypoxia, although for a limited time. Glucose-6-phosphatase (G6Pase) is a key enzyme contributing to maintain blood glucose homeostasis through gluconeogenesis and glycogenolysis. To our knowledge, there are no current detailed studies about cDNA or gene sequences of G6Pase from any crustacean reported. Herein we report the shrimp P. (L.) vannamei cDNA and gene sequences. The gene contains seven exons interrupted by six introns. The deduced amino acid sequence has 35% identity to other homolog proteins, with the catalytic amino acids conserved and phylogenetically close to the corresponding invertebrate homologs. Protein molecular modeling predicted eight transmembrane helices with the catalytic site oriented towards the lumen of the endoplasmic reticulum. G6Pase expression under normoxic conditions was evaluated in hepatopancreas, gills, and muscle and the highest transcript abundance was detected in hepatopancreas. In response to different times of hypoxia, G6Pase mRNA expression did not change in hepatopancreas and became undetectable in muscle; however, in gills, its expression increased after 3 h and 24 h of oxygen limitation, indicating its essential role to maintain glycemic control in these conditions.

Asunto(s)

Clonación Molecular/métodos , Branquias/metabolismo , Gluconeogénesis/genética , Glucosa-6-Fosfatasa/metabolismo , Hepatopáncreas/metabolismo , Animales , Glucosa-6-Fosfatasa/genética , Penaeidae

RESUMEN

Climate warming has been increasing ocean water temperature and decreasing oxygen concentrations, exposing aquatic organisms to environmental stress conditions. The shrimp Litopenaeus vannamei manages to survive these harsh environmental conditions by enhancing their antioxidant defenses, among other strategies. In this study, we report the mitochondrial manganese superoxide dismutase (mMnSOD) nucleotide and deduced amino acid sequences and its gene expression in L. vannamei tissues. The deduced protein has 220 amino acids with a signal peptide of 20 amino acids. Expression of mMnSOD was analyzed in hepatopancreas, gills and muscle, where gills had highest expression in normoxic conditions. In addition, shrimp were subjected to high temperature, hypoxia and reoxygenation to analyze the effect on the expression of mMnSOD and SOD activity in mitochondria. High temperature and hypoxia showed a synergistic effect in the up-regulation on expression of mMnSOD in gills and hepatopancreas. Moreover, induction in SOD activity was found in the mitochondrial fraction from gills of normoxia at high temperature, probably due to an overproduction of reactive oxygen species caused by an elevated metabolic rate due to the stress temperature. These results suggest that the combined stress conditions of hypoxia and high temperature trigger molecularly the antioxidant response in L. vannamei in a higher degree than only one stressor.

Asunto(s)

Proteínas de Artrópodos , Mitocondrias/metabolismo , Oxígeno , Penaeidae , Superóxido Dismutasa , Temperatura , Secuencia de Aminoácidos , Animales , Proteínas de Artrópodos/genética , Proteínas de Artrópodos/metabolismo , Secuencia de Bases , Penaeidae/genética , Penaeidae/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo

RESUMEN

In marine animals, glycine betaine is one of the main osmolytes accumulated under osmotic stress conditions; nevertheless, in penaeids, shrimps little is known about the pathways involved in glycine betaine biosynthesis. In animal cells, glycine betaine is synthesized by the enzyme betaine aldehyde dehydrogenase (BADH). We herein investigated the salinity effect on the synthesis and concentration of glycine betaine on white shrimp Litopenaeus vannamei. Shrimps were subjected to 10, 20, 35, 40, 50, and 60 ppt salinity conditions for seven days. BADH activity increased in hepatopancreas and gills of shrimps subjected to salinities above 35 ppt salinity. In muscle, the BADH activity decreased at 35 ppt salinity. In hepatopancreas from shrimps subjected to 50 and 60 ppt salinities, BADH activity increased 1.1 and 1.7-fold. At 60 ppt salinity, BADH activity increased 1.5-fold respect to 35 ppt in gills. Glycine betaine concentration increased in hepatopancreas, gills, muscle, and hemolymph in shrimps subjected to salinities above 35 ppt. Glycine betaine concentration also increased at 20 ppt salinity, while at 10 ppt, not detected significant differences. The catch of glycine betaine from hemolymph by the cell likely is carried out to avoid protein denaturalization. Ammonia concentration in the aquarium's water only increased at salinities of 20 ppt and 10 ppt (1.1-fold relative to 35 ppt). Our data demonstrated that in L. vannamei, salinity regulates BADH activity and glycine betaine content in a tissue-specific manner.

Asunto(s)

Betaína Aldehído Deshidrogenasa/metabolismo , Betaína/metabolismo , Osmorregulación , Presión Osmótica , Penaeidae/metabolismo , Salinidad , Animales , Hemolinfa/metabolismo , Hepatopáncreas/metabolismo , Penaeidae/efectos de los fármacos

Asunto(s)

Coinfección/epidemiología , Infecciones por Mycoplasma/epidemiología , Mycoplasma/aislamiento & purificación , Papillomaviridae/aislamiento & purificación , Lesiones Precancerosas/epidemiología , Infecciones por Ureaplasma/epidemiología , Ureaplasma/aislamiento & purificación , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Genotipo , Humanos , México/epidemiología , Persona de Mediana Edad , Mycoplasma/clasificación , Infecciones por Mycoplasma/diagnóstico , Infecciones por Mycoplasma/microbiología , Papillomaviridae/genética , Reacción en Cadena de la Polimerasa , Prevalencia , Ureaplasma/clasificación , Infecciones por Ureaplasma/diagnóstico , Infecciones por Ureaplasma/microbiología

RESUMEN

Hypoxia inducible factor-1 (HIF-1) is a transcriptional factor that induces genes involved in glucose metabolism. HIF-1 is formed by a regulatory α-subunit (HIF-1α) and a constitutive ß-subunit (HIF-1ß). The white spot syndrome virus (WSSV) induces a shift in glucose metabolism and oxidative stress. HIF-1α is associated with the induction of metabolic changes in tissues of WSSV-infected shrimp. However, the contributions of HIF-1 to viral load and antioxidant responses in WSSV-infected shrimp have been not examined. In this study, the effect of HIF-1 silencing on viral load and the expression and activity of antioxidant enzymes (superoxide dismutase-SOD, glutathione S-transferase-GST, and catalase) along with oxidative damage (lipid peroxidation and protein carbonyl) in tissues of white shrimp infected with the WSSV were studied. The viral load increased in hepatopancreas and muscle after WSSV infection, and the accumulative mortality was of 100% at 72 h post-infection. The expression and activity of SOD, catalase, and GST decreased in each tissue evaluated after WSSV infection. Protein carbonyl concentrations increased in each tissue after WSSV infection, while lipid peroxidation increased in hepatopancreas, but not in muscle. Silencing of HIF-1α decreased the WSSV viral load in hepatopancreas and muscle of infected shrimp along with shrimp mortality. Silencing of HIF-1α ameliorated the antioxidant response in a tissue-specific manner, which translated to a decrease in oxidative damage. These results suggest that HIF-1 is essential for restoring the antioxidant response, which counters the oxidative injury associated with WSSV infection.

Asunto(s)

Regulación del Desarrollo de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/antagonistas & inhibidores , Penaeidae/virología , Virus del Síndrome de la Mancha Blanca 1/patogenicidad , Animales , Acuicultura , ADN Viral/aislamiento & purificación , Silenciador del Gen , Hepatopáncreas/crecimiento & desarrollo , Hepatopáncreas/metabolismo , Hepatopáncreas/virología , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inyecciones Intramusculares , Peroxidación de Lípido , México , Músculos/metabolismo , Músculos/virología , Especificidad de Órganos , Estrés Oxidativo , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Penaeidae/crecimiento & desarrollo , Penaeidae/metabolismo , Carbonilación Proteica , Interferencia de ARN , ARN Bicatenario/administración & dosificación , ARN Bicatenario/metabolismo , Carga Viral , Virus del Síndrome de la Mancha Blanca 1/aislamiento & purificación , Virus del Síndrome de la Mancha Blanca 1/fisiología

RESUMEN

The Costa Rica Vaccine Trial (CVT), a phase III randomized clinical trial, provided the initial data that one dose of the HPV vaccine could provide durable protection against HPV infection. Although the study design was to administer all participants three doses of HPV or control vaccine, 20% of women did not receive the three-dose regimens, mostly due to involuntary reasons unrelated to vaccination. In 2011, we reported that a single dose of the bivalent HPV vaccine could be as efficacious as three doses of the vaccine using the endpoint of persistent HPV infection accumulated over the first four years of the trial; findings independently confirmed in the GSK-sponsored PATRICIA trial. Antibody levels after one dose, although lower than levels elicited by three doses, were 9-times higher than levels elicited by natural infection. Importantly, levels remained essentially constant over at least seven years, suggesting that the observed protection provided by a single dose might be durable. Much work has been done to assure these non-randomized findings are valid. Yet, the group of recipients who received one dose of the bivalent HPV vaccine in the CVT and PATRICIA trials was small and not randomly selected nor blinded to the number of doses received. The next phase of research is to conduct a formal randomized, controlled trial to evaluate the protection afforded by a single dose of HPV vaccine. Complementary studies are in progress to bridge our findings to other populations, and to further document the long-term durability of antibody response following a single dose.

Asunto(s)

Anticuerpos Antivirales/inmunología , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Adolescente , Adulto , Ensayos Clínicos como Asunto , Costa Rica/epidemiología , Femenino , Humanos , Esquemas de Inmunización , Vacunación Masiva , Infecciones por Papillomavirus/epidemiología , Infecciones por Papillomavirus/terapia , Vacunas contra Papillomavirus/uso terapéutico , Suero/inmunología , Factores de Tiempo , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/terapia

RESUMEN

Introducción: La Fibroscópica de Trastornos Deglutorios (FEES) es una técnica que permite estudiar la fisiología de la deglución. Puede realizarse junto a la cama del paciente, haciendo esta técnica muy atractiva para realizar en Cuidados Intensivos (UCI), evitando el traslado fuera de la unidad para dicha evaluación. Objetivo: Factibilidad de realizar FEES en la cabecera de la cama en la UCI, y evaluar la incidencia de los trastornos deglutorios en pacientes extubados. Materiales y Métodos: Estudio de cohorte prospectiva, analítico y comparativo en pacientes luego de 24 hs post extubación por un periodo de 6 meses evaluación, incluyéndose todos los pacientes en forma consecutiva, que recibieron ventilación mecánica por un periodo ≥ 48 hs comenzando el reclutamiento desde marzo de 2015. Resultados: Se incluyeron en el protocolo 31 pacientes. La incidencia de los trastornos deglutorios en pacientes extubados que requirieron VM fue del 58% IC 95% (0,407-0,735) con 18 trastornos de 31 casos evaluados. Entre los pacientes con y sin trastornos deglutorios definidos por FEES, las diferencias significativas entre los grupos fueron el tiempo post extubación hasta la realización del FEES, la capacidad de tolerar el FEES en posición de 90° vs 60º, la anormalidad en la escala de Langmore y el movimiento anormal de las cuerdas vocales. La complicación registrada en los dos grupos fue la presencia de saturación de pulso < 90%. Conclusión: Este estudio demuestra que la implementación de FEES, como método de detección de trastornos deglutorios (en la cabecera del paciente) se puede aplicar en forma segura.

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Introduction: The Fiberoptic Endoscopic Evaluation of Swallowing (FEES) is a technique that allows the study of the physiology of swallowing. This technique can be applied at the patient's bedside, making it a very attractive choice for the critical care unit (CCU), since it is not necessary to transfer the patient to another place in order to carry out the evaluation. Objective: Feasibility to carry out the FEES at the patient's bedside at the CCU and assess the incidence of swallowing disorders in extubated patients. Materials and Methods: Comparative, prospective, analytical cohort study conducted 24 hours after extubation for a period of 6 months, including consecutively all the patients who received mechanical ventilation for a period ≥ 48 hours. The enrollment began in March, 2015. Results: 31 patients were included in the protocol. The incidence of swallowing disorders in extubated patients who required mechanical ventilation (MV) was 58%, 95% CI [confidence interval] (0.407-0.735) with 18 patients presenting disorders out of 31 evaluated cases. The significant differences between the groups of patients with and without swallowing disorders defined by the FEES were: the post-extubation time until the FEES, the capacity to tolerate the FEES at upright sitting position (90°) vs. semi-upright sitting position (60°), the abnormality of the Langmore scale and the abnormal movement of the vocal cords. The complication registered in both groups was the presence of oxygen saturation < 90%. Conclusion: This study shows that the implementation of the FEES as a method for detecting swallowing disorders (at the patient's bedside) is safe.

Asunto(s)

Trastornos de Deglución , Extubación Traqueal

RESUMEN

Introduction: The Fiberoptic Endoscopic Evaluation of Swallowing (FEES) is a technique that allows the study of the physiology of swallowing. This technique can be applied at the patient's bedside, making it a very attractive choice for the critical care unit (CCU), since it is not necessary to transfer the patient to another place in order to carry out the evaluation. Objective: Feasibility to carry out the FEES at the patient's bedside at the CCU and assess the incidence of swallowing disorders in extubated patients. Materials and Methods: Comparative, prospective, analytical cohort study conducted 24 hours after extubation for a period of 6 months, including consecutively all the patients who received mechanical ventilation for a period ≥ 48 hours. The enrollment began in March, 2015. Results: 31 patients were included in the protocol. The incidence of swallowing disorders in extubated patients who required mechanical ventilation (MV) was 58%, 95% CI [confidence interval] (0.407-0.735) with 18 patients presenting disorders out of 31 evaluated cases. The significant differences between the groups of patients with and without swallowing disorders defined by the FEES were: the post-extubation time until the FEES, the capacity to tolerate the FEES at upright sitting position (90°) vs. semi-upright sitting position (60°), the abnormality of the Langmore scale and the abnormal movement of the vocal cords. The complication registered in both groups was the presence of oxygen saturation < 90%. Conclusion: This study shows that the implementation of the FEES as a method for detecting swallowing disorders (at the patient's bedside) is safe

Asunto(s)

Trastornos de Deglución , Extubación Traqueal

RESUMEN

Introducción: el índice glucémico (IG) y la carga glucémica (CG) de productos lácteos fermentados (PLF) con lactobacilos puede ser una recomendación útil para pacientes diabéticos y para la población en general.Objetivo: el objetivo del estudio fue medir el IG y la CG de PLF con lactobacilos en sujetos sedentarios y deportistas, y evaluar si existe diferencia entre ellos.Métodos: el estudio se realizó en México (DF) de acuerdo con la ISO26642:210 (Organización Internacional de Normalización). Los participantes fueron: 10 sedentarios y 10 deportistas. Los PLF analizados fueron: Soful, Yakult, Gastroprotect, BeneGastro, Bonacult, Lala Bio 4 y leche descremada con sacarosa (LDS) y la cantidad de alimento que ingirieron dependió de ajustar a 25 g los HC en la porción.Resultados: el IG de la mayoría de los PLF fue bajo para ambos grupos de sujetos; en los deportistas los PLF Yakult y Bonacult presentaron los mayores IG y solo el Yakult puede considerarse como de IG medio para este grupo; estos dos PLF presentaron la menor relación de proteína/HC. La LDS, lácteo con los HC no fermentados, presentó un IG alto para ambos grupos. La CG de los PLF se encontró entre 4 a 7,6 y solo Gastroprotect presentó estadísticamente la menor CG, lo que pudo deberse a su bajo IG, aun cuando su tamaño de ración no fue la menor, entre los PLF.Conclusión: en general los valores de IG y CG de los PLF fueron bajos para ambos grupos. Por tanto, su consumo puede recomendarse en forma moderada. El IG y CG entre productos lácteos con azúcares fermentados y con azúcares no fermentados fueron diferentes.

Asunto(s)

Atletas , Productos Lácteos/análisis , Índice Glucémico , Conducta Sedentaria , Adulto , Femenino , Fermentación , Humanos , Lactobacillus , Masculino , México , Persona de Mediana Edad , Adulto Joven

RESUMEN

The cellular mechanisms used by the shrimp Litopenaeus vannamei to respond to hypoxia have been studied from the energetic metabolism and antioxidant angles. We herein investigated the participation of p53 and metallothionein (MT) in the apoptotic process in response to hypoxia in shrimp hemocytes. The Lvp53 or LvMT genes were efficiently silenced by injection of double stranded RNA for p53 or MT. The effects of silencing on apoptosis were measured as caspase-3 activity and flow cytometry in hemocytes after 24 and 48 h of hypoxia (1.5 mg DO L(-1)). Hemocytes from unsilenced animals had significantly higher apoptosis levels upon both times of hypoxia. The apoptotic levels were diminished but not suppressed in dsp53-silenced but not dsMT-silenced hemocytes after 24 h of hypoxia, indicating a contribution of Lvp53 to apoptosis. Apoptosis in normoxia was significantly higher in dsp53-and dsMT-silenced animals compared to the unsilenced controls, pointing to a possible cytoprotective role of LvMT and Lvp53 during the basal apoptotic program in normoxia. Overall, these results indicate that hypoxia augments apoptosis in shrimp hemocytes and high mRNA levels of Lvp53 and LvMT are not necessary for this response.

Asunto(s)

Apoptosis , Hemocitos/efectos de los fármacos , Metalotioneína/genética , Penaeidae/metabolismo , Proteína p53 Supresora de Tumor/genética , Animales , Antioxidantes/metabolismo , Apoptosis/genética , Caspasa 3/metabolismo , Hipoxia de la Célula , Silenciador del Gen , Hemocitos/metabolismo , Hemocitos/patología , Metalotioneína/metabolismo , Oxígeno/metabolismo , Penaeidae/citología , Penaeidae/genética , ARN Bicatenario/genética , ARN Mensajero/metabolismo , Superóxido Dismutasa/metabolismo , Proteína p53 Supresora de Tumor/metabolismo

RESUMEN

BACKGROUND: Previous Costa Rica Vaccine Trial (CVT) reports separately demonstrated vaccine efficacy against HPV16 and HPV18 (HPV16/18) infections at the cervical, anal, and oral regions; however, the combined overall multisite efficacy (protection at all three sites) and vaccine efficacy among women infected with HPV16 or HPV18 prior to vaccination are less known. METHODS: Women age 18 to 25 years from the CVT were randomly assigned to the HPV16/18 vaccine (Cervarix) or a hepatitis A vaccine. Cervical, oral, and anal specimens were collected at the four-year follow-up visit from 4186 women. Multisite and single-site vaccine efficacies (VEs) and 95% confidence intervals (CIs) were computed for one-time detection of point prevalent HPV16/18 in the cervical, anal, and oral regions four years after vaccination. All statistical tests were two-sided. RESULTS: The multisite woman-level vaccine efficacy was highest among "naïve" women (HPV16/18 seronegative and cervical HPV high-risk DNA negative at vaccination) (vaccine efficacy = 83.5%, 95% CI = 72.1% to 90.8%). Multisite woman-level vaccine efficacy was also demonstrated among women with evidence of a pre-enrollment HPV16 or HPV18 infection (seropositive for HPV16 and/or HPV18 but cervical HPV16/18 DNA negative at vaccination) (vaccine efficacy = 57.8%, 95% CI = 34.4% to 73.4%), but not in those with cervical HPV16 and/or HPV18 DNA at vaccination (anal/oral HPV16/18 VE = 25.3%, 95% CI = -40.4% to 61.1%). Concordant HPV16/18 infections at two or three sites were also less common in HPV16/18-infected women in the HPV vaccine vs control arm (7.4% vs 30.4%, P < .001). CONCLUSIONS: This study found high multisite vaccine efficacy among "naïve" women and also suggests the vaccine may provide protection against HPV16/18 infections at one or more anatomic sites among some women infected with these types prior to HPV16/18 vaccination.

Asunto(s)

Canal Anal/virología , Cuello del Útero/virología , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 18/inmunología , Mucosa Bucal/virología , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/farmacología , Adulto , Neoplasias del Ano/prevención & control , Neoplasias del Ano/virología , Costa Rica , Femenino , Humanos , Neoplasias de la Boca/prevención & control , Neoplasias de la Boca/virología , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/virología , Vacunas contra Papillomavirus/administración & dosificación , Resultado del Tratamiento , Neoplasias del Cuello Uterino/prevención & control , Neoplasias del Cuello Uterino/virología , Vacunación

RESUMEN

BACKGROUND: There is some evidence to suggest that one or two doses of the HPV vaccine provides similar protection to the three-dose regimen. The main aim of the study was to ascertain HPV-16/18 vaccine efficacy in both full and naive cohorts and to explore protection conferred against non-vaccine HPV types, by number of doses received. METHODS: Summary data from the Costa Rica Vaccine Trial (CVT; NCT00128661) and ~the PATRICIA trial (NCT001226810), two phase 3, double-blind, randomised controlled clinical trials of the HPV-16/18 AS04-adjuvanted vaccine in young women, were combined in a post-hoc analysis (GlaxoSmithKline [GSK] e-track number 202142) to investigate the efficacy of fewer than three doses of the HPV-16/18 vaccine after 4 years of follow-up. Women were randomly assigned to receive three doses of the HPV-16/18 vaccine or to a control vaccine; yet, some received fewer doses. After exclusion of women with less than 12 months of follow-up or those who were HPV-16/18 DNA-positive at enrolment (for the HPV-16/18 endpoint), we calculated vaccine efficacy against one-time detection of incident HPV infections after three, two, and one dose(s). The primary study endpoint was one-time detection of first incident HPV-16/18 infections accumulated during the follow-up phase. FINDINGS: We assessed vaccine efficacy against incident HPV-16/18 infection in the modified total vaccinated cohort (22 327 received three doses, 1185 two doses, 543 one dose). Vaccine efficacy against incident HPV-16/18 infections for three doses was 77·0% (95% CI 74·7-79·1), two doses was 76·0% (62·0-85·3), and one dose was 85·7% (70·7-93·7). Vaccine efficacy against incident HPV-31/33/45 infections for three doses was 59·7% (56·0-63·0), two doses was 37·7% (12·4-55·9), and one dose was 36·6% (-5·4 to 62·2). Vaccine efficacy against incident HPV-16/18 infection for two-dose women who received their second dose at 1 month was 75·3% (54·2-87·5) and 82·6% (42·3-96·1) for those who received the second dose at 6 months (CVT data only). Vaccine efficacy against HPV-31/33/45 for two-dose women who received their second dose at 6 months (68·1%, 27·0-87·0; CVT data only), but not those receiving it at one month (10·1%, -42·0 to 43·3), was similar to the three-dose group. INTERPRETATION: 4 years after vaccination of women aged 15-25 years, one and two doses of the HPV-16/18 vaccine seem to protect against cervical HPV-16/18 infections, similar to the protection provided by the three-dose schedule. Two doses separated by 6 months additionally provided some cross-protection. These data argue for a direct assessment of one-dose efficacy of the HPV-16/18 vaccine. FUNDING: US National Cancer Institute, National Institutes of Health Office of Research on Women's Health, and Ministry of Health of Costa Rica (CVT); GlaxoSmithKline Biologicals SA (PATRICIA).

Asunto(s)

Adyuvantes Inmunológicos/administración & dosificación , Infecciones por Papillomavirus/prevención & control , Vacunas contra Papillomavirus/administración & dosificación , Displasia del Cuello del Útero/prevención & control , Displasia del Cuello del Útero/virología , Adolescente , Adulto , Factores de Edad , Costa Rica , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Estudios de Seguimiento , Papillomavirus Humano 16/inmunología , Papillomavirus Humano 16/aislamiento & purificación , Papillomavirus Humano 18/inmunología , Papillomavirus Humano 18/aislamiento & purificación , Humanos , Medición de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos , Vacunación/métodos , Adulto Joven