Assessment of Hippocampal-Related Behavioral Changes in Adolescent Rats of both Sexes Following Voluntary Intermittent Ethanol Intake and Noise Exposure: A Putative Underlying Mechanism and Implementation of a Non-pharmacological Preventive Strategy.

Ethanol (EtOH) intake and noise exposure are particularly concerning among human adolescents because the potential to harm brain. Unfortunately, putative underlying mechanisms remain to be elucidated. Moreover, implementing non-pharmacological strategies, such as enriched environments (EE), would be pertinent in the field of neuroprotection. This study aims to explore possible underlying triggering mechanism of hippocampus-dependent behaviors in adolescent animals of both sexes following ethanol intake, noise exposure, or a combination of both, as well as the impact of EE. Adolescent Wistar rats of both sexes were subjected to an intermittent voluntary EtOH intake paradigm for one week. A subgroup of animals was exposed to white noise for two hours after the last session of EtOH intake. Some animals of both groups were housed in EE cages. Hippocampal-dependent behavioral assessment and hippocampal oxidative state evaluation were performed. Results show that different hippocampal-dependent behavioral alterations might be induced in animals of both sexes after EtOH intake and sequential noise exposure, that in some cases are sex-specific. Moreover, hippocampal oxidative imbalance seems to be one of the potential underlying mechanisms. Additionally, most behavioral and oxidative alterations were prevented by EE. These findings suggest that two frequently found environmental agents may impact behavior and oxidative pathways in both sexes in an animal model. In addition, EE resulted a partially effective neuroprotective strategy. Therefore, it could be suggested that the implementation of a non-pharmacological approach might also potentially provide neuroprotective advantages against other challenges. Finally, considering its potential for translational human benefit might be worth.

Valores típicos de dosis para tomografía computada de cerebro en pacientes adultos / Typical dose values for brain computed tomography in adult patients

Resumen: Debido al aumento en el uso de la Tomografía Computada (TC), y en consecuencia, la probabilidad de generar un incremento progresivo de la dosis recibida por los paciente y su relación en el potencial riesgo de los efectos de las radiaciones ionizantes, es importante implementar el uso de niveles de referencia diagnóstico (DRLs) en TC, como herramienta fundamental dentro de un programa de control de calidad que permita la evaluación y optimización de las dosis entregadas a los pacientes según la tarea clínica deseada. Con el objetivo de establecer valores típicos de dosis en TC de cerebro en Clínica Bupa Reñaca, se estudió una muestra de 73 informes dosimétricos generados en un equipo TC Toshiba Aquilion 64, en términos de indicadores de dosis para TC: Índice de dosis en TC por volumen (CTDIvol) y Producto dosis longitud (DLP). Con los datos obtenidos, se estimó el valor del percentil 50 (p50) para cada indicador de dosis, y se determinaron los valores típicos de dosis en cada grupo estudiado según sexo, edad e indicación clínica. Se logró definir y establecer una metodología que permitió la obtención de los valores típicos de dosis para TC de cerebro, optimizando las dosis sin producir una disminución en la calidad de la imagen necesaria para nuestro propósito clínico.

Abstract: Due to the increase in the use of Computed Tomography (CT), and consequently, the probability of generating a progressive increase in the dose received by the patient and its relationship in the potential risk of the effects of ionizing radiation, it is important to implement the use of diagnostic reference levels (DRLs) in CT, as a fundamental tool within a quality control program that allows the evaluation and optimization of the doses delivered to patients according to the desired clinical task. In order to establish typical dose values in brain CT at Bupa Reñaca Clinic, a sample of 73 dosimetric reports generated on a Toshiba Aquilion 64 CT unit was studied, in terms of dose indicators for CT: Dose rate on CT by volume (CTDIvol) and Dose Length Product (DLP). With the data obtained, the value of the 50th percentile (p50) for each dose indicator was estimated, and typical dose values were determined in each group studied according to sex, age and clinical indication. It was possible to define and establish a methodology that allowed obtaining typical dose values for brain CT, optimizing the doses without producing a decrease in the image quality necessary for our clinical purpose.

Epoetin alfa resistance in hemodialysis patients with chronic kidney disease: a longitudinal study.

Anemia is an inevitable complication of hemodialysis, and the primary cause is erythropoietin deficiency. After diagnosis, treatment begins with an erythropoiesis-stimulating agent (ESA). However, some patients remain anemic even after receiving this medication. This study aimed to investigate the factors associated with resistance to recombinant human erythropoietin therapy with epoetin alfa (αEPO). We performed a prospective, longitudinal study of hemodialysis patients receiving treatment with αEPO at our reference hospital from July 2015 to June 2016. Clinical data was collected, and the response to αEPO treatment was evaluated using the erythropoietin resistance index (ERI). The ERI was defined as the weekly weight-adjusted αEPO dose (U/kg per week)/hemoglobin level (g/dL). A longitudinal linear regression model was fitted with random effects to verify the relationships between clinical and laboratory data and ERI. We enrolled 99 patients (average age, 45.7 (±17.6) years; male, 51.5%; 86.8% with hypertension). The ERI showed a significant positive association with serum ferritin and C-reactive protein, percentage interdialytic weight gain, and continuous usage of angiotensin receptor blocker (ARB) hypertension medication. The ERI was negatively associated with serum iron and albumin, age, urea reduction ratio, and body mass index. Our findings indicate that resistance to αEPO was related to a low serum iron reserve, an inflammatory state, poor nutritional status, and continuous usage of ARBs.

Muerte inducida por medicamentos / FATAL ADVERSE DRUG REACTIONS

Introducción. Las Reacciones Adversas Medicamentosas (RAM) son una problemática subvalorada en la actualidad y con el incremento de hospitalizaciones por RAM también se esta percibiendo en el mundo un aumento de la incidencia de eventos fatales de RAM. Esto genera un replanteo sobre el uso racional de medicamentos y los costos que traen aparejados los medicamentos para los sistemas de salud. Material y métodos. Se realizó un estudio retrospectivo sobre una base de farmacovigilancia del Hospital General de Agudos Dr. Cosme Argerich con datos de cinco años. Se utilizó el score de Naranjo (tabla 1) para determinar la causalidad de una droga en un evento médico adverso. Fueron incluidos en el trabajo aquellos que fueron determinados como ¨ciertos¨ o ¨probables¨. Resultados. En el perído que involucra la base de farmacovigilancia se detectaron 18 eventos de muertes inducidas por medicamentos. Quimioterápicos, inmunosupresores, corticoides y AINEs fueron las drogas más frecuentemente involucradas. Hemorragia digestiva alta e infecciones las patologías que llevaron a la muerte más frecuentemente. Conclusión. Los grupos de drogas involucrados coinciden con los de la bibliografía internacional. Es preciso contar con sistemas de farmacovigilancia estables y sostenidos para poder determinar y cuantificar con más precisión esta problemática creciente

Adverse Drug Reactions (ADR) are one of the most common cause of death in developed countries and in developing countries too. New drugs and aging of the population are two of the mail causes of this. Approximately half of ADR are preventable. The aim of this Word was to determine the incidence of ADR ­ related death in a tertiary care hospital from Buenos Aires. A pharmacovigilance database was used and we applied the Naranjo Score to determine drug causality in adverse medical events. From a total of 2990 ADR, we detected 18 drug related ­ death. Anticancer, steroids and NSAIDs were the drugs most frequently involved

Stem cell-like transcriptional reprogramming mediates metastatic resistance to mTOR inhibition.

Inhibitors of the mechanistic target of rapamycin (mTOR) are currently used to treat advanced metastatic breast cancer. However, whether an aggressive phenotype is sustained through adaptation or resistance to mTOR inhibition remains unknown. Here, complementary studies in human tumors, cancer models and cell lines reveal transcriptional reprogramming that supports metastasis in response to mTOR inhibition. This cancer feature is driven by EVI1 and SOX9. EVI1 functionally cooperates with and positively regulates SOX9, and promotes the transcriptional upregulation of key mTOR pathway components (REHB and RAPTOR) and of lung metastasis mediators (FSCN1 and SPARC). The expression of EVI1 and SOX9 is associated with stem cell-like and metastasis signatures, and their depletion impairs the metastatic potential of breast cancer cells. These results establish the mechanistic link between resistance to mTOR inhibition and cancer metastatic potential, thus enhancing our understanding of mTOR targeting failure.

Effects produced by different types of laser in cornea of Guinea pigs: Identification of a laser capable of producing superficial lesions without leaving scars.

PURPOSE: Climatic droplets keratopathy (CDK) is closely associated with superficial corneal erosions and lack of protective mechanisms against the harmful effects of ultraviolet radiation (UVR) during a prolonged period of time. One of the difficulties in studying the pathogenic mechanisms involved in this human disease is the lack of an experimental animal model. In this paper, a study is conducted on the effects of 4 types of lasers at various powers and time conditions on the normal guinea pig corneas in order to select only one laser condition that reversibly injures the epithelium and superficial stroma, without leaving scarring. METHODS: Damage was induced in the cornea of Guinea pigs using different powers and exposure times of 4 types of laser: argon, CO2, diode and Nd-Yag, and any injuries were evaluated by biomicroscopy (BM) and optical microscopy. Corneas from other normal animals were exposed to argon laser (350 mW, 0.3s, 50 µm of diameter), and the induced alterations were studied at different times using BM, optical coherence tomography (OCT) and transmission electron microscopy (TEM). RESULTS: Only argon laser at 350 mW, 0.3s, 50 µm of diameter produced epithelium and superficial stroma lesions. Some leukomas were observed by BM, and they disappeared by day 15. Corneal thickness measured by OCT decreased in the eyes treated with argon laser during the first week. Using TEM, different ultra structural alterations in corneal epithelium and stroma were observed during the early days, which disappeared by day 15. CONCLUSIONS: It was possible to develop reproducible corneal epithelium and anterior stroma injuries using Argon laser at 350 mW, 0.3s, 50 µm of diameter. In vivo and in vitro studies showed that injured corneas with these laser conditions did not leave irreversible microscopic or ultra structural alterations. This protocol of corneal erosion combined with exposure to UVR and partial deficiency of ascorbate in the diets of the animals for an extended period of time has been used in order to try to develop an experimental model of CDK.

Impact of tuberculosis treatment length and adherence under different transmission intensities.

Tuberculosis (TB) is a leading cause of human mortality due to infectious disease. Treatment default is a relevant factor which reduces therapeutic success and increases the risk of resistant TB. In this work we analyze the relation between treatment default and treatment length along with its consequence on the disease spreading. We use a stylized model structure to explore, systematically, the effects of varying treatment duration and compliance. We find that shortening treatment alone may not reduce TB prevalence, especially in regions where transmission intensity is high, indicating the necessity of complementing this action with increased compliance. A family of default functions relating the proportion of defaulters to the treatment length is considered and adjusted to a particular dataset. We find that the epidemiological benefits of shorter treatment regimens are tightly associated with increases in treatment compliance and depend on the epidemiological background.

On the Cornea of Healthy Merino Sheep: A Detailed Ex Vivo Confocal, Histological and Ultrastructural Study.

Our study performed qualitative and quantitative studies on the corneal ultrastructure of healthy female Merino sheep of ages 4 months and 6 years old from the Argentinean Pampa. The corneas were evaluated using ex vivo laser-scanning confocal microscopy, light microscopy and transmission electron microscopy. Those studies allowed us to obtain detailed images of the corneal layers as well as quantitative data of the cellular and sub-basal nerve densities in the cornea from sheep of different ages. The density of the corneal cells was significantly different in the anterior versus the posterior epithelium and stroma. Moreover, the density of the epithelial, stromal cells and endothelial cells, as well as the sub-basal nerve density were significantly lower in adult than in young animals. Our work provided a wide-ranging description of the corneal ultrastructure of healthy female Merino sheep, which adds to the current knowledge about the ophthalmological aspects of this species and undoubtedly benefits veterinarians.

IgE sérica e IgA salival, total y específica para Dermatophagoides pteronyssinus y subpoblaciones leucocitarias en niños atópicos y no atópicos con asma y/o rinitis / Total and Dermatophagoides pteronyssinus specific IgE and salivary IgA and leukocyte populations in atopic and nonatopic children with asthma and/or rhinitis

Objetivo. Investigar inmunológicamente niños con problemas respiratorios de asma y/o rinitis (atópicos o no atópicos) en la búsqueda de evidencias que permitan una mejor comprensión del desbalance que padecen estos niños en su sistema inmune. Materiales y métodos. Se estudiaron 47 niños de ambos sexos, con edades comprendidas entre los 6 y 15 años, que concurrieron a la consulta por afecciones respiratorias compatibles con asma y/o rinitis a la División de Alergia e Inmunología del Hospital de Niños de la Santísima Trinidad de la Ciudad de Córdoba. Según la información obtenida en la anamnesis, examen físico y prick tests, fueron divididos en dos grupos: atópicos (n=25) y no atópicos (n=22). Luego que los padres firmaron el consentimiento informado y los niños mayores a 7 años dieron su asentimiento para participar del trabajo de investigación, se tomaron muestras de sangre y saliva, para determinar concentración y actividad específica en inmunoglobulinas (Igs) así como estudiar poblaciones leucocitarias y subpoblaciones linfocitarias. Resultados. Como era previsible, los niveles de IgE sérica total y los porcentajes relativos de eosinófilos sanguíneos se mostraron significativamente elevados en el grupo de los niños atópicos (A) con respecto a los no atópicos (NA). El estudio de IgE sérica específica para Dermatophagoides pteronyssinus solo arrojó resultados positivos en los pacientes A y se observó una correlación significativa entre los niveles de IgE total y específica para dicho alérgeno, y entre los niveles de prick y RAST. Los niveles séricos de IgG e IgA no demostraron diferencias de significación entre ambos grupos. El estudio de la IgA salival (IgAs) total permitió observar en el grupo de los niños NA concentraciones significativamente mayores que las correspondientes al grupo de pacientes A. Sin embargo, al estudiar la IgAs específica para el D. pteronyssinus, se observó lo inverso: los pacientes A tienen casi el doble de IgAs específica para el alérgeno respecto del grupo NA. En el estudio de subpoblaciones de células T (CD3, CD4 y CD8), no se observaron diferencias significativas entre ambos grupos. Las subpoblaciones de linfocitos B CD27-y linfocitos B CD27+ tuvieron valores similares en ambos grupos (aproximadamente 80% y 20%, respectivamente). En ambos grupos, alrededor de un 50% de los linfocitos B CD27+ expresaron IgD y el 50% restante fueron IgD­. Sin embargo, el grupo de niños A tuvo dos veces menos de linfocitos B que expresan alta densidad de la molécula CD27 (CD27+++) con respecto a los niños NA (p=0,044). Conclusión. Entre los parámetros inmunológicos investigados encontramos diferencias significativas entre niños A y NA en las concentraciones totales y específicas para el D. pteronyssinus en los isotipos de IgE e IgAs, y en una subpoblación de linfocitos B CD27+++. Dichos hallazgos son analizados en la discusión del manuscrito. (AU)

Purpose. To perform an immunologically investigation in children with respiratory problems of asthma and/or rhinitis (atopic or non atopic) in order to get a better understanding of the immune system imbalance in these patients. Materials and methods. 47 children of both sexes, aged between 6 and 15 years, who were attended for respiratory diseases at the Division of Allergy and Immunology at Children's Hospital de la Santísima Trinidad from Córdoba city were studied. According to information obtained on clinical history, physical examination and prick tests they were divided into two groups: Atopics (n=25) and non-atopic (n=22). After parents signed informed consent and children over 7 years assent to participate in the research work, samples of blood and saliva were taken to determine immune globulins concentrations and specific activities as well as to study leukocyte populations and lymphocytes subpopulations. Results. As expected, levels of total serum IgE and the relative percentages of blood eosinophils were significantly higher in the group of atopic (A) children with regard to non¬atopic (NA) children. The study of specific serum IgE for Dermatophagoides pteronissynus only showed positive results in the A group, and positive correlations between the levels of total and specific IgE, as well as prick and RAST values. Serum IgG and IgA levels showed no significant differences between both groups. Total salivary IgA concentrations were significantly higher in the group of NA children than in the group of A patients. Surprisingly, when specific salivary IgA for D. pteronyssinus was studied, the opposite was observed: Atopic patients have nearly twice specific salivary IgA for this allergen than the NA children. In the study of T cells subpopulations (CD3, CD4 and CD8), no significant differences between groups were observed. The subpopulations of CD27-B cells and CD27+ B cells were similar in both groups (roughly 80% and 20%, respectively). In both groups, approximately 50% of CD27+ B cells expressed IgD and the remaining 50% were IgD­. However, atopic children had less than half B cells expressing high density of CD27 molecule (CD27+++) with respect to the NA children (p=0.044). Conclusion: Among the immunological parameters investigated, we found significant differences between A and NA children in the concentrations of total and specific IgE and salivary IgA to the allergen, and in a subpopulation of CD27+++ B cells. These findings are debated in the discussion of the manuscript(AU)

Non-inferiority trial between two dry-powder inhalers containing fluticasone/salmeterol in asthmatic patients.

Asthma is an increasing pathology with poor compliance. Achievement of control is possible but under intensive treatment. In this setting, fluticasone/salmeterol association delivered by dry powder inhalers is a valuable and proved option. A prospective, parallel, open-label, phase IV, multicentre non-inferiority study was conducted to determine therapeutic similarity between 2 different inhalers: Generic DPI and Diskus®, which both deliver a fluticasone/salmeterol association (CAS 80474-14-2/CAS 89365-50-4). A 103 uncontrolled asthmatic patients were randomly assigned in 2 groups, Generic (G) and Diskus® (D), and received the association for 18 weeks through the appropriate device. They were evaluated according to Asthma Quality of Life Questionnaire and GINA/NIH guidelines. To demonstrate non-inferiority, the estimation of the Relative Risk between the Global Score Rate per group with its 95% confidence interval was calculated and compared against a non-inferiority margin obtained from a previous study. The Global Score Rate was 82% for G Group and 83% for D Group. The RR was 1.0124 (95% CI: 0.847-1.210). The margin set at 0.832 was not reached by the lower 95% CI (z=-2.097; p=0.018) pointing out non-inferiority. The results have demonstrated non-inferiority between groups. Thus, the 2 products are therapeutically similar.

Estudio del polimorfismo del gen de TNF-α, de dicha citocina, y de MCP-1 en pacientes con queratopatía climática esferoidea / Studies of TNF-α gene polymorphism, TNF-α and MCP-1 cytokines in patients with spheroidal climatic keratopathy

Objetivo. Investigar polimorfismo de nucleótidos únicos (SNP) en la posición -308 (G/A) del gen TNF-α y la participación de las citocinas TNF-α y MCP-1 en pacientes con queratopatía climática esferoidea (QCE) y en controles sanos. Materiales y métodos. Participaron 15 pacientes con QCE y 15 individuos sanos del departamento El Cuy, Provincia de Río Negro. Todos ellos, luego de firmar el consentimiento informado, recibieron un examen oftalmológico completo y se recolectaron muestras de sangre y lágrima para realizar diferentes estudios. EL ADN genómico fue obtenido de sangre de todos los individuos mediante el método de salting out y posteriormente amplificado y estudiado mediante reacción en cadena de la polimerasa (PCR) con el sistema de amplificación refractaria a la mutación (ARMS). También se investigaron concentraciones de algunas citocinas proinflamatorias en lágrimas y en sobrenadante de cultivo de células epiteliales corneales humanas (CECH) tratadas o no con radiación ultravioleta B (RUV-B). Resultados. Los resultados de SNP en la posición -308 (G/A) del gen TNF-α (frecuencia alélica y genotípica) indicaron ausencia de diferencias significativas entre pacientes y controles sanos. Fenotípicamente ambos grupos de individuos serían bajos o intermedios productores in vitro de la citocina TNF-α. Sin embargo en las lágrimas de pacientes con QCE se detectaron concentraciones significativamente superiores de TNF-α, IL-1ß y MCP-1 (citocinas proinflamatorias) que en lágrimas de individuos controles sanos (p<0,0001) En la periferia y limbo de la córnea las células dendríticas (CD) incrementaron significativamente con el progreso de la enfermedad (p<0,05). La contribución del epitelio corneal en el proceso inflamatorio fue investigada utilizando CECH expuestas o no a 10 mJ/cm2 de RUV-B. A pesar de la presencia de gelatinasas, IL-6 e IL-8 en sobrenadantes de cultivos obtenidos a las 48 horas (datos no mostrados) no observamos niveles detectables de TNF-α, IL-1ß ni MCP-1. Conclusión. Este trabajo aporta nuevos datos para aumentar los conocimientos sobre los mecanismos inmunológicos involucrados en la etiopatogenia y progresión de la QCE. Demostramos que las citocinas proinflamatorias MCP-1 y TNF-α están significativamente elevadas en lágrimas de individuos con QCE, como se observó previamente con IL-1ß. MCP-1 sería la responsable del aumento de CD en córnea periférica y limbo de estos pacientes a medida de que la enfermedad avanza. El hallazgo de que estas citocinas no pudieron ser detectadas en cultivos de CECH estresadas con RUV-B implica que otras células son las responsables de su producción o que además de RUV-B otros factores son necesarios para iniciar esta cascada de eventos que se observan en esta hipersensibilidad corneal humana(AU)

Purpose. To investigate Single Nucleotide Polymorphism (SNP) at -308 position (G/A) of TNF-α gen and involving of TNF-α and MCP-1 cytokines in Climatic Droplet Keratopathy (CDK) patients and healthy controls. Materials and methods. Fifteen patients with CDK and fifteen healthy controls from departamento El Cuy, province of Rio Negro were involved in this study. After informed consent was obtained from all participants, they had a complete eye examination and then tear and blood samples were collected to perform different assays. DNA was obtained from blood of all individuals using the method of "salting out" and then amplified and studied performing the polymerase chain reaction (PCR) with Amplification-refractory Mutation System (ARMS). Furthermore, some cytokines concentrations were measured in tears and supernatants from human corneal epithelial cells (HCEs) exposed or not to UVR-B radiation. Results. Analysis from SNP at position -308 (G/A) of TNF-α gen (allelic and genotypic frequency) showed no significant differences between patients and healthy controls. Phenotypically both groups of individuals would be low or intermediate in vitro producers of TNF-α cytokine. However, in tears from CDK's patients we detected significantly higher concentrations of TNF-α, IL-1ß and MCP-1 (pro-inflammatory cytokines) than in healthy control subjects tears (p<0.0001). At the corneal peripheral / limbus area, dendritic cells (DCs) increased significantly with the progression of the disease (p<0.05). The corneal epithelium contribution to the inflammatory process was investigated using HCEs exposed or not to 10 mJ/cm2 of UV radiation­B (UVR-B). Despite the presence of gelatinases, IL-6 and IL-8 in culture supernatants obtained after 48 hours (data not shown), detectable levels of TNF-α, IL-1ß and MCP-1 were not detected. Conclusion. This study provides new insights to increase our knowledge about the immunological mechanisms involved in the etiopathogenesis and progression of CDK. We showed that pro-inflammatory cytokines MCP-1 y TNF-α were significantly increased in tears from CDK's patients, as previously described with IL-1ß. MCP-1 would be responsible for the increasing of DCs on the corneal peripheral / limbus area of these subjects as the disease progresses. The fact that these cytokines could not be detected in cultures of HCEs stressed with UVR-B implies that other cells are responsible for their production or, in addition to UVR-B, other factors are necessary to initiate the cascade of events observed in this human corneal hypersensitivity. (AU)

Allee effect in exotic and introduced blowflies.

We combined two models to investigate the theoretical dynamics of five exotic and native blowfly species in response to the Allee effect by using demographic parameters estimated from experimental populations. Most of the results suggest stabilization of dynamic behavior in response to the Allee effect. However, the results depended on the magnitude of the demographic parameters of each species, and also indicated chaotic fluctuations and limit cycles. The results are discussed in the context of larval aggregation, an important biological process for blowflies, which naturally incorporates the Allee effect.

Allee effect in exotic and introduced blowflies

We combined two models to investigate the theoretical dynamics of five exotic and native blowfly species in response to the Allee effect by using demographic parameters estimated from experimental populations. Most of the results suggest stabilization of dynamic behavior in response to the Allee effect. However, the results depended on the magnitude of the demographic parameters of each species, and also indicated chaotic fluctuations and limit cycles. The results are discussed in the context of larval aggregation, an important biological process for blowflies, which naturally incorporates the Allee effect.

Cavidad oral: importante sitio de vigilancia inmunológica / Oral cavity: important site for immune surveillance

La cavidad oral es el principio del tracto digestivo y uno de los sitios del cuerpo más expuestos al ingreso de todo tipo de patógenos, tanto del aire como de los alimentos. Aunque varios excelentes artículos han examinado distintos aspectos de tejidos linfoides asociados a mucosas (MALT), no hay suficiente información acerca de la respuesta inmune en la cavidad oral. En esta revisión destacamos algunos aspectos sobre la anatomía / histología de la cavidad oral, estructuras asociadas y células o moléculas con crucial función inmunológica contra antígenos que ingresan en la boca. Los estudios sobre la mucosa oral han adquirido mucha notoriedad últimamente debido a que ofrece una excelente accesibilidad y evita la degradación de las proteínas y péptidos. En la cavidad bucal se puede generar una respuesta inmune apropiada contra microorganismos, en donde además de la IgA salival muchas otras moléculas son liberadas y cumplen un rol protagónico. A pesar de todos estos factores de defensa, existen momentos en donde el individuo se encuentra más expuesto, dependiendo de la edad, factores hormonales, genéticos, hábitos de fumar y la actividad física, ya que todo esto modifica la tasa de flujo salival, tasa de secreción y concentración de IgA salival y demás proteínas. (AU)

The oral cavity is the beginning of the digestive tract and one of the most exposed body sites to the entry of all types of pathogens in the air as food. Although several excellent articles have examined various aspects of mucosa-associated lymphoid tissue (MALT), there is insufficient information about the oral cavity immune response. In this review we highlight some aspects of the anatomy / histology of the oral cavity, associated structures and cells or molecules with crucial immunological function against antigens that enter the mouth. Studies on the oral mucosa have gained much notoriety lately because it offers excellent accessibility and prevents the degradation of proteins and peptides. In the oral cavity can generate an appropriate immune response against microorganisms, where salivary IgA in addition to many other molecules are released and play a role. Despite these defense factors, there are moments where the individual is more exposed, depending on age, hormonal factors, genetic, smoking habits and physical activity, and that this changes the rate of salivary flow rate secretion and concentration of salivary IgA and other proteins.(AU)

Participación de componentes inmunológicos en la etiopatogenia de la queratopatía climática esferoidea / Involvement of immune components in the etiopathogenia of climatic droplet keratopathy

Objetivo. Investigar si componentes de la inmunidad innata están involucrados en la iniciación/perpetuación de las anormalidades estructurales observadas en la capa de Bowman y el estroma superficial de la córnea de pacientes con queratopatía climática esferoidea (QCE). Materiales y métodos. En el estudio participaron 8 pacientes con QCE y 12 individuos sanos del Departamento El Cuy, Provincia de Río Negro, y 10 individuos sanos de la ciudad de Córdoba. Todos ellos, luego de firmar el consentimiento informado, recibieron un examen oftalmológico completo y se recolectaron muestras de lágrima para estudiar las concentraciones de diferentes citocinas, niveles y formas de metaloproteinasas de matriz (MMPs), y el inhibidor natural de MMPs (TIMP-1). Se realizó microscopía confocal in vivo (MCF) en algunos pacientes y controles. Biopsias de córneas provenientes de pacientes que fueron tratados con queratoplastia penetrante también fueron estudiadas mediante inmunohistoquímica (IHQ). Resultados. Los resultados de MCF indicaron claramente una progresión en la cantidad de depósitos a nivel subepitelial, a medida que la enfermedad avanza. El daño progresivo de las fibras nerviosas sub basales y estromales en los estadios 2 y 3 se correlaciona con pérdida de la sensibilidad corneal. Además de estas alteraciones, observamos que el número de células dendríticas (CD) en el limbo corneal aumentó significativamente a medida que la QCE progresa. En lágrimas de pacientes con QCE se detectaron concentraciones significativamente superiores de citocinas proinflamatorias (IL1ß e IL-8) que en individuos controles (p<0,005). No se halló IL-2, IL-17, IL-4, IL-13 ni IL-10 en pacientes y ni controles. Las actividades de gelatinasas (MMP-9 y -2) fueron significativamente mayores en QCE que en los controles (p<0,001), mientras que los niveles de TIMP-1 fueron significativamente menores en los pacientes (p<0,05). La concentración de MMP-8 fue mayor en controles pero los niveles de esta colagenasa-2 fueron 30 veces superiores, tanto en QCE como controles, con respecto a los valores de los individuos de un centro urbano. Mediante IHC observamos reactividad para MMP-9 en la mayoría de las células epiteliales, solamente en córneas con QCE. Conclusión. Demostramos un rol protagónico del eje citocinas proinflamatorias - gela-tinasas en el desarrollo de la QCE. Los altos niveles de IL-1ß e IL-8 en lágrimas de pacientes facilitan la producción de MMP-8 y gelatinasas, y los efectos de las mismas se exacerban, ya que los pacientes tienen bajos niveles de sus inhibidores naturales (TIMP-1). La MMP-9, además de degradar componentes de la matriz extracelular, cataliza la activación postranscripcional de IL-1ß, potenciando el proceso inflamatorio. Estos resultados son los primeros en explicar mecanismos inmunológicos involucrados en la etiopatogénesis de la QCE y aportan nuevas alternativas para el desarrollo de terapias preventivas utilizando inhibidores de IL-1ß y/o gelatinasas(AU)

Objective. To investigate whether components of innate immunity are involved in the initiation / perpetuation of the structural abnormalities observed in Bowman's layer and superficial stroma of the córnea of patients with Climatic droplet keratopathy (CDK). Materials and Methods. The study included 8 CDK patients and 12 healthy individuals from Department El Cuy, Province of Río Negro, and 10 healthy subjects from the city of Córdoba. All of them, after signing informed consent, received a thorough eye exam and tear samples were collected to study the concentrations of different cytokines, and levels and forms of matrix metalloproteinases (MMPs) and their natural inhibitor (TIMP-1). In vivo confocal microscopy (CFM) was performed in some patients and controls. Corneal biopsies from CDK patients treated with penetrating keratoplasty were also studied by immunohistochemistry (IHC). Results. CFM results clearly indicated a progression in the amount of deposits at corneal sub epithelial level as the disease progresses. The progressive damage in the nerve plexus in stages 2 and 3 correlated with a loss of corneal sensitivity. In addition to these alterations, we observed that the number of dendritic cells (DC) in the limbus increased significantly as the disease progresses.In tears of patients with CDK we detected significantly higher concentrations of pro-inflammatory cytokines (IL-1ß and IL-8) than in control subjects (p < 0.005). We found no IL-2, IL-17, IL-4, IL-13 and IL-10 in patients and controls. The activities of gelatinases (MMP-9 and -2) were significantly higher in CDK than in controls (p < 0.001), while TIMP-1 levels were significantly lower in patients (p < 0.05). The concentration of MMP-8 was higher in controls, but levels of this collagenase-2 were 30 times higher, both in CDK and controls, with respect to MMP-8 values of individuals inhabiting an urban area. By IHC we observed reactivity for MMP-9 in most epithelial cells only in CDK corneas. Conclussion. We demonstrated a key role of the axis pro-inflammatory cytokines ­ gelatinases in the development of CDK. High levels of IL-1ß and IL-8 in tears of patients facilitate the production of MMP-8 and gelatinases, and the effects of these molecules are exacerbated because patients have low levels of their natural inhibitors (TIMP-1). Since MMP-9 besides degrading extracellular matrix components, catalyzes the post translational activation of IL-1ß, the inflammatory process is fuelled. These results are the first to explain immunological mechanisms involved in the pathogenesis of the QCE and provide new alternatives for the development of preventive therapies using inhibitors of IL-1ß and / or gelatinases.(AU)

Prediction of intestinal absorption and metabolism of pharmacologically active flavones and flavanones.

Three glycosilated flavonoids (diosmin, hesperidin and naringin) and respective aglycones were characterized in terms of their apparent ionisation constants and bidirectional permeability using the cellular model Caco-2 as well as the artificial membrane model PAMPA. Ionisation curves were established by capillary electrophoresis. It was confirmed that significant amounts of the aglycones are ionised at physiological pH whereas the glycosides are in the neutral form. Permeation was not detected for the glycosides in either the apical-to-basolateral or basolateral-to-apical directions confirming the need for metabolism before absorption through the intestinal membrane. The aglycones permeated in both directions with apparent permeabilities (P(app)) in the range of 1-8x10(-5) cm/s. The results from both in vitro methods correlated providing some evidence of passive transport; however, the hypothesis of active transport cannot be excluded particularly in the case of diosmetin. Metabolism of the aglycones was detected with the cell model, more extensively when loading in the apical side. Some of the metabolites were identified as glucuronide conjugates by enzymatic hydrolysis.

Sex ratio and dynamic behavior in populations of the exotic blowfly Chrysomya albiceps (Diptera, Calliphoridae).

Sex ratio is an essential component of life history to be considered in population growth. Chrysomya albiceps is a blowfly species with a naturally biased sex ratio. In this study, we evaluated the impact of changes in sex ratio on the dynamic behavior of C. albiceps using a density-dependent mathematical model that incorporated demographic parameters such as survival and fecundity. These parameters were obtained by exponential regression, with survival and fecundity being estimated experimentally as a function of larval density. Bifurcation diagram of the results indicated the evolution of stable equilibrium points as a function of sex ratio. A continually increasing sex ratio yielded a hierarchy of bifurcating stable equilibrium points that evolved into a chaotic regime. The demographic parameters obtained by exponential regression were also changed to maximum and minimum values in order to analyze their influence on dynamic behavior with sex ratio being considered as an independent variable. Bifurcations with periodicity windows between chaos regimes were also found.

Sex ratio and dynamic behavior in populations of the exotic blowfly Chrysomya albiceps (Diptera, Calliphoridae)

Sex ratio is an essential component of life history to be considered in population growth. Chrysomya albiceps is a blowfly species with a naturally biased sex ratio. In this study, we evaluated the impact of changes in sex ratio on the dynamic behavior of C. albiceps using a density-dependent mathematical model that incorporated demographic parameters such as survival and fecundity. These parameters were obtained by exponential regression, with survival and fecundity being estimated experimentally as a function of larval density. Bifurcation diagram of the results indicated the evolution of stable equilibrium points as a function of sex ratio. A continually increasing sex ratio yielded a hierarchy of bifurcating stable equilibrium points that evolved into a chaotic regime. The demographic parameters obtained by exponential regression were also changed to maximum and minimum values in order to analyze their influence on dynamic behavior with sex ratio being considered as an independent variable. Bifurcations with periodicity windows between chaos regimes were also found.

A razão sexual é um componente essencial da biologia de organismos a ser considerado em crescimento populacional. Chrysomya albiceps é uma espécie de mosca varejeira que exibe um desvio na razão sexual em relação à proporção 1:1. Neste estudo avaliamos o impacto de alterações na razão sexual sobre o comportamento dinâmico de C. albiceps utilizando um modelo matemático dependente da densidade que incorpora parâmetros demográficos como sobrevivência e fecundidade. Os parâmetros foram obtidos por regressão exponencial, com sobrevivência e fecundidade sendo estimadas experimentalmente em função da densidade larval. O diagrama de bifurcação gerado pelos resultados indicou a evolução de pontos de equilíbrio estável em função da razão sexual. A sucessão contínua dos valores da razão sexual resultou em uma hierarquia de pontos de equilíbrio estável produzida por bifurcações, resultando em regime caótico. Os parâmetros demográficos obtidos por regressão exponencial foram também mudados para valores máximos e mínimos, a fim de analisar a influência deles sobre o comportamento dinâmico da espécie, tendo a razão sexual como variável independente. Bifurcações com janelas de periodicidade intercaladas com o regime caótico também foram encontradas.

What do we need to learn to optimize the SLIT alternative?

Allergen-specific immunotherapy (IT) is the only treatment of allergy in adults and children capable of modifying the immune response at early steps. As a consequence, IT improves symptoms, prevents the onset of new sensitizations, reduces the risk of developing asthma and its clinical efficacy lasts many years. The main rationale for administering sublingually IT (SLIT) is to reduce the occurrence of side effects, still yet preserving the immunological effects. SLIT with the most common allergens have been used in many studies with significant clinical effectiveness in both asthma and rhinitis. The pharmacokinetic of allergens administered through non injection routes is complex. Peptide absorption across oral mucosa occurs mainly by passive diffusion but delivery of proteins has some limitations. Moreover, the molecular mechanisms responsible for the efficacy of SLIT are poorly defined. In this review we focus on the anatomy/histology of the oral cavity as well as on the associated immunological structures to envisage what may happen when an allergen is kept in the mouth. Moreover, the induction of immune responses in this particular immunological environment is also discussed.