Effect of supplementation with vitamins D3 and K2 on undercarboxylated osteocalcin and insulin serum levels in patients with type 2 diabetes mellitus: a randomized, double-blind, clinical trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are characterized by chronic hyperglycemia as a consequence of decreased insulin sensitivity, which contributes to bone demineralization and could also be related to changes in serum levels of osteocalcin and insulin, particularly when coupled with a deficiency in the daily consumption of vitamins D3 and K2. The objective of this study was to evaluate the effect of vitamin D3 and vitamin K2 supplements alone or in combination on osteocalcin levels and metabolic parameters in patients with T2DM. METHODS: A double-blind, randomized clinical trial was carried out in 40 patients aged between 30 and 70 years old for 3 months. Clinical and laboratory assessment was carried out at the beginning and at the end of the treatment. The patients were divided into three groups: (a) 1000 IU vitamin D3 + a calcinated magnesium placebo (n = 16), (b) 100 µg of Vitamin K2 + a calcinated magnesium placebo (n = 12), and (c) 1000 IU vitamin D3 + 100 µg vitamin K2 (n = 12). RESULTS: After treatment in the total studied population, a significant decrease in glycemia (p = 0.001), HOMA-IR (Homeostatic model assessment-insulin resistance) (p = 0.040), percentage of pancreatic beta cells (p < 0.001), uOC/cOC index and diastolic blood pressure (p = 0.030) were observed; in vitamin D3 group, differences in serum undercarboxylated osteocalcin (p = 0.026), undercarboxylated to carboxylated osteocalcin index (uOC/cOC) (p = 0.039) glucose (p < 0.001) and  % of functional pancreatic beta cells (p < 0.001) were demonstrated. In vitamin K2 group a significant decrease in glycemia (p = 0.002), HOMA-IR (p = 0.041), percentage of pancreatic beta cells (p = 0.002), and in cOC (p = 0.041) were observed, conversely cOC concentration was found high. Finally, in the vitamins D3 + K2 a significant decrease in glycemia (p = 0.002), percentage of pancreatic beta cells (p = 0.004), and in the uOC/cOC index (p = 0.023) were observed. CONCLUSION: Individual or combined supplementation with vitamins D3 and K2 significantly decreases the glucose levels and  % of functional pancreatic beta cells, while D3 and D3 + K2 treatments also induced a reduction in the uOC/cOC index. Only in the group with vitamin D3 supplementation, it was observed a reduction in undercarboxylated osteocalcin while vitamin K2 increased the carboxylated osteocalcin levels.Trial registration NCT04041492.

Effectiveness of Workplace-Based Muscle Resistance Training Exercise Program in Preventing Musculoskeletal Dysfunction of the Upper Limbs in Manufacturing Workers.

Aims Given the high levels of absenteeism due to musculoskeletal disorders of the upper limbs, there is a need for preventive strategies to protect workers exposed to high risk levels. The purpose of this study was to determine the effect of a workplace-based muscle resistance training exercise program in the presence of pain and musculoskeletal dysfunction of the upper extremities in manufacturing workers exposed to repetitive movements and excessive effort in the workplace. Method Randomized controlled trial in manufacturing workers. A sample of 120 healthy workers was allocated at random to an experimental group, which received a resistance-based exercise program, and a control group, which performed stretching exercises. Results The muscle resistance training exercise had a protective effect on the intensity of pain perceived by workers in their upper limbs (RR: 0.62 95% CI 0.44-0.87) compared with the group of workers who performed stretching exercises. Conclusion A workplace-based muscle resistance training exercise program is an effective preventive strategy in factory workers exposed to risk; however, it is necessary for companies initially to adopt mechanisms to minimize exposure as a prevention strategy.

Encuesta de Percepción en Capacidad Instalada para la Formación de Médicos Residentes en Ortopedia (Traumatología) y Necesidades de la Atención en Patología Musculoesquelética Aguda y Crónica en México. Primera Parte / Installed Capacity Perception Survey for the Training of Resident's Program in Orthopedics and Care Needs in Acute and Chronic Musculoskeletal Pathology in Mexico

resumen está disponible en el texto completo

Abstract: Introduction: It is essential that orthopaedic resident physicians be highly proficient in all aspects, considering the balance between supply, demand, need and context. Fundamental to identify the capacity and quality installed for their training in Mexico. Material and methods: Observational Study, transverse, non-probabilistic sampling-conglomerates, in two phases. The instrument has 8 domains, 57 variables and 4,867 items. 60 graduate professors of 20 states, 50 hospital sites, 22 university programs. Results: 1,038 years of experience (collective intelligence), 17 years of experience/teacher (01 to 50 years). Identified: acute pathology 30 (2 to 90%), chronic pathology 30 (5 to 96%), patients ˂ 15 years, 10 (3 to 30%), patients between 15 and 65 years, 47 (2 to 78%), patients ˃ 65 years, 20 (2 to 60%), number of beds/seat 20 (2 to 510), number of clinics 3 (1 to 48), number of surgical procedures/headquarters per year at the national level, was 960 (50 to 24,650). The national average per resident doctor is 362 surgeries/year with 1,450 surgical times/year. Conclusions: The needs and resources for the training of physicians specializing in orthopedics/traumatology are highly heterogeneous, so it should be adapted to the epidemiological needs of the region of influence, in an area of epidemiological transition. 62.2% expressed not having or have bad academic and scientific infrastructure at its headquarters, more than 50% without rotation overseas and ˃ 90% without regular scientific production.

[Installed Capacity Perception Survey for the Training of Residents Program in Orthopedics and Care Needs in Acute and Chronic Musculoskeletal Pathology in Mexico]. / Encuesta de Percepción en Capacidad Instalada para la Formación de Médicos Residentes en Ortopedia (Traumatología) y Necesidades de la Atención en Patología Musculoesquelética Aguda y Crónica en México. Primera Parte.

INTRODUCTION: It is essential that orthopaedic resident physicians be highly proficient in all aspects, considering the balance between supply, demand, need and context. Fundamental to identify the capacity and quality installed for their training in Mexico. MATERIAL AND METHODS: Observational Study, transverse, non-probabilistic sampling-conglomerates, in two phases. The instrument has 8 domains, 57 variables and 4,867 items. 60 graduate professors of 20 states, 50 hospital sites, 22 university programs. RESULTS: 1,038 years of experience (collective intelligence), 17 years of experience/teacher (01 to 50 years). Identified: acute pathology 30 (2 to 90%), chronic pathology 30 (5 to 96%), patients 15 years, 10 (3 to 30%), patients between 15 and 65 years, 47 (2 to 78%), patients 65 years, 20 (2 to 60%), number of beds/seat 20 (2 to 510), number of clinics 3 (1 to 48), number of surgical procedures/headquarters per year at the national level, was 960 (50 to 24,650). The national average per resident doctor is 362 surgeries/year with 1,450 surgical times/year. CONCLUSIONS: The needs and resources for the training of physicians specializing in orthopedics/traumatology are highly heterogeneous, so it should be adapted to the epidemiological needs of the region of influence, in an area of epidemiological transition. 62.2% expressed not having or have bad academic and scientific infrastructure at its headquarters, more than 50% without rotation overseas and 90% without regular scientific production.

INTRODUCCIÓN: Es fundamental que los médicos residentes de ortopedia (traumatología) sean altamente competentes en todos los aspectos, considerando el equilibrio entre la oferta, demanda, necesidad y contexto. Es primordial identificar la capacidad y calidad instalada para su formación en México. MATERIAL Y MÉTODOS: Estudio observacional, transversal, muestreo no probabilístico-conglomerados, en dos fases. El instrumento tiene ocho dominios, 57 variables y 4,867 ítems. Sesenta profesores de postgrado de 20 estados, 50 sedes hospitalarias, 22 programas universitarios. RESULTADOS: 1,038 años de experiencia (inteligencia colectiva), 17 años de experiencia/profesor (01 a 50 años). Se identificó: patología aguda 30 (2 a 90%), patología crónica 30 (5 a 96%), pacientes 15 años, 10 (3 a 30%), pacientes entre 15 y 65 años, 47 (2 a 78%), pacientes 65 años, 20 (2 a 60%), número de camas/sede 20 (2 a 510), número de consultorios 3 (1 a 48), el número de procedimientos quirúrgicos/sede al año a nivel nacional fue de 960 (50 a 24,650). La media nacional por médico residente es de 362 cirugías/año con 1,450 momentos quirúrgicos/año. CONCLUSIONES: Las necesidades y recursos para la formación de médicos especialistas en ortopedia/traumatología son en alto grado heterogéneos, por lo cual se debería adaptar a las necesidades epidemiológicas de la región de influencia, en un ámbito de transición epidemiológica. Sesenta y dos punto dos por ciento expresó no tener o tener deficiente infraestructura académica y científica en su sede, más de 50% sin rotación al extranjero y 90% sin producción científica regular.

Evaluación temporal del efecto del status epilepticus inducido en la rata en desarrollo en la concentración cerebelar de ácido gama-aminobutírico y glutamato / Time course of the effect of status epilepticus induced in the developing rat on gama-amino butyric acid and glutamate cerebellar concentration

INTRODUCCIÓN: El status epilepticus (SE) es un tipo de actividad epiléptica que causa atrofia cerebelar y pérdida de células de Purkinje en humanos y en animales de experimentación. El cerebelo es una región con alto contenido de ácido gama-aminobutírico (GABA) y glutamato, y algunos estudios refieren cambios en su concentración después de las convulsiones. Sin embargo, hasta la fecha no existen estudios que hayan analizado su efecto en diferentes regiones cerebelares en ratas en desarrollo. El objetivo del presente estudio fue realizar un curso temporal del efecto del SE inducido en ratas Wistar de 14 días de edad (P14) sobre el contenido tisular de GABA y glutamato en el vermis y los hemisferios cerebelares. MÉTODOS: El SE se indujo con el modelo de litio-pilocarpina; las ratas control se inyectaron con salina. Seis h, 24 h o 30 días después del inicio del SE o de la aplicación de solución salina, las ratas se anestesiaron y decapitaron, se extrajo su cerebelo y se separaron el vermis y los hemisferios. Las ratas de ambos grupos se anestesiaron y decapitaron, se extrajo su cerebelo y se separaron el vermis y los hemisferios. Ambas regiones se homogeneizaron (ácido perclórico 0,1 M conteniendo metabisulfito de sodio 4 mM) y centrifugaron, y el sobrenadante se empleó para cuantificar la concentración tisular de GABA y glutamato por cromatografía de líquidos de alta resolución acoplada a un detector fluorométrico. RESULTADOS: El SE no modificó la concentración de GABA y glutamato a los diferentes tiempos de análisis ni en el vermis ni en los hemisferios cerebelares. CONCLUSIONES: El cerebelo en desarrollo es resistente a los cambios neuroquímicos a corto y largo plazo producidos por el SE

INTRODUCTION: Status epilepticus (SE) is an epileptic condition that can cause cerebellar atrophy and loss of Purkinje cells in both humans and research animals. Cerebellum is a region rich in γ-aminobutyric acid (GABA) and glutamate, and some studies have shown that their concentrations may be altered after convulsions. However, there are no studies showing the effect of seizures on different cerebellar regions in developing rats. Time course of the effect of status epilepticus induced in the developing rat on γ-amino butyric acid and glutamate cerebellar concentration. METHODS: SE was induced using the lithium-pilocarpine model; control rats were injected with saline solution. At 6h, 24h, and 1 month after SE o saline injection, rats were anaesthetised with pentobarbital and decapitated, and cerebella were extracted. The vermis and hemispheres were dissected and homogenised in 0.1M perchloric acid containing 4mM sodium bisulfite. Homogenates were centrifuged and supernatant was used to quantify GABA, and glutamate tissue concentrations by HPLC coupled with fluorometric detection. RESULTS: SE did not alter GABA and glutamate tissue concentration in the cerebellar vermis and hemispheres. CONCLUSION: The developing rat cerebellum is resistant to both short- and long-term neurochemical changes induced by SE

Time course of the effect of status epilepticus induced in the developing rat on γ-amino butyric acid and glutamate cerebellar concentration. / Evaluación temporal del efecto del status epilepticus inducido en la rata en desarrollo en la concentración cerebelar de ácido γ-aminobutírico y glutamato.

INTRODUCTION: Status epilepticus (SE) is an epileptic condition that can cause cerebellar atrophy and loss of Purkinje cells in both humans and research animals. Cerebellum is a region rich in γ-aminobutyric acid (GABA) and glutamate, and some studies have shown that their concentrations may be altered after convulsions. However, there are no studies showing the effect of seizures on different cerebellar regions in developing rats. Time course of the effect of status epilepticus induced in the developing rat on γ-amino butyric acid and glutamate cerebellar concentration. METHODS: SE was induced using the lithium-pilocarpine model; control rats were injected with saline solution. At 6h, 24h, and 1 month after SE o saline injection, rats were anaesthetised with pentobarbital and decapitated, and cerebella were extracted. The vermis and hemispheres were dissected and homogenised in 0.1M perchloric acid containing 4mM sodium bisulfite. Homogenates were centrifuged and supernatant was used to quantify GABA, and glutamate tissue concentrations by HPLC coupled with fluorometric detection. RESULTS: SE did not alter GABA and glutamate tissue concentration in the cerebellar vermis and hemispheres. CONCLUSION: The developing rat cerebellum is resistant to both short- and long-term neurochemical changes induced by SE.

La interleucina-1Beta aumenta la muerte neuronal en el giro dentado del hipocampo asociada al estado epiléptico en la rata en desarrollo / Interleukin-1Beta increases neuronal death in the hippocampal dentate gyrus associated with status epilepticus in the developing rat

Introducción: La interleucina 1β (IL-1Beta) aumenta la muerte neuronal necrótica debido al estado epiléptico (EE) en el área CA1 del hipocampo de ratas en desarrollo; sin embargo, se desconoce si ejerce un efecto similar en el giro dentado (GD) hipocampal. El objetivo de esta investigación fue analizar el efecto de IL-1Beta en la muerte neuronal inducida por el EE en el GD de ratas Wistar de 14 días de edad. Métodos: El EE se indujo con el modelo de litio-pilocarpina. Seis horas después del inicio del EE, la IL-1Beta se inyectó intracerebroventricularmente (0, 0,3, 3, 30 o 300 ng/μl); grupos adicionales se inyectaron con el antagonista natural del receptor tipoi (IL-1RI) de IL-1Beta (IL-1Ra, 30 ng/μl) en ausencia o presencia de IL-1Beta (3 ng/μl). La muerte neuronal se evaluó en la capa granular del GD 24 h después del EE mediante la tinción de hematoxilina-eosina. Las células muertas se caracterizaron por presentar citosol eosinofílico y núcleos condensados y fragmentados. Resultados: Se observó un incremento en el número de células eosinofílicas en el GD ipsilateral a la inyección de 3 y 300 ng/μl de IL-1Beta en comparación con el grupo vehículo; en el GD contralateral se observó un efecto similar únicamente con 3 ng/μl de IL-1Beta. La coadministración de IL-1Beta con el IL-1Ra no evitó el aumento en el número de células eosinofílicas. Conclusión: La IL-1Beta aumenta la muerte neuronal con morfología apoptótica provocada por el EE en el GD del hipocampo, mecanismo independiente de la activación del receptor IL-1RI (AU)

Background: Interleukin-1Beta (IL-1Beta) increases necrotic neuronal cell death in the CA1 area after induced status epilepticus (SE) in developing rats. However, it remains uncertain whether IL-1Beta has a similar effect on the hippocampal dentate gyrus (DG). In this study, we analysed the effects of IL-1Beta on 14-day-old Wistar rats experiencing DG neuronal death induced by SE. Methods: SE was induced with lithium-pilocarpine. Six hours after SE onset, a group of pups was injected with IL-1β (at 0, 0.3, 3, 30, or 300 ng/μL) in the right ventricle; another group was injected with IL-1Beta receptor (IL-1R1) antagonist (IL-1Ra, at 30 ng/μL) of IL-1RI antagonist (IL-1Ra) alone, and additional group with 30 ng/μL of IL-1Ra plus 3 ng/μL of IL-1Beta. Twenty-four hours after SE onset, neuronal cell death in the dentate gyrus of the dorsal hippocampus was assessed using haematoxylin-eosin staining. Dead cells showed eosinophilic cytoplasm and condensed and fragmented nuclei. Results: We observed an increased number of eosinophilic cells in the hippocampal DG ipsilateral to the site of injection of 3ng/μL and 300 ng/μL of IL-1Beta in comparison with the vehicle group. A similar effect was observed in the hippocampal DG contralateral to the site of injection of 3 ng/μL of IL-1Beta. Administration of both of IL-1Beta and IL-1Ra failed to prevent an increase in the number of eosinophilic cells. Conclusion: Our data suggest that IL-1Betaincreases apoptotic neuronal cell death caused by SE in the hippocampal GD, which is a mechanism independent of IL-1RI activation (AU)

Interleukin-1ß increases neuronal death in the hippocampal dentate gyrus associated with status epilepticus in the developing rat. / La interleucina-1ß aumenta la muerte neuronal en el giro dentado del hipocampo asociada al estado epiléptico en la rata en desarrollo.

BACKGROUND: Interleukin-1ß (IL-1ß) increases necrotic neuronal cell death in the CA1 area after induced status epilepticus (SE) in developing rats. However, it remains uncertain whether IL-1ß has a similar effect on the hippocampal dentate gyrus (DG). In this study, we analysed the effects of IL-1ß on 14-day-old Wistar rats experiencing DG neuronal death induced by SE. METHODS: SE was induced with lithium-pilocarpine. Six hours after SE onset, a group of pups was injected with IL-1ß (at 0, 0.3, 3, 30, or 300ng/µL) in the right ventricle; another group was injected with IL-1ß receptor (IL-1R1) antagonist (IL-1Ra, at 30ng/µL) of IL-1RI antagonist (IL-1Ra) alone, and additional group with 30ng/µL of IL-1Ra plus 3ng/µL of IL-1ß. Twenty-four hours after SE onset, neuronal cell death in the dentate gyrus of the dorsal hippocampus was assessed using haematoxylin-eosin staining. Dead cells showed eosinophilic cytoplasm and condensed and fragmented nuclei. RESULTS: We observed an increased number of eosinophilic cells in the hippocampal DG ipsilateral to the site of injection of 3ng/µL and 300ng/µL of IL-1ß in comparison with the vehicle group. A similar effect was observed in the hippocampal DG contralateral to the site of injection of 3ng/µL of IL-1ß. Administration of both of IL-1ß and IL-1Ra failed to prevent an increase in the number of eosinophilic cells. CONCLUSION: Our data suggest that IL-1ß increases apoptotic neuronal cell death caused by SE in the hippocampal GD, which is a mechanism independent of IL-1RI activation.

Modelling production per unit of food consumed in fish populations.

The ratio of production-to-consumption (ρ) reflects how efficiently a population can transform ingested food into biomass. Usually this ratio is estimated by separately integrating cohort per-recruit production and consumption per unit of biomass. Estimates of ρ from cohort analysis differ from those that consider the whole population, because fish populations are usually composed of cohorts that differ in their relative abundance. Cohort models for ρ also assume a stable age-structure and a constant population size (stationary condition). This may preclude their application to harvested populations, in which variations in fishing mortality and recruitment will affect age-structure. In this paper, we propose a different framework for estimating (ρ) in which production and consumption are modelled simultaneously to produce a population estimator of ρ. Food consumption is inferred from the physiological concepts underpinning the generalised von Bertalanffy growth function (VBGF). This general framework allows the effects of different age-structures to be explored, with a stationary population as a special case. Three models with different complexities, depending mostly on what assumptions are made about age-structure, are explored. The full data model requires knowledge about food assimilation efficiency, parameters of the VBGF and the relative proportion of individuals at age a at time y (Py(a)). A simpler model, which requires less data, is based on the stationary assumption. Model results are compared with estimates from cohort models for ρ using simulated fish populations of different lifespans. The models proposed here were also applied to three fish populations that are targets of commercial fisheries in the south-east Pacific. Uncertainty in the estimation of ρ was evaluated using a resampling approach. Simulation showed that cohort and population models produce different estimates for ρ and those differences depend on lifespan, fishing mortality and recruitment variations. Results from the three case studies show that the population model gives similar estimates to those reported by empirical models in other fish species. This modelling framework allows ρ to be related directly to population length- or age-structure and thus has the potential to improve the biological realism of both population and ecosystem models.

Genetic characterization of Latin-American Creole cattle using microsatellite markers.

Genetic diversity in and relationships among 26 Creole cattle breeds from 10 American countries were assessed using 19 microsatellites. Heterozygosities, F-statistics estimates, genetic distances, multivariate analyses and assignment tests were performed. The levels of within-breed diversity detected in Creole cattle were considerable and higher than those previously reported for European breeds, but similar to those found in other Latin American breeds. Differences among breeds accounted for 8.4% of the total genetic variability. Most breeds clustered separately when the number of pre-defined populations was 21 (the most probable K value), with the exception of some closely related breeds that shared the same cluster and others that were admixed. Despite the high genetic diversity detected, significant inbreeding was also observed within some breeds, and heterozygote excess was detected in others. These results indicate that Creoles represent important reservoirs of cattle genetic diversity and that appropriate conservation measures should be implemented for these native breeds in order to minimize inbreeding and uncontrolled crossbreeding.

Origins and genetic diversity of New World Creole cattle: inferences from mitochondrial and Y chromosome polymorphisms.

The ancestry of New World cattle was investigated through the analysis of mitochondrial and Y chromosome variation in Creoles from Argentina, Brazil, Mexico, Paraguay and the United States of America. Breeds that influenced the Creoles, such as Iberian native, British and Zebu, were also studied. Creoles showed high mtDNA diversity (H = 0.984 +/- 0.003) with a total of 78 haplotypes, and the European T3 matriline was the most common (72.1%). The African T1a haplogroup was detected (14.6%), as well as the ancestral African-derived AA matriline (11.9%), which was absent in the Iberian breeds. Genetic proximity among Creoles, Iberian and Atlantic Islands breeds was inferred through their sharing of mtDNA haplotypes. Y-haplotype diversity in Creoles was high (H = 0.779 +/- 0.019), with several Y1, Y2 and Y3 haplotypes represented. Iberian patrilines in Creoles were more difficult to infer and were reflected by the presence of H3Y1 and H6Y2. Y-haplotypes confirmed crossbreeding with British cattle, mainly of Hereford with Pampa Chaqueño and Texas Longhorn. Male-mediated Bos indicus introgression into Creoles was found in all populations, except Argentino1 (herd book registered) and Pampa Chaqueño. The detection of the distinct H22Y3 patriline with the INRA189-90 allele in Caracú suggests introduction of bulls directly from West Africa. Further studies of Spanish and African breeds are necessary to elucidate the origins of Creole cattle, and determine the exact source of their African lineages.

Influencia de razas bos indicus en los bovinos criollos de México / No disponible

Se investiga la influencia de tres poblaciones de Bos indicus (Brahman, Gyr y Nelore) sobre cinco de bovinos Criollos Mexicanos (Baja California, Chiapas, Chihuahua, Nayarit y Poblano) mediante la tipificación de 24 secuencias microsatélites. Se asignan los individuos a esas poblaciones y se detectan los mezclados mediante un algoritmo que utiliza cadenas de Markov. Los Criollos de Chiapas y Nayarit son los que mostraron mayor influencia de Cebú con 24,3% y 10,0%, respectivamente. Los otros tres grupos también muestran influencia de Cebú pero por debajo del 5,0%. (AU)

No disponible

Role of lymphotoxin and homeostatic chemokines in the development and function of local lymphoid tissues in the respiratory tract

Los órganos linfoides secundarios tienen una posición anatómica estratégica, con la finalidad de reclutar células presentadoras de antígeno activadas, células "naïve" y poblaciones de células T y B que se encuentran recirculando en la periferia. La estructura de los órganos linfoides secundarios, la cual incluye zonas definidas de células T y B, poblaciones especiales de células estromales, vénulas del endotelio alto y vasos linfáticos, ha evolucionado para facilitar los encuentros entre células presentadoras de antígeno y linfocitos, facilitando la proliferación y diferenciación de células B y T estimuladas por antígenos. La mayoría de los mecanismos que rigen el desarrollo y organización de los órganos linfoides secundarios han sido descubiertos en la década pasada y, ayudan a concluir que las interacciones celulares y moleculares específicas para el desarrollo y organización de los órganos linfoides secundarios son ligeramente diferentes y reflejan probablemente la presencia de poblaciones celulares específicas en un lugar y tiempo adecuados. En esta revisión se discuten los mecanismos involucrados en el desarrollo, organización y función de tejidos linfoides locales del tracto respiratorio, incluidos el tejido linfoide asociado a la nariz (NALT) y el tejido linfoide inducible asociado al bronquio (iBALT)

Secondary lymphoid organs are strategically placed to recruit locally activated antigen presenting cells (APCs) as well as naïve, recirculating T and B cells. The structure of secondary lymphoid organs - separated B and T zones, populations of specialized stromal cells, high endothelial venules and lymphatic vessels - has also evolved to maximize encounters between APCs and lymphocytes and to facilitate the expansion and differentiation of antigen- stimulated T and B cells. Many of the general mechanisms that govern the development and organization of secondary lymphoid organs have been identified over the last decade. However, the specific cellular and molecular interactions involved in the development and organization of each secondary lymphoid organ are slightly different and probably reflect the cell types available at that time and location. Here we review the mechanisms involved in the development, organization and function of local lymphoid tissues in the respiratory tract, including Nasal Associated Lymphoid Tissue (NALT) and inducible Bronchus Associated Lymphoid Tissue (iBALT)

Preparation of a respiratory syncytial virus human reference serum for use in the quantitation of neutralization antibody.

Respiratory syncytial virus (RSV) is the major cause of lower respiratory tract infection in infants, young children and the elderly. Yet, the development of a vaccine to protect against RSV infection still remains an unmet need. At present, immune responses to experimental vaccines under investigation are usually evaluated by ELISA and/or by neutralization assays against RSV. However, both types of assays are generally performed somewhat differently at different laboratories. An important step towards standardization of serology is the use of a standard human reference serum enabling normalization of results generated within and between laboratories. To fill this need, we prepared and characterized a human reference serum against the A2 strain of respiratory syncytial virus. The serum represents a pool of more than 400 individual human sera obtained from commercial sources. The sera were screened and selected on the basis of individual RSV neutralization titers. A final neutralization titer of 973 (95% C.I., 884-1072) was assigned to the final reference serum pool after it was tested three times in the presence of 10% guinea pig complement and a titer of 286 (95% C.I., 243-337) was assigned to the serum when it was tested in the absence of an exogenous complement source. Sterilely reconstituted lyophilized aliquots of the serum exhibited a stable neutralization titer for at least 1 month at room temperature and at 4 degrees C, as well as after 5 weekly freeze-and-thaw cycles at -20 degrees C. In the lyophilized state, the neutralization titer of the lyophilized reagent was stable for at least 6 months, the last time point tested. Two additional smaller pools of serum with high and medium neutralization titers of 2692 and 575, respectively, were also produced in parallel for use as positive controls and were designated as control sera. The reference serum can be used to normalize neutralization and/or other RSV-specific assay results from different laboratories and the control sera can be used for quality control purposes or as part of a panel to test operator proficiency. Individual lyophilized aliquots of the reference and control sera may be obtained from the US National Institute of Allergy and Infectious Diseases (NIAID) Reference Reagent Repository.

Percepción de la sexualidad en pacientes con enfermedades reumáticas: estudio piloto de casos y controles / Perception of sexuality in women with rheumatic disease: case-control pilot study

Introducción: Las enfermedades reumáticas se caracterizan por ser problemas inflamatorios crónicos con afección sistémica que frecuentemente se acompañan de limitación funcional y depresión. Su repercusión sobre la respuesta sexual ha sido pobremente estudiada. El objetivo del presente estudio fue evaluar la percepción sexual en mujeres con enfermedad reumática. Pacientes y métodos: Se aplicó un cuestionario que, además de incluir datos generales, aspectos socioeconómicos, características de la enfermedad y marcadores serológicos de inflamación, midió la percepción de la sexualidad por parte de los sujetos, rasgos de depresión y el nivel de autoestima de éstos. Resultados: Se entrevistó a 16 pacientes, 9 de las cuales tenían artritis reumatoide (AR), 6 lupus eritematoso sistémico (LES), 1 artritis psoriásica. Se seleccionó a 25 mujeres sanas como grupo control. Todas las pacientes recibían tratamiento y presentaban una clase funcional que les permitía valerse por sí mismas. Las pacientes presentaron una peor percepción de la sexualidad (p = 0,001), tendiendo a presentar más rasgos de depresión y una menor autoestima que el grupo control. Conclusiones: Los pacientes con enfermedades reumáticas se benefician del tratamiento, al ser éste un adyuvante en su calidad de vida y en su funcionalidad. La percepción de la sexualidad se afecta como parte de la enfermedad inflamatoria crónica, pero es independiente de la clase funcional del paciente(AU)

Introduction: Rheumatic diseases are characterized by chronic inflammation with systemic involvement and are often accompanied by functional limitation and depression. Their effect on sexual response has been little studied. The objective of the present study was to evaluate perception of sexuality in women with rheumatic disease. Patients and methods: We administered a questionnaire that included general data, socioeconomic aspects, disease characteristics, serum markers of inflammation and measured perception of sexuality, depression traits and self-esteem. Results: Sixteen patients were interviewed, of which nine had rheumatoid arthritis, six had systemic lupus erythematosus and one had psoriatic arthritis. Twentyfive women were selected as controls. All patients were receiving treatment and had a functional class that allowed them to be self-dependent. Patients presented a worse perception of sexuality than controls (p = 0.001) with a trend to more depressive traits and lower self-esteem. Conclusions: Patients with rheumatic disease gain benefits from treatment in terms of quality of life and functionality. Perception of sexuality is affected by chronic inflammatory disease but is independent of the patient’s functional class(AU)

[Perception of sexuality in women with rheumatic disease: case-control pilot study]. / Percepción de la sexualidad en pacientes con enfermedades reumáticas: estudio piloto de casos y controles.

INTRODUCTION: Rheumatic diseases are characterized by chronic inflammation with systemic involvement and are often accompanied by functional limitation and depression. Their effect on sexual response has been little studied. The objective of the present study was to evaluate perception of sexuality in women with rheumatic disease. PATIENTS AND METHODS: We administered a questionnaire that included general data, socioeconomic aspects, disease characteristics, serum markers of inflammation and measured perception of sexuality, depression traits and self-esteem. RESULTS: Sixteen patients were interviewed, of which nine had rheumatoid arthritis, six had systemic lupus erythematosus and one had psoriatic arthritis. Twentyfive women were selected as controls. All patients were receiving treatment and had a functional class that allowed them to be self-dependent. Patients presented a worse perception of sexuality than controls (p=0.001) with a trend to more depressive traits and lower self-esteem. CONCLUSIONS: Patients with rheumatic disease gain benefits from treatment in terms of quality of life and functionality. Perception of sexuality is affected by chronic inflammatory disease but is independent of the patient's functional class.

Emerging experimental therapeutics for bipolar disorder: insights from the molecular and cellular actions of current mood stabilizers.

Bipolar disorder afflicts approximately 1-3% of both men and women, and is coincident with major economic, societal, medical, and interpersonal consequences. Current mediations used for its treatment are associated with variable rates of efficacy and often intolerable side effects. While preclinical and clinical knowledge in the neurosciences has expanded at a tremendous rate, recent years have seen no major breakthroughs in the development of novel types of treatment for bipolar disorder. We review here approaches to develop novel treatments specifically for bipolar disorder. Deliberate (ie not by serendipity) treatments may come from one of two general mechanisms: (1) Understanding the mechanism of action of current medications and thereafter designing novel drugs that mimics these mechanism(s); (2) Basing medication development upon the hypothetical or proven underlying pathophysiology of bipolar disorder. In this review, we focus upon the first approach. Molecular and cellular targets of current mood stabilizers include lithium inhibitable enzymes where lithium competes for a magnesium binding site (inositol monophosphatase, inositol polyphosphate 1-phosphatase, glycogen synthase kinase-3 (GSK-3), fructose 1,6-bisphosphatase, bisphosphate nucleotidase, phosphoglucomutase), valproate inhibitable enzymes (succinate semialdehyde dehydrogenase, succinate semialdehyde reductase, histone deacetylase), targets of carbamazepine (sodium channels, adenosine receptors, adenylate cyclase), and signaling pathways regulated by multiple drugs of different classes (phosphoinositol/protein kinase C, cyclic AMP, arachidonic acid, neurotrophic pathways). While the task of developing novel medications for bipolar disorder is truly daunting, we are hopeful that understanding the mechanism of action of current mood stabilizers will ultimately lead clinical trials with more specific medications and thus better treatments those who suffer from this devastating illness.

Emerging experimental therapeutics for bipolar disorder: clues from the molecular pathophysiology.

Bipolar affective disorder (manic-depressive illness) is a common, severe, chronic, and often life-threatening illness, associated with significant comorbidity. The recognition of the significant morbidity and mortality of patients with bipolar disorder, as well as the growing appreciation that a high percentage of patients respond poorly to existing treatments, has made the task of discovering new therapeutic agents, that are both efficacious and have few side effects increasingly more important. Most recent agents introduced into the pharmacopeia for the treatment of bipolar disorder have been anticonvulsants and atypical antipsychotics. We propose that novel treatments developed specifically for bipolar disorder will arise from (1) understanding more precisely the molecular mechanisms of treatments that are clearly efficacious or (2) developing medications based on the knowledge obtained of the underlying pathophysiology of bipolar disorder. Knowledge with regard to the underlying pathophysiology of bipolar disorder is increasing at a rapid pace, including alterations in intracellular signaling cascades as well as impairments of cellular plasticity and resilience in critical neuronal circuits. We propose that therapeutics designed to enhance cellular plasticity and resilience and that counter maladaptive stress-responsive systems may have considerable utility for the treatment of bipolar disorder. Therapeutic strategies designed to address cellular resilience and plasticity include the regulation of neurotrophic pathways, glucocorticoid signaling, phosphodiesterase activity, and glutamatergic throughput and mitochondrial function. While the task of developing novel medications for bipolar disorder is truly daunting, these and similar approaches will ultimately lead to better medications for the millions who suffer from this devastating illness.

Identification and quantification of components in extracts of Uncaria tomentosa by HPLC-ES/MS.

The two main classes of secondary metabolites, alkaloids and quinovic acid glycosides, of Uncaria tomentosa (Willd.) DC. (Rubiaceae), a Peruvian plant commonly known as 'uña de gato', have been analysed. Separation of the alkaloidal fraction was achieved using a solid phase extraction method based on cationic exchange, and an analytical method employing HPLC-ES/MS has been developed. Quantitative data for commercial wild bark, cultivated bark and leaves are reported. The analysis of quinovic acid glycosides was performed directly on the crude extract using both a fast analytical method based on flow injection ES/MS, and a more complete analytical technique using HPLC-MS.