N-(levodopa) chitosan derivative based on click chemistry shows biological functionality in brain cells.

OBJECTIVE: To develop N-(levodopa) chitosan derivatives through click chemistry to study their effect in brain cells.Significance: This study presents a proof-of-concept that macromolecules such as N-(Levodopa) chitosan derivatives traverse brain cell membranes and induce biomedical functionalities. METHODS: Through click chemistry, we developed N-(levodopa) chitosan derivatives. They were physically and chemically characterized by FT-IR, 1H-NMR, TGA and Dynamic Light Scattering analyses. Solution and nanoparticles of N-(levodopa) chitosan derivatives were tested in primary cell cultures from the postnatal rat olfactory bulb, substantia nigra and corpus callosum. Ca2+ imaging and UPLC experiments were used to investigate if the biomaterial modulated the brain cell physiology. RESULTS: N-(levodopa) chitosan derivatives induced intracellular Ca2+ responses in primary cell cultures of the rat brain. UPLC experiments indicated that levodopa attached to chitosan was converted into dopamine by brain cells. CONCLUSION: The present study shows that N-(levodopa) chitosan may be useful to develop new treatment strategies, which could serve as molecular reservoirs of biomedical drugs to treat degenerative disorders of the nervous system.

Differentiation of circulating monocytes into macrophages with metabolically activated phenotype regulates inflammation in dyslipidemia patients.

Macrophages are mediators of inflammation having an important role in the pathogenesis of cardiovascular diseases. Recently, a pro-inflammatory subpopulation, known as metabolically activated macrophages (MMe), has been described in conditions of obesity and metabolic syndrome where they are known to release cytokines that can promote insulin resistance. Dyslipidemia represents an important feature in metabolic syndrome and corresponds to one of the main modifiable risk factors for the development of cardiovascular diseases. Circulating monocytes can differentiate into macrophages under certain conditions. They correspond to a heterogeneous population, which include inflammatory and anti-inflammatory subsets; however, there is a wide spectrum of phenotypes. Therefore, we decided to investigate whether the metabolic activated monocyte (MoMe) subpopulation is already present under dyslipidemia conditions. Secondly, we assessed whether different levels of cholesterol and triglycerides play a role in the polarization towards the metabolic phenotype (MMe) of macrophages. Our results indicate that MoMe cells are found in both healthy and dyslipidemia patients, with cells displaying the following metabolic phenotype: CD14varCD36+ABCA1+PLIN2+. Furthermore, the percentages of CD14++CD68+CD80+ pro-inflammatory monocytes are higher in dyslipidemia than in healthy subjects. When analysing macrophage differentiation, we observed that MMe percentages were higher in the dyslipidemia group than in healthy subjects. These MMe have the ability to produce high levels of IL-6 and the anti-inflammatory cytokine IL-10. Furthermore, ABCA1 expression in MMe correlates with LDL serum levels. Our study highlights the dynamic contributions of metabolically activated macrophages in dyslipidemia, which may have a complex participation in low-grade inflammation due to their pro- and anti-inflammatory function.

Evaluación del catastrofismo en pacientes con lumbalgia crónica en la unidad de dolor de un hospital universitario / Evaluation of pain catastrophizing in chronic back pain patientsof a university hospital pain unit

El catastrofismo es la percepción mental, negativa y exagerada, respecto a la experiencia del dolor, tanto real como anticipada. Comprende tres dimensiones: rumiación, magnificación y desesperanza. Sus consecuencias son: dolor más intenso, mayor consumo de analgésicos, disminución de las actividades diarias, incapacidad laboral, mayor sensibilidad al dolor, interferencia en el uso de estrategias de afrontamiento y peor pronóstico general. El objetivo de este estudio fue evaluar el nivel de catastrofismo ante el dolor en pacientes con lumbalgia crónica que consultan en nuestro hospital universitario, utilizando la escala de catastrofismo del dolor en su versión en español. La muestra fue de 69 pacientes, se encontró una correlación lineal positiva entre nivel total de catastrofismo y sus tres dimensiones con la intensidad del dolor y la interferencia que éste produce sobre las actividades diarias, medidas a través del inventario abreviado del dolor. Los niveles de catastrofismo encontrados fueron altos, mayores a 30, la intensidad del dolor y su interferencia fueron elevados (mayor de 6). Este es el primer estudio de evaluación del catastrofismo en pacientes con dolor crónico en nuestro país. Los niveles de catastrofismo encontrados obligan a ofrecer en nuestra unidad medidas de intervención que logren reducirlo, de modo de lograr mejores resultados de los tratamientos farmacológicos o intervencionistas que se indican en los pacientes con lumbalgia crónica.

Pain catastrophizing is a cognitive state characterized by a negative and exaggerated perception about actual or anticipating pain. It is conformed for three factors: rumiation, magnification and helplessness. Its consequences in pain perception are increase in pain intensity and analgesic consumption, interference in daily and labor activities, hiperalgesia, interference in coping strategies and general poor clinical prognosis of pain states. The aim of this study was to evaluate pain catastrophizing in chronic back pain outpatients in a university hospital pain unit, utilizing the spanish version of the pain catastrophizing scale. Sixty-nine patients with chronic back pain with or without lumbosacral radicular pain were included. A positive lineal correlation between total catastrophism and its three factors with pain intensity and pain daily activities interference. Pain intensity and interference evaluated by the brief pain Inventory were high (more than 6) and also was the total catastrophism (more than 30). This is the first study in our country about pain catastrophizing in chronic pain patients. The high levels of catastrophism observed in this study must be treated with specific psychological interventions, in order to reduce them in such a way that pharmacological and interventional pain treatments results could be improved.

The achievement of boar sperm in vitro capacitation is related to an increase of disrupted disulphide bonds and intracellular reactive oxygen species levels.

The aim of this work was to determine the relationship of intracellular reactive oxygen species (ROS) and the disulphide bonds established between sperm proteins with the achievement of capacitation in boar spermatozoa. With this purpose, spermatozoa were incubated in a specifically designed in vitro capacitation medium (CM) in the presence or absence of reduced glutathione (GSH). Incubation of boar spermatozoa in CM for 4 h significantly (p < 0.05) increased free cysteine residues, which is a marker of disrupted disulphide bonds, and also intracellular ROS levels. The addition of GSH to the medium prevented most capacitation-like changes in sperm motility, membrane lipid disorder, mitochondrial membrane potential, intracellular calcium levels and localization of tyrosine-phosphorylated proteins (pTyr), but not in tyrosine phosphorylation of P32. These effects were accompanied by the inhibition of the ability of sperm cells to trigger the acrosome exocytosis in response to progesterone. When GSH was added together with progesterone after 4 h of incubation, acrosome exocytosis was not altered, but the subsequent decrease in intracellular calcium observed in controls cells was inhibited. Furthermore, co-incubation of oocytes with spermatozoa previously incubated in CM in the presence of GSH for 4 h significantly (p < 0.05) increased the number of spermatozoa attached to the oocyte surface but decreased normal fertilization rates. Our results suggest that boar sperm capacitation is related to an increase in disrupted disulphide bonds and intracellular ROS levels and that both events are related to the regulation of hyperactivated motility, intracellular calcium dynamics, sperm binding ability to the oocyte and achievement of proper nuclear decondensation upon oocyte penetration.

[Risk factors and rejection frequency in patients undergoing penetrating keratoplasty]. / Factores de riesgo y frecuencia de rechazo en pacientes con queratoplastia penetrante.

BACKGROUND: Corneal transplantation is one of the surgical procedures most frequently performed worldwide and with better prognosis. Among its main indications include: keratoconus, bullous keratopathy, previous graft rejection, corneal dystrophy, and infection. The known risk factors for graft rejection are: recipient's age, presence of vessels in the recipient cornea, intraocular pressure, and retransplantation. The objective of this article is to determine the risk factors and frequency of corneal rejection in patients undergoing penetrant keratoplasty. METHODS: The study's design was descriptive, observational, transversal, analytical and retrospective. Patients operated of penetrating keratoplasty in cornea clinic with follow up during at least 6 months were studied. A review of the medical records of patients undergoing penetrating keratoplasty at the Hospital de Especialidades del Centro Médico Nacional Siglo XXI was performed. RESULTS: The 35.3 % of the transplanted patients had corneal transplant rejection. Corneal neovascularization of the recipient cornea previous to transplant was present in 21.3 %. CONCLUSIONS: In our study we found similar results to the reported in the literature, the most important risk factors for rejection was the use of threphine 7.50 mm, older patient with a history with previous corneal neovascularization, keratopathy and herpetic keratitis.

Introducción: el trasplante de córnea representa uno de los procedimientos quirúrgicos que con mayor frecuencia se realizan en todo el mundo y de los que tienen un mejor pronóstico. Dentro de sus principales indicaciones se encuentran: el queratocono, la queratopatía bullosa, el rechazo corneal previo, la distrofia corneal y la infección. Los factores de riesgo conocidos para rechazo del trasplante son: edad del receptor, presencia de vasos en la córnea receptora, presión intraocular y retrasplante. El objetivo de este artículo es determinar los factores de riesgo y la frecuencia de rechazo corneal en pacientes sometidos a queratoplastia penetrante. Métodos: el diseño del estudio fue descriptivo, observacional, transversal, retrospectivo y analítico. Se estudiaron los pacientes operados de queratoplastia penetrante en la consulta externa de córnea, con seguimiento mínimo de 6 meses. Se llevó a cabo una revisión de expedientes clínicos de pacientes operados de queratoplastia penetrante en Hospital de Especialidades del Centro Médico Nacional Siglo XXI del IMSS. Resultados: del total de los pacientes trasplantados 35.3 % presentaron rechazo del trasplante corneal. La neovascularización corneal previa al trasplante de la corona receptora estuvo presente en 21.3 %. Conclusiones: en nuestro estudio encontramos resultados similares a los reportados en la literatura, siendo los factores de riesgo más importantes para presentar rechazo: el uso de trépanos mayores a 7.50 mm, paciente con antecedentes de neovascularización corneal previa, queratopatía y queratitis herpética.

[RELATIONSHIP BETWEEN BODY MASS INDEX, PHYSICAL ACTIVITY AND MEAL TIMES IN MEXICAN ADOLESCENTS]. / RELACIÓN ENTRE EL ÍNDICE DE MASA CORPORAL, LA ACTIVIDAD FÍSICA Y LOS TIEMPOS DE COMIDA EN ADOLESCENTES MEXICANOS.

OBJECTIVES: 1) to describe the distribution of the body mass index (BMI), physical activity levels and meal times' frequency and; 2) to assess its relationships in a sample of high school Mexican adolescents. METHODS: a total of 1028 adolescents (41.1% males and 58.9% females) aged 15-19 years (M= 16.12; SD= 0.9) were included in the final analysis. BMI was calculated using the CDC-2000 as reference. Meal times were evaluated by one factor of the RFAEDP questionnaire (Risk Factors Associated to Eating Disorders in Pubescents). Physical activity was measured trough short version of the International Physical Activity Questionnaire (IPAQ). Pearson's correlations were used to determine relationship between the variables. RESULTS: overweight and obesity prevalence together reached, 29.2% for females and 29.3% in males. In meal times' factor, undernourished and low weight subjects achieved the highest values in the answer option always. In total sample, according to the physical activity, 31.9% reported low level. Meal times showed significant association with BMI (r= -0.142, p < 0.01) and physical activity level (r= 0.125, p < 0.01). DISCUSSION: important problems of malnutrition, meal times' frequency and inactivity were identified in the sample. From these findings, the need to design and implement programs with the aim of promoting healthy lifestyles among adolescent arises.

Objetivos: los objetivos de este estudio son: 1) describir la distribución del IMC, los niveles de actividad física y la frecuencia de los tiempos de comida, y 2) examinar la relación de estas variables con el IMC en una muestra de adolescentes mexicanos estudiantes de preparatoria. Métodos: participaron 1.028 adolescentes (58,9% mujeres y 41,1% hombres) de 15 a 19 años de edad (M= 16,12; DE= 0,9). Se calculó el IMC y se utilizó la referencia del CDC-2000. Los tiempos de comida se midieron con uno de los factores del cuestionario Factores de Riesgo Asociados a Trastornos Alimentarios para Púberes (FRATAP). La actividad física se evaluó mediante el International Physical Activity Questionnaire (IPAQ) en su versión corta. Se realizaron correlaciones de Pearson para ver la relación entre las variables. Resultados: la prevalencia combinada de sobrepeso y obesidad alcanzó el 29,2% para mujeres y el 29,3% en hombres. En el factor tiempos de comida, los sujetos con desnutrición y bajo peso fueron quienes siempre obtuvieron los valores más altos en la opción de respuesta. El 31,9% del total de la muestra reportó un nivel de actividad física bajo. Los tiempos de comida mostraron asociaciones significativas con el IMC (r= -0,142, p < 0,01) y los niveles de actividad física (r= 0,125, p < 0,01). Discusión: en la muestra se identificaron problemas importantes de malnutrición, frecuencia de comidas e inactividad física. De estos hallazgos surge la necesidad de diseñar e implantar programas para promover estilos de vida saludables en adolescentes.

PAX7-FKHR fusion gene inhibits myogenic differentiation via NF-kappaB upregulation.

OBJECTIVE: Alveolar rhabdomyosarcomas (ARMS) are characterised by a PAX3/7-FKHR translocation, which is presumed to promote a differentiation arrest in the myogenic lineage, in which setting secondary genetic events occur, resulting in sarcomagenesis. The aim of this study was to identify the mechanism by which PAX3/7-FKHR expression results in a myogenic differentiation block, as discrete from the secondary genetic events that complete the sarcomagenic process. METHODS: We performed a novel differential gene expression analysis comparing normal mesenchymal stem cells with previously generated non-tumorigenic mesenchymal stem cells expressing the PAX7-FKHR fusion gene, as well as with a known tumorigenic, PAX7-FKHR-expressing ARMS cell line, CW9019. RESULTS: This novel analysis uncovered the upregulation of the NF-kappaB pathway as a function of PAX3/7-FKHR expression, but distinct from the secondary sarcomagenic process; thus implicating NF-kappaB as a mediator of the PAX3/7-FKHR differentiation block. We further show that NF-kappaB activity is upregulated in PAX7-FKHR cells when compared to parental MSCs due to upregulation of the PI3K/AKT pathway. In addition we show that NF-kappaB inhibits myogenesis via activation of cyclinD1/ cdk4 complexes, which sequester MyoD1, a key myogenic transcription factor. CONCLUSIONS: Our results highlight the importance of the NF-kappaB pathway in myogenesis and sarcomagenesis and suggest that this pathway may be one of the potential therapeutic targets in the treatment of ARMS.

Alternate PAX3 and PAX7 C-terminal isoforms in myogenic differentiation and sarcomagenesis.

OBJECTIVE: Pax3 and Pax7 are closely related genes that are involved in commitment of cells to a myogenic lineage during skeletal muscle development and regeneration. Several Pax3 and Pax7 transcripts are expressed from the genes, generating different isoforms with potentially distinct DNA binding and transactivation properties. The aim of this study was to investigate the implication of Pax3 and Pax7 C-terminal isoforms during myogenic differentiation and tumorigenesis, since fusions involving these genes are commonly associated with alveolar rhabdomyosarcoma (ARMS). METHODS: Uncommitted (mouse mesenchymal stem cells, MSCs) and committed (C2C12) myogenic precursor cells were stably transfected with PAX3/FKHR and PAXC7/ FKHR fusion genes. We analysed gene and protein expression comparing the newly generated cells with the parental cells, to determine the functional importance of Pax3 and Pax7 C-terminal isoforms. RESULTS: We found that the transcript Pax3c was expressed at low levels in undifferentiated C2C12 and MSCs cells, but its expression levels increased considerably at later stages of differentiation. However, expression levels of Pax3d transcript increased only slightly after differentiation. Pax7 transcripts, present before differentiation in committed C2C12 cells, but absent in uncommitted MSCs, increased noticeably in MSCs after differentiation. We also found that the presence of PAX/FKHR fusions prevented both C2C12 and MSC cells from terminal myogenic differentiation and increased the expression of discrete endogenous Pax3/7 transcripts, in particular Pax3d and Pax7B. CONCLUSIONS: Our results suggest that both Pax3 and Pax7 transcripts are required for commitment of cells to the myogenic lineage, with each transcript having a distinct role. More specifically, the Pax3c isoform may be required for terminal myogenic differentiation whereas the Pax3d isoform may be involved in undifferentiated cell maintenance and/or proliferation.

Spanish version of the Family Interview for Genetic Studies (FIGS).

INTRODUCTION: The use of the Family Interview for Genetic Studies (FIGS), has made it possible to advance in the performance of family studies for research in genetic psychiatry. This study aimed to adapt this interview into Spanish and develop a validation process of the FIGS in a sample of Cuban families with a family background of schizophrenia. METHODS: The English version of the FIGS was translated into Spanish and was used in this study. The content was validated through the consensus score of several referees. The questionnaire was administered to at least two informants of 146 families of patients diagnosed of schizophrenia. Internal consistency of the items was analyzed, calculating Pearson's correlation coefficients and Cronbach's alpha of the FIGS and reliability. RESULTS: In general the Spanish version of the FIGS interview was found to be useful. Internal consistency of the FIGS as measured by Cronbach's alpha coefficient has been found to be 0.92 for depression, 0.99 for mania; 0.94 for psychosis, 0.94 for alcohol and drugs and 0.97 for personality disorders, which indicates values having satisfactory reliability. In addition, Pearson's correlation coefficient varied from the 0.41 to 0.99 for the different lists of symptoms mentioned above and all were statistically significant (p<0.0001). CONCLUSIONS: This questionnaire is reliable and valid for gathering diagnostic information about relatives of probands and thus suitable for use in genetic studies of Cuban families with a history of schizophrenia.

[Nursing professionals' reading habits; a study in a hospital in Granada]. / Hábitos de lectura en enfermería: estudio en un hospital de granada.

In all the hospital library standards, as well as in the existing Accreditation Norms for hospitals, a section is included which cites the distinct professionals who work at the institution which the library services must attend to provide for their scientific information needs. Among the sanitary collectives, nursing professionals are explicitly listed. Nonetheless, since the creation of hospital library services in Spain, many librarians have noticed that the nursing professionals, which compose the most numerous group in a hospital, have a very low library visitation rate in relationship to other collectives such as doctors in particular. Desiring to have objective data regarding library use, and not merely perceptions, the authors planned out a study in a large, 1.200 bed, hospital where more than 1.000 professionals comprise the nursing staff. The authors wanted to verify the nursing staff's needs for scientific information, their habits regarding their scientific information needs, and the possible difficulties which they encounter trying to acquire this type of information; furthermore, the authors wanted to know the nursing professionals' attitude towards this issue.

[Cognitive slowing in asymptomatic individuals who are seropositive for human immunodeficiency virus type 1]. / Enlentecimiento cognitivo en sujetos seropositivos asintomáticos al virus de inmunodeficiencia humana tipo 1.

INTRODUCTION: Reaction time (RT) is thought to be the most suitable measure to detect cognitive deficits in neurologically asymptomatic human immunodeficiency virus type I (HIV-1) infected individual since cognitive slowing is the earliest signal of cognitive-motor disorder related to HIV-1 infection. There is evidence suggesting that the greater the degree of central processing demands required by a task, the more likely that it will be sensitive to the effect of HIV-1 infection. Such statement suggests that the RT deficits exhibited by HIV-1 infected individuals at initial stages could be caused by the slowing of central information processing mechanisms. AIM: To assess the relationships between demands of central information processing and RT in HIV-1 seropositive individuals. SUBJECTS AND METHODS: 50 neurologically asymptomatic HIV-1 individuals were compared with 34 seronegative controls on four discriminative RT tasks of different levels of central processing demands except by the motor response requirements. RESULTS: Seropositive group was slower in RT and performed worse on the higher demanding task. On the lesser demanding tasks no differences in RT nor in accuracy were observed. For the task demanding sensory coding efforts seropositive individual were slower but achieved the same level of accuracy. CONCLUSIONS: Even when these results point to that RT slowing in HIV-1 asymptomatic individuals emerged with the increase in cognitive demands, the fact that RT slowing without accuracy declining can also appear in some tasks demanding sensory processing, preclude ruling out a peripheral deficit as the locus of the RT slowing in these subjects.

[Selective attention disorders associated with a history of occupational exposure to organic solvents]. / Alteraciones de la atención selectiva asociadas a la historia de exposición ocupacional a solventes orgánicos.

INTRODUCTION: The cognitive effects of long-term exposure to organic solvents could be similar to those triggered by certain neurodegenerative diseases. AIMS: The purpose of this study was to evaluate the effects exerted by accumulated exposure on the cognitive functions. PATIENTS AND METHODS: 105 subjects with an average history of exposure of 19.3 years were evaluated using seven computerised cognitive tasks (CPT, digit-symbol substitution, Stroop, memory span, word learning and recognition, and TRD) and results were later compared with the performance of a non-exposure group and with a normative reference. A study was made of the association between the length of exposure and performance in the variables in which the exposed subjects displayed significantly lower values than control subjects. In order to evaluate the effect exerted by age, regression functions between performance and age were calculated for each group. RESULTS: Only the indicators from the Stroop and digit-symbol tasks correlated with the length of exposure. The regression functions between performance and age for each group showed that the former decreased significantly faster among exposed subjects than among controls. CONCLUSIONS: Findings suggest that, while recent exposure seems to have an effect on a wide range of functions, chronic exposure exerts a selective influence on a smaller group. In this case, only selective attention appears to deteriorate. Similar deficits have been observed in the early stages of patients with Alzheimer's and Parkinson's.

[Ambulatory surgery in ophthalmology]. / Cirugía ambulatoria en oftalmología.

Traditionally intraocular ophthalmologic surgery has been performed on hospitalized patients. Nevertheless, surgical advances now allow ambulatory management with the same effectiveness. This communication about our experience with outpatient intraocular surgery shows that there were no complications but several advantages among which is mentioned the optimal use of the hospital facilities, mainly for those patients whose serious condition require hospitalization.