Comparative Analysis of the Biosimilar and Innovative G-CSF Modulated Pathways on Umbilical Cord Blood-Derived Mononuclear Cells.

Biosimilars of granulocyte colony-stimulating factor (G-CSF) have been routinely introduced into clinical practice. However, not functional genomics characterization has been performed yet in comparison with the innovator G-CSF. This study aimed to evaluate the transcriptomic changes in an in vitro model of umbilical cord blood cells (UBC) exposed to G-CSF for the identification of their modulated pathways. Umbilical cord blood cells-derived mononuclear cells (MNCs) were treated with biosimilar and innovator G-CSF for further gene expression profiling analysis using a microarray-based platform. Comparative analysis of biosimilar and innovator G-CSF gene expression signatures allowed us to identify the most commonly modulated pathways by both drugs. In brief, we observed predominantly upmodulation of transcripts related to PI3K-Akt, NF-kappaB, and tumor necrosis factor (TNF) signaling pathways as well as transcripts related to negative regulation of apoptotic process among others. In addition, hematopoietic colony-forming cell assays corroborate the G-CSF phenotypic effects over UBC-derived MNCs. In conclusion, our study suggests that G-CSF impacts UBC-derived cells through the modulation of several signaling pathways associated with cell survival, migration, and proliferation. The concordance observed between biosimilar and innovator G-CSF emphasizes their similarity in regards to their specificity and biological responses.

Energy expenditure of deskwork when sitting, standing or alternating positions.

BACKGROUND: Recent guidelines recommend accruing 2-4h of standing or light activity during the working day. Use of sit-stand desks could achieve this goal, but whether standing can meaningfully increase energy expenditure (EE) is unclear. AIMS: To study EE, heart rate, feelings and productivity during deskwork while sitting, standing or alternating positions. METHODS: We measured EE by indirect calorimetry in working adults over three randomly ordered 60-min conditions while performing deskwork: continuous sitting (SIT), 30min of each standing and sitting (STAND-SIT) and continuous standing (STAND). We also assessed heart rate, productivity and self-reported energy, fatigue and pain. Linear mixed models compared minute-by-minute EE and heart rate across conditions. Non-parametric tests compared remaining outcomes across conditions. RESULTS: The study group comprised 18 working adults. Compared with SIT, STAND-SIT engendered an additional 5.5±12.4 kcal/h (7.8% increase) and STAND engendered an additional 8.2±15.9 kcal/h (11.5% increase) (both P < 0.001). Alternating positions to achieve the recommended 4h/day of standing could result in an additional 56.9 kcal/day for an 88.9kg man and 48.3 kcal/day for a 75.5kg woman. STAND-SIT and STAND also increased heart rate over SIT by 7.5±6.8 and 13.7±8.8 bpm, respectively (both P < 0.001). We observed no meaningful differences in feelings or productivity. CONCLUSIONS: Desk-based workers could increase EE without added discomfort by using a sit-stand desk. These findings inform future research on sit-stand desks as a part of workplace interventions to increase EE and potentially improve health.

Vitiligo induced by specific immunotherapy with grass pollen: the Koebner phenomenon

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Frecuencia de ptthiosis cutánea en caballos de roducción en explotaciones Ganaaderas de córdoba, Colombia / Frequecy of cutaaneous pythiosis in dairy horses in farms of cordoba, Colomiia

La pythiosis cutánea equina es una enfermedad crónica, granulomatosa, pruriginosa y rápidamente progresiva, que ocurre en regiones con temperaturas que varían de clima templado a caliente (tropical y subtropical) y es causada por el oomiceto Pythium insidiosum. En la Costa Atlántica colombiana, la pythiosis se ve favorecida por las condiciones medioambientales y las inundaciones. El objetivo del presente estudio fue determinar la frecuencia de presentación de pythiosis cutánea en caballos de producción en explotaciones ganaderas del departamento de Córdoba, Colombia. A tal fin, se realizó un estudio descriptivo prospectivo entre los meses de noviembre (2012) y enero (2013); fueron evaluados clínica, epidemiológica e histopatológicamente 47 equinos con lesiones cutáneas granulomatosas compatibles con pythiosis, de un total de 175 equinos pertenecientes a siete explotaciones ganaderas ubicadas en zonas inundables de tres municipios del departamento de Córdoba. La frecuencia de la enfermedad fue de 26,9%. Las manifestaciones clínico-epidemiológicas, las características macroscópicas de las lesiones cutáneas y los hallazgos histopatológicos, indicaron una ocurrencia moderada de pythiosis cutánea en equinos de producción en explotaciones ganaderas de las zonas inundables de dicha zona colombiana.

The equine cutaneous pythiosis is a chronic, granulomatous, often pruriginous, rapidly progressive condition, caused by the oomycete Pythium insidiosum, and with occurrence in regions with temperatures ranging from temperate to hot (tropics and subtropics), as in the Colombian Atlantic Coast, where pythiosis is favored by environmental conditions and floods. The objective of this study was to determine the frequency of occurrence of cutaneous pythiosis in dairy horses of farms of the department of Cordoba, Colombia. We performed a prospective study in animals of convenience, between November of 2012 and January of 2013. We evaluated clinical, epidemiological and histopathologically 47 horses with granulomatous skin lesions compatible with pythiosis, from 175 equine belonging to 7 farms located in flood zones of 3 municipalities of the department of Cordoba, Colombia. The frequency of occurrence of equine cutaneous pythiosis in farms of Cordoba department, was 26.9%. It is concluded that clinical and epidemiological manifestations, macroscopic characteristics of the skin lesions and pathological findings, show a median pythiosis presence of equine dermal in 7 farms located in flood zones of the department of Cordoba, Colombia.

Response, remission and drop-out rates following high-frequency repetitive transcranial magnetic stimulation (rTMS) for treating major depression: a systematic review and meta-analysis of randomized, double-blind and sham-controlled trials.

BACKGROUND: Meta-analyses have shown that high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) has antidepressant properties when compared with sham rTMS. However, its overall response and remission rates in major depression (MD) remain unclear. Thus, we have systematically and quantitatively assessed the efficacy of HF-rTMS for MD based on randomized, double-blind and sham-controlled trials (RCTs). METHOD: We searched the literature from 1995 through to July 2012 using MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials, SCOPUS, and ProQuest Dissertations & Theses. We used a random-effects model, odds ratios (ORs) and the number needed to treat (NNT). RESULTS: Data from 29 RCTs were included, totaling 1371 subjects with MD. Following approximately 13 sessions, 29.3% and 18.6% of subjects receiving HF-rTMS were classified as responders and remitters, respectively (compared with 10.4% and 5% of those receiving sham rTMS). The pooled OR was 3.3 (p < 0.0001) for both response and remission rates (with associated NNTs of 6 and 8, respectively). Furthermore, we found HF-rTMS to be equally effective as an augmentation strategy or as a monotherapy for MD, and when used in samples with primary unipolar MD or in mixed samples with unipolar and bipolar MD. Also, alternative stimulation parameters were not associated with differential efficacy estimates. Moreover, baseline depression severity and drop-out rates at study end were comparable between the HF-rTMS and sham rTMS groups. Finally, heterogeneity between the included RCTs was not statistically significant. CONCLUSIONS: HF-rTMS seems to be associated with clinically relevant antidepressant effects and with a benign tolerability profile.

Descripción clíiica e histopatológica de la rintis micótica granulomatosa en oovinos de córdoba, Colombia / Clinicand histoppathological description of granulomatus fungal rhiniitis in sheep of cordoba, Colombia

El objetivo de este estudio fue describir clínica e histopatológicamente la rinitis micótica granulomatosa causada por Conidiobolus spp. en ovinos del departamento de Córdoba, Colombia. Fueron analizados siete ovinos criollos, hembras, con edades comprendidas entre 2 y 4 años, los cuales recibieron diagnóstico clínico e histopatológico de conidiobolomicosis. Se observaron manifestaciones clínicas similares en todos los ovinos: dificultad respiratoria debido a la obstrucción parcial de los orificios nasales, intolerancia al ejercicio, respiración ruidosa, secreción puro-sanguinolenta bilateral y aumento de volumen de la cavidad nasal. A la necropsia, las cabezas fueron seccionadas longitudinalmente sobre la línea media y se observaron masas de coloración amarillenta irregular con áreas focalizadas de color café oscuro, friable y con coágulos de sangre en la región rinofacial y conchas nasales. En la coloración de H-E, la mucosa de la cavidad nasal presentó necrosis piogranulomatosa multifocal, conteniendo estructuras semejantes a hifas escasamente coloreadas y circundadas por infiltrado de neutrófilos, macrófagos y células gigantes, además de tejido conjuntivo fibroso organizados de forma paralela al rededor del área de necrosis y rodeados por material de Splendore-Hoeppli. En la coloración de Grocott, se observaron hifas irregulares, filamentosas y raramente septadas, cuya morfología es característica de conidiobolomicosis. El diagnóstico se fundamentó en las características clínicas y en los hallazgos histopatológicos, siendo el primer reporte de esta enfermedad en ovinos del departamento de Córdoba y en Colombia.

The objective of this study was to describe clinic and histopathological granulomatous fungal rhinitis caused by Conidiobolusspp. in sheep of the department of Cordoba, Colombia. Seven native sheep were analyzed, females, aged between 2 and 4 years, who were diagnosed clinically with conidiobolomycosis and correlated with histopathological aspects. In describing cases similar clinical manifestations were observed in all animals, difficulty breathing due to partial obstruction of the nostrils, exercise intolerance, noisy breathing, bloody purulent bilateral, similarly showed increased volume of nasal cavity. At necropsy, the heads were sectioned longitudinally on the midline and observed masses of irregular yellowing targeted areas dark brown, friable and blood clots in the nasal region and shells rhinofacial. In the HE stain, the mucosa of the nasal cavity showed multifocal necrosis pyogranulomatous containing hyphae like structures slightly colored and surrounded by infiltration of neutrophils, macrophages and giant cells, and fibrous connective tissue arranged in parallel around the area of necrosis and surrounded by Splendore-Hoeppli material. In the Grocott stain, irregular, filamentous and rarely septate hyphae were observed, suggesting the morphology of the hyphae in the tissue, which is characteristic of conidiobolomycosis. The diagnosis was based on the clinic and histopathological findings, the first report of the disease in sheep of department of Córdoba and Colombia.

Crisis convulsivas afebriles en el contexto de una gastroenteritis aguda leve / Afebrile convulsions with mild acute gastroenteritis

Las crisis convulsivas febriles son las más frecuentes de la infancia, tienen un excelente pronóstico y habitualmente no requieren pruebas ni tratamiento a largo plazo. Por el contrario, las crisis afebriles suelen precisar de exploraciones adicionales y si recurren pueden necesitar antiepilépticos. La existencia de convulsiones durante una gastroenteritis sin deshidratación ni fiebre es una asociación definida como crisis parainfecciosa, conocida en nuestro medio, aunque probablemente infradiagnosticada. Es importante tenerla presente con el fin de evitar pruebas excesivas y/o tratamiento antiepiléptico prolongado. Se describen dos casos diagnosticados de esta entidad tras presentar convulsiones durante una gastroenteritis (AU)

Febrile seizures are the most frequent in the infancy; they have an excellent prognosis and usually don’t need tests or long-term treatment. On the other hand, afebrile convulsions usually need additional explorations and probably anti-epileptic drugs. The existence of convulsions during a mild gastroenteritis wit neither dehydration nor fever is a well known association named para-infectious crisis but probably it is infra-diagnosed. It is important to bear it in mind in order to avoid too many tests and/or antiepileptic long treatment. We describe two cases diagnosed after presenting seizures during a mild gastroenteritis (AU)

The G1359A-CNR1 gene polymorphism is associated to glioma in Spanish patients

INTRODUCTION: The cannabinoid receptor gene 1 (CNR1) encodes the human cannabinoid receptor CB1. This receptor has a widespread distribution in the central nervous system (CNS), the main ligands being anandamide, 2-araquidonoil glycerol and marijuana constituents. There is evidence to suggest an anti-neoplastic effect of these ligands in glial tissues mediated through stimulation of the receptor. MATERIAL AND METHODS: We have studied the G1359A polymorphism of the gene CNR1 with a TaqMan allelic discrimination assay in 200 patients diagnosed with glioma, 109 patients diagnosed with meningioma and 403 healthy subjects. Results Genotypic distribution of the G1359A CNR1 polymorphism in glioma patients showed significant differences when compared to the control group. DISCUSSION: Our results suggest that allele G of the CNR1 gene could be associated with a lower susceptibility to glioma (AU)

Cultivos de célllas de nervio ciático y de ganglio de la raíz dorsal de ratón adulto / Cell Cultures of the Sciatic Nerve and Dorsal Root Ganglia from Adult Mouse

Las células de Schwann (CS) son la glía de sistema nervio periférico. El diseño de prótesis nerviosas se ha centrado en la producción de CS autólogas cultivadas a partir de nervios ciáticos (NC) y de ganglios de la raíz dorsal (GRD). Muy poca literatura reporta cultivo de células perineurales (CP) y fibroblastos endoneurales (FE), y no son consideradas como elementos a incluir en una prótesis. En este trabajo, se describe la importancia de la microdisección del nervio ciático y de los GRD para obtener cultivos de CS, FE y CP con 98%±2 de purificación. Las CS crecen sobre diferentes soportes, con y sin mitógenos. Se obtuvo un porcentaje de CS elevado cuando se elimina el epineuro y perineuro de los NC 90%±3 y la cápsula de los GRD 94%±3 antes de la disociación enzimática, comparado a 70%±4,2 sin microdisección u 80%±3,5 sin epineuro. Los FE se adhieren preferencialmente en las primeras 24 h y 20% de suero favorece su crecimiento. En el primer sub-cultivo, son 99% CS o FE, siendo confluentes a los 6 y 8 días respectivamente. Las CP o de la cápsula de GRD no se disocian y no crecen en sub-cultivos, únicamente crecen a partir de explantes de perineuro; no forman monocapa sino una "lámina" de múltiples capas celulares. En conclusión, la microdisección del GRD y del NC y su disociación son indispensables para obtener en pocos días CS, FE y CP de animales adultos en cultivos altamente purificados.

The Schwann cells (SC) are glial of system peripheral nerve. The nervous prostheses are related to the production of autologous SC obtained from the peripheral nervous and from the dorsal root ganglia (DRG). There is a small amount of literature that reports perineural cells (PC) and endoneural fibroblast (EF) cultures as elements to take account of prostheses. In this work, the micro dissection importance is described in the sciatic nerve (SN) and in the DRG to achieve SC, EF and PC culture with a purity of 98%. The SC grows up on different supports with and without mitogens. An elevated percentage of SC was obtained when the epineurium and the perineurium were removed in the SN (90%±3) and in the GRD (94%±3) before the enzymatic dissociation compared to seventy percentage when the micro dissection was omitted or eighty percentage without the epineurium micro dissection. The EF was adhered in the first twenty four hours and the twenty percentage of serum improved their growth. In the first passage, there is 99 percentage SC or EF, and they get the confluence in the six and eight day, respectively. The PC or the cells of the DRG don´t have neither a good dissociation, nor a growth in subcultures, they only grow from the perineurium explants that forms a lamina of several cellular layers more than a monolayer. In conclusion, the DRG and SN micro dissection and dissociated are indispensable to acquire in few days SC, EF and PC cultures with a high purity from adult animals.

Tumores germinales gonadales en niños: experiencia en el SA: Hospital de Niños JM de Los Ríos 1985-1998 / Tumor germinal gonadal in children: experience in the SA: Hospital de Niños JM de Los Ríos 1985-1998

Entre enero 1985 y agosto 1998, 68 pacientes 137 pacientes con diagnóstico de Tumores Germinales (TG) ingresaron al S.A. Hospital de Niños J.M. de Los Ríos. De ellos, 68 pacientes con Tumor Germinal Gonadal (TGG) fueron incluidos en el protocolo 0021/85, todos se consideraron evaluables. 22 pacientes eran varones, la relación sexo V:H 1:2,09. El promedio de edad fue de 6,6 a., con una mínima de 4 meses y máxima de 17 años. Los síntomas y signos más frecuentes fueron: Masa 73,5 por ciento, Dolor 45,6 por ciento. Marcadores se determinaron en 26 pacientes (38,23 por ciento), resultando positivos en 16 pacientes La variedad histológica más frecuente fue: Teratoma Maduro (TM) 33 casos (48,52 por ciento), Tumor del Seno Endodérmico (TSE) 15 casos (22,05 por ciento), Teratoma Inmaduro (TI) 11 casos (16,17 por ciento), Disgerminoma (DSG) 8 casos (11,76 por ciento) y 1 caso Germinal Mixto (GM). Se utilizó el sistema de Estadiaje propuesto por Brodeur: Estadio I 48 pacientes (70,58 por ciento), Estadio II 10 pacientes (14,70 por ciento), Estadio III 9 pacientes (13,23 por ciento), Estadio IV 1 paciente (1,47 por ciento). Cirugía fue empleada como terapia inicial en todos los casos. Quimioterapia se utilizó en 24: 15 pacientes recibieron esquema PVB, y 6 pacientes esquema VIP Radioterapia fue administrada en 3 pacientes (4,41 por ciento). Respuesta Completa se obtuvieron en 62 pacientes (91,14 por ciento), Respuesta Parcial en 3 pacientes (4,41 por ciento) y Progresión 3 pacientes (4,41 por ciento). Sólo 2 pacientes fallaron a la terapia. La SLE según Histología fue: TM 100 por ciento a 159 meses, TSE 90 por ciento a 147 meses, TI 90 por ciento a 161 meses, DSG 100 por ciento a 135 meses; según Estadio: Est. I 100 por ciento a 159 meses, Est. II 87,5 por ciento a 141 meses, Est. III 100 por ciento a 161 meses; según esquema: PVB 90 por ciento a 161 meses, VIP 80 por ciento a 47 meses. No se demostró diferencia estadística significativa. La SLE general fue de 9677 por ciento a 161 meses. 3 pacientes fallecieron, la Sobrevida Global por Histología fue TM 100 por ciento a 159 meses, TSE 86,66 por ciento a 147 meses, TI 100 por ciento a 161 meses, DSG 87,5 por ciento a 135 meses; según Estadio: Est. I 100 por ciento a 159 meses, Est. II 70 por ciento a 141 meses, Est. III 100 por ciento a 161 meses; según Esquema: PVB 80 por ciento a 161 meses, VIP 100 por ciento a 47 meses. No se demostró diferencia estadística significativa