An atlas of cells in the human tonsil.

Palatine tonsils are secondary lymphoid organs (SLOs) representing the first line of immunological defense against inhaled or ingested pathogens. We generated an atlas of the human tonsil composed of >556,000 cells profiled across five different data modalities, including single-cell transcriptome, epigenome, proteome, and immune repertoire sequencing, as well as spatial transcriptomics. This census identified 121 cell types and states, defined developmental trajectories, and enabled an understanding of the functional units of the tonsil. Exemplarily, we stratified myeloid slan-like subtypes, established a BCL6 enhancer as locally active in follicle-associated T and B cells, and identified SIX5 as putative transcriptional regulator of plasma cell maturation. Analyses of a validation cohort confirmed the presence, annotation, and markers of tonsillar cell types and provided evidence of age-related compositional shifts. We demonstrate the value of this resource by annotating cells from B cell-derived mantle cell lymphomas, linking transcriptional heterogeneity to normal B cell differentiation states of the human tonsil.

SOX11 expression is restricted to EBV-negative Burkitt lymphoma and is associated with molecular genetic features.

ABSTRACT: SRY-related HMG-box gene 11 (SOX11) is a transcription factor overexpressed in mantle cell lymphoma (MCL), a subset of Burkitt lymphomas (BL) and precursor lymphoid cell neoplasms but is absent in normal B cells and other B-cell lymphomas. SOX11 has an oncogenic role in MCL but its contribution to BL pathogenesis remains uncertain. Here, we observed that the presence of Epstein-Barr virus (EBV) and SOX11 expression were mutually exclusive in BL. SOX11 expression in EBV-negative (EVB-) BL was associated with an IG∷MYC translocation generated by aberrant class switch recombination, whereas in EBV-negative (EBV-)/SOX11-negative (SOX11-) tumors the IG∷MYC translocation was mediated by mistaken somatic hypermutations. Interestingly, EBV- SOX11-expressing BL showed higher frequency of SMARCA4 and ID3 mutations than EBV-/SOX11- cases. By RNA sequencing, we identified a SOX11-associated gene expression profile, with functional annotations showing partial overlap with the SOX11 transcriptional program of MCL. Contrary to MCL, no differences on cell migration or B-cell receptor signaling were found between SOX11- and SOX11-positive (SOX11+) BL cells. However, SOX11+ BL showed higher adhesion to vascular cell adhesion molecule 1 (VCAM-1) than SOX11- BL cell lines. Here, we demonstrate that EBV- BL comprises 2 subsets of cases based on SOX11 expression. The mutual exclusion of SOX11 and EBV, and the association of SOX11 with a specific genetic landscape suggest a role of SOX11 in the early pathogenesis of BL.

SOX11 is a novel binding partner and endogenous inhibitor of SAMHD1 ara-CTPase activity in mantle cell lymphoma.

ABSTRACT: Sterile alpha motif and histidine-aspartate (HD) domain-containing protein 1 (SAMHD1) is a deoxynucleoside triphosphate triphosphohydrolase with ara-CTPase activity that confers cytarabine (ara-C) resistance in several hematological malignancies. Targeting SAMHD1's ara-CTPase activity has recently been demonstrated to enhance ara-C efficacy in acute myeloid leukemia. Here, we identify the transcription factor SRY-related HMG-box containing protein 11 (SOX11) as a novel direct binding partner and first known endogenous inhibitor of SAMHD1. SOX11 is aberrantly expressed not only in mantle cell lymphoma (MCL), but also in some Burkitt lymphomas. Coimmunoprecipitation of SOX11 followed by mass spectrometry in MCL cell lines identified SAMHD1 as the top SOX11 interaction partner, which was validated by proximity ligation assay. In vitro, SAMHD1 bound to the HMG box of SOX11 with low-micromolar affinity. In situ crosslinking studies further indicated that SOX11-SAMHD1 binding resulted in a reduced tetramerization of SAMHD1. Functionally, expression of SOX11 inhibited SAMHD1 ara-CTPase activity in a dose-dependent manner resulting in ara-C sensitization in cell lines and in a SOX11-inducible mouse model of MCL. In SOX11-negative MCL, SOX11-mediated ara-CTPase inhibition could be mimicked by adding the recently identified SAMHD1 inhibitor hydroxyurea. Taken together, our results identify SOX11 as a novel SAMHD1 interaction partner and its first known endogenous inhibitor with potentially important implications for clinical therapy stratification.

Motive and opportunity: MYC rearrangements in high-grade B-cell lymphoma with MYC and BCL2 rearrangements (an LLMPP study).

ABSTRACT: Rearrangements that place the oncogenes MYC, BCL2, or BCL6 adjacent to superenhancers are common in mature B-cell lymphomas. Lymphomas with diffuse large B-cell lymphoma (DLBCL) or high-grade morphology with both MYC and BCL2 rearrangements are classified as high-grade B-cell lymphoma with MYC and BCL2 rearrangements ("double hit"; HGBCL-DH-BCL2) and are associated with aggressive disease and poor outcomes. Although it is established that MYC rearrangements involving immunoglobulin (IG) loci are associated with inferior outcomes relative to those involving other non-IG superenhancers, the frequency of and mechanisms driving IG vs non-IG MYC rearrangements have not been elucidated. Here, we used custom targeted capture and/or whole-genome sequencing to characterize oncogene rearrangements across 883 mature B-cell lymphomas including Burkitt lymphoma, follicular lymphoma, DLBCL, and HGBCL-DH-BCL2 tumors. We demonstrate that, although BCL2 rearrangement topology is consistent across entities, HGBCL-DH-BCL2 have distinct MYC rearrangement architecture relative to tumors with single MYC rearrangements or with both MYC and BCL6 rearrangements (HGBCL-DH-BCL6), including both a higher frequency of non-IG rearrangements and different architecture of MYC::IGH rearrangements. The distinct MYC rearrangement patterns in HGBCL-DH-BCL2 occur on the background of high levels of somatic hypermutation across MYC partner loci in HGBCL-DH-BCL2, creating more opportunity to form these rearrangements. Furthermore, because 1 IGH allele is already disrupted by the existing BCL2 rearrangement, the MYC rearrangement architecture in HGBCL-DH-BCL2 likely reflects selective pressure to preserve both BCL2 and B-cell receptor expression. These data provide new mechanistic explanations for the distinct patterns of MYC rearrangements observed across different lymphoma entities.

B-cell non-Hodgkin lymphomas.

B-cell lymphomas occur with an incidence of 20 new cases per 100 000 people per year in high-income countries. They can affect any organ and are characterised by heterogeneous clinical presentations and courses, varying from asymptomatic, to indolent, to very aggressive cases. Since the topic of B-cell non-Hodgkin lymphomas was last reviewed in The Lancet in 2017, a deeper understanding of the biological background of this heterogeneous group of malignancies, the availability of new diagnostic methods, and the development and implementation of new targeted and immunotherapeutic approaches have improved our ability to treat patients. This Seminar provides an overview of the pathobiology, classification, and prognostication of B-cell non-Hodgkin lymphomas and summarises the current knowledge and standard of care regarding biology and clinical management of the most common subtypes of mature B-cell non-Hodgkin lymphomas. It also highlights new findings in deciphering the molecular background of disease development and the implementation of new therapeutic approaches, particularly those targeting the immune system.

SOX11/PRDX2 axis modulates redox homeostasis and chemoresistance in aggressive mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an incurable B-cell neoplasm characterized by an aggressive behavior, short responses to conventional therapies and SOX11 overexpression, which is associated with aggressive disease features and inferior clinical outcome of patients. Oxidative stress is known to induce tumorigenesis and tumor progression, whereas high expression levels of antioxidant genes have been associated with chemoresistance in different cancers. However, the role of oxidative stress in MCL pathogenesis and the involvement of SOX11 regulating redox homeostasis in MCL cells are largely unknown. Here, by integrating gene set enrichment analysis of two independent series of MCL, we observed that SOX11+ MCL had higher reactive oxygen species (ROS) levels compared to SOX11- MCL primary tumors and increased expression of Peredoxine2 (PRDX2), which upregulation significantly correlated with SOX11 overexpression, higher ROS production and worse overall survival of patients. SOX11 knockout (SOX11KO) significantly reduced PRDX2 expression, and SOX11KO and PRDX2 knockdown (PRDX2KD) had increased ROS levels and ROS-mediated tumor cell death upon treatment with drugs, compared to control MCL cell lines. Our results suggest an aberrant redox homeostasis associated with chemoresistance in aggressive MCL through SOX11-mediated PRDX2 upregulation, highlighting PRDX2 as promising target for new therapeutic strategies to overcome chemoresistance in aggressive MCLs.

Mutational, immune microenvironment, and clinicopathological profiles of diffuse large B-cell lymphoma and follicular lymphoma with BCL6 rearrangement.

BCL6-rearrangement (BCL6-R) is associated with a favorable prognosis of follicular lymphoma (FL), but the mechanism is unknown. We analyzed the clinicopathological, immune microenvironment (immune checkpoint, immuno-oncology markers), and mutational profiles of 10 BCL6-R-positive FL, and 19 BCL6-R-positive diffuse large B-cell lymphoma (DLBCL) cases (both BCL2-R and MYC-R negative). A custom-made panel included 168 genes related to aggressive B-cell lymphomas and FL. FL cases were nodal, histological grade 3A in 70%, low Ki67; and had a favorable overall and progression-free survival. DLBCL cases were extranodal in 60%, IPI high in 63%, non-GCB in 60%, EBER-negative; and had a progression-free survival comparable to that of DLBCL NOS. The microenvironment had variable infiltration of M2-like tumor-associated macrophages (TAMs) that were CD163, CSF1R, LAIR1, PD-L1, and CD85A (LILRB3) positive; but had low IL10 and PTX3 expression. In comparison to FL, DLBCL had higher TAMs, IL10, and PTX3 expression. Both lymphoma subtypes shared a common mutational profile with mutations in relevant pathogenic genes such as KMT2D, OSBPL10, CREBBP, and HLA-B (related to chromatin remodeling, metabolism, epigenetic modification, and antigen presentation). FL cases were characterized by a higher frequency of mutations of ARID1B, ATM, CD36, RHOA, PLOD2, and PRPRD (p < 0.05). DLBCL cases were characterized by mutations of BTG2, and PIM1; and mutations of HIST1H1E and MFHAS1 to disease progression (p < 0.05). Interestingly, mutations of genes usually associated with poor prognosis, such as NOTCH1/2 and CDKN2A, were infrequent in both lymphoma subtypes. Some high-confidence variant calls were likely oncogenic, loss-of-function. MYD88 L265P gain-of-function was found in 32% of DLBCL. In conclusion, both BCL6-R-positive FL and BCL6-R-positive DLBCL had a common mutational profile; but also, differences. DLBCL cases had a higher density of microenvironment markers.

Patient-derived follicular lymphoma spheroids recapitulate lymph node signaling and immune profile uncovering galectin-9 as a novel immunotherapeutic target.

Follicular lymphoma (FL), the most common indolent non-Hodgkin lymphoma, constitutes a paradigm of immune tumor microenvironment (TME) contribution to disease onset, progression, and heterogenous clinical outcome. Here we present the first FL-Patient Derived Lymphoma Spheroid (FL-PDLS), including fundamental immune actors and features of TME in FL lymph nodes (LNs). FL-PDLS is organized in disc-shaped 3D structures composed of proliferating B and T cells, together with macrophages with an intermediate M1/M2 phenotype. FL-PDLS recapitulates the most relevant B-cell transcriptional pathways present in FL-LN (proliferation, epigenetic regulation, mTOR, adaptive immune system, among others). The T cell compartment in the FL-PDLS preserves CD4 subsets (follicular helper, regulatory, and follicular regulatory), also encompassing the spectrum of activation/exhaustion phenotypes in CD4 and CD8 populations. Moreover, this system is suitable for chemo and immunotherapy testing, recapitulating results obtained in the clinic. FL-PDLS allowed uncovering that soluble galectin-9 limits rituximab, rituximab, plus nivolumab/TIM-3 antitumoral activities. Blocking galectin-9 improves rituximab efficacy, highlighting galectin-9 as a novel immunotherapeutic target in FL. In conclusion, FL-PDLS maintains the crosstalk between malignant B cells and the immune LN-TME and constitutes a robust and multiplexed pre-clinical tool to perform drug screening in a patient-derived system, advancing toward personalized therapeutic approaches.

Efecto de la procedencia y el almacenamiento en la calidad del café / Effect of provenance and storage on coffee quality

Resumen Antecedentes. La calidad del grano de café ha sido relacionada con su procedencia, su manejo agronómico y sus condiciones de almacenamiento. Objetivo. Determinar la actividad de la polifenil oxidasa, el contenido de lípidos, el color y las características organolépticas de cafés provenientes de 3 subestaciones experimentales. Materiales y métodos. Se siguió un diseño completamente aleatorio en arreglo factorial factorial 3x6 (lugares de procedencia del café y tiempo de almacenamiento respectivamente). Resultados. La actividad de la polifenil oxidasa es mayor en el café fresco-para las tres procedencias. El café procedente de Naranjal presentó actividades enzimáticas más altas que los cafés provenientes de las subestaciones Supía y la Catalina. El análisis de varianza mostró el efecto de la procedencia sobre la variable actividad enzimática. La actividad de la polifenil oxidasa en los cafés estudiados decrece con el tiempo de almacenamiento. El contenido de lípidos es menor a menor en la subestación de la Catalina. Todos los cafés fueron caracterizados de buena calidad en el tiempo cero de almacenamiento. Las características de aroma, intensidad del aroma y cuerpo presentaron altibajos en los diferentes meses de almacenamiento. El café de Naranjal, obtuvo en promedio una calificación aceptable a lo largo de los seis meses de almacenamiento. Conclusiones. Se encontraron diferencias significativas para las variables estudiadas por efecto de la procedencia y el almacenamiento. La actividad enzimática de la PFO presentó etapas de activación/inhibición, durante los seis meses de almacenamiento.

Abstract Background. The quality of the coffee bean has been related to its origin, the agronomic management and the storage conditions. Objective. To determine the activity of the polyphenyl oxidase, the lipid content, the color and the organoleptic characteristics of coffees from 3 experimental substations. Materials and methods. A completely randomized design was followed in a 3x6 factorial arrangement (places of coffee origin and storage time respectively). Results. The activity of polyphenyl oxidase is greater in fresh coffee-for the three provenances. The coffee from Naranjal presented higher enzymatic activities than the coffees from the Supía and the Catalina substations. The analysis of variance showed the effect of provenance on the enzyme activity variable. The activity of the polyphenyl oxidase in the coffees studied decreases with storage time. The lipid content is lower at a lower height in the Catalina. All coffees were characterized as good quality at zero storage time; but the characteristics of aroma, intensity of aroma and body presented ups and downs in the different months of storage. Naranjal coffee, on average, obtained an acceptable rating throughout the six months of storage. Conclusions. Significant differences were found for the variables studied due to the effect of provenance and storage. The enzymatic activity of the PFO showed activation / inhibition stages, during the six months of storage.

Aplicación seriada de paricalcitol intranodular ¿Es eficaz en el tratamiento del hiperparatiroidismo secundario refractario? / Serial intranodular application of paricalcitol Is effective in the treatment of secondary refractory hyperparathyroidism?

Objetivo: determinar la eficacia del paricalcitol en la reducción de los niveles de PTH intacta (PTHi) al aplicarlo directamente en las glándulas paratiroides en pacientes con enfermedad renal crónica estadio 5 (ERC E5) en terapia dialítica con hiperparatiroidismo refractario e hiperplasia nodular. Material y métodos: pacientes con ERC E5 en terapia de diálisis e hiperparatiroidismo secundario refractario y en quienes por ecografía de cuello se detectó hiperplasia de más de una glándula paratiroides, caracterizada por un volumen mayor de 500 mm³. A cada paciente por guía ecográfica dirigida se le aplicó 0.5 cc (2.5 ugs) de paricalcitol (Zemplar®) en cada glándula hiperplásica independientemente de su tamaño, y según el grupo. En el grupo 1 (G1) recibieron paricalcitol semanal para un máximo de dos glándulas por sesión siempre del mismo lado y por un total de dos dosis por glándula; para el grupo 2 (G2) paricalcitol cada 15 días en esquema semejante al grupo 1 para un total de dos dosis por glándula y finalmente para el grupo 3 (G3) paricalcitol cada mes, pero en cada sesión se inyectaron todas las glándulas para un total de cuatro dosis por glándula. Diseño: estudio de intervención sin grupo control. Análisis estadístico: se evaluó si la intervención daba lugar a reducción significativa en los valores de PTHi, y las variables calcio, fósforo, calcio x fósforo y fosfatasa alcalina. Resultados: en el G1 (seis pacientes) se encontró una disminución estadísticamente significativaentre el nivel promedio de PTHi inicial y PTHi a los 30 días de iniciado el tratamiento (p=0.0077), pero no a los 51 ni 81 días. En el G2 (seis pacientes) al comparar la PTHi inicial, con el valor detectado a los 51, 75, 105 y 135 días posaplicación de la última dosis de paricalcitol, no hubo cambios significativos. En el G3 (cuatro pacientes)con relación a la PTHi inicial hubo reducción significativa en sus valores a los 60 días (p=0.012), 120 días (p=0.0099) y 180 días (p=0.00095), pero no a los 240 días (p=0.214049). En las demás variables (calcio, fósforo, calcio x fósforo, fosfatasa alcalina) no se detectaron cambios significativos en ningún grupo. No se presentaron complicaciones importantes. Conclusiones: en pacientes con ERC E5, en terapia de diálisis e hiperparatiroidismo secundario refractario, la administración de paricalcitol intranodular logra reducir significativamente los nivelesde PTHi, siempre y cuando se administre en grupos de dos glándulas con un intervalo de tiempo no superior a una semana, o por administración mensual simultanea de todas las glándulas. (Acta Med Colomb 2015; 40: 125-131).

Objective: go determine the effectiveness of paricalcitol in reducing the levels of intact PTH (iPTH) when applied directly on the parathyroid glands in patients with Grade 5 chronic kidney disease (CKD G5) with refractory hyperparathyroidism and nodular hyperplasia in dialysis therapy. Materials and methods: CKD G5 patients on dialysis therapy with refractory secondary hyperparathyroidism in whom through neck echography hyperplasia of more than one parathyroid gland characterized by a volume greater than 500 mm³ was detected. Through directed ultrasound guidance to each patient 0.5 cc (2.5ugs) of paricalcitol (Zemplar®) was applied in each hyperplasticgland regardless of size and according to the group. Group 1 (G1) received weekly paricalcitol for up to two glands per session always on the same side, for a total of two doses per gland; Group 2 (G2) received paricalcitol every 15 days in similar scheme as group 1 for a total of two doses per gland and finally for group 3 (G3) paricalcitol each month, but in every session all the glands were injected for a total four doses per gland. Design: intervention study with no control group. Statistical analysis: an assessment whether the intervention resulted in significant reduction in iPTH and variables calcium, phosphorus, calcium x phosphorus and alkaline phosphatase, was made. Results: In G1 (six patients), a statistically significant decrease between the average level of initial iPTH and iPTH at 30 days of starting treatment (p = 0.0077), but not at 51 or 81 days was found. In G2 (six patients) by comparing the initial iPTH, with the detected value at 51, 75, 105 and 135 days post-application of the last dose of paricalcitol, there were no significant changes. In G3 (four patients) relative to the initial iPTH there was significant reduction in their values at 60 days (p = 0.012), 120 days (p = 0.0099) and 180 days (p = 0.00095), but not at 240 days (p = 0.214049). On the other variables (calcium, phosphorus, calcium x phosphorus, alkaline phosphatase), no significant changes were detected in either group. No major complications occurred. Conclusions: in patients with CKD G5 in dialysis therapy and refractory secondary hyperparathyroidism, administration of intranodular paricalcitol achieves significantly lower levels of iPTH, as long as it is administered in groups of two glands with a time interval not exceeding one week, or by simultaneous monthly administration of all glands. (Acta Med Colomb 2015; 40:125-131).

Valor agregado para el lacto suero de caprino proveniente de agroindustrias lácteas: ácido láctico como alternativa de descontaminación / Value added for goat whey from dairy agribusiness: lactic acid as decontamination alternative

El Lacto suero de leche de caprino (SLC) es un subproducto de bajo valor económico, concebido en Colombia como un desecho industrial con impacto ambiental negativo para los ecosistemas (DBO 60000 ppm y DQO de 80000 ppm). Este trabajo se enfocó en caracterizar el SLC, multiplicar la cepa Lactobacillus Helveticus (LH) 0-0.91-celulas libres y evaluar su pertinencia para la producción de ácido láctico a partir de SLC tratado y enriquecido con tres nutrientes; variables que se estudiaron siguiendo un diseño de cuadro greco latino. Para el efecto se llevaron a cabo 16 cinéticas en un biofermentador intermitente conteniendo 250 mililitros de LSLC en donde la mayor producción de ácido láctico-17.72 gramos por litro se logró después de las 50 horas para el medio que contiene extracto de levadura 2,5%, riboflavina 0,6% y sulfato de amonio 0,45% operando el biofermentador a 42°C. De esta forma, al producir ácido láctico se evitaría la contaminación de ecosistemas y se generaría un valor agregado a la industria quesera.

The lacto goat whey (SLC) is a low economic value sub product, considered as industrial waste in Colombia, with negative environmental impact on ecosystems- (BOD 60,000 COD ppm and 80,000 ppm). This study aimed to characterize the SLC, multiply Lactobacillus helveticus (LH) strain and assess its applicability to the production of lactic acid-AL from LSLC treated and enriched with three nutrients. Variables studied following a latin greco square design. For this purpose kinetic 16 were carried out in intermittent biofermenter containing 250 milliliters of LSLC. Increased production of lactic acid (17.72 grams per liter) was achieved after 50 hours using a media containing 2.5% yeast extract, riboflavin 0.6% and 0.45% ammonium sulfate and the biofermenter operating at 42° C.

La efcacia del etanol intraglandular en hiperparatiroidismo secundario se limita a una sola glándula hiperplásica / Effectiveness of intraglandular ethanol in secondary hyperparathyroidism limited to one only hyperplastic gland

Objetivo: determinar la eficacia del etanol al 99,5% en reducción de los niveles de PTH intacta (PTHI) al aplicarlo directamente en las glándulas paratiroides hiperplásicas de sujetos con enfermedad renal crónica (ERC) estadio 5 en terapia dialítica con hiperparatiroidismo secundario. Diseño: estudio de intervención sin grupo control. Analisis estadístico: se utilizaron pruebas de tendencia central y de dispersión (media, desviación estándar) y se realizó la comparación de medias a través de la prueba t de Student. Pacientes, material y métodos: durante un periodo de recolección de dos años se identificaron sujetos con ERC estadio 5 en terapia dialítica (hemodiálisis o diálisis peritoneal), mayores de 18 años, quienes presentaran niveles de PTHI séricos mayores a 600 pg/mL, e hiperplasia de glándulas paratiroides autónoma (volumen mayor a 500 mm³) confirmada por ultrasonografía de cuello. Bajo visión ecográfica se les aplicó etanol en cada glándula hiperplásica, volumen dependiente de tamaño glandular para un máximo de dos aplicaciones por glándula con un intervalo de 30 días; si habían más de dos glándulas alteradas sólo se permitió la infiltración de dos glándulas por sesión. Quince sujetos fueron sometidos a la terapia, en el grupo 1 (G1) se incluyeron cinco sujetos con una sola glándula hiperplásica, el grupo 5 (G5) incluyó diez sujetos con más de una glándula hiperplásica: grupos 2, 3 y 4 cada uno con tres, dos y cinco sujetos con dos, tres y cuatro glándulas hiperplásicas respectivamente. Los niveles de PTHI se evaluaron a los 30, 60, 90 y 120 días posterior a la última aplicación, al igual que las variables calcio, fósforo, producto calcio-fósforo y hemoglobina. La fosfatasa alcalina se evaluó inicialmente y a los tres meses. Resultados: la administración de etanol intraglandular disminuyó los valores de PTHI significativamente en la población total de sujetos desde un valor basal de 1263 ± 554pg/mL a 1065 ± 437pg/mL (valor p: 0.08), 989 ± 568pg/mL (valor p: 0.02), 1028 ± 643pg/mL (valor p: 0.04) y 1139 ± 749pg/mL (valor p: 0.194) a los intervalos previamente descritos. En el análisis de grupos se observó que sólo el G1 presentó una reducción significativa en los valores de PTHI, con disminución de un valor basal promedio de 910 ± 508pg/mL a 693 ± 432 (valor p: 0.04), 534 ± 426 (p: 0.006), 330 ± 379 (p: 0.01) y 322 ± 75 (p: 0.44). En los otros grupos consolidados en el grupo 5 (G5) con más de una glándula hiperplásica los valores de PTHI no se modificaron en forma importante, siendo su valor inicial 1430 ± 520pg/mL y sus valores posteriores 1251 ± 313 (p: 0.287), 1241 ± 482 (p: 0.255), 1378 ± 416 (p: 0.635) y 1489 ± 591 (p: 0.869). Los valores de calcio, fósforo, producto calcio-fósforo y fosfatasa alcalina, se disminuyeron en todos los grupos en forma no significativa, probablemente por el corto tiempo de seguimiento. El evento adverso más frecuente fue dolor y sensación de quemazón que se extendió de 5-10 segundos en el área inyectada, con presencia de hipotensión en un sujeto y disfonía en tres sujetos, resolviéndose con fonoaudiología en el curso de tres meses. Todos los sujetos con falla terapéutica fueron referidos a cirugía de cabeza y cuello con intención de paratiroidectomía, con hallazgos de grandes bandas fibrosas durante la cirugía en los ocho pacientes operados a la fecha. Conclusión: el etanol intraglandular controla eficazmente el hiperparatiroidismo secundario en sujetos con alteración de una glándula hiperplásica. Sujetos con más de una glándula hiperplásica deben ser manejados quirúrgicamente o con un calcimimético oral tipo Cinacalcet.

Objective: determine the efficacy of ethanol 99.5% in intact PTH (PTHi) levels reduction when applied directly in the hyperplastic parathyroid glands of subjects with chronic kidney disease (CKD) stage 5 on dialysis with secondary hyperparathyroidism. Design: intervention study without control group. Statistical analysis: we used central tendency and dispersion tests (mean, standard deviation) and the measurement comparison was made by Student's t test. Patients, materials and methods: over a collection period of two years, we identified subjects with CKD stage 5 on dialysis therapy (hemodialysis or peritoneal dialysis), over 18 years of age, who presented serum IPTH levels greater than 600 pg / ml, and autonomous parathyroid glands hyperplasia (volume greater than 500 mm³) confirmed by neck ultrasonography. Under ultrasound guidance ethanol was applied to each hyperplastic gland according to the glandular volume for a maximum of two applications per gland with an interval of 30 days; in case of more than 2 glands compromised, the infiltration of only 2 glands per session was allowed. 15 subjects underwent therapy. In group 1 (G1) were included 5 subjects with one only hyperplastic gland; group 5 (G5) included 10 subjects with more than one hyperplastic gland. Groups 2, 3 and 4 each one with 3, 2 and 5 subjects with two, three and four hyperplastic glands respectively. IPTH levels were assessed at 30, 60, 90 and 120 days after the last application, as well as variables like calcium, phosphorus, calcium-phosphorus product and hemoglobin. Alkaline phosphatase was assessed initially and at 3 months. Results: intraglandular ethanol administration decreased significantly IPTH values in the total population of subjects from a baseline value of 1263 ± 554 pg / ml to 1065 ± 437 pg / ml (p value: 0.08), 989 ± 568 pg / ml (p value: 0.02), 1028 ± 643 pg / ml (p value: 0.04) and 1139 ± 749 pg / ml (p value: 0.194) to the previously described intervals. In the analysis of groups, we observed that only G1 presented a significant reduction of IPTH values, with a decrease of a mean baseline value of 910 ± 508 pg / ml to 693 ± 432 (p value: 0.04), 534 ± 426 (p: 0.006), 330 ± 379 (p: 0.01) and 322 ± 75 (p = .44). In the other groups consolidated in group 5 (G5) with more than 1 hyperplastic gland, IPTH values were not significantly modified, being its initial value 1430 ± 520 pg / ml and its subsequent values 1251 ± 313 (p: 0.287), 1241 ± 482 (p: 0.255), 1378 ± 416 (p = 0.635) and 1489 ± 591 (p: 0.869). The values of calcium, phosphorus, calcium-phosphorus product and alkaline phosphatase decreased in all groups in a not significant way, probably because of the short follow-up time. The most common adverse event was pain and burning sensation that lasted for 5-10 seconds in the injected area, with presence of hypotension in one subject and dysphonia in 3 subjects, resolving with phonoaudiology therapy in the course of three months. All subjects with therapeutic failure were referred to head and neck surgery for parathyroidectomy, finding large fibrous bands during surgery in 8 patients operated to date. Conclusion: intraglandular ethanol effectively controls secondary hyperparathyroidism in patients with one impaired hyperplastic gland. Subjets with more than one hyperplastic gland should be treated surgically or with an oral calcimimetic, Cinacalcet type.

Prevalencia del síndrome intestino irritable en la población adulta venezolana / Prevalence of irritable bowel syndrome in venezuelan adults

El síndrome del intestino irritable (SII) es un trastorno digestivo funcional que afecta del 10 al 20% de la población general. Existen pocos estudios en Latinoamérica que muestren su prevalencia nacional, y en Venezuela no disponemos de investigación que reporte tan importante cifra. Estudio multicéntrico, descriptivo, transversal, durante los meses abril y mayo del 2011. Se utilizó el cuestionario validado de la Fundación Roma, con quienes firmamos convenio como Servicio de Gastroenterología del Hospital Vargas de Caracas. Se seleccionaron al azar 15 estados, en cada uno un municipio, y de estos lugares como iglesias, centros comerciales, reuniones de Consejos Comunales, paradas de autobuses, etc. Los valores obtenidos fueron transcritos en una base de datos en Excel y procesados con EPIDAT 3.1. De 1781 personas encuestadas, 299 presentaron criterios clínicos diagnósticos para SII de acuerdo a Roma III. La prevalencia nacional del SII fue de 16,80%, correspondiendo 81,6% a mujeres (244) y 18,4% a hombres (55). El grupo etario entre 38 y 47 años fue el más afectado (26,43%) y el subtipo mixto el más predominante. La prevalencia del SII en la población adulta venezolana según los criterios de Roma III es de 16,80%

Irritable bowel syndrome (IBS) is a functional digestive disorder that affects 10 to 20% of the general population. Few studies exist in Latin America that shows the national prevalence, and in Venezuela we don´t have investigation resources that support those numbers. Multicenter study, descriptive, transversal, during the months April and May 2011. The validated Roma Foundation questionnaire was used. This Foundation authorized its use by the Service of Gastroenterology Hospital Vargas de Caracas. 15 states were randomly selected, in each state one municipality, and in those places as churches, shopping centers, comunity meeting, bus stops, etc. The values obtained were transcribed into a database in Excel and processed EPIDAT 3.1. Of 1781 people encuested, 299 met the criteria for IBS according to Rome III. The national prevalence of IBS was 16.80%, with 81.6% women (244) and 18.4% men (55). The age group between 38 and 47 years was the most affected (26.43%) and the mix was the most predominant subtype. The prevalence of IBS in the Venezuelan adult population according to Rome III criteria is 16.80%

Método de superficie de respuesta para optimizar las condiciones de producción de ácido láctico a partir de subproductos lácteos: SLC / Response surface method for the optimization of lactic acid production conditions from dairy sub products

Mediante un diseño experimental 2k combinado con un diseño compuesto central y un análisis de superficie de respuesta se optimizo la producción de ácido láctico (AL) a partir de suero de leche de caprino (SLC) como sustrato principal y se determinó la combinación de los efectos de la concentración de tres nutrimentos: riboflavina, extracto de levadura y sulfato de amonio. Según el experimento realizado (confiabilidad; 95%) existe evidencia que tanto la temperatura y la concentración del complemento como la interacción de ambos inciden en la producción de ácido láctico (AL), que se obtiene al fermentar suero de leche de caprino. Las mayores producciones de ácido lactico-23,68 g/litro y crecimiento bacteriano se obtuvieron con mayores concentraciones de los nutrimentos a una temperatura de 42oC.

In the study the production of lactic acid from whey goats as main substrate (SLC) was optimized, following 2k experimental design combined with a central composite design and response surface analysis. It was also determined the combined effects of the concentration of three nutrient level (Riboflavin, yeast extract, ammonium sulfate): X1 and temperature (0C): X2 in lactic acid concentration. According with the results there is enough statistical evidence (95% confidence) that showed that the temperature and the concentration of complement and their interaction influence the production of lactic acid obtained by fermenting goat whey. The greatest lactic acid production (23, 68 g / liter) and bacterial growth were gotten with higher concentrations of nutrients and temperature of 42°C.

Detección de hiperplasia de paratiroides por ultrasonografía y correlación con signos clínicos y de laboratorio en pacientes con enfermedad renal crónica / Ultrasound detection of parathyroid hyperplasia and correlation with clinical and laboratory findings in patients with chronic kidney disease

Objetivo: Determinar la correlación entre la hiperplasia de paratiroides detectada por ecografía de alta resolución y variables clínicas y de laboratorio en pacientes con hiperparatiroidismo secundario a enfermedad renal crónica (ERC) estadio 5 en terapiadialítica en RTS Ltda, sucursal Caldas, Hospital Santa Sofía, Hospital Infantil. Métodos: A lospacientes detectados se les practicó ultrasonografía de tiroides y paratiroides con un equipo de alta resolución. Se analizaron variables como etiología, duración de la ERC, tiempo en terapia dialítica, tipo de diálisis, presencia de síntomas relacionados con hiperparatiroidismo (dolor óseo, fracturas, prurito) y las variables de laboratorio PTH intacta, calcio, fósforo,producto calcio por fósforo y fosfatasa alcalina. Resultados: De 403 pacientes evaluados, 92 cumplieron con los criterios de inclusión y se realizó ultrasonografía en 86. En este grupo de pacientes la causa más común de ERC fue nefroesclerosis hipertensiva, con un tiempo promedio en diálisis de 61,4 ± 36,6 meses. De los pacientes, 37 se encontraron en diálisis peritoneal y 49 en hemodiálisis. La correlación entre las variables de laboratorio y la presencia de hiperplasia de paratiroides no demostró significancia estadística cuando se comparó contra el grupo sin documentación ecográfica de crecimiento glandular paratiroideo.Conclusión: La hiperplasia de paratiroides puede estar presente en cualquier paciente con ERC estadio 5 y valores de PTH intacta mayores a 400 pg/ml, independientemente de sus variables clínicas y de laboratorio. Es necesario practicarle ultrasonografía a todos los pacientes con cifras altas de PTH, con el fin de asignarles una terapia eficiente.