Fatores associados ao autocuidado praticado por pessoas com estomias de eliminação / Factors associated with self-care practiced by people with intestinal elimination stomas / Factores asociados al autocuidado practicado por personas con estomas de eliminación

Objetivo: avaliar os fatores associados ao autocuidado praticado por pessoas com estomias de eliminação. Método: estudo transversal analítico, baseado nas respostas de 153 pessoas com estomia de eliminação, atendidas em um ambulatório de referência no cuidado de pessoas com estomas, no município de Teresina. A coleta de dados ocorreu por meio de um formulário semiestruturado com dados demográficos e acerca do autocuidado. Os dados foram analisados mediante estatística descritiva e inferencial. O teste Qui-quadrado de Pearson foi utilizado na análise inferencial. Resultados: o esvaziamento da bolsa, limpeza do estoma, secagem da pele periestoma, descolamento da placa, medição do estoma, realização do molde, adaptação, autoestima e isolamento social apresentaram associação significativa com o autocuidado (p<0,05). Conclusão: evidenciou-se que os fatores associados ao autocuidado foram os cuidados com o estoma e com o equipamento coletor, além dos impactos na autoestima e na vida social(AU)

Objective: to evaluate the factors associated with self-care practiced by people with elimination stomas. Method: analytical cross-sectional study, based on the responses of 153 people with elimination stoma, treated at a reference outpatient clinic for the care of people with stoma, in the city of Teresina. Data collection took place through a semi-structured form with demographic data and about self-care. Analyzes were performed using inferential statistics, using the chi-square test. Results: Emptying the pouch, cleaning the stoma, drying the peristomal skin, detaching the plaque, measuring the stoma, making the mold, fitting, , self-esteem and social isolation were significantly associated with self-care (p<0.05). Conclusion: it was evident that the factors associated with self-care were care for the stoma and the collection equipment, in addition to the impacts on self-esteem and social life(AU)

Objetivo: evaluar los factores asociados al autocuidado practicado por personas con estomas de eliminación. Método: estudio transversal analítico, basado en las respuestas de 153 personas con estoma de eliminación, atendidos en un ambulatorio de referencia para la atención de personas con estoma, en la ciudad de Teresina. Se realizó la recolección de datos a través de un formulario semiestructurado con datos demográficos y sobre autocuidado. Los datos se analizaron utilizando estadística descriptiva e inferencial, utilizando la prueba Chi-cuadrado de Pearson. Resultados: vaciar la bolsa, limpiar la estoma, secar la piel periestomal, despegar la placa, medir la estoma, hacer el molde, adaptarlo, vaciar la bolsa, la autoestima y el aislamiento social se asociaron significativamente con el autocuidado (p<0,05). Conclusión: se evidenció que los factores asociados al autocuidado fueron el cuidado de la estoma y del equipo de recolección, además de los impactos en la autoestima y la vida social(AU)

Myocardial Milieu Favors Local Differentiation of Regulatory T Cells.

BACKGROUND: In the past years, several studies investigated how distinct immune cell subsets affects post-myocardial infarction repair. However, whether and how the tissue environment controls these local immune responses has remained poorly understood. We sought to investigate how antigen-specific T-helper cells differentiate under myocardial milieu's influence. METHODS: We used a transgenic T cell receptor (TCR-M) model and major histocompatibility complex-II tetramers, both myosin-specific, combined with single-cell transcriptomics (single-cell RNA sequencing [scRNA-seq]) and functional phenotyping to elucidate how the antigen-specific CD4+ T cells differentiate in the murine infarcted myocardium and influence tissue repair. Additionally, we transferred proinflammatory versus regulatory predifferentiated TCR-M-cells to dissect how they specially contribute to post-myocardial infarction inflammation. RESULTS: Flow cytometry and scRNA-/TCR-seq analyses revealed that transferred TCR-M cells acquired an induced regulatory phenotype (induced regulatory T cell) in the infarcted myocardium and blunted local inflammation. Myocardial TCR-M cells differentiated into 2 main lineages enriched with either cell activation and profibrotic transcripts (eg, Tgfb1) or suppressor immune checkpoints (eg, Pdcd1), which we also found in human myocardial tissue. These cells produced high levels of LAP (latency-associated peptide) and inhibited IL-17 (interleukin-17) responses. Endogenous myosin-specific T-helper cells, identified using genetically barcoded tetramers, also accumulated in infarcted hearts and exhibited a regulatory phenotype. Notably, TCR-M cells that were predifferentiated toward a regulatory phenotype in vitro maintained stable in vivo FOXP3 (Forkhead box P3) expression and anti-inflammatory activity whereas TH17 partially converted toward a regulatory phenotype in the injured myocardium. Overall, the myosin-specific Tregs dampened post-myocardial infarction inflammation, suppressed neighboring T cells, and were associated with improved cardiac function. CONCLUSIONS: These findings provide novel evidence that the heart and its draining lymph nodes actively shape local immune responses by promoting the differentiation of antigen-specific Tregs poised with suppressive function.

Characterization of the effect of the GLUT-1 inhibitor BAY-876 on T cells and macrophages.

Increased aerobic glycolysis is a metabolic hallmark of proinflammatory leukocytes including macrophages and T cells. To take up glucose from the environment and fuel glycolysis, activated leukocytes upregulate the glucose transporter GLUT1. The orally bioavailable selective GLUT1 inhibitor BAY-876 was developed primarily as an anti-tumor drug. Our study assessed its activity on activated macrophages and CD4+ T cells. BAY-876 significantly attenuated glucose uptake by cultured CD4+ T cells and macrophages by 41% and 15%, respectively. Extracellular flux analysis of activated CD4+ T cells in vitro showed that BAY-876 significantly decreases glycolytic proton flux rate and lactate production, effects that are accompanied by an increased oxidative phosphorylation-mediated ATP production rate, leaving intracellular ATP levels per cell unchanged. However, GLUT1 inhibition reduced CD4+ T cell proliferation without compromising cell viability and reduced IFN-γ secretion by 20%. Moreover, TNF secretion from macrophages was reduced by 27%. We conclude that GLUT1-specific inhibitors, like BAY-876, deserve further in vivo testing in a broad range of (auto-) inflammatory disease models.

Ohmic heating treatment in high-protein vanilla flavored milk: Quality, processing factors, and biological activity.

The processing of high-protein vanilla-flavored milk was performed under different electric field strengths of ohmic heating (5.22 V/cm, OH6; 6.96 V/cm, OH8; 8.70 V/cm, OH10; 10.43 V/cm, OH12) to evaluate the energy consumption, processing parameters, and microbiological, rheological, and biological aspects, compared with the sample submitted to conventional pasteurization (PAST, 72 °C/15 s). All samples showed higher than 12 g/100 mL of protein, consisting of high-protein content products. In addition, Ohmic Heating (OH) generated lower energy expenditure and more significant microbial inactivation of lactic acid bacteria, molds and yeasts, total mesophiles, and psychotropics. Furthermore, OH at lower electric field strengths, mainly OH8, improved anti-diabetic, anti-oxidant, and anti-hypertensive activities and rheological properties, and resulted in lower hydroxymethylfurfural contents, and higher whey protein nitrogen index. The results suggest that OH is a technology that can be used in flavored milk with high-protein content, being recommended an electric field strength of 6.96 V/cm. However, more studies are necessary to evaluate the effect of OH on high-protein dairy products, mainly by studying other OH processing parameters.

The era of in vivo T cell engineering.

Cell therapy with genetically engineered T cells has revolutionized the treatment of malignant diseases, but its potential use beyond the realms of oncology has been underexplored. In a recent study, Rurik et al.1 built on the technologies underlying mRNA vaccines to transduce T cells in vivo, harnessing them to target cardiac fibrosis.

Upregulation of Phosphodiesterase 2A Augments T Cell Activation by Changing cGMP/cAMP Cross-Talk.

3',5'-cyclic adenosine monophosphate (cAMP) is well-known for its diverse immunomodulatory properties, primarily inhibitory effects during T cell activation, proliferation, and production of pro-inflammatory cytokines. A decrease in cAMP levels, due to the hydrolyzing activity of phosphodiesterases (PDE), is favoring inflammatory responses. This can be prevented by selective PDE inhibitors, which makes PDEs important therapeutic targets for autoimmune disorders. In this study, we investigated the specific roles of PDE2A and PDE3B in the regulation of intracellular cAMP levels in different mouse T cell subsets. Unexpectedly, T cell receptor (TCR) activation led to a selective upregulation of PDE2A at the protein level in conventional T cells (Tcon), whereas no changes were detected in regulatory T cells (Treg). In contrast, protein expression of PDE3B was significantly higher in both non-activated and activated Tcon subsets as compared to Treg, with no changes upon TCR engagement. Live-cell imaging of T cells expressing a highly sensitive Förster resonance energy transfer (FRET)-based biosensor, Epac1-camps, has enabled cAMP measurements in real time and revealed stronger responses to the PDE2A inhibitors in activated vs non-activated Tcon. Importantly, stimulation of intracellular cGMP levels with natriuretic peptides led to an increase of cAMP in non-activated and a decrease of cAMP in activated Tcon, suggesting that TCR activation changes the PDE3B-dependent positive to PDE2A-dependent negative cGMP/cAMP cross-talk. Functionally, this switch induced higher expression of early activation markers CD25 and CD69. This constitutes a potentially interesting feed-forward mechanism during autoimmune and inflammatory responses that may be exploited therapeutically.

The healing myocardium mobilizes a distinct B-cell subset through a CXCL13-CXCR5-dependent mechanism.

AIMS: Recent studies have revealed that B cells and antibodies can influence inflammation and remodelling following a myocardial infarction (MI) and culminating in heart failure-but the mechanisms underlying these observations remain elusive. We therefore conducted in mice a deep phenotyping of the post-MI B-cell responses in infarcted hearts and mediastinal lymph nodes, which drain the myocardium. Thereby, we sought to dissect the mechanisms controlling B-cell mobilization and activity in situ. METHODS AND RESULTS: Histological, flow cytometry, and single-cell RNA-sequencing (scRNA-seq) analyses revealed a rapid accumulation of diverse B-cell subsets in infarcted murine hearts, paralleled by mild clonal expansion of germinal centre B cells in the mediastinal lymph nodes. The repertoire of cardiac B cells was largely polyclonal and showed no sign of antigen-driven clonal expansion. Instead, it included a distinct subset exclusively found in the heart, herein termed 'heart-associated B cells' (hB) that expressed high levels of Cd69 as an activation marker, C-C-chemokine receptor type 7 (Ccr7), CXC-chemokine receptor type 5 (Cxcr5), and transforming growth factor beta 1 (Tgfb1). This distinct signature was not shared with any other cell population in the healing myocardium. Moreover, we detected a myocardial gradient of CXC-motif chemokine ligand 13 (CXCL13, the ligand of CXCR5) on Days 1 and 5 post-MI. When compared with wild-type controls, mice treated with a neutralizing CXCL13-specific antibody as well as CXCR5-deficient mice showed reduced post-MI infiltration of B cells and reduced local Tgfb1 expression but no differences in contractile function nor myocardial morphology were observed between groups. CONCLUSION: Our study reveals that polyclonal B cells showing no sign of antigen-specificity readily infiltrate the heart after MI via the CXCL13-CXCR5 axis and contribute to local TGF-ß1 production. The local B-cell responses are paralleled by mild antigen-driven germinal centre reactions in the mediastinal lymph nodes that might ultimately lead to the production of specific antibodies.

Tuberculosis situation in the program area of a general acute care hospital in Buenos Aires City, 2017-2019 / Tuberculosis situation in the program area of a general acute care hospital in Buenos Aires City, 2017-2019

INTRODUCCIÓN: La tuberculosis (TB) genera una gran carga de enfermedad a nivel global. Su elevada presencia en grandes ciudades se explica porque ellas son escenarios de urbanización acelerada, fuertes inequidades sociales y concentración de circunstancias de vulnerabilidad. El objetivo fue analizar la situación epidemiológica de la TB en un área programática (AP) de la Ciudad de Buenos Aires entre 2017 y 2019. MÉTODOS: Se realizó un estudio descriptivo de corte transversal. La población de estudio fueron los casos notificados de TB en residentes en el AP del Hospital Fernández (HF). La fuente de datos principal fue el Sistema Nacional de Vigilancia de Salud. RESULTADOS: Se registraron 375 casos. En 2017 se presentó la tasa de notificación de TB más alta del AP (29,2). Los casos se concentraron en el barrio de Retiro y alcanzaron su mayor tasa en 2018 (134,5). Los barrios populares presentaron 12 veces la tasa del AP (305,1). De todos los casos, 213 fueron de género masculino (56,8%), con 29 años como mediana de edad. Mayormente fueron notificados por la red de efectores del AP del HF. Respecto a la evolución, en 169 casos fue satisfactoria (45,1%), y 138 no registraron datos de evolución (36,8%). DISCUSIÓN: El análisis epidemiológico desagregado reveló la gran complejidad del territorio respecto a este padecimiento de salud. Las redes de abordaje interdisciplinarias e intersectoriales resultan claves para garantizar la accesibilidad al cuidado y tratamiento en esta población.

Treatment of mice with a ligand binding blocking anti-CD28 monoclonal antibody improves healing after myocardial infarction.

Both conventional and regulatory CD4+ T-cells rely on costimulatory signals mediated by cell surface receptors including CD28 for full activation. We showed previously that stimulation of CD4+ Foxp3+ regulatory T-cells by superagonistic anti-CD28 monoclonal antibodies (mAb) improves myocardial healing after experimental myocardial infarction (MI). However, the effect of ligand binding blocking anti-CD28 monoclonal antibodies has not yet been tested in this context. We hypothesize that ligand blocking anti-CD28 mAb treatment might favorably impact on healing after MI by limiting the activation of conventional CD4+ T-cells. Therefore, we studied the therapeutic effect of the recently characterized mAb E18 which blocks ligand binding to CD28 in a mouse permanent coronary ligation model. E18 or an irrelevant control mAb was applied once on day two after myocardial infarction to wildtype mice. Echocardiography was performed on day 7 after MI. E18 treatment improved the survival and reduced the incidence of left ventricular ruptures after experimental myocardial infarction. Accordingly, although we found no difference in infarct size, there was significantly less left ventricular dilation after E18 treatment in surviving animals as determined by echocardiography at day 7 after MI. In sham operated control mice neither antibody had an impact on body weight, survival, and echocardiographic parameters. Mechanistically, compared to control immunoglobulin, E18 treatment reduced the number of CD4+ T-cells and monocytes/macrophages within the infarct and periinfarct zone on day 5. This was accompanied by an upregulation of arginase which is a marker for alternatively differentiated macrophages. The data indicate that CD28-dependent costimulation of CD4+ T-cells impairs myocardial healing and anti-CD28 antibody treatment constitutes a potentially clinically translatable approach to improve the outcome early after MI.

Transitional Cell Carcinoma of the Bladder in Pediatric Patients: Where Do We Stand? / Carcinoma de células transicionales de vejiga en pacientes pediatricos: ¿Dónde nos encontramos?

Introduction Transitional cell carcinoma of the bladder (TCCB) is uncommon in the pediatric population, and its etiology, natural history and epigenetics remain poorly understood. We aim to describe six cases of TCCB in pediatric patients and discuss the state of the art in the management and follow-up of the patients with this uncommon early presentation. Methods The clinicopathological data of 6 patients with TCCB who underwent transurethral resection of bladder tumor (TURBT) were obtained from our institutional database. The patient data were collected retrospectively. A review of the literature was performed, and the most relevant and trending data were analyzed. Results A total of 6 patients (4 female, 2 male) were treated at our institution between 2004 and 2019. The mean age of the sample was 12 years, and the presenting symptoms were macroscopic hematuria (3 cases), suprapubic pain (2 cases), and 1 case was an incidental finding during pelvic ultrasonography. The long-term follow-up (median follow-up of 61 months) did not reveal recurrence. Conclusion Transitional cell carcinoma of the bladder rarely presents in the pediatric population. Genetic and epigenetic anomalies have been proposed as causes, as well as carcinogenic exposure. The reported cases tend to have a good prognosis, and most are non-invasive at the diagnosis. Follow-up protocols are still lacking, as well as molecular insights on tumor development and prognostic markers.

Introducción Carcinoma de células transicionales de vejiga (CCTV) es una patología rara en la población pediátrica, su etiología, historia natural y epigenetica son pobremente entendidos. El objetivo de este articulo es describir 6 casos de CCTV en pacientes pediátricos, discutir el estado del arte en el manejo y seguimiento de los pacientes. Métodos Los datos clinicopatologicos de 6 pacientes con CCTV sometidos a resección transuretral de tumor vesical (RTU-TV) se analizaron de nuestra base de datos institucional. Los datos fueron recolectados y analizados de manera retrospectiva. Se realizo una revisión de la literatura y solo los artículos mas relevantes fueron analizados. Resultados Un total de 6 pacientes (4 mujeres, 2 hombres) fueron tratados en nuestra institución entre el 2004 y el 2019. La media de edad fue 12 años y los síntomas mas frecuentes fueron hematuria macroscópica (3 casos), dolor suprapúbico (2 casos) y en un caso fue un hallazgo incidental durante una ultrasonografía pélvica. El seguimiento a largo plazo (mediana de seguimiento de 61 meses) no mostro recurrencia en ningún paciente. Conclusión CCTV se presenta infrecuentemente en la población pediátrica, Anomalías genéticas y epigeneticas han sido propuestas como causas predisponentes al igual que la exposición a carcinogénicos. Los casos reportados tienden a tener un buen pronostico y la gran mayoría son no musculo invasivos al momento del diagnostico. Protocolos de seguimiento no están claramente definidos igual que vías moleculares en la tumorogenésis y marcadores pronósticos

Microbiota-derived peptide mimics drive lethal inflammatory cardiomyopathy.

Myocarditis can develop into inflammatory cardiomyopathy through chronic stimulation of myosin heavy chain 6-specific T helper (TH)1 and TH17 cells. However, mechanisms governing the cardiotoxicity programming of heart-specific T cells have remained elusive. Using a mouse model of spontaneous autoimmune myocarditis, we show that progression of myocarditis to lethal heart disease depends on cardiac myosin-specific TH17 cells imprinted in the intestine by a commensal Bacteroides species peptide mimic. Both the successful prevention of lethal disease in mice by antibiotic therapy and the significantly elevated Bacteroides-specific CD4+ T cell and B cell responses observed in human myocarditis patients suggest that mimic peptides from commensal bacteria can promote inflammatory cardiomyopathy in genetically susceptible individuals. The ability to restrain cardiotoxic T cells through manipulation of the microbiome thereby transforms inflammatory cardiomyopathy into a targetable disease.

Characterization of Acinetobacter spp. from raw goat Milk / Caracterização de Acinetobacter spp. isolados de leite caprino cru

ABSTRACT: Goat's milk has been suggested as an alternative to cow's milk, being a better digestible and hypoallergenic option. However, the presence of contaminating bacteria may significantly affect the safety of the product. In this research, we reported the isolation and characterization of Acinetobacter spp. isolates from raw goat milk samples purchased in the state of Rio de Janeiro, Brazil. Twenty-one samples were analyzed and ten isolates of Acinetobacter spp. were obtained. Six were identified as A. guillouiae, three as A. ursingii, and one as A. bereziniae. These isolates were characterized and eight showed proteolytic activity, seven showed lipolytic activity, and five isolates were able to produce both enzymes. None of the isolates was biofilm producer. However, when the production of antibiotic resistance enzymes KPC and ESBL were investigated, all isolates presented ESBL-positive phenotype, while eight (80%) were KPC-positive. This research, therefore, demonstrated that raw goat's milk can also be a source of Acinetobacter spp., which can produce important thermostable deteriorating enzymes and may play a role of reservoirs of antibiotic resistance genes.

RESUMO: O leite de cabra tem sido sugerido como alternativa ao leite de vaca, sendo uma opção com melhor digestibilidade e menor alergenicidade. No entanto, a presença de bactérias contaminantes pode afetar significativamente a segurança do produto. Neste trabalho, relatamos o isolamento e caracterização de Acinetobacter spp. isolados de amostras de leite cru de cabra adquiridas no Estado do Rio de Janeiro, Brasil. Vinte e uma amostras foram analisadas e dez isolados de Acinetobacter spp. foram obtidos, sendo seis identificados como A. guillouiae, três como A. ursingii e um como A. bereziniae. Estes isolados foram caracterizados e oito apresentaram atividade proteolítica, sete mostraram atividade lipolítica e cinco foram capazes de produzir ambas as enzimas. Nenhum dos isolados foi produtor de biofilme. No entanto, todos os isolados apresentaram fenótipo ESBL-positivo, enquanto oito (80%) foram positivos para KPC. Este trabalho demonstra, portanto, que o leite de cabra cru também pode ser uma fonte de Acinetobacter spp., que podem produzir enzimas deteriorantes termoestáveis e desempenhar, também, um papel de reservatórios de genes de resistência a antibióticos.

Nefrolitotomía percutánea ambulatoria: serie de casos y revisión de la literatura / Percutaneous Nephrolithotomy Ambulatory: Case Series and Literature Review

La nefrolitotomía percutánea (PCNL), es un procedimiento mínimamente invasivo, considerado como el tratamiento de elección para el manejo de los cálculos renales de gran tamaño o de formación compleja. Esa técnica fue introducida en la urología desde hace más de 30 años. Inicialmente fue Goodwin en 1955 quien realizó el primer abordaje percutáneo en un riñón.1 Posteriormente en 1976 Fernstórm y Johansson, efectuaron la primera extracción de un cálculo renal por vía percutánea2; permitiendo así el inicio y desarrollo de una nueva técnica mínimamente invasiva para el manejo de la litiasis renal. Aquella técnica, si bien presenta menor morbilidad que la cirugía abierta, no es un procedimiento libre de complicaciones, por lo cual se han realizado una seria de modificaciones de la técnica inicial.

Percutaneous nephrolithotomy (PCNL) is a procedure minimally invasive, considered to be the treatment of choice for the handling of large kidney stones size or complex formation. This technique was introduced into urology over 30 years ago. Initially it was Goodwin in 1955 who made the first percutaneous approach in a kidney.1 Subsequently in 1976 Fernstórm and Johansson, carried out the first extraction of the a percutaneous renal stone2; thus allowing the initiation and development of a new technique minimally invasive for the management of renal lithiasis. This technique, although it presents less morbidity than the open surgery, it is not a procedure free of complications, for which a series of tests have been carried out. modifications to the initial technique

Myocardial fibrosis seen through the lenses of T-cell biology.

Lymphocytes came recently into focus as modulators of non-infectious myocardial diseases. Several lines of experimental evidence now indicate that CD4(+) T-cells can influence the healing and scarring processes that follow a myocardial infarction episode. Furthermore, such heart-directed T-cell activity has also been implicated in the pathogenesis cardiac remodeling that develops in response to chronic pressure-overload conditions. Mechanistically, different T-cell subsets can secrete several mediators and growth factors that influence the myocardial molecular milieu and directly interfere with the macrophages' and fibroblasts' activity. Therefore, the present review summarizes the current experimental evidence on the role of T-cells in myocardial scar formation after infarction and myocardial fibrosis as central mechanism of ventricular remodeling.

[High frequency of thyroid abnormalities in polycystic ovary syndrome]. / Alta frecuencia de trastornos tiroideos en el síndrome de ovario poliquístico.

The prevalence of thyroid abnormalities (TA) has not been sufficiently assessed in polycystic ovary syndrome (PCOS). Our aim was to evaluate this relationship. In this prospective study 194 women were included. The PCOS group consisted of 142 patients (diagnosed by Rotterdam 2003 criteria) and the control group included 52 age-matched healthy women. Fasting blood samples were drawn for free T4, thyrotropin, thyroperoxidase antibodies (TPOAb), fasting insulin, glucose and HOMA-IR were calculated. A total of 52 PCOS patients had either autoimmune thyroiditis (AIT+) and/or subclinical hypothyroidism (HSC) (36.6%) (thyroid abnormalities:TA+) compared with 7 women of the control group (13.5%), accounting for more than a five fold higher prevalence of TA in PCOS patients, compared with the age-matched controls (adjusted odds ratio: 5.6; CI 95%: 2.1 -14.9; p<0.001). TA+ patients had significantly higher FI and HOMA-IR values than patients without thyroid abnormalities (p<0.05). These results demonstrate a high rate of TA in young PCOS women, associated with higher levels of FI and HOMA-IR. As PCOS, hypothyroidism and thyroid autoimmunity may have a profound impact on reproductive health, our data indicate that PCOS patients should be screened for TA.

Alta frecuencia de trastornos tiroideos en el síndrome de ovario poliquístico / High frequency of thyroid abnormalities in polycystic ovary syndrome

La prevalencia de trastornos tiroideos (TT) no ha sido suficientemente evaluada en mujeres con síndrome de ovario poliquístico (SOP). El propósito de esta investigación fue examinar dicha relación. En este estudio prospectivo de diseño caso-control, se incluyeron 194 mujeres. El grupo SOP consistió en 142 pacientes diagnosticadas por criterios Rotterdam 2003, y el grupo control incluyó a 52 mujeres sanas apareadas por edad. Se extrajeron muestras de sangre en ayuno para dosajes de T4 libre, tirotrofina, anticuerpos antiperoxidasa (ATPO), insulinemia y glucemia y se calculó el índice HOMA. Un total de 52 pacientes con SOP presentó autoinmunidad tiroidea (AIT+) y/o hipotiroidismo subclínico (HSC) (36.6%) (TT+) en comparación con 7 mujeres del grupo de control (13.5%), lo que representa una frecuencia cinco veces mayor de TT en pacientes con SOP en comparación con los controles (odds ratio ajustado: 5.6; IC 95%: 2.1-14.9; p < 0.001). Las pacientes TT+ tuvieron valores de insulinemia y HOMA significativamente más altos que aquellas sin trastornos tiroideos (TT-) (p < 0.05).Este estudio muestra una alta tasa de TT en mujeres con SOP asociada a mayores niveles de insulinemia y HOMA. Teniendo en cuenta que el SOP, el hipotiroidismo y la autoinmunidad tiroidea pueden tener un profundo impacto en la salud reproductiva, nuestros datos sugieren que las pacientes con SOP deberían ser evaluadas para descartar TT.

The prevalence of thyroid abnormalities (TA) has not been sufficiently assessed in polycystic ovary syndrome (PCOS). Our aim was to evaluate this relationship. In this prospective study 194 women were included. The PCOS group consisted of 142 patients (diagnosed by Rotterdam 2003 criteria) and the control group included 52 age-matched healthy women. Fasting blood samples were drawn for free T4, thyrotropin, thyroperoxidase antibodies (TPOAb), fasting insulin, glucose and HOMA-IR were calculated. A total of 52 PCOS patients had either autoimmune thyroiditis (AIT+) and/or subclinical hypothyroidism (HSC) (36.6%) (thyroid abnormalities:TA+) compared with 7 women of the control group (13.5%), accounting for more than a five fold higher prevalence of TA in PCOS patients, compared with the age-matched controls (adjusted odds ratio: 5.6; CI 95%: 2.1 -14.9; p < 0.001). TA+ patients had significantly higher FI and HOMA-IR values than patients without thyroid abnormalities(p < 0.05). These results demonstrate a high rate of TA in young PCOS women, associated with higher levels of FI and HOMA-IR. As PCOS, hypothyroidism and thyroid autoimmunity may have a profound impact on reproductive health, our data indicate that PCOS patients should be screened for TA.

Eficacia de la Lamotrigina en pacientes epilépticos fármaco resistentes a tratamientos en un centro neurológico de referencia en la ciudad de Cali / Efficacy of Lamotrigine in epilepsy patients resistant to drug tratments in a neurological reference center in the city of Cali

Introducción: la epilepsia es una enfermedad neurológica frecuente, con una incidencia estimada de 50 por cada 100,000 habitantes y una prevalencia de cinco a diez por 1,000 habitantes en los países desarrollados. Se le llama refractaria cuando las crisis epilépticas son tan frecuentes que limitan la habilidad del paciente para vivir plenamente o cuando los efectos secundarios del manejo tratamiento son limitantes para el desarrollo normal de la persona pese al mejor manejo médico instaurado. La Lamotrigina es un antiepiléptico que inhibe los canales de sodio voltaje-dependientes, modulando la liberación presináptica de transmisores excitatorios de tipo glutamato y aspartato. Objetivo: determinar la efectividad de la Lamotrigina como monoterapia o en asociación con fármacos antiepilépticos convencionales en pacientes con Epilepsia Refractaria. Materiales y métodos: estudio descriptivo. Periodo de tiempo: mayo 2009 a noviembre 2012. Análisis de las variables por medio de frecuencias, promedios y proporciones. Resultados: muestra: 115 historias clínicas de pacientes con epilepsia refractaria. El 97,4% (112) tiene reducción en el número de crisis, siendo en el 85,2% (98) mayor o igual al 50%. Hubo un promedio de 9,45 crisis por mes, con una mediana de seis episodios, previo al manejo con este medicamento, mientras que tras la administración del medicamento, el promedio de episodios fue de 3,65 por mes, con mediana de 1 episodio/mes. El promedio de fármacos utilizados antes de introducir la Lamotrigina fue de 1,9 con un uso mínimo de 1 y máximo 6 y a partir del inicio de la Lamotrigina el promedio fue 2,3, con uso mínimo de 1 y máximo de 4 medicamentos. Conclusión: la Lamotrigina es un medicamento de última generación con adecuada efectividad y pocos efectos adversos que puede reducir de forma efectiva la frecuencia de crisis epilépticas en los pacientes de difícil manejo con refractariedad farmacológica.

Introduction: Epilepsy is a common neurological condition with an estimated incidence of 50 per 100,000 population and a prevalence five to ten per 1,000 population in developed countries. It is considered refractory when seizures are so frequent that the patient's ability to live fully is limited, when treatment does not control seizures, or when side effects are limiting for the normal development of the person. Lamotrigine is an antiepileptic drug that inhibits the sodium channel voltage-dependent presynaptic modulating excitatory transmitter glutamate and aspartate type. Objective: To determine the effectiveness of Lamotrigine as monotherapy or in combination with conventional antiepileptic drugs in patients with refractory epilepsy. Materials and methods: A descriptive study. Period May 2009 to November 2012. Variable analysis by frequency, averages and ratios. Results: Sample: 115 medical records. 97.4% (112) of the patients have reduced the number of seizures, so than 85.2% (98) have had a reduction greater than or equal to 50%. There was an average of 9.45 attacks per month, with a median of 6 episodes, prior to treatment with this medicine, whereas after administering medication, the average was 3.65 episodes per month, with a median of 1 crisis/month. The average drugs used before initiating the Lamotrigine was 1.9 with a minimum of 1 and maximum of 6 and from the beginning of the Lamotrigine the average was 1.54, with minimum use of 1 and maximum of 4 drugs. Conclusion: Lamotrigine is a last generation drug with great effectiveness and few side effects, which can effectively reduce the frequency of seizures in patients with refractory epilepsy.

Foxp3+ CD4+ T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation.

RATIONALE: An exaggerated or persistent inflammatory activation after myocardial infarction (MI) leads to maladaptive healing and subsequent remodeling of the left ventricle. Foxp3(+) CD4(+) regulatory T cells (Treg cells) contribute to inflammation resolution. Therefore, Treg cells might influence cardiac healing post-MI. OBJECTIVE: Our aim was to study the functional role of Treg cells in wound healing post-MI in a mouse model of permanent left coronary artery ligation. METHODS AND RESULTS: Using a model of genetic Treg-cell ablation (Foxp3(DTR) mice), we depleted the Treg-cell compartment before MI induction, resulting in aggravated cardiac inflammation and deteriorated clinical outcome. Mechanistically, Treg-cell depletion was associated with M1-like macrophage polarization, characterized by decreased expression of inflammation-resolving and healing-promoting factors. The phenotype of exacerbated cardiac inflammation and outcome in Treg-cell-ablated mice could be confirmed in a mouse model of anti-CD25 monoclonal antibody-mediated depletion. In contrast, therapeutic Treg-cell activation by superagonistic anti-CD28 monoclonal antibody administration 2 days after MI led to improved healing and survival. Compared with control animals, CD28-SA-treated mice showed increased collagen de novo expression within the scar, correlating with decreased rates of left ventricular ruptures. Therapeutic Treg-cell activation induced an M2-like macrophage differentiation within the healing myocardium, associated with myofibroblast activation and increased expression of monocyte/macrophage-derived proteins fostering wound healing. CONCLUSIONS: Our data indicate that Treg cells beneficially influence wound healing after MI by modulating monocyte/macrophage differentiation. Moreover, therapeutic activation of Treg cells constitutes a novel approach to improve healing post-MI.