Boldine prevents the inflammatory response of cardiac fibroblasts induced by SGK1-NFκB signaling pathway activation.

Cardiac fibroblasts (CF) are mesenchymal-type cells responsible for maintaining the homeostasis of the heart's extracellular matrix (ECM). Their dysfunction leads to excessive secretion of ECM proteins, tissue stiffening, impaired nutrient and oxygen exchange, and electrical abnormalities in the heart. Additionally, CF act as sentinel cells in the cardiac tissue microenvironment, responding to various stimuli that may affect heart function. Deleterious stimuli induce an inflammatory response in CF, increasing the secretion of cytokines such as IL-1ß and TNF-α and the expression of cell adhesion molecules like ICAM1 and VCAM1, initially promoting damage resolution by recruiting immune cells. However, constant harmful stimuli lead to a chronic inflammatory process and heart dysfunction. Therefore, it is necessary to study the mechanisms that govern CF inflammation. NFκB is a key regulator of the cardiac inflammatory process, making the search for mechanisms of NFκB regulation and CF inflammatory response crucial for developing new treatment options for cardiovascular diseases. SGK1, a serine-threonine protein kinase, is one of the regulators of NFκB and is involved in the fibrotic effects of angiotensin II and aldosterone, as well as in CF differentiation. However, its role in the CF inflammatory response is unknown. On the other hand, many bioactive natural products have demonstrated anti-inflammatory effects, but their role in CF inflammation is unknown. One such molecule is boldine, an alkaloid obtained from Boldo (Peumus boldus), a Chilean endemic tree with proven cytoprotective effects. However, its involvement in the regulation of SGK1 and CF inflammation is unknown. In this study, we evaluated the role of SGK1 and boldine in the inflammatory response in CF isolated from neonatal Sprague-Dawley rats. The involvement of SGK1 was analyzed using GSK650394, a specific SGK1 inhibitor. Our results demonstrate that SGK1 is crucial for LPS- and IFN-γ-induced inflammatory responses in CF (cytokine expression, cell adhesion molecule expression, and leukocyte adhesion). Furthermore, a conditioned medium (intracellular content of CF subject to freeze/thaw cycles) was used to simulate a sterile inflammation condition. The conditioned medium induced a potent inflammatory response in CF, which was completely prevented by the SGK1 inhibitor. Finally, our results indicate that boldine inhibits both SGK1 activation and the CF inflammatory response induced by LPS, IFN-γ, and CF-conditioned medium. Taken together, our results position SGK1 as an important regulator of the CF inflammatory response and boldine as a promising anti-inflammatory drug in the context of cardiovascular diseases.

Use of coumarins as complementary medicine with an integrative approach against cervical cancer: background and mechanisms of action.

Cervical cancer is characterized by the cellular transformation caused by Human Papillomavirus (HPV), favoring cell proliferation, migration, invasion, and metastasis. Cervical cancer is conventionally treated with radiation therapy, and chemotherapy focused on the destruction of tumor cells. However, chemoresistance and low selectivity between tumor and non-tumor cells have been reported, causing side effects in patients. Metabolites of natural origin have shown selectivity against tumor cells, suggesting their use for reducing the side effects caused by drugs used in conventional therapy. Among these compounds, several natural coumarins stand out, such as auraptene, scopoletin, osthole, and praeruptorin, of which antiproliferative, anti-migratory, and anti-invasive activity have been reported. Auraptene, scopoletin, osthole, and praeruptorin show a cytotoxic or antiproliferative effect on cervical tumor cells, arresting the cell cycle by inducing the overexpression of negative regulators of the cell cycle, or inducing cell death by increasing the expression of pro-apoptotic proteins and decreasing that of anti-apoptotic proteins. On the other hand, auraptene, scopoletin, and praeruptorin inhibit the capacity for migration, invasion, and metastasis of cervical tumor cells, mainly by inhibiting the expression and activity of matrix metalloproteinase-2 and -9. The PI3K/Akt signal pathway appears to be central to the anti-tumor activity of the coumarins analyzed in this review. In addition, auraptene, osthole, and praeruptorin are useful in sensitizing tumor cells to radiotherapy or chemotherapeutic molecules, such as FOLFOX, cisplatin, or DOX. Coumarins offer an excellent possibility for developing new drugs as complementary medicine with an integrative approach against cervical cancer.

Vivencias y expectativas de los actores sociales partícipes en evaluación del desarrollo psicomotor, en relación a las escalas EEDP y TEPSI utilizadas en la Araucanía, Chile, durante los años 2017-2018 / Vivências e expectativas dos acionistas sociais partícipes na avaliação do desenvolvimento do psicomotor, em relação às escalas EEDP e TEPSI usadas no Araucania, Chile, durante o ano 2017-2018 / Experiences and expectations of the social actors participating in the evaluation of psychomotor development, in relation to the EEDP and TEPSI scales used in la Araucania, Chile, in 2017-2018

Resumen: En Chile, la Escala de Evaluación del Desarrollo Psicomotor (EEDP) y Test de Desarrollo Psicomotor (TEPSI) son herramientas no actualizadas, que carecen de confiabilidad y validación internacional conocida; por ello se hace necesario analizar el proceso evaluativo desde los actores de salud y educación, Enfermeras y Educadoras de párvulos respectivamente. El objetivo fue develar las vivencias de estos actores sociales, partícipes en el proceso evaluativo del desarrollo psicomotor en menores de tres años, según determinantes sociales. Se trata de un estudio cualitativo exploratorio, basado en la fenomenología de Alfred Schütz, realizado en siete informantes claves, cinco enfermeras y dos educadoras de párvulos, por medio de la entrevista semiestructurada. El análisis se circunscribió a transcripción, codificación, agrupamiento en categorías y síntesis. Se develan las metacategorías: A: Dilemas e incertidumbres por nudos críticos y categorías intermedias: a) Brecha entre políticas públicas y realidad local, no favorece el desarrollo de los niños, b) Instrumentos desactualizados y descontextualizados, c) Mitos y expectativas de los padres frente a la evaluación, d) Instrumentos sin pertinencia social; y B: Expectativas y categorías intermedias: a) Actualización del marco político para un avance continuo y efectivo, b) Incorporación y empoderamiento de los padres en el proceso, c) Capacitación y perfeccionamiento de profesionales. Se concluye que es necesario la actualización de las estrategias evaluativas y disponer de instrumentos validados, actualizados, con pertinencia social y que consideren a los padres

Resumo: No Chile, as Escala de Avaliação do Desenvolvimento Psicomotor (EEDP) e Teste de Desenvolvimento Psicomotor (TEPSI) não são ferramentas atualizadas, que carecem de confiabilidade e validação internacionalmente conhecidas, por essa razão, é necessário analisar o processo de avaliação dos atores de saúde e educação, enfermeiros e educadoras de creches, respectivamente. Lo objetivo foi revelar as experiências dos atores sociais participantes, enfermeiros e educadoras de creches, no processo de avaliação do desenvolvimento psicomotor em crianças menores de 3 anos, segundo os determinantes sociais. Foi realizado um estudo qualitativo exploratório baseado na fenomenologia de Alfred Schütz, realizado em 7 informantes-chave, 5 enfermeiros e 2 educadoras de creches, por meio de entrevista semiestruturado. A análise foi limitada à transcrição; codificação; agrupamento em categorias e síntese. Dilemas e incertezas de nós críticos e categorias intermediárias: a) lacuna entre política pública e da realidade local, não favorece o desenvolvimento das crianças, b) instrumentos desatualizados e, c) Mitos descontextualizadas e expectativas dos metacategorias são revelados os pais na frente da avaliação, d) Instrumentos sem relevância social; e B: Expectativas e categorias intermediárias: a) Atualização do arcabouço político para o progresso contínuo e efetivo, b) Incorporação e empoderamento dos pais no processo, c) Treinamento e aperfeiçoamento dos profissionais. É necessário atualizar as estratégias de avaliação e validar instrumentos atualizados e de relevância social que considerem os pais

Abstract: In Chile, the Psychomotor Development Evaluation Scale (EEDP in Spanish) and the Psychomotor Development Test (TEPSI in Spanish) are outdated tools that lack international reliability and validation. It is necessary to analyze the evaluation process from the point of view of the health and education professionals, that is, nurses and early childhood educators. The purpose was to reveal the experiences of these actors in the evaluation process of psychomotor development in children under three years of age, according to social determinants. This is a qualitative exploratory study based on the Alfred Schütz phenomenology, carried out in seven key informants, five nurses and two educators, through semi-structured interviews. The analysis was limited to transcription, coding, grouping into categories and synthesis. The meta categories revealed are: A: Dilemmas and uncertainties by critical nodes and intermediate categories: a) The gap between public policies and local reality does not favor the development of children, b) Outdated and decontextualized instruments, c) Myths and expectations of the parents regarding the evaluation, d) Instruments without social relevance; and B: Expectations and intermediate categories: a) Political framework update for continuous and effective progress, b) Parents incorporation and empowerment in the process, c) Professionals training and improvement. It was concluded that it is necessary to update the evaluation strategies and have validated, updated and socially relevant instruments that include the parents

Evaluation of the match between anthropometric measures and school furniture dimensions in Chile.

BACKGROUND: Students are exposed to the first systematic tasks or activities that a human being carries out in his/her life while at school. In this workplace situation, school furniture is a key factor for the adoption of proper body posture. OBJECTIVE: The aim of this paper was to observe and determine the potential mismatch between school furniture dimensions and anthropometric characteristics of the students from the Valparaíso region of Chile. METHODS: The sample consisted of 3,078 volunteer participants from 18 schools (public, semi-public, private). Eight anthropometric measures were gathered, together with six furniture dimensions. Mismatch analyses were carried out by using pre-defined mismatch criteria. RESULTS: Many different types of school furniture were presented at the schools. Also, a high level of mismatch was registered for seat height, desk height and seat-to-desk clearance. Finally, the analysis of all considered dimensions together showed that there was a high level of cumulative mismatch. CONCLUSIONS: It can be concluded that there were high levels of mismatch between the school furniture and student anthropometric characteristics and that this mismatch varied within the difference types of schools. This situation may have occurred because furniture acquisition was made without considering any ergonomic criteria.

4-Phenylbutyric acid prevent cytotoxicity induced by thapsigargin in rat cardiac fibroblast.

Cardiac fibroblast (CF) survival is important for the maintenance of the extracellular matrix homeostasis in the heart; providing a functional support to cardiomyocytes necessary for the correct myocardial function. Endoplasmic reticulum (ER) stress causes cellular dysfunction and cell death by apoptosis; and thapsigargin is a well-known ER stress inducer. On the other hand, the chemical chaperone, 4-phenylbutyric acid (4-PBA) had showed to prevent ER stress; however, in cardiac fibroblast both the ER stress induced by thapsigargin and prevention by 4-PBA, have not been studied in detail. Neonate rat CF were treated with thapsigargin in presence or absence of 4-PBA, and cell viability was evaluated by trypan blue exclusion and apoptosis by flow cytometry; whereas CHOP, BIP, PDI, ATF4 and procollagen protein levels were assessed by western blot. In CF, thapsigargin triggered the unfolded protein response detected by early increases in ATF4, CHOP, PDI and BIP protein levels as well as, the accumulation of intracellular procollagen. Thapsigargin also stimulated CF death in a time and concentration-dependent manner. ER stress, CF death and apoptosis induced by thapsigargin were prevented by 4-PBA. Conclusion our data suggest that 4-PBA prevent ER stress, intracellular procollagen accumulation, CF death and apoptosis induced by thapsigargin.

Morbilidad neonatal de los prematuros tardíos en embarazos únicos: estudio de caso-control / Neonatal morbidity of late preterm: a case-control study

Objetivo: Comparar los riesgos de morbilidad neonatal entre los prematuros tardíos (PT) y neonatos de término. Método: Estudio de caso control. Se revisan fichas clínicas de partos durante el año 2007. Se excluyen neonatos con malformaciones congénitas mayores, alteración neuromuscular, embarazos múltiples y aneuploidias. Los casos corresponden a todo PT nacido durante el periodo estudiado y los controles a nacidos de término en el mismo periodo. Los resultados neonatales fueron obtenidos y los riesgos calculados usando pruebas de Chi cuadrado y exacto de Fisher. Resultados: Se identifican 1536 partos, con una tasa de PT de 7,1 por ciento (109 casos), 62 cumplieron con criterios de inclusión. El grupo control consistió en 124 partos de término. PT presentaron 2 veces más riesgo de cesárea (p=0,0094) que los de término. El riesgo de ser admitido en UCIN fue de 88 (p=0,000). Los riesgos de morbilidad neonatal fueron: SDR (OR 23; p=0,000), hipoglicemia (OR 6; p=0,014), hipocalcemia (OR 6; p=0,014), hiperbilirrubinemia (OR 28; p=0,000) y necesidad de fototerapia (OR 23; p=0,000). No hubo diferencias en la presentación de enterocolitis necrotizante (p=0,478) ni sepsis neonatal (p=0,615). La mortalidad neonatal fue significativamente superior en los PT (p=0,044). Conclusión: Los PT deben ser considerados de alto riesgo en el período neonatal. Nuestros resultados son importantes para tomar decisiones clinicas respecto al mejor momento de finalizar un embarazo con riesgo inminente de prematurez.

Objective: To compare neonatal morbidity risks between late preterm (LP) and term deliveries. Methods: Case control study. Medical records in 2007 were reviewed. Major congenital malformations, neuromuscular handicap, twin pregnancies and aneuploidies were excluded. The Study group corresponds to all LP births during that period and the control group to term deliveries in the same period. Neonatal outcomes were collected and different risks were calculated using Chi square test and Fisher exact tests. Results: 1536 deliveries with a LP rate of 7.1 percent (109 cases) were observed, 62 cases met inclusion criteria. The control group consisted in 124 single term deliveries. LP had 2 times more risk of cesarean section (p=0.0094) than term deliveries. The risk of NICU admission was 88 (p=0.000). Neonatal morbidity risks were: RDS (OR 23, p=0.000), hypoglycemia (OR 6, p=0.014), hypocalcaemia (OR 6, p=0.014), hyperbillirrubinemia (OR 28, p=0.000) and phototherapy (OR 23, p=0.000). There were no differences in necrotizing enterocolitis (p=0.478) and risk of neonatal sepsis (p=0.615). Neonatal mortality was significantly higher in LP babies (p=0.044). Conclusion: LP newborn must be considered as high risk in the neonatal period. These results are important in making clinical decisions about the better time to end pregnancy.

Rol de interleuquina-6 en artritis reumatoide: nuevos conceptos: [revisión] / Role of inteleukin-6 in rheumatoid arthritis: new concepts: [review]

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology that involves complex and not completely elucidated mechanisms. In the recent years, the development of targeted therapies has given new insights into the nature of immunologic interactions involved in its pathogenesis. Until recently, the RA was thought to be predominantly a Th1 disease. New evidence established the preponderant role of the Th17 axis, of which IL-17 and IL-23 are major components. IL-6 has an important role in the differentiation of the Th17 and T regulatory (Treg) lymphocytes. Herein, we review current evidence regarding the role of cytokines in the pathogenesis of RA, especially in the differentiation of Th17 and Treg systems, as well as the deleterious effects of IL-6 and the molecular and clinical consequences of its blockade.

Perfil de producción de citoquinas en linfocitos T de sangre periférica de pacientes con poliposis nasal y asma bronquial en respuesta a la estimulación con enterotoxina estafilocócica B / Cytokine production profile in peripheral blood T lymphocytes from patients with nasal poliposis and bronchial asthma in response to staphylococcal enterotoxin B

Introducción: La poliposis nasal (PN) se presenta frecuentemente asociada a asma bronquial (AB). La enterotoxina estafilocócica B (SEB) jugaría un papel en su patogenia. No se ha estudiado si el perfil de citoquinas inducido por SEB en linfocitos T (LT) de pacientes con PNyAB difiere del de controles sanos. Objetivo: Comparar el perfil de citoquinas de LT de sangre periférica de pacientes con PN-AByde controles, estimulados con SEB o concanavalina A (ConA). Material y método: Células mononucleares de sangre periférica de 9 pacientes con PN-AB y de 6 controles se estimularon con SEB o ConA. El porcentaje LT CD4+ productores de interferón (IFN)-y, interleuquina (IL) IL-4, IL-5, IL-17 e IL-21 se determinó mediante citometrfa de flujo. Resultados: El grupo PN-AB presentó un menor porcentaje de LT productores de IL-5 que los controles al estimularse con SEB y con ConA. No hubo diferencia en las otras citoquinas estudiadas. Discusión: Nuestros resultados en sangre periférica difieren de lo descrito en tejido de pólipos nasales. Conclusión: Se sugiere que la respuesta inflamatoria de la PN se originaría localmente ya que los LT de sangre de pacientes con PN-AB no muestran una polarización hacia perfiles proinflamatorios con los estímulos utilizados.

Introduction: Nasal poliposis (NP) is frequently associated with bronchial asthma (BA) and its pathogenesis is still unknown. Staphylococcal enterotoxin B (SEB) has been implicated in the development of NP, however if the SEB-induced cytoklne profile of peripheral blood T lymphocytes (TL) of PN-BA patients differs from that of normal controls has not been studied. Aim: To compare the cytoklne profile of CD4+ TL from NP-BA and controls stimulated with SEB or concanavalin A (ConA). Material and method: Peripheral blood mononuclear cells from 9 NP-BA patients and from 6 controls were stimulated with SEB or ConA. The percentage of interferon (IFN)-y, interleukin {II) 11-4,11-5,11-17, and 11-21 producing TL was analyzed by flow cytometry Results: The percentage of SEB and ConA stimulated CD4+ IL-5-producing TLs was lower in the NP-BA group compared to the control group. There were no differences in the other cytokine-producing populations. Discussion: Unlike what is described in nasal polyp tissue, our findings show a diminished production of IL-5 by peripheral TL from the NP-AB group. Conclusion: A local sinonasal origin of the chronic inflammation is suggested since peripheral blood TL of NP-BA patients do not show a pro-inflammatory polarization with the tested stimuli.

Distrofia miotónica tipo I (enfermedad de steinert) y embarazo: descripción de un caso clínico / Myotonic distrophy type I (steinert disease) and pregnancy: a clinical case description

Type I myotonic dystrophy or Steinert's disease (DM1, OMIM 160900), is an autosomal dominant mulsystem disease of variable expresión caused by a (CTG)n, expansion mutation in the gene encoding for the myotonic dystrophy protein kinase (DMPK) in 19ql3. The disease is characterized by a phenomenon of anticipation, resulting in a more severe expression of the disease in successive generations, in correlation with the size of the triplet expansion. The congenital form of the disease, ussually of maternal transmisión, may cause polyhidramnios, foetal or neonatal death, or a sever neonatal floppy infant syndrome charaterized by facial diplegia, dysphagia, respiratory distress syndrome and a variable degree of mental retardation in 60 percent of the cases. The aim of this report is to describe a DM1 affecting a 35 years old woman and her fetus of 28 weeks of gestation at the moment of diagnosis. We describe the evolution of the pregnancy and her neonate, we discuss the reciprocal influence between pregnancy and the disease, enhacing the antenatal and neonatal complications.

La distrofia miotónica de Steinert o tipo I (DM1, OMIM 160900), es una enfermedad multisistémica, autosómica dominante de penetrancia variable, causada por la expansión del tupíete (CTG)n, en el gen que codifica para la proteína kinasa de la distrofia miotónica (DMPK) en el cromosoma 19ql3. La enfermedad se caracteriza por un fenómeno de anticipación, producto del cual su expresión es mayor en generaciones sucesivas y correlaciona con la talla de la expansión. La forma congénita de la enfermedad, habitualmente de transmisión materna puede producir polthidramnios, muerte fetal o neonatal o un síndrome hipotónico neonatal severo con diplegia facial, disfagia, distress respiratorio y retardo mental de grado variable en un 60 por ciento de los casos. El presente reporte tiene por objeto comunicar un caso de DM1 en una mujer de 35 años y en su feto de 28 semanas de gestación al momento del diagnóstico. Describimos la evolución del embarazo y del neonato, se discute la influencia recíproca entre la enfermedad y el embarazo, con énfasis en las complicaciones antenatales y neonatales.

[Transient renal failure in a newborn due angiotensin receptor II antagonist use during pregnancy: report of a case]. / Efectos sobre la función renal fetal y neonatal del tratamiento con antagonista del receptor de angiotensina II en el embarazo: Caso clínico.

Fetal renal structure and function can be altered by medications prescribed to pregnant women. We report a chronic hypertensive pregnant woman treated with losartan before and throughout pregnancy. At 30 weeks the patient was referred to our Fetal Medicine Unit due to absent amniotic fluid with normal uterine artery Doppler and fetal growth. During her hospitalization a new scan was performed showing that both fetal kidneys were enlarged and slightly hyperechogenic and placental and fetal artery Doppler showed signs of hypovolemia or increased resistance to feto-placental blood flow. Ductus venosous was normal. The fetus was delivered after three days by caesarean section at 30+4 weeks of gestation due to abnormal fetal heart rate tracing. Following delivery, the preterm newborn was treated for a transient renal failure characterized by anuria-oliguria and high plasma creatinine levels (from 3.8 mg/dL at day 5 to 0.8 mg/dL at 16 days). At 30 days of age, ultrasound showed kidneys of normal form and size. The adverse effects of Angiotensin II receptor antagonists in fetal nephrogenesis and function are discussed.

Efectos sobre la función renal fetal y neonatal del tratamiento con antagonista del receptor de angiotensina II en el embarazo: Caso clínico / Transient renal failure in a newborn due angiotensin receptor II antagonist use during pregnancy: Report of one case

Fetal renal structure and function can be altered by medications prescribed to pregnant women. We report a chronic hypertensive pregnant woman treated with ¡osarían before and throughout pregnancy. At 30 weeks the patient was referred to our Fetal Medicine Unit due to absent amniotic fluid with normal uterine artery Doppler and fetal growth. During her hospitalization a new scan was performed showing that both fetal kidneys were enlarged and slightly hyperechogenic and placental and fetal artery Doppler showed signs of hypovolemia or increased resistance to feto-placental blood flow. Ductus venosous was normal. The fetus was delivered after three days by caesarean section at 30+4 weeks of gestation due to abnormal fetal heart rate tracing. Following delivery, the preterm newborn was treated for a transient renal failure characterized by anuria-oliguria and high plasma creatinine levels (from 3.8 mg/dL at day 5 to 0.8 mg/dL at 16 days). At 30 days of age, ultrasound showed kidneys of normal form and size. The adverse effects of Angiotensin II receptor antagonists in fetal nephrogenesis and function are discussed

Pallial oviduct of Pomacea canaliculata (Gastropoda): ultrastructural studies of the parenchymal cellular types involved in the metabolism of perivitellins.

Seasonal variations in the morphology of the parenchymal mass and function of the albumen gland/capsule gland complex have been studied in Pomacea canaliculata, together with the cellular types involved in the synthesis and secretion of perivitellin fluid components. The two major parenchymal cell types, albumen secretory cells (AS) and labyrinthic cells (LC), undergo seasonal variations throughout the annual reproductive cycle, which is divided into three periods. Both cellular types show maximal development and structural complexity during the reproductive period (spring and summer). AS cells have a well-developed Golgi complex and rough endoplasmic reticulum and their secretory granules show electron-dense particles of about 20 nm (probably galactogen). These cells are uniquely involved in ovorubin and PV2 perivitellin synthesis and their secretory granules are the single storage site for these two major perivitellins, as revealed by immunoelectron microscopy. AS also possess calcium deposits that infiltrate the cytoplasmic matrix. The luminal surfaces of LC exhibit long cilia intermingled with sparce short microvilli. Basally, the plasma membrane shows deep irregular folds that extend through the cytoplasm up to the subapical region. Calcium deposits infiltrate the cytoplasm and accumulate in the extracellular space of the basal labyrinth. Nerve terminals seem to be involved in the regulation of parenchymal cell secretion. At the post-reproductive period, AS markedly change their aspect following the release of most of the secretory granules into the acinar lumen. LC decrease in volume, the number of their cilia decreases, their cytoplasmic folds are much thinner and their extracellular spaces lack calcium particles. At the pre-reproductive period (winter), AS and LC recover and prepare for the subsequent period.

Impacto economico de la prematurez y las malformaciones congénitas sobre el costo de la atención neonatal

Objetivos: Calcular los costos de la atención neonatal de recién nacidos prematuros y en portadores de malformaciones congénitas mayores compatibles con la vida. Pacientes y Método: Estudio retrospectivo efectuado en el Departamento de Ginecología y Obstetricia del Hospital Clínico de la Universidad de Chile, en 82 recién nacidos menores de 34 semanas de gestación y en 14 con malformaciones congénitas mayores, de más de 37 semanas de gestación, compatibles con la vida, atendidos entre enero y diciembre de 2004. Resultados evaluados son los costos de la atención neonatal subdivididos en componentes. Resultados: El costo promedio de la atención neonatal en recién nacidos menores de 34 semanas fue igual a $2.519.508, en menores de 32 semanas igual a $3.766.999, en menores de 1500 gramos igual a $12.017.650 y en portadores de malformaciones congénitas mayores compatibles con la vida de $30.967.180. El día cama representa el componente más significativo dentro cada paquete con más del 60 por ciento del costo promedio. Conclusiones: El costo de la atención neonatal de prematuros menores de 34 semanas o portadores de malformaciones congénitas mayores compatibles con la vida es mayor al contemplado en los paquetes de prestaciones a todo evento, representando el día cama su componente más significativo.

Objective: To calculate the cost involved in the neonatal care of premature or live born babies carriers of mayor congenital abnormalities compatible with life. Patients and method: Retrospective study who analyzed 82 premature live born of less than 34 weeks and 14 live born carriers of mayor congenital abnormalities compatible with life, from January to December 2004, at the Maternity Ward from the University of Chile Clinical Hospital. The outcome measures were the neonatal care average cost package subdivided by components. The cost was expressed in chilean currency. Results: Neonatal care average cost was $2.519.508 in live born of less than 34 weeks, $3.766.999 in less than 32 weeks, $12.017.650 in less than 1500 grams babies and $30.967.180 in carriers of mayor congenital abnormalities. In bed day cost represents the most significant component from the package, representing more than 60 percent of its total cost. Conclusions: Neonatal care cost of premature live born of less than 34 weeks or carriers of mayor congenital abnormalities compatible with life is higher than the maximum cost considered in the every-event health packages, representing in bed day its most significant component.

Impacto de las malformaciones congénitas en una unidad de cuidados especiales neonatales / Importance of congenital diseases in a neonatal special care unit

Introducción: Las malformaciones congénitas (MFC) constituyen actualmente, la segunda causa de muerte en el primer año de vida, lo que las transforma en un problema de Salud Pública. Objetivos: Este estudio pretende evaluar los efectos de esta patología en la Unidad de Cuidados Especiales Neonatales (UCEN) del Hospital Clínico Universidad de Chile. Pacientes y Método: Se estudió todos los recién nacidos (RN) malformados de 500 gramos o más, vivos y mortinatos, período 2000–2003. Se utilizó la base de datos del ECLAMC (Estudio Colaborativo Latino Americano de Malformaciones Congénitas) y de la UCEN. Resultados: En el período hubo 7 858 nacimientos. Sesenta casos (0,76 por ciento) fueron mortinatos y 16 de ellos (26,6 por ciento) tenían MFC. Se encontró 639 nacidos vivos con malformaciones (8,2 por ciento), 139 de ellos con defectos severos, 13 fallecieron poco después de nacer, 126 (19,8 por ciento) necesitaron hospitalización y 49 (38,9 por ciento) requirieron tratamiento quirúrgico. Observamos una mortalidad de los RN hospitalizados de 65,4 por ciento en malformados y 34,6 por ciento por otras causas. La mortalidad por malformaciones fue de 4,6 por 1 000 NV. Conclusiones: Los niños hospitalizados por MFC tienen una mortalidad el doble que los fallecidos por otras causas, con un período de hospitalización mayor.

Terapias emergentes en artritis reumatoide / Emergent therapies for rheumatoid arthritis

The use of biological agents such as etanercept, infliximab, adalimumab and anakinra has been recently approved for the treatment of rheumatoid arthritis. All are effective controlling signs and symptoms and inhibiting disease progression. To overcome the problems generated by their high costs and possible participation in reactivating latent infections, other therapeutic tools are being developed. Gene therapy using expression vectors carrying genes coding for specific proteins, may interfere in key points involved in the pathogenesis of the disease. Intra-articular administration of cDNA coding for soluble TNF receptors, IL-1, or IL-1Ra decreases signs of the disease in animal models. Vectors, expressing inhibitors of signal transduction pathways involving to NF-kB and JAK-STAT-3, are effective in modulating joint inflammation in mice. The use of antigen-pulsed antigen presenting cells or dendritic cells (DC) bound to apoptosis-inducing molecules, specifically eliminates autoreactive T cells. Other novel approach attempts the development of T regulatory-inducing tolerogenic DC-based vaccines that inhibit autoreactive T cells, through the secretion of suppressing cytokines or by other mechanisms to be elucidated. Oral tolerance induction to auto-antigens is also a successful experimental strategy under study. Current research aims to control peripheral tolerance in rheumatoid arthritis patients.

Factores de riesgo asociados al bajo peso al nacer / Risk factors associated to low birth weight

En Chile, existe un porcentaje de niños con bajo peso al nacer, cifra muy similar a las tasas de países desarrollados. Estos presentan mayor riesgo de déficit de desarrollo neurológico, metabólico y capacidad cognitiva, requiriendo además de costosos cuidados especiales a lo largo de su desarrollo. El presente trabajo busca estimar los factores de riesgo para bajo peso al nacer, con el fin de detectarlos a tiempo y evitar así su ocurrencia. Nuestro estudio consideró a los niños nacidos vivos con pesos menores a 2.500 gramos (n = 334), en la Maternidad de Hospital Clínico de la Universidad de Chile entre los años 2001 y 2002. La información se obtuvo durante la atención prenatal y el parto, se compararon los niños con muy bajo peso (< 2.000 gramos) con aquellos que pesaron 2.000 gramos y más. El análisis estadístico consideró la evaluación de la calidad y consistencia de los datos obtenidos, para esto se empleó el programa Stata 8.0. Se observó que el factor de riesgo mayormente asociado a muy bajo peso al nacer es la prematurez (89 por ciento), seguido por la edad materna extrema (50,7 por ciento) y, en tercer lugar, la preeclampsia (44,5 por ciento). Este trabajo concluye que los factores de riesgo de muy bajo peso al nacer han variado en la última década. Esto explicado por el cambio en el perfil epidemiológico que la población chilena experimentó en los últimos años, transformando los problemas de malnutrición por déficit por los de exceso y los programas ministeriales que centraron sus esfuerzos en las poblaciones de riesgo nutricional, reduciendo así la malnutrición por déficit. El bajo peso de un niño prematuro es explicable por la ganancia de peso de entre 200 y 300 gramos en promedio por cada semana de permanencia dentro del útero, especialmente hacia el final de la gestación. Con respecto a la edad materna extrema, se puede afirmar que las mujeres adolescentes presentan un mayor riesgo de parto prematuro o de recién nacido de término con bajo peso debido a un estado nutricional pre concepcional deficitario (escasa ganancia de peso durante el embarazo y malos controles). En pacientes mayores de 35 años, se plantea que la existencia de patología crónica (diabetes, hipertensión, etc) motivaría adelantar el parto. La preeclampsia es un factor de riesgo conocido de bajo peso de nacimiento, que ocasiona alteraciones dela placentación...

Nuevas armas inmunológicas para la medicina del siglo XXI: Terapia biológica basada en el uso de anticuerpos monoclonales de última generación / New immunological weapons for Medicine at XXI century: biological therapy based on the use of last generation monoclonal antibodies

The fusion of a murine B cell and a myeloma cell generates a hybridoma that produces monoclonal antibody (mAb). These murine mAb induce the HAMA (human anti-mouse antibodies) response. Murine mAb have been modified by genetic engineering, producing molecules with a higher proportion of human protein. At present, chimeric, humanized and fully human mAb are available. mAb block interactions between target molecules and their ligands or trigger the lyses of mAb-coated tumor cells. Numerous mAb have been developed using the recombinant DNA technology and several are available in the market. Trastuzumab, against HER2/neu, is useful in breast cancer; rituximab, against CD20 in B lymphocytes is useful in lymphoma; alemtuzumab, against CD52 is used in lymphoma and leukemia; daclizumab and basiliximab block the IL-2 receptor interaction and reduce acute rejection in kidney transplantion; abciximab, an antagonist of GPIIb/IIIa platelet receptor, is used in patients undergoing acute coronary syndromes. In autoimmunity diseases, blocking tumor necrosis factor by infliximab and adalimumab has demonstrated excellent results. Thus, infliximab is useful in the treatment of rheumatoid arthritis (RA), Crohn's disease and ulcerative colitis while adalimumab is the first fully human mAb available for RA. Infliximab and adalimumab reduce signs and symptoms in RA and they also interfere with progression of joint damage. Finally, the direct benefits of antagonist treatment can occur at the expense of a major adverse effect in some other biological function (Rev Méd Chile 2003; 131: 1445-53).

Prevalencia de colonizacion por streptococcus agalactiae (grupo b) en el tercer trimestre del embarazo pesquisado en medio de cultivo no selectivo

El Streptococcus agalactiae es el principal agente bacteriano responsable de sepsis neonatal. Para evitar la infección perinatal se recomienda la pesquisa de la bacteria en región vagino-perianal durante el tercer trimestre, indicando tratamiento antibiótico durante el parto en aquellas gestantes colonizadas. La prevalencia de colonización varía según el tipo de cultivo utilizado (selectivo vs no selectivo). El objetivo de este estudio es conocer la prevalencia de colonización del Streptococcus agalactiae en la población de embarazadas controladas en nuestra maternidad durante los años 2001-2002. Se tomó cultivo en medio no selectivo, entre las 35-37 semanas de gestación a 1658 pacientes, encontrando una prevalencia de colonización vagino-perianal de 6,2%. Esta cifra es bastante menor a la comunicada en otros estudios en embarazadas chilenas, por lo que creemos importante la implementación de medios de cultivos selectivos para mejorar el rendimiento de pesquisa.

Diagnóstico y manejo perinatal de trisomía 9 / Diagnosis and perinatal management of trisomy 9

Presentamos 2 casos clínicos de diagnóstico antenatal de trisomía 9. Esta aneuploidía se sospecho en la evaluación ultrasonográfica durante la segunda mitad del embarazo, siendo confirmada por cordocentesis citogenética o amniocentesis. Comentamos la conducta a seguir frente a estos casos. Se realiza una revisión de la literatura destacando la escasa incidencia de diagnóstico pre y postnatal con esta patología

Incidencia de labio leporino y paladar hendido en la maternidad del Hospital Clínico de la Universidad de Chile y en las maternidades chilenas participantes en el estudio colaborativo latino americano de malformaciones congénitas, ECLAMC, período 1991-1999 / Incidence of orofacial cleft at Universidad de Chile maternity hospital and other hospitals participating in the Latin American collaborative study of congenital malformations, ECLAMC

Background: ECLAMC is a registry, aimed to assess the incidence of congenital malformations, that started in 1967 and Chile incorporated to it in 1969. Aim: To report the incidence of cleft lip/palate, updated to 1999 in the University of Chile Maternity Hospital and other Chilean hospitals participating in the ECLAMC. Patients and methods: A review of the ECLAMC database that registers all births or stillbirths of more than 500 g. Results : The incidence of orofacial cleft, at the University of Chile Maternity Hospital, in the period 1991-1999 was 17.8 per 10000 (12.6 for cleft lip and 5.2 for cleft palate). The incidence in the rest of participating hospitals was 12.04 and 4.6 respectively. Males had a higher incidence of cleft lip and 80 percent of children with cleft palate, had other malformations, most of them as part of a syndrome (13 and 18 trisomy, holoproscencephalia, Pierre Robin, Apert en EE syndromes, anencephaly etc). In three of 12 children with cleft lip but without cleft palate, there was a relative with the same malformation. Conclusions: It is proposed that both entities, cleft lip with or without cleft palate and cleft palate without cleft lip, are two etiopathogenically different conditions