ABSTRACT
Se ha declarado una pandemia ante la propagación de un nuevo virus con alta contagiosidad, llamado síndrome respiratorio agudo severo coronavirus 2 (severe acute respiratory syndrome coronavirus 2, SARS-CoV2). El mundo ha quedado detenido ante la rápida expansión del virus, con una letalidad que en algunos países llega a 15%. En Chile, el gobierno ha tomado medidas rápidas y agresivas que han permitido mantener la curva de contagios a un nivel que permita atender de manera adecuada a la población. Dentro de estas medidas, se contempla la suspensión de cirugías y consultas ambulatorias. Como cirujanos ortopédicos, nos hemos visto afectados por estas medidas, y existe confusión respecto a cuál es la conducta más adecuada. Quisimos hacer esta guía para resumir parte de las evidencias disponibles y orientar a los cirujanos ortopédicos respecto a esta patología. El comportamiento de esta guía es dinámico, dadas las múltiples opiniones, experiencias y evidencias, que surgen diariamente, por lo que recomendamos mantenerlo como referencia, no como certeza.
A pandemic has been declared due to a new highly contagious virus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). The world has come to a halt due to the rapid expansion of a virus whose lethality has reached 15% in some countries. In Chile, the government has taken decisive, aggressive measures in an attempt to control disease spread and provide healthcare to those who need it. These decisions include the suspension of elective surgeries and other ambulatory procedures. As Orthopedic surgeons we have been affected by these measures and there is doubt regarding the best course of action. We prepared this guide to summarize available evidence and orient our colleagues regarding this pathology. This guide is meant to be dynamic, as new opinions, evidence and experiences arise every day. Therefore, we advise the reader to keep it as a reference, not an undisputable truth.
Subject(s)
Humans , Orthopedics/organization & administration , Orthopedic Procedures , COVID-19/prevention & control , Surgery Department, Hospital/organization & administration , Emergencies , Pandemics/prevention & controlABSTRACT
Anterior Cruciate Ligament (ACL) injury is an important cause of days lost in athletes. Most ACL injuries are non-contact and are associated with biomechanical risk factors that increase tension in the ACL: increased knee valgus (KV) and hip flexion (HF) and decreased flexion of knee (KF). Muscle around the knee contributes to knee stability, so fatigue produced by exercise could alter knee balance, increasing LCA tension. The aim of the study is to determine the angular behavior before and after a physical load for CF, RR and RV in children born in 2002-2003. A non-randomized clinical trial was conducted. The sample consisted of 50 students from soccer schools born between 2002 and 2003. The angular behavior of CF, RR and VR was compared, before and after performing standardized training. The angular behavior was measured by performing the DJ test with data obtained by inertial sensors. After exercise, the 3 variables increased, but only HF reached significant difference. Other important finding was the difference found in KV between the dominant leg and the support limb, at both times: rest and post exercise. It was concluded that the angular behavior of CF increases significantly in both limbs post-exercise and that preventive measures should be applied for the management of valgus in the supporting limb.
La lesión del ligamento cruzado anterior (LCA) constituye una causa importante de reposo en deportistas. En su mayoría, las lesiones del LCA no requieren contacto externo y se asocian con factores de riesgo biomecánicos que aumentan la tensión en el LCA: el aumento del ángulo de valgo de rodilla (VR), flexión de cadera (FC) y una menor flexión de rodilla (FR). El LCA requiere cooperación de los grupos musculares perirrodilla, por lo que la fatiga producida por el ejercicio alteraría el balance y pondría en riesgo a este ligamento. El objetivo del estudio es determinar el comportamiento angular antes y después de una carga física para FC, FR y VR en niños nacidos en los años 2002-2003. Se realizó un estudio clínico no aleatorizado. La muestra consistió en 50 alumnos de escuelas de fútbol nacidos en los años 2002 y 2003. Se comparó el comportamiento angular de FC, FR y VR antes y después de realizar un entrenamiento estandarizado. El comportamiento angular fue medido a través de la realización de la prueba DJ, con datos obtenidos por sensores inerciales. Posterior al ejercicio, aumentaron las tres variables; sólo fue significativo el incremento en la flexión de cadera. Por otra parte, destaca la diferencia encontrada tanto en reposo como postejercicios entre la extremidad de apoyo y la hábil en el peak de valgo angular. Se concluyó que el comportamiento angular de FC aumenta significativamente en ambas extremidades postentrenamiento y que se deben aplicar medidas preventivas para el manejo del valgo en la extremidad de apoyo.
Subject(s)
Anterior Cruciate Ligament Injuries , Exercise , Knee Joint , Anterior Cruciate Ligament Injuries/etiology , Anterior Cruciate Ligament Injuries/prevention & control , Biomechanical Phenomena , Child , Exercise/physiology , Humans , Knee Joint/physiology , Lower Extremity , SportsABSTRACT
Resumen: La lesión del ligamento cruzado anterior (LCA) constituye una causa importante de reposo en deportistas. En su mayoría, las lesiones del LCA no requieren contacto externo y se asocian con factores de riesgo biomecánicos que aumentan la tensión en el LCA: el aumento del ángulo de valgo de rodilla (VR), flexión de cadera (FC) y una menor flexión de rodilla (FR). El LCA requiere cooperación de los grupos musculares perirrodilla, por lo que la fatiga producida por el ejercicio alteraría el balance y pondría en riesgo a este ligamento. El objetivo del estudio es determinar el comportamiento angular antes y después de una carga física para FC, FR y VR en niños nacidos en los años 2002-2003. Se realizó un estudio clínico no aleatorizado. La muestra consistió en 50 alumnos de escuelas de fútbol nacidos en los años 2002 y 2003. Se comparó el comportamiento angular de FC, FR y VR antes y después de realizar un entrenamiento estandarizado. El comportamiento angular fue medido a través de la realización de la prueba DJ, con datos obtenidos por sensores inerciales. Posterior al ejercicio, aumentaron las tres variables; sólo fue significativo el incremento en la flexión de cadera. Por otra parte, destaca la diferencia encontrada tanto en reposo como postejercicios entre la extremidad de apoyo y la hábil en el peak de valgo angular. Se concluyó que el comportamiento angular de FC aumenta significativamente en ambas extremidades postentrenamiento y que se deben aplicar medidas preventivas para el manejo del valgo en la extremidad de apoyo.
Abstract: Anterior Cruciate Ligament (ACL) injury is an important cause of days lost in athletes. Most ACL injuries are non-contact and are associated with biomechanical risk factors that increase tension in the ACL: increased knee valgus (KV) and hip flexion (HF) and decreased flexion of knee (KF). Muscle around the knee contributes to knee stability, so fatigue produced by exercise could alter knee balance, increasing LCA tension. The aim of the study is to determine the angular behavior before and after a physical load for CF, RR and RV in children born in 2002-2003. A non-randomized clinical trial was conducted. The sample consisted of 50 students from soccer schools born between 2002 and 2003. The angular behavior of CF, RR and VR was compared, before and after performing standardized training. The angular behavior was measured by performing the DJ test with data obtained by inertial sensors. After exercise, the 3 variables increased, but only HF reached significant difference. Other important finding was the difference found in KV between the dominant leg and the support limb, at both times: rest and post exercise. It was concluded that the angular behavior of CF increases significantly in both limbs post-exercise and that preventive measures should be applied for the management of valgus in the supporting limb.
Subject(s)
Humans , Child , Exercise/psychology , Anterior Cruciate Ligament Injuries/etiology , Anterior Cruciate Ligament Injuries/prevention & control , Knee Joint/physiology , Sports , Biomechanical Phenomena , Lower ExtremityABSTRACT
OBJECTIVES: This case study describes the implementation of an academic institution's disaster management plan. STUDY DESIGN: Case study. METHODS: USFQ's Medical School developed a six-phase disaster relief plan consisting of: induction, establishing a base camp, crisis management and mental health aid, creation of multidisciplinary teams and multi-agency teams, and reconstruction. Each phase uses a community-oriented approach to foster survivor autonomy and recovery. RESULTS: Our methodology facilitated the successful implementation of multidisciplinary interventions to manage the earthquake's aftermath on the personal, community and regional levels, treated and prevented psychological and physical morbidity among survivors and promoted healthy living conditions and independence. CONCLUSIONS: A multidisciplinary response team that addresses medical needs, mental health, education, food, nutrition and sanitation is highly effective in contributing to timely, effective relief efforts. The short- and long-term solutions we describe could be applicable to other academic centres' interventions in future disaster scenarios around the world.
Subject(s)
Disaster Planning/organization & administration , Earthquakes , Relief Work , Disasters , Ecuador , Female , Humans , Institutional Management Teams/organization & administration , Mental HealthABSTRACT
Variability of mixed Trypanosoma cruzi congenital infection in Chile in twenty one congenital samples of Chagas disease is reported. Recognition of infecting strains was performed by minicircle hybridization tests. Seven newborns with double infection were found. Trypanosoma cruzi TcII and TcV lineages were the most frequent in single and mixed infections. With these results we pretend to understand the epidemiological significance of the T. cruzi lineages for which the placenta does not seem to represent an actual barrier in congenital infections.
Subject(s)
Chagas Disease/congenital , Genetic Variation , Trypanosoma cruzi/genetics , Chagas Disease/parasitology , Genotype , Humans , Infant, NewbornABSTRACT
Background: Microvascular free tissue transfer has gained world-wide acceptance as a means of reconstructive plastic surgery. Since 1979, the authors have introduced this microsurgical procedure in our country and a total of 317 free flaps have been carried out during a period of 33 years. Aim: To present the consecutive free flaps performed at Hospital Clinico Universidad de Chile and Hospital Mutual de Seguridad between 1979-2011. Patients and Methods: Retrospective analysis of 293 patients underwent 317 microsurgical flaps. Results: 293 patients. Median age 43 years old (range 12-81). The lower limb has been the most common site (181 cases), followed by head and neck, upper limb and trunk. The most frequently used flap was the gracilis flap. A survival rate of 95 percent has been achieved. Follow-up range from 6 months to 9 years. Conclusion: This pioneering series in Chile using microsurgical flaps, shows a satisfactory solution in an one-stage procedure. The authors believe that free flap would be part of the armamentarium of modern plastic surgeons, frequently as a first choice...
Introducción: La transferencia de colgajos libres se ha posicionado como una opción ampliamente aceptada en todo el mundo en la cirugía plástica reconstructiva. En el año 1979, los autores introdujeron los primeros procedimientos microquirúrgicos en nuestro país, realizando en 33 años un total de 317 colgajos libres. Objetivo: Presentar los colgajos libres consecutivos efectuados por nuestro grupo entre 1979-2011 en el Hospital Clínico de la Universidad de Chile y Hospital Mutual de Seguridad. Pacientes y Método: Análisis retrospectivo de nuestra base de datos de los 293 pacientes reconstruidos con 317 colgajos microvascularizados. Seguimiento entre 9 años y 6 meses. Resultados: La serie estuvo constituida por 293 pacientes. La mediana de edad fue 43 años (rango 12-81). La principal indicación fue reconstrucción de extremidad inferior, luego cabeza y cuello, extremidad superior y tronco. El colgajo más usado fue el colgajo de músculo gracilis (45 por ciento). El éxito vascular total fue 95 por ciento. Conclusión: En esta serie pionera en Chile, la utilización de colgajos libres demostró ser de utilidad, dando soluciones satisfactorias en un tiempo. Los autores creen que los colgajos libres deben formar parte del armamentario de los cirujanos plásticos modernos, muchas veces como primera elección...
Subject(s)
Humans , Male , Adolescent , Adult , Female , Child , Young Adult , Middle Aged , Aged, 80 and over , Free Tissue Flaps , Microsurgery , Plastic Surgery Procedures/statistics & numerical data , Retrospective StudiesABSTRACT
The size complexity of the human genome has been traditionally viewed as an obstacle that frustrates efforts aimed at identifying the genetic correlates of complex human phenotypes. As such complex phenotypes are attributed to the combined action of numerous genomic loci, attempts to identify the underlying multi-locus interactions may produce a combinatorial sum of false positives that drown out the real signal. Faced with such grim prospects for successfully identifying the genetic basis of complex phenotypes, many geneticists simply disregard epistatic interactions altogether. However, the emerging picture from systems biology is that the cellular programs encoded by the genome utilize nested signaling hierarchies to integrate a number of loosely coupled, semiautonomous, and functionally distinct genetic networks. The current view of these modules is that connections encoding inter-module signaling are relatively sparse, while the gene-to-gene (protein-to-protein) interactions within a particular module are typically denser. We believe that each of these modules is encoded by a finite set of discontinuous, sequence-specific, genomic intervals that are functionally linked to association rules, which correlate directly to features in the environment. Furthermore, because these environmental association rules have evolved incrementally over time, we explore theoretical models of cellular evolution to better understand the role of evolution in genomic complexity. Specifically, we present a conceptual framework for (1) reducing genomic complexity by partitioning the genome into subsets composed of functionally distinct genetic modules and (2) improving the selection of coding region SNPs, which results in an increased probability of identifying functionally relevant SNPs. Additionally, we introduce the notion of 'genomic closure,' which provides a quantitative measure of how functionally insulated a specific genetic module might be from the influence of the rest of the genome. We suggest that the development and use of theoretical models can provide insight into the nature of biological systems and may lead to significant improvements in computational algorithms designed to reduce the complexity of the human genome.
Subject(s)
Epistasis, Genetic , Evolution, Molecular , Gene Expression Regulation/genetics , Genome, Human , Models, Genetic , Phenotype , Humans , Polymorphism, Single Nucleotide/genetics , Signal Transduction/genetics , Systems Biology/methodsABSTRACT
Trypanosoma cruzi transplacental infection represents a serious public health concern in all the countries like Chile where recent success of insecticide spraying programs eliminated the vector. Because children infected with T. cruzi are usually asymptomatic, a study was designed including infected mothers and their children. The study was conducted for three years to establish diagnostic, treatment, and clinical observations variables. Mothers were tested for T. cruzi IgG, and the new born were examined for parasite DNA using PCR amplification. They were treated with nifurtimox and it was 100% effective, confirmed by successive PCR tests. It has been determined that there are 800 to 1000 new cases a year of transplacental Chagas' disease in Chile. This level of infection in the population should justify the establishment of a control and follow-up program for transplacental Chagas' disease.
Subject(s)
Animals , Child, Preschool , Female , Infant , Humans , Infant, Newborn , Pregnancy , Chagas Disease/transmission , Infectious Disease Transmission, Vertical , Pregnancy Complications, Parasitic , Trypanosoma cruzi , Chile/epidemiology , Pregnancy Complications, Parasitic/diagnosis , DNA, Protozoan , Chagas Disease/diagnosis , Chagas Disease/therapy , Follow-Up Studies , Immunoglobulin G/blood , Polymerase Chain Reaction , Trypanosoma cruzi/isolation & purificationABSTRACT
El tratamiento de las fracturas periprotésicas femorales es compleja, asociado a frecuentes complicaciones. Las estrategias varían de acuerdo al tipo de fractura, la calidad del tejido óseo, la presencia o no de aflojamiento del implante y el estado general del paciente. Se presentan cinco casos de fracturas femorales periprotésicas, tratadas mediante osteosíntesis con placa y cables o asas de alambre y aloinjertos corticales diafisiarios dispuestos en forma "onlay". Las cinco pacientes eran mujeres, con edades entre los 66 y 80 años (promedio 73 años). En los cinco casos hubo consolidación de la fractura e incorporación de los injertos, con restauración del fémur proximal, lo que permitió el reimplante de un nuevo vástago en dos caoso y conservación de un vástago firme en otros dos. En el caso restante, el reimplante de defirió para un segundo tiempo por las características de la paciente. Una paciente presentó luxación de la prótesis en el postoperatorio, que fue tratada exitosamente mediante reducción ortopédica y contención externa. Las cuatro pacientes con revisiones o conservación de la prótesis recuperaron la capacidad de ambulación con uso de un bastón
Subject(s)
Humans , Female , Fracture Fixation, Internal , Femoral Neck Fractures/surgery , Transplantation, HomologousABSTRACT
1. The regulation of Maxi Cl(-) channels by 17beta-oestradiol and non-steroidal triphenylethylene antioestrogens represents a rapid, non-classical effect of these compounds. In the present study we have investigated the signalling pathways used for the regulation of Maxi Cl(-) channel activity by oestrogens and antioestrogens in C1300 neuroblastoma cells. 2. Whole-cell Maxi Cl(-) currents were readily and reversibly activated by tamoxifen, toremifene and the membrane-impermeant ethyl-bromide tamoxifen, only when applied to the extracellular medium. 3. Pre-treatment of C1300 cells with oestrogen or cAMP prevented the antioestrogen-induced activation of Maxi Cl(-) channels. The inhibitory effect of 17beta-oestradiol and cAMP was abolished by the kinase inhibitor staurosporine. 4. Current activation was unaffected by the removal of intracellular Ca(2+) and Mg(2+), but was completely abolished in the presence of okadaic acid. These results are consistent with the participation of an okadaic acid-sensitive serine/threonine protein phosphatase in the activation of Maxi Cl(-) channels. However, neither oestrogen or antioestrogen treatment modified the total activity of the two major serine/threonine phosphatases, PP1 and PP2A, in C1300 cells. 5. Although the role of these Maxi Cl(-) channels remains unknown, our findings suggest strongly that their modulation by oestrogens and antioestrogens is linked to intracellular signalling pathways.
Subject(s)
Carcinogens/pharmacology , Chloride Channels/metabolism , Estrogen Antagonists/pharmacology , Neuroblastoma , Okadaic Acid/pharmacology , Stilbenes/pharmacology , Animals , Chlorides/metabolism , Cyclic AMP/pharmacology , Enzyme Inhibitors/pharmacology , Estradiol/pharmacology , Ion Channel Gating/drug effects , Ion Channel Gating/physiology , Mice , Patch-Clamp Techniques , Phosphoprotein Phosphatases/metabolism , Phosphorylation , Selective Estrogen Receptor Modulators/pharmacology , Signal Transduction/drug effects , Signal Transduction/physiology , Staurosporine/pharmacology , Tamoxifen/pharmacology , Toremifene/pharmacology , Tumor Cells, CulturedABSTRACT
BACKGROUND: In 1999 an International Commission of Experts evaluated the sanitary interventions that started in 1980 to eliminate Triatoma infestans, the biological vector of Chagas disease, to certify if the conditions needed to interrupt the transmission, were achieved. AIM: To report the data used by the International certification commission to certify the interruption of vectorial transmission of Chagas disease in Chile. MATERIAL AND METHODS: A comparative evaluation of the prevalence of Trypanosoma cruzi antibodies in children surveyed between 1994 and 1995 and between 1995 and 1999. RESULTS: In the first period, 5,948 children were surveyed and in the second, 5,069 children were studied. Twenty children (0.4%) were positive for Trypanosoma cruzi antibodies in the second survey. These figures were significantly lower than the 1.1% prevalence detected between 1994 and 1995. In only three of the 20 cases, the transmission through vectors was confirmed, which represents a 99.4% reduction of this way of transmission. CONCLUSIONS: Based on these findings, the Commission certified that Chile is the second country in Latin America to interrupt the vector transmission of Chagas disease. The successful public health program for Chagas disease will have a positive impact improving the quality of life of rural populations, that are most exposed to the disease.
Subject(s)
Antibodies, Protozoan/blood , Chagas Disease/prevention & control , Animals , Chagas Disease/immunology , Chagas Disease/transmission , Child , Child, Preschool , Chile/epidemiology , Disease Vectors , Humans , Infant , Infant, Newborn , Population Surveillance , Prevalence , Rural Population , TriatomaABSTRACT
BACKGROUND: Bone morphogenetic proteins (BMPs) are osteogenic but also have diverse functions during development. BMP3 is a major component of osteogenin, which has osteogenic activity. However, recombinant BMP3 (rhBMP3) has no apparent osteogenic function, raising the possibility that BMP3 has no bone-inducing activity or that the recombinant material is not properly processed. To resolve this apparent discrepancy, we utilized a retroviral system to study the effects of BMP3 in vitro. In addition, we generated Bmp3-deficient mice to elucidate the function of BMP3 in vivo. METHODS: Retroviral as well as mammalian expression constructs were utilized to express BMP3 and to create BMP3 conditioned medium. Alkaline phosphatase (ALP) activity and transcriptional response assays were used to monitor the ability of BMP3 to elicit either a BMP-like or a transforming growth factor beta (TGF-beta)/activin-like response in osteoblastic cell lines. Finally, mice deficient in BMP3 were generated to investigate BMP3 function in vivo. RESULTS: BMP3 was unable to induce an osteogenic response in W-20-17, MC3T3-E1, or C3H10T1/2 cells, although all three cell lines were responsive to BMP2. However, BMP3 inhibited responsiveness to BMP2 in these assays, suggesting that BMP3 antagonizes BMP2 signaling. This inhibition did not occur through inhibition of binding of BMP2 to its receptors. BMP3 activated the TGF-beta/activin-pathway in these cells, suggesting that BMP3 exerts its inhibiting effects by activating a signaling pathway that antagonizes the BMP pathway. To examine the potential functional consequences of BMP3 action, Bmp3-/- mice, which lack BMP3, were generated. On an outbred genetic background, Bmp3-/- mice are viable and show no obvious skeletal phenotype as embryos or neonates. However, adult mice exhibit twice as much trabecular bone as do their wild-type littermates. This observation is consistent with our in vitro observations suggesting that BMP3 is an inhibitor of osteogenesis in vitro and of bone formation in vivo. CONCLUSIONS: BMP3 is an inhibitor of osteogenic BMPs and can signal through a TGF-beta/activin pathway. The ability of BMP3 to antagonize BMP2 activity may thus be a consequence of competition for signaling components common to TGF-beta/activin and BMP pathways. BMP3, the most abundant BMP in demineralized bone, may therefore play an essential role as a modulator of the activity of osteogenic BMPs in vivo. CLINICAL RELEVANCE: Therapies to accelerate bone healing usually utilize administration of exogenous BMP either in recombinant form or by gene therapy approaches. It is conceivable that the potency of osteogenic BMPs would be increased by inhibiting the activation of antagonistic signaling pathways or by increasing levels of rate-limiting signaling components shared by both BMP and TGF-beta/activin pathways.
Subject(s)
Bone Morphogenetic Proteins/physiology , Receptors, Growth Factor , Animals , Bone Morphogenetic Protein 3 , Bone Morphogenetic Protein Receptors , Cell Division , Cells, Cultured , Humans , Osteogenesis/physiology , Receptors, Cell Surface/physiology , Signal Transduction/physiologyABSTRACT
Background: In 1999 an International Commission of Experts evaluated the sanitary interventions that started in 1980 to eliminate Triatoma infestans, the biological vector of Chagas disease, to certify if the conditions needed to interrupt the transmission, were achieved. Aim: To report the data used by the International certification commission to certify the interruption of vectorial transmission of Chagas disease in Chile. Material and methods : A comparative evaluation of the prevalence of Trypanosoma cruzi antibodies in children surveyed between 1994 and 1995 and between 1995 and 1999. Results : In the first period, 5.948 children were surveyed and in the second, 5.069 children were studied. Twenty children (0.4 percent) were positive for Trypanosoma cruzi antibodies in the second survey. These figures were significantly lower than the 1.1 percent prevalence detected between 1994 and 1995. In only three of the 20 cases, the transmission through vectors was confirmed, which represents a 99.4 percent reduction of this way of transmission. Conclusions: Based on these findings, the Commission certified that Chile is the second country in Latin America to interrupt the vector transmission of Chagas disease. The successful public health program for Chagas disease will have a positive impact improving the quality of life of rural populations, that are most exposed to the disease
Subject(s)
Humans , Chagas Disease/transmission , Certification/standards , Triatoma/parasitology , Chagas Disease/epidemiology , Serologic Tests/methodsSubject(s)
Humans , Female , Pregnancy , Trypanosoma cruzi/pathogenicity , Chagas Disease/transmission , Maternal-Fetal ExchangeABSTRACT
Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta (TGF-beta) superfamily. Many BMPs are produced in bone and show osteogenic activity, suggesting that they may be determinants of bone mass. BMP3 was originally purified from bone as osteogenin, which induces osteogenic differentiation. Recombinant BMP3 (rhBMP3) has no biological activity, however, leaving its role in skeletal growth unclear. Here we show that BMP3 is an antagonist of osteogenic BMPs: BMP3 dorsalizes Xenopus laevis embryos, inhibits BMP2-mediated induction of Msx2 and blocks BMP2-mediated differentiation of osteoprogenitor cells into osteoblasts. These effects appear to be mediated through activin receptors. Finally, Bmp3(-/-) mice have twice as much trabecular bone as wild-type littermates, indicating that BMP3, the most abundant BMP in adult bone, is a negative determinant of bone density.
Subject(s)
Bone Density/drug effects , Bone Morphogenetic Proteins/pharmacology , Transforming Growth Factor beta , Activin Receptors , Animals , Bone Morphogenetic Protein 2 , Bone Morphogenetic Protein 3 , Bone Morphogenetic Proteins/antagonists & inhibitors , Bone Morphogenetic Proteins/deficiency , Bone Morphogenetic Proteins/genetics , Bone Morphogenetic Proteins/metabolism , Cell Differentiation/drug effects , Cell Line , Culture Media, Conditioned/pharmacology , DNA-Binding Proteins/genetics , Embryo, Nonmammalian/cytology , Embryo, Nonmammalian/drug effects , Female , Femur/drug effects , Femur/metabolism , Gene Targeting , Growth Differentiation Factor 5 , Growth Substances/genetics , Homeodomain Proteins , Humans , In Situ Hybridization , Male , Mesoderm/cytology , Mesoderm/drug effects , Mesoderm/metabolism , Mice , Oocytes/metabolism , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , RNA, Messenger/analysis , RNA, Messenger/genetics , Receptors, Growth Factor/metabolism , Recombinant Proteins , Stem Cells/cytology , Stem Cells/drug effects , Stem Cells/metabolism , Time Factors , Transcription, Genetic/drug effects , Up-Regulation/drug effects , Xenopus laevis/embryologyABSTRACT
The aim of this study was to evaluate the use of transplantation of genetically modified allogeneic cells as a method to induce bone formation. In this study, we infected a murine osteoprogenitor cell line with a retroviral vector containing the human bone morphogenic protein 2 (BMP2) gene. Transduced cells exhibited more alkaline phosphatase activity than cells treated with any of the tested doses of recombinant human BMP2 protein (rhBMP2). The transduced cells were suspended in a collagen solution and injected into the quadriceps muscle in immunocompetent outbred mice. Radiographic and histological examinations demonstrate abundant ectopic bone formation in 85% of the transplanted animals (n = 13). PCR and Southern blot analysis for the puromycin resistance gene revealed that the transplanted cells were detectable for up to 1 week, but not at later time points. None of the animals developed tumors. Our results suggest that allogeneic BMP2-expressing transduced cells may have therapeutic potential for enhancing new bone formation. This model also provides a simple, inexpensive, and sensitive assay for evaluating in vivo the osteoinductive potentials of secreted proteins without the requirement of protein purification or the use of immunodeficient animals.
Subject(s)
Bone Morphogenetic Proteins/biosynthesis , Bone Remodeling/genetics , Transforming Growth Factor beta , Animals , Base Sequence , Bone Morphogenetic Protein 2 , Bone Morphogenetic Proteins/genetics , DNA Primers , Genetic Vectors , Humans , Male , Mice , Recombinant Proteins/genetics , Retroviridae/genetics , Transplantation, AutologousABSTRACT
Maxi-K channels consist of a pore-forming alpha subunit and a regulatory beta subunit, which confers the channel with a higher Ca(2+) sensitivity. Estradiol bound to the beta subunit and activated the Maxi-K channel (hSlo) only when both alpha and beta subunits were present. This activation was independent of the generation of intracellular signals and could be triggered by estradiol conjugated to a membrane-impenetrable carrier protein. This study documents the direct interaction of a hormone with a voltage-gated channel subunit and provides the molecular mechanism for the modulation of vascular smooth muscle Maxi-K channels by estrogens.
Subject(s)
Estradiol/metabolism , Potassium Channels, Calcium-Activated , Potassium Channels/metabolism , Animals , Cattle , Cell Line , Electrophysiology , Estradiol/genetics , Humans , Large-Conductance Calcium-Activated Potassium Channel alpha Subunits , Large-Conductance Calcium-Activated Potassium Channel beta Subunits , Large-Conductance Calcium-Activated Potassium Channels , Patch-Clamp Techniques , Protein Binding , RNA, Messenger , Rats , Xenopus laevisABSTRACT
During 1997 a seroepidemiological study on Chagas' disease was carried out in 18 localities of three provinces (Tocopilla, El Loa and Antofagasta) of Region II (20 degrees 56'-26 degrees South Lat.; 70 degrees 38'-67 degrees West Long.), in order to assess the impact of the control program against Triatoma infestans launched in 1988, based on insecticide spraying of dwellings. By means of ELISA and an indirect hemagglutination test for Chagas' disease blood samples from 1,034 children under 10 years of age were examined, arising a 0.5% (3 cases) positivity. Test resulted positive in 2 (0.9%) children from the locality of San Pedro de Atacama and 1 (0.4%) from Calama city, all in the age group 6-10 year-old. However, none of their dwellings were found infested with T. infestants. These results indicate that the control program has a good possibility to prevent new human infections. It is advisable to continue the seroepidemiological and entomological vigilance and remark the necessity of increasing the effort in the study of transmission through other routes, to adopt or reinforce the pertinent preventive measures.
Subject(s)
Chagas Disease/epidemiology , Endemic Diseases , Adult , Chagas Disease/diagnosis , Child , Child, Preschool , Chile/epidemiology , Female , Humans , Infant , Infant, Newborn , Program Evaluation , Seroepidemiologic StudiesABSTRACT
During 1997 a seroepidemiological study on Chagas' disease was carried out in 18 localities of three provinces (Tocopilla,El Loa and Antofagasta) of Region II (20º 56'-26º south lat.; 70º 38'- 67º west long.), in order to asses the impact of the control program against triatoma infestans launched in 1988, based on insecticide spraying of dwellings. By means of ELISA and an indirect hemagglutination test for chagas' disease blood samples from 1,034 children under 10 years of age were examined, arising a 0.5 por ciento (3 cases) positivity. Test resulted positivite in 2 (0.9 percent) children from the locality of San Pedro de Atacama and 1 (0.4 percent) from Calama city, all in the age group 6-10 year -old. However, none of their dwellings were found infested with T.infestants. These result indicate that the control program has a good possibility to prevent new human infections. It is advisable to continue the seroepidemiological and entomological vigilance and remark the necessity of increasing the effort in the study of transmission through other routes, to adopt or reinforce the pertinent preventive measures