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Resumen: La hipertermia maligna es un raro desorden farmacogenético potencialmente mortal, que se presenta como una respuesta hipermetabólica a los anestésicos volátiles y relajantes musculares despolarizantes en individuos susceptibles. Esta susceptibilidad se asocia a mutaciones en tres genes: RYR1, CACNA1S y STAC3. Puede manifestarse con síntomas leves o como una crisis fulminante, con rabdomiólisis severa, fibrilación ventricular e insuficiencia renal y circulatoria aguda, por lo tanto, el pronóstico depende de qué tan pronto se sospeche del diagnóstico y qué tan rápido se inicie el tratamiento. El diagnóstico definitivo se basa en una prueba de sensibilidad en biopsia muscular fresca y en pruebas genéticas. La mejor manera de prevenir un evento es la detección precoz de los pacientes susceptibles así como contar con el equipo para responder ante una crisis en cada centro donde se administren anestésicos volátiles y la capacitación del personal. Esta revisión sintetiza los conceptos actuales clínicos y biomédicos para detección, prevención, diagnóstico y manejo de la hipertermia maligna.
Abstract: Malignant hyperthermia is a rare, life-threatening pharmacogenetic disorder which presents as a hypermetabolic response to volatile anesthetics and depolarizing muscle relaxants in susceptible individuals. This susceptibility is associated with mutations in three genes: RYR1, CACNA1S and STAC3. Can manifest with mild symptoms or as a fulminant crisis, with severe rhabdomyolysis, ventricular fibrillation and acute renal and circulatory failure, therefore the prognosis depends on how soon the diagnosis is suspected and how fast treatment is started. The definitive diagnosis is based on a fresh muscle biopsy sensitivity test and genetic testing. The best way to prevent an event is the early detection of susceptible, as well as have equipment to respond to a crisis in each center where volatile anesthetics are administered and the training of staff. This review synthesizes current clinical and biomedical concepts for detection, prevention, diagnosis and management of malignant hyperthermia.
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Resumen: Debido a la naturaleza de las reacciones alérgicas y a las dificultades en su diagnóstico en el entorno quirúrgico, hay pocas publicaciones sobre anafilaxia en la infancia y pese a ser adecuadamente investigadas, sólo una pequeña parte puede ser confirmada. Los agentes etiológicos principalmente relacionados con esta entidad en el período perioperatorio son los bloqueadores neuromusculares, el látex y los antibióticos. El diagnóstico puede ser complicado y si no se reconoce a tiempo, el tratamiento se retrasa o no se administra de manera adecuada, con consecuencias fatales. A continuación se hace una revisión de la literatura de la anafilaxia perioperatoria, entidad que permanece subestimada, poco reportada y con ello, también su diagnóstico y oportuno tratamiento.
Abstract: Due to the nature of allergic reactions and the difficulties in their diagnosis in the surgical setting, there are few publications on anaphylaxis in childhood and, when properly investigated, only a small part can be confirmed. The etiological agents mainly related to this entity in the perioperative period are neuromuscular blockers, latex and antibiotics. The diagnosis can be complicated and if it is not recognized in time, treatment is delayed or not administered properly, with fatal consequences. The following is a review of the literature on perioperative anaphylaxis, an entity that remains underestimated, underreported and thus also its diagnosis and timely treatment.
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The ciliate Tetrahymena thermophila can either synthesize tetrahymanol or when available, assimilate and modify sterols from its diet. This metabolic shift is mainly driven by transcriptional regulation of genes for tetrahymanol synthesis (TS) and sterol bioconversion (SB). The mechanistic details of sterol uptake, intracellular trafficking and the associated gene expression changes are unknown. By following cholesterol incorporation over time in a conditional phagocytosis-deficient mutant, we found that although phagocytosis is the main sterol intake route, a secondary endocytic pathway exists. Different expression patterns for TS and SB genes were associated with these entry mechanisms. Squalene synthase was down-regulated by a massive cholesterol intake only attainable by phagocytosis-proficient cells, whereas C22-sterol desaturase required ten times less cholesterol and was up-regulated in both wild-type and mutant cells. These patterns are suggestive of at least two different signaling pathways. Sterol trafficking beyond phagosomes and esterification was impaired by the NPC1 inhibitor U18666A. NPC1 is a protein that mediates cholesterol export from late endosomes/lysosomes in mammalian cells. U18666A also produced a delay in the transcriptional response to cholesterol, suggesting that the regulatory signals are triggered between lysosomes and the endoplasmic reticulum. These findings could hint at partial conservation of sterol homeostasis between eukaryote lineages.
Assuntos
Colesterol/metabolismo , Regulação da Expressão Gênica , Homeostase , Fagocitose , Pinocitose , Proteínas de Protozoários/metabolismo , Esteróis/metabolismo , Tetrahymena thermophila/metabolismo , Animais , Transporte Biológico , Retículo Endoplasmático/metabolismo , Endossomos/metabolismo , Humanos , Proteínas de Protozoários/genética , Transdução de Sinais , Tetrahymena thermophila/genética , Tetrahymena thermophila/crescimento & desenvolvimentoRESUMO
The ciliate Tetrahymena thermophila does not require sterols for growth and synthesizes pentacyclic triterpenoid alcohols, mainly tetrahymanol, as sterol surrogates. However, when sterols are present in the environment, T. thermophila efficiently incorporates and modifies them. These modifications consist of desaturation reactions at positions C5(6), C7(8), and C22(23), and de-ethylation at C24 of 29-carbon sterols (i.e. phytosterols). Three out of four of the enzymes involved in the sterol modification pathway have been previously identified. However, identification of the sterol C22 desaturase remained elusive, as did other basic aspects of this metabolism. To get more insights into this peculiar metabolism, we here perform a whole transcriptome analysis of T. thermophila in response to exogenous cholesterol. We found 356 T. thermophila genes to be differentially expressed after supplementation with cholesterol for 2 h. Among those that were upregulated, we found two genes belonging to the long spacing family of desaturases that we tentatively identified by RNAi analysis as sterol C22 desaturases. Additionally, we determined that the inhibition of tetrahymanol synthesis after supplementation with cholesterol occurs by a transcriptional downregulation of genes involved in squalene synthesis and cyclization. Finally, we identified several uncharacterized genes that are likely involved in sterols transport and signaling.
Assuntos
Colesterol/metabolismo , Genoma de Protozoário , Tetrahymena thermophila/genética , Tetrahymena thermophila/metabolismo , Colesterol/administração & dosagem , Meios de Cultura , Perfilação da Expressão GênicaRESUMO
Trypanosoma cruzi, the etiological agent of Chagas' disease, presents nutritional requirements for several metabolites. It requires heme for the biosynthesis of several heme-proteins involved in essential metabolic pathways like mitochondrial cytochromes and respiratory complexes, as well as enzymes involved in the biosynthesis of sterols and unsaturated fatty acids. However, this parasite lacks a complete route for its synthesis. In view of these facts, T. cruzi has to incorporate heme from the environment during its life cycle. In other words, their hosts must supply the heme for heme-protein synthesis. Although the acquisition of heme is a fundamental issue for the parasite's replication and survival, how this cofactor is imported and distributed is poorly understood. In this work, we used different fluorescent heme analogs to explore heme uptake along the different life-cycle stages of T. cruzi, showing that this parasite imports it during its replicative stages: the epimastigote in the insect vector and the intracellular amastigote in the mammalian host. Also, we identified and characterized a T. cruzi protein (TcHTE) with 55% of sequence similarity to LHR1 (protein involved in L. amazonensis heme transport), which is located in the flagellar pocket, where the transport of nutrients proceeds in trypanosomatids. We postulate TcHTE as a protein involved in improving the efficiency of the heme uptake or trafficking in T. cruzi.
Assuntos
Proteínas de Transporte/metabolismo , Heme/metabolismo , Proteínas de Protozoários/metabolismo , Trypanosoma cruzi/metabolismo , Animais , Proteínas de Transporte/genética , Chlorocebus aethiops , Clonagem Molecular , Regulação da Expressão Gênica , Proteínas de Protozoários/genética , Trypanosoma cruzi/genética , Células VeroRESUMO
La región de Huatusco, Veracruz, es un área de alta producción de café en México. La temperatura y la precipitación son elementos climáticos a los que es sensible el cafeto. Estos parámetros están relacionados con la altitud, orientación de ladera y pendiente en los sistemas agroecológicos de sombra. Con la finalidad de tener un mejor conocimiento de los posibles impactos del cambio climático sobre la floración y desarrollo del fruto para las especies Coffea arabica y C. canephora, se realizó un escenario base, relacionando los períodos en los que estas fases reproductivas del cafeto se desarrollan con la climatología de la región a través de diagramas ombrotérmicos. Al diagrama ombrotérmico base, se le aplicaron los incrementos de temperatura y razones de cambio en precipitación de las salidas de dos modelos de cambio climático con el fin de medir para cada modelo los posibles impactos en las fases reproductivas señaladas. Según los dos escenarios de cambio climático aplicados, se pueden provocar diferencias importantes en la climatología regional y, por tanto, fuertes impactos, alterando el inicio de la floración que está relacionado con el promedio de lluvia mensual y la amplitud de la sequía preestival que se presenta durante los meses de invierno. Asimismo, el cambio climático impactaría sobre las variaciones en la disponibilidad de agua durante el crecimiento del fruto, relacionadas principalmente a modificaciones en el superávit hídrico y el incremento de la sequía intraestival que se presenta durante la estación lluviosa.
The region of Huatusco, in Veracruz, Mexico, is an area of high coffee production. Coffee trees are sensitive to temperature and precipitation variations. Those climatic elements are related to the altitude, aspect and slope in the agroecological shadow system. A baseline climatic scenario was introduced on ombrothermic diagrams to relate the periods in which the reproductive phases of the coffee tree develops with the climatology of the region. This method was developed in order to achieve a better knowledge of the possible impacts of climate change on the flowering and fruit development in the species Coffea arabica and C. Canephora. Increases of temperature and changes in precipitation were obtained using the outputs of two general circulation models, and applied to the basic ombrothermic diagram, in order to measure the possible impacts on the stated reproductive phases. According to those two climate change scenarios, important differences in regional climatology can be projected, and therefore strong impacts were detected: changes of the beginning of flowering which is related to the mean rainfall, and the extent of the preestival drought during the winter months. Also, climatic change could impact the water availability during the fruit growing period, which is related the modifications in water surplus and to the increase of the intraestival drought during the rainy season of the year.
A região de Huatusco, Veracruz, é uma área de alta produção de café no México. A temperatura e a precipitação são elementos climáticos aos quais o cafeeiro é sensível. Estes parâmetros estão relacionados com a altitude, orientação de ladeira e a pendente nos sistemas agroecológicos de sombra. Com a finalidade de ter um melhor conhecimiento dos posíveis impactos da mudança climática sobre a floração e desenvolvimento do fruto para as espécies Coffea arabica y C. canephora, se realizou um cenário base, relacionando os períodos em que estas fases reprodutivas do cafeeiro se desenvolvem com a climatologia da região através de diagramas ombrotérmicos. Ao diagrama ombrotérmico base, foram aplicados os incrementos de temperatura e padres de mudança em precipitação das saídas de dois modelos de mudança climática com o fim de medir, para cada modelo, os posíveis impactos nas fases reprodutivas apontadas. Segundo os dois cenários de mudança climática aplicados, podem ser provocadas diferências importantes na climatologia regional e, por tanto, fortes impactos, alterando o início da floração que está relacionado com a média de chuva mensal e a amplitude do veranico que se apresenta durante os meses de inverno. Da mesma forma, a mudança climática impactaria sobre as variações na disponibilidade de agua durante o crescimento do fruto, relacionadas principalmente a modificações no superávit hídrico e o incremento de veranicos que se apresentam durante a estação chuvosa.