RESUMO
RESUMEN Introducción. La pandemia del COVID-19, ocasionada por SARS-CoV-2, aumenta de manera exponencial, afectando el sistema de salud, la economía y poniendo en riesgo la vida de miles de personas por las características de contagio, además de la posibilidad de compromiso severo en adultos mayores e individuos inmunocomprometidos. Objetivos. Realizar una revisión en la literatura que aborde diferentes aspectos de la pandemia del COVID-19, dirigido a los profesionales de las ciencias de la salud o de otras disciplinas interesados en adquirir conocimientos sobre el SARS-CoV-2 con una visión integral. Materiales y métodos. Se realizó una búsqueda en la literatura utilizando términos Mesh en las siguientes bases de datos: Pubmed, Ovid, Clinical Key, Science Direct, para su análisis y selección de acuerdo con su relevancia en nuevos aportes. Resultados. Se evaluaron diversos estudios de cohortes, investigaciones clínicas experimentales, guías interinas de práctica de diversos organismos como el CDC y WHO, en donde se identifican las características epidemiológicas del patógeno, los estudios en CoVs previos, así como también los lineamientos preventivos, éticos y evaluación de fármacos ante el CO-VID-19. Conclusiones. Conocer el origen del patógeno, estructura, modo de transmisión, adecuada selección dentro de los criterios diagnósticos, entre otros puntos claves que contribuyen en el fortalecimiento de nuevas medidas preventivas y terapéuticas que puedan llegar a ser implementadas por el personal sanitario, generando mejoras en la atención de los pacientes con posible diagnóstico de COVID-19.
ABSTRACT Introduction. The COVID-19 pandemic, caused by SARS-CoV-2, increases exponentially, affecting the health system, the economy and putting at risk the lives of thousands of people due to the characteristics of contagion, in addition to the possibility of severe compromise in older adults and immunocompromised individuals. Objective. Carry out a review of the literature that addresses different aspects of the COVID-19 pandemic, aimed at professionals in the health sciences or other disciplines, interested in acquiring knowledge about SARS-CoV-2 with a comprehensive vision. Methods. A literature search was conducted using Mesh terms in the following databases: Pubmed, Ovid, Clinical Key, Science Direct for analysis and selection according to their relevance in new contributions. Results. Various cohort studies, experimental clinical studies, as well as interim practice guidelines from various agencies such as the CDC and WHO were evaluated, identifying the epidemiological characteristics of the pathogen from December 2019 to the present, as well as studies on previous CoVs, preventive guidelines and evaluation of drugs against COVID-19. Conclusion. Know the origin of the pathogen, structure, mode of transmission, adequate selection within the diagnostic criteria, among other key points that contribute to the strengthening of new preventive and therapeutic measures that may be implemented by health personnel, generating improvements in the care of patients with possible diagnosis of COVID-19.
RESUMO
In arid ecosystems, desert bighorn sheep are dependent on natural waterholes, particularly in summer when forage is scarce and environmental temperatures are high. To detect waterholes in Sierra Santa Isabel, which is the largest area of desert bighorn sheep habitat in the state of Baja California, Mexico, we used the normalized difference vegetation index (NDVI) and normalized difference water index (NDWI) from Sentinel-2 satellite images. Waterhole detection was based on the premise that sites with greater water availability, where NDVI was higher, can be identified by their density of vegetation greenness. For the detected waterholes, we estimated the escape terrain (presence of cliffs or steep, rocky slopes) around each by the vector ruggedness measure to determine their potential use by desert bighorn sheep based on the animals' presence as documented by camera traps. We detected 14 waterholes with the NDVI of which 11 were known by land owners and 3 were unrecorded. Desert bighorn were not detected in waterholes with high values of escape terrain, i.e., flat areas. Waterhole detection by NDVI is a simple method, and with the assistance and knowledge of the inhabitants of the Sierra, it was possible to confirm the presence each waterhole in the field.
Assuntos
Carneiro da Montanha/fisiologia , Recursos Hídricos , Animais , Clima Desértico , Ecossistema , Feminino , México , Imagens de Satélites , OvinosRESUMO
It was reported that aminochrome induces the formation of alpha synuclein (SNCA) oligomers during dopamine oxidation. We found that DT-diaphorase (NQO1) prevents the formation of SNCA oligomers in the presence of aminochrome determined by Western blot, transmission electron microscopy, circular dichroism, and thioflavin T fluorescence, suggesting a protective role of NQO1 by preventing the formation of SNCA oligomers in dopaminergic neurons. In order to test NQO1 protective role in SNCA neurotoxicity in cellular model, we overexpressed SNCA in both RCSN-3 cells (wild-type) and RCSN-3Nq7 cells, which have constitutive expression of a siRNA against NQO1. The expression of SNCA in RCSN-3SNCA and RCSN-3Nq7SNCA cells increased 4.2- and 4.4-fold, respectively. The overexpression of SNCA in RCSN-3Nq7SNCA cells induces a significant increase in cell death of 2.8- and 3.2-fold when they were incubated with 50 and 70 µM aminochrome, respectively. The cell death was found to be of apoptotic character determined by annexin/propidium iodide technique with flow cytometry and DNA laddering. A Western blot demonstrated that SNCA in RCSN-3SNCA is only found in monomer form both in the presence of 20 µM aminochrome or cell culture medium contrasting with RCSN-3Nq7SNCA cells where the majority SNCA is found as oligomer. The antioligomer compound scyllo-inositol induced a significant decrease in aminochrome-induced cell death in RCSN-3Nq7SNCA cells in comparison to cells incubated in the absence of scyllo-inositol. Our results suggest that NQO1 seems to play an important role in the prevention of aminochrome-induced SNCA oligomer formation and SNCA oligomers neurotoxicity in dopaminergic neurons.
Assuntos
Benzopiranos/toxicidade , Biopolímeros/metabolismo , NAD(P)H Desidrogenase (Quinona)/metabolismo , Sistema Nervoso/efeitos dos fármacos , alfa-Sinucleína/metabolismo , Linhagem Celular , HumanosRESUMO
The high-frequency ultrasound allows detailed knowledge of surface structures including tendons and their sheaths, joint capsule, cartilage and cortical bone surface. The gray scale ultrasonography, to visualize proliferative synovial tissue and bone erosions while power Doppler assesses the synovial hyperemia, which is the greatest predictor of future bone structural damage. Through ultrasound can document changes in synovial thickening and hyperemia in response to treatment. Ultrasonography has proved to be the best diagnostic tool for early arthritis and disease monitoring.
La ultrasonografía de alta frecuencia permite un conocimiento en detalle de estructuras superficiales, incluyendo tendones y sus vainas, cápsula articular, cartílago y superficie cortical ósea. La escala de grises en ultrasonografía permite visualizar tejido sinovial proliferativo y erosiones óseas, mientras que el Doppler de poder evalúa la hiperemia sinovial, que es el mayor predictor de futuro daño estructural óseo. A través de la ecografía se pueden documentar cambios en el engrosamiento sinovial e hiperemia como respuesta a un tratamiento. La ultrasonografía ha demostrado ser la mejor herramienta diagnóstica en artritis temprana y para monitoreo de la enfermedad.
Assuntos
Humanos , Artrite Reumatoide , UltrassonografiaRESUMO
La presente investigación surge de la observación de la vulnerabilidad multifactorial de los homosexuales, la cual ha sido poco enfocada por los programas de lucha contra el SIDA y las ITS, debido a que no constituyen un grupo homogéneo sino que representan una amplia gama de personas con estilos de vida y necesidades de salud distintas a la población heterosexual, diferenciando del mismo modo las necesidades en salud de los homosexuales seropositivos en relación a los homosexuales seronegativos. Los programas y mensajes para la prevención de la infección/reinfección del VIH y otras ITS deben incluir visiblemente a los individuos homosexuales seropositivos sin que se perciba culpabilización, estigma o se apele a su exclusiva responsabilidad. Se deben tener en cuenta los factores emocionales que influyen para que se impliquen en prácticas sexuales no seguras y no se asuman o juzguen como comportamientos irresponsables. Si bien muchos hombres se infectan con parejas sexuales que no saben de su estado serológico, el incremento de la incidencia del VIH y de las tasas de ITS subrayan la necesidad de entender a profundidad los estilos de vida de los homosexuales con VIH. Para conocer las necesidades de prevención, cuidado y soporte a los participantes homosexuales, se necesita un entendimiento profundo de este colectivo con respecto a: su situación de ser seropositivo, su sexualidad y prácticas sexuales, la percepción y significados del riesgo sexual, y los contextos sociales y familiares en los cuales se desenvuelven. Los resultados de esta investigación servirán para desarrollar intervenciones adaptadas, focalizadas y dirigidas particularmente a aumentar el acceso de este grupo vulnerable a la prevención y a los servicios de cuidado, apoyo y tratamiento del VIH. Razón por la que surge la necesidad de realizar un estudio cualitativo sobre "Estilos de vida del homosexual con VIH en Lima Metropolitana¬ 2011" que ofrece un profundo entendimiento de lo que para los participantes homosexuales significa ser seropositivo, el impacto que tiene el VIH en la vida, el cuidado y el riesgo sexual, y las necesidades que se generan por vivir con el VIH. El presente estudio es del tipo descriptivo con el uso de una técnica cualitativa como es la "Entrevista a Profundidad", ello debido a la naturaleza del fenómeno a investigar y está encaminado a conocer los estilos de vida del homosexual con VIH. La población estuvo constituida por 10 homosexuales con VIH captados en los talleres organizados por el GAM (Grupo de ayuda mutua) "Corazones chalacos" y el Centro Comunitario GLBT "5to PISO". Entre las consideraciones más resaltantes tenemos: para los participantes lo más importante es "'sentirse bien¼ y si eso lo consiguen sin los fármacos prescritos, pues lo prefieren así. También se ha identificado casos de negación de la enfermedad, es decir que no han encontrado aún los mecanismos de adaptación para aceptar su enfermedad, trayendo como consecuencia que no se preocupen de su tratamiento. De otro lado han cambiado su perspectiva de la vida y vivir el presente es lo primordial. En cuanto al aspecto sexual, tan crucial para todo ser humano, se ha encontrado participantes cuya responsabilidad esta primero que todo y actuar con prudencia y tomando todas las medidas de seguridad es su nueva actitud; frente a otros que continuaran con una vida sexual poco segura, constituyéndose en un peligro de salud pública
Assuntos
Humanos , Adulto , Pessoa de Meia-Idade , Estilo de Vida , Homossexualidade , Infecções por HIV , Pesquisa QualitativaRESUMO
Introducción: El carcinoma mucoepidermoide pulmonares un tumor relativamente raro bien definido, que seorigina en las glándulas serosas del epitelio traqueo bronquialy se caracteriza por la coexistencia de tres tipos de células:células epidermoides, mucosecretantes e intermedias,con lo cual se establecen distintos grados histológicos, queguardan relación estrecha con el pronóstico. Objetivos: Sepresentan dos casos de carcinoma mucoepidermoide, haciendoespecial énfasis en la forma de presentación, tipohistológico y tratamiento instaurado. Resultados: Dos mujeresde 46 y 21 años sin patologías previas, la primera pacientepresento neumonía a repetición acompañado de tos yhemoptisis intermitente a diferencia de la segunda que consultapor dolor torácico acompañado de disfonía y disfagia.La fibrobroncoscopia en ambos casos demostró presenciade obstrucción (tumor) endobronquial. En la TAC de Tóraxse evidencia atelectasia en el primer caso e infiltrado micronodulillarcon adenopatías en el segundo caso. Las dospacientes fueron sometidas a cirugías, logrando reseccióntumoral por toracotomía en el primer caso, en el segundocaso se realizó la toracoscopia diagnóstica encontrándosepatología avanzada por lo que va a tratamiento paliativo.Conclusión: El carcinoma mucoepidermoide pulmonar espoco frecuente. La sintomatología en la mayoría de los casosasemeja a una neumonía a repetición, donde la radiologíay la endoscopía bronquial pueden hacer el diagnóstico.El tratamiento y sobretodo el pronóstico dependerá del gradode diferenciación histológica, pudiendo asociarse luegode la exéresis quirúrgica a tratamientos complementarioscomo la quimio y/o radioterapia.
Assuntos
Adenocarcinoma Bronquioloalveolar , Carcinoma BroncogênicoRESUMO
In previous studies, we observed that cells treated with aminochrome obtained by oxidizing dopamine with oxidizing agents dramatically changed cell morphology, thus posing the question if such morphological changes were dependent on aminochrome or the oxidizing agents used to produce aminochrome. Therefore, to answer this question, we have now purified aminochrome on a CM-Sepharose 50-100 column and, using NMR studies, we have confirmed that the resulting aminochrome was pure and that it retained its structure. Fluorescence microscopy with calcein-AM and transmission electron microscopy showed that RCSN-3 cells presented an elongated shape that did not change when the cells were incubated with 50 muM aminochrome or 100 muM dicoumarol, an inhibitor of DT-diaphorase. However, the cell were reduced in size and the elongated shape become spherical when the cells where incubated with 50 muM aminochrome in the presence of 100 muM dicoumarol. Under these conditions, actin, alpha-, and beta-tubulin cytoskeleton filament networks became condensed around the cell membrane. Actin aggregates were also observed in cells processes that connected the cells in culture. These results suggest that aminochrome one-electron metabolism induces the disruption of the normal morphology of actin, alpha-, and beta-tubulin in the cytoskeleton, and that DT-diaphorase prevents these effects.
Assuntos
Actinas/efeitos dos fármacos , Indolquinonas/toxicidade , Substância Negra/citologia , Tubulina (Proteína)/efeitos dos fármacos , Actinas/ultraestrutura , Animais , Linhagem Celular Transformada/efeitos dos fármacos , Linhagem Celular Transformada/ultraestrutura , Indolquinonas/química , Microscopia Confocal/métodos , Microscopia Eletrônica de Transmissão/métodos , NAD(P)H Desidrogenase (Quinona)/metabolismo , Ressonância Magnética Nuclear Biomolecular/métodos , Ratos , Tubulina (Proteína)/ultraestruturaRESUMO
RCSN-3 cells are a cloned cell line derived from the substantia nigra of an adult rat. The cell line grows in monolayer and does not require differentiation to express catecholaminergic traits, such as (i) tyrosine hydroxylase; (ii) dopamine release; (iii) dopamine transport; (iv) norepinephrine transport; (v) monoamine oxidase (MAO)-A expression, but not MAO-B; (vi) formation of neuromelanin; (vii) VMAT-2 expression. In addition, this cell line expresses serotonin transporters, divalent metal transporter, DMT1, dopamine receptor 1 mRNA under proliferating conditions, and dopamine receptor 5 mRNA after incubation with dopamine or dicoumarol. Expression of dopamine receptors D(2), D(3) and D(4) mRNA were not detected in proliferating cells or when the cells were treated with dopamine, CuSO(4), dicoumarol or dopamine-copper complex. Angiotensin II receptor mRNA was also found to be expressed, but it underwent down regulation in the presence of aminochrome. Total quinone reductase activity corresponded 94% to DT-diaphorase. The cells also express antioxidant enzymes such as superoxide dismutase, catalase and glutathione peroxidase. This cell line is a suitable in vitro model for studies of dopamine metabolism, since under proliferating conditions the cells express all the pertinent markers.
Assuntos
Linhagem Celular Transformada , Dopamina/metabolismo , Neurônios/citologia , Neurônios/metabolismo , Animais , Linhagem Celular Transformada/metabolismo , Linhagem Celular Transformada/ultraestrutura , Células Cultivadas , Microscopia Confocal , Microscopia Eletrônica de Transmissão , Neurônios/ultraestrutura , Proteínas de Transporte de Neurotransmissores/metabolismo , Oxirredutases/metabolismo , Ratos , Ratos Endogâmicos F344 , Substância Negra/citologia , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Four decades after L-dopa introduction to PD therapy, the cause of Parkinson's disease (PD) remains unknown despite the intensive research and the discovery of a number of gene mutations and deletions in the pathogenesis of familial PD. Different model neurotoxins have been used as preclinical experimental models to study the neurodegenerative process in PD, such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and rotenone. The lack of success in identifying the molecular mechanism for the degenerative process in PD opens the question whether the current preclinical experimental models are suitable to understand the degeneration of neuromelanin-containing dopaminergic neurons in PD. We propose aminochrome as a model neurotoxin to study the neurodegenerative processes occurring in neuromelanin-containing dopaminergic neurons in PD. Aminochrome is an endogenous compound formed during dopamine oxidation and it is the precursor of neuromelanin, a substance whose formation is a normal process in mesencephalic dopaminergic neurons. However, aminochrome itself can induce neurotoxicity under certain aberrant conditions such as (i) one-electron reduction of aminochrome catalyzed by flavoenzymes to leukoaminochrome o-semiquinone radical, which is a highly reactive neurotoxin; or (ii) the formation of aminochrome adducts with alpha-synuclein, enhancing and stabilizing the formation of neurotoxic protofibrils. These two neurotoxic pathways of aminochrome are prevented by DT-diaphorase, an enzyme that effectively reduces aminochrome with two-electrons preventing both aminochrome one-electron reduction or formation alpha synuclein protofibrils. We propose to use aminochrome as a preclinical experimental model to study the neurodegenerative process of neuromelanin containing dopaminergic neurons in PD.
Assuntos
Modelos Animais de Doenças , Dopamina/metabolismo , Indolquinonas/toxicidade , Degeneração Neural/etiologia , Degeneração Neural/metabolismo , Doença de Parkinson/patologia , Animais , HumanosRESUMO
Reduction in corticosterone by acute adrenalectomy (5 d) promotes apoptosis in dentate gyrus (DG) granular neurons, an effect concomitant with variations in the expression of the Bcl-2 gene family implicated in apoptotic regulation. However, no studies exist correlating the effect of long-term adrenalectomy (30 d) on the hippocampus in terms of extent of apoptosis and the levels of proteins related to an apoptotic cascade. After 5 d of adrenalectomy, we found an increase in apoptosis of the DG granular region, correlated with an increase in the processing of caspase-9. The magnitude of apoptosis 30 d after adrenalectomy was reduced in the DG granular layer compared with 5 d after adrenalectomy, in close relation to a reduction in the level of processed caspase-9. To understand how the increase in cell survival long after adrenalectomy occurs, we analyzed changes in the expression of genes and proteins related to apoptosis. Long-term adrenalectomy did not change hippocampal pro-apoptotic Bax or antiapoptotic Bcl-2 mRNA levels or protein content with respect to control. However, we found an increase in mRNA levels of the GD's Bcl-x gene, in parallel with the increase in anti-apoptotic BCL-XL protein levels. These results suggest the reduction in apoptosis observed after long-term adrenalectomy occurs through mechanisms that repress proapoptotic genes previously found to be increased at shorter times of adrenalectomy.
Assuntos
Adrenalectomia/efeitos adversos , Apoptose , Hipocampo/citologia , Proteínas Proto-Oncogênicas c-bcl-2/fisiologia , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Caspase 9 , Caspases/metabolismo , Sobrevivência Celular , Hipocampo/fisiologia , Masculino , Modelos Biológicos , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
We report a new and specific mechanism for iron-mediated neurotoxicity using RCHT cells, which were derived from rat hypothalamus. RCHT cells exhibit immunofluorescent-positive markers for dopamine beta-hydroxylase and the norepinephrine transporter, NET. In the present study, we observed that iron-induced neurotoxicity in RCHT cells was dependent on (i) formation of an Fe-dopamine complex (100 microM FeCl3:100 microM dopamine); (ii) specific uptake of the Fe-dopamine complex into RCHT cells via NET (79+/-2 pmol 59Fe/mg/min; P<0.05), since the uptake of the 59Fe-dopamine complex by the cells was inhibited by 30 microM reboxetine, a specific NET inhibitor (78% inhibition, P<0.001); and (iii) intracellular oxidation of dopamine present in the Fe-dopamine complex to aminochrome; (iv) inhibition of DT-diaphorase, since incubation of RCHT cells with 100 microM Fe-dopamine complex in the presence of 100 microM dicoumarol, an inhibitor of DT-diaphorase, induced significant cell death (51+/-5%; P<0.001). However, this cell death was reduced by 75% when the cells were incubated in the presence of 30 microM reboxetine (P<0.01). No significant cell death was observed when the cells were incubated with 100 microM dopamine, 100 microM Fe-Dopamine complex, 100 microM dicoumarol, or 100 microM FeCl3 (8.3+/-2, 9+/-4, 8.5+/-3, or 9.7+/-2% of control, respectively). ESR studies using the spin trapping agent DMPO showed no formation of hydroxyl radicals when the cells were incubated with 100 microM FeCl3 alone. However, using the same ESR technique, the formation of hydroxyl radicals and a carbon-centered radical was detected when the cells were incubated with 100 microM Fe-dopamine complex in the presence of 100 microM dicoumarol. These studies suggest that iron can induce cell toxicity by a mechanism that requires the formation and NET-mediated uptake of an Fe-dopamine complex, ultimately resulting in the intracellular formation of reactive species.
Assuntos
Dopamina/metabolismo , Compostos Férricos/metabolismo , Hipotálamo/efeitos dos fármacos , Ferro/toxicidade , Inibidores da Captação Adrenérgica/farmacologia , Animais , Morte Celular/efeitos dos fármacos , Linhagem Celular , Cloretos , Dicumarol/farmacologia , Dopamina/farmacologia , Dopamina beta-Hidroxilase/metabolismo , Imunofluorescência , Hipotálamo/enzimologia , Hipotálamo/patologia , Indolquinonas/metabolismo , Ferro/metabolismo , Microscopia Confocal , Morfolinas/farmacologia , NAD(P)H Desidrogenase (Quinona)/antagonistas & inibidores , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Ratos , Ratos Endogâmicos F344 , Reboxetina , Simportadores/metabolismoRESUMO
The role of dopamine in iron uptake into catecholaminergic neurons, and dopamine oxidation to aminochrome and its one-electron reduction in iron-mediated neurotoxicity, was studied in RCSN-3 cells, which express both tyrosine hydroxylase and monoamine transporters. The mean +/- SD uptake of 100 microm 59FeCl3 in RCSN-3 cells was 25 +/- 4 pmol per min per mg, which increased to 28 +/- 8 pmol per min per mg when complexed with dopamine (Fe(III)-dopamine). This uptake was inhibited by 2 microm nomifensine (43%p < 0.05), 100 microm imipramine (62%p < 0.01), 30 microm reboxetine (71%p < 0.01) and 2 mm dopamine (84%p < 0.01). The uptake of 59Fe-dopamine complex was Na+, Cl- and temperature dependent. No toxic effects in RCSN-3 cells were observed when the cells were incubated with 100 microm FeCl3 alone or complexed with dopamine. However, 100 microm Fe(III)-dopamine in the presence of 100 microm dicoumarol, an inhibitor of DT-diaphorase, induced toxicity (44% cell death; p < 0.001), which was inhibited by 2 microm nomifensine, 30 microm reboxetine and 2 mm norepinephrine. The neuroprotective action of norepinephrine can be explained by (1) its ability to form complexes with Fe3+, (2) the uptake of Fe-norepinephrine complex via the norepinephrine transporter and (3) lack of toxicity of the Fe-norepinephrine complex even when DT-diaphorase is inhibited. These results support the proposed neuroprotective role of DT-diaphorase and norepinephrine.
Assuntos
Dopamina/metabolismo , Ferro/toxicidade , Moduladores de Transporte de Membrana , Proteínas de Membrana Transportadoras/antagonistas & inibidores , Neurônios/efeitos dos fármacos , Norepinefrina/farmacologia , Substância Negra/citologia , Inibidores da Captação Adrenérgica/farmacologia , Análise de Variância , Animais , Proteínas da Membrana Plasmática de Transporte de Catecolaminas , Morte Celular/efeitos dos fármacos , Células Cultivadas , Cloretos/metabolismo , Dicumarol/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina , Inibidores da Captação de Dopamina , Relação Dose-Resposta a Droga , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Embrião de Mamíferos , Inibidores Enzimáticos/farmacologia , Compostos Férricos/metabolismo , Compostos Férricos/farmacologia , Imunofluorescência/métodos , Imipramina/farmacologia , Indolquinonas/farmacologia , Isótopos de Ferro/farmacologia , Glicoproteínas de Membrana/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Microscopia Confocal/métodos , Modelos Biológicos , Morfolinas/farmacologia , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Nomifensina/farmacologia , Proteínas da Membrana Plasmática de Transporte de Norepinefrina , Ratos , Ratos Endogâmicos F344 , Ratos Wistar , Reboxetina , Proteínas da Membrana Plasmática de Transporte de Serotonina , Sódio/metabolismo , Simportadores/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Leukoaminochrome o-semiquinone radical is generated during one-electron reduction of dopamine oxidation product aminochrome when DT-diaphorase is inhibited. Incubation of 100 microM aminochrome with 100 microM dicoumarol, an inhibitor of DT-diaphorase during 2 h, induces 56% cell death (P < 0.001) with concomitant formation of (i) intracellular hydroperoxides (4.2-fold increase compared to control; P < 0.001); (ii) hydroxyl radicals, detected with ESR and spin trapping agents (2.4-fold increase when cells were incubated with aminochrome in the presence of dicoumarol compared to aminochrome alone); (iii) intracellular edema, and cell membrane deterioration determined by transmission electron microscopy; (iv) absence of apoptosis, supported by using anexin-V with flow cytometry; (v) a strong decrease of mitochondrial membrane potential determined by the fluorescent dye 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanineiodide (P < 0.01); (vi) swelling and disruption of outer and inner mitochondrial membranes determined by transmission electron microscopy. These results support the proposed role of leukoaminochrome o-semiquinone radical as neurotoxin in Parkinson's disease neurodegeneration and DT-diaphorase as neuroprotective enzyme.
Assuntos
Benzoquinonas/metabolismo , Dopamina/metabolismo , Mitocôndrias/metabolismo , Degeneração Neural/metabolismo , Neurônios/metabolismo , Neurotoxinas/metabolismo , Animais , Linhagem Celular , Radical Hidroxila/metabolismo , Potenciais da Membrana/fisiologia , Necrose , Neurônios/patologia , Neurônios/fisiologia , Oxirredução , Ratos , Ratos Endogâmicos F344 , Substância Negra/citologia , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: The ileo-anal pouch is the surgical procedure of choice for patients with Ulcerative Colitis or Familial Adenomatous Polyposis, but has functional limitations such as a higher frequency of bowel movements, anal leakage, and sometimes the necessity of a protective anal pad. OBJECTIVE: To analyze the functional results and quality of life after the pelvic pouch. MATERIAL AND METHODS: This is a descriptive, prolective, and cross-sectional study that analyzes the clinical variables, functional results and self-reported quality of life of patients after an ileo-anal pouch. A correlation between postoperative clinical variables and quality of life was searched. RESULTS: Twenty-seven patients were included. Mean age was 36 years. Surgical indications for the ileo-anal pouch were Ulcerative Colitis in 17 (63%), Familial Adenomatous Polyposis in 9 (33%) and a colo-rectostomy stricture in 1 (4%). Mean number of bowel movements was 4 at day and 1 at night. Eighteen percent of patients referred anal leakage, 11% had pouchitis, and 11% small bowel obstruction. Most of the patients reported high scores in all evaluated quality of life scales. There was a correlation between lower scores of quality of life and a higher number of bowel movements. CONCLUSIONS: The majority of patients reported an adequate quality of life after the ileo-anal pouch; there was a correlation between lower scores of quality of life and a higher number of bowel movements.
Assuntos
Bolsas Cólicas , Proctocolectomia Restauradora/psicologia , Qualidade de Vida , Polipose Adenomatosa do Colo/cirurgia , Adulto , Colite Ulcerativa/cirurgia , Estudos Transversais , Defecação , Encoprese/etiologia , Encoprese/psicologia , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/psicologia , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Although it is generally accepted that free radicals are involved in the neurodegenerative process occurring in the dopaminergic neurons of the nigro-striatal system in Parkinson's disease, the exact mechanism of neurodegeneration in vivo is still unknown. We propose that the degeneration of dopaminergic nigrostriatal system in this condition may depend on: (a) existence of free dopamine which oxidizes to aminochrome as a consequence of: (i) overproduction of dopamine; (ii) inhibition and/or low expression of synaptic vesicle catecholamine transporter; (iii) inhibition or low expression of monoamine oxidases; (b) one-electron reduction of aminochrome to leukoaminochrome o-semiquinone radical, which induces neurotoxicity, due to inhibition of DT-diaphorase or the existence of a polymorphism with a point mutation (C --> T) in the cDNA 609 expressing an inactive DT-diaphorase. We suggest that DT-diaphorase plays a neuroprotective role in dopaminergic neurons, which is supported by the following observations: (i) Cu-toxicity is dependent on DT-diaphorase inhibition with dicoumarol in RCSN-3 cells derived from the rat substantia nigra; (ii) the cytotoxic effect of monoamine oxidase-A inhibitor amiflamine in RCSN-3 cells is increased by 2.4-fold (p < 0.001) in the presence of the inhibitor of DT-diaphorase, dicoumarol; (iii) concomitant intracerebral administration of manganese (Mn3+) together with the DT-diaphorase inhibitor dicoumarol into the left medial forebrain bundle produced a behavioral pattern characterized by contralateral rotational behavior when the rats were stimulated with apomorphine, in a manner similar to that observed in animals injected unilaterally with 6-hydroxydopamine; (iv) incubation of RCSN-3 cells with salsolinol in the presence of DT-diaphorase inhibitor significantly decreased cell survival by 2.5-fold (p < 0.001).
Assuntos
Dopamina/metabolismo , Indolquinonas , Indóis/metabolismo , NAD(P)H Desidrogenase (Quinona)/fisiologia , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson/metabolismo , Animais , Dopamina/fisiologia , Humanos , Indóis/farmacologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Doenças Neurodegenerativas/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Oxirredução/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/enzimologiaRESUMO
Antecedentes. La proctocolectomía total y anastomosis ileo-anal (PCTAIA) es el procedimiento de elección para los pacientes con colitis ulcerativa crónica inespecífica y poliposis adenomatosa familiar que requieren cirugía. La frecuencia de presentación de estas enfermedades es baja en México, por lo que la experiencia con este procedimiento es escasa. Objetivo. Analizar la morbi-mortalidad operatoria y resultados funcionales a largo plazo en una serie de pacientes sometidos a esta operación en un hospital de referencia en México. Material y métodos. Se analizan retrospectivamente 44 pacientes consecutivos operados de PCTAIA entre 1987 y 1997. La operación incluyó resección mucosa de la zona de transición, anastomosis manual del reservorio ileal en "J" e ileostomía temporal en todos los pacientes. Se determinaron las causas y cifras de morbilidad y mortalidad posoperatorias, así como los resultados funcionales y complicaciones a largo plazo. Resultados. La edad promedio fue de 33 ñ 15 años. Hubo 23 mujeres (52 por ciento) y 21 hombres (48 por ciento). Los principales diagnósticos fueron colitis ulcerativa crónica inespecífica en 59 por ciento y poliposis adenomatosa familiar en 36 por ciento. La morbilidad global fue del 39 por ciento y la mortalidad del 2 por ciento. Con un seguimiento promedio de 24 meses, el promedio de evacuaciones diurnas que presentaron los pacientes fue de 4, 10 por ciento presentaron escurrimiento diurno, 30 por ciento escurrimiento nocturno, y ninguno presentó incontinencia. Tres pacientes han presentado inflamación del reservorio, con respuesta adecuada a antibióticos. Dos pacientes han presentado fístulas del reservorio ileal a largo plazo, pero ninguno requirió de su resección. Conclusiones. PCTAIA es una operación factible en nuestro medio que se acompaña de cifras aceptable de morbi-mortalidad y resultados funcionales satisfactorios
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Polipose Adenomatosa do Colo/cirurgia , Polipose Adenomatosa do Colo/terapia , Colite Ulcerativa/cirurgia , Colite Ulcerativa/terapia , Proctocolectomia Restauradora , Proctocolectomia Restauradora/estatística & dados numéricos , Anastomose Cirúrgica/métodos , Anastomose Cirúrgica , Cirurgia Colorretal/métodosRESUMO
Se realizó vulvuloplastía mitral percutánea con balón de Inoue en siete gestantes con estenosis mitral sever, en clase funcional III a IV de la New York Association (NYHA) que no respondieron a las medidas convencionales. Con la técnica habitual, puntaje ecocardiográfico de Wilkins de ocho a menos, excepto en una y edad gestacional promedio de 28.5 ñ 5.4 semanas. El gradiente valvular mitral midio de 19.8 ñ 6.4 mmHg, disminuyó a 3.6 ñ 2.9 mmHg (P< 0.01); y el área valvular aumentó de 0.84 ñ 0.01 a 2.2 ñ 0.06 cm2 (P<0.01), en cinco de siete pacientes (P< 0.05) hubo mínima insuficiencia mitral y no se detectó comunicación interauricular. Sólo dos tenían hipertensión pulmonar moderada y severa que disminuyeron al menos en forma leve de inmediato. La regresión de la calse funcional de NYHA fue significativa en todas. El tiempo de exposición a radiacciones al feto en promedio de siete minutos, con protección radiológica abdomino-pélvica y dos tuvieron ecocardiograma transesofágico durante la valvuloplastía. Una paciente se llevó a comisurotomía mitral abierta debido a la punción de la pared aórtica 1ue ocasionó mínimo hematoma. En dos pacientes se observó disminución transitoria de la frecuencia cardiaca fetal por hipotensión materna secundaria a la insuflación del balón de Inoue con recuperación espontánea. Todos los embarazos llegaron a término excepto uno; se resolvieron por vía vaginal en cuatro y tres cesáreas por indicación obstétrica. El peso y Apgar de los neonatos fueron satisfactorios. Consideramos que con la ausencia de mortalidad materno - fetal y neonatal los beneficios tan significativos obtenidos con leve trauma y pocas complicaciones justifican la preferencia actual del procedimiento
Assuntos
Humanos , Feminino , Gravidez , Adulto , Cateterismo , Cateterismo/instrumentação , Estenose da Valva Mitral/terapia , Complicações Cardiovasculares na Gravidez/terapiaRESUMO
Antecedentes: Se han desarrollado nuevas técnicas para el manejo quirúrgico de la colitis ulcerativa crónica inespecífica. Objetivo: En este artículo de revisión se analizan las alternativas quirúrgicas actuales para definir su papel en el manejo general de los pacientes con CUCI. Resultados: La proctocolectomía total no restaurativa con ileostomía permanente continúa la operación estándar de oro para la CUCI. La proctocolectomía total restaurativa, con o sin excisión de la zona de transición anal, se está convirtiendo en la operación más ampliamente utilizada. Evita una ileostomía permanente, y permite buenos resultados funcionales en la mayoría de los pacientes. La proctocolectomía subtotal con una bolsa de Hartmann es un procedimiento adecuado en los pacientes operados de urgencia, para permitir la realización de un reservorio ileoanal en una operación subsecuente. La colectomía con anastomosis ileorrectal, y la creación de una ileostomía continente son procedimientos que deben limitarse a candidatos selectos. Conclusiones: Actualmente, la proctocolectomía total con reservorio es la operación de elección en la mayoría de los pacientes, pero el estado general preoperatorio es importante para definir la mejor alternativa quirúrgica en cada individuo