Revisión sistemática de la literatura sobre el tratamiento con colchicina en pacientes adultos con osteoartritis de rodilla / Colchicine treatment in adult patients with knee osteoarthritis: Systematic review of the literature

Resumen Contexto: En la práctica clínica de muchos reumatólogos y en algunos ensayos clínicos se ha usado colchicina en pacientes con osteoartritis primaria. A pesar de ello, su papel en el tratamiento de la misma no está claro y las guías no establecen recomendaciones al respecto. Objetivos: Evaluar la eficacia y la seguridad del tratamiento con colchicina en pacientes adultos con osteoartritis de rodilla, tanto primaria como asociada al depósito de cristales de pirofosfato cálcico. Métodos: Se llevó a cabo una búsqueda estructurada de la literatura utilizando las bases de datos Pubmed, Embase, Cochrane Controlled Trials Register y LILACS. Se incluyeron ensayos clínicos controlados, aleatorizados, en donde se haya usado colchicina como intervención en pacientes adultos con osteoartritis de rodilla, primaria o relacionada con pirofosfato de calcio. Resultados: Se incluyeron 5 ensayos clínicos controlados. Se observó una tendencia común en todos los estimados puntuales de los artículos a favorecer el uso de la colchicina para la mejoría del dolor y de la funcionalidad. Se observó una mayor tendencia de efectos adversos gastrointestinales con el uso de la colchicina, sin embargo, el efecto no fue estadísticamente significativo en los estudios individuales. Ninguno de los estudios evaluó calidad de vida. Conclusiones: La colchicina parece ser una alternativa eficaz y segura para el tratamiento de pacientes adultos con osteoartritis de rodilla, tanto primaria como asociada al depósito de cristales de pirofosfato de calcio. Su uso reduce el dolor y mejora la funcionalidad, aunque puede producir síntomas gastrointestinales en algunos pacientes.

Abstract Background: Colchicine is often used in patients with osteoarthritis in which calcium pyrophosphate crystal deposition disease is suspected. Colchicine has also been used by many rheumatologists in clinical practice, and in some trials, on patients with primary osteoarthritis (apparently unrelated to calcium pyrophosphate). However, its role in the treatment of primary osteoarthritis is not clear, and international guidelines have not established recommendations. Objective: To evaluate the efficacy and safety of colchicine for the treatment of adult patients with primary knee osteoarthritis as well as the form associated with calcium pyrophosphate. Methods: A structured literature search was conducted using the PubMed, Embase, Cochrane Controlled Trials Register, and LILACS databases. Randomised controlled trials were included in which colchicine was used as intervention in patients with primary or pyrophosphate calcium-associated knee osteoarthritis. Results: The study included 5 randomised controlled trials, all of which showed a common trend in all estimated points of the joint, favouring the use of colchicine for improvement in pain and functionality. Although the effect was not statistically significant in individual studies, there was a greater tendency of gastrointestinal adverse effects with the use of colchicine. None of the studies assessed quality of life. Conclusions: Colchicine appears to be an effective and safe alternative for treatment of adult patients with knee osteoarthritis, either primary or associated with the deposit of calcium pyrophosphate crystals. Its use reduces pain and improves functionality, but it can cause gastrointestinal symptoms in some patients.

Parámetros productivos y sanguíneos en pollos de carne suplementados con cocarboxilasa / Productive and blood performance of broiler supplemented with cocarboxylase

El objetivo de este estudio fue evaluar el efecto de la cocarboxilasa sobre los parámetros productivos y niveles sanguíneos de glucosa y lipídos en pollos de carne. Fueron utilizados 11004 pollos machos de 1 día de edad los cuales fueron distribuidos al azar en 3 tratamientos con 4 repeticiones (917 pollos por cada repetición) y criados de forma convencional por 42 días. Los grupos formados fueron T1 (Dieta convencional), T2 (Dieta modificada, reducción del porcentaje de aceite de soya y la adición de cocarboxilasa) y T3 (Dieta modificada, reducción del porcentaje de aceite de soya y sin cocarboxilasa). El grupo tratado con cocarboxilasa (T2) obtuvo mayor peso final y ganancia de peso comparado con los otros dos tratamientos. La inclusión de cocarboxilasa tuvo influencia positiva en el peso por lo que podria ser utilizada como reemplazo parcial del aceite de soya utilizado en la dieta de pollos de carne.

The aim of this study was to evaluate the effect of cocarboxylase on productive performance, blood glucose and lipid profile in broilers. A total of 11004 one-day-old male broiler chickens were randomly allocated into 1 of 3 treatments with 4 replicates per treatment (917 chickens per replicate) and conventionally reared until 42 days old. The treatments were T1 (Conventional diet), T2 (Modified diet, reducing a percentage soybean oil and the addition of cocarboxylase) and T3 (Modified diet, reducing a percentage soybean oil without cocarboxylase). Broilers supplemented with cocarboxylase (T2) resulted in higher final weight and weight gain compared with the others treatments. The inclusion of cocarboxylase had positive influence on weight, which suggests its usefulness as a partial replacement of the oil used in chicken diets.

Eficacia del pirofosfato de tiamina o cocarboxilasa en el rescate del pie diabético / Efficacy of thiamine pyrophosphate or carboxylase in the salvage of diabetic foot

El pie diabético representa una de las complicaciones más comunes en pacientes que han tenido una larga evolución. La etiología se circunscribe a la neuropatía, infecciones e isquemia, que actuando en conjunto contribuyen a la secuencia de necrosis tisular, ulceración y gangrena. Lo difícil que resulta su tratamiento hace necesaria la búsqueda de opciones que colaboren en la resolución de esta problemática, que se centra en la hiperglucemia crónica como detonante. El pirofosfato de tiamina o cocarboxilasa realiza múltiples actividades metabólicas y no metabólicas que han sido consideradas importantes en la solución de las alteraciones del diabético por lo que en el presente trabajo se muestran los resultados al emplearlo en pacientes con pie diabético. En un período comprendido entre Enero de 1998 y Julio de 2012 se trataron 29 pacientes con pie diabético: 19 Wagner tipo III y 12 Wagner tipo IV. El manejo consistió en administrar antibióticos, procedimientos quirúrgicos parciales y pirofosfato de tiamina. Se logró el control del proceso infeccioso, la aparición de tejido de granulación y cicatrización de la lesión en un período comprendido entre 2 y 6 meses de acuerdo a la gravedad del problema. Por los datos clínicos y la evolución de los pacientes, se concluye que la administración del pirofosfato de tiamina permitió el control de las disfunciones metabólicas y no metabólicas que conducen a las complicaciones del diabético, por lo que se debe considerar una herramienta para el tratamiento de los diabéticos en general y para el rescate del pie diabético en particular.

Diabetic foot represents one of the most common complications in patients with a long standing disease. The etiology is neuropathy, infections and ischemia that together contribute to the sequence of tissue necrosis, ulceration and gangrene. Since treatment is very difficult, we must look for several options to solve these problems caused by chronic hyperglycemia. Thiamine pyrophosphate or carboxylase perform multiple metabolic and non-metabolic activities that are considered important in the resolution of diabetic impairments, therefore, this work shows the results when using it in patients with diabetic foot. 29 patients with diabetic foot were treated between January 1998 and July 2012: 19 Wagner type III and 12 Wagner type IV. Management was the administration of antibiotics, partial surgical procedures and thiamine pyrophosphate. The infectious process was controlled, the appearance of granulation tissue and scarring of the lesion in a period of 2 to 6 months depending on the severity of the problem. Given the clinical data and evolution of the patients, we conclude that the administration of thiamine pyrophosphate was able to control metabolic and non-metabolic dysfunctions that lead to complications in diabetic patients, therefore we must consider it a tool in the treatment of diabetic patients in general and for diabetic foot salvage in particular.

El pirofosfato de tiamina reduce el daño celular inducido por hipoxia en el cerebro de ratas neonatas / Thiamine pyrophosphate reduces hypoxia-induced cellular damage in neonatal rat brain

La encefalopatía por hipoxia es causa de discapacidad y requiere de nuevas estrategias terapéuticas. El pirofosfato de tiamina (PPT) es un cofactor esencial de enzimas fundamentales en el metabolismo de la glucosa, cuya disminución puede conducir a la falla en la síntesis de ATP y a la muerte celular. El objetivo de este estudio fue determinar si la administración de PPT, puede reducir el daño celular en un modelo de hipoxia neonatal en ratas. Animales de 11 días de edad fueron tratados con PPT (130 mg/kg) en dosis única o solución salina, una hora antes del protocolo de hipoxia o al término de ésta. Los cerebros fueron colectados para la evaluación del daño celular. Además, se tomaron muestras sanguíneas para evaluar los indicadores gasométricos de presión de dióxido de carbono (PaCO2) y de oxígeno (PaO2) en sangre arterial y pH. Los resultados muestran que la administración de PPT previa a la inducción de hipoxia, reduce el daño celular y restablece los indicadores gasométricos. Estos datos indican que el uso de PPT reduce el daño inducido por la hipoxia en animales neonatos.

Hypoxic encephalopathy is a leading cause of disability and requires new therapeutic strategies. Thiamine pyrophosphate (TPP) is an essential cofactor of fundamental enzymes involved in glucose metabolism. TPP reduction may lead to ATP synthesis failure and cell death. The objective of this study was to determine if TPP administration can reduce cellular damage in a model of neonatal hypoxia in rats. Eleven day old animals were treated with TPP (130 mg/kg) as a single dose or with saline solution one hour before the hypoxia protocol or after ending the protocol. The brains were collected to evaluate cellular damage. Blood samples were also collected to evaluate arterial oxygen tension (PaO2), carbon dioxide tension (PaCO2) and acidity (pH). The results showed that TPP administration previous to hypoxia induction reduces cellular damage and reestablishes arterial blood gases. These data indicate that TPP use reduces the damage induced by hypoxia in neonatal animals.

Regulacin de la mineralizacin sea por factores inorgnicos y peptdicos / Regulation of Bone Mineralization by inorganic and peptide factors

La mineralizacin ortotpica comienza con la produccin de las vesculas de matriz, por brotacin polarizada de la superficie de condrocitos, osteoblastos y odontoblastos. Esta transcurre en dos etapas. La primera es la formacin de cristales de hidroxiapatita dentro de las vesculas de matriz, seguido por la propagacin de la hidroxiapatita a travs de la membrana de la vescula dentro de la matriz extracelular. En la regulacin de la mineralizacin ortotpica, aparte de las clulas tejido especficas, intervienen un gran nmero de enzimas, factores inorgnicos y peptdicos, que tienen complejas interacciones. Para que la mineralizacin normal contine se necesita un ajustado balance entre los niveles de fosfato inorgnico (Pi) y de pirofosfato inorgnico (PPi) extracelular. El PPi antagoniza la habilidad del Pi para cristalizar con el calcio y formar hidroxiapatita y por lo tanto suprime su propagacin. Se han identificado tres molculas reguladoras centrales de los niveles extracelulares de PPi: la fosfatasa alcalina tejido-no especfica (TNAP), que hidroliza el PPi, la nucletido pirofosfato fosfodiesterasa 1 (NPP1), que genera PPi de nuclesidos trifosfato y la protena transmembrana de mltiples-pasos ANK, que media la transferencia intracelular al extracelular de PPi. A su vez existen dos protenas SIBLING llamadas DMP1 y MEPE reguladoras de la mineralizacin. La expresin de DMP1 por el osteocito se induce en forma marcada en respuesta a la carga mecnica incrementando la mineralizacin sea. La protena MEPE contiene un motivo peptdico proteasa resistente llamado ASARM, que se cree es un candidato a ser un inhibidor de la mineralizacin (minhibina). La osteropontina es otro inhibidor de la mineralizacin en su forma fosforilada y su secrecin est marcadamente reducida en los ratones "knockout" para NPP1. Los datos actuales parecen sostener la hiptesis que estas molculas podran ser las transductoras del "strain" seo y participar en la regulacin de la mineralizacin del espacio osteoctico perilacunar.

Orthotopic mineralization begins with the production of matrix vesicles that are produced by polarized budding of the surface of condrocytes, osteoblasts and odontoblasts. It occurs in two steps: The first one is the formation of hydroxiapatite crystals within the matrix vesicles, followed by the propagation of the hydroxiapatite crystals through the membrane vesicle into the extra cellular matrix. In the regulation of orthotopic mineralization, apart from tissue-specific cells, a great number of enzymes, inorganic and peptide factors participate, that have complex interactions among them. Inorganic pyrophosphate (PPi) antagonizes the ability of phosphate (Pi) to crystallize with calcium and to form hydroxiapatite, thus suppressing its propagation. For the normal mineralization to continue, an adjusted balance of the extra cellular Pi and PPi levels is needed. Three molecules have been identified that have a central role in the regulation of extra cellular PPi levels: tissue non-specific alkaline phosphatase (TNAP), which hydrolyzes PPi, the nucleotide pyrophosphatase phosphodiesterase 1 (NPP1), which generates PPi from triphosphate nucleosides, and the multiple-steps transmembrane protein ANK which transfers PPi from the intracellular to the extracellular compartment. There are, in turn, two SIBLING proteins called DMP1 and MEPE that regulate mineralization. The expression of DMP1 by the osteocyte is dramatically induced in response to mechanical loading increasing bone mineralization. MEPE protein contains a protease resistant motif called ASARM, which is believed to be the candidate for the mineralization inhibitor (minhibin). Osteopontin is another mineralization inhibitor in its phosphorilated form and its secretion is markedly reduced in knockout mice for NPP1. Present data seem to support the hypothesis that these molecules could be the translators of bone strain and participate in the regulation of mineralization of the perilacunar osteocytic space.

Ressonância magnética vs cintilografia com pirofosfato marcado com tecnécio-99m para a detecção de necrose miocárdica perioperatória / Magnetic resonance vs technetium-99m pyrophosphate scintigraphy in the detection of perioperative myocardial necrosis

FUNDAMENTO: O infarto do miocárdio perioperatório (IMPO) é uma complicação da cirurgia de revascularização miocárdica (CRM) com potencial impacto prognóstico. A cintilografia miocárdica (CM) com pirofosfato marcado com tecnécio-99m é utilizada no diagnóstico de IMPO, mas demonstra limitada sensibilidade para lesões subendocárdicas. A ressonância magnética cardiovascular (RMC), por sua vez, detém alta acurácia para a detecção de necrose miocárdica. OBJETIVO: Comparar a RMC e a CM para a detecção de IMPO após CRM. MÉTODOS: Foram estudados 24 pacientes portadores de doença arterial coronária crônica, com a técnica de realce tardio pela RMC e com a CM, antes e depois da CRM, analisando-se o surgimento de áreas de necrose miocárdica perioperatória (IMPO). Mensuraram-se também marcadores bioquímicos de lesão miocárdica (CKMB e troponina I), antes e depois da cirurgia. RESULTADOS: Dezenove pacientes completaram o estudo. Desses, 6 (32 por cento) apresentaram IMPO à RMC, e 4 (21 por cento) à CM (p = NS). Dos 323 segmentos do ventrículo esquerdo avaliados, 17 (5,3 por cento) exibiram necrose perioperatória à RMC, e 7 (2,2 por cento) à CM (p = 0,013). Observou-se moderada concordância entre os métodos (kappa = 0,46), havendo divergência, quanto ao diagnóstico de IMPO, em 4 (21 por cento) casos, a maioria com pequenas áreas de necrose perioperatória à RMC, não visualizadas à CM. Em todos os casos com IMPO à RMC, houve elevação significativa de CKMB e troponina I. CONCLUSÃO: Houve moderada concordância diagnóstica entre os métodos para a detecção de IMPO, mas a RMC permitiu a visualização de pequenas áreas de necrose miocárdica perioperatória, não identificadas pela CM e associadas à elevação de marcadores bioquímicos de lesão miocárdica.

BACKGROUND: Perioperative myocardial infarction (POMI) is a complication of coronary artery bypass grafting (CABG) with a potential prognostic impact. Technetium-99m pyrophosphate myocardial scintigraphy (MS) is used in the diagnosis of POMI; however it shows a limited sensitivity for subendocardial lesions. Cardiovascular magnetic resonance imaging (CMRI), in turn, has a high accuracy in the detection of myocardial necrosis. OBJECTIVE: To compare CMRI and MS for the detection of POMI after CABG. METHODS: A total of 24 patients with chronic coronary artery disease were studied using the delayed contrast enhanced CMRI and MS before and after CABG by analyzing the development of areas of perioperative myocardial necrosis (POMI). Biochemical markers of myocardial injury (CKMB and troponin I) were also determined before and after surgery. RESULTS: Nineteen patients completed the study. Of these, 6 (32 percent) presented POMI on CMRI and 4 (21 percent) on MS (p = NS). Of the 323 left ventricular segments assessed, 17 (5.3 percent) showed perioperative necrosis on CMRI and 7 (2.2 percent) on MS (p = 0.013). Moderate agreement was observed between the methods (kappa = 0.46). There was disagreement regarding the diagnosis of POMI in 4 (21 percent) cases, most of them with small areas of perioperative necrosis on CMRI which were not visualized on MS. In all cases with POMI on CMRI, significant CKMB and troponin I elevations were observed. CONCLUSION: Moderate diagnostic agreement was observed between the methods for the detection of POMI, but CMRI enabled visualization of small areas of perioperative myocardial necrosis which were not identified on MS and were associated with elevation of biochemical markers of myocardial injury.