ABSTRACT
INTRODUCTION AND OBJECTIVES: In patients with chronic obstructive pulmonary disease (COPD), lactate dehydrogenase (LDH) levels in skeletal muscles are normal or tend to be elevated; on exercise, these levels increase more rapidly than in individuals without COPD. As it is likely that concentrations of LDH isozymes LDH(4) and LDH(5) are elevated in such patients, we measured those isozymes in peripheral muscle of patients with COPD. PATIENTS AND METHODS: Eighteen patients with COPD and 10 healthy nonsmokers were included in the study. Spirometry and the 6-minute walk test were performed, and a biopsy of the quadriceps muscle was taken to measure levels of both total LDH and LDH isozymes by agarose gel electrophoresis and to classify the types of muscle fibers. RESULTS: Controls and patients had similar concentrations of total LDH (mean [SE], 130 [30]micromol/min/g vs 152 [50]micromol/min/g, respectively) and LDH isozymes. A subgroup of 5 patients showed increased levels of isozymes LDH(1), LDH(2), and LDH(3), with decreased LDH(5) levels; these patients were women and had a lower oxygen saturation. The LDH(5) level was directly correlated with the 6-minute walk test and oxygen saturation. The percentage of type IIA fibers correlated directly with LDH(3) and LDH(4) concentrations whereas type IIX fibers were inversely correlated with LDH(3) concentration. CONCLUSION: Measurement of LDH isozyme concentrations enabled a subgroup of patients to be identified with a higher concentration of cardiac isoenzymes and lower concentration of muscle isoenzymes, a situation which might indicate adaptation that favors aerobic metabolism.
Subject(s)
L-Lactate Dehydrogenase/analysis , Muscle, Skeletal/chemistry , Pulmonary Disease, Chronic Obstructive/enzymology , Female , Humans , Isoenzymes/analysis , Male , Middle Aged , Muscle, Skeletal/enzymologyABSTRACT
Introducción y objetivos. En los pacientes con enfermedad pulmonar obstructiva crónica (EPOC), las cifras de la enzima lactatodeshidrogenasa (LDH) en los músculos esqueléticos son normales o tienen cierta tendencia a aumentar; cuando dichos pacientes hacen ejercicio, los valores se elevan más rápidamente que en personas sin la enfermedad. Es probable que las concentraciones de las isoenzimas 4 y 5 de la LDH puedan estar aumentadas en estos pacientes, por lo que se han determinado las isoenzimas de la LDH en el músculo periférico de pacientes con EPOC. Pacientes y métodose ha estudiado a 18 pacientes con EPOC y a 10 personas sanas no fumadoras. Se les realizaron pruebas de función pulmonar, la prueba de la marcha de 6min y biopsia del músculo cuádriceps para medir tanto la LDH total como las isoenzimas de la LDH por electroforesis en gel de agarosa, así como para clasificar los tipos de fibras. Resultadoslas concentraciones de LDH total (media¡Àerror estándar: 130¡À30 frente a 152¡À50¦Ìmol/min/g) y sus isoenzimas fueron similares en controles y pacientes. Un subgrupo de 5 pacientes mostró un aumento de las isoenzimas LDH1, LDH2 y LDH3, con disminución de la LDH5; estos pacientes eran mujeres y tenían menor saturación de oxígeno. El valor de la LDH5 se relacionó directamente con la prueba de la marcha de 6min y la saturación de oxígeno. El porcentaje de fibras IIA mostró una correlación directa con la concentración de LDH3 y LDH4, y las fibras IIX se relacionaron inversamente con la LDH3. Conclusión. A partir de las concentraciones de las isoenzimas de la LDH se pudo identificar a un subgrupo de pacientes con una concentración mayor de las isoenzimas cardíacas y menor de las musculares, lo que eventualmente podría representar una adaptación que favorezca el metabolismo aeróbico(AU)
Introduction and Objectives. In patients with chronic obstructive pulmonary disease (COPD), lactate dehydrogenase (LDH) levels in skeletal muscles are normal or tend to be elevated; on exercise, these levels increase more rapidly than in individuals without COPD. As it is likely that concentrations of LDH isozymes LDH4 and LDH5 are elevated in such patients, we measured those isozymes in peripheral muscle of patients with COPD. Patients and MethodsEighteen patients with COPD and 10 healthy nonsmokers were included in the study. Spirometry and the 6-minute walk test were performed, and a biopsy of the quadriceps muscle was taken to measure levels of both total LDH and LDH isozymes by agarose gel electrophoresis and to classify the types of muscle fibers. ResultsControls and patients had similar concentrations of total LDH (mean [SE], 130 [30]¦Ìmol/min/g vs 152 [50]¦Ìmol/min/g, respectively) and LDH isozymes. A subgroup of 5 patients showed increased levels of isozymes LDH1, LDH2, and LDH3, with decreased LDH5 levels; these patients were women and had a lower oxygen saturation. The LDH5 level was directly correlated with the 6-minute walk test and oxygen saturation. The percentage of type IIA fibers correlated directly with LDH3 and LDH4 concentrations whereas type IIX fibers were inversely correlated with LDH3 concentration. ConclusionMeasurement of LDH isozyme concentrations enabled a subgroup of patients to be identified with a higher concentration of cardiac isoenzymes and lower concentration of muscle isoenzymes, a situation which might indicate adaptation that favors aerobic metabolism(AU)
Subject(s)
Humans , Female , Middle Aged , L-Lactate Dehydrogenase/analysis , Muscle, Skeletal/chemistry , Pulmonary Disease, Chronic Obstructive/enzymology , Muscle, Skeletal/enzymology , Isoenzymes/analysisABSTRACT
El cáncer colo-rectal es uno de los cánceres más comunes en el mundo actual, para lo cual el 5-Fluorouracilo (5-FU) es usualmente parte importante del tratamiento quimioterapéutico. La Timidilato Sintetasa (TS), es la enzima blanco para el 5-FU. Estudios recientes sugieren que la TS puede predecir el pronóstico y el éxito de la terapia basada en el 5-FU. El propósito de este estudio retrospectivo fue determinar la expresión de la TS en muestras de biopsias de cáncer de colon incluidas en parafina, mediante la técnica de inmunohistoquímica y correlacionarla con factores de riesgo, antígeno carcinoembrionario (CEA), CA-19-9, evolución del paciente y respuesta al tratamiento con 5-FU. La población en estudio consistió en 34 muestras de biopsias de cáncer de colon obtenidas de pacientes quienes fueron tratados con 5-FU y Leucovorina. A las muestras de adenocarcinomas colónicas incluidas en parafina se les realizó la detección de TS a través de inmunohistoquímica. Los pacientes en cuyos tumores había una alta expresión de la TS, mostraron una sobrevida significativamente menor comparado son aquellos pacientes que mostraron baja expresión de la enzima en sus tumores (p=0,004). La expresión de la TS puede ser utilizada como un importante marcador pronóstico de sobrevida y de respuesta a la quimioterapia en pacientes con cáncer colo-rectal.
Colorectal cancer is one of the most common cancers in the world today, for which a 5-fluorouracil (5-FU) is usually an important part of the chemotherapeutic treatment. The thymidylate synthase (TS), is the target enzyme for 5-FU. Recent studies suggest that TS can predict the prognosis and the success of therapy based on 5-FU. The purpose of this retrospective study was to determine the expression of TS in samples from biopsies of colon cancer in paraffin, using the technique of immunohistochemistry and its correlation with risk factors, carcinoembryonic antigen (CEA), CA-19-9, patients evolution and response to treatment with 5-FU. The study population consisted of 34 biopsy samples obtained from colon cancer patients who were treated with 5-FU and Leucovorin. A sample of colonic adenocarcinoma in paraffin was performed to detect TS through immunohistochemistry. Patients whose tumours had a high expression of TS showed a significantly lower survival rate compared with those patients who showed low expression of the enzyme in their tumours (p = 0.004). The expression of TS can be used as an important marker of survival prognosis and response to chemotherapy in patients with colon cancer.
