Enfermedad de Pompe: historia, epidemiología, fisiopatología y manifestaciones clínicas

Introducción: La enfermedad de Pompe o glucogenosis tipo II pertenece al grupo de las miopatías metabólicas y es producida por la deficiencia parcial o total de la enzima alfa glucosidasa ácida. La ausencia/ déficit de esta enzima genera un almacenamiento de glucógeno en el interior de los lisosomas en diversos tejidos, incluidos el músculo esquelético, el miocardio y las células del músculo liso. Se trata de una enfermedad multisistémica que puede tener un inicio temprano o tardío de los síntomas. Contenidos: En este artículo se describirán los aspectos históricos de la enfermedad, su fisiopatología y sus manifestaciones clínicas, con el énfasis puesto en su inicio temprano o tardío. Conclusiones: Es necesario reconocer la enfermedad de Pompe debido a que esta patología es susceptible de tratamiento.

Introduction: Pompe's disease or glucogenosis type II belongs to the group of metabolic myopathies and is caused by a partial or total deficiency of the acid alpha glucosidase enzyme. The lack/deficiency of this enzyme generates glycogen storage inside the lysosomes in various tissues including skeletal muscle, myocardium and smooth muscle cells. It is a multisystemic disease that can have an early onset or a late onset. Contents: In this article, the historical aspects, the pathophysiology and the clinical manifestations of the disease, will be described. Conclusions: It is necessary to recognize Pompe disease because this pathology is treatable.

Enfermedad de Pompe Infantil: A propósito del primer caso reportado en Panamá / Pompe Disease in Children: First case reported in Panama

La enfermedad de Pompe (EP) es una rara enfermedad hereditaria causada por la deficiencia de la enzima alfa glucosidasa ácida (AGA) encargada de degradar el glucógeno intralisososmal. Se considera una enfermedad de depósito y existe en dos formas: la infantil o de aparición temprana y la de inicio tardío con manifestaciones luego del del año de edad. La forma infantil es rápidamente progresiva, causando la muerte antes del primer año de vida si no hay intervención terapéutica oportuna y adecuada. A partir del desarrollo de la terapia de reemplazo enzimática (TRE) el diagnóstico temprano cobra mayor relevancia. Se presenta el caso de una paciente de 8 meses de edad con dificultad respiratoria, hipotonía, alteración del desarrollo y la alimentación. La exploración cardiológica demostró hallazgos de miocardiopatía. Los hallazgos clínicos orientan hacia Enfermedad de Pompe. Se realiza la prueba en papel filtro que reporta positiva para enfermedad de Pompe. Sin embargo, la paciente fallece el día 25 de hospitalización antes de iniciar la terapia con reemplazo enzimático. Es el primer caso reportado en nuestro medio.

Pompe disease is a rare hereditary disease caused by deficiency of the enzyme alpha glucosidase acid (AGA) responsible for degrading intralisosomal glycogen. It is considered a deposit disease and exists in two forms: infantile or early onset and late onset with manifestations after one year of age. The infantile form is rapidly progressive, causing death before the first year of life if there is no timely and adequate therapeutic intervention. From the development of enzyme replacement therapy (ERT), early diagnosis becomes more relevant. The case of an 8-month-old patient with respiratory distress, hypotonia, impaired development and diet is presented. Cardiological examination showed findings of cardiomyopathy. Clinical findings point to Pompe disease. The test is done on filter paper that reports positive for Pompe disease. However, the patient dies on the 25th day of hospitalization before starting enzyme replacement therapy. It is the first case reported in our environment.

Glucogenosis hepática: a propósito de un caso / Hepatic glycogenosis: a case report

RESUMEN Las glucogenosis abarcan un rango de enfermedades que se caracterizan por el almacenamiento o utilización anormal del glucógeno, siendo los órganos más afectados el músculo y/o el hígado. La hepatomegalia puede ser un signo clínico que guie al diagnóstico. Describimos a un paciente de 15 años de edad con hepatomegalia, hipertransaminasemia y retraso del crecimiento, a quien se le diagnosticó glucogenosis por biopsia hepática.

ABSTRACT The glycogen storage diseases contain a range of diseases that are characterized by the abnormal storage or utilization of glycogen, the organs most affected being muscle and / or liver. Hepatomegaly may be a clinical sign that could guide to the diagnosis. We describe a 15-year-old patient with hepatomegaly, hypertransaminasemia and growth retardation. He was diagnosed with a glycogen storage disease by liver biopsy.

Glucogenosis Hepática. Características clínicas, laboratoriales e imagenológicas en pacientes pediátricos menores de 15 años / Hepatic glycogenosis. Clinical, laboratory and imaging characteristics in pediatric patients under 15 years old

Antecedentes: La glucogenosis (GSD) hepática es una enfermedad hereditaria autosómica recesiva caracterizada por la alteración del depósito de glucógeno en los tejidos. La enfermedad se presenta con hepatomegalia, debilidad muscular y retraso del crecimiento. Esta patología usualmente se diagnostica clínicamente a partir de los 6 meses de edad cuando la ingesta de alimentos del lactante es más espaciada y puede debutar con sintomatología de hipoglicemia. Debido a la inespecificidad de la presentación clínica de la enfermedad es muy importante la sospecha diagnóstica desde los centros de primer nivel de atención y su derivación oportuna a centros de especialidad. Objetivo: Evaluar y describir el perfil nutricional y clínico en pacientes menores de 15 años con Glucogenosis Hepática. Método: Se describe una serie de casos de 14 pacientes menores de 15 años con diagnóstico clínico de GSD hepática, atendidos en la consulta de Gastroenterología y Nutrición Pediátrica del Hospital Carlos Andrade Marín entre 2016 y 2018. El diagnóstico se lo realizó de acuerdo a la clínica que presentó cada paciente como la presencia de distensión abdominal, hepatomegalia, adinamia, retraso en el crecimiento y datos laboratoriales como niveles de glicemia en sangre periférica, transaminasas, y realización de elastografía entre los principales. Se analizaron datos sociodemográficos, antropométricos, de laboratorio (transaminasas, glicemia periférica) y elastografía hepática. Para el análisis de datos se creó una base de datos en Microsoft Excel 2013 y se procesó con el programa Epi Info 7. Resultados: En este grupo de casos, los tipos específicos de GSD hepática fueron tipo IX, 57,14% (8), tipo III, 28,57% (4) y tipo Ia-b, 14,29% (2) pacientes. La prevalencia de características clínicas ante la sospecha de la GSD hepática fueron: hepatomegalia 100% (14), y retraso en el crecimiento el 64,3% (9). De acuerdo a los exámenes de sangre periférica los valores promedio de transaminasas hepáticas (AST/TGO U/L) (ALT/TGP U/L) y glucosa, fueron de 364±384, 302±255 y 61±15 mg/dL, respectivamente. La elastografía con la que se evaluó el nivel de fibrosis hepática al momento del diagnóstico arrojó los siguientes resultados: F0 (no fibrosis hepática) en el 28,57% (4), F1 con el 28,57% (4), F2-F3 con el 35,71% (5), y F4 7,14%. Conclusión: La Glucogenosis es una patología que debería ser sospechada a tiempo en centros del primer nivel de salud para luego referir oportunamente los casos a los centros de referencia. La hepatomegalia y el retardo en el crecimiento son signos cardinales de alerta para la sospecha de esta patología.

Enfermedad de Pompe infantil: Diagnóstico y tratamiento / Infantile-onset Pompe disease: Diagnosis and management

La enfermedad de Pompe, o deficiencia de maltasa ácida o glucogenosis tipo II, es una grave enfermedad genética, autosómica recesiva, progresiva, poco frecuente, causada por la deficiencia en la enzima alfa glucosidasa. En la edad pediátrica, puede presentarse con la "forma clásica", la más conocida, con grave compromiso cardíaco y franca hipotonía, o con la "forma no clásica", con comienzo temprano del compromiso motor. La "forma de comienzo tardío" del adulto también puede ocurrir en la infancia o en la adolescencia. Se actualizan los hallazgos clínicos y de diagnóstico disponibles, ya que un tratamiento temprano con reemplazo de la enzima faltante puede mejorar la supervivencia y la calidad de vida del paciente. Se revisan los beneficios y los efectos adversos del tratamiento disponible y nuevas líneas de investigación terapéutica.

Pompe disease, also known as acid maltase deficiency or glycogenosis type II, is a rare severe, autosomal, recessive, and progressive genetic disorder caused by deficiency in alpha-glucosidase. The classic infantile-onset is the most broadly known form of Pompe disease, which presents with severe heart involvement and clear hypotonia, while the non-classic presentation occurs with early motor involvement. Late-onset Pompe disease develops in adults, but it may also occur during childhood or adolescence. Here we update the available clinical and diagnostic findings because an early management with enzyme replacement therapy may improve patients' survival and quality of life. We also review the benefits and adverse effects of available treatments and new lines of therapeutic research.

Prevalence of mutations responsible for glycogen storage disease type-II and congenital myasthenic syndrome in Brazilian Brahman cattle / Prevalência de mutações responsáveis pela estocagem de glicogênio tipo II e síndrome miastênica congênita em bovinos brasileiros da raça Brahman

Glycogen storage disease type II (GSD-II) and congenital myasthenic syndrome (CMS) are important autosomal recessive disorders in Brahman cattle. The objective of this study was to investigate the presence of mutations responsible for GSD II (E7, c.1057_1058delTA; and E13, c.1783C>T) and CMS (c.470del20) in purebred Brazilian Brahman cattle and in purebred Brahman bulls that were routinely used in breeding programs in Brazil. A total of 276 purebred Brahman cattle (167 females and 109 males, with ages ranging from 12-24 months) and 35 frozen semen samples taken from purebred Brahman bulls (22 bulls from the USA, 11 Brazilian bulls, one Argentine bull and one Australian bull) were used in this study. Genomic DNA was purified from hair root samples and from semen samples. Purified DNA was used in PCR genotyping to mutations c.1057_1058delTA (E7) and c.1783C>T (E13) in the GAA gene and c.470del20 in the CHRNE gene. The PCR products were purified and sequenced. The genotypic frequencies per polymorphism were estimated separately. Of the 276 Brahman cattle tested, 7.3% were identified as heterozygous for E7. All Brahman cattle studied were homozygous for the wild-type E13 allele. The E7 mutations was identified as heterozygous in 8.6% (3/35) of the commercial semen samples, whereas the E13 mutations was not identified. The c.470del20 mutation was identified as heterozygous in 0.73% of the hair root samples, but this mutation was not present in any semen sample assessed. No study had previously evaluated the prevalence of mutations responsible for GSD II or CMS in Brazilian Brahman cattle. In summary, the E7 and c.470del20 mutations are present in the Brazilian Brahman herd, and control measures should be adopted to prevent an increase in the incidence of GSD-II and CMS in Brahman cattle in Brazil.(AU)

A doença de armazenamento de glicogênio tipo II (DAG-II) e a síndrome miastênica congênita (SMC) são importantes doenças autossômicas recessivas no gado Brahman. O objetivo deste estudo foi investigar a presença das mutações responsáveis pela DAG-II (E7, c.1057_1058delTA; e E13, c.1783C>T) e pela SMC (c.470del20) em bovinos da raça Brahman e em touros Brahman que são rotineiramente utilizados em programas de reprodução no Brasil. Um total de 276 amostras de bulbo piloso de bovinos Brahman (167 fêmeas e 109 machos, com idade variando de 12 a 24 meses) e 35 amostras de sêmen congeladas de touros Brahman (22 touros americanos, 11 touros brasileiros, um touro argentino e um touro australiano) foram usados neste estudo. O DNA genômico foi purificado, das amostras de bulbo piloso e de sêmen, e utilizado na genotipagem por PCR das mutações c.1057_1058delTA (E7) e c.1783C>T (E13) no gene GAA e c.470del20 no gene CHRNE. Os produtos de PCR foram purificados e sequenciados. A frequência genotípica para cada polimorfismo foi estimada separadamente. Dos 276 Brahman testados, 7,3% foram identificados como heterozigotos para E7. Todos os Brahman foram homozigotos wild-type para o alelo E13. A mutação E7 foi identificada em homozigose em 8,6% (3/35) das amostras de sêmen comerciais, enquanto que a mutação E13 não foi identificada. A mutação c.470del20 foi identificada em heterozigose em 0,73% das amostras de bulbo piloso, mas esta mutação não estava presente nas amostras de sêmen avaliadas. Nenhum estudo prévio avaliou a prevalência das mutações responsáveis pela DAG-II ou SMC em bovinos Brahman brasileiro. Em suma, as mutações E7 e c.470del20 estão presentes no rebanho Brahman brasileiro, e medidas de controle devem ser adotadas para prevenir o aumento da incidência da DAG-II e SMC em bovinos da raça Brahman no Brasil.(AU)

Consenso argentino sobre enfermedad de Pompe de inicio tardío / Argentine consensus on late-onset Pompe's disease

La enfermedad de Pompe (EP) es un desorden metabólico autosómico recesivo infrecuente, producido por la ausencia o deficiencia de la enzima lisosomal alfa-glucosidasa ácida en los tejidos de los individuos afectados. Se considera enfermedad de Pompe de inicio tardío (EPIT) en aquellos individuos de más de un año de edad al comienzo de los síntomas. El objetivo del presente consenso es el de actualizar las pautas y recomendaciones para un correcto tratamiento de los pacientes con EPIT, tomando como referencia los lineamientos del Consenso Argentino para el diagnóstico, seguimiento y tratamiento de la enfermedad de Pompe publicado en el año 2013. Se organizó un consenso que reunió profesionales con experiencia en la EP en las áreas de clínica médica, diagnóstico de laboratorio, neuropatología, neumonología, nutrición, neurología, enfermedades metabólicas, enfermedades neuromusculares y rehabilitación. Se realizó una actualización de la bibliografía sobre EPIT, con especial atención en las publicaciones relevantes de los últimos cuatro años. Los términos finales del documento fueron consensuados por todo el grupo de trabajo. Cada participante proporcionó su declaración de conflicto de intereses. El resultado es una actualización del último Consenso Argentino para la EP, con particular enfoque en su forma de comienzo tardío. Tratándose de una afección infrecuente, en la que los datos disponibles son limitados, las presentes recomendaciones deben ser consideradas como opinión de expertos.

Pompe's disease (PD) is an infrequent metabolic autosomic recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Delayed-onset PD is considered whenever symptoms onset start after one year of age. We present an update of the recommendations for the management of delayed-onset PD, taking as reference the guidelines from the Argentine Consensus for diagnosis, treatment and follow-up of PD published in 2013. The present consensus gathered several experts in PD in the areas of internal medicine, laboratory diagnosis, neuropathology, pulmonology, nutrition, neurology, metabolic and neuromuscular disorders as well as rehabilitation to perform an update of the literature of delayed-onset PD, with special attention on relevant information published within the last 4 years. The entire working group approved the final version of the consensus. Each participant provided a declaration of conflict of interest. As a result, it is an update of the previous Argentine PD Consensus with focus on the delayed-onset presentation of the disease. Being such infrequent disorder, available data were rather limited and thus, the recommendations represent expert opinions.

Diagnóstico y tratamiento de la enfermedad de Pompe / Diagnosis and treatment of Pompe disease

INTRODUCCIÓN: la enfermedad de Pompe es una glucogenosis tipo II con patrón de herencia autosómico recesivo, causada por la deficiencia de la enzima alfa-glucosidasa ácida, que provoca acúmulo de glucógeno en los lisosomas de los macrófagos. El gen está mapeado en el cromosoma 17q25, y han sido detectadas más de 460 mutaciones. Están descritas 3 formas clínicas de la enfermedad, que incluyen, la variedad infantil, la juvenil y la tardía. La variedad infantil se caracteriza por miocardiopatía hipertrófica o infiltrativa, hipotonía, hepatomegalia y macroglosia. En la variedad juvenil hay fiebre recurrente, infecciones respiratorias a repetición y discapacidad motora progresiva. La terapia de reemplazo enzimático modifica el curso clínico de la enfermedad. PRESENTACIÓN DE CASOS: se presentan los elementos al diagnóstico de 4 casos con esta enfermedad, 3 de ellos con la variedad infantil y uno con la variedad juvenil, y se discuten los resultados de estudio molecular. Se informa la evolución clínica de 2 de ellos, luego de 6 meses y un año de tratamiento con la terapia de reemplazo enzimático con alfa-glucosidasa ácida (myozyme), lo que ha llevado a la mejoría de parámetros bioquímicos y clínicos en ambos casos. CONCLUSIONES: en pacientes con enfermedad de Pompe la cuidadosa evaluación clínica para diagnosticar precozmente la enfermedad y el comienzo de la terapia de reemplazo enzimático contribuyen a mejorar las funciones musculares, motoras y cardiovasculares, lo cual impacta en la supervivencia y calidad de vida de estos niños(AU)

INTRODUCTION: Pompe disease is a type II glycogenosis with recessive autosomal inheritance pattern, which is caused by the acid alpha-glucosidase enzyme that brings about buildup of glycogen in macrophage lysosomes. The gene is already mapped in Chromosome 17q25 and has been so far detected over 460 mutations. Three clinical forms of disease were described, including infantile, juvenile and late-onset varieties. The infantile variety is characterized by hpertrophic or infiltratin myocardiopathy, hypotonia, hepatomegaly and macroglossia. The juvenile type comprises recurrent fever, repeated respiratory infections and progressive motor disability. Enzyme replacement therapy changes the clinical course of disease. CASE PRESENTATION: the elements for diagnosis of 4 cases were submitted, 3 of them with infantile form and one with juvenile one. The results of the molecular study were discussed. The clinical progress of 2 of them after 6 monts and one year of treatment with the enzymatic replacement therapy using acid alpha-glucosidase (myozyme), which led to improvement of biochemical and clinical parameters in both cases. CONCLUSIONS: careful clinical assessment of patients with Pompe disease to early diagnose it and the onset of the enzyme replacement therapy help to improve muscle, motor and cardiovascular functions, which has an impact on survival and quality of life of these children(AU)

Carcinoma neuroendocrino de timo con enfermedad de pompe del adulto / Thymic neuroendocrine carcinoma with Pompe's disease of the adult

La enfermedad de Pompe (glucogenosis tipo II) es una enfermedad de depósito lisosomal, autosómica recesiva causada por una deficiencia de ácido alfa-glucosidasa. Los tumores neuroendocrinos tímicos son neoplasias primarias con diferenciación neuroendocrina que generalmente se presentan como una masa en el mediastino anterior. Ambas enfermedades se consideran raras en sí mismas. En nuestro conocimiento, la enfermedad de Pompe y un tumor neuroendocrino del timo en el mismo paciente no ha sido antes comunicada. No pudimos encontrar la plausibilidad biológica entre ambas enfermedades. Se necesitan más estudios para confirmar el hallazgo y para aumentar aún más nuestra comprensión de esta asociación. Los datos clínicos de los estudios epidemiológicos, los informes de casos, las series de casos y los pequeños ensayos clínicos abiertos o controlados pueden definir tanto la plausibilidad clínica como la causalidad entre las dos enfermedades.

Pompe disease (glycogenosis type II) is an inherited autosomal recessive lysosomal storage disease caused by a deficiency of acid alpha-glucosidase. Thymic neuroendocrine tumors, are primary thymic neoplasms with neuroendocrine differentiation that generally present as a mass within the anterior mediastinum. Both diseases are considered rare. To our knowledge the co-existence of Pompe disease and thymic neuroendocrine tumor in the same patient has not been previously reported. We could not find biological plausibility between both diseases. Further studies are needed to confirm the finding and to further increase our understanding of this association. Clinical data from epidemiological studies, case reports, case series and small formal open or controlled clinical trials may define both clinical plausibility and causality between the two conditions.

Quantitative computed tomography of the liver in dogs submitted to prednisone therapy / Tomografia computadorizada quantitativa do fígado de cães submetidos à terapia com prednisona

The aim of this study is to evaluate the possible alterations in radiodensity of the hepatic parenchyma and spleen resulting from the corticotherapy with prednisone, correlating these findings with serum biochemical hepatic transaminase activity. A clinical trial was performed on eight healthy dogs with the intent of evaluating possible hepatic alterations after prednisone therapy using quantitative computed tomography. All animals received prednisone orally at a dose of 2mg/kg of weight for 30 days. The radiodensity of the liver and spleen was determined before and after the period that the medication was administered. An increase in the radiodensity of the hepatic parenchyma between the initial and final experimental stages was observed. In the present study the existence of early hepatic alterations were verified, which are compatible with glycogen storage.

O objetivo deste estudo é avaliar as possíveis alterações na radiodensidade do parênquima hepático e esplênico decorrentes da corticoterapia com prednisona, correlacionando estes achados com níveis séricos de transaminase bioquímicas hepáticas. Um ensaio clínico foi realizado em oito cães sadios com o objetivo de avaliar possíveis alterações hepáticas após a terapia com prednisona por meio de tomografia computadorizada quantitativa. Todos os animais receberam prednisona por via oral na dose de 2mg / kg de peso por 30 dias. A radiodensidade do fígado e do baço foi determinada antes e após o período em que a medicação foi administrada. Foi observado aumento da radiodensidade do parênquima hepático entre os estágios iniciais e finais do experimento. No presente estudo, foi verificada a existência de alterações hepáticas precoces, que são compatíveis com o acúmulo de glicogênio.

Death of a Severe Underweight Infant with Pulmonary Interstitial Glycogenosis / 대한법의학회지

Pulmonary interstitial glycogenosis (PIG) is a very rare interstitial lung disease in infants. It is poorly understood, but its pathological features are distinct; they include uniform alveolar septal thickening, caused by a group of oval to spindle-shaped cells containing abundant glycogen, without apparent inflammation or fibrosis. PIG is usually associated with a good prognosis. However, in the present report, we describe the case of a 5-month-old male infant who died due to PIG; he was severely underweight and not administered proper treatment or care. The pathology of PIG was determined following a medico-legal autopsy.

Tomografia computadorizada no diagnóstico de hepatopatia esteroidal em cão: relato de caso / Computed tomography in the diagnosis of steroidal hepatopathy in a dog: case report

It is reported a case of an eight-year-old Yorkshire Terrier dog, with a history of prolonged use of prednisone in a dosage of 1mg/kg of body weight each 24 hours during two years. The helical computed tomography revealed hepatomegaly associated to a hyperattenuation of the parenchyma, with a radiodensity value of 82.55 Hounsfield units (HU). The spleen presented a mean radiodensity of 57.17HU, and a radiodensity difference of 25.38HU was observed between the two organs. Based on the history and findings of imaging technique, it was determined the presumptive diagnosis of steroidal hepatopathy compatible with accumulation of hepatic glycogen. It was concluded that computed tomography enabled the characterization of hepatic injury and the presumed diagnosis of steroidal hepatopathy.

Relata-se o caso de um cão da raça Yorkshire, de oito anos de idade, com histórico de tratamento com prednisona na dose de 1mg/kg de peso, a cada 24 horas, por dois anos. A tomografia computadorizada helicoidal revelou hepatomegalia associada à hiperatenuação, com radiodensidade de 82,55 unidades Hounsfield (HU). O baço apresentava radiodensidade média de 57,17HU, sendo observada diferença de radiodensidade de 25,38HU entre os dois órgãos. Por meio do histórico e dos achados da técnica de imagem, foi possível determinar o diagnóstico presuntivo de hepatopatia esteroidal compatível com acúmulo de glicogênio hepático. Concluiu-se que a tomografia computadorizada possibilitou caracterizar a lesão hepática e presumir o diagnóstico de hepatopatia esteroidal.

A Case of Hepatomegaly due to Diabetic Glycogenosis Reversed by Glycemic Control / 대한내분비학회지

Diabetes mellitus is well known to be associated with various structural and functional liver abnormalities. If diabetic patients are accompanied by hepatomegaly or abnormal findings from a liver function test, the most common pathological findings are steatosis and glycogenosis. The steatosis is characterized by deposition of macrovesicular fat droplets in the hepatocytes, which is common in obese, type 2 diabetes mellitus. If macrovesicular steatosis is combined with mixed inflammatory infiltrate, without evidence of alcoholic hepatitis, the case could be diagnosed as nonalcoholic steatohepatitis (NASH). NASH has the possibility of progressing to cirrhosis. Secondary glycogenosis is common in uncontrolled type 1 diabetes mellitus, and is completely reversible. A 22-year-old male, with uncontrolled type 1 diabetes mellitus, was admitted with anorexia, nausea and right upper quadrant pain. Hepatomegaly and elevated aminotransferases were noted. He was diagnosed as diabetic glycogenosis using computed tomogram and liver biopsy. The hepato megaly and liver function test abnormalities were markedly improved with glycemic control

Effect of α-tocopherol on doxorubicin induced alterations in glucose metabolism—A pilot study.

The effect of doxorubicin on glucose metabolism was studied in rats with or without the supplementation of α-tocopherol. Rats were treated with doxorubicin, 2 mg/kg body wt. (intravenously), twice a week, for 6 weeks. α-Tocopherol (400 mg/kg body wt.) was co-administered orally for 2 months. Glycolysis was found to be increased with a significant decrease in the activities of tricarboxylic acid cycle enzymes. A significant increase in liver glycogen was noted in doxorubicin treated rats. Activities of glycogen Phosphorylase, glucose-6-phosphate dehydrogenase and glucose-6-phosphatase were found to be decreased. α-Tocopherol co-administration was found to reduce the alterations in the above mentioned enzyme activities. The results are discussed with reference to the drug metabolism, lipid peroxidation and the antioxidant nature of α-tocopherol.

Changes in the content of glycogen and its metabolites during acute exposure of Anabas testudineus (Bloch) to furadan.

Significant differences were observed in glycogen metabolism of Anabas testudineus exposed to an acute lethal (1.56 mg/litre) and a sublethal (0.56 mg/litre) concentration of furadan. At sublethal concentration, the muscle glycogen which was utilized during the early periods of exposure, was replenished in the later period of exposure and at 120 h, the muscle glycogen levels were higher than the control. At higher concentration, the liver glycogen levels showed an increase presumably at the expense of fuel reserves of the muscle.