RESUMEN
Myotoxicity is a significant factor contributing to the poor adherence and reduced effectiveness in the treatment of statins. Genetic variations and high drug plasma exposure are considered as critique causes for statin-induced myopathy (SIM). This study aims to explore the sequential influences of rosuvastatin (RST) pharmacokinetic and myopathy-related single-nucleotide polymorphisms (SNPs) on the plasma exposure to RST and its metabolites: rosuvastatin lactone (RSTL) and N-desmethyl rosuvastatin (DM-RST), and further on RST-induced myopathy. A total of 758 Chinese patients with coronary artery disease were enrolled and followed up SIM incidents for 2 years. The plasma concentrations of RST and its metabolites were determined through a validated ultra-performance liquid chromatography mass spectrometry method. Nine SNPs in six genes were genotyped by using the Sequenom MassArray iPlex platform. Results revealed that ABCG2 rs2231142 variations were highly associated with the plasma concentrations of RST, RSTL, and DM-RST (Padj < 0.01, FDR < 0.05). CYP2C9 rs1057910 significantly affected the DM-RST concentration (Padj < 0.01, FDR < 0.05). SLCO1B1 rs4149056 variant allele was significantly associated with high SIM risk (OR: 1.741, 95% CI: 1.180-2.568, P = 0.0052, FDR = 0.0468). Glycine amidinotransferase (GATM) rs9806699 was marginally associated with SIM incidents (OR: 0.617, 95% CI: 0.406-0.939, P = 0.0240, FDR = 0.0960). The plasma concentrations of RST and its metabolites were not significantly different between the SIM (n = 51) and control groups (n = 707) (all P > 0.05). In conclusion, SLCO1B1 and GATM genetic variants are potential biomarkers for predicting RST-induced myopathy, and their effects on SIM are unrelated to the high plasma exposure of RST and its metabolites.
Asunto(s)
Amidinotransferasas/genética , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Enfermedades Musculares/inducido químicamente , Rosuvastatina Cálcica/sangre , Amidinotransferasas/sangre , Amidinotransferasas/metabolismo , China , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/metabolismo , Variación Genética , Humanos , Transportador 1 de Anión Orgánico Específico del Hígado/sangre , Transportador 1 de Anión Orgánico Específico del Hígado/metabolismo , Enfermedades Musculares/genética , Polimorfismo de Nucleótido Simple/genética , Rosuvastatina Cálcica/metabolismo , Rosuvastatina Cálcica/farmacocinéticaRESUMEN
Disclaimer: These ACMG Standards and Guidelines are intended as an educational resource for clinical laboratory geneticists to help them provide quality clinical laboratory genetic services. Adherence to these standards and guidelines is voluntary and does not necessarily assure a successful medical outcome. These Standards and Guidelines should not be considered inclusive of all proper procedures and tests or exclusive of others that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, clinical laboratory geneticists should apply their professional judgment to the specific circumstances presented by the patient or specimen. Clinical laboratory geneticists are encouraged to document in the patient's record the rationale for the use of a particular procedure or test, whether or not it is in conformance with these Standards and Guidelines. They also are advised to take notice of the date any particular guideline was adopted, and to consider other relevant medical and scientific information that becomes available after that date. It also would be prudent to consider whether intellectual property interests may restrict the performance of certain tests and other procedures.Cerebral creatine deficiency syndromes are neurometabolic conditions characterized by intellectual disability, seizures, speech delay, and behavioral abnormalities. Several laboratory methods are available for preliminary and confirmatory diagnosis of these conditions, including measurement of creatine and related metabolites in biofluids using liquid chromatography-tandem mass spectrometry or gas chromatography-mass spectrometry, enzyme activity assays in cultured cells, and DNA sequence analysis. These guidelines are intended to standardize these procedures to help optimize the diagnosis of creatine deficiency syndromes. While biochemical methods are emphasized, considerations for confirmatory molecular testing are also discussed, along with variables that influence test results and interpretation.Genet Med 19 2, 256-263.
Asunto(s)
Amidinotransferasas/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/genética , Encefalopatías Metabólicas Innatas/genética , Creatina/deficiencia , Creatina/metabolismo , Guanidinoacetato N-Metiltransferasa/deficiencia , Discapacidad Intelectual/genética , Trastornos del Desarrollo del Lenguaje/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Trastornos del Movimiento/congénito , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/deficiencia , Proteínas Represoras/genética , Trastornos del Habla/genética , Amidinotransferasas/sangre , Amidinotransferasas/líquido cefalorraquídeo , Amidinotransferasas/genética , Amidinotransferasas/orina , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Errores Innatos del Metabolismo de los Aminoácidos/líquido cefalorraquídeo , Errores Innatos del Metabolismo de los Aminoácidos/orina , Encefalopatías Metabólicas Innatas/sangre , Encefalopatías Metabólicas Innatas/líquido cefalorraquídeo , Encefalopatías Metabólicas Innatas/orina , Técnicas de Laboratorio Clínico/métodos , Creatina/sangre , Creatina/líquido cefalorraquídeo , Creatina/genética , Creatina/orina , Discapacidades del Desarrollo/sangre , Discapacidades del Desarrollo/líquido cefalorraquídeo , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/orina , Pruebas Genéticas/normas , Genética Médica/normas , Genómica , Guanidinoacetato N-Metiltransferasa/sangre , Guanidinoacetato N-Metiltransferasa/líquido cefalorraquídeo , Guanidinoacetato N-Metiltransferasa/genética , Guanidinoacetato N-Metiltransferasa/orina , Guías como Asunto , Humanos , Discapacidad Intelectual/sangre , Discapacidad Intelectual/líquido cefalorraquídeo , Discapacidad Intelectual/orina , Trastornos del Desarrollo del Lenguaje/sangre , Trastornos del Desarrollo del Lenguaje/líquido cefalorraquídeo , Trastornos del Desarrollo del Lenguaje/orina , Discapacidad Intelectual Ligada al Cromosoma X/sangre , Discapacidad Intelectual Ligada al Cromosoma X/líquido cefalorraquídeo , Discapacidad Intelectual Ligada al Cromosoma X/orina , Trastornos del Movimiento/sangre , Trastornos del Movimiento/líquido cefalorraquídeo , Trastornos del Movimiento/genética , Trastornos del Movimiento/orina , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/sangre , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/líquido cefalorraquídeo , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/genética , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/orina , Proteínas Represoras/sangre , Proteínas Represoras/líquido cefalorraquídeo , Proteínas Represoras/orina , Trastornos del Habla/sangre , Trastornos del Habla/líquido cefalorraquídeoAsunto(s)
Aspirina/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/diagnóstico , Eosinófilos/fisiología , Linfocitos/patología , Fiebre Reumática/tratamiento farmacológico , Amidinotransferasas/sangre , Aspirina/uso terapéutico , Niño , Síndrome de Hipersensibilidad a Medicamentos/etiología , Diagnóstico Precoz , Femenino , Humanos , Fiebre Reumática/complicaciones , Fiebre Reumática/diagnósticoRESUMEN
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthesis, whereas L-arginine (Arg) and L-homoarginine (hArg) serve as substrates for NO synthesis. ADMA and other methylated arginines are generally believed to exclusively derive from guanidine (N (G))-methylated arginine residues in proteins by protein arginine methyltransferases (PRMTs) that use S-adenosylmethionine (SAM) as the methyl donor. L-Lysine is known for decades as a precursor for hArg, but only recent studies indicate that arginine:glycine amidinotransferase (AGAT) is responsible for the synthesis of hArg. AGAT catalyzes the formation of guanidinoacetate (GAA) that is methylated to creatine by guanidinoacetate methyltransferase (GAMT) which also uses SAM. The aim of the present study was to learn more about the mechanisms of ADMA and hArg formation in humans. Especially, we hypothesized that ADMA is produced by N (G)-methylation of free Arg in addition to the known PRMTs-involving mechanism. In knockout mouse models of AGAT- and GAMT-deficiency, we investigated the contribution of these enzymes to hArg synthesis. Arg infusion (0.5 g/kg, 30 min) in children (n = 11) and ingestion of high-fat protein meals by overweight men (n = 10) were used to study acute effects on ADMA and hArg synthesis. Daily Arg ingestion (10 g) or placebo for 3 or 6 months by patients suffering from peripheral arterial occlusive disease (PAOD, n = 20) or coronary artery disease (CAD, n = 30) was used to study chronic effects of Arg on ADMA synthesis. Mass spectrometric methods were used to measure all biochemical parameters in plasma and urine samples. In mice, AGAT but not GAMT was found to contribute to plasma hArg, while ADMA synthesis was independent of AGAT and GAMT. Arg infusion acutely increased plasma Arg, hArg and ADMA concentrations, but decreased the plasma hArg/ADMA ratio. High-fat protein meals acutely increased plasma Arg, hArg, ADMA concentrations, as well as the plasma hArg/ADMA ratio. In the PAOD and CAD studies, plasma Arg concentration increased in the verum compared to the placebo groups. Plasma ADMA concentration increased only in the PAOD patients who received Arg. Our study suggests that in humans a minor fraction of free Arg is rapidly metabolized to ADMA and hArg. In mice, GAMT and N (G)-methyltransferases contribute to ADMA and hArg synthesis from Arg, whereas AGAT is involved in the synthesis of hArg but not of ADMA. The underlying biochemical mechanisms remain still elusive.
Asunto(s)
Arginina/análogos & derivados , Arginina/administración & dosificación , Enfermedad de la Arteria Coronaria/sangre , Homoarginina/biosíntesis , Enfermedad Arterial Periférica/sangre , Adolescente , Adulto , Amidinotransferasas/sangre , Amidinotransferasas/deficiencia , Amidinotransferasas/genética , Amidinotransferasas/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Errores Innatos del Metabolismo de los Aminoácidos/tratamiento farmacológico , Errores Innatos del Metabolismo de los Aminoácidos/genética , Animales , Arginina/biosíntesis , Niño , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/genética , Discapacidades del Desarrollo/sangre , Discapacidades del Desarrollo/tratamiento farmacológico , Discapacidades del Desarrollo/genética , Femenino , Guanidinoacetato N-Metiltransferasa/sangre , Guanidinoacetato N-Metiltransferasa/deficiencia , Guanidinoacetato N-Metiltransferasa/genética , Guanidinoacetato N-Metiltransferasa/metabolismo , Humanos , Discapacidad Intelectual/sangre , Discapacidad Intelectual/tratamiento farmacológico , Discapacidad Intelectual/genética , Trastornos del Desarrollo del Lenguaje/sangre , Trastornos del Desarrollo del Lenguaje/tratamiento farmacológico , Trastornos del Desarrollo del Lenguaje/genética , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Trastornos del Movimiento/sangre , Trastornos del Movimiento/congénito , Trastornos del Movimiento/tratamiento farmacológico , Trastornos del Movimiento/genética , Enfermedad Arterial Periférica/tratamiento farmacológico , Enfermedad Arterial Periférica/genética , Trastornos del Habla/sangre , Trastornos del Habla/tratamiento farmacológico , Trastornos del Habla/genéticaRESUMEN
BACKGROUND: To develop an accurate stable isotope dilution assay for simultaneous quantification of creatine metabolites ornithine, arginine, creatine, creatinine, and guanidinoacetate in very small blood sample volumes to study creatine metabolism in mice. METHODS: Liquid-chromatography (C18) tandem mass spectrometry with butylation was performed in positive ionization mode. Stable isotope dilution assay with external calibration was applied to three different specimen types, plasma, whole blood and dried blood spot (DBS). RESULTS: Analytical separation, sensitivity, accuracy, and linearity of the assay were adequate. The stable isotope dilution assay in plasma revealed no significant bias to gold standard methods for the respective analytes. Compared to plasma, we observed an overestimate of creatine and creatinine (2- to 5-fold and 1.2- to 2-fold, respectively) in whole-blood and DBS, and an underestimate of arginine (2.5-fold) in DBS. Validation of the assay in mouse models of creatine deficiency revealed plasma creatine metabolite pattern in good accordance with those observed in human GAMT and AGAT deficiency. Single dose intraperitoneal application of ornithine in wild-type mice lead to fast ornithine uptake (Tmax ≤ 10 min) and elimination (T1/2=24 min), and a decline of guanidinoacetate. CONCLUSION: The assay is fast and reliable to study creatine metabolism and pharmacokinetics in mouse models of creatine deficiency.
Asunto(s)
Amidinotransferasas/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Creatina/sangre , Creatina/deficiencia , Pruebas con Sangre Seca/métodos , Guanidinoacetato N-Metiltransferasa/deficiencia , Discapacidad Intelectual/sangre , Trastornos del Desarrollo del Lenguaje/sangre , Trastornos del Movimiento/congénito , Plasma/metabolismo , Trastornos del Habla/sangre , Amidinotransferasas/sangre , Amidinotransferasas/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Animales , Cromatografía Liquida , Creatina/metabolismo , Discapacidades del Desarrollo/sangre , Discapacidades del Desarrollo/metabolismo , Modelos Animales de Enfermedad , Guanidinoacetato N-Metiltransferasa/sangre , Guanidinoacetato N-Metiltransferasa/metabolismo , Humanos , Discapacidad Intelectual/metabolismo , Isótopos/química , Trastornos del Desarrollo del Lenguaje/metabolismo , Límite de Detección , Modelos Lineales , Ratones , Trastornos del Movimiento/sangre , Trastornos del Movimiento/metabolismo , Reproducibilidad de los Resultados , Trastornos del Habla/metabolismo , Espectrometría de Masas en TándemRESUMEN
Cerebral creatine deficiency syndromes (CCDS) are a group of inborn errors of creatine metabolism that involve AGAT and GAMT for creatine biosynthesis disorders and SLC6A8 for creatine transporter (CT1) deficiency. Deficiencies in the three enzymes can be distinguished by intermediate metabolite levels, and a definitive diagnosis relies on the presence of deleterious mutations in the causative genes. Mutations and unclassified variants were identified in 41 unrelated patients, and 22 of these mutations were novel. Correlation of sequencing and biochemical data reveals that using plasma guanidinoacetate (GAA) as a biomarker has 100% specificity for both AGAT and GAMT deficiencies, but AGAT deficiency has decreased sensitivity in this assay. Furthermore, the urine creatine:creatinine ratio is an effective screening test with 100% specificity in males suspected of having creatine transporter deficiency. This test has a high false-positive rate due to dietary factors or dilute urine samples and lacks sensitivity in females. We conclude that biochemical screening for plasma GAA and measuring of the urine creatine:creatinine ratio should be performed for suspected CCDS patients prior to sequencing. Also, based on the results of this study, we feel that sequencing should only be considered if a patient has abnormal biochemical results on repeat testing.
Asunto(s)
Amidinotransferasas/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Encefalopatías Metabólicas Innatas/diagnóstico , Creatina/deficiencia , Guanidinoacetato N-Metiltransferasa/deficiencia , Discapacidad Intelectual/diagnóstico , Trastornos del Desarrollo del Lenguaje/diagnóstico , Discapacidad Intelectual Ligada al Cromosoma X/diagnóstico , Trastornos del Movimiento/congénito , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/deficiencia , Trastornos del Habla/diagnóstico , Amidinotransferasas/sangre , Amidinotransferasas/química , Amidinotransferasas/genética , Amidinotransferasas/metabolismo , Errores Innatos del Metabolismo de los Aminoácidos/genética , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Encefalopatías Metabólicas Innatas/genética , Encefalopatías Metabólicas Innatas/metabolismo , Creatina/genética , Creatina/metabolismo , Creatinina/orina , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/metabolismo , Femenino , Guanidinoacetato N-Metiltransferasa/sangre , Guanidinoacetato N-Metiltransferasa/genética , Guanidinoacetato N-Metiltransferasa/metabolismo , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/metabolismo , Trastornos del Desarrollo del Lenguaje/genética , Trastornos del Desarrollo del Lenguaje/metabolismo , Masculino , Proteínas de Transporte de Membrana/genética , Discapacidad Intelectual Ligada al Cromosoma X/genética , Discapacidad Intelectual Ligada al Cromosoma X/metabolismo , Modelos Moleculares , Trastornos del Movimiento/diagnóstico , Trastornos del Movimiento/genética , Trastornos del Movimiento/metabolismo , Mutación , Fenotipo , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/genética , Proteínas de Transporte de Neurotransmisores en la Membrana Plasmática/metabolismo , Conformación Proteica , Trastornos del Habla/genética , Trastornos del Habla/metabolismo , SíndromeRESUMEN
Low plasma homoarginine has emerged as a risk marker for cardiovascular disease. We exploited cells of a patient with a rare inborn error of metabolism to explore potential pathways of homoarginine synthesis, using stable isotopes and mass spectrometry. Control lymphoblasts, as opposed to lymphoblasts from an arginine:glycine amidinotransferase (AGAT)-deficient patient, were able to synthesize homoarginine from arginine and lysine. In contrast, in a patient with a deficiency of the urea cycle enzyme argininosuccinate synthase, plasma homoarginine was not decreased. We conclude that promiscuous activity of AGAT, a key enzyme in creatine synthesis, plays a pivotal role in homoarginine synthesis.
Asunto(s)
Amidinotransferasas/metabolismo , Enfermedades Cardiovasculares/metabolismo , Homoarginina/biosíntesis , Amidinotransferasas/sangre , Amidinotransferasas/deficiencia , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Errores Innatos del Metabolismo de los Aminoácidos/metabolismo , Discapacidades del Desarrollo/sangre , Discapacidades del Desarrollo/metabolismo , Homoarginina/sangre , Humanos , Recién Nacido , Discapacidad Intelectual/sangre , Discapacidad Intelectual/metabolismo , Masculino , Factores de Riesgo , Trastornos del Habla/sangre , Trastornos del Habla/metabolismo , Especificidad por SustratoAsunto(s)
Amidinotransferasas/sangre , Linfocitos/enzimología , Amidinotransferasas/deficiencia , Arginina/metabolismo , Isótopos de Carbono , Línea Celular , Pruebas Enzimáticas Clínicas/métodos , Glicina/metabolismo , Humanos , Marcaje Isotópico , Activación de Linfocitos , Isótopos de Nitrógeno , Valores de ReferenciaRESUMEN
The influence of regulatory peptides (somatostatin, calcitonin, and dalargin) on xanthine oxidase activity and lipid peroxidation level in pancreatic tissues as well as on the release of pancreatic enzymes (alpha-amylase, trypsin, lipase, and transamidinase) into blood was studied in 205 rats with experimental acute pancreatitis. Somatostatin and dalargin were shown to have obvious antioxidant effect seen by reduced xanthine oxidase activity and MDA level. All studied peptides stimulate reduced release of pancreatic enzymes. Particularly, reduction of dalargin and somatostatin is caused by inhibition of their synthesis as well as by pancreas protective effect of the peptides. Release of enzymes reduced by calcitonin is probably associated only with inhibition of secretory activity of the pancreas.
Asunto(s)
Calcitonina/farmacología , Leucina Encefalina-2-Alanina/análogos & derivados , Encefalina Leucina/análogos & derivados , Páncreas/efectos de los fármacos , Pancreatitis/fisiopatología , Somatostatina/farmacología , Simpaticolíticos/farmacología , Enfermedad Aguda , Amidinotransferasas/sangre , Animales , Encefalina Leucina/farmacología , Lipasa/sangre , Peroxidación de Lípido , Masculino , Páncreas/enzimología , Páncreas/fisiopatología , Ratas , Tripsina/sangre , Xantina Oxidasa/metabolismo , alfa-Amilasas/sangreRESUMEN
This study investigates the diabetes-induced lesions in liver and kidney and in addition the possible side effects of the diabetogenic substance streptozotocin (SR) on these organs in non-diabetic animals. 5-week-old female Wistar rats were injected 65 or 130 mg SR/kg body mass. Some animals of the drug group did not become hyperglycemic; thus it was possible to separate the drug effect from the diabetic influence on liver and kidney. In serum investigations some metabolic changes concerning the activities of the liver enzymes aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and the concentrations of urea and creatinine up to 30 days after drug application were studied. SR in hyperglycemic animals causes a time and dose dependent rise in all investigated parameters. Also in normoglycemic rats a significant increase in alkaline phosphatase and in creatinine was observed after 10 days. After 21 and 30 days there were no differences compared to untreated control rats, whereas elevated levels were observed in the hyperglycemic rats. Thus our results support the view of a short damaging effect of SR on liver and kidney without inducing a diabetic state; in hyperglycemic rats the damaging effect is more pronounced.
Asunto(s)
Amidinotransferasas/sangre , Creatina/sangre , Estreptozocina/farmacología , Urea/sangre , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Animales , Aspartato Aminotransferasas/sangre , Femenino , Ratas , Ratas EndogámicasRESUMEN
The activities of GGT (EC 2.3.2.1.) and glycine transaminidase (EC 2.6.2.1.) increased in all studied groups after at minimum four years of exposure to: acetobenzene, furfurol, ethylene--derivatives, polypropylene and butadiene. Besides these universal indicators the specific ones were found for a particular group of exposure: for acetobenzene--sialic acid, haptoglobine and IgA, for furfurol--sialic acid and haptoglobine, for ethylene--derivatives--haptoglobine, ceruloplasmine and the activity of arginase of the red blood cells, for polypropylene--IgA, for butadiene--proteolytic activity. These changes are treated as a manifestation of adaptive processes--the answer of the body to the environmental stimuli but not as the signs of early damage. The need of verification of the results by prospective studies is stressed.
Asunto(s)
Industria Química , Enfermedades Profesionales/inducido químicamente , Petróleo/efectos adversos , Adulto , Amidinotransferasas/sangre , Pruebas Enzimáticas Clínicas , Activación Enzimática/efectos de los fármacos , Humanos , Persona de Mediana Edad , Enfermedades Profesionales/diagnóstico , gamma-Glutamiltransferasa/sangreRESUMEN
Eleven non-routine biochemical and clinical indicators (selected of 26 preliminarily estimated) in Petrochemical Plant workers and in controls, localized in an increasing distance from the Plant (3-18-40 km), have been measured. Even in the 3 km distance, no effects of the Petrochemical Plant have been found. All the exposed groups exhibited changes in enzymes GGT and TA. We estimate these indicators as universal. The concentration of haptoglobin (Hp) changed in 3 groups, whereas sialic acid and arginase--in 2 exposed groups.
Asunto(s)
Industria Química , Enfermedades Profesionales/inducido químicamente , Petróleo/toxicidad , Amidinotransferasas/sangre , Arginasa/sangre , Femenino , Haptoglobinas/análisis , Humanos , Masculino , Ácido N-Acetilneuramínico , Enfermedades Profesionales/diagnóstico , Ácidos Siálicos/sangre , gamma-Glutamiltransferasa/sangreRESUMEN
In diagnosis of acute pancreatitis of special importance is determination of the activity of transamidinase, phospholipase A, lipase, concentration of copper, calcium and triglycerides in blood serum as well as laparoscopy with biopsy and local thermometry of the pancreas. The dosage of 5-fluoruracil in the complex treatment of patients should be differentiated corresponding to the form of the disease: 3 mg/kg in the endomatous form, 5 mg/kg in the destructive form. The general lethality was 1.4%. In conservative treatment there were no lethal outcomes.
Asunto(s)
Pancreatitis/diagnóstico , Enfermedad Aguda , Adulto , Amidinotransferasas/sangre , Calcio/sangre , Pruebas Enzimáticas Clínicas , Terapia Combinada , Cobre/sangre , Femenino , Humanos , Lipasa/sangre , Masculino , Persona de Mediana Edad , Pruebas de Función Pancreática , Pancreatitis/terapia , Fosfolipasas A/sangre , Termografía , Triglicéridos/sangreRESUMEN
Histological and electron microscopic study of the pancreas and biochemical determination of pancreatic enzymes in blood serum were performed in animals with experimental pancreonecrosis and after the treatment with 5-fluorouracil. The treatment resulted in the decreased secretion of pancreatic acinus tissue, diminution of destructive and inflammatory lesions and the decreased levels of trypsin, alpha-amylase and transamidinase. It is suggested that 5-fluorouracil may be used in the combined treatment of acute pancreonecrosis.
Asunto(s)
Fluorouracilo/uso terapéutico , Páncreas/ultraestructura , Enfermedades Pancreáticas/tratamiento farmacológico , Enfermedad Aguda , Amidinotransferasas/sangre , Animales , Masculino , Microscopía Electrónica , Necrosis , Enfermedades Pancreáticas/patología , Ratas , Tripsina/sangre , alfa-Amilasas/sangreRESUMEN
A 10-month-old infant with hypoplasia of the intestinal mucosa had the fat overload syndrome develop while receiving intravenous fat emulsion at a dosage of 5 g/kg/day of fat for five weeks. This syndrome was characterized by fever, jaundice, easy bruisability, increased levels of serum transaminases, conjugated hyperbilirubinemia, and abnormal results of clotting studies. Management consisted of withdrawal of parenteral nutrition for 72 hours, followed by gradual reinstitution of protein and subsequent introduction of fat at a lower dosage.
Asunto(s)
Hiperlipidemias/etiología , Nutrición Parenteral Total/efectos adversos , Nutrición Parenteral/efectos adversos , Amidinotransferasas/sangre , Pruebas de Coagulación Sanguínea , Femenino , Fiebre/etiología , Humanos , Lactante , Enfermedades Intestinales/terapia , Ictericia/etiologíaRESUMEN
The authors studied four children with Reye's syndrome aged 16 months, 6 years, 8 years and 11 years respectively with severe liver failure and progressive coma. The laboratory investigations in all of them showed a marked elevation of serum transaminases, hyperammoniaemia and a prolongation of the prothrombin time. The electroencephalograms showed a grossly abnormal picture with generalised continuous delta activity. Three children survived with return to normal of the liver function tests whilst the fourth child died. In the last two patients an electroencephalogram carried out every six hours has enabled certain prognostic features to be determined. Improvement in the E.E.G. correlates closely with clinical improvement and vice versa. The authors also advocate serial E.E.G. recordings in Reye's syndrome. The role of hyperammonaemia in the genesis of encephalopathy and the electroencephalographic changed is discussed. The role played by raised intracranial pressure is stressed and the importance of controlling it in order to prevent further damage and improve the prognosis of this serious illness.