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A correct perioperative fluid administration represents one of the most important items proposed by the Enhanced Recovery After Surgery Society. Upper gastrointestinal (UGI) surgery patients undergoing major oncological procedures are often elderly and frail. Should we prefer a wet or a dry patient? Both conditions should probably be avoided in this surgical setting. We present a narrative review on perioperative fluid administration in UGI patients undergoing major surgery, also analyzing the role of Goal Directed therapy.
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Procedimientos Quirúrgicos del Sistema Digestivo , Especialidades Quirúrgicas , Humanos , Anciano , Fluidoterapia/métodos , Tiempo de Internación , Complicaciones Posoperatorias/prevención & controlRESUMEN
AIMS: This survey was conducted to assess psychosocial problems and functional status among patients on maintenance dialysis in Hungary. METHODS: All adult patients (n = 4,321) receiving maintenance dialysis in the 56 dialysis centers in Hungary in 2006 were approached to participate in a national, cross-sectional survey. Patients completed a brief self-reported questionnaire. Socio-demographic parameters, disease-related information and data about functional status were collected. Self-rated health and depressive symptoms were also assessed. RESULTS: Mean age was 62 ± 14 y; 52% were males. The prevalence of diabetes was 30%. 46% of participants reported having depressive symptoms. Significant functional limitation was frequent. In multivariable regression models, female gender, poor self-reported finances, less education, history of acute myocardial infarction (AMI) or cerebrovascular disease, the presence of visual or hearing impairment and difficulties with basic activities of daily living were independently associated with the presence of depressive symptoms. In a separate model, age, dialysis vintage, history of AMI or cerebrovascular disease, the presence of visual or hearing impairments, difficulties with basic activities of daily living and also having depressive symptoms were independently associated with self-rated health score. CONCLUSIONS: Chronic dialysis patients in Hungary have disadvantaged socioeconomic status, frequent depressive symptoms and many functional limitations. Professional psychosocial help would be particularly important for this underprivileged patient population in addition to high quality dialysis to optimize outcomes.
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Estado de Salud , Diálisis Renal/psicología , Anciano , Estudios Transversales , Depresión/epidemiología , Depresión/etiología , Femenino , Humanos , Hungría , Trasplante de Riñón , Masculino , Persona de Mediana Edad , Análisis Multivariante , Calidad de Vida , Clase Social , Listas de EsperaRESUMEN
The importance of therapeutic hypothermia in selected categories of patients has been widely demonstrated. Laboratory, animal, and human studies permitted to understand the molecular mechanisms underlying cooling and its importance in preventing the ischemia/reperfusion injury of the brain. The development of new technologies offered the possibility to reach the desired temperature effectively and rapidly, reducing related side effects. Nevertheless, the application of systematic protocols of cooling has not been adequately reached in many hospitals. In this paper the most recent findings regarding hypothermia, its physiological bases and ways of application are reviewed.
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AIMS: This study comprised part of a larger cross-sectional survey performed in Hungary in the period 2005-2006, which was designed first to reveal the representative age-, gender- and height-specific percentile values for the systolic blood pressure (SBP) and the diastolic blood pressure (DBP) in Hungarian children aged 11-16 years. The second aim was to determine the prevalence of overweight and obesity. METHODS: Analyses were performed on 14,290 Hungarian children aged 11-16 years. All blood pressure (BP) measurements were made with a validated, automated, digital device. The criteria recommended by international guidelines were used. RESULTS: The prevalence of overweight and obesity among the Hungarian children was found to be 23.4% (3347 adolescents; International Obesity Task Force criteria). Previous studies have reported that the strongest correlation is observed between the BP values and weight, and our results are in accordance with this. CONCLUSIONS: Regional differences in morphometry (different prevalences of overweight and obesity) and the genetic background, disparate eating habits and other cultural factors may account for the differences in BP levels during childhood. As the prevalence of overweight and obesity is increasing worldwide, it is important that countries carefully monitor the weight and BP status of their children and adolescents.
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Presión Sanguínea , Índice de Masa Corporal , Obesidad/epidemiología , Sobrepeso/epidemiología , Adolescente , Estatura , Peso Corporal , Niño , Estudios Transversales , Femenino , Humanos , Hungría/epidemiología , Masculino , PrevalenciaRESUMEN
AIMS: Variation of the action of erythropoiesis-stimulating agent (ESA) may modify oxidative stress in hemodialyzed (HD) patients. Our aim was to follow changes of oxidative stress during withdrawal and subsequent resumption of ESA therapy. PATIENTS AND METHODS: After a 14-day suspension of epoietin-beta treatment, 11 HD patients received epoietin-beta and 10 patients darbepoietin-alpha. The whole blood oxidized and reduced glutathione (GSSG, GSH) and erythrocyte malondialdehyde (E-MDA) concentrations and the erythrocyte superoxide dismutase (E-SOD) and catalase (E-CAT) activities were determined before the ESA-free interval (baseline) and at Weeks 2, 6, 10 and 14. RESULTS: In both groups, the ratios GSSG/ GSH were increased at Weeks 2 and 6 (p < 0.001). The E-MDA levels were elevated (p < 0.01) and the E-SOD activities were decreased (p < 0.001) at Week 6. By Week 14, these markers had returned to the baseline, whereas the GSH (p < 0.001) and E-CAT activity levels (p < 0.001) had increased. CONCLUSIONS: An increase in oxidative stress was revealed by the ratio GSSG/GSH directly after the short-term withdrawal of epoietin-b therapy in HD. This new finding may have implications in conditions involving transiently depressed ESA action. For both ESAs, the early phase of readministration was associated with similarly increased oxidative stress, with a subsequent return to the baseline level.
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Eritropoyetina/análogos & derivados , Eritropoyetina/farmacología , Hematínicos/farmacología , Fallo Renal Crónico/sangre , Estrés Oxidativo/fisiología , Diálisis Renal/métodos , Privación de Tratamiento , Anemia/sangre , Anemia/etiología , Anemia/prevención & control , Darbepoetina alfa , Eritrocitos/enzimología , Femenino , Estudios de Seguimiento , Disulfuro de Glutatión/sangre , Hemoglobinas/metabolismo , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Recombinantes , Superóxido Dismutasa/sangreRESUMEN
INTRODUCTION: Fenoldopam has been used to protect renal function in critically ill patients and in those undergoing major surgery, where a possible damage of kidney is expected. Numerous randomized studies and meta-analysis demonstrated the efficacy of fenoldopam in this setting. We performed this study to demonstrate the feasibility of administering fenoldopam, trough an elastomeric pump connected to a peripheral vein, to patients undergoing nephron sparing surgery. MATERIALS AND METHODS: Twenty consecutive patients, ASA physical status class I-III, undergoing laparoscopic or laparotomic renal tumorectomy were enrolled. Fenoldopam was infused trough an elastomeric pump at a fixed dosage of 0.1 mcg/kg/min, obtained after diluting the drug with saline solution according to the weight of the patient. We injected the drug trough a peripheral vein from the induction of anaesthesia for 48 hours after the end of surgery. RESULTS: The infusion of fenoldopam did not modify the haemodynamic parameters. We did not find episodes of hypotension and only in three patients we registered episodes of tachycardia, not requiring the suspension of the infusion. No other side-effect was noted. CONCLUSIONS: The administration of fenoldopam, trough an elastomeric pump, in patients undergoing renal tumorectomy is feasible through a peripheral vein access.
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The analysis of urinary organic acids is crucial for the diagnosis of many inborn errors of metabolism. A vital part of the analytical process is the extraction procedure. The sensitivity and linearity of the analysis of 26 diagnostically important urinary metabolites with tetrahydrofuran (THF) and ethyl acetate (EtOAc) as extraction solvents were determined by gas chromatography-mass spectrometry. Good linearity (r (2) > 0.90) was observed for all of the compounds in the investigated concentration range (290-900 mumol/L) for both solvents. For less polar compounds, THF extraction yielded lower or similar sensitivities as compared with EtOAc (sensitivity ratio: 0.6-1.3). For more polar compounds, however, much higher sensitivities were observed when THF was used (sensitivity ratio: 1.8-17.2). Our results provide information concerning the use of THF for the sensitive quantitative analysis of polar urinary metabolites which are difficult to quantify using EtOAc.
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Acetatos/farmacología , Ácidos/aislamiento & purificación , Ácidos/orina , Furanos/farmacología , Urinálisis/métodos , Ácidos/análisis , Adulto , Ácidos Carboxílicos/análisis , Ácidos Carboxílicos/orina , Humanos , Iones/análisis , Iones/orina , Enfermedades Metabólicas/diagnóstico , Enfermedades Metabólicas/orina , Compuestos Orgánicos/análisis , Compuestos Orgánicos/aislamiento & purificación , Compuestos Orgánicos/orina , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Solventes/farmacologíaRESUMEN
AIM: The aim of this paper was to compare wash-in and wash-out curves of desflurane in morbidly obese and nonobese patients. METHODS: Fourteen patients (7 obese and 7 nonobese) were studied. In the nonobese patients, anaesthesia was started by administering 2 mg/kg propofol bolus and a target controlled effect site concentration of remifentanil set at 2.5 ng/mL. Obese patients were intubated using a flexible fiberoptic bronchoscopic technique facilitated by a target controlled effect site concentration of remifentanil set at 2.5 ng/mL. After endotracheal intubation, general anaesthesia was started by administering a 1.5 mg/kg propofol bolus dose. Ten minutes after induction of anaesthesia, 4% desflurane was administered for 30 min. Desflurane kinetics was determined by collecting end-tidal samples from first breaths at 1, 5, 10, 15, 20, 25 and 30 min. At last skin suture, the end-tidal concentration of desflurane was recorded from 5 consecutive breaths before their discontinuation, then the end-tidal samples of the inhalational agent were collected at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5 and 5 min after terminating its administration. The period of time from discontinuation of desflurane to opening eyes, squeezing the observer's hand, extubation, stating the patients' name and providing date of birth was also recorded. RESULTS: The FA/FI ratio was higher in the nonobese group from the 10th to the 15th min. Wash-out curves of desflurane and recovery times were similar. CONCLUSION: Our results show that desflurane provides similar kinetic and recovery profiles in obese and nonobese patients.
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Anestésicos por Inhalación/farmacocinética , Isoflurano/análogos & derivados , Obesidad Mórbida/metabolismo , Adulto , Anciano , Anestesia por Inhalación , Anestésicos Intravenosos , Desflurano , Femenino , Humanos , Intubación Intratraqueal , Isoflurano/farmacocinética , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio , Obesidad Mórbida/complicaciones , Piperidinas , RemifentaniloRESUMEN
Hypertension is an increasing public health problem all over the world. Essential hypertension accounts for more than 90% of cases of hypertension. It is a complex genetic, environmental and demographic trait. New method in molecular biology has been proposed a number of candidate genes, but the linkage or association with hypertension has been problematic (lack of gene-gene and gene-environment interaction). It is well known that genetic influences are more important in younger hypertensives, because children are relatively free from the common environmental factors contributing to essential hypertension. The association studies compare genotype ferquencies of the candidate gene between patient groups and the controls, in pathways known to be involved in blood pressure regulation. This study examined three polymorphisms of these factors encoding genes (ET-1 G+5665T (Lys198Asn), endothelial nitric oxide synthase (eNOS) T-786C promoter polymorphism and 27-bp repeat polymorphism in intron 4) in adolescents with juvenile essential and obesity-associated hypertension. Significant differences were found in the G/T genotype of the ET-1 polymorphism in the hypertensive and obese+hypertensive patients (body mass index (BMI) > 30). A strong association was detected between the BMI and the polymorphism of the ET-1 gene. It seems that ET-1 gene polymorphism plays a role in the development of juvenile hypertension associated with obesity. Although no significant differences were seen in the case of the eNOS promoter polymorphism and the eNOS 4th intron 27-bp repeat polymorphism. It seems that eNOS may play a role, but this is not the main factor in the control of blood pressure; it is rather a fine regulator in this process. This study with adolescents facilitates an understanding of the genetic factors promoting juvenile hypertension and obesity.
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Endotelina-1/genética , Hipertensión/genética , Óxido Nítrico Sintasa de Tipo III/genética , Adolescente , Índice de Masa Corporal , Niño , Frecuencia de los Genes , Humanos , Hipertensión/etiología , Masculino , Óxidos de Nitrógeno/sangre , Obesidad/complicaciones , Polimorfismo GenéticoRESUMEN
BACKGROUND: The aim of this study was to assess the predictive performance of 'Servin's formula' for bispectral index (BIS)-guided propofol-remifentanil target-controlled infusion (TCI) in morbidly obese patients. METHODS: Twenty patients (ASA physical status II-III, age 32-64 yr) undergoing bilio-intestinal bypass surgery, were recruited. Anaesthesia was induced by using a TCI of propofol with an initial target plasma concentration of 6 microg ml(-1), then adapted to maintain stable BIS values ranging between 40 and 50. A TCI of remifentanil was added to achieve pain control and haemodynamic stability. For propofol, weight was corrected as suggested by Servin and colleagues. With ideal body weight (IBW) corrected according to formula suggested by Lemmens and colleagues. For remifentanil, weight was corrected according to IBW. Arterial blood samples for the determination of blood propofol concentrations were collected at different surgical times. The predictive performance of propofol TCI was evaluated by examining performance accuracy. RESULTS: Median prediction error and median absolute prediction error were -32.6% (range -53.4%; -2.5%) and 33.1% (10.8%; 53.4%), respectively. Wobble median value was 5.9% (2.5%; 25.2%) while divergence median value was -1.5% h(-1) (-7.7; 33.8% h(-1)). CONCLUSION: Significant bias between predicted and measured plasma propofol concentrations was found while the low wobble values suggest that propofol TCI system is able to maintain stable drug concentrations over time. As already suggested before, a computer simulation confirmed that the TCI system performance could be significantly improved when total body weight is used.
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Anestésicos Intravenosos/administración & dosificación , Sistemas de Liberación de Medicamentos , Obesidad Mórbida/sangre , Piperidinas/administración & dosificación , Propofol/administración & dosificación , Adulto , Analgésicos Opioides/administración & dosificación , Anestésicos Intravenosos/sangre , Peso Corporal , Simulación por Computador , Electroencefalografía/efectos de los fármacos , Femenino , Derivación Gástrica , Humanos , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Obesidad Mórbida/cirugía , Propofol/sangre , Estudios Prospectivos , RemifentaniloRESUMEN
AIM: The aim of this paper was to assess the effects of low-dose systemic corticosteroid therapy in complex regional pain syndrome (CRPS), to measure the long-term functional outcome, and to evaluate an arbitrary scale of severity of CRPS. METHODS: An evaluation of 31 consecutive subjects diagnosed with CRPS before and after they underwent corticosteroid therapy was carried out. The clinical and functional variables considered were evaluated at baseline, halfway through therapy, at the end and after 1, 6 and 12 months after the end of treatment. A clinical severity scale of CRPS was devised. RESULTS: The comparison between baseline and post-treatment data of the principal variables resulted in all cases significant (P<0.001), as did, in most cases, the changes in variables between successive time intervals (P<0.05), supporting the long-term efficacy of treatment. The score of the clinical severity scale of CRPS showed a significant improvement in the one-year follow-up. CONCLUSION: Corticosteroid therapy in CRPS provides a short-term response to the pain with a low risk of side effects. The improvement in all the variables considered persisted at one-year follow-up. The arbitrary scale of clinical severity of CRPS should be further tested in order to propose it as an instrument for use in following the course of CRPS.
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Corticoesteroides/uso terapéutico , Síndromes de Dolor Regional Complejo/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Síndromes de Dolor Regional Complejo/fisiopatología , Femenino , Fuerza de la Mano , Humanos , Masculino , Persona de Mediana Edad , Dimensión del Dolor , Rango del Movimiento Articular , Recuperación de la Función , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
In patients with a space-occupying lesion of the pancreas at first a primary ductal adenocarcinoma is considered as the cause. Other tumours or metastases are assumed to occur very rarely. Therapy and prognosis of other pancreas tumours differ from therapy and prognosis of a primary ductal adenocarcinoma. We therefore examined the question of how frequently a space-occupying lesion of the pancreas was not due to a ductal adenocarcinoma in our case materials. Retrospectively 70 patients who had undergone a percutaneous puncture of a space-occupying mass of the pancreas under ultrasonographic control were included in the study (34 women, 36 men). In 62 patients a clear histological diagnosis was possible on the basis of the biopsy. In 53 cases (76 %) a primary adenocarcinoma of the pancreas could be diagnosed. In 5 patients (7 %) these masses turned out to be metastases of a previously known malignant tumour disease (2 x mammary carcinoma, 2 x gastric carcinoma, 1 x sigmoid carcinoma). Other tumours could be detected in 4 cases (6 %) including a tuberculoma, an endocrine tumour, a fusocellular sarcoma with partial neurogenic differentiation and a large-cell and pleomorphic-cell anaplastic, partly sarcomatoid carcinoma. In patients with a space-occupying lesion of the pancreas, tumours other than a ductal adenocarcinoma are not rare. In particular, in cases of a previously known malignant tumour disease a space-occupying lesion of the pancreas can also turn out to be a metastasis. Every other individual tumour entity is rare. Other tumour entities at large, however, are found in daily routine. The preoperative biopsy of space-occupying lesions of the pancreas, therefore, still has a clinical importance for the further therapy planning.
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Carcinoma Ductal Pancreático/epidemiología , Carcinoma Ductal Pancreático/patología , Neoplasias Pancreáticas/epidemiología , Neoplasias Pancreáticas/patología , Anciano , Anciano de 80 o más Años , Femenino , Alemania/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana EdadRESUMEN
Guidelines for Helicobacter pylori therapy were proposed at the Maastricht 2/2000 conference. Since then no further major developments have been made. An evidenced based choice of treatment is thereby nearly impossible as large randomized trials have not been performed. Minor progress could be achieved in the areas of second-line and rescue treatment options after failure of the standard therapy. At present proton pump inhibitors are the most powerful drugs for the treatment of gastro-oesophageal reflux disease. No additional progress has been achieved concerning therapy of reflux disease in the last years. Reasonable anxiety about the safety of long-term acid suppression with proton pump inhibitors diminished over years as no significant increase in cancer development could be detected.
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Antiácidos/administración & dosificación , Antibacterianos/administración & dosificación , Reflujo Gastroesofágico/tratamiento farmacológico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/efectos de los fármacos , Inhibidores de la Bomba de Protones , Animales , Enfermedad Crónica , Reflujo Gastroesofágico/etiología , Infecciones por Helicobacter/complicaciones , Humanos , Pautas de la Práctica en Medicina/tendencias , Resultado del TratamientoRESUMEN
CLINICAL FEATURES: A 40-year-old female presented with chronic diarrhoea, intermittent abdominal pain, and melena. She reported of a 7 kg loss of weight within the preceding 6 weeks and showed signs of mild abdominal pain upon palpation of the right lower quadrant. Our clinical diagnosis was Crohn's disease or infectious gastro-enteritis as a CT scan showed thickening of the colonic wall in the right lower quadrant. However a previously performed ileocolonoscopy was normal. TECHNICAL EXAMINATIONS: Magnetic resonance imaging showed a thickened terminal ileum with extensive narrowing of the bowel lumen, in addition a polyp obstructing the lumen of the terminal ileum at 30 cm was detected during colonoscopy. THERAPY: The involved portion of ileum was resected. Intraoperatively an intussusception with the polyp forming the leading edge was found. Histological analysis led to the diagnosis "lipoma". Postoperatively the patient is now feeling well without any abdominal pain. CONCLUSION: Tumours of the small bowel are rare and are therefore often forgotten in the list of differential diagnoses of abdominal pain. If symptomatic, these tumours present mainly with uncharacteristic and unspecific signs, often leading to a delay in correct diagnosis as in the presented case. We therefore suggest that small bowel tumours should be considered at earlier stages in the differential diagnosis of unexplained abdominal pain in the middle-aged patient with signs of intestinal obstruction.
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Dolor Abdominal/etiología , Diarrea/etiología , Neoplasias del Íleon/diagnóstico , Obstrucción Intestinal/diagnóstico , Pólipos Intestinales/diagnóstico , Lipoma/diagnóstico , Melena/etiología , Adulto , Biopsia , Enfermedad Crónica , Colonoscopía , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades del Íleon/diagnóstico , Enfermedades del Íleon/patología , Enfermedades del Íleon/cirugía , Neoplasias del Íleon/patología , Neoplasias del Íleon/cirugía , Íleon/patología , Íleon/cirugía , Obstrucción Intestinal/patología , Obstrucción Intestinal/cirugía , Pólipos Intestinales/patología , Pólipos Intestinales/cirugía , Intususcepción/diagnóstico , Intususcepción/patología , Intususcepción/cirugía , Lipoma/patología , Lipoma/cirugía , Imagen por Resonancia MagnéticaRESUMEN
Primary lymphoedema associated with chylous reflux is a very rare clinical entity. We report a 3-year-old girl with unilateral lymphoedema, xanthomatosis and vaginal lymphorrhoea. Biopsy also revealed intestinal lymphangiectasia. This paper also presents a brief review of the literature and draws attention to the significance of the xanthomatous eruption in the diagnosis of a chylous reflux.
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Enfermedades en Gemelos , Linfangiectasia Intestinal/complicaciones , Linfedema/complicaciones , Excreción Vaginal/complicaciones , Xantomatosis/complicaciones , Preescolar , Femenino , Humanos , Linfangiectasia Intestinal/diagnóstico , Linfedema/diagnóstico , Linfocitos , Dedos del Pie , Excreción Vaginal/diagnóstico , Xantomatosis/diagnósticoRESUMEN
Although the role of calcium (Ca2+) in the signal transduction and pathobiology of the exocrine pancreas is firmly established, the role of magnesium (Mg2+) remains unclear. We have characterized the intracellular distribution of Mg2+ in response to hormone stimulation in isolated mouse pancreatic acinar cells and studied the role of Mg2+ in modulating Ca2+ signaling using microspectrofluorometry and digital imaging of Ca2+- or Mg2+-sensitive fluorescent dyes as well as Mg2+-sensitive intracellular microelectrodes. Our results indicate that an increase in intracellular Mg2+ concentrations reduced the cholecystokinin (CCK) -induced Ca2+ oscillations by inhibiting the capacitive Ca2+ influx. An intracellular Ca2+ mobilization, on the other hand, was paralleled by a decrease in [Mg2+]i, which was reversible upon hormone withdrawal independent of the electrochemical gradients for Mg2+, Ca2+, Na+, and K+, and not caused by Mg2+ efflux from acinar cells. In an attempt to characterize possible Mg2+ stores that would explain the reversible, hormone-induced intracellular Mg2+ movements, we ruled out mitochondria or ATP as potential Mg2+ buffers and found that the CCK-induced [Mg2+]i decrease was initiated at the basolateral part of the acinar cells, where most of the endoplasmic reticulum (ER) is located, and progressed from there toward the apical pole of the acinar cells in an antiparallel fashion to Ca2+ waves. These experiments represent the first characterization of intracellular Mg2+ movements in the exocrine pancreas, provide evidence for possible Mg2+ stores in the ER, and indicate that the spatial and temporal distribution of intracellular Mg concentrations profoundly affects acinar cell Ca2+ signaling.
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Señalización del Calcio , Calcio/metabolismo , Magnesio/metabolismo , Páncreas/citología , Páncreas/metabolismo , Animales , Carbonil Cianuro p-Trifluorometoxifenil Hidrazona/farmacología , Quelantes/farmacología , Colecistoquinina/farmacología , Ciclosporina/farmacología , Ácido Edético/farmacología , Ácido Egtácico/análogos & derivados , Ácido Egtácico/farmacología , Inhibidores Enzimáticos/farmacología , Colorantes Fluorescentes/metabolismo , Procesamiento de Imagen Asistido por Computador , Técnicas In Vitro , Transporte Iónico , Ionóforos/farmacología , Masculino , Potenciales de la Membrana/fisiología , Ratones , Páncreas/efectos de los fármacos , Espectrometría de Fluorescencia , Tapsigargina/farmacologíaRESUMEN
OBJECTIVES: Leber's hereditary optic neuropathy (LHON) is a maternally inherited disease characterised by acute or subacute bilateral visual loss in young patients. The primary aetiological event is a mutation in the mitochondrial genome (mtDNA) affecting in most cases mtDNA-encoded subunits of the respiratory chain NADH: coenzyme Q oxidoreductase (complex I). The impaired function of complex I leads to a decline in mitochondrial energy production and enhances free radical generation. METHODS: The concentrations of some non-enzymatic antioxidants (alpha-tocopherol, beta-carotene, lycopene, glutathione, free sulphydryl groups) and the lipid peroxides in the blood of patients with LHON, carriers with homoplasmic DNA mutation at 11 778, and controls were investigated using high performance liquid chromatography and spectrophotometric methods to assess the function of their antioxidant defence systems. RESULTS: The alpha-tocopherol/cholesterol+ triglyceride ratio was significantly reduced (p<0.05) both in the patients and asymptomatic carriers. The concentrations of the other antioxidants and the lipid peroxides were not different from those of control subjects. CONCLUSION: The low concentration of plasma alpha-tocopherol most probably reflects the consumption of the antioxidant by the affected tissues. Furthermore, it suggests that alpha-tocopherol may be the primary scavenger molecule against the free radicals induced by complex I deficiency.
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ADN Mitocondrial/genética , Peróxidos Lipídicos/sangre , Atrofias Ópticas Hereditarias/sangre , Atrofias Ópticas Hereditarias/genética , Vitamina E/sangre , Adulto , Femenino , Glutatión/sangre , Heterocigoto , Humanos , Masculino , Mutación/genéticaRESUMEN
In the neonatal period, there is a high iron load, while both the level and molar oxidase activity of ceruloplasmin are low. On the other hand, the neonatal xanthine oxidase (XO) activity is higher than later in life and XO has a significant iron-oxidizing capacity. We therefore studied the physiological contribution of XO to the ferroxidase activity of the plasma in 20 full-term newborn infants. Ferroxidase activity was measured spectrophotometrically, with Fe++ as substrate. The uric acid formed by XO was assayed by means of HPLC, with electrochemical detection. The total ferroxidase activity in the plasma was about one-fourth of the adult level and rapidly increased doubling within 3 days after birth. About 90% of the plasma ferroxidase activity was due to ceruloplasmin, the remainder being accounted for by ferroxidase II. The XO activity underwent a 30% (statistically non-significant) elevation at 24 h, though ferroxidase activity attributable to XO was not detected at any time. Accordingly, XO does not seem to add substantially to the total iron-oxidizing capacity of the plasma in the neonatal period. The high molar ferroxidase activity is probably of importance at the endothelial cell surface.