RESUMEN
Continuous normobaric hypoxia (CNH) renders the heart more tolerant to acute ischemia/reperfusion injury. Protein kinase C (PKC) is an important component of the protective signaling pathway, but the contribution of individual PKC isoforms under different hypoxic conditions is poorly understood. The aim of this study was to analyze the expression of PKCepsilon after the adaptation to CNH and to clarify its role in increased cardiac ischemic tolerance with the use of PKCepsilon inhibitory peptide KP-1633. Adult male Wistar rats were exposed to CNH (10 % O(2), 3 weeks) or kept under normoxic conditions. The protein level of PKCepsilon and its phosphorylated form was analyzed by Western blot in homogenate, cytosolic and particulate fractions; the expression of PKCepsilon mRNA was measured by RT-PCR. The effect of KP-1633 on cell viability and lactate dehydrogenase (LDH) release was analyzed after 25-min metabolic inhibition followed by 30-min re-energization in freshly isolated left ventricular myocytes. Adaptation to CNH increased myocardial PKCepsilon at protein and mRNA levels. The application of KP-1633 blunted the hypoxia-induced salutary effects on cell viability and LDH release, while control peptide KP-1723 had no effect. This study indicates that PKCepsilon is involved in the cardioprotective mechanism induced by CNH.
Asunto(s)
Adaptación Fisiológica/genética , Hipoxia/genética , Hipoxia/fisiopatología , Proteína Quinasa C-epsilon/genética , Animales , Supervivencia Celular/efectos de los fármacos , Hipoxia/enzimología , L-Lactato Deshidrogenasa/metabolismo , Masculino , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/genética , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Proteína Quinasa C-epsilon/antagonistas & inhibidores , Proteína Quinasa C-epsilon/biosíntesis , Inhibidores de Proteínas Quinasas/farmacología , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Ratas , Ratas WistarRESUMEN
Increasing hemodynamic load during early postnatal development leads to rapid growth of the left ventricular (LV) myocardium, which is associated with membrane phospholipid (PL) remodeling characterized by n-3 polyunsaturated fatty acids (PUFA) accumulation. The aim of this study was to examine the influence of additional workload imposed early after birth when ventricular myocytes are still able to proliferate. Male Wistar rats were subjected to abdominal aortic constriction (AC) at postnatal day 2. Concentrations of PL and their fatty acid (FA) profiles in the LV were analyzed in AC, sham-operated (SO) and intact animals on postnatal days 2 (intact only), 5 and 10. AC resulted in LV enlargement by 22 % and 67 % at days 5 and 10, respectively, compared with age-matched SO littermates. Concentrations of phosphatidylcholine, cardiolipin, phosphatidylinositol, phosphatidylethanolamine, phosphatidylserine and sphingomyelin decreased in AC myocardium, albeit with different time course and extent. The main effect of AC on FA remodeling consisted in the accumulation of n-3 PUFA in PL. The most striking effect of AC on FA composition was observed in phosphatidylinositol and cardiolipin. We conclude that excess workload imposed by AC inhibited the normal postnatal increase of PL concentration while further potentiating the accumulation of n-3 PUFA as an adaptive response of the developing myocardium to accelerated growth.
Asunto(s)
Ácidos Grasos Omega-3/metabolismo , Miocardio/metabolismo , Fosfolípidos/metabolismo , Animales , Animales Recién Nacidos , Aorta Abdominal , Presión Sanguínea , Proliferación Celular , Constricción Patológica , Hemodinámica , Masculino , Miocardio/citología , Ratas , Ratas WistarRESUMEN
PURPOSE: To assess the impact of clinical and nutritional factors on overall survival (OS) and time to disease progression of oesophageal cancer patients treated with neoadjuvant chemoradiotherapy (CRT) and surgery. METHODS: We retrospectively studied and analysed several clinical and nutritional factors, such as performance status, weight changes before and during CRT, dysphagia, nutritional support, and serum albumin to see whether they exerted any impact on OS and time to disease progression. RESULTS: In 107 patients the average weight loss was 9.7% from the onset of signs of disease to the beginning of therapy and 3% during CRT. In univariate analysis, significant unfavorable impact on survival was proved for low performance status, severe dysphagia, need for nasogastric tube insertion, above-average weight loss before treatment, weight loss >5% during CRT, and serum albumin ≤ 35 g/l before or after CRT. Patients supported by oral nutritional supplements (ONS) had higher probability to attain full dosage of CRT and radical resection than did those obtaining dietary advice alone. In multivariate analysis, serum albumin level, nasogastric (NG) tube insertion and pretreatment body weight loss were independent prognostic factors for OS, while serum albumin level after CRT and NG tube insertion were prognosticators for time to progression. CONCLUSION: Serum albumin level can serve as a useful prognostic factor for the outcome of patients with oesophageal cancer treated with neoadjuvant CRT and surgery. Appropriate nutritional support of these patients increased the probability of attaining full dosage of CRT and radical disease resection.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Trastornos de Deglución , Neoplasias Esofágicas/mortalidad , Esofagectomía , Estado Nutricional , Adolescente , Adulto , Anciano , Terapia Combinada , Progresión de la Enfermedad , Neoplasias Esofágicas/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Cuidados Preoperatorios , Pronóstico , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , Factores de Tiempo , Adulto JovenRESUMEN
Chronic intermittent hypoxia (CIH) is associated with increased production of reactive oxygen species that contributes to the adaptive mechanism underlying the improved myocardial ischemic tolerance. The aim was to find out whether the antioxidative enzyme manganese superoxide dismutase (MnSOD) can play a role in CIH-induced cardioprotection. Adult male Wistar rats were exposed to intermittent hypobaric hypoxia (7000 m, 8 h/day, 25 exposures) (n=14) or kept at normoxia (n=14). Half of the animals from each group received N-acetylcysteine (NAC, 100 mg/kg) daily before the hypoxic exposure. The activity and expression of MnSOD were increased by 66 % and 23 %, respectively, in the mitochondrial fraction of CIH hearts as compared with the normoxic group; these effects were suppressed by NAC treatment. The negative correlation between MnSOD activity and myocardial infarct size suggests that MnSOD can contribute to the improved ischemic tolerance of CIH hearts.
Asunto(s)
Acetilcisteína/farmacología , Depuradores de Radicales Libres/farmacología , Hipoxia , Daño por Reperfusión Miocárdica/prevención & control , Superóxido Dismutasa/metabolismo , Regulación hacia Arriba , Acetilcisteína/uso terapéutico , Animales , Depuradores de Radicales Libres/uso terapéutico , Masculino , Mitocondrias/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/metabolismo , Ratas , Ratas Wistar , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/genéticaRESUMEN
Protein kinase C (PKC) appears to play a significant role in the signal transduction of cardiac growth and development. The aim of this study was to determine changes in the total PKC activity and the expression of PKC isoforms alpha, delta and epsilon in the rat heart that was affected by pressure overload imposed at postnatal day (d) 2. Three groups of Wistar rats were employed for the experiment: rats submitted to the abdominal aortic constriction (AC), sham-operated controls (SO) and intact controls. Animals were sacrificed at d2, d3, d5 and d10. The total PKC activity was measured by the incorporation of (32)P into histone IIIS and the expression of PKC was analyzed by immunoblotting in the homogenate of the left ventricular myocardium and in the cytosolic, membrane-enriched (10(5) g) and nuclear-cytoskeletal-myofilament-enriched (10(3) g) fractions. We observed the significant transient increase in both the total PKC activity and the expression of all isoforms at d5 (the third day after the operation) in the cardiac homogenate of AC rats as compared with SO animals. Aortic constriction did not significantly affect the distribution of activity and isoform abundance among individual cellular fractions except for PKCdelta, which increased significantly at d10 in the cytosolic fraction at the expense of the membrane-enriched fraction. It is concluded that PKCalpha, PKCdelta and PKCepsilon undergo transient upregulation associated with the accelerated cardiac growth induced by pressure overload imposed in the very early postnatal period.
Asunto(s)
Cardiopatías/enzimología , Hipertensión/complicaciones , Miocardio/enzimología , Proteína Quinasa C/metabolismo , Animales , Animales Recién Nacidos , Presión Sanguínea , Western Blotting , Fraccionamiento Celular , Modelos Animales de Enfermedad , Cardiopatías/etiología , Cardiopatías/patología , Cardiopatías/fisiopatología , Histonas/metabolismo , Hipertensión/enzimología , Hipertensión/patología , Hipertensión/fisiopatología , Isoenzimas , Masculino , Miocardio/patología , Fosforilación , Proteína Quinasa C-alfa/metabolismo , Proteína Quinasa C-delta/metabolismo , Proteína Quinasa C-epsilon/metabolismo , Ratas , Ratas Wistar , Factores de Tiempo , Regulación hacia ArribaRESUMEN
Fluorophore types and their photochemical stability have been tested in two samples of humic acids (HA) and four types of fulvic acids (FA) extracted from upper soil horizons (O and A horizons) in Norway spruce forest mountain ecosystems. Only one type of fluorophore occurred in all samples, with an excitation maximum at 310 nm for both HA and FA samples and emission maxima between 420-435 and 440-450 for HA and FA, respectively. HA weak native fluorescence increased significantly during irradiation in the first 12 h. Fluorophores in FA were uniformly degraded from the beginning of irradiation. Addition of metal (aluminium or ferric) ions did not affect the positions of fluorescence maxima in any of the studied samples; mild effects on fluorescence intensities were observed.
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Aluminio/química , Benzopiranos/química , Colorantes Fluorescentes/química , Sustancias Húmicas/análisis , Hierro/química , Rayos Ultravioleta , IonesRESUMEN
Normal increase in hemodynamic load during early postnatal life is associated with heart growth and maturation of membrane structures that is accompanied by remodeling of membrane protein and lipid components. This review describes remodeling of phospholipids (PL) in rat myocardium during normal postnatal development and during accelerated cardiac growth induced by additional workload (aorta constriction, chronic hypoxia and hyperthyroidism) imposed on the heart early after birth. Normal physiological load after birth stimulates the development of membrane structures and synthesis of PL. While hyperthyroidism accelerates these processes, pressure overload has an inhibitory effect. These changes primarily influence the maturation of mitochondrial membranes as cardiolipin is one of the most affected PL species. The most sensitive part of PL structure in their remodeling process are PL acyl chains, particularly polyunsaturated fatty acids that are the key components determining the basic physicochemical properties of the membrane bilayer and thus the function of membrane-bound proteins and membrane-derived signaling lipid molecules. It is evident that PL remodeling may significantly influence both normal and pathological postnatal development of myocardium.
Asunto(s)
Corazón/crecimiento & desarrollo , Hemodinámica , Miocardio/metabolismo , Fosfolípidos/metabolismo , Adaptación Fisiológica , Factores de Edad , Animales , Ácidos Grasos Insaturados/metabolismo , Corazón/fisiopatología , Cardiopatías/metabolismo , Cardiopatías/fisiopatología , Mitocondrias Cardíacas/metabolismo , Membranas Mitocondriales/metabolismo , Conformación Molecular , Fosfolípidos/química , RatasRESUMEN
Total protein kinase C (PKC) activity, its isoform expression, and concentration and fatty acid (FA) composition of diacylglycerol (DAG) were determined in the left ventricular myocardium of the rat during early postnatal development (d 2, 3, 5, 7, and 10). PKC activity measured by the incorporation of 32P into histone IIIS decreased between d 2 and 10 in the homogenate as well as in cytosolic, membrane (100,000 g), and nuclear-cytoskeletal-myofilament fractions (1000 g). Likewise, the expression of PKC isoforms (alpha, delta, and epsilon) determined by immunoblotting generally declined during the period analyzed, although with a variable pattern. In the membrane and nuclear cytoskeletal myofilament fractions, PKCdelta and PKCepsilon expression decreased markedly by d 3, returning to or close to the d 2 level immediately on d 5. PKCalpha expression in the membrane fraction remained almost unchanged by d 7, declining thereafter. PKCdelta and PKCepsilon were associated predominantly with particulate fractions, whereas PKCalpha was more abundant in the cytosolic fraction. DAG concentration exhibited a significant decline by d 5, consistent with the decrease in maximal PKC activity. The unsaturation index of FA in DAG tended to decrease on d 3 owing to the lowered proportion of all polyunsaturated FA of n-6 and n-3 series. These results demonstrate that the developmental decrease in PKC activity and expression in the rat myocardium is not linear and that subcellular localization of the enzyme exhibits isoform-specific day-by-day changes during the early postnatal period. These changes are compatible with the view that PKC signaling may be involved in the control of a rapid switch of myocardial growth pattern during the first week of life.
Asunto(s)
Regulación del Desarrollo de la Expresión Génica/fisiología , Regulación Enzimológica de la Expresión Génica/fisiología , Miocardio/enzimología , Proteína Quinasa C/metabolismo , Envejecimiento/metabolismo , Animales , Activación Enzimática , Isoenzimas/metabolismo , Masculino , Ratas , Ratas Wistar , Distribución TisularRESUMEN
Malnutrition represents a serious risk factor, which can bring about prolongation of the hospitalization, higher incidence of complications and higher mortality. Such relation is well documented in several epidemiologic studies. The treatment of malnutrition, though large progress has been reached in the treatment, forms and indications of enteral and parenteral artificial nourishment, is based first of all on the elimination of the original cause, i.e. in the treatment of the primary disease. Nevertheless the role of artificial nourishment is irreplaceable. It serves as a supportive therapy namely to overcome the period till the alimentation per os is restituted. In other cases, when the normal alimentation route is not possible to restitute in sufficient extent, the parenteral or enteral artificial nourishment remain the permanent necessity and the life rescuing treatment.
Asunto(s)
Desnutrición/terapia , Apoyo Nutricional , Humanos , Desnutrición/etiología , Desnutrición/prevención & control , Factores de RiesgoRESUMEN
BACKGROUND: Oesophageal cancer patients with substantial weight loss have worse prognosis. Weight loss is often refractory to the nutritional support. Causes of the weight loss are multiple: oesophageal stricture, frequent alcohol abuse, cancer related cachexia. It may be a consequence of metabolic changes mediated by cytokines, hormones and tumour derived products. Leptin, a protein produced by adipocytes, is an important signalling molecule in energy regulation, metabolism of fatty acids and it can also augment tumour growth of various cancer cell lines. Enhanced intake of poly-unsaturated fatty acids may play an important role in the reversal of cancer related weight loss. METHODS AND RESULTS: In this study we examined the nutritional status (pre-treatment weight-loss, actual weight, body mass index), serum levels of leptin, soluble leptin receptor, TNF-alpha, IGF-1 and plasma phosphatidyl-cholin fatty acids before the beginning of treatment, after the onset of treatment and shortly before its completion. In the group of 38 pts (33 men, 5 women), mean age 58 years, statistically significant mean pre-treatment weight-loss 8 kg and significant mean weight loss 2 kg after chemoradiotherapy was observed. Concomitant chemoradiation led to transient elevation of serum leptin level despite the weight loss during chemoradiotherapy. Significant changes in the distribution of fatty acids in plasmatic phosphatidyl-cholin were observed. CONCLUSIONS: Our results show the possibility for direct influence of chemoradiotherapy on body weight regulation in advanced oesophageal cancer patients.
Asunto(s)
Neoplasias Esofágicas/sangre , Ácidos Grasos/sangre , Leptina/sangre , Receptores de Superficie Celular/sangre , Adulto , Anciano , Terapia Combinada , Neoplasias Esofágicas/terapia , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Persona de Mediana Edad , Fosfatidilcolinas/química , Receptores de Leptina , Factor de Necrosis Tumoral alfa/análisis , Pérdida de PesoRESUMEN
Anorexia nervosa is a model of simple starvation accompanied by secondary hyperlipoproteinemia. The pattern of plasma fatty acids influences the levels of plasma lipids and lipoproteins. The concentration of plasma lathosterol is a surrogate marker of cholesterol synthesis de novo, concentrations of campesterol and beta-sitosterol reflect resorption of exogenous cholesterol. The aim of the study was to evaluate fatty acids in plasma lipid classes and their relationship to plasma lipids, lipoproteins, cholesterol precursors and plant sterols. We examined 16 women with anorexia nervosa and 25 healthy ones. Patients with anorexia nervosa revealed increased concentrations of total cholesterol, triglycerides, HDL-cholesterol, campesterol and beta-sitosterol. Moreover, a decreased content of n-6 polyunsaturated fatty acids was found in all lipid classes. These changes were compensated by an increased content of monounsaturated fatty acids in cholesteryl esters, saturated fatty acids in triglycerides and both monounsaturated and saturated fatty acids in phosphatidylcholine. The most consistent finding in the fatty acid pattern concerned a decreased content of linoleic acid and a raised content of palmitoleic acid in all lipid classes. The changes of plasma lipids and lipoproteins in anorexia nervosa are the result of complex mechanisms including decreased catabolism of triglyceride-rich lipoproteins, normal rate of cholesterol synthesis and increased resorption of exogenous cholesterol.
Asunto(s)
Anorexia Nerviosa/sangre , Ácidos Grasos/sangre , Esteroles/sangre , Adulto , Apolipoproteínas/sangre , Ésteres del Colesterol/sangre , Cromatografía de Gases , Femenino , Humanos , Lípidos/sangre , Lipoproteínas/sangre , Pruebas de Función Hepática , Masculino , Fosfatidilcolinas/sangre , Triglicéridos/sangreRESUMEN
Samples of myocardial tissue were obtained during cardiac surgery from children operated for different types of normoxemic and hypoxemic congenital heart diseases. The phospholipid composition was analyzed by thin layer chromatography. The concentration of total phospholipids (PL), phosphatidylcholine and phosphatidylethanolamine (PE) was found lower in atrial tissue of both normoxemic and hypoxemic groups in comparison with the ventricles. When comparing the difference between hypoxemic and normoxemic defects, hypoxemia was found to increase the concentration of total PL, PE and phosphatidylserine in ventricles and total PL and PE in the atria. The increased level of particular phospholipid species may represent adaptive mechanisms to hypoxemia in children with congenital heart diseases.
Asunto(s)
Atrios Cardíacos/metabolismo , Cardiopatías Congénitas/metabolismo , Ventrículos Cardíacos/metabolismo , Hipoxia/metabolismo , Miocardio/metabolismo , Fosfolípidos/metabolismo , Niño , Femenino , Cardiopatías Congénitas/complicaciones , Humanos , Hipoxia/congénito , Masculino , Isquemia Miocárdica/congénito , Isquemia Miocárdica/metabolismo , Especificidad de Órganos , Distribución TisularRESUMEN
Hemodynamic support during the circulatory failure with vasodilation, most frequently during the septic shock, is based on volume recovery and administration of inotropic drugs. If such therapy is not sufficient, vasoconstriction drugs are subsequently or parallel added to maintain the perfusion pressure. As a standard therapy, norepinephrine or other catecholamines with alpha-adrenergic effect are used in rising doses. Some patients do not respond to such therapy with desired hemodynamic changes--they develop catecholamine resistant shock. Because of serious side effects of high doses of catecholamines, alternative vasopressors are necessary. Vasopressin, antidiuretic hormone, has in physiological conditions only minimal effect of the vascular tone. During hypovolemia its concentration rises and it may significantly contribute to the maintenance of arterial pressure by vasoconstriction. Contrary to it, during septic shock the levels of vasopressine are very low and vasodilation clinically dominates. At the same time, the septic shock is accompanied by an increased sensitivity to vasopressin administration. In a critical shock a serious deficit of endogenous vasopressin is expected. At present several pilot studies with vasopressine administration in septic shock exist in literature describing beneficial effect of vasopressin on hemodynamic parameters. Such comparatively low doses have no side effects on perfusion and function of body organs. Terlipressin, which is available in Czech Republic, is a synthetic analogue of vasopressin with extended effect. Its intermittent administration is used for the treatment of portal hypertension complications. Terlipressin in animal model of septic shock has similarly beneficial effects as vasopressin. High doses of Terlipressin have, similarly to vasopressin, adverse effects on pulmonary circulation and other systems. Till present, only casuistic experience has been published with low doses of Terlipressin in the treatment of septic shock resistant to catecholamines, which has shown similar effects to vasopressin. In shock states with the deficit of endogenous vasopressin, which are resistant to high doses of catecholamines, administration of vasopressin analogues represents a new perspective therapy. The treatment should be studied from the point of morbidity and mortality. A careful approach has to be used in septic patients with pre-existing obliterative vassal disease.
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Lipresina/análogos & derivados , Lipresina/uso terapéutico , Choque/tratamiento farmacológico , Vasoconstrictores/uso terapéutico , Animales , Humanos , Choque/fisiopatología , Choque Séptico/tratamiento farmacológico , Choque Séptico/fisiopatología , Terlipresina , Vasodilatación , Vasopresinas/fisiologíaRESUMEN
Heatstroke syndrome is a well-described state, which usually occurs in areas with warm climates. Two forms are commonly distinguished: the exertional and the classic heatstroke. Increased serum levels of liver enzymes are often detected in this condition. However, acute hepatic failure following exertional heatstroke is rare. We report a case of a 30 years old man with exertional heatstroke, acute hepatic failure, serious coagulation impairment and a rhabdomyolysis following ten kilometers run. Acute hepatic failure completely developed the forth day of hospitalisation. On the fifth day, the patient fulfilled London criteria for liver transplantation and was referred to the transplantation center for the optimal management assessment. After the conservative management of acute phase, spontaneous recovery of liver functions occurred and the patient finally was not transplanted. 23 days after admission to the hospital, the patient was discharged with residual cholestasis and was followed up on outpatient basis. Serum levels of liver enzyme returned to the normal 3 months after the liver injury. In several cases, the liver failure following heatstroke is reversible and conservative management can be successful. Additionally, in 3 reported cases, emergency liver transplantation for acute hepatic failure due to heatstroke with renal failure and coma showed very poor outcome. Our case demonstrates that conservative management even in patients fulfilling accepted criteria for emergency liver transplantation can be effective and should be considered in similar condition.
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Golpe de Calor/complicaciones , Fallo Hepático Agudo/etiología , Esfuerzo Físico , Adulto , Humanos , Fallo Hepático Agudo/diagnóstico , Fallo Hepático Agudo/terapia , Masculino , CarreraRESUMEN
Ventilator-associated pneumonia represents a severe complication in patients who are receiving mechanical ventilation. The incidence is presumed to be 25% of the total number of mechanically ventilated patients. The clinical assessment is usually based on the presence of a new radiographic infiltrate, fever, blood leukocytosis, or leukopenia and purulent tracheal secretions. According to the time after tracheal intubation when VAP occurs we can distinguish early and late onset VAP, which differs in terms of infectious agent. The early and adequate antibiotic therapy together with the basic preventive treatment represents the only possibility to avoid the complications. The article reviews the actual knowledge of this phenomenon, the adequate diagnostic attitudes and therapeutic possibilities.
Asunto(s)
Bronconeumonía/etiología , Infección Hospitalaria , Neumonía Bacteriana/etiología , Bronconeumonía/diagnóstico , Bronconeumonía/terapia , Unidades de Cuidados Coronarios , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/terapia , Humanos , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/terapia , Factores de RiesgoRESUMEN
The effect of the saprotrophic ascomycete Chalara longipes on the decomposition of humic acids was determined in a cultivation experiment. The fungus was incubated in liquid cultures in a full-strength (F system) and an organic nitrogen-free medium (F-N system), both amended with pure humic acids isolated from spruce forest litter. Fungal biomass production was highest in the F system with humic acids and lowest in the F-N system, the effect of organic nitrogen and humic acids being significant (p < 0.05). The presence of organic nitrogen seems to be essential for growth. The fungus utilized humic acids; molar mass distribution in media obtained by gel-permeation chromatography showed decrease in the humic acids fraction. Decolorization of the media reached 75 and 64 % in the F and F-N systems, respectively. The molar mass of humic acids probably also decreased as estimated from the increase in the absorbance A465/A665 (A4/A6) ratio. It is assumed that the utilization of humic acids may be mediated by the production of organic acids (as their components) and production of some oxidative enzymes.
Asunto(s)
Ascomicetos/metabolismo , Sustancias Húmicas/análisis , Picea/química , Ascomicetos/crecimiento & desarrollo , Biodegradación Ambiental , Biomasa , Ecosistema , Peso Molecular , Microbiología del SueloRESUMEN
Previous studies from our laboratory have indicated that secondary hyperaldosteronism affects phospholipids of rat colonic enterocytes. To assess whether this represents a direct effect of mineralocorticoids on enterocytes, the role of aldosterone and dexamethasone in the regulation of lipid metabolism was examined in Caco-2 cells during development of their enterocyte phenotype. Differentiation of Caco-2 cells was associated with increased levels of triglycerides (TG) and cholesteryl esters (CE), a decreased content of cholesterol and phospholipids and changes in individual phospholipid classes. The phospholipids of differentiated cells had a higher content of n-6 polyunsaturated fatty acids (PUFA) and lower amounts of monounsaturated (MUFA) and saturated fatty acids than subconfluent undifferentiated cells. Differentiated cells exhibited a higher ability to incorporate [3H]arachidonic acid (AA) into cellular phospholipids and a lower ability for incorporation into TG and CE. Incubation of subconfluent undifferentiated cells with aldosterone or dexamethasone was without effect on the content of lipids, their fatty acids and [3H]AA incorporation. In contrast, aldosterone treatment of differentiated cells diminished the content of TG, increased the content of phospholipids and modulated their fatty acid composition. The percentage of n-6 and n-3 PUFA in phospholipids was increased and that of MUFA decreased, whereas no changes in TG were observed. The incorporation of [3H]AA into phospholipids was increased and into TG decreased and these changes were blocked by spironolactone. Treatment of differentiated cells with dexamethasone increased their CE content but no effect was identified upon other lipids, their fatty acid composition and on the incorporation of [3H]AA. As expected for the involvement of corticosteroid hormones the mineralocorticoid and glucocorticoid receptors were identified in Caco-2 cells by RT-PCR. The results suggest that aldosterone had a profound influence on lipid metabolism in enterocytes and that its effect depends on the stage of differentiation. The aldosterone-dependent changes occurring in phospholipids and their fatty acid composition may reflect a physiologically important phenomenon with long-term consequences for membrane structure and function.
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Aldosterona/farmacología , Diferenciación Celular/fisiología , Dexametasona/farmacología , Enterocitos/efectos de los fármacos , Enterocitos/metabolismo , Metabolismo de los Lípidos , Aldosterona/metabolismo , Ácido Araquidónico/metabolismo , Células CACO-2 , Colesterol/metabolismo , Enterocitos/citología , Ácidos Grasos/metabolismo , Humanos , Fosfolípidos/metabolismo , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Receptores de Glucocorticoides/biosíntesis , Receptores de Mineralocorticoides/biosíntesis , Espironolactona/farmacología , Triglicéridos/metabolismo , TritioRESUMEN
BACKGROUND: Anorexia nervosa is a model of simple starvation accompanied by secondary hyperlipoproteinemia. Plasma fatty acid pattern influences levels of plasma lipids and lipoproteins. Level of plasma lathosterol represents a marker of cholesterol synthesis de novo; levels of plant sterols reflect resorption of exogenous cholesterol. The aim of the study was to evaluate fatty acids in plasma lipid classes and their relationships to plasma lipids, lipoproteins, lathosterol, campesterol and beta-sitosterol. METHODS AND RESULTS: We examined 16 women with anorexia nervosa and 25 matched controls. Main lipid classes were separated by thin-layer chromatography, fatty acids and non-cholesterol sterols were evaluated by capillary gas chromatography. Patients with anorexia nervosa revealed increased concentrations of total cholesterol, triglycerides, HDL-cholesterol, campesterol and beta-sitosterol; changes in plasma levels of lathosterol did not reach statistical significance. The most consistent finding in fatty acid composition was a decreased content of linoleic acid and raised content of palmitoleic acid in all lipid classes. CONCLUSIONS: Changes of plasma lipids and lipoproteins in anorexia nervosa result from complex mechanisms including increased synthesis of triglyceride-rich lipoproteins along with unchanged cholesterol synthesis rate. Hypercholesterolemia in anorexia nervosa may also result from increased resorption of exogenous cholesterol.