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1.
J Synchrotron Radiat ; 21(Pt 3): 594-9, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24763650

RESUMEN

The progress of tomographic coherent diffractive imaging with hard X-rays at the ID10 beamline of the European Synchrotron Radiation Facility is presented. The performance of the instrument is demonstrated by imaging a cluster of Fe2P magnetic nanorods at 59 nm 3D resolution by phasing a diffraction volume measured at 8 keV photon energy. The result obtained shows progress in three-dimensional imaging of non-crystalline samples in air with hard X-rays.

2.
Artículo en Inglés | MEDLINE | ID: mdl-21721370

RESUMEN

BACKGROUND: Pollen is one of the main causes of allergic sensitization. It is not easy to make an etiological diagnosis of pollen-allergic patients because of the wide variety of sensitizing pollens, association with food allergy, and increasing incidence of polysensitization, which may result from the presence of allergens that are common to different species, as is the case of panallergens. OBJECTIVE: To compare the results of skin prick tests (SPT) using whole pollen extract with specific immunoglobulin (Ig) E determination for several allergens (purified panallergens included) in the diagnosis of polysensitized pollen-allergic patients. METHODS: The study sample comprised 179 pollen-sensitized patients who underwent SPT with pollen extract and allergen-specific IgE determination against different allergens. RESULTS: The level of concordance between the traditional diagnostic test (SPT) and IgE determination was low, especially in patients sensitized to the panallergens profilin and polcalcin. In the case of SPT, the results demonstrated that patients who are sensitized to either of these panallergens present a significantly higher number of positive results than patients who are not. However, IgE determination revealed that while patients sensitized to polcalcins are sensitized to allergens from a higher number of pollens than the rest of the sample, this is not the case in patients sensitized to profilins. On the other hand, sensitization to profilin or lipid transfer proteins was clearly associated with food allergy. CONCLUSIONS: Sensitization to panallergens could be a confounding factor in the diagnosis of polysensitized pollen-allergic patients as well as a marker for food allergy. However, more studies are required to further investigate the role of these molecules.


Asunto(s)
Alérgenos/inmunología , Inmunoglobulina E/inmunología , Polen/inmunología , Rinitis Alérgica Estacional/diagnóstico , Adolescente , Adulto , Anciano , Especificidad de Anticuerpos , Antígenos de Plantas/inmunología , Asma/diagnóstico , Asma/etiología , Asma/inmunología , Proteínas de Unión al Calcio/inmunología , Niño , Conjuntivitis Alérgica/diagnóstico , Conjuntivitis Alérgica/etiología , Conjuntivitis Alérgica/inmunología , Femenino , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/etiología , Hipersensibilidad a los Alimentos/inmunología , Humanos , Inmunoglobulina E/sangre , Masculino , Persona de Mediana Edad , Profilinas/inmunología , Rinitis Alérgica Estacional/etiología , Rinitis Alérgica Estacional/inmunología , Pruebas Cutáneas , Especificidad de la Especie , Encuestas y Cuestionarios , Adulto Joven
3.
Allergol Immunopathol (Madr) ; 39(2): 79-84, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21236554

RESUMEN

INTRODUCTION: Sensitisation to Alternaria is a cause of respiratory disease in Spain, particularly in childhood, but it is also a significant marker of the severity of this disease. Therefore, the use of an aetiological treatment (allergen specific immunotherapy) is essential, and both subjective and objective clinical parameters should be used to follow up this treatment. OBJECTIVE: This open-label, uncontrolled, observational, prospective study was designed in order to study the evolution of these patients on allergen specific immunotherapy therapy in daily clinical practice and to assess the use of different monitoring tools. MATERIAL AND METHODS: A total of 99 patients were included. They were monosensitised to this perennial allergen and treated with subcutaneous allergen specific immunotherapy. After one year of follow-up, these patients were assessed for the presence of symptoms, use of medication, clinical incidents, quality of life and asthma control. RESULTS: After one year of treatment a significant fall was observed in the use of concomitant medication (ß2-agonists: p=0.0278, inhaled corticosteroids: p=0.0007, anti-leukotrienes: p=0.0495), nasal symptoms (p=0.0081), quality of life (PAQLQ, p<0.0001) and asthma control (ACQ, p<0.0001). Twenty-one patients had to attend emergency department due to exacerbation of their allergic disease, and only one of them had to be admitted to hospital. CONCLUSION: respiratory allergic disease due to Alternaria alternata is a disease which is hard to control, and in our daily practice, the use of specific subcutaneous immunotherapy can be of significant benefit in our paediatric patients.


Asunto(s)
Desensibilización Inmunológica , Hipersensibilidad Respiratoria/tratamiento farmacológico , Adolescente , Alternaria , Antiinflamatorios/uso terapéutico , Antígenos de Plantas/inmunología , Antígenos de Plantas/uso terapéutico , Asma , Niño , Preescolar , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Inyecciones Subcutáneas , Masculino , Calidad de Vida , Hipersensibilidad Respiratoria/inmunología , España
4.
J Exp Med ; 183(6): 2571-9, 1996 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-8676078

RESUMEN

It has been demonstrated that neutrophils from healthy donors or from patients with inflammatory disorders can bind immunoglobulin (Ig) E proteins through binding to Mac-2/epsilon bp. Functional responses to allergens were assessed by measuring the respiratory burst and intracellular Ca2+ levels, and binding of allergens to neutrophils was assessed by flow cytometry analysis and fluorescence microscopy. In this article, we demonstrate that neutrophils sensitized to specific allergens (from allergic patients), but not from healthy donors, are sensitive to allergens of the same type as those that produce clinical allergic symptoms. The activation of neutrophils was analyzed by the induction of a respiratory burst that was detected with luminol-dependent chemiluminescence. Intracellular Ca2+ levels increased parallel to those of the inducing allergens. In addition, the specific binding of allergens on the cell surface was revealed by flow cytometry and allergen-FITC-labeled staining analyses. The present data suggest a restricted recognition of allergen by sensitive neutrophils, probably associated with the specific binding of the allergen to its corresponding IgE molecule, which is bound to the Mac-2/epsilon bp structure. These findings demonstrate a functional role of allergen-associated neutrophils during the allergic state.


Asunto(s)
Alérgenos , Antígenos , Diterpenos , Hipersensibilidad/sangre , Hipersensibilidad/inmunología , Neutrófilos/inmunología , Antígenos de Diferenciación/inmunología , Carcinógenos/farmacología , Galectina 3 , Humanos , Inmunoglobulina E/sangre , Inflamación/inmunología , Glicoproteínas de Membrana/inmunología , Neutrófilos/efectos de los fármacos , Poaceae , Valores de Referencia , Terpenos/farmacología
5.
Allergy ; 63(11): 1550-8, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18925892

RESUMEN

BACKGROUND: Allergy diagnosis in patients exposed to multiple pollen species is complex and misdiagnosis is often a cause for unsuccessful specific immunotherapy. OBJECTIVE: We studied the sensitization profile of individual allergens (major, minor and pan-allergens) in pollen-sensitized patients in a region with high exposure to olive pollen by investigating the influence of minor allergens on allergic disease and the association between pan- and minor allergen sensitizations. METHODS: A panel of 13 purified allergens, which included the most relevant allergens in the area, as well as minor olive allergens and pan-allergens, were screened using a high-capacity technology (ADVIA-Centaur) in 891 patients. RESULTS: Olive allergy as measured by specific IgE to Ole e 1 was the leading pollinosis in the area. The minor olive allergens Ole e 7 and Ole e 9 were markers of more severe allergic illness. Profilin sensitization was associated mainly with grass allergy, the second most prevalent pollinosis. Salsola kali pollen allergy was the third most common cause of pollinosis in the area. The prevalence of sensitization to the peach allergen Pru p 3, a nonspecific lipid-transfer protein, was notable. CONCLUSION: Epidemiological analysis by component-resolved diagnosis is a new method, which elucidates the interaction between allergen exposure gradient and patient sensitization. High exposure leads to differential sensitization profiles some of which are associated with more severe allergic conditions. Profilin sensitization, related mainly to grass pollinosis, was a marker of more severe grass pollen sensitization.


Asunto(s)
Alérgenos/inmunología , Olea/inmunología , Polen/inmunología , Profilinas/inmunología , Rinitis Alérgica Estacional/epidemiología , Humanos , Inmunoglobulina E/sangre , Epidemiología Molecular , Poaceae/inmunología , Rinitis Alérgica Estacional/diagnóstico , Rinitis Alérgica Estacional/inmunología , España/epidemiología
6.
J Clin Invest ; 96(2): 665-75, 1995 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-7635959

RESUMEN

To elucidate mechanisms of glucagon-induced bicarbonate-rich choleresis, we investigated the effect of glucagon on ion transport processes involved in the regulation of intracellular pH (pHi) in isolated rat hepatocyte couplets. It was found that glucagon (200 nM), without influencing resting pHi, significantly stimulates the Cl-/HCO3- exchange activity. The effect of glucagon was associated with a sevenfold increase in cAMP levels in rat hepatocytes. The activity of the Cl-/HCO3- exchanger was also stimulated by DBcAMP + forskolin. The effect of glucagon on the Cl-/HCO3- exchange was individually blocked by two specific and selective inhibitors of protein kinase A, Rp-cAMPs (10 microM) and H-89 (30 microM), the latter having no influence on the glucagon-induced cAMP accumulation in isolated rat hepatocytes. The Cl- channel blocker, NPPB (10 microM), showed no effect on either the basal or the glucagon-stimulated Cl-/HCO3 exchange. In contrast, the protein kinase C agonist, PMA (10 microM), completely blocked the glucagon stimulation of the Cl-/HCO3- exchange; however, this effect was achieved through a significant inhibition of the glucagon-stimulated cAMP accumulation in rat hepatocytes. Colchicine pretreatment inhibited the basal as well as the glucagon-stimulated Cl-/HCO3- exchange activity. The Na+/H+ exchanger was unaffected by glucagon either at basal pHi or at acid pHi values. In contrast, glucagon, at basal pHi, stimulated the Na(+)-HCO3- symport. The main findings of this study indicate that glucagon, through the cAMP-dependent protein kinase A pathway, stimulates the activity of the Cl-/HCO3- exchanger in isolated rat hepatocyte couplets, a mechanism which could account for the in vivo induced bicarbonate-rich choleresis.


Asunto(s)
Antiportadores/efectos de los fármacos , Bilis/metabolismo , Colagogos y Coleréticos/farmacología , Glucagón/farmacología , Hígado/efectos de los fármacos , Intercambiadores de Sodio-Hidrógeno/efectos de los fármacos , Sulfonamidas , Animales , Bicarbonatos/metabolismo , Bucladesina/farmacología , Células Cultivadas , Antiportadores de Cloruro-Bicarbonato , Cloruros/metabolismo , Colchicina/farmacología , Colforsina/farmacología , AMP Cíclico/análogos & derivados , AMP Cíclico/farmacología , Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Proteínas Quinasas Dependientes de AMP Cíclico/fisiología , Concentración de Iones de Hidrógeno , Líquido Intracelular/efectos de los fármacos , Isoquinolinas/farmacología , Masculino , Nitrobenzoatos/farmacología , Ratas , Ratas Wistar , Sodio/metabolismo , Acetato de Tetradecanoilforbol/farmacología , Tionucleótidos/farmacología
7.
Value Health ; 10(6): 466-77, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17970929

RESUMEN

OBJECTIVES: To develop and validate an instrument to measure health-related quality of life (HRQOL) specific to patients with allergic rhinitis (AR) and primarily for use in Spanish and Spanish-speaking populations. METHODS: An initial item pool was generated from literature review, focus groups with AR patients, and consultations with clinical experts. Item reduction was performed using clinimetric and psychometric approaches after administration of the item pool to 400 AR patients. The resulting instrument's internal consistency, test-retest (2-4 weeks) reliability, known groups and convergent validity, and sensitivity to change were tested in a longitudinal, observational, multicenter study in 210 AR patients who also completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ). RESULTS: The new questionnaire took a mean (SD) of 7.1 (5.4) minutes to answer. Floor and ceiling effects were less than 15% on all dimensions. Cronbach's alpha values and intraclass correlation coefficient values for six of the sevendimensions and the overall score exceeded 0.70. Statistically significant differences (P < 0.01) were observed on all ESPRINT-28 dimensions and the overall score between patients with mild (mean overall score 1.97, SD 0.99), moderate (mean overall score 2.78, SD 0.88), and severe AR (mean overall score 3.89, SD 0.87). Patients with persistent AR had worse scores (P < 0.05) on all dimensions than patients with intermittent AR. Correlations between the ESPRINT-28 and the RQLQ were generally as expected. Effect sizes for score changes between the two study visits ranged from 0.96 to 1.76 for individual dimensions and the overall score. CONCLUSIONS: This new, Spanish-developed instrument to measure HRQOL in AR patients has shown good reliability, validity, and sensitivity to change. It has also proved easy to use and administer.


Asunto(s)
Estado de Salud , Calidad de Vida , Rinitis Alérgica Perenne , Rinitis Alérgica Estacional , Encuestas y Cuestionarios , Adulto , Femenino , Humanos , Estudios Longitudinales , Masculino , Reproducibilidad de los Resultados , España
8.
Nanoscale ; 9(16): 5094-5101, 2017 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-28397910

RESUMEN

Hysteresis losses in magnetic nanoparticles constitute the basis of magnetic hyperthermia for delivering a local thermal stress. Nevertheless, this therapeutic modality is only to be realised through a careful appraisal of the best possible intrinsic and extrinsic conditions to the nanoparticles for which they maximise and preserve their heating capabilities. Low frequency (100 kHz) hysteresis loops accurately probe the dynamical magnetic response of magnetic nanoparticles in a more reliable manner than calorimetry measurements, providing conclusive quantitative data under different experimental conditions. We consider here a set of iron oxide or cobalt ferrite nanocubes of different sizes, through which we experimentally and theoretically study the influence of the viscosity of the medium on the low frequency hysteresis loops of magnetic colloids, and hence their ability to produce and dissipate heat to the surroundings. We analyse the role of nanoparticle size, size distribution, chemical composition, and field intensity in making the magnetisation dynamics sensitive to viscosity. Numerical simulations using the stochastic Landau-Lifshitz-Gilbert equation model the experimental observations in excellent agreement. These results represent an important contribution towards predicting viscosity effects and hence to maximise heat dissipation from magnetic nanoparticles regardless of the environment.

9.
J Mater Chem B ; 5(24): 4587-4594, 2017 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-29308203

RESUMEN

With the aim of producing Au-Fe x O y dimers with outstanding heating performances under magnetic hyperthermia conditions applicable to human patients, here we report two synthesis routes, a two-pot and a one-pot method. The addition of chloride ions and the absence of 1,2-hexadecanediol (HDDOL), a commonly used chemical in this synthesis, are the key factors that enable us to produce dimers at low temperature with crystalline iron oxide domains in the size range between 18-39 nm that is ideal for magnetic hyperthermia. In the case of two-pot synthesis, in which no chloride ions are initially present in the reaction pot, dimers are obtained only at 300 °C. In order to lower the reaction temperature to 200 °C and to tune the size of the iron oxide domain, the addition of chloride ions becomes the crucial parameter. In the one-pot method, the presence of chloride ions from the start of the synthesis (as counter ions of the gold salt precursor) enables a prompt formation of dimers directly at 200 °C. In this case, the reaction time is the main parameter used to tune the iron oxide size. A record value of specific absorption rates (SARs) up to 1300 W gFe-1 at 330 kHz and 24 kA m-1 was measured for dimers with an iron oxide domain of 24 nm in size.

10.
Transplant Proc ; 38(5): 1389-93, 2006 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16797312

RESUMEN

OBJECTIVE: The aim of this open/retrospective study was to evaluate the outcomes of intensive care unit patients treated for fulminant hepatic failure (FHF) for predictive indices. METHODS: All patients were recovered in the intensive care units with a diagnosis of FHF. We considered three groups of patients: (1) survivors, deceased, and transplanted. SUBJECTS: All patients were fully screened, including liver function indices such as AST, ALT, total and bound bilirubin, albumin and pre-albumin, factors 5 and 7, alpha fetal protein (alpha-PP), other coagulation tests (PT, aPTT, INR, ATIII), and renal function (BUN and creatinine) parameters. For each patient Apache II score was calculated upon admission to the intensive care unit. RESULTS: Apache II score showed efficacy. alpha-PP increased in both surviving and deceased, but not in the transplanted group. After intensive care unit admission, AST and ALT peaks were higher in the deceased DP than in the transplanted group. The INR value at the third day after ICU admission improved in the survivors compared with the other two cohorts. Factor 5 levels were lower among patients undergoing transplantation, but increased in the other two groups. The prognosis was strictly dependent upon the development of renal failure. CONCLUSION: The Apache II score was a sensitive predictive index for outcome. alpha-PP and factor 5 were not related to outcome, but useful for decision making when determining potential liver transplantation. INR can be used as a prognostic index. Intensive treatment beforehand is of primary importance to prevent multiple organ failure.


Asunto(s)
Cuidados Críticos , Fallo Hepático Agudo/terapia , Trasplante de Hígado , APACHE , Adulto , Femenino , Humanos , Pruebas de Función Renal , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/cirugía , Masculino , Tasa de Supervivencia , Sobrevivientes , Resultado del Tratamiento
11.
Biochim Biophys Acta ; 1214(1): 63-72, 1994 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-8068730

RESUMEN

Crystal observation time is a rough estimate of the first microscopic appearance of cholesterol monohydrate crystals in an isotropic bile, and does not provide information on crystal growth kinetics. We have developed a method for quantitating cholesterol crystal growth in gallbladder bile. Crystals were separated from other biliary particles by ultracentrifugation on a discontinuous NaBr gradient, after bile density adjustment to d = 1.060 g/ml. More than 95% of crystals, both of native or synthetic source, floated in the density range 1.045-1.055. This density fraction was collected and crystal mass was measured by photometric turbidity, after calibration with suspensions of different-sized cholesterol crystals. The recovery of crystals added to original bile samples averaged 96.0 +/- 2.8%. Contamination with vesicles, which may potentially interfere with the turbidimetric assay, was excluded by gel-chromatography. The method was sequentially applied, until the 20th day of incubation, to biles obtained at surgery from patients with (A, n = 6) or without cholesterol gallstone (B, n = 4), and from gallstone patients pretreated for 1 week with oral ursodeoxycholic acid (C, n = 5). Crystal growth curves greatly differed, being much steeper in group A and almost flat in patients receiving ursodeoxycholic acid. The mean percent mass of biliary cholesterol in crystalline form at the 20th day was 19.2 +/- 13.5%, 1.2 +/- 0.8% and 2.7 +/- 1.1% in A, B and C, respectively (A vs. B: P = 0.014; A vs. C: P = 0.008). We conclude that the method allows a precise estimate of cholesterol crystal growth and can be usefully applied to human gallbladder biles.


Asunto(s)
Bilis/química , Colesterol/química , Vesícula Biliar/metabolismo , Centrifugación por Gradiente de Densidad , Ácido Quenodesoxicólico/farmacología , Colelitiasis/metabolismo , Colesterol/aislamiento & purificación , Cristalización , Humanos , Cinética , Nefelometría y Turbidimetría , Espectrofotometría , Ácido Ursodesoxicólico/farmacología
12.
Aliment Pharmacol Ther ; 14 Suppl 2: 54-7, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10903005

RESUMEN

Parenteral nutrition is often associated with hepatobiliary complications. Hepatic steatosis, intrahepatic cholestasis and biliary sludge are the most frequent. Cholestasis predominates in infants, steatosis in adults, and biliary sludge in both. Other less frequent complications are steatohepatitis and gallstones. All hepatobiliary complications are more likely to occur after extended periods of total parenteral nutrition, and are prevented by the concomitant consumption of nutrients by the enteral route. The pathogenic causes are multiple and only partially known. They include lack of gastrointestinal stimuli for biliary secretion and gall-bladder motility, abnormalities in bile acid metabolism, the presence of sepsis, and the potentially unfavourable effects of individual components in the total parenteral nutrition formulae, including an excess of calories. Each potential mechanism and its clinical relevance is discussed in this review.


Asunto(s)
Colelitiasis/etiología , Colestasis Intrahepática/etiología , Motilidad Gastrointestinal , Nutrición Parenteral Total/efectos adversos , Adulto , Bilis , Humanos , Recién Nacido
13.
Artículo en Inglés | MEDLINE | ID: mdl-9161938

RESUMEN

Serum IgE levels have been documented in patients of acute type B hepatitis. There are very few studies on serum IgE in acute type A hepatitis and, to our knowledge, there are no data on serum IgE in acute delta hepatitis patients. The purpose of this study was to measure total IgE levels in 38 patients with acute A, B and delta hepatitis and in 181 controls in order to determine the possible existence of changes in this parameter in the course of these infections. Our results showed a relevant increase in IgE levels in the three groups (hepatitis A, B and delta) with respect to the control group. Moreover, the hepatitis B group showed increased total serum IgE levels with respect to the hepatitis delta group.


Asunto(s)
Hepatitis A/inmunología , Hepatitis B/inmunología , Hepatitis D/inmunología , Inmunoglobulina E/análisis , Inmunoglobulina E/metabolismo , Enfermedad Aguda , Adulto , Anciano , Niño , Femenino , Hepatitis A/sangre , Hepatitis B/sangre , Hepatitis D/sangre , Humanos , Masculino , Persona de Mediana Edad
14.
Artículo en Inglés | MEDLINE | ID: mdl-14989109

RESUMEN

In order to evaluate the tolerance of a cluster schedule on specific immunotherapy (SIT), 306 patients were included in a multicenter study. The patients were suffering from rhinoconjunctivitis with/without asthma, caused by sensitization to olive and/or grass pollen. SIT was administered subcutaneously according to a cluster schedule in which the maintenance dose is reached after four visits (3 weeks). The extracts were biologically standardized with major allergens quantified in mass units. Local reactions appeared in 7.2% of the patients and 1.3% of the doses. Systemic reactions (SR) were recorded in 1.2% of the doses administered to 9.5% of the patients. No anaphylactic shock was registered, and all the SR responded fully and rapidly to treatment. There was no difference in SR according to diagnosis or allergen extract used. The majority of SR occurred with the administration of vial of higher concentration (Vial 2: 7 SR (22%), Vial 3: 32 SR (78%), p < 0.05). Of the 32 SR recorded with Vial 3, 13 (41%) were immediate, with no existing association between dose administered and appearance of SR. However, of the 18 delayed SR (56%), 14 occurred after the administration of the first two doses of Vial 3 and four occurred after administration of the second two doses (78% vs 22%, p < 0.05). On the other hand, this regime realized an important saving in cost and time compared to the conventional schedule (1581 fewer doses and 2754 fewer visits were necessary to reach the optimal dose). Considering all these factors, the clinical profile of the proposed regime may be qualified as good. However, future studies are necessary in order to better adjust the schedule to avoid the delayed SR that occurred after the administration of the first two doses of Vial 3.


Asunto(s)
Inmunización/métodos , Inmunoterapia/métodos , Olea/inmunología , Polen/inmunología , Hipersensibilidad Respiratoria/terapia , Adulto , Alérgenos/administración & dosificación , Asma/terapia , Conjuntivitis Alérgica/terapia , Tolerancia a Medicamentos , Femenino , Humanos , Masculino , Rinitis Alérgica Estacional/terapia , Seguridad , Estaciones del Año
15.
Free Radic Res ; 48(12): 1494-504, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25236567

RESUMEN

Beta cell destruction in type 1 diabetes (TID) is associated with cellular oxidative stress and mitochondrial pathway of cell death. The aim of this study was to determine whether oxidative stress and mitochondrial dysfunction are present in T1D model (non-obese diabetic mouse, NOD) and if they are related to the stages of disease development. NOD mice were studied at three stages: non-diabetic, pre-diabetic, and diabetic and compared with age-matched Balb/c mice. Mitochondria respiration rates measured at phosphorylating and resting states in liver and soleus biopsies and in isolated liver mitochondria were similar in NOD and Balb/c mice at the three disease stages. However, NOD liver mitochondria were more susceptible to calcium-induced mitochondrial permeability transition as determined by cyclosporine-A-sensitive swelling and by decreased calcium retention capacity in all three stages of diabetes development. Mitochondria H2O2 production rate was higher in non-diabetic, but unaltered in pre-diabetic and diabetic NOD mice. The global cell reactive oxygen species (ROS), but not specific mitochondria ROS production, was significantly increased in NOD lymphomononuclear and stem cells in all disease stages. In addition, marked elevated rates of 2',7'-dichlorodihydrofluorescein (H2DCF) oxidation were observed in pancreatic islets from non-diabetic NOD mice. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) and lipidomic approach, we identified oxidized lipid markers in NOD liver mitochondria for each disease stage, most of them being derivatives of diacylglycerols and phospholipids. These results suggest that the cellular oxidative stress precedes the establishment of diabetes and may be the cause of mitochondrial dysfunction that is involved in beta cell death.


Asunto(s)
Enfermedades Autoinmunes/metabolismo , Diabetes Mellitus Experimental/metabolismo , Mitocondrias/metabolismo , Proteínas de Transporte de Membrana Mitocondrial/metabolismo , Estrés Oxidativo , Animales , Femenino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos NOD , Poro de Transición de la Permeabilidad Mitocondrial , Permeabilidad , Especies Reactivas de Oxígeno/metabolismo
16.
Front Physiol ; 4: 103, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23720630

RESUMEN

Mitochondrial redox imbalance has been implicated in mechanisms of aging, various degenerative diseases and drug-induced toxicity. Statins are safe and well-tolerated therapeutic drugs that occasionally induce myotoxicity such as myopathy and rhabdomyolysis. Previous studies indicate that myotoxicity caused by statins may be linked to impairment of mitochondrial functions. Here, we report that 1-h incubation of permeabilized rat soleus muscle fiber biopsies with increasing concentrations of simvastatin (1-40 µM) slowed the rates of ADP-or FCCP-stimulated respiration supported by glutamate/malate in a dose-dependent manner, but caused no changes in resting respiration rates. Simvastatin (1 µM) also inhibited the ADP-stimulated mitochondrial respiration supported by succinate by 24% but not by TMPD/ascorbate. Compatible with inhibition of respiration, 1 µM simvastatin stimulated lactate release from soleus muscle samples by 26%. Co-incubation of muscle samples with 1 mM L-carnitine, 100 µM mevalonate or 10 µM coenzyme Q10 (Co-Q10) abolished simvastatin effects on both mitochondrial glutamate/malate-supported respiration and lactate release. Simvastatin (1 µM) also caused a 2-fold increase in the rate of hydrogen peroxide generation and a decrease in Co-Q10 content by 44%. Mevalonate, Co-Q10 or L-carnitine protected against stimulation of hydrogen peroxide generation but only mevalonate prevented the decrease in Co-Q10 content. Thus, independently of Co-Q10 levels, L-carnitine prevented the toxic effects of simvastatin. This suggests that mitochondrial respiratory dysfunction induced by simvastatin, is associated with increased generation of superoxide, at the levels of complexes-I and II of the respiratory chain. In all cases the damage to these complexes, presumably at the level of 4Fe-4S clusters, is prevented by L-carnitine.

18.
Nanotechnology ; 19(47): 475704, 2008 Nov 26.
Artículo en Inglés | MEDLINE | ID: mdl-21836285

RESUMEN

The effect of surface anisotropy on the distribution of energy barriers in magnetic fine particles of nanometer size is discussed within the framework of the Tln(t/τ(0)) scaling approach. The comparison between the distributions of the anisotropy energy of the particle cores, calculated by multiplying the volume distribution by the core anisotropy, and of the total anisotropy energy, deduced by deriving the master curve of the magnetic relaxation with respect to the scaling variable Tln(t/τ(0)), enables the determination of the surface anisotropy as a function of the particle size. We show that the contribution of the particle surface to the total anisotropy energy can be well described by a size-independent value of the surface energy per unit area which permits the superimposition of the distributions corresponding to the particle core and effective anisotropy energies. The method is applied to a ferrofluid composed of non-interacting Fe(3-x)O(4) particles of 4.9 nm average size and x about 0.07. Even though the size distribution is quite narrow in this system, a relatively small value of the effective surface anisotropy constant K(s) = 2.9 × 10(-2) erg cm(-2) gives rise to a dramatic broadening of the total energy distribution. The reliability of the average value of the effective anisotropy constant, deduced from magnetic relaxation data, is verified by comparing it to that obtained from the analysis of the shift of the ac susceptibility peaks as a function of the frequency.

19.
Clin Exp Allergy ; 35(9): 1204-13, 2005 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16164449

RESUMEN

BACKGROUND: L-selectin (CD62L) is an adhesion molecule involved in leucocyte attachment to endothelium at sites of inflammation, and it has been demonstrated that L-selectin is rapidly shed after neutrophil activation. Recently, it has been reported that there is increasing evidence of neutrophil participation in asthma and the allergic process. OBJECTIVE: The present study was designed to determine whether an IgE-dependent mechanism can modulate L-selectin expression on the surface of neutrophils. Moreover, we analyse the potential implication of intracellular signal-transduction pathways and whether specific immunotherapy (IT), glucocorticoids and antihistamines might regulate this process. METHODS: Peripheral blood neutrophils from three groups of donors (asthmatic group without IT treatment, IT-treated asthmatic group and healthy group) were used. Cells were challenged in vitro with the specific allergen that produced clinical symptoms in asthmatic patients and also with the allergen to which the patients were not sensitive. Neutrophils from healthy donors were also challenged with allergens. Expression of CD62L on the neutrophil surface was analysed by flow cytometry, and soluble CD62L (sCD62L) in culture supernatant by ELISA. In an attempt to discover which IgE receptor is involved, we also challenged the neutrophils with monoclonal antibody to FcepsilonRI, FcepsilonRII (CD23) and galectin-3 receptors. RESULTS: When neutrophils from allergic patients were challenged with specific allergens that produce clinical allergy symptoms, L-selectin was down-regulated from the surface of those cells, accompanied by a concomitant up-regulation of soluble L-selectin in the supernatant. The challenge with antibodies against FCepsilonRI, FCepsilonRII (CD23) and galectin-3, induces down-modulation of L-selectin on the surface of the neutrophils in all three cases. Calphostin C, wortmannin and manoalide attenuated CD62L down-regulation, suggesting the potential implication of protein kinase C, phosphatidylinositol 3-kinase and phospholipase A(2) in the process. IT and glucocorticoids modulated allergen-dependent CD62L down-regulation, whereas antihistamines (terfenadine, loratadine and cetirizine) or nedocromil sodium did not affect the shedding of L-selectin. CONCLUSIONS: We present evidence that the neutrophil surface expression of CD62L can be modulated by an allergen-dependent mechanism. The modulation of CD62L expression can be induced through the three receptors of IgE. This process can be affected by IT.


Asunto(s)
Hipersensibilidad/metabolismo , Inmunoglobulina E/inmunología , Selectina L/análisis , Neutrófilos/química , Adolescente , Adulto , Alérgenos/farmacología , Análisis de Varianza , Estudios de Casos y Controles , Células Cultivadas , Medios de Cultivo Condicionados/química , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Citometría de Flujo , Humanos , Hipersensibilidad/inmunología , Hipersensibilidad/terapia , Inmunoterapia , Masculino , Persona de Mediana Edad , Factores de Tiempo
20.
An Esp Pediatr ; 29(1): 15-22, 1988 Jul.
Artículo en Español | MEDLINE | ID: mdl-3056141

RESUMEN

Cholesterol, low/high density lipoprotein cholesterol (LDLc, HDLc), triglycerides and phospholipids plasma concentrations were measured in arterial (UA) and venous (UV) cord blood samples collected at birth in 22 healthy newborn infants (G-I) in 24 intrapartum stressed newborn infants (G-II) and in plasma of their 46 mothers at delivery. Chol was measured by ALLAIN'S, HDLcUA by LOPES-VIRELLA'S (and LDLc by FRIEDEWALD'S formula), TG by HOPPE'S and Ph by TAKAYAMA'S enzymatic methods. TGUA concentrations were higher (p less than 0.01) and HDLc ones lower (p less than 0.005) in G-II than in G-I group. These phenomena were found to be a sign of fetal stress, since there was a significant correlation between TGUA and pHUA (r, -0.42; p less than 0.005) and HDLc and pHUA (r, 0.41; p less than 0.0025). Furthermore, there was a correlation between TGUA HDLUA (r, 0.46; p less than 0.0025). Intrapartum hypoxia has a profound effect on lipid stores of the fetus during delivery. Data suggest that high levels of triglycerides in plasma might fall lecitin cholesterol acid transferase activity and this way to explain lower HDLc concentrations of newborn infants with intrapartum acidosis.


Asunto(s)
Asfixia Neonatal/sangre , Colesterol/sangre , Hipoxia/sangre , Sangre Fetal/análisis , Humanos , Recién Nacido , Lipoproteínas HDL/sangre , Triglicéridos/sangre
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