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1.
Allergol Immunopathol (Madr) ; 41(5): 337-45, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23287585

RESUMEN

Strategies to prevent or reduce the risk of allergic diseases are needed. The time of exclusive breastfeeding and introduction of solid foods is a key factor that may influence the development of allergy. For this reason, the aim of this review was to examine the association between exposure to solid foods in the infant's diet and the development of allergic diseases in children. Classical prophylactic feeding guidelines recommended a delayed introduction of solids for the prevention of atopic diseases. Is it really true that a delayed introduction of solids (after the 4th or 6th month) is protective against the development of eczema, asthma, allergic rhinitis and food or inhalant sensitisation? In recent years, many authors have found that there is no statistically significant association between delayed introduction of solids and protection for the development of allergic diseases. Furthermore, late introduction of solid foods could be associated with increased risk of allergic sensitisation to foods, inhalant allergens and celiac disease in children. Tolerance may be driven by the contact of the mucosal immune system with the allergen at the right time of life; the protective effects seem to be enhanced by the practice of the breastfeeding at the same time when weaning is started. Therefore, recent guidelines propose a "window" approach for weaning practice starting at the 17th week and introducing almost all foods within the 27th week of life to reduce the risk of chronic diseases such as allergic ones and the celiac disease. Guidelines emphasize the role of breastfeeding during the weaning practice.


Asunto(s)
Conducta Alimentaria , Hipersensibilidad a los Alimentos/epidemiología , Destete , Alérgenos/efectos adversos , Alérgenos/inmunología , Animales , Lactancia Materna , Niño , Progresión de la Enfermedad , Medicina Basada en la Evidencia , Alimentos/efectos adversos , Hipersensibilidad a los Alimentos/inmunología , Humanos , Lactante , Riesgo
2.
Eur Ann Allergy Clin Immunol ; 45(6): 209-11, 2013 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-24619083

RESUMEN

Food protein-induced enterocolitis syndrome (FPIES) is a potentially severe non-IgE-mediated food allergy usually caused by cow's milk or soy, and more rarely by solid foods such as rice, oats, barley, chicken, turkey, egg white, green peas and peanuts. In children with FPIES, the presence of specific IgE antibodies to the causative food, either at presentation or during follow-up, defines an "atypical form" of FPIES characterized by a lesser probability of developing tolerance and a potential progression to typical IgE-mediated hypersensitivity. Although it is uncommon, the shift from non-IgE-mediated milk-protein induced enterocolitis syndrome to IgE-mediated milk allergy has recently been described. We report the first case, to our knowledge, of a shift from IgE-mediated cow's milk allergy to pure non-IgE-mediated FPIES, in a 4-month-old male infant.

3.
Int Arch Allergy Immunol ; 155(4): 389-94, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21346369

RESUMEN

BACKGROUND: The aim of this study was to determine the occurrence of gluten sensitivity (GS) in a group of allergic patients and to assess the efficacy of a gluten-free diet (GFD) on the improvement of the symptomatology in those who were diagnosed with GS. METHODS: 262 unrelated allergic patients with gastrointestinal symptoms of obscure origin were tested for GS condition by biopsy. All patients were also genotyped for the typical celiac DQ2 and DQ8 molecules and investigated for several hematological parameters such as antigliadin and antiendomysial antibodies. Patients displaying mucosal lesions were invited to follow a GFD. RESULTS: Seventy-seven of the 262 allergic patients were positive to mucosal lesions, but negative to the antiAGA, antiEMA and to DQ2 and DQ8 molecules. We found, instead, a prevalence of the DQA1*05 allele, whereas anemia of inflammatory origin represented the predominant complaint in our subjects. The positive patients, who, after the GS diagnosis, followed a GFD, exhibited control of symptoms as well as stabilization of the hematological parameters even if allergic manifestations were not abated. CONCLUSIONS: A nonceliac gluten-sensitive enteropathy (NCGSE) commonly occurs in allergic patients. Based on the high prevalence of NCGSE in allergy, it is recommended that biopsy should be part of the routine investigation of allergic disease to offer the benefits of treatment with a GFD to the patients.


Asunto(s)
Enfermedad Celíaca/epidemiología , Glútenes/efectos adversos , Hipersensibilidad/complicaciones , Anemia , Asma/complicaciones , Asma/epidemiología , Biopsia , Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/dietoterapia , Enfermedad Celíaca/patología , Dermatitis por Contacto/complicaciones , Dermatitis por Contacto/epidemiología , Dieta Sin Gluten , Duodeno/patología , Femenino , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/dietoterapia , Enfermedades Gastrointestinales/epidemiología , Enfermedades Gastrointestinales/patología , Antígenos HLA-DQ/metabolismo , Prueba de Histocompatibilidad , Humanos , Hipersensibilidad/epidemiología , Inflamación , Mucosa Intestinal/patología , Masculino , Rinitis/complicaciones , Rinitis/epidemiología
4.
Eur Rev Med Pharmacol Sci ; 15(6): 601-36, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21796866

RESUMEN

The present work on drug-induced ototoxicity, tinnitus and vertigo represents the update and revision of a previous guide to adverse drug reactions for italian physicians (2005). The panorama of drug-induced side effects causing ototoxicity or symptoms such as tinnitus or dizziness and vertigo has enlarged in recent years, thanks to a better knowledge and a more specific attention of pharmaceutical firms and drug-control institutions. In daily clinical practice, there is a need for the family physician and the ENT specialist or audiologist (also in consideration of the possible medico-legal implications) to focus the attention on the possible risk of otological side effects. This would allow a clinical risk-benefit evaluation, weighing the possible clinical advantage in their field of competence against possible otological side-effects. The list of active ingredients and drugs is subdivided in categories based on their audiological and otoneurological side-effects, that have been signaled by the drug companies and/or ministerial notes. Drugs have also been subcategorized with regards to the field in which they are applied, the therapeutic indications and the clinical behaviour. They have also been organized in alphabetical order, for an easier consultation. The guide above, even if initially conceived for being used in Italy, also presents a more general and international interest, expecially as for as the concepts of pharmacology and the features of the active ingredients are concerned. The guide is, therefore, useful as for as we are concerned to any physician, regardless of the country he/she operates in.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Pérdida Auditiva Sensorineural/inducido químicamente , Acúfeno/inducido químicamente , Vértigo/inducido químicamente , Sistemas de Registro de Reacción Adversa a Medicamentos , Interacciones Farmacológicas , Humanos , Riesgo
5.
Abdom Radiol (NY) ; 45(10): 2989-2996, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-31506758

RESUMEN

PURPOSE: To identify the predictors of malignancy on CT for the evaluation of gastrointestinal stromal tumors (GIST) by correlating CT findings with the mitotic index in order to propose a "CT-based predictive model of Miettinen index." METHODS: One radiologist and one resident in radiology with 14- and 4-year experience in oncological field reviewed the CT findings of 42 patients by consensus, with respect to lesion site, size, contour, tumor growth pattern, enhancing pattern, degree of enhancement of tumor, percentage of tumor necrosis, mesenteric fat infiltration, ulceration, calcification, regional lymphadenopathy, direct invasion to adjacent organs, and distant metastasis. All parameters were correlated with the mitotic index evaluated at histopathological analysis following surgery. Normality of variables was evaluated using Shapiro-Wilk test. Pearson's correlation test was used to assess the interaction between variables. The diagnostic accuracy percentage of tumor necrosis was measured by receiver operating characteristic (ROC) analysis for detecting whether the number of mitosis per 50 high-power fields was > 5. RESULTS: A significant statistical correlation was found between percentage of tumor necrosis and the mitotic index (p < 0.005), dimension, and location of the tumor. CONCLUSION: CT could be an accurate technique in the prediction of malignancy of GIST in a CT risk assessment system, based on the location of the tumor, its size, and the percentage of tumor necrosis.


Asunto(s)
Tumores del Estroma Gastrointestinal , Medición de Riesgo , Tomografía Computarizada por Rayos X , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Humanos , Estudios Retrospectivos , Factores de Riesgo
6.
Sci Total Environ ; 401(1-3): 81-9, 2008 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-18486189

RESUMEN

Daily time series measurements of elements or compounds are widely used to apportion the contribution of specific sources of particulate matter concentration in the atmosphere. We present results obtained for the urban area of Genoa (Italy) based on several hundred of PM10, PM2.5 and PM1 daily samples collected in sites with different geo-morphological and urbanization characteristics. Elemental concentrations of Na to Pb were obtained through Energy Dispersive X-Ray Fluorescence (ED-XRF), and the contributions of specific sources of particulate matter (PM) concentration were apportioned through Positive Matrix Factorization (PMF). By sampling at different sites we were able to obtain, in each PM fraction, the average and stable values for the tracers of specific sources, in particular traffic (Cu, Zn, Pb) and heavy oil combustion (V, Ni). We could also identify and quote the contamination of anthropogenic PM in "natural" sources (sea, soil dust). Sampling at several sites in the same urban area allowed us to resolve local characteristics as well as to quote average values.


Asunto(s)
Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Metales/análisis , Material Particulado/análisis , Emisiones de Vehículos/análisis , Movimientos del Aire , Ciudades , Cobre/análisis , Geografía , Italia , Plomo/análisis , Níquel/análisis , Tamaño de la Partícula , Sodio/análisis , Espectrometría por Rayos X , Factores de Tiempo , Vanadio/análisis , Zinc/análisis
7.
Biosens Bioelectron ; 88: 196-203, 2017 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-27660019

RESUMEN

Efficient direct electron transfer (DET) between cellobiose dehydrogenase from Corynascus thermophilus (CtCDH) and a novel gold electrode platform, obtained by covalent linking of green AuNPs and AgNPs modified with a dithiol self-assembled monolayer, consisting of biphenyl-4,4'-dithiol (BPDT), was presented. The green AuNPs and AgNPs were synthesized using quercetin as reducing agent at room temperature. TEM experiments showed that the AuNPs and AgNPs were circular in shape with an average diameter of 5 and 8nm, respectively. Cyclic voltammetry of CtCDH immobilized onto the AuNPs/BPDT/AuE and the AgNPs/BPDT/AuE electrode platforms were carried out and compared with naked AuE, BPDT/AuE, AuNPs/AuE, and AgNPs/AuE. A pair of well-defined redox waves in neutral pH solution due to efficient DET of CtCDH was present with both MNPs/BPDT/AuE platforms. No DET communication was found with platforms without MNPs linked to BPDT. The apparent heterogeneous electron transfer rate constants (kS) of CtCDH were calculated to be 21.5±0.8s-1 and 10.3±0.7s-1, for the AuNPs/BPDT/AuE and the AgNPs/BPDT/AuE platforms, respectively. The modified electrodes were successively used to develop an eco-friendly biosensor for lactose detection. The CtCDH/AuNPs/BPDT/AuE based biosensor showed the best analytical performances with an excellent stability, a detection limit of 3µM, a linear range between 5 and 400µM and a sensitivity of 27.5±2.5µAcm-2mM-1. Such performances were favorably compared with other lactose biosensors reported in literature. The biosensor was successively tested to quantify lactose content in real milk and cream samples. No significant interference present in the sample matrices was observed.


Asunto(s)
Técnicas Biosensibles/métodos , Deshidrogenasas de Carbohidratos/química , Oro/química , Lactosa/análisis , Nanopartículas del Metal/química , Leche/química , Plata/química , Sordariales/enzimología , Animales , Electrodos , Transporte de Electrón , Enzimas Inmovilizadas/química , Análisis de los Alimentos/métodos , Tecnología Química Verde/métodos , Límite de Detección , Nanopartículas del Metal/ultraestructura , Modelos Moleculares
8.
Eur Rev Med Pharmacol Sci ; 21(4): 687-694, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-28272715

RESUMEN

OBJECTIVE: Aim of this study is to evaluate the possibility of limb magnetic resonance lymphography (MRL) to differentiate lymphatic vessels from pathological veins, collect a specimen of the identified lymphatic vessel during operations of super microsurgical lymphatic-venular anastomosis (s-LVA) and perform immunohistochemical stainings to confirm the nature of the collected vessels. PATIENTS AND METHODS: Twenty patients presenting lymphedema were enrolled in this study. Five patients reported lower limb lymphedema and 15 patients reported upper limb lymphedema. All patients had the indication for s-LVA and underwent preoperative MRL imaging of the affected limb. A total of 57 lymphatic vessels were identified by MRL and used to guide s-LVA: all these vessels have also been used to perform an intraoperative biopsy for immunohistochemical evaluation. RESULTS: A total of 53/57 vascular structures resulted compatible with lymphatic vessels at the immunohistochemical study performed with D2-40 antibody; 3/57 specimen showed the absence of the D2-40 antibody. A significant association was found between preoperative MRL and immunohistochemical marker D2-40 on collected specimen. CONCLUSIONS: Most of the articles in the international literature report the concomitant presence of both lymphatic and venous vessels at MRL. However, no one in literature describes the possibility to differentiate venous vessels from lymphatic vessels, and this is a crucial issue for the correct evaluation of the lymphatic system in patients with limb lymphedema undergoing a future surgical correction. In the present study, MRL allowed to identify active lymphatic vessels. MRL was predictive to determine preoperatory lymphatic vessels and to perform successful s-LVA in lymphedema patients. This is the first study to prove the nature of the vessels identified at the preoperative MRL with immunohistochemical stainings.


Asunto(s)
Vasos Linfáticos/diagnóstico por imagen , Linfedema/diagnóstico por imagen , Linfografía , Imagen por Resonancia Magnética , Microcirugia , Anastomosis Quirúrgica , Femenino , Humanos , Persona de Mediana Edad
9.
Nucleic Acids Res ; 31(7): 1897-903, 2003 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-12655006

RESUMEN

The human protein OGG1 (hOGG1) targets the highly mutagenic base 7,8-dihydro-8-oxo-2'-deoxyguanosine (8-oxodG) and shows a high specificity for the opposite DNA base. Abasic sites can arise in DNA in close opposition to 8-oxodG either during repair of mismatched bases (i.e. 8-oxodG/A mismatches) or, more frequently, as a consequence of ionizing radiation exposure. Bistranded DNA lesions may remain unrepaired and lead to cell death via double-strand break formation. In order to explore the role of damaged-DNA dynamics in recognition/excision by the hOGG1 repair protein, specific oligonucleotides containing an 8-oxodG opposite an abasic site, at different relative distances on the complementary strand, were synthesized. Rotational dynamics were studied by means of fluorescence polarization anisotropy decay experiments and the torsional elastic constant as well as the hydrodynamic radius of the DNA fragments were evaluated. Efficiency of excision of 8-oxodG was tested using purified human glycosylase. A close relation between the twisting flexibility of the DNA fragment and the excision efficiency of the oxidative damage by hOGG1 protein within a cluster was found.


Asunto(s)
Reparación del ADN , ADN/metabolismo , Desoxiguanosina/análogos & derivados , Desoxiguanosina/metabolismo , N-Glicosil Hidrolasas/metabolismo , 8-Hidroxi-2'-Desoxicoguanosina , Anisotropía , ADN/química , ADN/genética , Daño del ADN , ADN-Formamidopirimidina Glicosilasa , Desoxiguanosina/genética , Polarización de Fluorescencia/métodos , Humanos , Ácidos Nucleicos Heterodúplex/química , Ácidos Nucleicos Heterodúplex/genética , Ácidos Nucleicos Heterodúplex/metabolismo , Oligonucleótidos/química , Oligonucleótidos/genética , Oligonucleótidos/metabolismo
10.
Chemosphere ; 62(2): 226-32, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-15982708

RESUMEN

The particulate matter (PM) concentration and composition, the PM10, PM2.5, PM1 fractions, were studied in the urban area of Genoa, a coastal town in the northwest of Italy. Two instruments, the continuous monitor TEOM and the sequential sampler PARTISOL, were operated almost continuously on the same site from July 2001 to September 2004. Samples collected by PARTISOL were weighted to obtain PM concentration and then analysed by PIXE (particle induced X-ray emission) and by ED-XRF (energy dispersion X-ray fluorescence), obtaining concentrations for elements from Na to Pb. Some of the filters used in the TEOM microbalance were analysed by ED-XRF to calculate Pb concentration values averaged over 7-30 d periods.


Asunto(s)
Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Ciudades , Italia , Tamaño de la Partícula , Estaciones del Año
11.
Eur Rev Med Pharmacol Sci ; 20(14): 2955-73, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-27460721

RESUMEN

OBJECTIVE: The aim of this study is to develop a diagnostic-therapeutic algorithm for those suffering from tinnitus who seek emergency aid. MATERIALS AND METHODS: A literature review has been performed on articles from the last 30 years. RESULTS: It is important to activate medical or surgical diagnostic and therapeutic strategies, in order to safeguard and rehabilitate the various functions affected. Psychiatric comorbidity is the most frequent pathological condition of those with serious or catastrophic tinnitus. In these cases, mortality risk is linked to suicide, morbidity to tinnitus-correlated distress. CONCLUSIONS: Tinnitus, mainly linked to loss of hearing, is a frequent symptom among the population at large. About 7% of those affected by tinnitus turn to their doctor to solve their problem, while between 0.5 and 2% request urgent medical assistance. Their cry for help may be the result of an acute onset of tinnitus or the rapid impairment of an already chronic condition. Tinnitus is not considered an urgent ear, nose and throat (ENT) condition by the Associazione Otorinolaringologi Ospedalieri Italiani (AOOI) [Italian Association of Hospital ENT], even though there are many pathological conditions, sometimes serious, associated with tinnitus and emergency action is necessary to reduce the risk of morbidity and mortality.


Asunto(s)
Enfermedad Crónica , Servicios Médicos de Urgencia , Acúfeno/diagnóstico , Humanos , Suicidio
12.
Biochim Biophys Acta ; 1171(3): 288-94, 1993 Jan 23.
Artículo en Inglés | MEDLINE | ID: mdl-8424952

RESUMEN

The thermodynamic and dielectric properties of a 21 base pair DNA have been evaluated and compared with those of samples with some defects. In particular, fragments in which the absence of a phosphate group (nick) or of two nucleotides (gap) causes chain interruptions were studied. Measurements of ultraviolet absorption as a function of temperature at different oligomer concentrations and at various ionic strengths were performed. Dielectric spectroscopy at radiofrequencies (1 MHz-1 GHz) was applied on aqueous solutions of the duplexes at 5 degrees C, where the solutes are thermally stable. Dielectric dispersions with 30-40 MHz characteristic frequencies were defined. The results of melting experiments indicate a thermal destabilization of the oligomers containing the defects. Electrophoretic data and the dielectric results show that the conformations of the nicked and control samples are very similar, while the oligomer with a gap is more compact with a different charge distribution at the ends.


Asunto(s)
ADN/química , Soluciones , Composición de Base , Secuencia de Bases , Electroforesis en Gel de Poliacrilamida , Datos de Secuencia Molecular , Estructura Molecular , Oligonucleótidos/química , Temperatura , Termodinámica
13.
Biochim Biophys Acta ; 740(3): 300-12, 1983 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-6347258

RESUMEN

Ribosomal subunits of Caldariella acidophila (max.growth temp., 90 degrees C) have been compared to subunits of Bacillus acidocaldarius (max. growth temp., 70 degrees C) and Escherichia coli (max. growth temp., 47 degrees C) with respect to (a) bihelical content of rRNA; (b) G . C content of bihelical domains and (c) tightness of rRNA-protein interactions. The principal results are as follows. Subunits of C. acidophilia ribosomes (Tm = 90-93 degrees C) exhibit considerable thermal tolerance over their B. acidocaldarius (Tm = 77 degrees C) and E. coli counterparts (Tm = 72 degrees C). Based on the "melting' hyperchromicities of the intact ribosomal subunits a 51-55% fraction of the nucleotides appears to participate in hydrogen-bonded base pairing regardless of ribosome source, whereas a larger fraction, 67-70%, appears to be involved in hydrogen bonding in the naked rRNA species. The G . C content of bihelical domains of both free and ribosome-bound rRNA increases with increasing thermophily; based on hyperchromicity dispersion spectra of intact subunits and free rRNA, the bihelical parts of C. acidophila rRNA are estimated to contain 63-64% G . C, compared to 58.5% G . C for B. acidocaldarius and 55% G . C for E. coli. The increment of ribosome Tm values with increasing thermophily is greater than the increase in Tm for the free rRNA, indicating that within ribosomes bihelical domains of the thermophile rRNA species are stabilized more efficiently than their mesophile counterparts by proteins or/ and other component(s). The efficiency of the rRNA-protein interactions in the mesophile and thermophile ribosomes has been probed by comparing the releases, with LiCl-urea, of the rRNA species from the corresponding ribosomal subunits stuck to a Celite column through their protein moiety; it has been established that the release of C. acidophila rRNA from the Celite-bound ribosomes occurs at salt-urea concentrations about 4-fold higher than those required to release rRNA from Celite-bound E. coli ribosomes. Compared to E. coli the C. acidophila 50 and 30 S ribosomal subunits are considerably less susceptible to treatment designed to promote ribosome unfolding through depletion of magnesium ions.


Asunto(s)
Bacillus/metabolismo , Bacterias/metabolismo , Escherichia coli/metabolismo , Conformación de Ácido Nucleico , Nucleoproteínas/genética , ARN Ribosómico/genética , Ribonucleoproteínas/genética , Proteínas Ribosómicas/genética , Ribosomas/metabolismo , Calor , Cinética , Desnaturalización de Ácido Nucleico , Especificidad de la Especie , Espectrofotometría Ultravioleta , Temperatura
15.
Br J Pharmacol ; 131(7): 1391-8, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11090112

RESUMEN

1. S-Nitrosothiols are nitric oxide (NO) donor drugs that have been shown to inhibit platelet aggregation in platelet rich plasma (PRP) in vitro and to inhibit platelet activation in vivo. The aim of this study was to compare the platelet effects of a novel S-nitrosated glyco-amino acid, RIG200, with an established S-nitrosothiol, S-nitrosoglutathione (GSNO) in PRP, and to investigate the effects of cell-free haemoglobin and red blood cells on S-nitrosothiol-mediated inhibition of platelet aggregation. 2. The effects of GSNO and RIG200 in collagen (2.5 microg ml(-1))-induced platelet aggregation in PRP and whole blood were investigated in vitro. Both compounds were found to be powerful inhibitors of aggregation in PRP, and RIG200 was significantly more potent (IC(50)=2.0 microM for GSNO and 0.8 microM for RIG200; P=0.04). 3. Neither compound inhibited aggregation in whole blood, even at concentrations of 100 microM. Red blood cell concentrations as low as 1% of the haematocrit, and cell-free haemoglobin (> or = 2.5 microM), significantly reduced their inhibitory effects on platelets. 4. Experiments involving measurement of cyclic GMP levels, electrochemical detection of NO and electron paramagnetic resonance of haemoglobin in red blood cells, indicated that scavenging of NO generated from S-nitrosothiols by haemoglobin was responsible for the lack of effect of S-nitrosothiols on platelets in whole blood. 5. These studies suggest that scavenging of NO by haemoglobin in blood might limit the therapeutic application of S-nitrosothiols as anti-platelet agents.


Asunto(s)
Eritrocitos/fisiología , Glucosamina/análogos & derivados , Glutatión/análogos & derivados , Hemoglobinas/farmacología , Mercaptoetanol , Compuestos Nitrosos/farmacología , Penicilamina/análogos & derivados , Inhibidores de Agregación Plaquetaria/farmacología , Agregación Plaquetaria/efectos de los fármacos , S-Nitrosotioles , Adulto , GMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Espectroscopía de Resonancia por Spin del Electrón , Eritrocitos/citología , Fibrinolíticos/farmacología , Glucosamina/metabolismo , Glucosamina/farmacología , Glutatión/metabolismo , Glutatión/farmacología , Humanos , Masculino , Óxido Nítrico/metabolismo , Compuestos Nitrosos/metabolismo , Penicilamina/metabolismo , Penicilamina/farmacología , S-Nitrosoglutatión
16.
Br J Pharmacol ; 126(3): 639-48, 1999 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10188974

RESUMEN

Previous studies show that linking acetylated glucosamine to S-nitroso-N-acetyl-D,L-penicillamine (SNAP) stabilizes the molecule and causes it to elicit unusually prolonged vasodilator effects in endothelium-denuded, isolated rat femoral arteries. Here we studied the propanoyl (SNPP; 3 carbon side-chain), valeryl (SNVP; 5C) and heptanoyl (SNHP; 7C) N-substituted analogues of SNAP (2C), to further investigate other molecular characteristics that might influence chemical stability and duration of vascular action of S-nitrosothiols. Spectrophotometric analysis revealed that SNVP was the most stable analogue in solution. Decomposition of all four compounds was accelerated by Cu(II) and cysteine, and neocuproine, a specific Cu(I) chelator, slowed decomposition of SNHP. Generation of NO from the compounds was confirmed by electrochemical detection at 37 degrees C. Bolus injections of SNAP (10 microl; 10(-8)-10(-3) M) into the perfusate of precontracted, isolated rat femoral arteries taken from adult male Wistar rats (400-500 g), caused concentration-dependent, transient vasodilatations irrespective of endothelial integrity. Equivalent vasodilatations induced by SNVP and SNHP were transient in endothelium-intact vessels but failed to recover to pre-injection pressures at moderate and high concentrations (10(-6)-10(-3) M) in those denuded of endothelium. This sustained effect (> 1 h) was most prevalent with SNHP and was largely reversed by the NO scavenger, haemoglobin. We suggest that increased lipophilicity of SNAP analogues with longer sidechains facilitates their retention by endothelium-denuded vessels; subsequent slow decomposition within the tissue generates sufficient NO to cause prolonged vasodilatation. This is a potentially useful characteristic for targeting NO delivery to areas of endothelial damage.


Asunto(s)
Penicilamina/análogos & derivados , 1-Octanol , Animales , Endotelio Vascular/fisiología , Arteria Femoral/efectos de los fármacos , Arteria Femoral/fisiología , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico/fisiología , Donantes de Óxido Nítrico/farmacología , Penicilamina/química , Penicilamina/metabolismo , Penicilamina/farmacología , Ratas , Ratas Wistar , Solubilidad , Vasodilatación/efectos de los fármacos , Agua
17.
Biosens Bioelectron ; 8(6): 307-14, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8251133

RESUMEN

This paper describes the implementation of a bienzyme sensor for the direct determination of glucose and lactate in undiluted biological samples. The biosensor exploits the competitive action versus the substrate itself by two different enzymes immobilized into a sandwich of two different membranes. In this way the quantity of substrate reaching the indicating electrode is reduced and this determines an extension of the linearity range.


Asunto(s)
Técnicas Biosensibles , Líquidos Corporales/química , Glucosa/análisis , Lactatos/análisis , Calibración , Humanos , Ácido Láctico
18.
Eur J Pharmacol ; 408(3): 335-43, 2000 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-11090652

RESUMEN

Organic nitrates, such as glyceryltrinitrate, are nitric oxide (NO) donor drugs that engender tolerance with long-term use. Here, we tested the hypothesis that our novel S-nitrosothiols, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6, tetra-O-acetyl-beta-D-glucopyranose (RIG200) and S-nitroso-N-valeryl-D-penicillamine (D-SNVP), do not induce vascular tolerance ex vivo. Femoral arteries from adult male Wistar rats were preconstricted with phenylephrine and perfused with the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). Perfusion pressure was measured during 20 h treatment with supramaximal concentrations of NO donor (10 microM). Perfusion with glyceryltrinitrate caused a vasodilatation, which recovered over 2-20 h. In contrast, the S-nitrosothiols caused vasodilatations that were maintained throughout the 20 h perfusion period. Responses to S-nitrosothiols were partially reversed by the NO scavenger ferrohaemoglobin and fully reversed by the soluble guanylate cyclase inhibitor [1H-[1,2,4] oxadiazole [4,3-a]quinoxaline-1-one (ODQ). Glyceryltrinitrate-tolerant vessels were fully responsive to bolus injections of S-nitrosothiols. Resistance to tolerance is an attractive property of our novel compounds, particularly in view of their sustained activity in arteries with damaged endothelium.


Asunto(s)
Arteria Femoral/efectos de los fármacos , Glucosamina/análogos & derivados , Glutatión/análogos & derivados , Nitroglicerina/farmacología , Compuestos Nitrosos/farmacología , Penicilamina/análogos & derivados , Vasodilatación/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos , Inhibidores Enzimáticos/farmacología , Arteria Femoral/fisiología , Glucosamina/farmacología , Glutatión/farmacología , Guanilato Ciclasa/antagonistas & inhibidores , Técnicas In Vitro , Masculino , Metahemoglobina/farmacología , Donantes de Óxido Nítrico/farmacología , Compuestos Nitrosos/química , Oxadiazoles/farmacología , Penicilamina/farmacología , Fenilefrina/farmacología , Quinoxalinas/farmacología , Ratas , Ratas Wistar , S-Nitroso-N-Acetilpenicilamina , S-Nitrosoglutatión , Vasoconstrictores/farmacología
19.
Eur J Pharmacol ; 403(1-2): 111-9, 2000 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-10969151

RESUMEN

Organic nitrates, such as glyceryl trinitrate, are nitric oxide (NO) donor drugs that engender tolerance with long-term use. Here, we tested the hypothesis that our novel S-nitrosothiols, N-(S-nitroso-N-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6, tetra-O-acetyl-beta-D-glucopyranose (RIG200) and S-nitroso-N-valeryl-D-penicillamine (D-SNVP), do not induce vascular tolerance ex vivo. Femoral arteries from adult male Wistar rats were preconstricted with phenylephrine and perfused with the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). Perfusion pressure was measured during 20-h treatment with supramaximal concentrations of NO donor (10 microM). Perfusion with glyceryltrinitrate caused a vasodilatation, which recovered over 2-20 h. In contrast, the S-nitrosothiols caused vasodilatations that were maintained throughout the 20-h perfusion period. Responses to S-nitrosothiols were partially reversed by the NO scavenger ferrohaemoglobin and fully reversed by the soluble guanylate cyclase inhibitor [1H-[1,2,4] oxadiazole [4,3-a]quinoxaline-1-one (ODQ). Glyceryltrinitrate-tolerant vessels were fully responsive to bolus injections of S-nitrosothiols. Resistance to tolerance is an attractive property of our novel compounds, particularly in view of their sustained activity in arteries with damaged endothelium.


Asunto(s)
Arteria Femoral/efectos de los fármacos , Glucosamina/análogos & derivados , Glucosamina/farmacología , Glutatión/análogos & derivados , Nitroglicerina/farmacología , Penicilamina/análogos & derivados , Penicilamina/farmacología , Vasodilatadores/farmacología , Animales , Relación Dosis-Respuesta a Droga , Tolerancia a Medicamentos , Inhibidores Enzimáticos/farmacología , Arteria Femoral/fisiología , Hemoglobinas/farmacología , Técnicas In Vitro , NG-Nitroarginina Metil Éster/farmacología , Donantes de Óxido Nítrico/farmacología , Compuestos Nitrosos/farmacología , Oxadiazoles/farmacología , Perfusión , Fenilefrina/farmacología , Quinoxalinas/farmacología , Ratas , Ratas Wistar , S-Nitrosoglutatión , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología
20.
Biophys Chem ; 94(1-2): 175-84, 2001 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-11744198

RESUMEN

We have studied the torsional elastic constant (alpha) of short DNA (27mer) oligomers of various sequence by fluorescence polarization anysotropy (FPA) measurements. The lowest alpha values were found in samples with sequence rich in AA dinucleotides or containing the alternating d(A-T) x d(A-T) motif. The torsional rigidity of our DNA samples was compared to that calculated according to the current values of twist angle fluctuations derived for ten dinucleotide steps by recent analyses of DNA crystal structure database. The values of torsional rigidity derived from crystals are higher than our experimental ones, obtained by FPA analysis, suggesting that packing force in crystals may notably hinder the dinucleotide twist angle fluctuations that occur in solution. This behaviour is more evident for samples containing AA, TA and AT steps. In all the samples there is about a twofold change of the alpha value in the 10-40 degrees C range. An activation enthalpy (Delta H (#)) of about 17.4 kJ mol(-1), on average, was obtained for the temperature dependence of eight of the ten samples studied. A correlation with the stacking energy is discussed.


Asunto(s)
Biopolímeros/química , ADN/química , Conformación de Ácido Nucleico , Secuencia de Bases , Dicroismo Circular , Inmunoensayo de Polarización Fluorescente , Datos de Secuencia Molecular
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