RESUMEN
BACKGROUND AND PURPOSE: Ataxia-telangiectasia (A-T) is a rare neurodegenerative disease, due to A-T mutated (ATM) gene mutations, which typically presents with signs of progressive neurological dysfunction, cerebellar ataxia and uncoordinated movements. A-T severely affects patients' quality of life. Successful treatment options are still not available. The aim of this multicenter study, performed with a blind evaluation procedure, was to define the minimal effective dosage of oral betamethasone, thus preventing the occurrence of side effects. METHODS: Nine A-T patients were enrolled to receive betamethasone at increasing dosages of 0.001, 0.005 and 0.01 mg/kg/day. Neurological assessment and the evaluation of quality of life were performed through the Scale for the Assessment and Rating of Ataxia and the Italian version of the Childhood Health Assessment Questionnaire (CHAQ) at each time-point. The drug safety profile was evaluated. Patients were categorized as responders, partial responders and non-responders. RESULTS: Four of nine patients had a benefit at a dose of 0.005 mg/kg/day of oral betamethasone. Using the higher dosage, only one additional patient had a positive response. Conversely, a daily dose of 0.001 mg/kg was ineffective. A correlation between the serum adrenocorticotropic hormone levels and the clinical response was observed. Five of 30 CHAQ items improved in four patients. CONCLUSIONS: These data suggest that a short-term betamethasone oral treatment, at a daily dosage of 0.005 mg/kg, is effective in some patients. Pre-existing risk factors for side effects should be taken into account before therapy.
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Ataxia Telangiectasia/tratamiento farmacológico , Betametasona/administración & dosificación , Glucocorticoides/administración & dosificación , Adolescente , Betametasona/uso terapéutico , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Femenino , Glucocorticoides/uso terapéutico , Humanos , Masculino , Fenotipo , Calidad de Vida , Resultado del Tratamiento , Adulto JovenRESUMEN
Kawasaki disease (KD) is a pediatric acute multisystemic vasculitis complicated by development of coronary artery lesions. The breakthrough theory on KD etiopathogenesis points to pathogens/environmental factors triggered by northeastern wind coming from China. Natural Killer cells and T lymphocytes express the inhibitory/activating Killer Immunoglobulin-like Receptors (KIR) to elicit an immune response against pathogens by binding to human leukocyte antigens (HLA) class I epitopes. We first report on the role of KIR/HLA genetic epistasis in a sample of 100 Italian KD children. We genotyped KIR, HLA-A, HLA-B and HLA-C polymorphisms, and compared KD data with those from 270 Italian healthy donors. The HLA-A*11 ligand for KIR2DS2/2DS4/3DL2 was a KD susceptibility marker by itself (odds ratio (OR)=3.85, confidence interval (CI)=1.55-9.53, P=0.004). Although no epistasis between HLA-A*11 and KIR2DS2/S4 emerged, HLA-A*11 also engages KIR3DL2, a framework gene encoding for a pathogen sensor of CpG-oligodeoxynucleotides (CpG-ODN), and KD blood mononuclear cells are actually prone to pathogen CpG-ODN activation in the acute phase. Moreover, carriers of KIR2DS2/HLA-C1 and KIR2DL2/HLA-C1 were more frequent among KD, in keeping with data demonstrating the involvement of these HLA/KIR couples in autoimmune endothelial damage. The highest KD risk factor was observed among carriers of KIR2DL2 and two or more HLA ligands (OR=10.24, CI=1.87-56.28; P=0.007).
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Antígenos HLA/genética , Antígenos HLA/inmunología , Síndrome Mucocutáneo Linfonodular/genética , Síndrome Mucocutáneo Linfonodular/inmunología , Receptores KIR/genética , Receptores KIR/inmunología , Estudios de Casos y Controles , Niño , Preescolar , Susceptibilidad a Enfermedades/inmunología , Epistasis Genética , Femenino , Frecuencia de los Genes , Antígeno HLA-A11/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Inmunoglobulinas/genética , Inmunoglobulinas/inmunología , Masculino , Polimorfismo GenéticoRESUMEN
Primary immunodeficiencies (PIDs) are rare diseases characterized by an increased susceptibility to infections. Early diagnosis and appropriate treatment are critical for reducing morbidity and mortality. Based on available data, the efficacy of antibiotic administration for the prophylaxis of infections remains uncertain, and recommendations supporting this practice are poor. The use of antimicrobial prophylaxis is mainly based on single institution-specific experience without controlled measurements of patient safety and quality health outcomes. To address this issue an Italian Network on Primary Immunodeficiencies (IPINet) has been set up in 1999 within the Italian Association of Pediatric Hematology and Oncology (AIEOP) to increase the awareness of these disorders among physicians. Further, diagnostic and treatment guideline recommendations have been established to standardize the best clinical assistance to all patients, including antibiotic prophylaxis, and for a national epidemiologic monitoring of PIDs. The aim of this review is not only to give a scientific update on the use of antimicrobial prophylaxis in selected congenital immunological disorders but also to draw a picture of this practice in the context of the Italian Primary Immunodeficiency Network (IPINet). Controlled multicenter studies are necessary to establish if, when and how you should start an efficacious antimicrobial prophylaxis.
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Profilaxis Antibiótica , Síndromes de Inmunodeficiencia/complicaciones , Inmunodeficiencia Variable Común/complicaciones , Síndrome de DiGeorge/complicaciones , Enfermedad Granulomatosa Crónica/complicaciones , Humanos , Deficiencia de IgA/complicaciones , Enfermedades por Inmunodeficiencia Combinada Ligada al Cromosoma X/complicacionesRESUMEN
A multi-residual method is described for the simultaneous determination of 23 personal care products (PCPs), which display a wide range of physicochemical properties, present at trace levels in water samples. A one-step procedure was developed based on solid-phase microextraction (SPME) coupled with GC-MS analysis. A chemometric approach consisting of an experimental design (design of experiments) was applied to systematically investigate how four operating parameters--extraction temperature and time and desorption temperature and time--affect extraction recovery of PCPs in water. The optimum SPME procedure operating conditions, those yielding the highest extraction recovery for all the compounds, were determined; they correspond to an extraction time of 90 min and temperature of 80 °C and a desorption time of 11 min and temperature of 260 °C. Under these optimized conditions, the SPME procedure shows good analytical performance characterized by high reproducibility (RSD% intra-day accuracy varying in the 0.01-1.3% range) as well as good linearity and low detection limits (LODs lower than 2 ppb for most of the investigated PCPs).
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Cosméticos/aislamiento & purificación , Microextracción en Fase Sólida/métodos , Contaminantes Químicos del Agua/aislamiento & purificación , Cosméticos/análisis , Cromatografía de Gases y Espectrometría de Masas , Contaminantes Químicos del Agua/análisisRESUMEN
Dominant-negative mutations in STAT-3 have recently been found in the majority of patients with sporadic or autosomal-dominant hyper IgE syndrome (HIES). Since STAT-3 plays a role in B cell development and differentiation, we analyzed memory B cells in 20 patients with HIES, 17 of which had STAT-3 mutations. All but four patients had reduced non-switched and/or class-switched memory B cells. No reduction in these B cell populations was found in 16 atopic dermatitis patients with IgE levels above 1000 KU/L. There was no correlation between the reduction of memory B cells and the ability to produce specific antibodies. Moreover, there was no correlation between the percentage of memory B cells and the infection history. Analysis of memory B cells can be useful in distinguishing patients with suspected HIES from patients with atopic disease, but probably fails to identify patients who are at high risk of infection.
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Linfocitos B/inmunología , Memoria Inmunológica/inmunología , Síndrome de Job/inmunología , Adolescente , Adulto , Anticuerpos Antivirales/sangre , Formación de Anticuerpos , Linfocitos B/patología , Niño , Estudios de Cohortes , ADN/química , ADN/genética , Dermatitis Atópica/genética , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Genotipo , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina E/metabolismo , Memoria Inmunológica/genética , Síndrome de Job/genética , Síndrome de Job/patología , Masculino , Persona de Mediana Edad , Mutación , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/inmunología , Adulto JovenRESUMEN
Transient hypogammaglobulinemia of infancy (THI) is a heterogeneous disorder characterized by reduced serum IgG levels in early infancy. A putative diagnosis is initially made after exclusion of other causes of hypogammaglobulinemia while a definitive diagnosis of THI can only be made a posteriori in patients with normalization of IgG levels. The aim of this study is to characterize clinical and immunological features of children with an initial diagnosis of THI in correlation to natural outcome, and to assess predictive laboratory parameters of clinical evolution for this disorder. We prospectively analysed clinical and immunological characteristics of 77 THI children at initial diagnosis and of 57 patients at follow-up. Memory B cell subsets and in vitro immunoglobulin production were evaluated. Seventy patients (91 percent) showed clinical symptoms. Patients suffered from infections (91 percent), allergies (47 percent) and autoimmune disease (4 percent). During follow-up 41/57 children (72 percent) normalized IgG values, mostly within 24 months of age (p less than 0.001), allowing the diagnosis of THI. The 16 children who did not normalize their IgG levels showed a higher frequency of severe infections and autoimmune disease (p less than 0.01). Moreover, they expressed a reduced frequency of IgM and switched memory B cells (p less than 0.01) and an inability to produce IgG in vitro (p less than 0.02). We conclude that most patients with an initial diagnosis of THI spontaneously recover within 24 months of age and have a benign clinical course, while a subgroup of children with undefined hypogammaglobulinemia share a clinical and immunological profile with other primary immunodeficiencies. Early recognition of children with hypogammaglobulinemia during infancy who are likely to suffer from permanent immunodeficiencies later in life would allow prompt and appropriate laboratory and clinical interventions.
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Agammaglobulinemia/epidemiología , Síndromes de Inmunodeficiencia/epidemiología , Envejecimiento/inmunología , Linfocitos B/inmunología , Preescolar , Progresión de la Enfermedad , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Inmunoglobulinas/biosíntesis , Memoria Inmunológica/inmunología , Lactante , Italia/epidemiología , Masculino , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Circulating T cells from four patients with the hyper-IgE syndrome were found to produce significantly lower concentrations of interferon-gamma (IFN-gamma) in response to stimulation with phytohemagglutinin (PHA) than did T cells from eight age-matched healthy controls, three patients with atopic dermatitis and one patient with chronic granulomatous disease. A clonal analysis revealed that patients with hyper-IgE syndrome had markedly lower proportions of circulating T cells able to produce IFN-gamma and tumor necrosis factor-alpha (TNF-alpha) in comparison with controls. In contrast, the proportions of peripheral blood T cells able to produce IL-4 or IL-2 were not significantly different in patients and controls. All the four patients with hyper-IgE syndrome showed high proportions of circulating CD4+ helper T cells able to induce IgE synthesis in allogeneic B cells, as well. Such an activity for IgE synthesis appeared to be positively correlated with IL-4 production by T cells and inversely related to the ability of the same T cells to produce IFN-gamma. Since IFN-gamma exerts an inhibitory effect on the synthesis of IgE and both IFN-gamma and TNF-alpha play an important role in inflammatory reactions, we suggest that the defective production of IFN-gamma may be responsible for hyperproduction of IgE and the combined defect of IFN-gamma and TNF-alpha may contribute to the undue susceptibility to infections seen in patients with hyper-IgE syndrome.
Asunto(s)
Hipergammaglobulinemia/sangre , Inmunoglobulina E , Interferón gamma/biosíntesis , Linfocitos T/metabolismo , Factor de Necrosis Tumoral alfa/biosíntesis , Adolescente , Adulto , Niño , Femenino , Humanos , Inmunoglobulina E/biosíntesis , Recuento de Leucocitos , Fitohemaglutininas/farmacología , Síndrome , Linfocitos T/patología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/patología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/patologíaRESUMEN
This work describes a GC-MS method for enantioselective separation of amino acids. The method is based on a derivatization reaction which employs a mixture of alkyl chloroformate-alcohol-pyridine, as reagents to obtain the N(O,S)-alkyl alkoxy carbonyl esters of amino acids. Various reaction parameters are investigated and optimized to achieve a reproducible derivatization procedure suitable for separation of amino acid enantiomers on Chirasil-L-Val chiral stationary phase. In particular, the following topics are investigated for 20 proteinogenic amino acids: (i) the proper reagent and reaction conditions to obtain the highest derivative yield; (ii) the amino acid reactivity and the MS properties of the obtained derivatives; (iii) the linearity and sensitivity of the analytical method; (iv) the retention behavior of the derivatives and their enantiomeric separation on the Chirasil-L-Val chiral stationary phase. By combining the resolution power of the Chirasil-L-Val column and the high selectivity of the SIM MS detection mode, the described procedure enables the enantiomeric separation and quantification of 16 enantiomeric pairs of amino acids. The procedure is simple and fast and reproducible. It displays a wide linearity range at ppb detection limits for quantitative determinations: these properties make this derivatization method a suitable candidate for amino acid GC-MS analysis on board of the spacecrafts in space exploration missions of solar system body environments.
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Aminoácidos/química , Formiatos/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Aminoácidos/análisis , Estructura Molecular , Reproducibilidad de los Resultados , EstereoisomerismoRESUMEN
Gas chromatography-mass spectrometry (GC-MS) will be used in future space exploration missions, in order to seek organic molecules at the surface of Mars, and especially potential chemical indicators of life. Carboxylic acids are among the most expected organic species at the surface of Mars, and they could be numerous in the analysed samples. For this reason, a chemometric method was applied to support the interpretation of chromatograms of carboxylic acid mixtures. The method is based on AutoCovariance Function (ACVF) in order to extract information on the sample--number and chemical structure of the components--and on separation performance. The procedure was applied to standard samples containing targeted compounds which are among the most expected to be present in the Martian soil: n-alkanoic and benzene dicarboxylic acids. ACVF was computed on the obtained chromatograms and plotted versus retention time: peaks of the ACVF plot can be related to specific molecular structures and are diagnostic for chemical identification of compounds.
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Exobiología , Cromatografía de Gases y Espectrometría de Masas/métodos , Marte , Suelo/análisisRESUMEN
A quantitative study of the relationship between structure and receptor binding affinity of a series of 16 beta-carbolines showed the influence of lipophilic character and hydrogen bonding capability of substituents in position 3. Some data taken from the literature enabled us to add some evidence about the influence of planarity of ring C and bulky substituents in position 1 in determining the receptor binding affinity.
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Carbolinas/metabolismo , Receptores de GABA-A/metabolismo , Animales , Enlace de Hidrógeno , Técnicas In Vitro , Ratas , Solubilidad , Relación Estructura-ActividadRESUMEN
A commercial latex agglutination (LA) kit (Wellcogen, Wellcome Diagnostics) used to detect bacterial polysaccharide antigens (Haemophilus influenzae type b and Streptococcus pneumoniae) was compared with a modified counterimmunoelectrophoresis technique and blood culture for etiologic diagnosis of presumptive bacterial pneumonia requiring hospitalization in 60 infants and children. Serum, urine and either sputum or nasopharyngeal secretions were collected during the first 5 days of therapy for antigen detection. Blood culture was positive in 6 of 52 (11.5%) of cases. Antigens were detected by counterimmunoelectrophoresis and/or LA in 13 of 60 (21.7%) serum samples, 2 of 16 (12.5%) unconcentrated urine samples, 19 of 42 (45.2%) urine samples concentrated 25-fold and 21 of 45 (46.7%) sputum or nasopharyngeal secretions. Antibiotic treatment for 5 days did not affect the antigen detection rate. Counter-immunoelectrophoresis was more sensitive than LA in serum and urine but not in sputum. However, because false positive reactions were frequently obtained with LA on nasopharyngeal secretions of an age-matched control group, this test appears unreliable.
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Infecciones Bacterianas/diagnóstico , Contrainmunoelectroforesis , Haemophilus influenzae/aislamiento & purificación , Inmunoelectroforesis , Pruebas de Fijación de Látex , Neumonía/diagnóstico , Streptococcus pneumoniae/aislamiento & purificación , Adolescente , Niño , Preescolar , Diagnóstico Diferencial , Infecciones por Haemophilus/diagnóstico , Humanos , Lactante , Infecciones Estreptocócicas/diagnósticoRESUMEN
The hypothesis that benzodiazepines interact with their receptors in the CNS via hydrogen bonding mediated by the carbonyl and imine groups has been studied by correlating a physicochemical parameter affected by hydrogen bonds potentially accepted or donated by benzodiazepines with their binding constants to synaptosomal rat brain membranes. The reference physicochemical system chosen was normal phase high-performance liquid chromatography on mu-Bondapack NH2 (propylamine groups chemically bonded to porous silica) eluted with mixtures of n-hexane and 2-propanol. A strong correlation has been found for binding of the implicated groups to the column and to the receptor.
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Receptores de GABA-A/metabolismo , 1-Propanol , Animales , Fenómenos Químicos , Química Física , Cromatografía Líquida de Alta Presión , Hexanos , Enlace de Hidrógeno , Técnicas In Vitro , Cinética , Modelos Químicos , Ratas , Receptores de GABA-A/química , Dióxido de Silicio , Solventes , Sinaptosomas/metabolismoRESUMEN
Here is referred the case history of a boy - age 6 yrs - who was hospitalised for a persistent high temperature with generalised limphonodes hypertrophy. The limphonode biopsy together with decreased NK activity and increased antiEAD and antiVCA antibodies allowed the diagnosis of chronic mononucleosis.
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Mononucleosis Infecciosa/inmunología , Anticuerpos Antivirales/análisis , Formación de Anticuerpos , Niño , Enfermedad Crónica , Herpesvirus Humano 4/inmunología , Humanos , Inmunidad Celular , MasculinoRESUMEN
Twenty-one children, age range 5 mo - 14 yrs, affected by candidosis, were treated with ketoconazole (tablets or suspension). Patients had alimentary tract involvement (12), oesophagitis (1), urinary tract candidosis (3), vaginitis (2), septicaemia (1), endophtalmitis (1) and chronic pulmonary illness with persistence of Candida albicans in sputum (3). Daily drug doses ranged from 3 to 13 mg/Kg and treatment period from 7 days to 14 months. Pharmacokinetic study in 15 children showed large individual variability of drug serum levels. Pharmacokinetic parametres, related to different schedules of the two ketoconazole formulations (tablets and suspension) are reported; drug levels after chronic administration are also evaluated. A daily dose of 3 mg/Kg of ketoconazole suspension, given in 3 administrations, did not result in sufficiently high levels, which indeed were obtained with a daily dose of 10 mg/Kg (3.3 X 3). The effect of treatment is proven by negativization of cultures in 90% of patients, by disappearance of clinical signs in 67% by improvement in 9%. The therapeutic effect on the remaining 24% (5 patients) is not evaluable. Adverse effects were only nausea and pyrosis in four cases; no laboratory abnormalities were found. A daily dosage from 7 to 10 mg/Kg, in two or three administrations, is suggested to obtain therapeutic levels in children.
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Candidiasis/tratamiento farmacológico , Cetoconazol/sangre , Administración Oral , Adolescente , Niño , Preescolar , Ensayos Clínicos como Asunto , Evaluación de Medicamentos , Femenino , Humanos , Lactante , Cetoconazol/uso terapéutico , Cinética , MasculinoRESUMEN
The paper describes the characterization of polycyclic aromatic hydrocarbons (PAHs) in atmospheric aerosol samples using Gas Chromatography-Mass Spectrometry analysis. A data handling of GC/MS signals based on Experimental Autocovariance Function (EACVF) is described in order to directly characterize PAHs with a simple and reliable method suitable for processing large batches of samples. The method was successfully applied to 42 aerosol samples collected in different seasons (summer, fall and winter) in two locations in Northern Italy: Milan, a large urban area, and Oasi Le Bine, a rural site. The reliability of the EACVF results was verified by comparison with the values computed with the conventional GC/MS signal treatment and the data of independent studies. Two main emission sources were identified and described by PAH concentration profiles: the road traffic source (TR), characterized by high contributions of FLNT, PYR and CHR, and the residential combustion (COMB) mainly containing pyrogenic high molecular weight PAHs, i.e., CHR, BaP, BeP, BbF and BkF. In addition, some PAH diagnostic ratios were directly computed for the EACVF plot, to distinguish between traffic and combustion dominated emissions, i.e. the ratios CHR/BaP, PYR/BaP and PYR/BeP.
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Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Hidrocarburos Policíclicos Aromáticos/análisis , Italia , Reproducibilidad de los ResultadosRESUMEN
Liquid chromatography (LC) combined with tandem mass spectrometry (MS/MS), based on the use of a hybrid quadrupole-time-of-flight mass analyzer, was used to investigate the reactivity of nine fungicides in free chlorine-containing water samples. Three of the selected compounds (fenhexamid, FEN; pyrimethanil, PYR; and cyprodinil, CYP) displayed a poor stability in presence of moderate chlorine levels; thus, the effects of different parameters on their half-lives (t(1/2)) were evaluated. Sample pH, bromide traces, and the water matrix affected their relative stabilities. Despite such variations, the three fungicides are degraded at significant rates not only in ultrapure, but also in surface water spiked with chlorine levels up to 2 µg ml(-1), and when mixed with chlorinated tap water, generating several transformation products (TPs). The time-course of precursor species and their TPs was followed in the LC-MS mode, using the information contained in accurate, full scan mass spectra (MS) to propose the empirical formulae of TPs. Thereafter, their ion product scan (MS/MS) spectra were considered to set their chemical structures; allowing, in some cases, to distinguish between isomeric TPs. The reaction pathway of FEN, the less stable fungicide, involved just an electrophilic substitution of hydrogen per chlorine, or bromine, and cleavage of the molecule to render an amide. PYR and CYP shared common reaction routes consisting of halogenation, hydroxylation, and condensation processes leading to complex mixtures of TPs, which were relatively stable to further transformations.
RESUMEN
The work compares two GC-MS methods for enantioselective separation of amino acids as suitable candidate for stereochemical analysis of chiral amino acids on board spacecrafts in space exploration missions of solar system body environments. Different derivatization reagents are used: a mixture of alkyl chloroformate-alcohol-pyridine to obtain the alkyl alkoxy carbonyl esters and a mixture of perfluorinated alcohols and anhydrides to form perfluoroacyl perfluoroalkyl esters. 20 proteinogenic amino acids were derivatized with the two procedures and submitted to GC-MS analysis on a Chirasil-l-Val stationary phase. The results were then compared in terms of the enantiomeric separation achieved and intensity of MS response. The combination of methyl chloroformate (MCF) and heptafluoro-1-butanol (HFB) allows separation of 14 enantiomeric pairs, five of which display a resolution (R(s)>or=1.2) supposed to be sufficient to quantify the enantiomeric excess. Three mixtures of trifluoroacetic (TFAA) and heptafluorobutyric (HFBA) anhydrides were combined with the corresponding perfluorinated alcohols - TFE (2,2,2-trifluoro-1-ethanol) and HFB (2,2,3,3,4,4,4-heptafluoro-1-butanol) - to give three different reagents (TFAA-TFE, TFAA-HFB, HFBA-HFB): the derivatives obtained show separation of the same number of proteinogenic amino acids (14 of 20) at a temperature lower than column bleeding limit (200 degrees C) and 8 of them give a separation with R(s)>or=1.2. Linearity study and limit of detection (X(LOD)) computation show that both methods are suitable for quantitative determination of several amino acid diastereomers at trace level (X(LOD) approximately 0.5nmol as derivatized quantity). Both the procedures were coupled with automatic data handling to increase their suitability for space analysis: the simplified data treatment is especially helpful to handle the low quality data recovered from space experiments and labor and time are saved, as imposed by the space experiments requiring a rapid delivery of the results. To achieve this aim, a chemometric approach based on the computation of the Autocovariance Function (ACVF) was applied to extract information on the enantiomeric pairs present in the sample and the enantioseparation achieved on the chiral column.
Asunto(s)
Aminoácidos/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Procesamiento de Señales Asistido por Computador , Alcoholes/química , Biomarcadores/química , Formiatos/química , Modelos Lineales , Sensibilidad y Especificidad , Estereoisomerismo , TemperaturaRESUMEN
The paper describes the characterization of n-alkane homologous series present in PM samples performed by gas chromatography-mass spectrometry analysis. The PM samples were collected in three locations in northern Italy: Milan, a large urban area, Oasi Bine, a rural site far from big city centers, and Alpe San Colombano, a remote, high altitude site in the Alps. They represent different particle sizes (PM(1), PM(2.5), PM(10)) and seasons (summer, fall, and winter). The analyzed samples were characterized in terms of PM total mass, total concentration of C(20)-C(32) n-alkanes and carbon preference index, CPI, to quantify the relative abundance of odd versus even n-alkanes. As alternative to the conventional method based on peak integration, a chemometric approach based on autocovariance function (EACVF) computation was found reliable to characterize the homologous series. In particular two parameters have proven useful chemical markers for tracking the biogenic and anthropogenic origins of n-alkanes: CPI(EACVF) and series %, estimating the % n-alkanes abundance relative to total alkane concentration. The investigated samples display a large variation in the n-alkanes relative abundance: the lowest values (series % = 1-14%) were found in summer and the highest (series % = 24-48%) in winter. In addition, a considerable seasonal variation of CPI(EACVF) values can be identified for all the sampling sites: the CPI(EACVF) values are close to 1 (CPI(EACVF) = 0.8-1.2) in the cold seasons, revealing a strong contribution from anthropogenic emissions, while spreader values (CPI(EACVF) = 0.9-3) were found in the warm season, that is, reflecting a variable contribution from biogenic sources in combination with anthropogenic emissions.
Asunto(s)
Aerosoles/química , Alcanos/análisis , Cromatografía de Gases y Espectrometría de Masas/métodos , Italia , Tamaño de la PartículaAsunto(s)
Cefotaxima/uso terapéutico , Neumonía/tratamiento farmacológico , Adolescente , Cefotaxima/efectos adversos , Niño , Preescolar , Infecciones por Haemophilus/tratamiento farmacológico , Haemophilus influenzae , Humanos , Lactante , Recién Nacido , Neumonía/etiología , Neumonía Neumocócica/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenesRESUMEN
Autosomal-recessive agammaglobulinemia is a rare and heterogeneous disorder, characterized by early-onset infections, profound hypogammaglobulinemia of all immunoglobulin isotypes and absence of circulating B lymphocytes. To investigate the molecular basis of the disease, 23 patients with early-onset disease and no mutations in Bruton tyrosine kinase, the gene responsible for X-linked agammaglobulinemia, were selected and analyzed by direct sequencing of candidate genes. Two novel mutations in the mu heavy chain (muHC) gene (IGHM) were identified in three patients belonging to two unrelated families. A fourth patient carries a previously described G>A nucleotide substitution at the -1 position of an alternative splice site in IGHM; here, we demonstrate that this mutation is indeed responsible for aberrant splicing. Comparison of bone marrow cytofluorimetric profiles in two patients carrying different mutations in the IGHM gene suggests a genotype-phenotype correlation with the stage at which B-cell development is blocked. Several new single nucleotide polymorphisms (SNPs) both in the muHC and in the lambda5-like/VpreB-coding genes were identified. Two unrelated patients carry compound heterozygous variations in the VpreB1 gene that may be involved in disease ethiology.