RESUMEN
The present study reports the characteristics of the biochemical profile of human gastric adenocarcinoma in comparison with that of healthy gastric mucosa, using ex vivo HR-MAS Magnetic Resonance Spectroscopy. Healthy human mucosa is mainly characterized by the presence of small metabolites (more than 50 identified) and macromolecules, whereas the adenocarcinoma spectra are dominated by the presence of signals due to triglycerides, whose content on the contrary is very low in healthy gastric mucosa. The use of spin-echo experiments enable us to detect some metabolites in the unhealthy tissues and to determine their variation with respect to the healthy ones. We have observed that the Cho:ChoCC ratio changes from 20:80 in the healthy tissues to 80:20 in the neoplastic gastric mucosa.
Asunto(s)
Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Mucosa Gástrica/metabolismo , Espectroscopía de Resonancia Magnética , Neoplasias Gástricas/metabolismo , Adenocarcinoma/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Ácidos Grasos/metabolismo , Femenino , Mucosa Gástrica/patología , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Neoplasias Gástricas/diagnósticoRESUMEN
The present case report was aimed at identifying the molecular profile characteristic of a primitive neuro-ectodermal tumor (PNET) in a 3-year-old child affected by a lesion localized in the cerebellar region. The histological diagnosis was medulloblastoma. In vivo single voxel 1H magnetic resonance spectroscopy (MRS) shows high specificity in detecting the main metabolic alterations in the primitive cerebellar lesion; a very high amount of the choline-containing compounds and very low level of creatine derivatives and N-acetylaspartate. Ex vivo high resolution magic angle spinning (HR-MAS) 1H magnetic resonance spectroscopy, performed at 9.4 Tesla on the neoplastic specimen collected during surgery, allows for the unambiguous identification of several metabolites giving a more in-depth evaluation of the metabolic pattern of the lesion. The ex vivo HR-MAS MR spectra show that the spectral detail is much higher than that obtained in vivo and that, for example, myo-inositol, taurine and phosphorylethanolamine contribute to the in vivo signal at 3.2 ppm, usually attributed to choline-containing compounds. In addition, the spectroscopic data appear to correlate with some morphological features of the medulloblastoma. Consequently, the present study shows that ex vivo HR-MAS 1H MRS is able to strongly improve the clinical possibility of in vivo MRS and can be used in conjunction with in vivo spectroscopy for clinical purposes.
Asunto(s)
Neoplasias Cerebelosas/diagnóstico , Espectroscopía de Resonancia Magnética/métodos , Meduloblastoma/diagnóstico , Tumores Neuroectodérmicos Primitivos/diagnóstico , Antígeno CD56/análisis , Neoplasias Cerebelosas/metabolismo , Preescolar , Diagnóstico Diferencial , Humanos , Inmunohistoquímica , Masculino , Meduloblastoma/metabolismo , Tumores Neuroectodérmicos Primitivos/metabolismoRESUMEN
The present study was aimed at identifying the molecular profile characteristic of the healthy human gastric mucosa. Ex vivo HR-MAS magnetic resonance spectroscopy performed at 9.4 Tesla (400.13 MHz for (1)H) on gastric specimens collected during endoscopy, permits the identification of more than forty species giving a detailed picture of the biochemical pattern of the gastric tissues. These preliminary data will be used for a comparison with gastric preneoplastic and neoplastic situations. Moreover, the full knowledge of the biochemical pattern of the healthy gastric tissues is the necessary presupposition for the application of magnetic resonance spectroscopy directly in vivo.
Asunto(s)
Mucosa Gástrica/química , Mucosa Gástrica/metabolismo , Biopsia , Humanos , Espectroscopía de Resonancia MagnéticaRESUMEN
The stability of chondroitin sulfate (CS) was studied under acidic, neutral and basic conditions at 30 and 60 degrees C. CS is remarkably stable under neutral conditions at low temperature, while it degrades at 60 degrees C producing low-molecular-mass fragments and desulfated products. This decomposition process begins at ca. 500-600 h and is consistent with an acid-catalyzed hydrolysis of glycosidic linkages caused by a drop in pH resulting from acidic products. Under basic conditions, a breakdown of glycosidic linkages causes a decrease in molecular mass due to the beta-elimination reaction, confirmed by a strong increase of absorbance at 232 nm and 1H NMR. Virtually no loss of O-sulfate groups can be detected in the base-treated CS. Under acidic conditions, the molecular mass decreases probably through hydrolysis of polysaccharidic linkages resulting in an increased number of reducing end groups. Little or no beta-elimination occurs. A loss of O-sulfate groups was detected, producing desulfated derivatives.
Asunto(s)
Sulfatos de Condroitina/química , Temperatura , Animales , Bovinos , Glicosaminoglicanos/química , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Factores de Tiempo , Tráquea/químicaRESUMEN
A series of 1,3-dioxolane-based ligands, bearing hydroxymethyl or ester functionalities, was synthesized and tested as potential muscarinic antagonists. The compounds display moderate to low affinity for the three receptor subtypes M1-M3, with some of them showing a significant selectivity for the M3 subtype. The configurational and conformational properties were studied using NOE experiments and vicinal coupling constants. The 1H and 13C NMR chemical shifts show stereochemically dependent trends. Quantitative analysis of conformer populations showed that the exocyclic CH2N CH3)3 group is prevalently in a pseudo-axial orientation in the cis isomers and in a pseudo-equatorial orientation in the trans isomers.
Asunto(s)
Dioxolanos/química , Dioxolanos/farmacología , Antagonistas Muscarínicos/química , Antagonistas Muscarínicos/farmacología , Animales , Dioxolanos/síntesis química , Cobayas , Íleon/efectos de los fármacos , Íleon/metabolismo , Espectroscopía de Resonancia Magnética , Masculino , Modelos Moleculares , Estructura Molecular , Antagonistas Muscarínicos/síntesis química , Miocardio/metabolismo , Conejos , Relación Estructura-Actividad , Conducto Deferente/efectos de los fármacos , Conducto Deferente/metabolismoRESUMEN
A series of 1,3-dioxolane-based ligands, bearing ether, thioether and related sulfoxide and sulfone functionalities, were synthesised and tested as potential muscarinic antagonists. The compounds display moderate to low affinity for the three receptor subtypes M1-M3, with some of them showing a significant selectivity for the M1-M3 over the M2 subtype.
Asunto(s)
Dioxolanos/síntesis química , Antagonistas Muscarínicos/síntesis química , Sulfonas/síntesis química , Sulfóxidos/síntesis química , Animales , Dioxolanos/química , Dioxolanos/farmacología , Cobayas , Corazón/efectos de los fármacos , Íleon/efectos de los fármacos , Técnicas In Vitro , Masculino , Antagonistas Muscarínicos/química , Antagonistas Muscarínicos/farmacología , Conejos , Receptor Muscarínico M1 , Receptor Muscarínico M2 , Receptor Muscarínico M3 , Receptores Muscarínicos/efectos de los fármacos , Relación Estructura-Actividad , Sulfonas/química , Sulfonas/farmacología , Sulfóxidos/química , Sulfóxidos/farmacología , Conducto Deferente/efectos de los fármacosRESUMEN
A regioregular head-to-head/ tail-to-tail poly(beta,beta'-disubstituted bithiophene) P1 was synthesised by chemical and electrochemical polymerisation of 2,2'-bithiophene that bears (S)-2-methylbutylsulfanyl chains in the beta and beta'-positions. The polymer was characterised by GPC, NMR and UV/Vis spectroscopy, CD, AFM and by electrochemical and conductivity measurements. The CD spectra of P1 in solutions in which poor solvents are present show interesting features and allow the presence of different optically active species to be distinguished. Upon varying the casting conditions of P1, different relative amounts of grainy and homogeneous aggregated phases were observed in AFM micrographies of films and corresponding negative or positive first Cotton effects were found in the CD spectra. AFM, CD and UV/Vis characterisations were also performed on an electrogenerated optically active polymer PE1, in order to make a comparison with the chemically synthesised one. The interesting, small band gap of P1 allows for easy p- and n-electrochemical doping.