RESUMO
Searches for dark matter axions involve the use of microwave resonant cavities operating in a strong magnetic field. Detector sensitivity is directly related to the cavity quality factor, which is limited, until recently, to the use of non-superconducting metals by the presence of the external magnetic field. In this paper, we present a cavity of novel design whose quality factor is not affected by a magnetic field. It is based on a photonic structure by the use of sapphire rods. The quality factor at cryogenic temperature is in excess of 5 × 105 for a selected mode.
RESUMO
The stability of silver nanoplatelet (NP) suspensions prepared with different concentrations of trisodium citrate (TSC) was studied by depolarized dynamic light scattering (DDLS) and UV-vis spectrometry. The morphology of the nanoparticles, as well as the color and stability of the sols, are tuned by the concentration of the capping agent. The nanoparticles prepared with high TSC concentration (>10-4 M) are blue triangular NPs showing a slight truncation of the tips with aging. When low TSC concentrations are used, the color of the sols changes from blue to yellow with aging time and a strong modification of the morphology occurs: the nanoparticle shape changes from triangular to spherical. Remarkably, they show a high degree of anisotropy. The aging process was followed by the UV-vis spectra and by measuring the rotational diffusion coefficient by DDLS, providing information on the nanoparticle size and shape evolution. The high intensity of depolarized signal and the high value of rotational diffusion coefficient suggest that the aging process increases the thickness and the roughness of the nanoparticles.
RESUMO
A method for the separation of a mixture of terbutaline and non-steroidal anti-inflammatory drugs was developed using capillary electrophoresis with a new hemispherodextrin, ad hoc designed, the lysine - bridged hemispherodextrin (THLYSH). The use of lysine residues to bridge the trehalose capping unit moiety to the cyclodextrin cavity gives rise to a receptor with two long chains with amine nitrogen atoms, whose charge can be easily tuned as a function of the solution pH. The new hemispherodextrin was accurately characterised by ESI-MS and NMR spectroscopy, also highlighting its protonation behaviour. Circular dichroism and ESR spectroscopy measurements were also carried out to test its inclusion ability towards anthraquinone-3-sulfonate and its metal coordination ability towards copper(II) ion, respectively. Analogously to the other hemispherodextrins, the main skill of this new derivative lies in its chiral selector properties, as shown by the separation of the enantiomeric pairs of terbutaline and ibuprofen, flurbiprofen, suprofen and tiaprofenic acid by capillary electrophoresis. The focused use of the solution equilibria involved in the separations made it possible to understand the phenomena occurring in solution, and to finely tune the charge status of the receptor. In this way the chiral separation of the racemic mixture was successfully obtained, even if the receptor was individually used, differently by the other hemispherodextrins previously studied whose chiral separation capabilities are present only if used as binary mixtures.
Assuntos
Eletroforese Capilar , Ciclodextrinas , Concentração de Íons de Hidrogênio , Lisina , Estereoisomerismo , TerbutalinaRESUMO
Psychotropic medications target glycogen synthase kinase 3ß (GSK3ß), but the functional integration with other factors relevant for drug efficacy is poorly understood. We discovered that the suggested psychiatric risk factor FK506 binding protein 51 (FKBP51) increases phosphorylation of GSK3ß at serine 9 (pGSK3ß(S9)). FKBP51 associates with GSK3ß mainly through its FK1 domain; furthermore, it also changes GSK3ß's heterocomplex assembly by associating with the phosphatase PP2A and the kinase cyclin-dependent kinase 5. FKBP51 acts through GSK3ß on the downstream targets Tau, ß-catenin and T-cell factor/lymphoid enhancing factor (TCF/LEF). Lithium and the antidepressant (AD) paroxetine (PAR) functionally synergize with FKBP51, as revealed by reporter gene and protein association analyses. Deletion of FKBP51 blunted the PAR- or lithium-induced increase in pGSK3ß(S9) in cells and mice and attenuated the behavioral effects of lithium treatment. Clinical improvement in depressive patients was predicted by baseline GSK3ß pathway activity and by pGSK3ß(S9) reactivity to ex vivo treatment of peripheral blood mononuclear lymphocytes with lithium or PAR. In sum, FKBP51-directed GSK3ß activity contributes to the action of psychotropic medications. Components of the FKBP51-GSK3ß pathway may be useful as biomarkers predicting AD response and as targets for the development of novel ADs.
Assuntos
Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas de Ligação a Tacrolimo/genética , Adulto , Animais , Antidepressivos/farmacologia , Biomarcadores/sangue , Técnicas de Cultura de Células , Linhagem Celular , Quinase 5 Dependente de Ciclina , Feminino , Glicogênio Sintase Quinase 3 beta , Células HEK293 , Humanos , Leucócitos Mononucleares/metabolismo , Lítio , Masculino , Camundongos , Pessoa de Meia-Idade , Fosforilação/efeitos dos fármacos , Psicotrópicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas de Ligação a Tacrolimo/metabolismo , beta Catenina/metabolismoRESUMO
Major depressive disorder (MDD) is one of the leading causes of global disability. It is a risk factor for noncompliance with medical treatment, with about 40% of patients not responding to currently used antidepressant drugs. The identification and clinical implementation of biomarkers that can indicate the likelihood of treatment response are needed in order to predict which patients will benefit from an antidepressant drug. While analyzing the blood plasma proteome collected from MDD patients before the initiation of antidepressant medication, we observed different fibrinogen alpha (FGA) levels between drug responders and nonresponders. These results were replicated in a second set of patients. Our findings lend further support to a recently identified association between MDD and fibrinogen levels from a large-scale study.
Assuntos
Antidepressivos/farmacologia , Transtorno Depressivo Maior/sangue , Transtorno Depressivo Maior/tratamento farmacológico , Fibrinogênio/análise , Resultado do Tratamento , Adulto , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteoma/análise , Adulto JovemRESUMO
The enantioseparation of the enantiomeric pairs of 10 Dns derivatives of alpha-amino acids was successfully carried out by using for the first time the 3-amino derivative of the gamma-cyclodextrin. The effects of pH and selector concentration on the migration times and the resolutions of analytes were studied in detail. 3-Deoxy-3-amino-2(S),3(R)-gamma-cyclodextrin (GCD3AM) shows very good chiral recognition ability even at very low concentrations at all the three investigated values of pH, as shown by the very large values of selectivity and resolution towards several pairs of amino acids. The role played by the cavity, the substitution site and the protonation equilibria on the observed properties of chiral selectivity, on varying the specific amino acid involved, is discussed.
Assuntos
Aminoácidos/análise , Eletrocromatografia Capilar/métodos , Compostos de Dansil/análise , gama-Ciclodextrinas/química , Aminoácidos/química , Compostos de Dansil/química , Concentração de Íons de Hidrogênio , Sensibilidade e Especificidade , EstereoisomerismoRESUMO
Enantiomeric pairs of 11 dansyl derivatives of alpha-amino acids were used as analytes in electrokinetic chromatography to test the ability as chiral selectors of two pure derivatives of beta-cyclodextrin: the ethylendiamine derivative in primary position (CDen) and a member of a new class of receptors, the cysteamine-bridged hemispherodextrin THCMH. The selectivity obtained by the presence of the hemispherodextrin, appears particularly promising as shown by the large values of resolution obtained. The importance of a detailed analysis of these data is discussed in terms of suggestions for a rational approach to separation science.
Assuntos
Aminoácidos/isolamento & purificação , Cromatografia Capilar Eletrocinética Micelar/métodos , Ciclodextrinas , Compostos de Dansil , Eletroforese Capilar , EstereoisomerismoRESUMO
The separation of three pairs of enantiomeric herbicides has been successfully achieved by capillary electrophoresis at two different pH values in the presence of cyclodextrin derivatives previously synthesized in our laboratory. Two of these derivatives constitute a new class of receptor, the hemispherodextrins, in which a trehalose capping moiety is bonded to beta-cyclodextrin. Because of their peculiar structure hemispherodextrins have very promising characteristics and the low receptor concentration required to achieve separation deserves particular interest.
Assuntos
Ciclodextrinas/química , Eletroforese Capilar/métodos , Algoritmos , Sequência de Carboidratos , Dados de Sequência Molecular , EstereoisomerismoRESUMO
A capped cyclodextrin derivative (THCMH), called hemispherodextrin, was observed to behave as a very efficient chiral selector for a variety of phenoxyacid enantiomeric pairs, both at pH 6 and pH 9. The very low concentration necessary to obtain separation was particularly impressive. The behaviour of THCMH was compared with that of other hemispherodextrins and cyclodextrin derivatives and the conclusions are reported. Some interesting conclusions are drawn by comparing the behaviour of THCMH with that of other hemispherodextrins reported elsewhere.
Assuntos
Ciclodextrinas/química , Eletroforese Capilar/instrumentação , Concentração de Íons de Hidrogênio , EstereoisomerismoRESUMO
The authors report three cases of pregnant women who were incapable or unable to freed themselves enterally and were monitored by the Division of Obstetrics and Gynecology at the "Burlo Garofolo" Institute for Infancy from 1992 to 1996. The series included two patients suffering from severe hyperemesis gravidarum and a third patient with severe atopic eczema secondary to food allergens. Starting at different stages of pregnancy these patients were treated using total parenteral nutrition (TPN) following the placement of a venous catheter using percutaneous access through the subclavian artery and leading into the superior vena cava. This solution not only ensured an appropriate calorie intake but also enabled electrolytic controls to be performed, adapting the intake of these elements to the real needs of the patients assessed by means of regular hematochemical tests. It is also worth pointing out that the calorie intake supplied during TPN was achieved through the use of lipid emulsions whose administration during pregnancy has been regarded as being risky owing to the possible onset of fatty placental infiltrations and the enhanced risk of premature birth. The authors underline the good results obtained in this series using TPN both with regard to the satisfactory level of maternal nutrition and the optimal evolution of pregnancy leading to the birth of healthy neonates with a normal weight.
Assuntos
Dermatite Atópica/complicações , Hiperêmese Gravídica/complicações , Nutrição Parenteral Total , Complicações na Gravidez/terapia , Adulto , Feminino , Humanos , Gravidez , Trimestres da GravidezRESUMO
A modified beta-cyclodextrin bearing a 2-aminomethylpyridine binding site for copper(II) (6-deoxy-6-[N-(2-methylamino)pyridine)]-beta-cyclodextrin, CDampy) was synthesized by C6-monofunctionalization. The acid-base properties of the new ligand in aqueous solution were investigated by potentiometry and calorimetry, and its conformations as a function of pH were studied by NMR and circular dichroism (c.d.). The formation of binary copper(II) complexes was studied by potentiometry, EPR, and c.d.. The copper(II) complex was used as chiral selector for the HPLC enantiomeric separation of underivatized aromatic amino acids. Enantioselectivity in the overall stability constants of the ternary complexes with D- or L-Trp was detected by potentiometry, whereas the complexes of the Ala enantiomers did not show and difference in stability. These results were consistent with a preferred cis coordination of the amino group of the ligand and of the amino acid in the ternary complexes ("cis effect"), which leads to the inclusion of the aromatic side chain of D-Trp, but not of that of L-Trp. In Trp-containing ternary complexes, the two enantiomers showed differences in the fluorescence lifetime distribution, consistent with only one conformer of D-Trp and two conformers of L-Trp, and the latter were found to be more accessible to fluorescence quenching by acrylamide and KI.
Assuntos
Aminopiridinas/química , Cobre/química , Ciclodextrinas/química , beta-Ciclodextrinas , Alanina/química , Aminopiridinas/síntese química , Calorimetria , Cromatografia Líquida de Alta Pressão , Dicroísmo Circular , Ciclodextrinas/síntese química , Espectroscopia de Ressonância de Spin Eletrônica , Espectroscopia de Ressonância Magnética , Conformação Molecular , Potenciometria , Espectrometria de Fluorescência , Espectrofotometria Ultravioleta , Estereoisomerismo , Termodinâmica , Triptofano/químicaRESUMO
The isolation by gel-permeation chromatography on Sephadex G-100 of a non-covalent complex of Cibacron Blue F3G-A (CB) with human serum albumin (HSA) is described. The complex presents a molar ratio of 3:1 CB-HSA and can be re-chromatographed under the same conditions without modification of its composition. However, complete dissociation occurs when the complex is chromatographed in the presence of denaturing agents. The effect of pH on the molar composition of the complex was also investigated by gel-permeation chromatography. Analogous complexes between CB and A and C cyanogen bromide fragments of unreduced HSA were also isolated by gel-permeation chromatography on Sephadex G-50. They present a molar ratio of 0.8:1 and 1.3:1 CB-protein for fragments A and C, respectively. These results suggest that two of the three molecules of CB bound to HSA may be located in the hydrophobic pocket corresponding to subdomain IIA, with the other molecule in the hydrophobic site corresponding to subdomain IIIA. The UV-Vis and dichroic circular spectra of the isolated complexes are reported.
Assuntos
Cromatografia em Gel/métodos , Albumina Sérica/isolamento & purificação , Triazinas/isolamento & purificação , Cromatografia por Troca Iônica , Corantes , Brometo de Cianogênio/química , Humanos , Concentração de Íons de Hidrogênio , Fragmentos de Peptídeos/isolamento & purificação , Albumina Sérica/química , Espectrofotometria Ultravioleta , Triazinas/químicaRESUMO
The determination of the tryptic peptide mapping of sequence 299-585 (cyanogen bromide fragment A) of human serum albumin (HSA) by chemical and enzymatic cleavages and combined use of HPLC and FAB-MS is described. Reduction and carboxymethylation of A gave four subfragments which were separated by HPLC and digested with trypsin. Tryptic fragments were separated by HPLC and identified by FAB-MS. A total coverage of about 95% of the entire sequence was obtained. Tryptic fragments not identified include mostly single amino acids and very hydrophilic peptides which were absent in the chromatograms. The high reproducibility of the experiments and the satisfactory yield of the tryptic fragments identified demonstrate the great potential of the combined use of HPLC separation and FAB-MS analysis for the structural investigation of HSA.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Albumina Sérica/química , Espectrometria de Massas de Bombardeamento Rápido de Átomos/métodos , Sequência de Aminoácidos , Humanos , Dados de Sequência Molecular , Mapeamento de Peptídeos , Reprodutibilidade dos Testes , TripsinaRESUMO
The cytotoxicity of some copper(II) compounds against the mouse cancer cell line B16, murine L929, human KB cells, and fibroblasts was investigated. All the copper(II) systems tested were shown to have pronounced toxicity against transformed cells and a cytostatic effect against untransformed cells, i.e., human fibroblasts. A careful speciation of the actual in vitro conditions reveals that copper(II) is essentially present as mixed complexes formed with the amino acids of the culture medium, [Cu(glutamine)(histidine)] being the main species. It was found that the cytotoxic activity is related to the amount of copper(II) contained in the tested compounds.
Assuntos
Antineoplásicos/síntese química , Cobre/química , Acetatos/química , Acetatos/farmacologia , Aminoácidos , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Cobre/farmacologia , Cobre/uso terapêutico , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Imidazóis/química , Imidazóis/farmacologia , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/patologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Células Tumorais CultivadasRESUMO
Cefixime, a new orally absorbed iminomethoxyaminothiazolyl cephalosporin, was tested against some microorganisms involved in upper and lower respiratory tract infections such as Haemophilus (influenzae and parainfluenzae), Moraxella catarrhalis and Streptococcus pneumoniae, isolated in the period from November 1990 to April 1991. Its activity was compared to nine other antimicrobial agents: erythromycin, trimethoprim-sulfamethoxazole, ampicillin, amoxicillin-clavulanate, cefaclor, ceftazidime, ceftriaxone, cefotaxime and ofloxacin. Cefixime inhibits 90% of S. pneumoniae, H. influenzae and H. parainfluenzae, both beta-lactamase producers (BLP) or not (NBLP) at concentrations of less than 0.25 mg/l. It inhibits 90% of M. catarrhalis (BLP and NBLP) at concentrations of less than 1 mg/l. In general, cefixime has a superior in vitro activity with respect to cefaclor and the other cephalosporins as well as erythromycin and amoxicillin (the last one in BLP strains). In the evaluation of the antibacterial activity of beta-lactam against Haemophilus and M. catarrhalis, the authors observed different indications in the guidelines for ampicillin. Cefixime is not destroyed by the plasmid-mediated beta-lactamase produced by Haemophilus sp. and M. catarrhalis (TEM and ROB in Haemophilus strains and BRO in M. catarrhalis). In view of its excellent in vitro activity against the commonly encountered respiratory tract pathogens, cefixime is indicated in the therapy of these infections.
Assuntos
Cefotaxima/análogos & derivados , Haemophilus influenzae/efeitos dos fármacos , Haemophilus/efeitos dos fármacos , Moraxella catarrhalis/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Administração Oral , Cefixima , Cefotaxima/farmacologia , Cefalosporinas/farmacologia , Testes de Sensibilidade Microbiana , Especificidade da EspécieRESUMO
The authors have studied the effects of an oral or intravenous glucose load, of insulinic hypoglycemia, of arginine and the effects of the 2-deoxi-glucose on the plasmatic concentration of HPL and GH on pregnant women at different times during their pregnancy. None of the used tests seemed able to modify in any way the plasmatic concentration of the placental lactogen hormone; the somatotropinic response to the different stimuli happens to be lower than that found in non pregnant women of the same age. We and by asserting that unlike what happens with the GH, there does not exist a direct "feedback" between the modifications of plasmatic concentration of the main underlayers and HPL.