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CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy, and safety of antidepressants. This article is an instruction manual and a guide for the deployment, in hospitals, of pharmacogenetics as an aid to the prescription of an antidepressant. It synthesizes the recommendations of two learned societies, the Clinical Pharmacogenetics Implementation Consortium (CPIC) and the Dutch Pharmacogenetics Working Group (DPWG), to produce a recommendation table adapted to a wide panel of antidepressants.
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Citocromo P-450 CYP2D6 , Farmacogenética , Antidepressivos/efeitos adversos , Citocromo P-450 CYP2D6/genética , Humanos , Polimorfismo Genético , PrescriçõesRESUMO
Ketamine, a non-competitive NMDA receptor antagonist, is used as a fast-acting antidepressant therapy in depressive disorders. This treatment provokes dissociative effects associating derealization and depersonalization, and a synaptogenic signaling cascade promoting brain plasticity. Despite several preliminary studies suggesting the usefulness of its combination with psychotherapy, administration of ketamine isn't generally combined with per- and post-infusion psychotherapy protocols in its clinical antidepressant use. However, the phenomenology of psychodysleptic experiences and the synaptogenic effect could potentiate cognitive and behavioral therapies (CBT). In this article, we purpose a practical protocol to Ketamine Augmented Psychotherapy (KAP) synthesizing contemporary data from the literature and our clinical experience. We detail proposals for clinical practice, and propose four important steps for the use of a psychodysleptic molecule for antidepressant purposes: preparation, administration, integration, and prolongation. Finally, we discuss the limits and prospects of this combination in the management of mood disorders.
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Ketamina , Antidepressivos/uso terapêutico , Transtornos Dissociativos , Humanos , Ketamina/uso terapêutico , Transtornos do Humor/tratamento farmacológico , Psicoterapia/métodosRESUMO
Samples of pasture vegetation, mainly Trifolium pratensis, were collected at the Botanic Garden of the University of Bologna during the period 1998-2000 and measured by gamma-spectrometry for determining thoron progeny. Concentrations of (212)Pb were between 1.5 and 20 Bq m(-2), with individual peaks up to 70 Bq m(-2). Soil samples were collected at the same location and physically characterised. Their chemical composition (particularly Th and U) was determined by X-ray fluorescence spectroscopy. Lead-212 on plants mainly originates from dry and wet deposition of this isotope generated in the lower atmosphere by the decay of its short-lived precursor (220)Rn, which is produced in the upper soil layers as a member of the natural thorium decay chain and exhales into the atmosphere. Concentrations of (220)Rn in the atmosphere depend on (1) the amount of Th present in soil, (2) the radon fraction which escapes from the soil minerals into the soil pore space, (3) its transport into the atmosphere, and (4) its redistribution within the atmosphere. The mobility of radon in soil pore space can vary by orders of magnitude depending on the soil water content, thus being the main factor for varying concentrations of (220)Rn and (212)Pb in the atmosphere. We present a simple model to predict concentrations of thoron in air and its progeny deposited from the atmosphere, which takes into account varying soil moisture contents calculated by the OPUS code. Results of this model show close agreement with our observations.
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Poluentes Radioativos do Ar/química , Atmosfera/química , Radônio/química , Poluentes Radioativos do Solo/química , Solo , Trifolium/química , Poluentes Radioativos do Ar/análise , Itália , Radioisótopos de Chumbo/análise , Radioisótopos de Chumbo/química , Modelos Teóricos , Radônio/análise , Poluentes Radioativos do Solo/análise , Espectrometria por Raios XRESUMO
Pulsed slit-jet high resolution (up to 0.0009 cm(-1) FWHM) infrared diode laser spectra of CF(3)Br, with natural isotopic abundance, were obtained in the region around 9.2 microm at the rotational temperature of about 50 K. In addition, diode laser spectra at reduced temperature (200 K) were recorded. We present here the rovibrational analysis of the nu(1) fundamental in the range 1075-1090 cm(-1). The fine structure of many P(J) and R(J) clusters has been well resolved for the first time. The assignment of rovibrational transitions has been accomplished up to K = 27, J = 63 for CFBr and K = 33, J = 62 for CFBr. A total of 636 (CFBr) and 880 (CFBr) lines were used in the final fit and a very accurate set of molecular constants, including the quartic centrifugal distortion coefficients for the v(1) = 1 state of both the bromine isotopologues, was obtained. In addition, spectral features belonging to the nu(1) + nu(6)-nu(6) hot band were unambiguously identified and a set of spectroscopic parameters were determined.
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Capillary electrophoresis-electrospray ionization multiple-stage ion-trap mass spectrometry (CE-MSn) and computer simulation of fragmentation are demonstrated to be effective tools to detect and identify phase I and phase II metabolites of oxycodone (OCOD) in human urine. OCOD is a strong analgesic used for the management of moderate to severe mainly postoperative or cancer-related pain whose metabolism in man is largely unknown. Using an aqueous pH 9 ammonium acetate buffer and CE-MSn (n < or = 5), OCOD and its phase I metabolites produced by O-demethylation, N-demethylation, 6-ketoreduction and N-oxidation (such as oxymorphone, noroxycodone, noroxymorphone, 6-oxycodol, nor-6-oxycodol, oxycodone-N-oxide and 6-oxycodol-N-oxide) and phase II conjugates with glucuronic acid of several of these compounds could be detected in alkaline solid-phase extracts of a patient urine that was collected during a pharmacotherapy episode with daily ingestion of 240-320 mg of OCOD chloride. The data for three known OCOD metabolites for which the standards had to be synthesized in-house, 6-oxycodol, nor-6-oxycodol and oxycodone-N-oxide, were employed to identify two new metabolites, the N-oxidized derivative of 6-oxycodol and an O-glucuronide of this compound. CE-MSn and computer simulation of fragmentation also led to the identification of the N-glucuronide of noroxymorphone, another novel OCOD metabolite for which no standard compound or mass spectra library data were available.
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Analgésicos Opioides/urina , Eletroforese Capilar/métodos , Espectrometria de Massas/métodos , Oxicodona/urina , HumanosRESUMO
The gas-phase infrared spectrum of cis-1-bromo-2-fluoroethene has been studied at low resolution in the range 200-6500 cm(-1), leading to a complete assignment of the fundamentals, except the lowest vibrational mode nu9 predicted at 167 cm(-1). The remaining vibrational structure has been mainly interpreted in terms of first overtone or two quanta combination bands. Isotopic (79/91)Br shift has been observed only in the nu8 fundamental. The equilibrium structure and the quadratic force field have been investigated theoretically at CCSD(T) level of theory employing Dunning's correlation consistent triple-zeta basis set. Cubic and semidiagonal quartic force field have been calculated using second-order Møller-Plesset perturbation theory and Ahlrich' split valence (SV) contracted basis set. After a minor scaled quantum mechanical (SQM) adjustment of the quadratic force constants, the vibrational analysis, based on the second-order perturbation theory, has been carried out with the calculated force constants.
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Etilenos/química , Hidrocarbonetos Halogenados/química , Gases , Estrutura Molecular , Teoria Quântica , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
INTRODUCTION: Up till now the phases adapted treatment of a pleural empyema unfortunately is still not obvious, but recently the operative spectrum has been widened in the field of video-assisted thoracoscopic surgery (VATS) of the pleural empyema. PATIENTS AND METHODS: In the present study we examined all our patients with a pleural empyema and we followed them for a postoperative period of 4 years analysing our therapy-efficacy and our treatment concept of pleural empyema. RESULTS: 52 out of 102 patients--who suffered from a pleural empyema in the last 10 years--were reexamined postoperatively. In 96% of the 102 cases we found a phase II-III empyema. Initially all patients were treated with a closed-chest-tube drainage, followed by an operation in 78%. In 6 cases a video-assisted-thoracoscopic evacuation of the cavity with an early decortication was performed. All the 52 patients who were treated in an early phase showed the best functional results 4 years later. CONCLUSION: Especially in phase III the open operative revision of a pleural empyema is the method of choice. In the fibrinopurulent phase the drainage therapy may be sufficient. If the empyema cavity is divided we recommend the early video-assisted-thoracoscopic revision of the thoracic empyema.
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Empiema Pleural/cirurgia , Cirurgia Torácica Vídeoassistida , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Tubos Torácicos , Criança , Pré-Escolar , Empiema Pleural/classificação , Empiema Pleural/etiologia , Empiema Pleural/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Taxa de SobrevidaRESUMO
The vapor-phase infrared spectrum of monofluoroacetonitrile (CH(2)FCN) has been recorded at high resolution in the nu(4) band region (1363-1398 cm(-1)) using a tunable diode laser spectrometer. A detailed assignment of the rotational structure of the expected a-/b-hybrid band has been made for a-type transitions with K(a)=19, J=61. The b-type transitions were too weak to be observed. Upper state spectroscopic constants including the sextic terms have been obtained from a set of unperturbed data employing the Watson A-reduced Hamiltonian in the I(r) representation. A number of perturbed transitions have been accounted for, including b- and c-type Coriolis resonances and anharmonic resonances between nu(4) and the nearby levels nu(5)+nu(12) and nu(11)+nu(12). The vibrational energies of these perturbing levels have been obtained from the reanalysis of the low-resolution infrared spectrum. Rotational constants and the band origin of the perturbers along with the interaction parameters with the v(4)=1 state have also been determined. Copyright 2001 Academic Press.
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The gas-phase IR spectrum of the nu(2) (A(1), 1610.33 cm(-1)) band of the deuterated isotopomer of diazirine, D(2)CN(2), a three-membered ring compound which belongs to the molecular symmetry point group C(2v), has been studied at a resolution of about 0.005 cm(-1). This vibrational mode which can be approximately described as N&dbond;N stretching is widely perturbed. This is due to various interactions with the tetrad consisting of the binary combinations nu(6) + nu(7) (A(1)), nu(7) + nu(9) (A(2)), nu(5) + nu(6) (B(2)), and nu(5) + nu(9) (B(1)), which form a relatively isolated pentad together with nu(2) in the wavenumber region 1560-1610 cm(-1). A simultaneous upper state analysis of nu(2) from a pentad model including these resonances has been performed and a set of spectroscopic parameters has been obtained. Since the four combination bands of the pentad are dark states, only band centers could be determined; in addition for nu(5) + nu(9) and nu(7) + nu(9) also the term (B - C)/2 has been obtained. A number of Coriolis interaction constants and the vibrational resonance (with nu(6) + nu(7)) parameter have been calculated as well. Copyright 2001 Academic Press.
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The gas-phase infrared spectrum of the nu(4) fundamental band of CH(2)(79)BrF was recorded in the 1010-1116 cm(-1) wavenumber region using a TDL spectrometer. In this first high-resolution investigation of the synthesized (79)Br isotopic form, more than 10 200 transitions of this a/b-hybrid band centered at 1068.5385 cm(-1) were assigned and, using the Watson's A-reduced Hamiltonian in the I(r)-representation, a reliable set of molecular constants for the excited state v(4) = 1 was determined. From ground state combination differences having rotational quantum numbers J and K(a) up to 97 and 21, respectively, improved and extended ground state rotational and centrifugal distortion constants were calculated as well. Comparison between the observed and calculated band intensities in appropriate regions of the spectrum gave an estimate of the transition dipole-moment ratio along the a and b axes as ||Deltaµ(a)/Deltaµ(b) || = 2.0 +/- 0.2, in agreement with the predicted theoretical value of 1.99. Copyright 2000 Academic Press.
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The existence of distinct tubulins in microtubules forming the sperm axoneme has been demonstrated in various species, whereas little is known about the distribution of tubulin variants in insect spermatozoa. In the present study, a panel of specific antibodies has been used to investigate the presence and localization of tubulin isotypes and post-translationally modified tubulins in the spermatozoon of the stick insect Bacillus rossius. Indirect immunofluorescence and immunogold staining showed differences in labelling in the mature sperm and that the tubulin epitopes localized differentially in the axoneme. In particular, the tyrosinated alpha-tubulin mainly occurs on doublets. These results provide an insight into the molecular composition of the microtubules forming the sperm axoneme of B. rossius and suggest that the structural specificity could reflect distinct functional roles within axonemal microtubules.
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Insetos/metabolismo , Insetos/ultraestrutura , Espermatozoides/metabolismo , Espermatozoides/ultraestrutura , Tubulina (Proteína)/metabolismo , Sequência de Aminoácidos , Animais , Epitopos/química , Epitopos/metabolismo , Masculino , Microscopia de Fluorescência , Microscopia Imunoeletrônica , Dados de Sequência Molecular , Processamento de Proteína Pós-Traducional , Cauda do Espermatozoide/metabolismo , Cauda do Espermatozoide/ultraestrutura , Tubulina (Proteína)/química , Tubulina (Proteína)/imunologiaRESUMO
The spectra of CH2F37Cl (95% isotopically pure sample) have been recorded at high resolution with a tunable diode laser spectrometer in the regions 979-1030 and 1108-1136 cm-1. The spectral analysis allowed us to assign about 2000 lines (J = 61, Ka = 26) of the nu9 band (nu0 = 1001.9360 cm-1), which, besides the expected c-type component, shows a more intense Coriolis-induced parallel component deriving its intensity from mixing with the nu4 vibrational state. In addition, the assignments of the nu4 band (nu0 = 1067.7138 cm-1), previously investigated, have been extended to higher Ka values and about 1300 new lines (J = 69, 17 = Ka = 26) have been identified. The nu4 and nu9 bands have been fitted simultaneously to account for the first-order a- and b-type Coriolis coupling; interaction constants and excited state parameters up to the sextic terms have been obtained using Watson's A-reduction Hamiltonian in the Ir representation. Copyright 1999 Academic Press.
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The two mid-infrared bands of the CF2&dbond;CHF molecule, nu5 centered at 1172.673 cm-1 and nu6 + nu9 at 1155.105 cm-1, were measured on a tunable diode laser spectrometer with a resolution near the Doppler limit. These vibrations of A' species give rise to a/b hybrid bands, even though our analysis has pointed out that the intensity of the a-type component is predominant. Most of the J and K structure has been resolved in different subbranches, and the rovibrational analysis led to the assignment of about 1400 (J = 60, Ka = 22, Kc = 60) and 90 (J = 56, Ka = 5, Kc = 56) lines of the nu5 and nu6 + nu9 bands, respectively. Using Watson's A-reduction Hamiltonian in the Ir representation, a set of accurate spectroscopic constants for the upper states has been derived from transitions free of major resonance effects. The rotational structure of the nu5 vibration also exhibits effects of Coriolis perturbation by a state identified as nu7 + nu11. Parameters for the perturber were determined from the interaction effects near the observed crossings, using a dyad model including first-order b-Coriolis interaction. Copyright 1998 Academic Press.
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Diode laser spectra of CH2 F37 Cl (95% isotopically pure sample) have been recorded in the 9.4 µm region characterized by the nu4 fundamental. The spectral analysis allowed the assignment of more than 3700 transitions with J = 92 and Ka = 16 of the expected a /b -hybrid structure. The nu4 fundamental, whose origin is at 1067.7140 cm-1 , mainly interacts through a - and b -type Coriolis coupling with the nu9 fundamental located at lower wavenumbers near 1002 cm-1 . Local effects arising from Fermi resonance with nu5 + nu6 have been observed for the K a ' = 14 level. An effective set of upper state molecular constants was determined by fitting the less perturbed transitions to the Watson's A-reduction Hamiltonian in the Ir representation. Due to the second-order a -type Coriolis resonance, a number of perturbation-allowed transitions of nu9 were observed and assigned near the avoided crossing. Using a suitable program, we experienced a two band system analysis which produced the molecular constants of the v 4 = 1 and v 9 = 1 states along with the interaction parameter. From spectral simulation of nu4 , the |Deltaµa /Deltaµb | dipole moment ratio was estimated to be 1.8 +/- 0.2.
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The 2nu1 + nu2 + 2nu3 band of ozone, occurring in the 4780 cm-1 region, has been observed for the first time, using a Fourier transform spectrometer, at 0.008 cm-1 resolution and using a large path length pressure product. Assignments of vibration-rotational transitions have been made up to J = 48 and Ka = 9. As a few levels with Ka = 1 or 2 are perturbed, it has been necessary to take into account the Coriolis resonance between the (212) and (141) vibrational states. With the effective Hamiltonian explicitly accounting for the interaction between these two states, the fit on 165 energy levels leads to the rms deviation of 1.9 x 10(-3) cm-1, which is near the experimental accuracy. Line intensities of the 2nu1 + nu2 + 2nu3 band have been measured and calculated. The set of spectroscopic parameters for interacting bands, as well as transition moment constants, is given. A complete list of line positions and intensities, with a cutoff of 1 x 10(-26) cm-1/molecule.cm-2 at 296 K up to J = 65 and Ka = 15, has been generated, which leads to the integrated band intensity Sv (2nu1 + nu2 + 2nu3) = (5.1 +/- 2.0) x 10(-23) cm-1/molecule.cm-2. Copyright 1997Academic Press
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The morphological organization of the male brood pouch epithelium of Syngnathus abaster, before, during, and after the breeding period, was observed by light and electron microscopy. Before gestation, the epithelium of the pouch wall was compact and consisted of three kinds of cells: typical epithelial cells (pavement cells), mitochondria-rich cells (MR cells), and, presumably, differentiating MR cells. In this stage, very few capillaries were observed beneath the epithelium. During egg incubation, the capillaries increased in number and size, large intercellular spaces formed among epithelial cells at their basal sides, MR cells were abundant, and differentiating MR cells were only occasionally observed. After incubation, MR cells degenerated by necrosis and apoptosis. The intercellular spaces between the epithelial cells disappeared and the number and size of the capillaries beneath the epithelium decreased. The presence of MR cells during gestation and their degeneration after incubation suggest that these cells play a pivotal role in the physiological functions of the brood pouch. The similar cytological characteristics of syngnathid pouch MR cells and chloride cells of the teleostean gills suggests that the Syngnathidae brood pouch is involved in osmoregulation of the fluid surrounding the developing embryos.
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A tunable diode laser has been incorporated as a source in an operating high resolution vacuum grating spectrometer. The advantages of such a system for recording molecular spectra have been elaborated. In the process of developing this system, several practical problems came about, and it has been considered useful to document the manner in which they have been resolved. In particular, for work in the region of 15 microm, it was advantageous to develop an air-spaced Fabry-Perot etalon to record fringes simultaneously with the scanning of molecular spectra. This was successfully done, and the upsilon(2) band lines of the HCN molecule at 14 microm have proved to be ideally suited for determining the fringe spacing spectroscopically.