RESUMEN
OBJECTIVE: This study aimed to quantitatively investigate airborne particle load in the operating room during endoscopic or microscopic epitympanectomy or mastoidectomy. METHOD: In the transcanal endoscopic ear surgery group, drilling was performed underwater. A particle counter was used to measure the particle load before, during and after drilling during transcanal endoscopic ear surgery or microscopic ear surgery. The device counted the numbers of airborne particles of 0.3, 0.5 or 1.0 µm in diameter. RESULTS: The particle load during drilling was significantly higher in the microscopic ear surgery group (n = 5) than in the transcanal endoscopic ear surgery group (n = 11) for all particle sizes (p < 0.01). In the transcanal endoscopic ear surgery group, no significant differences among the particle load observed before, during and after drilling were seen for any of the particle sizes. CONCLUSION: Bone dissection carries a lower risk of airborne infection if it is performed using the endoscopic underwater drilling technique.
Asunto(s)
Quirófanos , Procedimientos Quirúrgicos Otológicos , Humanos , Procedimientos Quirúrgicos Otológicos/métodos , Endoscopía/métodos , Mastoidectomía , Disección , Estudios RetrospectivosRESUMEN
Osteoporosis is a chronic degenerative disease of bones in which the primary type of it affects generally women after postmenopause. According to the literature the panoramic indices are valuable morphometric and visual tools to detect the disorder in a n early and asymptomnatic stage. The goals of study were to evaluate the reproducibility of mandibular cortical and panoramic indices and to assess population-specific index parameters. Panoramic radiographs of 50 osteoporotic (age = 65,1 ? 5,9) and 36 control (age = 66,4 ? 7,1) women were evaluated for the cortical (MCI) and panoramic (PMI) indices by 2 experienced clinicians and 40 dental students with basic clinical experiences. Statistical analysis of data was preformed using SPSS software. the result of MCI and PMI indexes demonstrated high interobserver agreement between the two clinicians but in MCI data, recorded by the clinicians and students, showed statistically significant differences. On the other hand the mean and threshold values of the indices proved to be different from what we had expected from other surveys. Although the panoramic images are taken for specific dental indications that would improve the screening efficiency of osteoporosis when the clinician recognizes the signs of it on the radiographs.
Asunto(s)
Mandíbula/diagnóstico por imagen , Osteoporosis/diagnóstico por imagen , Radiografía Panorámica , Anciano , Competencia Clínica , Femenino , Humanos , Estudiantes de OdontologíaRESUMEN
High throughput screening of our small molecule combinatorial library identified a class of benzoylnaphthalenehydrazones with modest affinity for the human glucagon receptor. Optimization of this initial hit through a series of targeted libraries and traditional medicinal chemistry led to ligands with nanomolar affinities. Pharmacological evaluation demonstrated that these ligands were competitive glucagon receptor antagonists. Intravenous administration of a representative benzoylnaphthalenehydrazone into rats attenuated glucagon-stimulated glucose levels.
Asunto(s)
Benzamidas/síntesis química , Hidrazonas/síntesis química , Receptores de Glucagón/antagonistas & inhibidores , Animales , Benzamidas/química , Benzamidas/farmacología , Unión Competitiva , Glucemia/análisis , Línea Celular , Técnicas Químicas Combinatorias , AMP Cíclico/biosíntesis , Glucagón/farmacología , Humanos , Hidrazonas/química , Hidrazonas/farmacología , Técnicas In Vitro , Hígado/metabolismo , Masculino , Ensayo de Unión Radioligante , Ratas , Ratas Sprague-Dawley , Ratas Wistar , Receptores de Glucagón/metabolismo , Relación Estructura-ActividadRESUMEN
Two combinatorial filtering methods for efficiently selecting reaction products with desired properties are presented. The first, "direct reactants" method is applicable only to those molecular properties that are strictly additive or approximately additive, with relatively small interference between neighboring fragments. This method uses only the molecular properties of reactants. The second, "basis products" method can be used to filter not only the strictly additive properties but also the approximately additive molecular properties where a certain degree of mutual influence occurs between neighboring fragments. This method requires the molecular properties of the "basis products," which are the products formed by combining all the reactants for a given reaction component with the simplest set of complementary reactant partners. There is a one-to-one correspondence between the reactants and the "basis products." The latter is a product representation of the former. High efficiency of both methods is enhanced further by a tree-sorting and hierarchical selection algorithm, which is performed on the reaction components in a limited space determined systematically from the filtering criteria. The methods are illustrated with product logPs, van der Waals volumes, solvent accessible surface areas, and other product properties. Good results are obtained when filtering for a number of important molecular properties in a virtual library of 1.5 billion.
Asunto(s)
Técnicas Químicas Combinatorias/métodos , Algoritmos , Diseño de Fármacos , Modelos QuímicosRESUMEN
Intrahelical photoinduced electron transfer processes (ET) in conformationally restricted oligopeptides have been studied by nanosecond time-resolved transient spectroscopy. The helical peptides were constructed from sterically hindered alpha-aminoisobutyric acid (Aib) and two cyclic alpha-amino acids (Aib class) bearing electron acceptor and donor side chains (DkNap, ThQx). This helical backbone design provides high conformation stability, as previously demonstrated, and yields reliable 3(10)-helical architectures in solution. The forward ET between ThQx and 3DkNap is followed by a slow back ET thus giving rise to an accumulation of the charge-separated ion pairs for hundreds of nanoseconds. We demonstrate the modulation of electronic interactions by the number of intervening Aib residues separating acceptor-donor side chains and propose modifications of the peptide framework by inclusion of a non-Aib amino acid residue. These well-defined and sterically stable frameworks are suited for the precise evaluation of intrahelical electron transfer processes mediated by peptides.
Asunto(s)
Oligopéptidos/química , Ácidos Aminoisobutíricos/química , Transporte de Electrón , Técnicas In Vitro , Modelos Moleculares , Oxidación-Reducción , Fotoquímica , Estructura Secundaria de ProteínaRESUMEN
An analysis of protrusive jaw movement was carried out using Quick-Axis mandibular motion analyser. The condylar path tracings were recorded of 46 individuals (21 women and 25 men). Three recordings were performed on each side and a tangent to the condylar curves was drawn to calculate the condylar angle. Considering all dates the mean value of angulation was 52.2 degrees. There were no statistically significant differences between the two sexes and sides. The authors' findings suggest it is advisable to perform three consecutive registrations on each side and calculate a mean condylar angle to gain a better result.
Asunto(s)
Mandíbula/fisiología , Cóndilo Mandibular/fisiología , Articulación Temporomandibular/fisiología , Adulto , Femenino , Humanos , Masculino , Mandíbula/anatomía & histología , Cóndilo Mandibular/anatomía & histología , Articulación Temporomandibular/anatomía & histologíaRESUMEN
1D and 2D NMR spectroscopy is used to determine the helical stability of two Aib-rich peptides, iBoc-(Aib)3-DkNap-Leu-Aib-Ala-(Aib)2-NH(CH2)2OCH3 (Dk4[7/9]) and Ac-(Aib)2-beta-(1'-naphthyl)Ala-(Aib)2-Phe-(Aib)2-NHMe (Nap3Phe6[6/8]), where the bracket notation indicates the number of Aib-class residues/total number of residues. 2D ROESY experiments, carried out previously on Nap3Phe6[6/8] in DMSO (Basu & Kuki, 1993), showed that this compound adopts the 3(10)-helical conformation at 20 degrees C. The first step in the present work is to apply this technique to the peptide Dk4[7/9], demonstrating that it likewise adopts the 3(10)-helical conformation in chloroform at 20 degrees C. The amide proton shifts of Nap3-Phe6[6/8] in DMSO and Dk4[7/9] in C2D2Cl4 were then monitored by means of 1D NMR over a large temperature range, up to 150 and 120 degrees C, respectively. The nonamer Dk4[7/9] exhibits no evidence of any conformational or unfolding transition as the temperature is raised. The nearly temperature independent amide proton chemical shifts of this nonamer are an indication of retention of the intrahelical hydrogen bonding, which was then verified directly by solvent perturbation with DMSO at 120 degrees C. The resulting hydrogen-bonding pattern confirms that Dk4[7/9] retains its 3(10)-helical conformation in C2D2Cl4 over the entire temperature range. This conformational quietness is exploited to examine the intrinsic temperature dependence of free versus intrahelically hydrogen bonded amide proton shifts within the same peptide structure. It is also shown that Nap3Phe6[6/8] retains its 3(10)-helical conformation over the entire temperature range in the stronger hydrogen-bonding solvent DMSO. The extreme thermal stability of these octameric and nonameric Aib-rich peptides in both solvents is contrasted with that of much longer alanine-rich peptides in water.
Asunto(s)
Ácidos Aminoisobutíricos/química , Oligopéptidos/química , Secuencia de Aminoácidos , Estabilidad de Medicamentos , Enlace de Hidrógeno , Espectroscopía de Resonancia Magnética , Datos de Secuencia Molecular , Estructura Molecular , Conformación Proteica , Estructura Secundaria de Proteína , Solventes , TemperaturaRESUMEN
We examined the effect of total parathyroidectomy (PTX) on renal anemia in 20 dialysis patients with secondary hyperparathyroidism. We obtained the following results. (1) Before PTX, 13 of these patients were not treated with erythropoietin (EPO) while the remaining 7 patients received EPO therapy. (2) In 8 out of 13 cases without recombinant human EPO treatment before PTX, a 10% increase in RBC was observed after PTX. (3) In 7 of the patients who were treated with EPO before PTX, anemia was improved after PTX despite discontinuation of EPO therapy in 2, a reduced dose of EPO in 3 and the same dose of EPO in 2. Our data is consistent with the notion that elevated blood levels of PTH in patients with chronic renal failure participate in the genesis of anemia of renal failure.
Asunto(s)
Anemia/tratamiento farmacológico , Eritropoyetina/uso terapéutico , Hiperparatiroidismo Secundario/etiología , Fallo Renal Crónico/tratamiento farmacológico , Diálisis Renal/efectos adversos , Adulto , Anemia/etiología , Femenino , Humanos , Hiperparatiroidismo Secundario/cirugía , Masculino , Persona de Mediana Edad , Paratiroidectomía , Proteínas Recombinantes/farmacologíaRESUMEN
Two sterically constrained peptides [iBoc-Aib-Aib-Aib-DkNap-Leu-Qx-Ala-Aib-Aib-Fl, (Dk4Qx6[7/9]) and iBoc-Aib-Aib-Aib-DkNap-Leu-Aib-Ala-Aib-Aib-Fl, (Dk4[7/9])] containing alpha-aminoisobutyric acid (Aib) and Aib-class amino acids in conjunction with selected mono-alpha-alkyl amino acids were synthesized by an optimized TBTU/HOBt procedure. The use of Aib-class amino acids (e.g. DkNap and Qx), defined and discussed here, gives rise to the same overwhelmingly 3(10)-helical backbone conformation as that provided by simpler Aib-rich peptides and homopeptides. The synthetic alpha,alpha-dialkylamino acids (DkNap, Qx) are aromatic homologues of the known alicyclic variants of Aib, the Ac5c and Ac6c amino acids. Two new organic solubilizing groups for peptides, iBoc and 2-methoxyethylamine, are introduced. The 1H nuclear magnetic resonance analyses of the Dk4[7/9] and Dk4Qx6[7/9] peptides demonstrate the unambiguous 3(10)-helical hydrogen bonding pattern of these peptides, confirming the design objective of these sequence patterns containing greater than 50% Aib and Aib-class composition.
Asunto(s)
Aminobutiratos/química , Oligopéptidos/química , Secuencia de Aminoácidos , Enlace de Hidrógeno , Datos de Secuencia Molecular , Oligopéptidos/síntesis química , Conformación ProteicaRESUMEN
The very strong helical propensity of peptides rich in alpha-aminoisobutyric acid (Aib) has enabled the design of a set of helices containing as guest amino acids one fluorescent chromophore, beta-(1'-naphthyl)-L-alanine, and one heavy atom perturber, p-bromo-L-phenylalanine. The fluorescence of the chromophoric residue was monitored in this set to explore heavy atom induced enhanced intersystem crossing as a potentially useful tool for exploring remote electronic interactions in biomolecules. The peptides in this set were sequence isomers of each other and were designed such that the chromophore and the perturber were separated by two, one, or zero Aib residues. The respective distances between the aromatic side chains are then modulated by the twist of the helix. All peptides showed steady-state fluorescence quenching, and on the basis of further time-resolved triplet-triplet absorption experiments, two mechanisms for the heavy atom induced fluorescence quenching were established: (i) a weak and nominally spin-forbidden singlet-triplet energy transfer and (ii) the remote heavy atom effect (RHAE) on the intersystem crossing within the fluorophore. Both the rate of singlet-triplet energy-transfer and the RHAE are at their maxima in the peptide with the largest sequence separation but the smallest direct distance between the chromophore and the perturber. Thus neither quenching mechanism is controlled by the length of the intervening covalent pathway. Subtle factors arising from the structure of the intervening peptide backbone apparently contribute to the RHAE for the peptides with shorter sequence separation. Because the sensitivity to the remote heavy atom is a measure of electronic delocalization, this result may have significance for the understanding of the role of helices in biological electron-transfer interactions.
Asunto(s)
Ácidos Aminoisobutíricos/química , Péptidos/química , Bromobencenos , Electroquímica , Transferencia de Energía , Fluorescencia , Colorantes Fluorescentes , Enlace de Hidrógeno , Espectroscopía de Resonancia Magnética , Estructura Molecular , Fenilalanina/análogos & derivados , Conformación Proteica , Estructura Secundaria de Proteína , Soluciones , Espectrometría de Fluorescencia , beta-Alanina/análogos & derivadosRESUMEN
The analysis of the factors that control the helical folding of Aib-rich peptides is extended to include sensitivity to sequence patterns, and in particular the presence of contiguous non-Aib alpha-mono-alkylated residues. The distinct hydrogen-bonding network of the 3(10)-helix, as contrasted with that of the competing alpha-helical structure, is explicitly incorporated into a theoretical model for the 3(10)-helix/alpha-helix equilibrium constant for a given peptide. Finite length effects and the "extra" intrahelical hydrogen bond of the 3(10) form are expressed naturally as a result of this loop analysis. This semiempirical model captures all the established features of existing empirical rules for helical conformational transitions in Aib-rich sequences, as well as the recently detected helical transition induced solely by sequence permutation.
Asunto(s)
Ácidos Aminoisobutíricos/química , Oligopéptidos/química , Secuencia de Aminoácidos , Enlace de Hidrógeno , Matemática , Modelos Moleculares , Datos de Secuencia Molecular , Conformación ProteicaRESUMEN
The solution conformation of peptides rich in the alpha, alpha-dialkylated amino acid Aib has proven to be a subtle problem, not because of helix/coil transitions, but rather because of alpha-helical/3(10)-helical competition. A special series of peptides containing 75% Aib has been synthesized that feature identical amino acid composition but differing sequences; they are sequence permutation isomers. Nuclear magnetic resonance hydrogen-bonding studies reveal that there is a sequence permutation induced transition between the two alternative helical forms within this set. The implications for the design and conformational prediction of helical Aib-rich peptides are discussed.
Asunto(s)
Ácidos Aminoisobutíricos , Oligopéptidos/química , Secuencia de Aminoácidos , Enlace de Hidrógeno , Datos de Secuencia Molecular , Oligopéptidos/síntesis química , Conformación ProteicaRESUMEN
One of the crucial issues in biological electron transfer is the determination of the role of spatially intermediate amino acid residues in controlling or directing the electronic tunneling interaction between redox sites. A quantum path integral Monte Carlo method is developed for the analysis of electronic tunneling pathways in a highly structured environment. This path integral method is applied to intramolecular electron transfer in a ruthenium-modified myoglobin that contains a tryptophan in the "line-of-flight." A principal result is the identification of the relevant cylindrical zone swept out by the tunneling electron.
Asunto(s)
Transporte de Electrón , Proteínas/metabolismo , Modelos Teóricos , Método de Montecarlo , Teoría Cuántica , TermodinámicaRESUMEN
Excitation transport in synthetic zinc chlorophyllide substituted hemoglobin has been observed by pico -second time-resolved fluorescence depolarization experiments. In this hybrid molecular system, two zinc chlorophyllide molecules are substituted into the beta-chains of hemoglobin, while deoxy hemes remain in the alpha-chains. The rate of excitation transfer between the two chlorophyllides is analyzed in terms of the distance and orientation dependences predicted by the F orster dipole-dipole theory. In this analysis, the beta-beta interchromophore geometry is assumed to be that of the deoxyhemoglobin crystal structure. When combined with steady-state fluorescence depolarization data of the complementary hybrid containing zinc chlorophyllide in the alpha-chains, these experiments provide the necessary information to determine the orientation of the S1 transition dipole moment in the zinc chlorophyllide molecule. We also find that the fluorescence lifetime of the zinc chlorophyllide is 1.42 ns when the heme is in the deoxy state but 3.75 ns when the heme is ligated to carbon monoxide. This is explained by irreversible excitation transfer from the S1 state of the zinc chlorophyllide to the lower energy excited states present in deoxy heme.
Asunto(s)
Clorofila , Hemoglobinas , Transporte de Electrón , Modelos Biológicos , Modelos Moleculares , Espectrometría de Fluorescencia , Relación Estructura-ActividadRESUMEN
Three chlorophyllide-substituted human hemoglobin (Hb) complexes have been prepared: the tetrameric complex in which zinc pyrochlorophyllide alpha (ZnPChl alpha) is substituted for all four hemes and the two complementary hybrids in which ZnPChl alpha is substituted for heme in either the alpha- or beta-chains, while heme remains in the other chains. In each of these complexes, intramolecular Chl-Chl singlet energy transfer occurs. A variety of probes demonstrate that ZnPChl alpha-deoxyheme hybrids and the ZnPChl alpha-Hb complexes consistently exhibit properties associated with the well-known T-state tertiary and quaternary structure of deoxyHb itself. Using the known crystal structure of human deoxyHb, we have analyzed the steady-state fluorescence anisotropy of these complexes within the framework of the Förster energy-transfer theory. The result is the determination of the orientation of the Qy transition dipole moment of ZnPChl alpha. Nuclear magnetic resonance data for the hybrids offer insight into specific tertiary structural changes in the heme pocket surrounding the diamagnetic ZnPChl alpha, which accompany changes in the ligation state of the heme on the opposite chain.
Asunto(s)
Clorofila , Clorofilidas , Oxihemoglobinas , Clorofila/análogos & derivados , Dicroismo Circular , Transferencia de Energía , Polarización de Fluorescencia , Humanos , Sustancias Macromoleculares , Espectroscopía de Resonancia Magnética , Oxihemoglobinas/aislamiento & purificación , Unión Proteica , Conformación Proteica , Multimerización de ProteínaRESUMEN
The orientations of the transition dipole moments in chlorophyll (Chl) are among the most useful spectroscopic properties for determining macromolecular architecture in photosynthetic complexes; however, the relationships between these orientations and the Chl molecular geometry are unknown. In order to solve this problem, we have prepared single crystals of the synthetic 1:1 complex between pyrochlorophyllide a and apomyoglobin. The protein crystallizes readily in the orthorhombic (B) form, space group P2(1)2(1)2(1), and the unit cell dimensions are determined to be within 0.5% of those for native MetMb crystals of the same type. These green crystals are highly dichroic, and the strong absorption along the crystallographic a axis in the Q(y) band is red-shifted by about 9 nm, relative to the corresponding feature in a solution of the protein. Although the crystal structure for native Mb in this space group has not been determined, the direction cosines of the heme normal relative to the crystal axes have been measured. By using these values, an appropriate trigonometric analysis, and the measured polarized single-crystal spectra, the orientation of the Chl transition dipole moment for the Q(y) transition can be specified relative to the crystal axes. With the completion of the protein crystal structure, this result will lead directly to the orientations of the optical transition dipole moments relative to the molecular geometry. The effects of vibronic coupling and the protein environment on the absorption properties of Chl are discussed in detail.