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1.
J Helminthol ; 94: e58, 2019 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-31272516

RESUMEN

The order Onchoproteocephalidea (Eucestoda) was recently erected to accommodate the hook-bearing tetraphyllideans and the proteocephalideans, which are characterized by internal proglottization and a tetra-acetabulate scolex. The recognized subfamilies in the Proteocephalidae appeared to be non-monophyletic based on 28S recombinant DNA (rDNA) sequence data. Other molecular markers with higher phylogenetic resolution, such as large mitochondrial DNA fragments and multiple genes, are obviously needed. Thus the mitochondrial genome of Gangesia oligonchis, belonging to the putative earliest diverging group of the Proteocephalidae, was sequenced. The circular mitogenome of G. oligonchis was 13,958 bp in size, and contained the standard 36 genes: 22 transfer RNA genes, two rRNA genes and 12 protein-coding genes, as well as two major non-coding regions. A short NCR and a large NCR (lNCR) region were 216 bp and 419 bp in size, respectively. Highly repetitive regions in the lNCR region were detected with that of 11 repeat units. The mitogenome of G. oligonchis shared 71.1% nucleotide identity with Testudotaenia sp. WL-2016. Phylogenetic analyses of the complete mitochondrial genomes with Bayesian inference and maximum likelihood methods indicated that G. oligonchis formed a sister clade with Testudotaenia sp. WL-2016 with maximum support. The ordinal topology is (Caryophyllidea, (Diphyllobothriidea, (Bothriocephalidea, (Onchoproteocephalidea, Cyclophyllidea)))). The mitogenomic gene arrangement of G. oligonchis was identical to that of Testudotaenia sp. WL-2016. Both mitogenomic and nuclear sequence data for many more taxa are required to effectively explore the inter-relationships among the Onchoproteocephalidea.


Asunto(s)
Cestodos/clasificación , Cestodos/genética , Genoma Mitocondrial , Filogenia , Animales , Teorema de Bayes , Bagres/parasitología , ADN Mitocondrial/genética , Análisis de Secuencia de ADN
2.
J Helminthol ; 92(4): 455-466, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28660842

RESUMEN

Despite the worldwide distribution and pathogenicity of monogenean parasites belonging to the largest helminth genus, Dactylogyrus, there are no complete Dactylogyrinae (subfamily) mitogenomes published to date. In order to fill this knowledge gap, we have sequenced and characterized the complete mitogenome of Dactylogyrus lamellatus, a common parasite on the gills of grass carp (Ctenopharyngodon idella). The circular mitogenome is 15,187 bp in size, containing the standard 22 tRNA genes, 2 rRNA genes, 12 protein-encoding genes and a long non-coding region (NCR). There are two highly repetitive regions in the NCR. We have used concatenated nucleotide sequences of all 36 genes to perform the phylogenetic analysis using Bayesian inference and maximum likelihood approaches. As expected, the two dactylogyrids, D. lamellatus (Dactylogyrinae) and Tetrancistrum nebulosi (Ancyrocephalinae), were closely related to each other. These two formed a sister group with Capsalidae, and this cluster finally formed a further sister group with Gyrodactylidae. Phylogenetic affinity between Dactylogyrinae and Ancyrocephalinae was further confirmed by the similarity in their gene arrangement. The sequencing of the first Dactylogyrinae, along with a more suitable selection of outgroups, has enabled us to infer a much better phylogenetic resolution than recent mitogenomic studies. However, as many lineages of the class Monogenea remain underrepresented or not represented at all, a much larger number of mitogenome sequences will have to be available in order to infer the evolutionary relationships among the monogeneans fully, and with certainty.


Asunto(s)
Infecciones por Cestodos/veterinaria , Enfermedades de los Peces/parasitología , Genoma de los Helmintos , Genoma Mitocondrial , Filogenia , Platelmintos/genética , Animales , Secuencia de Bases , Carpas/parasitología , Infecciones por Cestodos/parasitología , Branquias/parasitología , Masculino , Datos de Secuencia Molecular , Platelmintos/clasificación , Platelmintos/aislamiento & purificación , Análisis de Secuencia de ADN
3.
Zhonghua Yi Xue Za Zhi ; 97(2): 127-130, 2017 Jan 10.
Artículo en Zh | MEDLINE | ID: mdl-28088958

RESUMEN

Objective: To discuss the clinical safety and efficacyof endovascular aneurysm repair (EVAR) for aortic pseudoaneurysms. Methods: From October 2008 to October 2015, 13 patients (11 male, 2 female, with a mean age of 55.6) with aortic pseudoaneurysms treated by EVAR wereenrolled. All the 13 casesunderwentcomputed tomographic arteriography (CTA). The etiology diagnosis withdescendingaortic pseudoaneurysms, infected abdominal aortic pseudoaneurysms, abdominal aortic pseudoaneurysmsin Behcet's syndrome, and uncertain reasons were 4, 4, 4, and 1 case, respectively. Results: In this group, 14 stentswere planted.All the patients hadno accidents and complications in perioperative period.Twelve patients were successfully followed up, 1 patient died of recurrent abdominal aortic pseudoaneurysmsin Behcet's syndrome, and 1 patient with recurrent infected abdominal aortic pseudoaneurysm wascured by pseudoaneurysm resection and extra-anatomic bypass grafting. Concluson: EVAR is a safe and effective option for aortic pseudoaneurysms.


Asunto(s)
Aneurisma Falso , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Angiografía , Aorta Abdominal , Aneurisma de la Aorta Abdominal , Síndrome de Behçet , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X , Resultado del Tratamiento
4.
J Biol Regul Homeost Agents ; 29(4): 841-6, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26753645

RESUMEN

Traumatic shock is a serious threat to life and health. The aim of this study is to investigate the effect of different resuscitation fluid compositions on the emergency resuscitation for patients with traumatic shock. Sixty patients were enrolled and divided into two groups, Group A and Group B. The patients in Group A were treated with resuscitation fluid, with 2:1 ratio of crystal (0.9% sodium chloride injection) and colloid (hydroxyethyl starch 40 injection). The patients in Group B were treated with hypertonic sodium chloride hydroxyethyl starch 40 injection (HSH40). Both vital signs and fluid dosage were monitored and recorded. At the beginning of resuscitation (T0) and 30 min (T1), 60 min (T2) and 120 min (T3) after resuscitation, indicator parameters including hemoglobin (HB), hematocrit (HCT), prothrombin time (PT), arterial blood lacic acid (LA) and C-reactive protein (CRP) were monitored and recorded. Tissue oxygenation and hemodynamic profile were also analyzed. At T1, T2and T3after fluid resuscitation, the heart rates of the patients in Group B were lower than those in Group A, whereas the average arterial pressure in Group B was significantly higher than that in Group A. Notably, significant decreases of HB and HCT were detected at T1, T2and T3compared with T0 in Group A. In contrast, no significant difference was shown in detected HCT at T2and T3compared with T0 in Group B, while the detected HB value was smaller. a statistically significant decrease of LA was detected at T1, T2and T3in Group A and Group B compared with that at T0. At T2and T3in Group A and Group B, a statistically significant increase of PT was detected compared with the beginning of resuscitation. At T2and T3after resuscitation, CRP in both Group A and Group B was significantly increased compared with that upon admission to hospital, and was lower in Group B than in Group A.


Asunto(s)
Resucitación , Choque Traumático/terapia , Urgencias Médicas , Femenino , Hematócrito , Hemoglobinas/análisis , Humanos , Derivados de Hidroxietil Almidón/administración & dosificación , Masculino , Solución Salina Hipertónica/administración & dosificación , Choque Traumático/sangre
5.
J Fish Dis ; 37(1): 11-20, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-24341506

RESUMEN

The original description of Myxobolus hearti is supplemented with new data on spore morphology, histopathology and molecular phylogeny. Myxobolus hearti are found in the heart ventricle of the gibel carp, Carassius gibelio (Bloch), where they form whitish oval or irregularly shaped plasmodia. Mature spores are oval or shortly ellipsoidal in frontal view, lemon-shaped in sutural view and eye-shaped in apical view. The spores are 14.12 ± 0.35 (13.6-15) µm long (mean ± SD), 11.85 ± 0.34 ± 0.36 (11-12) µm wide and 7.32 ± 0.36 (7-8) µm thick. The two polar capsules are equal in size, 6.11 ± 0.29 (6-7) µm long and 3.89 ± 0.31(3-4) µm wide, and are long pyriform in shape. Polar filaments have six or seven coils situated perpendicular to the longitudinal axis of the polar capsules. Histopathology indicates that the plasmodia are encased by the host connective tissue, and no inflammatory responses are found in the heart ventricles. Phylogenetic analysis based on the 18S small-subunit ribosomal DNA sequences indicates that M. hearti is, genetically, most similar to Henneguya doneci, a gill-infecting species.


Asunto(s)
Cyprinidae/parasitología , Enfermedades de los Peces/parasitología , Corazón/parasitología , Myxobolus/clasificación , Myxobolus/fisiología , Enfermedades Parasitarias en Animales/parasitología , Filogenia , Animales , Enfermedades de los Peces/patología , Datos de Secuencia Molecular , Myxobolus/anatomía & histología , Myxobolus/genética , Enfermedades Parasitarias en Animales/patología , ARN Ribosómico 18S/genética , Esporas Protozoarias/citología
6.
Nano Lett ; 12(6): 2877-82, 2012 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-22545811

RESUMEN

We have investigated the correlated surface electronic and optical properties of [0001]-oriented epitaxial InN nanowires grown directly on silicon. By dramatically improving the epitaxial growth process, we have achieved, for the first time, intrinsic InN both within the bulk and at nonpolar InN surfaces. The near-surface Fermi-level was measured to be ∼0.55 eV above the valence band maximum for undoped InN nanowires, suggesting the absence of surface electron accumulation and Fermi-level pinning. This result is in direct contrast to the problematic degenerate two-dimensional electron gas universally observed on grown surfaces of n-type degenerate InN. We have further demonstrated that the surface charge properties of InN nanowires, including the formation of two-dimensional electron gas and the optical emission characteristics can be precisely tuned through controlled n-type doping. At relatively high doping levels in this study, the near-surface Fermi-level was found to be pinned at ∼0.95-1.3 eV above the valence band maximum. Through these trends, well captured by the effective mass and ab initio materials modeling, we have unambiguously identified the definitive role of surface doping in tuning the surface charge properties of InN.


Asunto(s)
Cristalización/métodos , Indio/química , Nanoestructuras/química , Nanoestructuras/ultraestructura , Electricidad Estática , Sustancias Macromoleculares/química , Ensayo de Materiales , Conformación Molecular , Tamaño de la Partícula , Propiedades de Superficie
7.
8.
J Phys Condens Matter ; 33(44)2021 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-34348242

RESUMEN

Atomic precision advanced manufacturing (APAM) leverages the highly reactive nature of Si dangling bonds relative to H- or Cl-passivated Si to selectively adsorb precursor molecules into lithographically defined areas with sub-nanometer resolution. Due to the high reactivity of dangling bonds, this process is confined to ultra-high vacuum (UHV) environments, which currently limits its commercialization and broad-based appeal. In this work, we explore the use of halogen adatoms to preserve APAM-derived lithographic patterns outside of UHV to enable facile transfer into real-world commercial processes. Specifically, we examine the stability of H-, Cl-, Br-, and I-passivated Si(100) in inert N2and ambient environments. Characterization with scanning tunneling microscopy and x-ray photoelectron spectroscopy (XPS) confirmed that each of the fully passivated surfaces were resistant to oxidation in 1 atm of N2for up to 44 h. Varying levels of surface degradation and contamination were observed upon exposure to the laboratory ambient environment. Characterization byex situXPS after ambient exposures ranging from 15 min to 8 h indicated the Br- and I-passivated Si surfaces were highly resistant to degradation, while Cl-passivated Si showed signs of oxidation within minutes of ambient exposure. As a proof-of-principle demonstration of pattern preservation, a H-passivated Si sample patterned and passivated with independent Cl, Br, I, and bare Si regions was shown to maintain its integrity in all but the bare Si region post-exposure to an N2environment. The successful demonstration of the preservation of APAM patterns outside of UHV environments opens new possibilities for transporting atomically-precise devices outside of UHV for integrating with non-UHV processes, such as other chemistries and commercial semiconductor device processes.

9.
Science ; 247(4945): 954-8, 1990 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-2106161

RESUMEN

The 11-kD protease (PR) encoded by the human immunodeficiency virus 1 (HIV-1) is essential for the correct processing of viral polyproteins and the maturation of infectious virus, and is therefore a target for the design of selective acquired immunodeficiency syndrome (AIDS) therapeutics. To facilitate the identification of novel inhibitors of HIV-1 PR, as well as to permit detailed studies on the enzymology and inhibition of this enzyme, a continuous assay for its activity was developed that was based on intramolecular fluorescence resonance energy transfer (RET). The assay used the quenched fluorogenic substrate 4-(4-dimethylaminophenylazo)benzoic acid (DABCYL)--Ser Gln Asn Tyr Pro Ile Val Gln--5-[(2-aminoethyl)amino]naphthalene-1 sulfonic acid (EDANS), whose peptide sequence is derived from a natural processing site for HIV-1 PR. Incubation of recombinant HIV-1 PR with the fluorogenic substrate resulted in specific cleavage at the Tyr-Pro bond and a time-dependent increase in fluorescence intensity that was linearly related to the extent of substrate hydrolysis. An internally quenched fluorogenic substrate was also designed that was selectively cleaved by the related PR from avian myeloblastosis virus (AMV). The fluorescence quantum yields of the HIV-1 PR and AMV PR substrates in the RET assay increased by 40.0- and 34.4-fold, respectively, per mole of substrate cleaved. Because of its simplicity, rapidity, and precision in the determination of reaction rates required for kinetic analysis, this method offers many advantages over the commonly used high-performance liquid chromatography- or electrophoresis-based assays for peptide substrate hydrolysis by retroviral PRs.


Asunto(s)
Endopeptidasas/metabolismo , Productos del Gen pol/metabolismo , VIH-1/enzimología , Naftalenosulfonatos/metabolismo , Secuencia de Aminoácidos , Transferencia de Energía , Colorantes Fluorescentes , Proteasa del VIH , Hidrólisis , Datos de Secuencia Molecular , Oligopéptidos/metabolismo , Pepstatinas/farmacología , Inhibidores de Proteasas , Espectrometría de Fluorescencia , p-Dimetilaminoazobenceno/metabolismo
10.
Nanotechnology ; 20(3): 035706, 2009 Jan 21.
Artículo en Inglés | MEDLINE | ID: mdl-19417308

RESUMEN

A new methodology for determining the radial elastic modulus of a one-dimensional nanostructure laid on a substrate has been developed. The methodology consists of the combination of contact resonance atomic force microscopy (AFM) with finite element analysis, and we illustrate it for the case of faceted AlN nanotubes with triangular cross-sections. By making precision measurements of the resonance frequencies of the AFM cantilever-probe first in air and then in contact with the AlN nanotubes, we determine the contact stiffness at different locations on the nanotubes, i.e. on edges, inner surfaces, and outer facets. From the contact stiffness we have extracted the indentation modulus and found that this modulus depends strongly on the apex angle of the nanotube, varying from 250 to 400 GPa for indentation on the edges of the nanotubes investigated.

11.
Acta Virol ; 53(1): 29-34, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19301948

RESUMEN

Rubella virus (RUBV) infects cells via an acid-triggered membrane fusion process. RUBV virions contain two cysteine-rich glycoproteins, E2 and E1. The latter is believed to be involved in the membrane fusion. Using a recombinant plasmid containing RUBV E1 and E2, 11 of total 20 cysteines present in the ectodomain of wild type E1 were mutated to test their role in the fusion via the formation of disulfide bridges. The recombinant plasmids containing mutated E1 (Cys2-Cys20) or wild type (wt) E1 were expressed in BHK-21 cells. Their fusogenic and hemadsorption activities in addition to a potential of cell surface expression of E1 and E2 were assayed. The results showed that the fusogenic activity was lost in all tested mutants, while the hemadsorption activity and cell surface expression potential were affected differently in individual mutants. Since only the Cys5 and Cys8 mutations led to a reduction of both hemadsorption and cell surface expression, we assume that these mutations prevented the formation of the disulfide bridge, what led to a misfolding of E1 and consequently to a failure of recognition of E1 by E2. In conclusion, the disulfide bridges disrupted in all the tested mutants appear essential for the cell fusion, while only the disulfide bridge C(5)-C(8) seems to be crucial for the transport of E1 and E2 in the cell.


Asunto(s)
Disulfuros/química , Virus de la Rubéola/química , Virus de la Rubéola/fisiología , Proteínas del Envoltorio Viral/química , Proteínas del Envoltorio Viral/fisiología , Internalización del Virus , Sustitución de Aminoácidos , Animales , Línea Celular , Cricetinae , Cisteína/genética , Hemabsorción , Mutagénesis Sitio-Dirigida , Transporte de Proteínas , Proteínas del Envoltorio Viral/genética
12.
Eur Rev Med Pharmacol Sci ; 23(21): 9625-9632, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31773713

RESUMEN

OBJECTIVE: To investigate the effects of ranolazine on the cardiac function and myocardial apoptosis in rats with heart failure and its possible mechanisms. MATERIALS AND METHODS: Thirty Wistar rats were randomly divided into sham operation (negative control; NC), chronic heart failure (CHF), and ranolazine groups. Suprarenal abdominal aortic coarctation was used to induce CHF in rats. Five weeks later, rats in the ranolazine group received ranolazine (50 mg/kg) daily, whereas those in the CHF group received normal saline. After 4 weeks, changes in hemodynamic parameters, cardiac structure and pathology, myocardial apoptosis, and protein expression were assessed. RESULTS: The left ventricular end-diastolic pressure (LVEDP) significantly increased in the CHF group; whereas the maximal rate of left ventricular pressure rise and fall (±dp/dtmax) decreased, compared to those in the NC group. Ranolazine significantly reduced LVEDP and increased ±dp/dtmax (p<0.01), compared to those in the CHF group. Severe impairment of cardiomyocytes was observed in the CHF group with evident inflammation; however, ranolazine reversed these deficits. Rats in the CHF group exhibited an increase in TUNEL-positive cells, which was inhibited by ranolazine, where the apoptotic index significantly decreased in ranolazine-treated rats (p<0.01). Also, ranolazine downregulated caspase-9 expression and upregulated pAKT and Bcl-2 expression in rat cardiomyocytes. Moreover, ranolazine significantly inhibited myocardial apoptosis and caspase-9 expression, promoted AKT phosphorylation, and upregulated pAKT and Bcl-2 expression in vitro, compared to those in the control group (p<0.001). LY294002 inhibited ranolazine-induced suppression of myocardial apoptosis (p<0.001). CONCLUSIONS: Ranolazine improved cardiac function and inhibited myocardial apoptosis in rats with CHF, which could be attributed to the regulation of AKT phosphorylation.


Asunto(s)
Fármacos Cardiovasculares/farmacología , Insuficiencia Cardíaca/tratamiento farmacológico , Ranolazina/farmacología , Animales , Apoptosis/efectos de los fármacos , Fármacos Cardiovasculares/administración & dosificación , Células Cultivadas , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/patología , Inyecciones Intraperitoneales , Masculino , Ranolazina/administración & dosificación , Ratas , Ratas Wistar
13.
Vet Parasitol ; 147(1-2): 125-31, 2007 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-17459589

RESUMEN

The seasonal population dynamics and maturation cycle of the nematode Camallanus cotti in the posterior intestine of Chinese hooksnout carp Opsariichthys bidens have been studied in the Danjiangkou Reservoir of the Hubei Province in central China from September 2004 to November 2005. The overall prevalence, mean abundance and intensity of C. cotti among fish sampled (n=700 fish) were 47%, 2.29+/-12.38 (+/-S.D.) and 1-307 (average 4.89+/-17.74), respectively. The overall sexual ratio of female to male nematodes (excluding L3 and L4 juveniles) was 1.17:1. Statistical results showed weakly positive correlations between fish length and the number of nematodes per host. The dynamics of infection of the nematode exhibited significant seasonal pattern in changes in mean abundance. A similar pattern was found for changes in nematode prevalence, although this was not statistically significant. Higher levels of infection were observed among fish sampled in summer months and the lower in the winter. Neither the prevalence nor the abundance of the parasite was significantly different between male and female hosts. The pattern of frequency distribution of the parasite in the host was found to be over-dispersed throughout the sampling period. In addition, studies on the development and maturation of the parasite in O. bidens revealed that development (maturation), recruitment of the next generation, and reproduction may be continuous year-round, although reproduction may peak during the winter.


Asunto(s)
Cyprinidae/parasitología , Enfermedades de los Peces/parasitología , Infecciones por Spirurida/veterinaria , Espirúridos/fisiología , Animales , Tamaño Corporal , China , Femenino , Enfermedades de los Peces/epidemiología , Masculino , Densidad de Población , Dinámica Poblacional , Prevalencia , Espirúridos/crecimiento & desarrollo , Espirúridos/aislamiento & purificación , Infecciones por Spirurida/epidemiología , Infecciones por Spirurida/parasitología , Factores de Tiempo
14.
J Gen Physiol ; 113(4): 541-54, 1999 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-10102935

RESUMEN

Gating of the cystic fibrosis transmembrane conductance regulator (CFTR) involves a coordinated action of ATP on two nucleotide binding domains (NBD1 and NBD2). Previous studies using nonhydrolyzable ATP analogues and NBD mutant CFTR have suggested that nucleotide hydrolysis at NBD1 is required for opening of the channel, while hydrolysis of nucleotides at NBD2 controls channel closing. We studied ATP-dependent gating of CFTR in excised inside-out patches from stably transfected NIH3T3 cells. Single channel kinetics of CFTR gating at different [ATP] were analyzed. The closed time constant (tauc) decreased with increasing [ATP] to a minimum value of approximately 0.43 s at [ATP] >1.00 mM. The open time constant (tauo) increased with increasing [ATP] with a minimal tauo of approximately 260 ms. Kinetic analysis of K1250A-CFTR, a mutant that abolishes ATP hydrolysis at NBD2, reveals the presence of two open states. A short open state with a time constant of approximately 250 ms is dominant at low ATP concentrations (10 microM) and a much longer open state with a time constant of approximately 3 min is present at millimolar ATP. These data suggest that nucleotide binding and hydrolysis at NBD1 is coupled to channel opening and that the channel can close without nucleotide interaction with NBD2. A quantitative cyclic gating scheme with microscopic irreversibility was constructed based on the kinetic parameters derived from single-channel analysis. The estimated values of the kinetic parameters suggest that NBD1 and NBD2 are neither functionally nor biochemically equivalent.


Asunto(s)
Adenosina Trifosfato/fisiología , Canales de Cloruro/fisiología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/fisiología , Activación del Canal Iónico/fisiología , Células 3T3 , Transportadoras de Casetes de Unión a ATP/metabolismo , Adenosina Trifosfato/metabolismo , Algoritmos , Animales , Sitios de Unión/fisiología , Electrofisiología , Hidrólisis , Cinética , Ratones , Modelos Biológicos , Nucleótidos/química , Nucleótidos/metabolismo , Técnicas de Placa-Clamp , Fosforilación
15.
J Phys Chem B ; 109(27): 13210-3, 2005 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-16852647

RESUMEN

The photoassisted charge behavior of hydrogen storage alloy modified with TiO2/Pt nanocomposites (HSA-TiO2/Pt electrode) was investigated. The HSA-TiO2/Pt electrode can be photocharged under current. The mechanism of photoassisted behavior of the HSA-TiO2/Pt electrode was explained through the results of cyclic voltammogram and impedance measurements of the HSA-TiO2/Pt electrode. Upon illumination, the photogenerated electrons can charge the electrode, but the photogenerated holes may oxidize the hydrogen storage alloy to form a layer of metal oxide. Because the current could keep the electrode active, the H atoms produced by photogenerated electrons diffused to the hydrogen storage alloy and a metal hydride formed. The electrode delivered a higher discharge capacity due to the assistance of photocharge.

16.
Methods Enzymol ; 241: 70-86, 1994.
Artículo en Inglés | MEDLINE | ID: mdl-7854193

RESUMEN

This chapter has described a number of approaches for continuous assay of retroviral proteases using either chromogenic or fluorogenic synthetic substrates. The significant progress in this area has been catalyzed by the intense interest in HIV protease as a therapeutic target, but these versatile methods will be used widely in future for studies of many other proteases.


Asunto(s)
Ácido Aspártico Endopeptidasas/análisis , Proteínas de los Retroviridae/análisis , Retroviridae/enzimología , Secuencia de Aminoácidos , Ácido Aspártico Endopeptidasas/metabolismo , Compuestos Cromogénicos/metabolismo , Colorimetría/métodos , Colorantes Fluorescentes , Fluorometría/métodos , Proteasa del VIH/análisis , Proteasa del VIH/metabolismo , Hidrólisis , Datos de Secuencia Molecular , Fragmentos de Péptidos/análisis , Péptidos/síntesis química , Péptidos/metabolismo , Proteínas de los Retroviridae/metabolismo , Sensibilidad y Especificidad , Especificidad por Sustrato , Factores de Tiempo
17.
J Med Chem ; 38(16): 2995-3002, 1995 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-7636862

RESUMEN

Solid phase synthesis of non-oligomeric organic compounds has been pursued for high-efficiency generation of large numbers of structurally diverse compounds for drug screening. Known as chemical diversity libraries or combinatorial libraries (when the synthesis is carried out in a combinatorial fashion), these compounds can be used for de novo discovery of drug leads or for expedient structure--activity relationship (SAR) studies. To expand the scope of solid phase synthesis beyond the capability of the traditional method of solid phase synthesis for peptides, a strategy was developed for bi-directional solid phase synthesis starting with diamino alcohol or diamino diol core structures. The strategy relies on using bifunctional linkers to modify the core structures, simultaneously protecting the hydroxyl group or the diol moiety of the core and providing a carboxyl group for attachment of the modified cores to a solid support. The two NH2 groups of the modified cores attached to the solid support were then deprotected and reacted with a wide variety of amine-reactive reagents (carboxylic acids, sulfonyl chlorides, isocyanates, chloroformates, etc.) to extend the molecule in both directions. This strategy was successfully applied to automated parallel synthesis of a library of C2 symmetric inhibitors of HIV protease containing the known symmetry-based diamino diol and diamino alcohol core structures, thus enabling expedient access of large numbers of analogs in this series. A library of over 300 discrete compounds was synthesized using this methodology in order to identify potent (IC50 < 100 nM) HIV protease inhibitors with reduced size. This paper describes the technical aspects of this technology.


Asunto(s)
Inhibidores de la Proteasa del VIH/síntesis química , Alcoholes/química , Alcoholes/farmacología , Estudios de Factibilidad , Inhibidores de la Proteasa del VIH/química , Humanos , Compuestos de Metilurea/química , Piridinas/química , Relación Estructura-Actividad , Valina/análogos & derivados
18.
J Med Chem ; 44(8): 1192-201, 2001 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-11312919

RESUMEN

The discovery of (+/-)-(2S,3R,4R)-2-(trifluoroacetamido)methyl-3-amino-1-(N'-ethyl-N'-isopropylcarbamyl)pyrrolidine-4-carboxylic acid (A-192558, 20e) as a potent inhibitor of influenza neuraminidase (NA) is described. Efficient syntheses of two core structures, cis-3-(allyloxycarbonyl)amino-1-(9'-fluorenylmethoxycarbonyl)pyrrolidine-4-carboxylic acid (7) and tert-butyl (+/-)-(2S,3R,4R)-2-aminomethyl-3-bis(tert-butyloxycarbonyl)amino-1-(N'-ethyl-N'-isopropylcarbamyl)pyrrolidine-4-carboxylate (18b), were developed. Starting with these core structures and using available structural information of the NA active site as the guide, analogues were synthesized in both the tri- and tetrasubstituted pyrrolidine series by means of high-throughput parallel synthesis in solid or solution phase for expeditious SAR. These studies accelerated the identification of (+/-)-(2S,3R,4R)-2-(trifluoroacetamido)methyl-3-amino-1-(N-ethyl-N-isopropylcarbamyl)pyrrolidine-4-carboxylate (20e, A-192558) as the most potent NA inhibitor in this series (IC50 = 0.2 microM against NA A and 8 microM against NA B). The X-ray crystallographic structure of A-192558 bound to NA revealed the predicted interaction of the carboxylic group with the positively charged pocket (Arg118, Arg292, Arg371) and interaction of the trifluoroacetamino residue with the hydrophobic pocket (Ile222, Trp178) of the enzyme active site. Surprisingly, the ethyl and isopropyl groups of the urea functionality induced a conformational change of Glu276, turning the Glu276/Glu277 hydrophilic pocket, which normally accommodates the triglycerol side chain of substrate sialic acid, into an induced hydrophobic pocket.


Asunto(s)
Antivirales/síntesis química , Inhibidores Enzimáticos/síntesis química , Neuraminidasa/antagonistas & inhibidores , Orthomyxoviridae/enzimología , Pirrolidinas/síntesis química , Antivirales/química , Cristalografía por Rayos X , Diseño de Fármacos , Inhibidores Enzimáticos/química , Modelos Moleculares , Estructura Molecular , Pirrolidinas/química
19.
Vet Parasitol ; 41(3-4): 203-9, 1992 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1502783

RESUMEN

Moxidectin, a systemic insecticide, was evaluated for its efficacy against the migrating first instars of the common cattle grub, Hypoderma lineatum, and against nematode egg production in beef cattle. It was observed that all three levels (0.1, 0.2 and 0.4 mg moxidectin kg-1) were 100% effective against cattle grubs when administered as a s.c. injection. The same levels of treatment were very effective (90-100%) in reducing trichostrongyle nematode egg production. However, there was a slight indication that at least one species, Cooperia oncophora, was not completely eliminated, as it was observed that small numbers of eggs began to appear after 2 weeks post-treatment when there had been no opportunity for reinfection.


Asunto(s)
Antibacterianos/uso terapéutico , Antinematodos/uso terapéutico , Enfermedades de los Bovinos/tratamiento farmacológico , Hipodermosis/veterinaria , Insecticidas/uso terapéutico , Tricostrongiloidiasis/veterinaria , Animales , Antibacterianos/administración & dosificación , Antibacterianos/farmacología , Antinematodos/administración & dosificación , Antinematodos/farmacología , Bovinos , Heces/parasitología , Femenino , Hipodermosis/tratamiento farmacológico , Inyecciones Subcutáneas/veterinaria , Insecticidas/administración & dosificación , Macrólidos , Masculino , Oviposición/efectos de los fármacos , Recuento de Huevos de Parásitos/veterinaria , Distribución Aleatoria , Trichostrongyloidea/efectos de los fármacos , Trichostrongyloidea/fisiología , Tricostrongiloidiasis/tratamiento farmacológico
20.
Vet Parasitol ; 43(3-4): 293-9, 1992 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-1413460

RESUMEN

Twenty male Holstein calves averaging 105 kg in weight and naturally infected with gastrointestinal nematodes and small numbers of lungworm and hookworm, were given experimental infections with the two latter species to provide adult and larval stages for anthelmintic evaluation. Following random allotment, one group of 10 calves was injected subcutaneously with moxidectin at a dosage of 0.2 mg kg-1 of body weight. A second group of 10 was injected subcutaneously with unmedicated blank vehicle at a dosage of 1 ml per 50 kg of body weight. Fecal samples were examined before treatment and at 7 and 13 days after treatment. The 20 calves were necropsied for worm recovery at 13 and 14 days after treatment. All calves were positive for lungworm and hookworm on the treatment date. Treatment was 100% effective in elimination of hookworm eggs and lungworm larvae and 99.9% in reducing total egg counts at both 7 and 13 days after treatment. Moxidectin was 100% effective (P less than 0.01) in eliminating the following 11 species of nematodes. Dictyocaulus viviparus mature and immature adults (E5), Bunostomum phlebotomum adults and L4, Ostertagia ostertagi adults and early L4, Ostertagia lyrata adult males, Haemonchus placei adults. Trichostrongylus axei adults, Cooperia spp., including Cooperia punctata, Cooperia spatulata, and Cooperia pectinata adults, Oesophagostomum radiatum adults and Trichuris discolor adults. No adverse reactions to moxidectin treatment were observed.


Asunto(s)
Antibacterianos/uso terapéutico , Enfermedades de los Bovinos/tratamiento farmacológico , Infecciones por Dictyocaulus/tratamiento farmacológico , Infecciones por Uncinaria/veterinaria , Parasitosis Intestinales/veterinaria , Animales , Antihelmínticos/administración & dosificación , Antihelmínticos/uso terapéutico , Antibacterianos/administración & dosificación , Bovinos , Infecciones por Dictyocaulus/complicaciones , Heces/parasitología , Infecciones por Uncinaria/complicaciones , Infecciones por Uncinaria/tratamiento farmacológico , Inyecciones Subcutáneas/veterinaria , Parasitosis Intestinales/complicaciones , Parasitosis Intestinales/tratamiento farmacológico , Macrólidos , Masculino , Infecciones por Nematodos/complicaciones , Infecciones por Nematodos/tratamiento farmacológico , Infecciones por Nematodos/veterinaria , Recuento de Huevos de Parásitos/veterinaria , Distribución Aleatoria
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