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1.
Artigo em Inglês | MEDLINE | ID: mdl-38676629

RESUMO

Gas crossover is critical in proton exchange membrane (PEM)-based electrochemical systems. Recently, single-layer graphene (SLG) has gained great research interest due to its outstanding properties as a barrier layer for small molecules like hydrogen. However, the applicability of SLG as a gas-blocking interlayer in PEMs has yet to be fully understood. In this work, two different approaches for transferring SLG from a copper or a polymeric substrate onto PEMs are compared regarding their application in low-temperature PEM fuel cells. The SLG is sandwiched between two Nafion XL membranes to form a stable composite membrane. The successful transfer is confirmed by Raman spectroscopy and in ex situ hydrogen permeation experiments in the dry state, where a reduction of 50% upon SLG incorporation is achieved. The SLG composite membranes are characterized by their performance and hydrogen-blocking ability in a fuel cell setup at typical operating conditions of 80 °C and with fully humidified gases. The performance of the fuel cell incorporating an SLG composite membrane is equal to that of the reference cell when avoiding the direct etching process from a copper substrate, as remnants from copper etching deteriorate the performance of the fuel cell. For both transfer processes, the hydrogen crossover reduction of SLG composite membranes is only 15-19% (1.5 barabs) in the operating fuel cell. Further, hydrogen pumping experiments suggest that the barrier function of SLG impairs the water transport through the membrane, which may affect water management in electrochemical applications. In summary, this work shows the successful transfer of SLG into a PEM and confirms the effective hydrogen-blocking capability of the SLG interlayer. However, the hydrogen-blocking ability is significantly reduced when running the cell at the typical humidified operating conditions of PEM fuel cells, which follows from a combination of reversible interlayer alteration upon humidification and irreversible defect formation upon PEM fuel cell operation.

2.
J Mater Chem A Mater ; 11(41): 22347-22359, 2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-38013811

RESUMO

We report the synthesis of a polystyrene-based anion exchange polymer bearing the cationic charge at a C6-spacer. The polymer is prepared by a functionalized monomer strategy. First, a copper halide catalyzed C-C coupling reaction between a styryl Grignard and 1,6-dibromohexane is applied, followed by quaternization with N-methylpiperidine and free radical polymerization. The novel polymer is blended with the polybenzimidazole O-PBI to yield mechanically stable blend membranes representing a new class of anion exchange membranes. In this regard, the ratio of the novel anion exchange polymer to O-PBI is varied to study the influence on water uptake and ionic conductivity. Blend membranes with IECs between 1.58 meq. OH- g-1 and 2.20 meq. OH- g-1 are prepared. The latter shows excellent performance in AEMWE, reaching 2.0 A cm-2 below 1.8 V in 1 M KOH at 70 °C, with a minor degradation rate from the start. The blend membranes show no conductivity loss after immersion in 1 M KOH at 85 °C for six weeks indicating high alkaline stability.

3.
iScience ; 26(10): 107775, 2023 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-37736046

RESUMO

High-entropy alloys are claimed to possess superior stability due to thermodynamic contributions. However, this statement mostly lies on a hypothetical basis. In this study, we use on-line inductively coupled plasma mass spectrometer to investigate the dissolution of five representative electrocatalysts in acidic and alkaline media and a wide potential window targeting the most important applications. To address both model and applied systems, we synthesized thin films and carbon-supported nanoparticles ranging from an elemental (Pt) sample to binary (PtRu), ternary (PtRuIr), quaternary (PtRuIrRh), and quinary (PtRuIrRhPd) alloy samples. For certain metals in the high-entropy alloy under alkaline conditions, lower dissolution was observed. Still, the improvement was not striking and can be rather explained by the lowered concentration of elements in the multinary alloys instead of the synergistic effects of thermodynamics. We postulate that this is because of dissolution kinetic effects, which are always present under electrocatalytic conditions, overcompensating thermodynamic contributions.

4.
J Am Chem Soc ; 144(22): 9753-9763, 2022 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-35609284

RESUMO

The electrochemical activity of modern Fe-N-C electrocatalysts in alkaline media is on par with that of platinum. For successful application in fuel cells (FCs), however, also high durability and longevity must be demonstrated. Currently, a limited understanding of degradation pathways, especially under operando conditions, hinders the design and synthesis of simultaneously active and stable Fe-N-C electrocatalysts. In this work, using a gas diffusion electrode half-cell coupled with inductively coupled plasma mass spectrometry setup, Fe dissolution is studied under conditions close to those in FCs, that is, with a porous catalyst layer (CL) and at current densities up to -125 mA·cm-2. Varying the rate of the oxygen reduction reaction (ORR), we show a remarkable linear correlation between the Faradaic charge passed through the electrode and the amount of Fe dissolved from the electrode. This finding is rationalized assuming that oxygen reduction and Fe dissolution reactions are interlinked, likely through a common intermediate formed during the Fe redox transitions in Fe species involved in the ORR, such as FeNxCy and Fe3C@N-C. Moreover, such a linear correlation allows the application of a simple metric─S-number─to report the material's stability. Hence, in the current work, a powerful tool for a more applied stability screening of different electrocatalysts is introduced, which allows on the one hand fast performance investigations under more realistic conditions, and on the other hand a more advanced mechanistic understanding of Fe-N-C degradation in CLs.

5.
Front Vet Sci ; 8: 755258, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34957277

RESUMO

Mast cell neoplasms are one of the most frequently diagnosed malignancies in dogs. The clinical picture, course, and prognosis vary substantially among patients, depending on the anatomic site, grade and stage of the disease. The most frequently involved organ is the skin, followed by hematopoietic organs (lymph nodes, spleen, liver, and bone marrow) and mucosal sites of the oral cavity and the gastrointestinal tract. In cutaneous mast cell tumors, several grading and staging systems have been introduced. However, no comprehensive classification and no widely accepted diagnostic criteria have been proposed to date. To address these open issues and points we organized a Working Conference on canine mast cell neoplasms in Vienna in 2019. The outcomes of this meeting are summarized in this article. The proposed classification includes cutaneous mast cell tumors and their sub-variants defined by grading- and staging results, mucosal mast cell tumors, extracutaneous/extramucosal mast cell tumors without skin involvement, and mast cell leukemia (MCL). For each of these entities, diagnostic criteria are proposed. Moreover, we have refined grading and staging criteria for mast cell neoplasms in dogs based on consensus discussion. The criteria and classification proposed in this article should greatly facilitate diagnostic evaluation and prognostication in dogs with mast cell neoplasms and should thereby support management of these patients in daily practice and the conduct of clinical trials.

6.
ACS Appl Mater Interfaces ; 13(47): 56584-56596, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34784464

RESUMO

High-temperature proton-exchange membrane fuel cells (HT-PEMFCs) are mostly based on acid-doped membranes composed of polybenzimidazole (PBI). A severe drawback of acid-doped membranes is the deterioration of mechanical properties upon increasing acid-doping levels. Cross-linking of different polymers is a way to mitigate stability issues. In this study, a new ion-pair-coordinated membrane (IPM) system with quaternary ammonium groups for the application in HT-PEMFCs is introduced. PBI cross-linked with poly(vinylbenzyl chloride) and quaternized with three amines (DABCO, quinuclidine, and quinuclidinol) are manufactured and compared to the state-of-the-art commercial Dapazol PBI membrane ex situ as well as by evaluating their HT-PEMFC performance. The IPMs show reduced swelling and better mechanical properties upon doping, which enables a reduction in membrane thickness while maintaining a comparably low gas crossover and mechanical stability. The HT-PEMFC based on the best-performing IPM reaches up to 530 mW cm-2 at 180 °C under H2/air conditions at ambient pressure, while Dapazol is limited to less than 430 mW cm-2 at equal parameters. This new IPM system requires less acid doping than conventional PBI membranes while outperforming conventional PBI membranes, which renders these new membranes promising candidates for application in HT-PEMFCs.

7.
Polymers (Basel) ; 13(11)2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198895

RESUMO

Diamond-like carbon coatings may decrease implant wear, therefore, they are helping to reduce aseptic loosening and increase service life of total knee arthroplasties (TKAs). This two-part study addresses the development of such coatings for ultrahigh molecular weight polyethylene (UHMWPE) tibial inlays as well as cobalt-chromium-molybdenum (CoCr) and titanium (Ti64) alloy femoral components. While the deposition of a pure (a-C:H) and tungsten-doped hydrogen-containing amorphous carbon coating (a-C:H:W) as well as the detailed characterization of mechanical and adhesion properties were the subject of Part I, the tribological behavior is studied in Part II. Pin-on-disk tests are performed under artificial synovial fluid lubrication. Numerical elastohydrodynamic lubrication modeling is used to show the representability of contact conditions for TKAs and to assess the influence of coatings on lubrication conditions. The wear behavior is characterized by means of light and laser scanning microscopy, Raman spectroscopy, scanning electron microscopy and particle analyses. Although the coating leads to an increase in friction due to the considerably higher roughness, especially the UHMWPE wear is significantly reduced up to a factor of 49% (CoCr) and 77% (Ti64). Thereby, the coating shows continuous wear and no sudden failure or spallation of larger wear particles. This demonstrated the great potential of amorphous carbon coatings for knee replacements.

8.
Polymers (Basel) ; 13(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208302

RESUMO

Diamond-like carbon (DLC) coatings have the potential to reduce implant wear and thus to contribute to avoiding premature failure and increase service life of total knee replacements (TKAs). This two-part study addresses the development of such coatings for ultrahigh molecular weight polyethylene (UHMWPE) tibial inlays as well as cobalt-chromium-molybdenum (CoCr) and titanium (Ti64) alloy femoral components. While a detailed characterization of the tribological behavior is the subject of part II, part I focusses on the deposition of pure (a-C:H) and tungsten-doped hydrogen-containing amorphous carbon coatings (a-C:H:W) and the detailed characterization of their chemical, cytological, mechanical and adhesion behavior. The coatings are fabricated by physical vapor deposition (PVD) and display typical DLC morphology and composition, as verified by focused ion beam scanning electron microscopy and Raman spectroscopy. Their roughness is higher than that of the plain substrates. Initial screening with contact angle and surface tension as well as in vitro testing by indirect and direct application indicate favorable cytocompatibility. The DLC coatings feature excellent mechanical properties with a substantial enhancement of indentation hardness and elastic modulus ratios. The adhesion of the coatings as determined in modified scratch tests can be considered as sufficient for the use in TKAs.

9.
Nat Commun ; 12(1): 2231, 2021 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-33850142

RESUMO

Recent research indicates a severe discrepancy between oxygen evolution reaction catalysts dissolution in aqueous model systems and membrane electrode assemblies. This questions the relevance of the widespread aqueous testing for real world application. In this study, we aim to determine the processes responsible for the dissolution discrepancy. Experimental parameters known to diverge in both systems are individually tested for their influence on dissolution of an Ir-based catalyst. Ir dissolution is studied in an aqueous model system, a scanning flow cell coupled to an inductively coupled plasma mass spectrometer. Real dissolution rates of the Ir OER catalyst in membrane electrode assemblies are measured with a specifically developed, dedicated setup. Overestimated acidity in the anode catalyst layer and stabilization over time in real devices are proposed as main contributors to the dissolution discrepancy. The results shown here lead to clear guidelines for anode electrocatalyst testing parameters to resemble realistic electrolyzer operating conditions.

10.
Angew Chem Int Ed Engl ; 60(16): 8882-8888, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33410273

RESUMO

Pt dissolution has already been intensively studied in aqueous model systems and many mechanistic insights have been gained. Nevertheless, transfer of new knowledge to real-world fuel cell systems is still a significant challenge. To close this gap, we present a novel in situ method combining a gas diffusion electrode (GDE) half-cell with inductively coupled plasma mass spectrometry (ICP-MS). With this setup, Pt dissolution in realistic catalyst layers and the transport of dissolved Pt species through Nafion membranes were evaluated directly. We observed that 1) specific Pt dissolution increased significantly with decreasing Pt loading, 2) in comparison to experiments on aqueous model systems with flow cells, the measured dissolution in GDE experiments was considerably lower, and 3) by adding a membrane onto the catalyst layer, Pt dissolution was reduced even further. All these phenomena are attributed to the varying mass transport conditions of dissolved Pt species, influencing re-deposition and equilibrium potential.

11.
Biosci Biotechnol Biochem ; 83(9): 1663-1675, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31094292

RESUMO

Members of the casein kinase 1 (CK1) family are key regulators in numerous cellular signal transduction pathways and in order to prevent the development of certain diseases, CK1 kinase activity needs to be tightly regulated. Modulation of kinase activity by site-specific phosphorylation within the C-terminal regulatory domain of CK1δ has already been shown for several cellular kinases. By using biochemical methods, we now identified residues T161, T174, T176, and S181 within the kinase domain of CK1δ as target sites for checkpoint kinase 1 (Chk1). At least residues T176 and S181 show full conservation among CK1δ orthologues from different eukaryotic species. Enzyme kinetic analysis furthermore led to the hypothesis that site-specific phosphorylation within the kinase domain finally contributes to fine-tuning of CK1δ kinase activity. These data provide a basis for the extension of our knowledge about the role of site-specific phosphorylation for regulation of CK1δ and associated signal transduction pathways.


Assuntos
Quinase 1 do Ponto de Checagem/química , Quinase 1 do Ponto de Checagem/metabolismo , Humanos , Fosforilação , Transdução de Sinais
12.
Sci Rep ; 9(1): 7646, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113972

RESUMO

Neural probes provide many options for neuroscientific research and medical purposes. However, these implantable micro devices are not functionally stable over time due to host-probe interactions. Thus, reliable high-resolution characterization methods are required to understand local tissue changes upon implantation. In this work, synchrotron X-ray tomography is employed for the first time to image the interface between brain tissue and an implanted neural probe, showing that this 3D imaging method is capable of resolving probe and surrounding tissue at a resolution of about 1 micrometer. Unstained tissue provides sufficient contrast to identify electrode sites on the probe, cells, and blood vessels within tomograms. Exemplarily, we show that it is possible to quantify characteristics of the interaction region between probe and tissue, like the blood supply system. Our first-time study demonstrates a way for simultaneous 3D investigation of brain tissue with implanted probe, providing information beyond what was hitherto possible.


Assuntos
Córtex Cerebral/diagnóstico por imagem , Eletrodos Implantados , Tomografia Computadorizada por Raios X/métodos , Animais , Córtex Cerebral/fisiologia , Imageamento Tridimensional/métodos , Microeletrodos , Ratos , Ratos Sprague-Dawley
13.
Biochim Biophys Acta Proteins Proteom ; 1867(7-8): 710-721, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31096047

RESUMO

Members of the casein kinase 1 (CK1) family are involved in regulation of crucial cellular pathways including chromosomal segregation, DNA repair, and apoptosis. Therefore, the activity of CK1 isoforms needs to be tightly regulated in order to avoid pathogenesis of proliferative diseases. Regulation of cellular CK1 activity is mainly mediated by (auto-) phosphorylation within its C-terminal regulatory domain. Cellular kinases, among them protein kinase A (PKA), checkpoint kinase 1 (Chk1), protein kinase C α (PKCα), and cyclin-dependent kinases (CDKs) have already been identified to C-terminally phosphorylate CK1δ, thereby modulating its kinase activity. In the present study we analyzed the CK1δ kinase domain for phosphorylation sites targeted by PKCα. Several phosphorylation sites were identified in vitro by initially using GST-CK1δ wild type and phosphorylation-site mutant protein fragments originating from the CK1δ kinase domain. Residues S53, T176, and S181 could finally be confirmed as targets for PKCα. Determination of kinetic parameters of full-length wild type and mutant GST-CK1δ-mediated substrate phosphorylation revealed that integrity of residue T176 is crucial for maintaining CK1δ kinase activity. Functional biochemical and cell culture-based analysis discovered that site-specific phosphorylation of CK1δ by PKCα contributes to fine-tuning of CK1δ kinase activity. In summary, our work for the first time demonstrates the effects of PKCα-mediated site-specific phosphorylation in the CK1δ kinase domain and enhances our knowledge about the regulation of the disease-associated CK1 kinase family.


Assuntos
Proteína Quinase C-alfa/metabolismo , Proteína Quinase C-delta/metabolismo , Substituição de Aminoácidos , Células HEK293 , Humanos , Mutação de Sentido Incorreto , Fosforilação/genética , Domínios Proteicos , Proteína Quinase C-alfa/genética , Proteína Quinase C-delta/genética
14.
Food Environ Virol ; 11(1): 1-8, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30465253

RESUMO

Increasing numbers of hepatitis E cases are currently recognized in many European countries. The zoonotic hepatitis E virus (HEV) genotype 3 mainly circulates in domestic pigs and wild boars, and can be transmitted to humans via consumption of insufficiently heated meat or meat products produced from those animals. Here, a detailed protocol for detection of HEV RNA in meat products is provided, which is based on the method originally described by Szabo et al. (Intl J Food Microbiol 215:149-156, 2015). It consists of a TRI Reagent®/chloroform-based food matrix homogenization, a silica bead-based RNA extraction and a real-time RT-PCR-based RNA detection. The method was further validated in a ring trial with nine independent laboratories using pork liver sausage samples artificially contaminated with different amounts of HEV. The results indicate sufficient sensitivity, specificity, and accuracy of the method for its broad future use in survey studies, routine food control or outbreak investigations.


Assuntos
Vírus da Hepatite E/genética , Carne/virologia , Técnicas de Amplificação de Ácido Nucleico/normas , RNA Viral , Virologia/normas , Animais , Limite de Detecção , RNA Viral/análise , RNA Viral/genética , RNA Viral/isolamento & purificação , Reprodutibilidade dos Testes , Sus scrofa/virologia
15.
High Alt Med Biol ; 16(1): 11-7, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25803140

RESUMO

BACKGROUND: Abnormally high pulmonary artery pressure (PAP) in hypoxia due to exaggerated hypoxic pulmonary vasoconstriction (HPV) is a key factor for development of high-altitude pulmonary edema (HAPE). It was shown that about 10% of a healthy Caucasian population has an exaggerated HPV that is comparable to the response measured in HAPE-susceptible individuals. Therefore, we hypothesized that those with exaggerated HPV are HAPE-susceptible. METHODS AND RESULTS: We screened 421 healthy Caucasians naïve to high altitude for HPV using Doppler echocardiography for assessment of systolic PAP in normobaric hypoxia (PASPHx; Po2 corresponding to 4500 m). Subjects with exaggerated HPV and matched controls were exposed to 4559 m with an identical protocol that causes HAPE in 62% of HAPE-S. Screening revealed 39 subjects with exaggerated HPV, of whom 33 (PASPHx 51±6 mmHg) ascended within 24 hours to 4559 m. Four (13%) of them developed HAPE during the 48 h-stay. This incidence is significantly lower than the recurrence rate of 62% previously observed in HAPE-S in the same setting. None of the control subjects (PASPHx 33±5 mmHg) developed HAPE. CONCLUSION: An exaggerated HPV cannot be considered a surrogate maker for HAPE-susceptibility although excessively elevated PAP is a hallmark in HAPE, while a normal HPV appears to protect from HAPE in this study.


Assuntos
Doença da Altitude/etiologia , Hipertensão Pulmonar/etiologia , Hipóxia/complicações , Artéria Pulmonar/fisiopatologia , Vasoconstrição , Adulto , Altitude , Doença da Altitude/epidemiologia , Pressão Arterial , Estudos de Casos e Controles , Suscetibilidade a Doenças , Humanos , Hipertensão Pulmonar/epidemiologia , Pulmão/irrigação sanguínea , Pessoa de Meia-Idade , Fatores de Tempo , População Branca
16.
J Transl Med ; 12: 119, 2014 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-24885819

RESUMO

BACKGROUND: Multiple myeloma is characterized by clonal expansion of B cells producing monoclonal immunoglobulins or fragments thereof, which can be detected in the serum and/or urine and are ideal target antigens for patient-specific immunotherapies. METHODS: Using phage particles as immunological carriers, we employed a novel chemically linked idiotype vaccine in a clinical phase I/II trial including 15 patients with advanced multiple myeloma. Vaccines composed of purified paraproteins linked to phage were manufactured successfully for each patient. Patients received six intradermal immunizations with phage idiotype vaccines in three different dose groups. RESULTS: Phage idiotype was well tolerated by all study participants. A subset of patients (80% in the middle dose group) displayed a clinical response indicated by decrease or stabilization of paraprotein levels. Patients exhibiting a clinical response to phage vaccines also raised idiotype-specific immunoglobulins. Induction of a cellular immune response was demonstrated by a cytotoxicity assay and delayed type hypersensitivity tests. CONCLUSION: We present a simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible patient-specific therapy for patients with advanced multiple myeloma and produced promising anti-tumor activity in a subset of patients.


Assuntos
Anticorpos Anti-Idiotípicos/imunologia , Bacteriófago M13/imunologia , Vacinas Anticâncer/uso terapêutico , Mieloma Múltiplo/terapia , Formação de Anticorpos , Vacinas Anticâncer/administração & dosagem , Vacinas Anticâncer/imunologia , Humanos , Mieloma Múltiplo/imunologia
17.
J Transl Med ; 11: 267, 2013 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-24152874

RESUMO

BACKGROUND: B cell malignancies are characterized by clonal expansion of B cells expressing tumor-specific idiotypes on their surface. These idiotypes are ideal target antigens for an individualized immunotherapy. However, previous idiotype vaccines mostly lacked efficiency due to a low immunogenicity of the idiotype. The objective of the present study was the determination of the feasibility, safety and immunogenicity of a novel chemically linked phage idiotype vaccine. METHODS: In the murine B cell lymphoma 1 model, tumor idiotypes were chemically linked to phage particles used as immunological carriers. For comparison, the idiotype was genetically expressed on the major phage coat protein g8 or linked to keyhole limpet hemocynanin. After intradermal immunizations with idiotype vaccines, tolerability and humoral immune responses were assessed. RESULTS: Feasibility and tolerability of the chemically linked phage idiotype vaccine was demonstrated. Vaccination with B cell lymphoma 1 idiotype expressing phage resulted in a significant survival benefit in the murine B cell lymphoma 1 protection model (60.2±23.8 days vs. 41.8±1.6 days and 39.8±3.8 days after vaccination with wild type phage or phosphate buffered saline, respectively). Superior immunogenicity of the chemically linked phage idiotype vaccine compared to the genetically engineered phage idiotype and keyhole limpet hemocynanin-coupled idiotype vaccine was demonstrated by significantly higher B cell lymphoma 1 idiotype-specific IgG levels after vaccination with chemically linked phage idiotype. CONCLUSION: We present a novel, simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible therapy and may produce a superior immune response compared to previously employed idiotype vaccination strategies.


Assuntos
Bacteriófagos/imunologia , Vacinas Anticâncer/imunologia , Modelos Animais de Doenças , Linfoma de Células B/imunologia , Animais , Formação de Anticorpos , Vacinas Anticâncer/efeitos adversos , Vacinas Anticâncer/química , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Camundongos
19.
Ann Intern Med ; 145(7): 497-506, 2006 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-17015867

RESUMO

BACKGROUND: High-altitude pulmonary edema (HAPE) is caused by exaggerated hypoxic pulmonary vasoconstriction associated with decreased bioavailability of nitric oxide in the lungs and by impaired reabsorption of alveolar fluid. OBJECTIVE: To investigate whether dexamethasone or tadalafil reduces the incidence of HAPE and acute mountain sickness (AMS) in adults with a history of HAPE. DESIGN: Randomized, double-blind, placebo-controlled study performed in summer 2003. SETTING: Ascent from 490 m within 24 hours and stay for 2 nights at 4559 m. PATIENTS: 29 adults with previous HAPE. INTERVENTION: Prophylactic tadalafil (10 mg), dexamethasone (8 mg), or placebo twice daily during ascent and stay at 4559 m. MEASUREMENTS: Chest radiography was used to diagnose HAPE. A Lake Louise score greater than 4 defined AMS. Systolic pulmonary artery pressure was measured by using Doppler echocardiography, and nasal potentials were measured as a surrogate marker of alveolar sodium transport. RESULTS: Two participants who received tadalafil developed severe AMS on arrival at 4559 m and withdrew from the study; they did not have HAPE at that time. High-altitude pulmonary edema developed in 7 of 9 participants receiving placebo and 1 of the remaining 8 participants receiving tadalafil but in none of the 10 participants receiving dexamethasone (P = 0.007 for tadalafil vs. placebo; P < 0.001 for dexamethasone vs. placebo). Eight of 9 participants receiving placebo, 7 of 10 receiving tadalafil, and 3 of 10 receiving dexamethasone had AMS (P = 1.0 for tadalafil vs. placebo; P = 0.020 for dexamethasone vs. placebo). At high altitude, systolic pulmonary artery pressure increased less in participants receiving dexamethasone (16 mm Hg [95% CI, 9 to 23 mm Hg]) and tadalafil (13 mm Hg [CI, 6 to 20 mm Hg]) than in those receiving placebo (28 mm Hg [CI, 20 to 36 mm Hg]) (P = 0.005 for tadalafil vs. placebo; P = 0.012 for dexamethasone vs. placebo). No statistically significant difference between groups was found in change in nasal potentials and expression of leukocyte sodium transport protein messenger RNA. LIMITATIONS: The study involved a small sample of adults with a history of HAPE. CONCLUSIONS: Both dexamethasone and tadalafil decrease systolic pulmonary artery pressure and may reduce the incidence of HAPE in adults with a history of HAPE. Dexamethasone prophylaxis may also reduce the incidence of AMS in these adults. ClinicalTrials.gov identifier: NCT00274430.


Assuntos
Doença da Altitude/prevenção & controle , Carbolinas/uso terapêutico , Dexametasona/uso terapêutico , Edema Pulmonar/prevenção & controle , Vasodilatadores/uso terapêutico , 3',5'-GMP Cíclico Fosfodiesterases/efeitos dos fármacos , Adulto , Doença da Altitude/fisiopatologia , Gasometria , Nucleotídeo Cíclico Fosfodiesterase do Tipo 5 , Método Duplo-Cego , Feminino , Hemodinâmica , Humanos , Masculino , Inibidores de Fosfodiesterase/uso terapêutico , Edema Pulmonar/fisiopatologia , Canais de Sódio/metabolismo , Tadalafila
20.
Radiology ; 236(3): 1083-93, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16055691

RESUMO

PURPOSE: To prospectively compare the accuracy of 16-detector row computed tomographic (CT) angiography with conventional digital subtraction angiography (DSA) as the reference standard in the assessment of aortoiliac and lower extremity arteries in patients with peripheral arterial disease. MATERIALS AND METHODS: This study was approved by the institutional review board, and informed consent was obtained. A total of 39 consecutive patients (27 men [mean age, 66 years] and 12 women [mean age, 64 years]) with peripheral arterial disease underwent both conventional DSA and 16-detector row CT angiography. For data analysis, the arterial vascular system was divided into 35 segments. A total of 1365 arterial segments were analyzed for arterial stenosis by two independent blinded readers using a four-point grading system (grade 1, <10% luminal narrowing; grade 2, 10%-49% luminal narrowing; grade 3, 50%-99% luminal narrowing; grade 4, occlusion). Interobserver agreements were calculated by using kappa statistics. A third independent blinded reader assessed possible reasons for disagreements between 16-detector row CT angiographic findings and conventional DSA findings. Effective radiation dose was calculated for both imaging modalities. RESULTS: Sixteen-detector row CT angiographic and conventional DSA findings were diagnostic in all vascular segments. Compared with conventional DSA, the sensitivity and specificity of 16-detector row CT angiography with regard to detection of hemodynamically significant stenosis in all 35 arterial segments were 96% and 97%, respectively, for both readers. Readers 1 and 2 overestimated arterial stenosis in 42 (3%) and 34 (2%) arterial segments, respectively, and underestimated arterial stenosis in 13 (1%) and 10 (1%) arterial segments, respectively. Interobserver agreement was excellent (kappa = 0.84-1.00). Presence of anteroposteriorly located luminal narrowing and extensive vascular wall calcification were considered main reasons for disagreements between imaging modalities. Effective radiation dose was lower for 16-detector row CT angiography (1.6-3.9 mSv) than for conventional DSA (6.4-16.0 mSv). CONCLUSION: Sixteen-detector row CT angiography is an accurate and reliable noninvasive alternative to conventional DSA in the assessment of aortoiliac and lower extremity arteries in patients with peripheral arterial disease.


Assuntos
Angiografia Digital , Angiografia/métodos , Doenças Vasculares Periféricas/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Idoso , Aorta Abdominal/diagnóstico por imagem , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Processamento de Imagem Assistida por Computador , Perna (Membro)/irrigação sanguínea , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade
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