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1.
Sci Rep ; 13(1): 20184, 2023 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-37978236

RESUMEN

Hexavalent chromium [Cr(VI)] is one of the most carcinogenic and mutagenic toxins, and is commonly released into the environemt from different industries, including leather tanning, pulp and paper manufacturing, and metal finishing. This study aimed to investigate the performance of dual chamber microbial fuel cells (DMFCs) equipped with a biocathode as alternative promising remediation approaches for the biological reduction of hexavalent chromium [Cr(VI)] with instantaneous power generation. A succession batch under preliminary diverse concentrations of Cr(VI) (from 5 to 60 mg L-1) was conducted to investigate the reduction mechanism of DMFCs. Compared to abiotic-cathode DMFC, biotic-cathode DMFC exhibited a much higher power density, Cr(VI) reduction, and coulombic efficiency over a wide range of Cr(VI) concentrations (i.e., 5-60 mg L-1). Furthermore, the X-ray photoelectron spectroscopy (XPS) revealed that the chemical functional groups on the surface of biotic cathode DMFC were mainly trivalent chromium (Cr(III)). Additionally, high throughput sequencing showed that the predominant anodic bacterial phyla were Firmicutes, Proteobacteria, and Deinococcota with the dominance of Clostridiumsensu strict 1, Enterobacter, Pseudomonas, Clostridiumsensu strict 11 and Lysinibacillus in the cathodic microbial community. Collectively, our results showed that the Cr(VI) removal occurred through two different mechanisms: biosorption and bioelectrochemical reduction. These findings confirmed that the DMFC could be used as a bioremediation approach for the removal of Cr(VI) commonly found in different industrial wastewater, such as tannery effluents. with simultaneous bioenergy production.


Asunto(s)
Fuentes de Energía Bioeléctrica , Fuentes de Energía Bioeléctrica/microbiología , Cromo/química , Bacterias/genética , Aguas Residuales
2.
RSC Adv ; 13(23): 15856-15871, 2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37250226

RESUMEN

Exploration of economical, highly efficient, and environment friendly non-noble-metal-based electrocatalysts is necessary for hydrogen and oxygen evolution reactions (HER and OER) but challenging for cost-effective water splitting. Herein, metal selenium nanoparticles (M = Ni, Co & Fe) are anchored on the surface of reduced graphene oxide and a silica template (rGO-ST) through a simple one-pot solvothermal method. The resulting electrocatalyst composite can enhance mass/charge transfer and promote interaction between water molecules and electrocatalyst reactive sites. NiSe2/rGO-ST shows a remarkable overpotential (52.5 mV) at 10 mA cm-2 for the HER compared to the benchmark Pt/C E-TEK (29 mV), while the overpotential values of CoSeO3/rGO-ST and FeSe2/rGO-ST are 246 and 347 mV, respectively. The FeSe2/rGO-ST/NF shows a low overpotential (297 mV) at 50 mA cm-2 for the OER compared to RuO2/NF (325 mV), while the overpotentials of CoSeO3-rGO-ST/NF and NiSe2-rGO-ST/NF are 400 and 475 mV, respectively. Furthermore, all catalysts indicate negligible deterioration, indicating better stability during the process of HER and OER after a stability test of 60 h. The water splitting system composed of NiSe2-rGO-ST/NF||FeSe2-rGO-ST/NF electrodes requires only ∼1.75 V at 10 mA cm-2. Its performance is nearly close to that of a noble metal-based Pt/C/NF||RuO2/NF water splitting system.

3.
RSC Adv ; 12(4): 2207-2218, 2022 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-35425267

RESUMEN

Oxygen reduction reaction (ORR) remains a pivotal factor in assessing the overall efficiency of energy conversion and storage technologies. A promising family of ORR electrocatalysts is mixed transition-metal oxides (MTMOs), which have recently gained a growing research interest. In this study, we developed MTMOs with different compositions (designated as A x B3-x O4; A = Cu, B = Co or Mn) anchored on two different carbon supports (activated carbon Vulcan XC-72 (AC) and graphene (G)) for catalyzing ORR in neutral media. Four different MTMO electrocatalysts (i.e., MnO2-CuO/AC, CoO-CuO/AC, CoO-CuO/G, and MnO2-CuO/G) were synthesized by a simple and scalable co-precipitation method. We documented the morphology and electrocatalytic properties of MTMO electrocatalysts using transmission and scanning electron microscopy, X-ray diffraction (XRD), X-ray photoelectron spectrometer (XPS), energy dispersive X-ray (EDX), and electrochemical techniques. Generally, MTMOs exhibited remarkably high ORR electrocatalytic activity with MTMOs anchored on an activated carbon support outperforming their respective MTMOs anchored on a graphene support, highlighting the importance of the catalyst support in determining the overall ORR activity of electrocatalysts. MnO2-CuO/AC has the highest diffusion limiting current density (j) value of 4.2 mA cm-2 at -600 mV (vs. SHE), which is ∼1.1-1.7-fold higher than other tested electrocatalysts (i.e., 3.9, 3.5, and 2.7 mA cm-2 for CoO-CuO/AC, CoO-CuO/G, and MnO2-CuO/G, respectively), and slightly lower than Pt/C (5.1 mA cm-2) at the same potential value. Moreover, all electrocatalysts exhibited good linearity and parallelism of the Koutechy-Levich (K-L) plots, suggesting that ORR followed first-order reaction kinetics with the number of electrons involved being close to four. Benefiting from their remarkable ORR electrochemical activities and low cost, our results reveal that non-precious MTMOs are efficient enough to replace expensive Pt for broad applications in energy conversion and electrocatalysis in neutral media, such as microbial fuel cells.

4.
J Genet Eng Biotechnol ; 20(1): 12, 2022 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-35072828

RESUMEN

BACKGROUND: Although microbial fuel cells (MFCs) represent a promising technology for capturing renewable energy from wastewater, their scaling-up is significantly limited by a slow-rate cathodic oxygen reduction reaction (ORR) and the development of a resilient anodic microbial community. In this study, mixed transition metal oxides of nickel and copper (Ni and Cu), supported on a graphene (G) (NiO-CuO/G) electrocatalyst, were synthesized and tested as a cost-effective cathode for ORR in MFCs. Electrochemical measurements of electrocatalyst were conducted using a rotating disk electrode (RDE) and linear sweep voltammetry (LSV) in a neutral electrolyte, and compared with a benchmark Pt/C catalyst. Furthermore, the long-term performance of the as-synthesized electrocatalyst was evaluated in a single-chamber MFC by measuring organic matter removal and polarization behavior. The successful enrichment of electroactive biofilm was also monitored using transmission electron microscopy and the Vitek2 compact system technique. RESULTS: When compared with the benchmark platinum cathode, the NiO-CuO/G electrocatalyst exhibited high selectivity toward ORR. The rotating disk electrode (RDE) experiments reveal that ORR proceeds via a 4-electron ORR mechanism. Furthermore, the NiO-CuO/G electrocatalyst also exhibited a high power density of 21.25 mW m-2 in an air-cathode MFC, which was slightly lower than that of Pt/C-based MFC (i.e., 50.4 mW m-2). Biochemical characterization of the most abundant bacteria on anodic biofilms identified four genera (i.e., Escherichia coli, Shewanella putrefaciens, Bacillus cereus, and Bacillus Thuringiensis/mycoides) that belonged to Gammaproteobacteria, and Firmicutesphyla. CONCLUSIONS: This study demonstrates that the NiO-CuO/G cathode had an enhanced electrocatalytic activity toward ORR in a pH-neutral solution. This novel mixed transition metal oxide electrocatalyst could replace expensive Pt-based catalysts for MFC applications.

5.
Chemphyschem ; 17(7): 1054-61, 2016 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-26748621

RESUMEN

Pt-CeO2 /C, Pt-TiO2 /C, and Pt-ZrO2 /C electrocatalysts were prepared by using a modified microwave-assisted polyol process. Physical characterization was performed by using XRD, TEM, and EDX analyses. The incorporation of different metal oxides increased the dispersion degree of Pt nanoparticles and reduced their diameter to 2.50 and 2.33 nm when TiO2 and ZrO2 were introduced to Pt/C, respectively. The electrocatalytic activity of various electrocatalysts was examined towards methanol oxidation in H2 SO4 solution by using cyclic voltammetry, chronoamperometry, and electrochemical impedance spectroscopy. Among the studied composites, Pt-ZrO2 /C was selected to be a candidate electrocatalyst for better electrochemical performance in direct methanol fuel cells.

6.
Phys Chem Chem Phys ; 16(22): 10414-8, 2014 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-24760311

RESUMEN

A multifunctional catalyst may represent a valid route to enhance methanol electro-oxidation. Ternary catalysts based on Pt modified with both Ru and Ir oxides show better performance for methanol electro-oxidation than bi-metallic Pt-Ru catalysts.

7.
Phys Rev Lett ; 107(27): 271102, 2011 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-22243300

RESUMEN

The gravitational-wave (GW) sky may include nearby pointlike sources as well as stochastic backgrounds. We perform two directional searches for persistent GWs using data from the LIGO S5 science run: one optimized for pointlike sources and one for arbitrary extended sources. Finding no evidence to support the detection of GWs, we present 90% confidence level (C.L.) upper-limit maps of GW strain power with typical values between 2-20×10(-50) strain(2) Hz(-1) and 5-35×10(-49) strain(2) Hz(-1) sr(-1) for pointlike and extended sources, respectively. The latter result is the first of its kind. We also set 90% C.L. limits on the narrow-band root-mean-square GW strain from interesting targets including Sco X-1, SN 1987A and the Galactic center as low as ≈7×10(-25) in the most sensitive frequency range near 160 Hz.

8.
Nature ; 460(7258): 990-4, 2009 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-19693079

RESUMEN

A stochastic background of gravitational waves is expected to arise from a superposition of a large number of unresolved gravitational-wave sources of astrophysical and cosmological origin. It should carry unique signatures from the earliest epochs in the evolution of the Universe, inaccessible to standard astrophysical observations. Direct measurements of the amplitude of this background are therefore of fundamental importance for understanding the evolution of the Universe when it was younger than one minute. Here we report limits on the amplitude of the stochastic gravitational-wave background using the data from a two-year science run of the Laser Interferometer Gravitational-wave Observatory (LIGO). Our result constrains the energy density of the stochastic gravitational-wave background normalized by the critical energy density of the Universe, in the frequency band around 100 Hz, to be <6.9 x 10(-6) at 95% confidence. The data rule out models of early Universe evolution with relatively large equation-of-state parameter, as well as cosmic (super)string models with relatively small string tension that are favoured in some string theory models. This search for the stochastic background improves on the indirect limits from Big Bang nucleosynthesis and cosmic microwave background at 100 Hz.

9.
Phys Rev Lett ; 102(11): 111102, 2009 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-19392186

RESUMEN

We report on an all-sky search with the LIGO detectors for periodic gravitational waves in the frequency range 50-1100 Hz and with the frequency's time derivative in the range -5 x 10{-9}-0 Hz s{-1}. Data from the first eight months of the fifth LIGO science run (S5) have been used in this search, which is based on a semicoherent method (PowerFlux) of summing strain power. Observing no evidence of periodic gravitational radiation, we report 95% confidence-level upper limits on radiation emitted by any unknown isolated rotating neutron stars within the search range. Strain limits below 10{-24} are obtained over a 200-Hz band, and the sensitivity improvement over previous searches increases the spatial volume sampled by an average factor of about 100 over the entire search band. For a neutron star with nominal equatorial ellipticity of 10{-6}, the search is sensitive to distances as great as 500 pc.

10.
Eur Respir J ; 28(4): 847-61, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17012631

RESUMEN

Chronic pulmonary aspiration (CPA) in children is an important cause of recurrent pneumonia, progressive lung injury, respiratory disability and death. It is sporadic, intermittent and variable, and often occurs in children with complicated underlying medical conditions and syndromes that produce symptoms indistinguishable from CPA. For most types of aspiration there is no gold-standard diagnostic test. The diagnosis of CPA is currently made clinically with some supporting diagnostic evaluations, but often not until significant lung injury has been sustained. Despite multiple diagnostic techniques, the diagnosis or exclusion of CPA in children is challenging. This is of particular concern given the outcome of unrecognised progressive lung injury and the invasiveness of definitive therapies. Although new techniques have been introduced since the 1990s and significant advances in the understanding of dysphagia and gastro-oesophageal reflux have been made, characterisation of the aspirating child remains elusive.


Asunto(s)
Aspiración Respiratoria/diagnóstico , Niño , Enfermedad Crónica , Colorantes , Trastornos de Deglución/complicaciones , Reflujo Gastroesofágico/complicaciones , Humanos , Radiografía Torácica , Aspiración Respiratoria/etiología , Aspiración Respiratoria/fisiopatología , Aspiración Respiratoria/terapia , Tomografía Computarizada por Rayos X
11.
Conf Proc IEEE Eng Med Biol Soc ; 2004: 3864-6, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-17271139

RESUMEN

We have developed an arterial transfer function using aortic and peripheral blood pressure waves measured simultaneously in healthy children undergoing diagnostic catheterization. We have applied this transfer function to peripheral blood pressure pulses measured during specific stages of sleep and at distinct points in the respiratory cycle in a different set of children with and without sleep disordered breathing to estimate the central aortic pressure wave shape.

12.
J Pediatr ; 139(1): 85-92, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11445799

RESUMEN

OBJECTIVE: To determine the contribution of surfactant protein abnormalities to the development of chronic lung injury in a familial form of interstitial lung disease. STUDY DESIGN: An 11-year-old girl, her sister, and their mother who were diagnosed with chronic interstitial lung disease underwent laboratory investigation of surfactant protein expression in bronchoalveolar lavage fluid and lung biopsy specimens. Nineteen patients with idiopathic pulmonary fibrosis and 9 patients who were investigated for pulmonary malignancy but who did not have interstitial lung disease served as control subjects. RESULTS: The 3 family members were found to have absent surfactant protein C (SP-C) and decreased levels of SP-A and SP-B in bronchoalveolar lavage fluid (BALF). Immunostaining for pulmonary surfactant proteins in lung biopsy specimens obtained from both children demonstrated a marked decrease of pro-SP-C in the alveolar epithelial cells but strong staining for pro-SP-B, SP-B, SP-A, and SP-D. No deviations from published surfactant protein B or C coding sequences were identified by DNA sequence analysis. All control subjects had a detectable level of SP-C in the BALF. CONCLUSION: The apparent absence of SP-C and a decrease in the levels of SP-A and SP-B are associated with familial interstitial lung disease.


Asunto(s)
Glicoproteínas/deficiencia , Enfermedades Pulmonares Intersticiales/genética , Surfactantes Pulmonares/deficiencia , Adulto , Biopsia , Western Blotting , Líquido del Lavado Bronquioalveolar/química , Estudios de Casos y Controles , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Pulmón/patología , Masculino , Persona de Mediana Edad , Proteolípidos , Proteína A Asociada a Surfactante Pulmonar , Proteínas Asociadas a Surfactante Pulmonar
13.
J Thorac Imaging ; 15(4): 297-300, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11039620

RESUMEN

The radiographic abnormalities of primary Kaposi's sarcoma of the lung in a patient with a renal transplant are reported. The findings are similar to other malignancies and infections that are well recognized in the renal transplant population. In the appropriate clinical setting, the radiologist should consider the diagnosis of Kaposi's sarcoma even in the absence of cutaneous lesions as reducing immunosuppression can be curative therapy.


Asunto(s)
Trasplante de Riñón , Neoplasias Pulmonares/diagnóstico por imagen , Sarcoma de Kaposi/diagnóstico por imagen , Humanos , Pulmón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X
15.
Radiographics ; 19 Spec No: S201-14, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10517455

RESUMEN

Owing to recent advances in magnetic resonance (MR) imaging, the role of obstetric MR imaging has increased in cases in which the results of ultrasonography are equivocal. Fast MR imaging sequences, such as T2-weighted fast spin-echo (SE), half-Fourier single-shot fast SE, 0.5-signal-acquired single-shot fast SE, and echo-planar imaging, have virtually eliminated the need for fetal premedication, with a concomitant improvement in image resolution and diminished blurring. Artifacts related to maternal respiratory motion and fetal motion no longer limit the anatomic detail that can be demonstrated with MR imaging. With such advances in obstetric MR imaging, knowledge of normal fetal anatomy at MR imaging is essential to detect disease in utero. MR imaging can demonstrate fetal anatomy in detail, especially the brain, thorax, abdomen, pelvis, and vasculature. Major developmental structures of the fetus, particularly the cranial nervous system, naso- and oropharynx, lungs, and major abdominal viscera, can be adequately evaluated with targeted fast MR imaging as early as the beginning of the second trimester. However, MR imaging of the heart remains limited. Fetal MR imaging during the first trimester remains controversial secondary to biosafety issues and is limited due to diminutive fetal size.


Asunto(s)
Feto/anatomía & histología , Imagen por Resonancia Magnética , Imagen Eco-Planar , Femenino , Humanos , Embarazo , Diagnóstico Prenatal , Valores de Referencia
16.
Am J Respir Cell Mol Biol ; 21(3): 388-94, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10460756

RESUMEN

In an earlier study, we showed that a recombinant adenovirus vector with deletions in the E1 and E3 regions of the viral genome (AV1LacZ4) induces expression of interleukin (IL)-8 in A549 cells (a human respiratory cell line). IL-8 can be induced through several pathways, including activation by IL-1. We tested the hypothesis that the induction of IL-8 by the AV1LacZ4 adenovirus is accomplished by means of the IL-1/IL-8 activation pathway, which could be blocked by IL-1 receptor antagonist (IRAP). Viral infections of A549 cells were performed at a multiplicity of infection (MOI) of 50 in the presence and absence of IRAP (50 ng/ml). A549 cells were also stimulated with tumor necrosis factor (TNF)-alpha (100 ng/ml), a known stimulant of IL-8, in the presence and absence of IRAP. IL-8 expression was evaluated by Northern blot analysis and enzyme-linked immunosorbent assay. Levels of IL-8 protein and messenger RNA (mRNA) were greater in the infected cells than in the uninfected ones at 24, 48, and 96 h (P < 0.01). Virus-infected cells treated with IRAP expressed 75% less IL-8 mRNA and protein (P < 0.01) than did untreated cells, whereas IRAP pretreatment of TNF-alpha-stimulated cells did not affect IL-8 production. IL-1 production by the virus-infected cells was detectable by concentration of the supernatants and reverse transcription-polymerase chain reaction. We conclude that IL-8 is produced by virus vector-infected cells, partly through IL-1 activation that can be downregulated by IRAP.


Asunto(s)
Adenoviridae/genética , Bronquios/efectos de los fármacos , Interleucina-8/metabolismo , Receptores de Interleucina-1/antagonistas & inhibidores , Sialoglicoproteínas/farmacología , Virus Defectuosos/genética , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Células Epiteliales/efectos de los fármacos , Vectores Genéticos , Humanos , Proteína Antagonista del Receptor de Interleucina 1 , Interleucina-1/farmacología , Interleucina-1/fisiología , Proteínas Recombinantes/metabolismo , Recombinación Genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo , Células Tumorales Cultivadas
17.
Hum Gene Ther ; 7(14): 1669-81, 1996 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-8886838

RESUMEN

A significant number of pulmonary exacerbations in patients with cystic fibrosis (CF) and asthma are associated with respiratory virus infections. The molecular mediators of this process are beginning to be understood. Viral infection of respiratory epithelial cultures in vitro leads to the production of intercellular adhesion molecule-1 (ICAM-1) (a ligand for inflammatory cell adhesion and activation) and a number of proinflammatory cytokines. Human gene therapy vectors derived from human adenoviruses (AV) are currently under evaluation for CF transmembrane regulator (CFTR) gene delivery to the airway epithelium of CF patients. However, studies in animal models using these AV vectors demonstrate pulmonary inflammation following AV exposure. Using an in vitro model, we examined the hypothesis that exposure of respiratory epithelial cells to AV vectors results in upregulation of ICAM-1 gene expression. Infections were performed using a replication-deficient, first-generation AV vector. A549 cells (a human pulmonary adenocarcinoma cell line) were exposed to AV at multiplicity of infection of 50-150 plaque-forming units/cell (resulting in > 90% of cells expressing the reporter gene by 48 hr following exposure). Measurements of ICAM-1 expression were made at time intervals following virus exposure using enzyme immunoassay, flow cytometry, and Northern blot analysis. Cell-bound ICAM-1 was significantly increased 96 hr following vector exposure, two to four times control, p < 0.001). The AV-exposed A549 cells also supported increased levels of adhesion of activated neutrophils 96 hr following AV exposure (four times control, p < 0.001) that was blocked by antibody to CD18. AV exposure of A549 monolayers increases expression of biologically active ICAM-1. Strategies to minimize host cellular proinflammatory responses to the replication-deficient AV vectors may improve their safety for gene therapy.


Asunto(s)
Adenovirus Humanos/fisiología , Regulación de la Expresión Génica/fisiología , Vectores Genéticos/fisiología , Molécula 1 de Adhesión Intercelular/genética , Neutrófilos/citología , Adenocarcinoma , Antígenos CD18/inmunología , Adhesión Celular , Epitelio , Técnicas de Transferencia de Gen , Humanos , Molécula 1 de Adhesión Intercelular/biosíntesis , Neoplasias Pulmonares , Activación Neutrófila , ARN Mensajero/análisis , Células Tumorales Cultivadas
18.
Am J Respir Crit Care Med ; 153(6 Pt 1): 1914-7, 1996 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-8665055

RESUMEN

The goal of this study was to evaluate the safety and efficacy of recombinant human DNase (rhDNase) in hospitalized patients with cystic fibrosis (CF) experiencing acute pulmonary exacerbations. Eighty patients with documented CF were enrolled at 11 CF centers when admitted for antibiotic therapy. Patients were at least 5 yr old with a forced vital capacity (FVC) > or = 35% of predicted and an oxygen saturation > or = 90% on a fraction of inspired oxygen (FIO2) < 0.5. Patients were randomized to receive rhDNase 2.5 mg in 2.5 ml excipient twice a day (n = 43) or 2.5 ml excipient alone twice daily (n = 37) along with conventional treatment for exacerbations. Administration of rhDNase was not associated with acute adverse events or deaths, and no patients experienced allergic or anaphylactic reactions. Although forced expiratory volume in one second (FEV1) and FVC improved in both treatment groups during the double-blind period, there were no statistically significant differences in the mean change from baseline in FEV1 or FVC between the two groups. rhDNase therapy is safe and well tolerated in CF patients with acute exacerbations requiring hospitalization, but the study did not demonstrate a statistically significant therapeutic effect of rhDNase when added to a regimen of antibiotics and chest physical therapy.


Asunto(s)
Fibrosis Quística/tratamiento farmacológico , Desoxirribonucleasa I/uso terapéutico , Expectorantes/uso terapéutico , Enfermedad Aguda , Adulto , Aerosoles , Fibrosis Quística/fisiopatología , Desoxirribonucleasa I/administración & dosificación , Método Doble Ciego , Quimioterapia Combinada , Expectorantes/administración & dosificación , Femenino , Hospitalización , Humanos , Masculino , Oxígeno/sangre , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Pruebas de Función Respiratoria , Resultado del Tratamiento
19.
Hum Gene Ther ; 7(3): 301-18, 1996 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-8835218

RESUMEN

To define the toxicity of cystic fibrosis transmembrane conductance regulator gene (CFTR) gene therapy with a replication-deficient recombinant adenovirus (Av1Cf2) in a nonhuman primate model, 10(10) plaque forming units (pfu) were instilled directly through a bronchoscope into the right lung of 5 macaques, and a lower dose of 4 x 10(6) pfu was administered to the right lung of 1 macaque. One sham-treated control received phosphate-buffered saline (PBS). The macaques were evaluated sequentially by clinical examination, vital signs, weight, hematology, blood chemistry, chest radiography, pulse oximetry, and bronchoalveolar lavage (BAL) at baseline and 3-28 days post-treatment. After the period of observation, macaques were sacrificed for autopsy and histological examination. The macaques tolerated the experimental therapy clinically with no changes in body temperature, oxygen saturation, heart rate, body weight, or blood pressure. However, 1 macaque with visible evidence of aspiration at the time of initial bronchoscopy developed tachypnea with right lower lobe (RLL) pneumonia on chest radiograph and by histology. There were no changes in Hgb, Wbc, BUN, plasma electrolytes, bilirubin, or hepatic transaminases. In the macaques that received 10(10) pfu, there was a progressive increase in the number of CD8+ lymphocytes in BAL that was maximal at 28 days. Histological examination of the treated lungs of the high-dose macaques at 3 days showed marked peribronchial and perivascular cuffing by inflammatory cells and alveolar accumulation of neutrophils and macrophages. The alveolitis appeared to be resolving at 28 days, although the perivascular and peribronchial aggregates of mononuclear cells were still present. In the high-dose macaques, BAL interleukin-8 (IL-8) was increased at all time points (256-388 pg/ml versus 1-84 pg/ml at baseline and in control), whereas IL-1 beta was increased only at days 21 and 28 (341-852 pg/ml versus 30-92 pg/ml at baseline and in control). There were no increases in BAL cell counts, IL-1 beta or IL-8, and histological changes were mild in the macaque that received 4 x 10(6) pfu. Evaluation for Av1Cf2-derived human CFTR expression using RS-PCR demonstrated expression at 3, 10, and 21, but not 28 days in macaques treated with 10(10) pfu of Av1Cf2. In situ hybridization analysis demonstrated human CFTR mRNA in the alveolar regions of the lobes that received the vector at 10 and 21 days. There was no evidence of expression after treatment with 4 x 10(6) pfu. This study showed that high-dose adenoviral vector administration to the lung achieved CFTR gene transfer and expression but was associated with increased concentrations of cytokines in BAL and alveolar inflammation. A low dose, equivalent to the maximum clinical dose currently proposed for phase I trials in human subjects, was not associated with cellular or cytokine evidence of inflammation, and histological abnormalities were mild.


Asunto(s)
Adenoviridae/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , ADN Complementario/administración & dosificación , Virus Defectuosos/genética , Vectores Genéticos/genética , Pulmón/metabolismo , Proteínas Recombinantes de Fusión/biosíntesis , Transfección , Adenoviridae/patogenicidad , Animales , Secuencia de Bases , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/biosíntesis , Virus Defectuosos/patogenicidad , Femenino , Terapia Genética , Vectores Genéticos/toxicidad , Hemodinámica , Humanos , Hibridación in Situ , Interleucina-1/análisis , Interleucina-8/análisis , Pruebas de Función Renal , Pruebas de Función Hepática , Pulmón/patología , Macaca fascicularis , Datos de Secuencia Molecular , Neumonía por Aspiración/etiología , Neumonía por Aspiración/patología , Neumonía Viral/etiología , Neumonía Viral/patología , Pruebas de Función Respiratoria , Método Simple Ciego , Distribución Tisular
20.
Scott Med J ; 32(1): 22-4, 1987 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-3563473

RESUMEN

A 49 year old man presented with near-fatal, fulminant, haemorrhagic cardiac tamponade. He responded well to emergency pericardiocentesis and subsequent investigation revealed the cause to be an unknown squamous carcinoma of the bronchus with pericardial involvement. He died 13 weeks later. Such a dramatic presentation of this type of tumour in a male patient has not been previously described.


Asunto(s)
Neoplasias de los Bronquios/complicaciones , Carcinoma de Células Escamosas/complicaciones , Taponamiento Cardíaco/etiología , Taponamiento Cardíaco/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Radiografía
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