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1.
Sci Total Environ ; 918: 170598, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38340837

RESUMEN

Indoor air quality is crucial for human health due to the significant time people spend at home, and it is mainly affected by internal sources such as solid fuel combustion for heating. This study investigated the indoor air quality and health implications associated with residential coal burning covering gaseous pollutants (CO, CO2 and total volatile organic compounds), particulate matter, and toxicity. The PM10 chemical composition was obtained by ICP-MS/OES (elements), ion chromatography (water-soluble ions) and thermal-optical analysis (organic and elemental carbon). During coal combustion, PM10 levels were higher (up to 8.8 times) than background levels and the indoor-to-outdoor ratios were, on average, greater than unity, confirming the existence of a significant indoor source. The chemical characterisation of PM10 revealed increased concentrations of organic carbon and elemental carbon during coal combustion as well as arsenic, cadmium and lead. Carcinogenic risks associated with exposure to arsenic exceeded safety thresholds. Indoor air quality fluctuated during the study, with varying toxicity levels assessed using the Aliivibrio fischeri bioluminescence inhibition assay. These findings underscore the importance of mitigating indoor air pollution associated with coal burning and highlight the potential health risks from long-term exposure. Effective interventions are needed to improve indoor air quality and reduce health risks in coal-burning households.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire Interior , Arsénico , Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Arsénico/análisis , Carbono/análisis , Carbón Mineral/análisis , Monitoreo del Ambiente , Material Particulado/análisis
2.
J Magn Reson Imaging ; 57(6): 1676-1695, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36912262

RESUMEN

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.


Asunto(s)
Neoplasias Encefálicas , Glioma , Imagen por Resonancia Magnética , Humanos , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Medios de Contraste , Glioma/diagnóstico por imagen , Glioma/cirugía , Glioma/patología , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos , Periodo Preoperatorio
3.
J Magn Reson Imaging ; 57(6): 1655-1675, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36866773

RESUMEN

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2.


Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Imagen por Resonancia Magnética/métodos , Glioma/diagnóstico por imagen , Glioma/cirugía , Glioma/patología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/patología , Espectroscopía de Resonancia Magnética/métodos , Imagen de Difusión por Resonancia Magnética
4.
Sci Total Environ ; 778: 146090, 2021 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-34030360

RESUMEN

The aim of this study was a detailed chemical characterisation of the particles released during the preparation of popular Portuguese dishes. PM2.5 samples were collected from the exhaust stacks on the roofs of a university canteen, a charcoal-grilled chicken restaurant and a wood-oven roasted piglet restaurant. The speciation of organic compounds was carried out by gas chromatography-mass spectrometry. The canteen was responsible for the lowest emissions of PM2.5, while emissions from the roasted piglet restaurant were the highest. Naphthalene was quantified as the most abundant aromatic compound in particle emissions from the canteen, while phenanthrene, fluoranthene, pyrene and chrysene were the dominant polycyclic aromatic hydrocarbons in samples from the other establishments. Benzo[a]pyrene equivalent concentrations obtained for the charcoal-grilled chicken and piglet restaurant indicate a dangerous carcinogenic potential to human health. Cholesterol was the prevalent sterol. Its highest values were obtained in particles from the charcoal-grilled chicken restaurant (621 ± 233 µg g-1 PM2.5). Oleic and palmitoleic were the unsaturated fatty acids identified at highest concentrations (from trace levels to 34.4 and to 6.89 mg g-1 PM2.5, respectively). Resin acids, such as dehydroabietic and abietic, were detected in all samples from the wood-oven roasted piglet restaurant. Nicotinamide was the amide detected at highest amount in emissions from the university canteen during the preparation of stews (7.67 mg g-1 PM2.5). Levoglucosan and its isomers were identified in all samples from the roasted piglet restaurant, but only the first monosaccharide anhydride was present in emissions from the university canteen and the charcoal-grilled chicken restaurant. Additionally, emission rates were estimated for the most representative compounds, taking into account the specific activity of each restaurant.

5.
Sci Total Environ ; 754: 142045, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-32916490

RESUMEN

A one-year aerosol sampling campaign, between 2016 and 2017, was conducted in a suburban area of León city, Spain. An association between the Positive Matrix Factorization (PMF) results and air masses through circulation weather types was carried out, through the construction of linear models from the PM10 concentrations and its chemical composition. The aerosol sources, identified by PMF six-factor solution, were: traffic (29%), aged sea salt (26%), secondary aerosols (16%), dust (13%), marine aerosol (7%) and biomass burning (3%). Traffic and secondary factors showed the highest PM10 contribution in the hybrid cyclonic types with wind component from the first and second quadrant. Anticyclonic types with wind component from the first quadrant exhibited high values of secondary, aged sea salt and dust factors. The highest contributions of the dust factor were also associated with northerly types. The linear models built for estimating the source apportionment of PM10, from aerosol chemical composition and geostrophic flow, showed positive coefficients for: westerly flows (WF) in marine factor, southerly flows (SF) in secondary and traffic factors, and shear southerly vorticities (ZS) in dust factor. Negative dependences were observed for ZS in aged sea salt factor and for SF in dust factor. The PM10 mass concentration calculated by the linear models and by the PMF model were strongly correlated. This can be very useful to determine the contribution of a specific source to PM10 in León, only by knowing some meteorological and chemical variables.

6.
Artículo en Inglés | MEDLINE | ID: mdl-32708187

RESUMEN

Passive diffusion tubes for volatile organic compounds (VOCs) and carbonyls and low volume particulate matter (PM2.5) samplers were used simultaneously in kitchens and outdoor air of four dwellings. PM2.5 filters were analysed for their carbonaceous content (organic and elemental carbon, OC and EC) by a thermo-optical technique and for polycyclic aromatic hydrocarbon (PAHs) and plasticisers by GC-MS. The morphology and chemical composition of selected PM2.5 samples were characterised by SEM-EDS. The mean indoor PM2.5 concentrations ranged from 14 µg m-3 to 30 µg m-3, while the outdoor levels varied from 18 µg m-3 to 30 µg m-3. Total carbon represented up to 40% of the PM2.5 mass. In general, the indoor OC/EC ratios were higher than the outdoor values. Indoor-to-outdoor ratios higher than 1 were observed for VOCs, carbonyls and plasticisers. PAH levels were much higher in the outdoor air. The particulate material was mainly composed of soot aggregates, fly ashes and mineral particles. The hazard quotients associated with VOC inhalation suggested a low probability of non-cancer effects, while the cancer risk was found to be low, but not negligible. Residential exposure to PAHs was dominated by benzo[a]pyrene and has shown to pose an insignificant cancer risk.


Asunto(s)
Contaminantes Atmosféricos/análisis , Contaminación del Aire Interior/análisis , Material Particulado/análisis , Monitoreo del Ambiente , Gases , Humanos , Tamaño de la Partícula , Hidrocarburos Policíclicos Aromáticos/análisis
7.
Acta Reumatol Port ; 43(2): 154-155, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30091960

RESUMEN

A 39-year-old female with systemic lupus erythematous (SLE) presented with fever, headaches and rash and was treated with empiric antibiotics for a presumable meningitis. However, cerebrospinal fluid turned out to be sterile and fever persisted with onset of hyporeflexive paraparesis with sensory loss below D10. Magnetic resonance imaging (MRI) demonstrated intradural-extramedullary hematoma (related to traumatic lumbar puncture), which was successfully drained. Subsequent surgical scar infection occurred and was treated accordingly. Due to persistent deficits and urinary retention development, she repeated MRI, which showed holocord abnormal T2 hyperintensity. After excluding other causes, SLE-associated longitudinal extensive transverse myelitis was diagnosed and treated with high-dose steroids and intravenous human immunoglobulin (IVIG), with reduction in intensity and extension of abnormal T2 signal within only one week. Monthly IVIG was kept for 6 months with progressive ability to walk and MRI findings resolution in 3 months. Four months after IVIG suspension no recurrence occurred.


Asunto(s)
Inmunoglobulinas Intravenosas/uso terapéutico , Mielitis Transversa/tratamiento farmacológico , Adulto , Femenino , Humanos , Lupus Eritematoso Sistémico/complicaciones , Mielitis Transversa/etiología , Índice de Severidad de la Enfermedad
8.
Int J Pediatr Otorhinolaryngol ; 111: 187-191, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29958608

RESUMEN

INTRODUCTION: Myringotomy with tympanostomy tube is the most common otologic surgery and some patients are still advised to avoid water. However, there is no evidence supporting this, with published papers questioning the need for this advice. METHODS: A Multiphase Computational Fluid Dynamics (CFD) model was created using computerized tomography images of a child's healthy ear. It was then used to study the flow of fluids through the external ear, tympanic cavity, and auditory tube, with and without submersion. RESULTS: The model accurately described the behavior of the air retained in the patient's nasopharynx and tympanic cavity. A simulated elevation of pressure in the external auditory canal without submersion, without increase of pressure in the nasopharynx, demonstrated that fluids promptly crossed the tympanostomy tube into the middle ear. However, simulated elevation of pressure in the external auditory canal with concurrent elevation of air pressure in the nasopharynx during submersion did not lead to passive tube opening nor to any detectable flow through the tympanostomy tube. CONCLUSIONS: In the model, submersion increases pressure in the nasopharynx which offsets the pressure in the external auditory canal. So, in the absence of a pressure gradient, no passive tubal opening took place, and no air or fluid flow was detected through the transtympanic tube. This model now includes the exhaust function of the auditory tube in the model and shows its relevance.


Asunto(s)
Simulación por Computador , Trompa Auditiva/fisiología , Hidrodinámica , Ventilación del Oído Medio , Modelos Biológicos , Fenómenos Biomecánicos , Preescolar , Conducto Auditivo Externo/fisiología , Oído Medio/fisiología , Oído Medio/cirugía , Humanos , Ventilación del Oído Medio/instrumentación , Cuidados Posoperatorios , Natación , Agua
9.
AAPS PharmSciTech ; 19(3): 1274-1286, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29313262

RESUMEN

Praziquantel (PZQ) is the recommended, effective, and safe treatment against all forms of schistosomiasis. Solid dispersions (SDs) in water-soluble polymers have been reported to increase solubility and bioavailability of poorly water-soluble drugs like PZQ, generally due to the amorphous form stabilization. In this work, poloxamer (PLX) 237 and poly(vinylpyrrolidone) (PVP) K30 were evaluated as potential carriers to revert PZQ crystallization. Binary and ternary SDs were prepared by the solvent evaporation method. PZQ solubility increased similarly with PLX either as binary physical mixtures or SDs. Such unpredicted data correlated well with crystalline PZQ and PLX as detected by solid-state NMR (ssNMR) and differential scanning calorimetry in those samples. Ternary PVP/PLX/PZQ SDs showed both ssNMR broad and narrow superimposed signals, thus revealing the presence of amorphous and crystalline PZQ, respectively, and exhibited the highest PZQ dissolution efficiency (up to 82% at 180 min). SDs with PVP provided a promising way to enhance solubility and dissolution rate of PZQ since PLX alone did not prevent recrystallization of amorphous PZQ. Based on ssNMR data, novel evidences on PLX structure and molecular dynamics were also obtained. As shown for the first time using ssNMR, propylene glycol and ethylene glycol constitute the PLX amorphous and crystalline components, respectively.


Asunto(s)
Antihelmínticos/química , Portadores de Fármacos/química , Poloxámero/química , Povidona/química , Praziquantel/química , Antihelmínticos/administración & dosificación , Rastreo Diferencial de Calorimetría , Cristalización , Praziquantel/administración & dosificación , Solubilidad
10.
Sci Total Environ ; 595: 494-504, 2017 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-28395264

RESUMEN

Atmospheric particulate matter (PM2.5) samples were collected over two one month periods during winter and summer in three Southern European cities (Oporto - traffic site, Florence - urban background, Athens - suburban). Concentrations of 27 polycyclic aromatic hydrocarbons (PAHs), 15 nitro-PAHs (NPAHs), 15 oxygenated-PAHs (OPAHs) and 4 azaarenes (AZAs) were determined. On average, the winter-summer concentrations of ΣPAHs were 16.3-5.60, 7.75-3.02 and 3.44-0.658ngm-3 in Oporto, Florence and Athens, respectively. The corresponding concentrations of ΣNPAHs were 15.8-9.15, 10.9-3.36 and 15.9-2.73ngm-3, whilst ΣOPAHs varied in the ranges 41.8-19.0, 11.3-3.10 and 12.6-0.704ngm-3. Concentrations of ΣAZAs were always below 0.5ngm-3. Irrespective of the city, the dominant PAHs were benzo[b+j+k]fluoranthene, retene, benzo[ghi]perylene and indeno[1,2,3-cd]pyrene. The most abundant OPAH in all cities was 1,8-naphthalic anhydride, whereas 5-nitroacenaphthene was the prevailing NPAH. The ΣOPAHs/ΣPAHs and ΣNPAHs/ΣPAHs were higher in summer than in winter, suggesting increasing formation of derivatives by photochemical degradation of PAHs. Molecular diagnostic ratios suggested that, after traffic, biomass burning was the dominant emission source. Apart from being influenced by seasonal sources, the marked differences between winter and summer may indicate that these diagnostic ratios are particularly sensitive to photodegradation, and thus should be applied and interpreted cautiously. The lifetime excess cancer risk from inhalation was, in part, attributable to PAH derivatives, acclaiming the need to include these compounds in regular monitoring programmes. On average, 206, 88 and 26 cancer cases per million people were estimated, by the World Health Organisation method, for the traffic-impacted, urban background and suburban atmospheres of Oporto, Florence and Athens, respectively.

11.
J Environ Sci (China) ; 53: 122-131, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28372736

RESUMEN

In summer 2010, twenty eight (14 PM2.5 samples plus 14 samples PM2.5-10) smoke samples were collected during wildfires that occurred in central Portugal. A portable high-volume sampler was used to perform the sampling, on quartz fibre filters of coarse (PM2.5-10) and fine (PM2.5) smoke samples. The carbonaceous content (elemental and organic carbon) of particulate matter was analysed by a thermal-optical technique. Subsequently, the particulate samples were solvent extracted and fractionated by vacuum flash chromatography into three different classes of organic compounds (aliphatics, polycyclic aromatic hydrocarbons (PAHs) and carbonyl compounds). The organic speciation was performed by gas chromatography-mass spectrometry (GC-MS). Emissions were dominated by the fine particles, which represented around 92% of the PM10. A clear predominance of carbonaceous constituents was observed, with organic to elemental carbon (OC/EC) ratios ranging between 1.69 and 245 in both size fractions. The isoprenoid ketone 6,10,14-trimethyl-2-pentadecanone, a tracer for secondary organic aerosol formation, was one of the dominant constituents in both fine and coarse particles. Retene was the most abundant compound in all samples. Good correlations were obtained between OC and both aliphatic and PAH compounds. Pyrogenic processes, thermal release of biogenic compounds and secondary processing accounted for 97% of the apportioned PM2.5 levels.


Asunto(s)
Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Incendios , Hidrocarburos/análisis , Material Particulado/análisis , Aerosoles/análisis , Hidrocarburos Policíclicos Aromáticos , Portugal , Estaciones del Año
12.
Br J Clin Pharmacol ; 83(3): 540-553, 2017 03.
Artículo en Inglés | MEDLINE | ID: mdl-27763682

RESUMEN

AIMS: To compare the levodopa/carbidopa (LC) and levodopa/benserazide (LB) pharmacokinetic profiles following repeated doses of opicapone (OPC) administered apart from levodopa. METHODS: Two randomized, double blind, sex-balanced, placebo-controlled studies in four groups of 12 or 18 healthy subjects each. In each group, enrolled subjects received a once-daily morning (5, 15 and 30 mg) or evening (5, 15 and 50 mg) administration of OPC or placebo for up to 28 days. On the morning of Day 11, 12 h after the OPC or placebo evening dose, or the morning of Day 21, 1 h after the OPC or placebo dose, a single dose of immediate-release 100/25 mg LC was administered. Similarly, on Day 18 morning, 12 h after the OPC or placebo evening dose, or Day 28 morning, 1 h after the OPC or placebo dose, a single dose of immediate-release 100/25 mg LB was administered. RESULTS: All OPC treatments, in relation to the placebo group, presented a higher extent of exposure (AUC) to levodopa following either LC or LB doses. A relevant but not dose-dependent increase in the levodopa AUC occurred with all OPC dose groups in relation to placebo. All active treatments significantly inhibited both peak (Emax ) and extent (AUEC) of the catechol-O-methyltransferase activity in relation to placebo. The tolerability profile was favourable. CONCLUSION: Opicapone, as once-daily oral evening regimen and/or 1 h apart from levodopa therapy, increases the bioavailability of levodopa associated with its pronounced, long-lasting and sustained catechol-O-methyltransferase inhibition. The tolerability profile was favourable and similar between OPC and placebo.


Asunto(s)
Benserazida/farmacocinética , Levodopa/farmacocinética , Oxadiazoles/farmacología , Oxadiazoles/farmacocinética , Adulto , Antiparkinsonianos/farmacocinética , Benserazida/efectos adversos , Benserazida/sangre , Benserazida/farmacología , Disponibilidad Biológica , Carbidopa/efectos adversos , Carbidopa/farmacología , Inhibidores de Catecol O-Metiltransferasa/efectos adversos , Inhibidores de Catecol O-Metiltransferasa/sangre , Inhibidores de Catecol O-Metiltransferasa/farmacocinética , Inhibidores de Catecol O-Metiltransferasa/farmacología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Levodopa/efectos adversos , Levodopa/sangre , Levodopa/farmacología , Masculino , Persona de Mediana Edad , Oxadiazoles/efectos adversos , Oxadiazoles/sangre
13.
Int J Pharm ; 511(2): 983-93, 2016 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-27506511

RESUMEN

The saturation solubility of PVP:PZQ physical mixtures (PMs) and solid dispersions (SDs) prepared from ethanol (E/E) or ethanol/water (E/W) by the solvent evaporation method at 1:1, 2:1 and 3:1 ratio (w/w) was determined. The presence of PVP improves the solubility of PZQ (0.31±0.01mg/mL). A maximum of 1.29±0.03mg/mL of PZQ in solution was achieved for the 3:1 SD (E/E). The amount of PZQ in solution depends on the amount of polymer and on the preparation method. Solid-state NMR (ssNMR) and DSC were used to understand this behavior. Results show that PMs are a mixture of crystalline PZQ with the polymer, while SDs show different degrees of drug amorphization depending on the solvent used. For E/W SDs, PZQ exists in amorphous and crystalline states, with no clear correlation between the amount of crystalline PZQ and the amount of PVP. For E/E SDs, formulations with a higher percentage of PZQ are amorphous with the components miscible in domains larger than 3nm ((1)H ssNMR relaxation measurements). Albeit its higher saturation solubility, the 3:1 E/E PVP:PZQ sample has a significant crystalline content, probably due to the water introduced by the polymer. High PVP content and small crystal size account for this result.


Asunto(s)
Antihelmínticos/química , Povidona/química , Praziquantel/química , Solventes/química , Antihelmínticos/metabolismo , Rastreo Diferencial de Calorimetría/métodos , Cristalización , Composición de Medicamentos , Espectroscopía de Resonancia Magnética/métodos , Povidona/metabolismo , Praziquantel/metabolismo , Solubilidad , Solventes/metabolismo
14.
Eur J Public Health ; 26(5): 887-889, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27335325

RESUMEN

The rate of invasive pneumococcal disease has markedly declined after the introduction of pneumococcal conjugated vaccines. In spite of the high effectiveness of this vaccine, there are some reports of vaccine failure and vaccine breakthroughs. Data on children with pneumococcal pneumonia in a European tertiary Hospital, from 2012 to 2014, were retrospectively collected before the implementation of pneumococcal conjugated vaccines in our country. We found four cases of pneumococcal serotype 3 vaccine failure and three cases of vaccine breakthroughs (two with serotype 3 and one with serotype 19A). All of these children were previously healthy.


Asunto(s)
Vacunas Neumococicas/uso terapéutico , Neumonía Neumocócica/prevención & control , Streptococcus pneumoniae/efectos de los fármacos , Centros de Atención Terciaria/estadística & datos numéricos , Vacunas Conjugadas/uso terapéutico , Adolescente , Niño , Preescolar , Femenino , Humanos , Incidencia , Lactante , Masculino , Neumonía Neumocócica/epidemiología , Portugal/epidemiología , Prevalencia , Estudios Retrospectivos
15.
Clin Pharmacol Drug Dev ; 5(3): 232-40, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27163503

RESUMEN

This study determined the effects of single doses of opicapone (OPC), a novel third-generation catechol-O-methyltransferase (COMT) inhibitor, on levodopa and 3-O-methyl-levodopa (3-OMD) pharmacokinetics (PK), COMT activity and motor fluctuations in patients with Parkinson disease (PD). Subjects received, in a double-blind manner, 25, 50, and 100 mg OPC or placebo (PLC) in 4 separate treatment periods. The washout period between doses was at least 10 days. During each period, the OPC/PLC capsules were to be coadministered with the morning dose of 100/25 mg levodopa/carbidopa (LC) or levodopa/benserazide (LB) on day 3. In relation to PLC, levodopa exposure increased 3.7%, 16.4%, and 34.8% following 25, 50, or 100 mg OPC, respectively. Maximum S-COMT inhibition (Emax ) ranged from 67.8% (25 mg OPC) to 100% (100 mg OPC). Peak and extent of S-COMT inhibition were dose-dependent. Maximum decrease in the plasma 3-OMD was observed following administration of 100 mg OPC. Opicapone administered concomitantly with standard-release 100/25 mg LC or LB improved motor performance. Treatments were generally well tolerated and safe. It was concluded that OPC is a new COMT inhibitor that significantly decreased COMT activity and increased systemic exposure to levodopa in PD patients with motor fluctuations.


Asunto(s)
Antiparkinsonianos/farmacocinética , Levodopa/farmacocinética , Oxadiazoles/administración & dosificación , Enfermedad de Parkinson/tratamiento farmacológico , Adulto , Anciano , Antiparkinsonianos/administración & dosificación , Benserazida/administración & dosificación , Carbidopa/administración & dosificación , Catecol O-Metiltransferasa/efectos de los fármacos , Catecol O-Metiltransferasa/metabolismo , Inhibidores de Catecol O-Metiltransferasa/administración & dosificación , Inhibidores de Catecol O-Metiltransferasa/efectos adversos , Inhibidores de Catecol O-Metiltransferasa/farmacología , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos , Interacciones Farmacológicas , Femenino , Humanos , Levodopa/administración & dosificación , Levodopa/efectos adversos , Masculino , Persona de Mediana Edad , Oxadiazoles/efectos adversos , Oxadiazoles/farmacología
16.
Clin Pharmacol Drug Dev ; 5(2): 150-61, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27138028

RESUMEN

Opicapone (OPC) is a novel third-generation catechol-O-methyltransferase (COMT) inhibitor. This randomized, double-blind, parallel, placebo-controlled and multiple ascending dose study in 3 sequential groups of up to 38 (19 Japanese plus 19 white subjects) aimed to compare the pharmacokinetics (PK) and pharmacodynamics (PD; COMT activity) of opicapone between healthy Japanese and matched white subjects. Enrolled subjects received a once-daily morning administration of OPC (5, 25, or 50 mg) or placebo for 10 days, with plasma and urine concentrations of opicapone and its metabolites measured up to 144 hours postdose, including S-COMT activity. Geometric mean ratios (GMRs) and confidence intervals (95%CIs) for the main PK and PD parameters of OPC were evaluated between populations. Both the PK and PD of OPC were similar in the Japanese and white populations. Overall, only minimal differences were noted between the 2 populations, which were not deemed to be statistically significant. When both populations were separated based on their COMT genotype, the observed PK and PD differences were also negligible. In conclusion, the PK and PD profiles of OPC were similar in the Japanese and white populations. Thus, ethnicity and COMT polymorphisms had no significant impact on the OPC PK and PD in the conditions of the study.


Asunto(s)
Inhibidores de Catecol O-Metiltransferasa/administración & dosificación , Catecol O-Metiltransferasa/efectos de los fármacos , Oxadiazoles/administración & dosificación , Adulto , Anciano , Pueblo Asiatico , Catecol O-Metiltransferasa/genética , Catecol O-Metiltransferasa/metabolismo , Inhibidores de Catecol O-Metiltransferasa/farmacocinética , Inhibidores de Catecol O-Metiltransferasa/farmacología , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oxadiazoles/farmacocinética , Oxadiazoles/farmacología , Polimorfismo Genético , Población Blanca , Adulto Joven
17.
Sci Total Environ ; 562: 822-833, 2016 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-27110993

RESUMEN

PM2.5 aerosol samples were collected from January 2013 to January 2014 on the kerbside of a major arterial route in the city of Oporto, Portugal, and later analyzed for carbonaceous fractions and water soluble ions. The average concentrations of organic carbon (OC), elemental carbon (EC) and water soluble organic carbon (WSOC) in the aerosol were 6.2µg/m(3), 5.0µg/m(3) and 3.8µg/m(3), respectively, and fit within the range of values that have been observed close to major roads in Europe, Asia and North America. On average, carbonaceous matter accounted for 56% of the gravimetrically measured PM2.5 mass. The three carbon fractions exhibited a similar seasonal variation, with high concentrations in late autumn and in winter, and low concentrations in spring. SO4(2-) was the dominant water soluble ion, followed by NO3(-), NH4(+), Cl(-), Na(+), K(+), oxalate, Ca(2+), Mg(2+), formate, methanesulfonate and acetate. Some of these ions exhibited a clear seasonal trend during the study period. The average OC/EC ratio for the entire set of samples was 1.28±0.61, which was consistent with a significant influence of vehicle exhaust emissions on aerosol composition. On the other hand, the average WSOC/OC ratio was 0.67±0.23, reflecting the influence of other emitting sources. WSOC was highly correlated with nssK(+), a tracer of biomass combustion, and was not correlated with nssSO4(2-), a species associated with secondary processes, suggesting that the main source of WSOC was biomass burning. Most of the SO4(2-) was anthropogenic in origin and was closely associated with NH4(+), pointing to the formation of secondary aerosols. Na(+), Cl(-) and methanesulfonate were clearly associated with marine sources while NO3(-) was related with combustion of both fossil and non-fossil fuels. Mixed sources explained the occurrence of the other water soluble ions.


Asunto(s)
Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Material Particulado/análisis , Portugal , Estaciones del Año
18.
J Clin Med Res ; 8(3): 260-2, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-26858803

RESUMEN

Viral bronchiolitis is the most common lower respiratory tract infection in infants and children under the age of 2. Respiratory syncytial virus (RSV) is the infecting agent in more than 50% of the cases. Usually the clinical course is uneventful and complications are uncommon. Secondary air leaks are a recognized rare complication of bronchiolitis, although the real incidence remains unknown. We report a case of a 21-month-old female that developed a spontaneous pneumothorax (PNO) with subcutaneous emphysema (SE) late in the course of RSV acute bronchiolitis. Additional investigation ruled out any underlying disease predisposing to spontaneous PNO. Physicians, especially those who work with small children, must be aware of this uncommon complication of bronchiolitis that may appear late in the course of the disease despite an initial clinical improvement.

19.
Cephalalgia ; 36(14): 1370-1378, 2016 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26826092

RESUMEN

BACKGROUND: Haemodialysis arteriovenous fistulas have common local and regional complications, but are rarely associated with neurological symptoms. CASE REPORT: A 43-year-old woman presented with short acute episodes of unilateral, non-throbbing, severe headache, vertigo and left lateropulsion. She had undergone renal transplantation and had a still-functioning left brachial arteriovenous fistula. No abnormality was detected on neurological examination or on brain parenchymal imaging. Colour Doppler ultrasonography showed a subclavian steal syndrome of the left vertebral artery and reversed flow in the left internal jugular vein. Ligation of the arteriovenous fistula had to be delayed as a result of renal graft dysfunction. Six months later she developed a headache attributed to intracranial hypertension. All symptoms subsided after ligation of the arteriovenous fistula. LITERATURE REVIEW: We identified 16 case reports of central neurological complications attributed to haemodialysis brachial fistulas. Headache descriptions were scarce and were not fully detailed. CONCLUSIONS: The case of our patient suggests that unilateral, episodic, non-throbbing, non-postural headache with transient neurological symptoms can be caused by combined arterial and venous flow abnormalities secondary to a high-flow arteriovenous brachial fistula. In this setting, this pattern of headache may precede overt signs of intracranial hypertension and may be used as a warning sign of cerebral venous congestion.


Asunto(s)
Fístula Arteriovenosa/complicaciones , Fístula Arteriovenosa/diagnóstico por imagen , Arteria Braquial/diagnóstico por imagen , Cefalea/diagnóstico por imagen , Cefalea/etiología , Hemodinámica/fisiología , Venas Yugulares/diagnóstico por imagen , Adulto , Velocidad del Flujo Sanguíneo/fisiología , Femenino , Humanos , Ultrasonografía Doppler en Color
20.
Int J Pharm ; 496(2): 812-21, 2015 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-26602291

RESUMEN

Praziquantel is the drug of choice to treat several parasitic infections including the neglected tropical disease schistosomiasis. Due to its low aqueous solubility, cyclodextrins have been tested as potential host candidates to prepare praziquantel inclusion complexes with improved solubility. For the first time, the interactions of praziquantel with ß-cyclodextrin and ß-cyclodextrin derivatives (methyl-ß-cyclodextrin and hydroxypropyl-ß-cyclodextrin) were investigated using high resolution solid-state NMR spectroscopy. The results of this work confirmed that solid-state NMR experiments provided structural characterization, demonstrating the formation of inclusion complexes most probably with PZQ adopting an anti conformation, also the most likely in amorphous raw PZQ. Further information on the interaction of praziquantel with methyl-ß-cyclodextrin was obtained from proton rotating-frame relaxation time measurements, sensitive to kilohertz-regime motions but modulated by spin-diffusion. Evidences were presented in all cases for praziquantel complexation through the aromatic ring. In addition, 1:2 drug:carrier molar ratio appears to be the most probable and therefore suitable stoichiometry to improve pharmaceutical formulations of this antischistosomal drug.


Asunto(s)
Ciclodextrinas/química , Espectroscopía de Resonancia Magnética/métodos , Praziquantel/química , Difracción de Rayos X
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