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1.
J Chem Phys ; 160(7)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38364009

RESUMO

Bromine atom (Br) reactions lead to ozone depletion in the troposphere and stratosphere. Photodegradation of bromocarbons is one of the main sources of bromine atoms in the atmosphere. Here, we use high-level ab initio methods, including spin-orbit effects, to study the photodissociation of the CH2Br radical. All possible fragmentation pathways, namely CH2Br + hν → CH2 + Br, HCBr + H, and CBr + H2, have been analyzed. Potential-energy curves of the ground and several excited electronic states along the corresponding dissociating bond distance of each pathway have been calculated. Considering the actinic fluxes of solar irradiation in the troposphere and in the stratosphere in the relevant range of frequencies, it is found that the first five excited states of CH2Br can be accessed from the ground state. Analysis of the potential curves shows that the pathways producing CH2 + Br and HCBr + H can proceed through a fast direct dissociation mechanism, while the pathway leading to CBr + H2 involves much slower dissociation mechanisms like internal conversion between electronic states, predissociation, or tunneling through exit barriers. The main implications are that the two faster channels are predicted to be dominant, and the slower pathway is expected to be less relevant. The tropospheric and stratospheric solar actinic fluxes also allow for further dissociation of the HCBr and CBr fragments, generating additional Br atoms, provided that they survive possible collisions with other atmospheric reagents. Finally, we discuss the possible effect of each of the three CH2Br dissociation pathways on the depletion of atmospheric ozone.

2.
Environ Res ; 239(Pt 1): 117344, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37821067

RESUMO

During the East Antarctic International Ice Sheet Traverse (Eaiist, december 2019), in an unexplored part of the East Antarctic Plateau, snow samples were collected to expand our knowledge of the latitudinal variability of iodine, bromine and sodium as well as their relation in connection with emission processes and photochemical activation in this unexplored area. A total of 32 surface (0-5 cm) and 32 bulk (average of 1 m depth) samples were taken and analysed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Our results show that there is no relevant latitudinal trend for bromine and sodium. For bromine they also show that it has no significant post-depositional mechanisms while its inland surface snow concentration is influenced by spring coastal bromine explosions. Iodine concentrations are several orders of magnitude lower than bromine and sodium and they show a decreasing trend in the surface samples concentration moving southward. This suggests that other processes affect its accumulation in surface snow, probably related to the radial reduction in the ozone layer moving towards central Antarctica. Even though all iodine, bromine and sodium present similar long-range transport from the dominant coastal Antarctic sources, the annual seasonal cycle of the ozone hole over Antarctica increases the amount of UV radiation (in the 280-320 nm range) reaching the surface, thereby affecting the surface snow photoactivation of iodine. A comparison between the bulk and surface samples supports the conclusion that iodine undergoes spring and summer snow recycling that increases its atmospheric lifetime, while it tends to accumulate during the winter months when photochemistry ceases.


Assuntos
Iodo , Bromo , Neve , Sódio , Regiões Antárticas
3.
Drug Metab Dispos ; 50(4): 327-340, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35042701

RESUMO

Lurbinectedin is a novel and potent selective inhibitor of active transcription of protein-coding genes, triggering apoptosis of cancerous cells. It has been approved for the treatment of patients with metastatic small-cell lung cancer with disease progression on or after platinum-based chemotherapy. Studies exploring the disposition and metabolism of lurbinectedin were performed in vitro and in vivo (by intravenous administration of lurbinectedin). Low blood cell partitioning for lurbinectedin in rats, nonhuman primates (NHP), and humans was determined as 23.4%, 29.8%, and 9.8%, respectively. Protein binding was very high (>95%) in total plasma (rat, NHP, and human), albumin, and α-1-acid glycoprotein (both human). In vitro, lurbinectedin underwent intense liver microsome-mediated metabolism-in 10 minutes, 80% of the compound is metabolized in human-with CYP3A4 being the isoform involved in that metabolism. Results also showed NHPs being the nonclinical species which, metabolically, most closely resembles humans. Mass balance studies performed in rats (both genders), NHPs (male only), and patients (both genders) demonstrated that the principal route of excretion of 14C-lurbinectedin-related radioactivity was through the feces (88.7% ± 10.1% in patients), with only a minor fraction recovered from the urine (5.6% ± 2.0% in patients). In plasma samples, the majority of lurbinectedin-related radioactivity was attributed to unchanged compound (95% ± 3.1% and 70.2% ± 10.9% in NHPs and humans, respectively). Plasma metabolic profiling demonstrated the major (% compared with unchanged compound) circulating metabolites were N-Desmethyl-lurbinectedin (0.4% ± 0.2% and 10.4% ± 2.2% in NHPs and patients, respectively) and 1',3'-Desmethylene-lurbinectedin (0.9% ± 0.7% and 14.3% ± 10.4% in NHP and patients, respectively). SIGNIFICANCE STATEMENT: Lurbinectedin is a novel and potent selective inhibitor of active transcription of protein-coding genes, triggering apoptosis of cancerous cells, and was recently approved for the treatment of patients with metastatic small-cell lung cancer with disease progression on or after platinum-based chemotherapy. The present study provides a complete set of information on the pharmacokinetics, biotransformation, and elimination of 14C-lurbinectedin and its metabolites, following a single intravenous administration to nonclinical species (rats and nonhuman primates) and patients.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Animais , Carbolinas/farmacologia , Carbolinas/uso terapêutico , Fezes , Feminino , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Masculino , Ratos , Carcinoma de Pequenas Células do Pulmão/induzido quimicamente , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia
5.
Phys Rev Lett ; 116(21): 214801, 2016 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-27284661

RESUMO

The Polarized Electrons for Polarized Positrons experiment at the injector of the Continuous Electron Beam Accelerator Facility has demonstrated for the first time the efficient transfer of polarization from electrons to positrons produced by the polarized bremsstrahlung radiation induced by a polarized electron beam in a high-Z target. Positron polarization up to 82% have been measured for an initial electron beam momentum of 8.19 MeV/c, limited only by the electron beam polarization. This technique extends polarized positron capabilities from GeV to MeV electron beams, and opens access to polarized positron beam physics to a wide community.

6.
Clin Radiol ; 67(4): 366-71, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22000959

RESUMO

Fatty liver disease is an important cause of chronic liver disease in Western countries. The purpose of this article is to describe and illustrate the diagnostic criteria and various morphological patterns of fatty liver disease on multidetector computed tomography (MDCT) with an emphasis on potential limitations and diagnostic pitfalls.


Assuntos
Fígado Gorduroso/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Adulto , Erros de Diagnóstico , Feminino , Humanos , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade
7.
Minerva Med ; 103(6): 441-64, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23229366

RESUMO

Optical coherence tomography (OCT) has revolutionized intracoronary imaging. The unprecedented spatial resolution of this technique (15 µm) provides unique insights on the microstructure of the coronary wall. Currently, OCT is increasingly used in clinical practice and also constitutes an emerging, highly robust, research tool. OCT allows detailed visualization of atherosclerotic plaques and provides reliable information on plaque composition (lipid, fibrous, calcified) although its limited tissue penetration usually precludes a comprehensive analysis of the total plaque burden. OCT is the only technique allowing accurate measurements of the thickness of the fibrous cap, a classical marker of plaque vulnerability, and readily detects thin-cap fibroatheromas. In patients with acute coronary syndromes, plaque ruptures, with associated red or white thrombus, are nicely identified. OCT is also valuable to assess the results of coronary interventions. Stent expansion can be easily ascertained. In addition, due to its 10-times higher resolution, OCT is superior to intravascular ultrasound in the detection of even minor degrees of strut malapposition, tissue prolapse, residual thrombus and edge dissections. Furthermore, during follow-up OCT has a unique value to unravel the presence of strut coverage and to detect mild amounts of neointimal proliferation that might represent a valid surrogate marker of drug-eluting stent safety and efficacy. Finally, OCT has been used to unravel the underlying mechanisms implicated in stent failure, namely in-stent restenosis and stent thrombosis. Therefore, OCT appears ideally suited to help to move forward our understanding on the pathophysiology of coronary artery disease and to improve clinical decision-making processes, meeting the ever-increasing demand on coronary artery anatomical information from clinicians and researchers.


Assuntos
Doença da Artéria Coronariana/diagnóstico , Tomografia de Coerência Óptica/tendências , Pesquisa Translacional Biomédica , Reestenose Coronária/diagnóstico , Estenose Coronária/diagnóstico , Vasos Coronários/anatomia & histologia , Humanos , Tomografia de Coerência Óptica/métodos
8.
Folia Primatol (Basel) ; 82(3): 189-96, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22156490

RESUMO

In 1986, in response to the rapid habitat destruction throughout the archipelago, the Philippine tarsier was classified as endangered. Since that time, this tarsier has been reclassified as data deficient and more recently as near threatened despite a significant lack of information on the population density of the species. Data were collected at the Philippine Tarsier Foundation Sanctuary from June to October 2010. Population density was estimated using a modified form of the quadrat census method. A total of 55 individuals were located within the sampled area. This is equivalent to approximately 1.55 tarsiers per hectare. Ecologically, there were significantly more tarsiers found in the young secondary forest than in areas characterized as old secondary forest. Extrapolating to the entire protected area, as many as 258 tarsiers may reside in the sanctuary. The vegetation plots where tarsiers were found had substantially more trees per plot, contained trees with larger diameters, and contained slightly taller trees than did the plots where no tarsiers were observed.


Assuntos
Conservação dos Recursos Naturais , Tarsiidae/fisiologia , Animais , Ecossistema , Filipinas , Densidade Demográfica
9.
Sci Total Environ ; 751: 141557, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-32882549

RESUMO

We have analyzed potential harmful trace elements (PHTE; Pb, Hg, Zn, As and Cu) on sediment cores retrieved from lake Marboré (LM) (2612 m a.s.l, 42°41'N; 0° 2'E). PHTE variability allowed us to reconstruct the timing and magnitude of trace metal pollutants fluxes over the last 3000 years in the Central Pyrenees. A statistical treatment of the dataset (PCA) enabled us to discern the depositional processes of PHTE, that reach the lake via direct atmospheric deposition. Indeed, the location of LM above the atmospheric boundary layer makes this lake an exceptional site to record the long-range transport of atmospheric pollutants in the free troposphere. Air masses back-trajectories analyses enabled us to understand the transport pathways of atmospheric pollutants while lead isotopic analyses contributed to evaluate the source areas of metal pollution in SW Europe during the Late Holocene. PHTE variability, shows a clear agreement with the main exploitation phases of metal resources in Southern Europe during the Pre-Industrial Period. We observed an abrupt lead enrichment from 20 to 375 yrs CE mostly associated to silver and lead mining and smelting practices in Southern Iberia during the Roman Empire. This geochemical data suggests that regional atmospheric metal pollution during the Roman times rivalled the Industrial Period. PHTE also increased during the High and Late Middle Ages (10-15th centuries) associated to a reactivation of mining and metallurgy activities in high altitude Pyrenean mining sites during climate amelioration phases. Atmospheric mercury deposition in the Lake Marboré record mostly reflects global emissions, particularly from Almadén mines (central Spain) and slightly fluctuates during the last three millennia with a significant increase during the last five centuries. Our findings reveal a strong mining-related pollution legacy in alpine lakes and watersheds that needs to be considered in management plans for mountain ecosystems as global warming and human pressure effects may contribute to their future degradation.

10.
J Appl Microbiol ; 108(1): 158-62, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19548885

RESUMO

AIMS: To assess the different phenotypes and mechanisms of fluoroquinolone (FQ) resistance in clinical and environmental isolates of Escherichia coli. METHODS AND RESULTS: We compared FQ-resistant E. coli isolates, measuring minimal inhibitory concentrations (MIC) of ciprofloxacin, along with susceptibility to other antibiotics. We also searched for the presence of efflux pumps, using efflux inhibitors, and for plasmid-borne FQ-resistance by PCR. We found that, aside from the higher FQ-resistance prevalence among clinical strains, environmental ones resist much lower concentrations of ciprofloxacin. Efflux pumps mediate fluoroquinolone resistance as frequently among environmental isolates than in clinical strains. Plasmid-borne qnrA genes were not detected in any resistant strain. CONCLUSIONS: Environmental FQ-resistant strains may have a nonclinical origin and/or a selective pressure different from the clinical use of FQs. SIGNIFICANCE AND IMPACT OF THE STUDY: The identification of the source of low-level FQ-resistant strains (ciprofloxacin MIC c. 8 microg ml(-1)) in the environment could be important to curb the rapid emergence and spread of FQ-resistance in clinical settings, as these strains can easily become fully resistant to FQ concentrations achievable in fluids and tissues during therapy.


Assuntos
Anti-Infecciosos/farmacologia , Ciprofloxacina/farmacologia , Farmacorresistência Bacteriana/fisiologia , Proteínas de Escherichia coli/metabolismo , Escherichia coli/isolamento & purificação , Escherichia coli/metabolismo , Infecção Hospitalar/genética , Infecção Hospitalar/metabolismo , Infecção Hospitalar/microbiologia , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Humanos , México , Plasmídeos/genética , Plasmídeos/metabolismo
11.
Zootaxa ; 4834(2): zootaxa.4834.2.2, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-33056120

RESUMO

We report the rediscovery of Telmatobius halli (Hall's water frog), which had not been found since its description (over 80 years) since its type locality was not clearly established. "Aguas Calientes" near Ollagüe is hypothesized as the original type locality where Frank Gregory Hall collected the type material in 1935. The tadpole is re-described, and new data on the external and internal morphology of adults is provided. These new morphological data are compared with Telmatobius spp. inhabiting geographically close to T. halli in Chile and Bolivia. In addition, comments on its ecology, conservation, and taxonomic status in relation with other Telmatobius spp. inhabiting nearby areas in Ascotán and Carcote salt pans are provided. No evidence of Batrachochytrium dendrobatidis and Ranavirus infection was found in T. halli and a sympatric amphibian species. Our work supports the validity of T. halli and suggests this species should be considered as Data Deficient in the IUCN Red List assessment until taxonomic issues are resolved.


Assuntos
Anuros , Animais , Larva
12.
Mater Sci Eng C Mater Biol Appl ; 117: 111335, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32919684

RESUMO

Among the nanomaterials, rare sesquioxides (lanthanide oxides such as Lu2O3) are of interest due to their adequate thermal conductivity, excellent chemical stability, and high light output. The prostate-specific membrane antigen (PSMA) is an integral multifunctional protein overexpressed in various types of cancer cells. The radiolabeled PSMA inhibitor peptides (iPSMA) have demonstrated their usefulness as specific probes in the treatment and detection of a wide variety of neoplasms, mainly due to their high in vivo recognition by the PSMA protein. The objective of this research was to synthesize Lu2O3-iPSMA nanoparticles (NPs) and characterize their physicochemical properties before and after neutron activation, as well as to assess their biodistribution profile and in vitro potential to target cells overexpressing PSMA. The Lu2O3 NPs were synthesized by the precipitation-calcination method and conjugated to the iPSMA peptide using DOTA (1,4,7,10-tetraazocyclodecane-N,N',N″,N‴-tetraacetic acid) as a linking agent. Results of the physicochemical characterization by FT-IR and UV-Vis spectroscopies, SEM, TEM, DLS, HRTEM, SAED, DSC-TGA, and X-ray diffraction indicated the formation of Lu2O3-iPSMA NPs (diameter of 29.98 ± 9.07 nm), which were not affected in their physicochemical properties after neutron activation. 177Lu2O3-iPSMA NPs showed high affinity (Kd = 5.7 ± 1.9 nM) for the PSMA protein, evaluated by the saturation assay on HepG2 hepatocellular carcinoma cells (PSMA-positive). The biodistribution profile of the nanosystem in healthy mice showed the main uptake in the liver. After irradiation, radioactive Lu2O3-iPSMA NPs exhibited radioluminescent properties, making the in vivo acquisition of their biodistribution, via optical imaging, possible. The results obtained from this research validate the execution of additional preclinical studies with the objective of evaluating the potential of the 177Lu2O3-iPSMA NPs for the targeted radiotherapy and in vivo imaging of tumors overexpressing the PSMA protein.


Assuntos
Nanopartículas , Neoplasias da Próstata , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Nêutrons , Óxidos , Espectroscopia de Infravermelho com Transformada de Fourier , Distribuição Tecidual
13.
J Biomed Nanotechnol ; 16(5): 689-701, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32919488

RESUMO

Developments in the design of lanthanide oxide nanoparticles (NPs) have unleashed a wide variety of biomedical applications. Several types of hepatic cancer cells overexpress two proteins: the gastrin-releasing peptide receptor (GRPr), which specifically recognizes the bombesin (BN) peptide, and the prostate-specific membrane antigen (PSMA), which specifically binds to several peptides that inhibit its activity (iPSMA). This research synthesized and physicochemically characterized Sm2O3 nanoparticles functionalized with the iPSMA-BN heterodimeric peptide and studied the effects on their structural, biochemical and preclinical properties after activation by neutron irradiation for possible use in molecular dual-targeted radiotherapy of hepatocellular carcinoma. The Sm2O3 NPs were synthesized by the precipitation-calcination method and functionalized with iPSMA-BN peptide using the DOTA macrocycle as a linking agent. Analysis of physicochemical characterization via TEM, EDS, XRD, UV-Vis, FT-IR, DSL, and zeta potential results showed the formation of Sm2O3-iPSMA-BN NPs (94.23 ± 5.98 nm), and their physicochemical properties were not affected after neutron activation. The nanosystem showed a high affinity with respect to PSMA and GRPr in HepG2 cells ( Kd = 6.6 ± 1.6 nM) and GRPr in PC3 cells ( Kd = 10.6 ± 1.9 nM). 153Sm2O3-iPSMA-BN NPs exhibited radioluminescent properties, making possible in vivo optical imaging of their biodistribution in mice. The results obtained from this research support further preclinical studies designed to evaluate the dosimetry and therapeutic efficacy of 153Sm2O3-iPSMA-BN nanoparticles for in vivo imaging and molecular dual-targeted radiotherapy of liver tumors overexpressing PSMA and/or GRPr proteins.


Assuntos
Nanopartículas Metálicas , Animais , Bombesina , Linhagem Celular Tumoral , Humanos , Camundongos , Óxidos , Radioisótopos , Samário , Espectroscopia de Infravermelho com Transformada de Fourier , Distribuição Tecidual
14.
Infection ; 37(5): 407-17, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19768381

RESUMO

BACKGROUND: Complicated skin and skin structure infections (cSSSIs) are an important healthcare concern worldwide, as they can be life-threatening and challenging to treat. cSSSIs are normally managed using a combination of surgical intervention and prompt antibiotic use. New therapeutic options, including novel antibiotics, are required to improve outcomes in terms of duration of illness and to reduce the consumption of healthcare resources. METHODS: This was a prospective, randomized, open-label, parallel-group, multinational clinical study comparing sequential intravenous/oral (iv/po) moxifloxacin, 400 mg once daily, and iv amoxicillin/clavulanate, 1,000 mg/ 200 mg three times daily followed by po amoxicillin/ clavulanate, 500 mg/125 mg three times daily, for 7-21 days in hospitalized patients. RESULTS: A total of 804 patients were enrolled (mean age 51.8 years). The most common clinical diagnosis was complicated erysipelas (32.1% moxifloxacin; 30.0% amoxicillin/ clavulanate) and major abscess (31.1% moxifloxacin; 29.3% amoxicillin/clavulanate). Overall clinical success rates at the test-of-cure (TOC) visit (14-28 days post-treatment) for the per-protocol population (primary efficacy variable) were 80.6% (254/315) for patients in the moxifloxacin group and 84.5% (268/317) for those receiving amoxicillin/clavulanate (95% confidence interval [CI] -9.41, 2.18). Similar results were obtained for the intention-to-treat population (95% CI -7.56, 4.31). In both treatment groups, the highest clinical success rates were recorded for patients with complicated erysipelas, major abscess, surgical wound infection, and cellulitis. The lowest clinical cure rates were reported for diabetic foot infection and necrotizing fasciitis. In the microbiologically evaluable population, the bacteriological success rate (eradication and presumed eradication) was 76.0% (127/ 167) in the moxifloxacin group and 81.4% (140/172) in the amoxicillin/clavulanate group (95% CI -12.96, 4.41). Staphylococcus aureus (137 isolates) and Escherichia coli (50 isolates) were the most frequently isolated skin pathogens. Adverse event rates were comparable between treatment groups. CONCLUSIONS: Treatment with sequential iv/po moxifloxacin monotherapy once daily is clinically comparable to that with iv/po amoxicillin/clavulanate three times daily in the management of cSSSIs. Moxifloxacin's simple dose regimen offers an advantage over amoxicillin/clavulanate and represents a valuable addition to current antibiotic regimens used in the treatment of cSSSIs.


Assuntos
Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Compostos Aza/administração & dosagem , Compostos Aza/efeitos adversos , Ácido Clavulânico/administração & dosagem , Ácido Clavulânico/efeitos adversos , Quinolinas/administração & dosagem , Quinolinas/efeitos adversos , Dermatopatias Bacterianas/tratamento farmacológico , Administração Oral , Adulto , Idoso , Feminino , Fluoroquinolonas , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Moxifloxacina , Estudos Prospectivos , Resultado do Tratamento
15.
Sci Total Environ ; 693: 133587, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31369892

RESUMO

We report the evolution of tropospheric NO2 over the south-east of the Iberian Peninsula from 2005 to 2017. We have used hourly NO2 levels measured at air-quality stations in urban and suburban environments. Annual averages ranged between 14 and 45 µg m-3, with peaks above 200 µg m-3. A monthly variation was observed, with higher concentrations in cold months (40-60 µg m-3) and lower levels in the warm season (13-17 µg m-3). A diurnal pattern was found in urban and suburban areas. The upward trend in NO2 observed during the whole period contrasts with the upward trend reported in 2013-2017. The NO2 tropospheric column levels measured by the Ozone Monitoring Instrument over the Iberian Peninsula indicated a similar behaviour; nevertheless, the largest Spanish metropolitan areas did not show this increase. The mean sea level pressure and wind field data of ERA5 (European Centre for Medium-Range Weather Forecasts) were used to investigate the weather conditions, the NO2 outputs of the Copernicus Monitoring Services being used for the assessment of the NO2 spatial distribution. NO2 regional events, with concentrations in the range 140-150 µg m-3, and which occurred both in the winter and summer season under anticyclonic conditions, are also described. A local origin is identified in winter, whereas in summer, they are associated with a high-pressure system that blocks Mediterranean outflows towards the Atlantic Ocean. The high NO2 levels are attributed mainly to two factors: i) local emissions, rather than contributions from the western Mediterranean (or even North Africa), and ii) an increase in the pressure gradient between the Atlantic and the Mediterranean pressure systems, associated with a decrease in wind speed, was found during the last five years compared with the previous eight. Meteorological and chemical changes in mid-latitudes associated with global warming should also be investigated in the future.

16.
J Pharm Biomed Anal ; 169: 70-74, 2019 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-30831452

RESUMO

A new method for the quantification of metabolites in the absence of a chemically synthetized authentic standard is described herein. Metabolites to be used as reference standards were obtained biologically from microsomes incubation. The method is a stepwise process in which, only the radiolabeled (14C) and non-radiolabeled parent compound are required. Briefly, the separation and principles of equimolar detection of LC-radioactivity were applied and, a calibration curve of the 14C-parent compound was used to quantify the formation of its 14C-metabolite. In turn, serial dilutions of this 14C-metabolite were the base for the calibration curve that allowed the quantification of the non-radiolabeled metabolite. This method was applied in plasma samples obtained from a dog pharmacokinetic study in which, a PharmaMar compound (lurbinectedin) and its N-desmethylated metabolite were quantified and, the results compared to those obtained by the classical approach (with the chemically synthetized N-desmethylated metabolite). Plasma concentrations obtained with the two methods were very similar, with standard relative errors between -11% to -4%. Similar, main pharmacokinetic parameters were calculated with the concentrations obtained either thru this method or by using a chemically synthetized authentic standard.


Assuntos
Análise Química do Sangue/métodos , Animais , Calibragem , Radioisótopos de Carbono/química , Cromatografia Líquida , Cães , Microssomos/química , Microssomos/metabolismo , Plasma/química , Padrões de Referência , Suínos , Porco Miniatura
17.
Rev Esp Quimioter ; 32(3): 238-245, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30968675

RESUMO

OBJECTIVE: To assess the impact of the first months of application of a Code Sepsis in a high complexity hospital, analyzing patient´s epidemiological and clinical characteristics and prognostic factors. METHODS: A long-term observational study was carried out throughout a consecutive period of seven months (February 2015 - September 2015). The relationship with mortality of risk factors, and analytic values was analyzed using uni- and multivariate analyses. RESULTS: A total of 237 patients were included. The in-hospital mortality was 24% at 30 days and 27% at 60 days. The mortality of patients admitted to Critical Care Units was 30%. Significant differences were found between the patients who died and those who survived in mean levels of creatinine (2.30 vs 1.46 mg/dL, p <0.05), lactic acid (6.10 vs 2.62 mmol/L, p <0.05) and procalcitonin (23.27 vs 12.73 mg/dL, p<0.05). A statistically significant linear trend was found between SOFA scale rating and mortality (p<0.05). In the multivariate analysis additional independent risk factors associated with death were identified: age > 65 years (OR 5.33, p <0.05), lactic acid > 3 mmol/L (OR 5,85, p <0,05), creatinine > 1,2 mgr /dL (OR 4,54, p <0,05) and shock (OR 6,57, P <0,05). CONCLUSIONS: The epidemiological, clinical and mortality characteristics of the patients in our series are similar to the best published in the literature. The study has identified several markers that could be useful at a local level to estimate risk of death in septic patients. Studies like this one are necessary to make improvements in the Code Sepsis programs.


Assuntos
Protocolos Clínicos , Sepse/terapia , APACHE , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores , Creatinina/sangue , Feminino , Mortalidade Hospitalar/tendências , Hospitais Universitários , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Prognóstico , Fatores de Risco , Sepse/mortalidade , Resultado do Tratamento
18.
Rev. esp. patol. torac ; 35(3): 195-201, oct. 2023. tab, graf
Artigo em Espanhol | IBECS (Espanha) | ID: ibc-227388

RESUMO

Objetivo: Describir el uso de la capnografía transcutánea en una población adulta y pediátrica de pacientes con déficit de timidina quinasa 2 y hacer un estudio comparativo de costes de una determinación de gasometría arterial y capnografía en la población de nuestra consulta de VMNI. Metodología: Se realizó una anamnesis y unas pruebas funcionales respiratorias para valorar afectación de la musculatura respiratoria y calidad del sueño. Para determinar la hipoventilación, se midió la pCO2 transcutánea en vigilia y/o durante el sueño. Se realizó un estudio económico para comparar el coste de una determinación de ptcCO2 frente a la determinación mediante GSA. El estudio económico se realizó estimando la población total de pacientes que se valoraba en la consulta de VMNI de manera anual. Resultados: 9 pacientes con déficit de TK2 (4 adultos y 5 niños). A 4 pacientes se les realizó una poligrafía respiratoria basal. A la población pediátrica se les realizó un registro continuo de ptcCO2 con pulsioximetria anual. Se realizaron 4 registros con ptcCO2 y VMNI. Elcoste de la determinación de ptCO2 en comparación con la GSA fue de 6,29 euros frente a 5,37 euros. Conclusiones: La medición de la ptcCO2 es útil en la consulta de VMNI para la realización de medidas puntuales en la consulta como para monitorización continua durante el sueño. Con el uso que realizamos en nuestra consulta de la capnografía transcutánea, la determinación puntual de la pCO2 transcutánea es más económica que la realización de la GSA. (AU)


Objective: to describe the use of transcutaneous capnography in an adult and pediatric population of patients with Thymidine inase 2 deficiency and to compare the costs between blood gases by arterial gasometry (BGA) and capnography in our population. Material and methods: an anamnesis, and respiratory functional tests to assess respiratory muscle involvement, sleep quality were performed.To assess the presence of alveolar hypoventilation the determination of transcutaneous pCO2while awake and/or during sleepwas performed. An economic study has been done to compare the cost of a determination of ptcCO2 versus the determination by BGA. Results: 9 patients with TK2 deficiency (4 adults and 5 children). 4 patients underwent baseline respiratory polygraphy. The pediatric patients underwent at least one continuous recording of ptcCO2 with pulse oximetry each year.4 studies of ptcCO2 duringNIV were performed. The cost in the adult population of a punctual determination of pCO2 by BGA was 6,29 euros while for capnography was 5,37 euros. Conclusions: the measurement of ptcCO2 is useful in the consultation of NIV for the realization of specific measurements in the consultation as for continuous monitoring of this parameter. In our practice of transcutaneous capnography, the punctual determination of transcutaneous pCO2 is cheaper than the BGA. (AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Adulto , Pessoa de Meia-Idade , Capnografia/economia , Gasometria/economia , Timidina Quinase/deficiência , Monitoramento Ambiental , Testes de Função Respiratória , Ventilação não Invasiva
19.
Rev Esp Quimioter ; 31(3): 247-256, 2018 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-29781595

RESUMO

OBJECTIVE: Our aim was to evaluate the efficiency of an ASP after its implementation in 2016 in a Spanish hospital quality system. METHODS: Efficiency of the ASP was measured by process and outcome indicators at the level of the patient's quality of life, antimicrobial consumption and percentage of resistance to them during the 2016-2017 period. In 2017, the failures mode and effects analysis (FMEA) methodology was applied. An annual satisfaction survey was conducted. RESULTS: The clinical indicators were within the threshold of acceptability, as well as the empirical prescription of antimicrobials, the consumption of antibiotics (reduction of 77 DDD in the first semester of 2016 to 26 in the second semester of 2017) and the renal (gentamicin) and neurological (carbapenems) toxicity. The FMEA identified as a main risk the lack of adequacy of the empirical treatment once the antibiogram was obtained; thus, a corrective action was taken in 2017. Regarding the microbiological indicators, the incidence of multi-drug resistant and carbapenemase-producing enterobacteria, and that of methicillin-resistant Staphylococcus aureus, were reduced. Eighty-three percent of the counselling activities carried out were accepted. The surveys revealed a good acceptance and spread of the program, the need for protocols and training in the use of antibiotics. CONCLUSIONS: The implementation of the ASP in the quality system was efficient. The consumption of antibiotics and the adverse effects derived from their use were reduced, improving the quality of life of patients, and reducing health costs.


Assuntos
Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/organização & administração , Antibacterianos/efeitos adversos , Gestão de Antimicrobianos/normas , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Farmacorresistência Bacteriana Múltipla , Uso de Medicamentos , Hospitais , Humanos , Staphylococcus aureus Resistente à Meticilina , Aceitação pelo Paciente de Cuidados de Saúde , Melhoria de Qualidade , Qualidade de Vida , Espanha , Falha de Tratamento
20.
Rev Esp Quimioter ; 31(3): 237-246, 2018 Jun.
Artigo em Espanhol | MEDLINE | ID: mdl-29781594

RESUMO

OBJECTIVE: To describe an outbreak of multi-drug resistant extended-spectrum ß-lactamases-producing Klebsiella pneumoniae (MDR-ESBL-KPN) and the impact of measures for its control. METHODS: We reviewed the patients´ clinical records with MDR-ESBL-KPN isolation during 2013-2016 with resistance to fluoroquinolones, aminoglycosides, fosfomycin, and nitrofurantoin; susceptible to imipenem, meropenem, colistin, and tigecycline and variable to ertapenem and cotrimoxazole (Vitek-2). The genetic relationship between 35 isolates was established by PFGE and MLST. Control measures were put in place in January 2016. RESULTS: We detected 269 patients colonized and/or infected by KPN-ESBL-MDR with a common resistance phenotype; the strains studied carried the blaCTX-M-15 gene and formed a single cluster belonging to ST11. The outbreak was detected at the end of 2015, although it began in 2013 in an elderly center. The acquisition source of the strains was: 6% community-acquired, 37% hospital-acquired (76% in internal medicine) and 57% related to long health care facilities (78% of hospitalizations in the last year). Ninety-four percent of patients had at least one underlying disease, 90% received antibiotics previously and 49% had some invasive devices. After the introduction of control measures, the incidence of cases in the quarter was reduced from 29 to 15. CONCLUSIONS: We detected a monoclonal outbreak of MDR-CTX-M-15-KPN in 2015, with predominance of health-care associated cases. The success in the rapid spread of the outbreak was due to the delay in its detection and to the fact that most of the patients had previously received antibiotics. The control measures reduced the number of isolates by 50%.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , beta-Lactamases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/farmacologia , Criança , Infecções Comunitárias Adquiridas/microbiologia , Infecção Hospitalar/microbiologia , Surtos de Doenças , Feminino , Humanos , Incidência , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Adulto Jovem , beta-Lactamases/genética
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