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1.
Am J Physiol Cell Physiol ; 324(1): C14-C28, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36409180

RESUMO

Skeletal muscle, the main metabolic engine in the body of vertebrates, is endowed with great plasticity. The association between skeletal muscle plasticity and two highly prevalent health problems: renal dysfunction and obesity, which share etiologic links as well as many comorbidities, is a subject of great relevance. It is important to know how these alterations impact on the structure and function of skeletal muscle because the changes in muscle phenotype have a major influence on the quality of life of the patients. This literature review aims to discuss the influence of a nontraditional axis involving kidney, bone, and muscle on skeletal muscle plasticity. In this axis, the kidneys play a role as the main site for vitamin D activation. Renal disease leads to a direct decrease in 1,25(OH)2-vitamin D, secondary to reduction in renal functional mass, and has an indirect effect, through phosphate retention, that contributes to stimulate fibroblast growth factor 23 (FGF23) secretion by bone cells. FGF23 downregulates the renal synthesis of 1,25(OH)2-vitamin D and upregulates its metabolism. Skeletal production of FGF23 is also regulated by caloric intake: it is increased in obesity and decreased by caloric restriction, and these changes impact on 1,25(OH)2-vitamin D concentrations, which are decreased in obesity and increased after caloric restriction. Thus, both phosphate retention, that develops secondary to renal failure, and caloric intake influence 1,25(OH)2-vitamin D that in turn plays a key role in muscle anabolism.


Assuntos
Qualidade de Vida , Vitamina D , Animais , Vitamina D/metabolismo , Hormônio Paratireóideo/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Rim/metabolismo , Fosfatos/metabolismo , Ingestão de Energia , Músculos
2.
Phys Rev Lett ; 131(22): 223801, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38101337

RESUMO

We present an approach to achieve zero modes in lattice models that do not rely on any symmetry or topology of the bulk, which are robust against disorder in the bulk of any type and strength. Such symmetry-free zero modes (SFZMs) are formed by attaching a single site or small cluster with zero mode(s) to the bulk, which serves as the "nucleus" that expands to the entire lattice. We identify the requirements on the couplings between this boundary and the bulk, which reveals that this approach is intrinsically non-Hermitian. We then provide several examples with either an arbitrary or structured bulk, forming spectrally embedded zero modes in the bulk continuum, midgap zero modes, and even restoring the "zeroness" of coupling or disorder-shifted topological corner states. Focusing on viable realizations using photonic lattices, we show that the resulting SFZM can be observed as the single lasing mode when optical gain is applied to the boundary.

3.
Phys Rev Lett ; 129(24): 243901, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36563238

RESUMO

An imaginary gauge transformation is at the core of the non-Hermitian skin effect. Here, we show that such a transformation can be performed in momentum space as well, which reveals that certain gain- and loss-modulated systems in their parity-time (PT) symmetric phases are equivalent to Hermitian systems with real potentials. Our analysis in momentum space also distinguishes two types of exceptional points (EPs) in the same system. Besides the conventional type that leads to a PT transition upon the continuous increase of gain and loss, we find real-valued energy bands connected at a Dirac EP in hybrid dimensions, consisting of a spatial dimension and a synthetic dimension for the gain and loss strength.

4.
Phys Rev Lett ; 126(16): 163901, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33961473

RESUMO

Photonic resonances play an essential role in the generation and propagation of light in optical and photonic devices, as well as in light-matter interaction, including nonlinear optical responses. Previous studies in lasers and other open systems have shown exotic roles played by non-Hermiticity on modifying passive resonances, defined in the absence of optical gain and loss. Here we report a new type of resonances in non-Hermitian photonic systems that does not originate from a passive resonance, identified by analyzing a unique quantization condition in the non-Hermitian extension of the Wentzel-Kramers-Brillouin method. Termed active photonic resonances, these unique resonances are found in non-Hermitian systems with a spatially correlated complex dielectric function, which is related to supersymmetry quantum mechanics after a Wick rotation. Remarkably, such an active photonic resonance shifts continuously on the real frequency axis as optical gain increases, suggesting the possibility of a tunable on-chip laser that can span a wavelength range over 100 nm.

5.
Sensors (Basel) ; 21(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209346

RESUMO

In contrast to previous works on data augmentation using LIDAR (Light Detection and Ranging), which mostly consider point clouds under good weather conditions, this paper uses point clouds which are affected by spray. Spray water can be a cause of phantom braking and understanding how to handle the extra detections caused by it is an important step in the development of ADAS (Advanced Driver Assistance Systems)/AV (Autonomous Vehicles) functions. The extra detections caused by spray cannot be safely removed without considering cases in which real solid objects may be present in the same region in which the detections caused by spray take place. As collecting real examples would be extremely difficult, the use of synthetic data is proposed. Real scenes are reconstructed virtually with an added extra object in the spray region, in a way that the detections caused by this obstacle match the characteristics a real object in the same position would have regarding intensity, echo number and occlusion. The detections generated by the obstacle are then used to augment the real data, obtaining, after occlusion effects are added, a good approximation of the desired training data. This data is used to train a classifier achieving an average F-Score of 92. The performance of the classifier is analyzed in detail based on the characteristics of the synthetic object: size, position, reflection, duration. The proposed method can be easily expanded to different kinds of obstacles and classifier types.

6.
J Environ Manage ; 294: 112917, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34119983

RESUMO

The interaction between climate change and biological invasions is a global conservation challenge with major consequences for invasive species management. However, our understanding of this interaction has substantial knowledge gaps; this is particularly relevant for invasive snakes on islands because they can be a serious threat to island ecosystems. Here we evaluated the potential influence of climate change on the distribution of invasive snakes on islands, using the invasion of the California kingsnake (Lampropeltis californiae) in Gran Canaria. We analysed the potential distribution of L. californiae under current and future climatic conditions in the Canary Islands, with the underlying hypothesis that the archipelago might be suitable for the species under these climate scenarios. Our results indicate that the Canary Islands are currently highly suitable for the invasive snake, with increased suitability under the climate change scenarios tested here. This study supports the idea that invasive reptiles represent a substantial threat to near-tropical regions, and builds on previous studies suggesting that the menace of invasive reptiles may persist or even be exacerbated by climate change. We suggest future research should continue to fill the knowledge gap regarding invasive reptiles, in particular snakes, to clarify their potential future impacts on global biodiversity.


Assuntos
Mudança Climática , Ecossistema , Animais , California , Ilhas , Serpentes , Espanha
7.
J Cell Mol Med ; 24(14): 8031-8044, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32519822

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HCT) is an effective therapy for the treatment of high-risk haematological malignant disorders and other life-threatening haematological and genetic diseases. Acute graft-versus-host disease (aGvHD) remains the most frequent cause of non-relapse mortality following allo-HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi-target drug successfully employed for prophylaxis and treatment of veno-occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo-HCT. Using a fully MHC-mismatched murine model of allo-HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD-associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo-HCT. Moreover, we performed in vitro mechanistic studies using human cells revealing that defibrotide inhibits leucocyte-endothelial interactions by down-regulating expression of key endothelial adhesion molecules involved in leucocyte trafficking. Together, these findings provide evidence that defibrotide may represent an effective and safe clinical alternative for both prophylaxis and treatment of aGvHD after allo-HCT, paving the way for new therapeutic approaches.


Assuntos
Comunicação Celular/efeitos dos fármacos , Endotélio/metabolismo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/metabolismo , Leucócitos/metabolismo , Polidesoxirribonucleotídeos/farmacologia , Doença Aguda , Animais , Biomarcadores , Biópsia , Comunicação Celular/imunologia , Linhagem Celular , Quimiotaxia de Leucócito/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Endotélio/efeitos dos fármacos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Mediadores da Inflamação/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Camundongos , Doadores de Tecidos , Transplante Homólogo
8.
Phys Rev Lett ; 125(8): 083902, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32909778

RESUMO

Noether's theorem relates constants of motion to the symmetries of the system. Here we investigate a manifestation of Noether's theorem in non-Hermitian systems, where the inner product is defined differently from quantum mechanics. In this framework, a generalized symmetry that we term pseudochirality emerges naturally as the counterpart of symmetries defined by a commutation relation in quantum mechanics. Using this observation, we reveal previously unidentified constants of motion in non-Hermitian systems with parity-time and chiral symmetries. We further elaborate the disparate implications of pseudochirality induced constant of motion: It signals the pair excitation of a generalized "particle" and the corresponding "hole" but vanishes universally when the pseudochiral operator is antisymmetric. This disparity, when manifested in a non-Hermitian topological lattice with the Landau gauge, depends on whether the lattice size is even or odd. We further discuss previously unidentified symmetries of this non-Hermitian topological system, and we reveal how its constant of motion due to pseudochirality can be used as an indicator of whether a pure chiral edge state is excited.

9.
Sensors (Basel) ; 20(15)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32752297

RESUMO

A semi-/autonomous driving car requires local weather information to identify if it is working inside its operational design domain and adapt itself accordingly. This information can be extracted from changes in the detections of a light detection and ranging (LIDAR) sensor. These changes are caused by modifications in the volumetric scattering of the atmosphere or surface reflection of objects in the field of view of the LIDAR. In order to evaluate the use of an automotive LIDAR as a weather sensor, a LIDAR is placed outdoor in a fixed position for a period of 9 months covering all seasons. As target, an asphalt region from a parking lot is chosen. The collected sensor raw data is labeled depending on the occurring weather conditions as: clear, rain, fog and snow, and the presence of sunlight: with or without background radiation. The influence of different weather types and background radiations on the measurement results is analyzed and different parameters are chosen in order to maximize the classification accuracy. The classification is done per frame in order to provide fast update rates while still keeping an F1 score higher than 80%. Additionally, the field of view is divided into two regions: atmosphere and street, where the influences of different weather types are most notable. The resulting classifiers can be used separately or together increasing the versatility of the system. A possible way of extending the method for a moving platform and alternatives to virtually simulate the scene are also discussed.

10.
Eat Weight Disord ; 25(6): 1827-1831, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31595460

RESUMO

INTRODUCTION: Anorexia nervosa (AN) is a serious disease with a high rate of chronification. In chronic and serious cases, psychotherapeutic and pharmacological treatments are not sufficient to control the disease. CASE REPORT: We present the case of a female patient with severe chronic restrictive anorexia nervosa resistant to psychomedical treatment. During the 31 years the illness evolved, the patient required multiple hospital admissions. With a body mass index (BMI) of 12.8 kg/m2 and consequent risk of death, stereotactic cingulotomy was performed comprising bilateral blocking of the anterior cingulate cortex by stereotactic radiofrequency thermocoagulation, confirmed by tractography 5 years later. After 10 years of follow-up, the patient is clinically stable with an increased BMI and improved neuropsychological indicators. DISCUSSION: Stereotactic surgery may be an option for patients with chronic anorexia nervosa where conventional treatments have proved insufficient.


Assuntos
Anorexia Nervosa , Anorexia Nervosa/complicações , Índice de Massa Corporal , Feminino , Seguimentos , Hospitalização , Humanos
11.
J Card Fail ; 24(4): 219-226, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29499322

RESUMO

BACKGROUND: Although pulmonary congestion can be quantified in heart failure (HF) by means of lung ultrasonography (LUS), little is known about LUS findings (B-lines) in different HF phenotypes. This prospective cohort study investigated the prevalence and clinical and echocardiographic correlates of B-lines in ambulatory HF patients with preserved (HFpEF) or reduced (HFrEF) ejection fraction compared with hypertensive patients. We related LUS findings to 12-month HF hospitalizations and all-cause mortality. METHODS AND RESULTS: We used LUS to examine hypertensive (n = 111), HFpEF (n = 46), and HFrEF (n = 73) patients (median age 66 y, 56% male, 79% white, and median EF 55%) undergoing clinically indicated outpatient echocardiography. B-line number was quantified offline, across 8 chest zones, blinded to clinical and echocardiographic characteristics. The proportion of patients with ≥3 B-lines was lower in hypertensive patients (13.5%) compared with both HFrEF (45.2%, P < .001) and HFpEF (34.8%; P = .05). HF patients with ≥3 B-lines had a higher risk of the composite outcome (age- and sex-adjusted hazard ratio 2.62, 95% confidence interval 1.15-5.96; P = .022). CONCLUSIONS: When performed at the time of outpatient echocardiography, LUS findings of pulmonary congestion differ between patients with known HF and those with hypertension, and may be associated with adverse outcomes.


Assuntos
Ecocardiografia/métodos , Insuficiência Cardíaca/fisiopatologia , Hipertensão/complicações , Pulmão/diagnóstico por imagem , Pacientes Ambulatoriais , Edema Pulmonar/diagnóstico , Volume Sistólico/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Humanos , Hipertensão/fisiopatologia , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Edema Pulmonar/etiologia , Adulto Jovem
12.
J Exp Biol ; 221(Pt 12)2018 06 22.
Artigo em Inglês | MEDLINE | ID: mdl-29691309

RESUMO

From a terrestrial ancestry, the fin whale (Balaenoptera physalus) is one of the largest animals on Earth with a sprinter anti-predator strategy, and a characteristic feeding mode, lunge feeding, which involves bouts of high-intensity muscle activity demanding high metabolic output. We investigated the locomotor muscle morphology and metabolism of this cetacean to determine whether its muscle profile (1) explains this unique swimming performance and feeding behaviour, (2) is or is not homogeneous within the muscle, and (3) predicts allometric variations inherent to an extreme body size. A predominantly fast-glycolytic phenotype characterized the fin whale locomotor muscle, composed of abundant fast-twitch (type IIA) fibres with high glycolytic potential, low oxidative capacity, relatively small size, and reduced number of capillaries. Compared with superficial areas, deep regions of this muscle exhibited a slower and more oxidative profile, suggesting a division of labour between muscle strata. As expected, the fin whale locomotor muscle only expressed the two slowest myosin heavy chain isoforms (I and IIA). However, it displayed anaerobic (glycolytic) and aerobic (lipid-based metabolism) capabilities higher than would be predicted from the allometric perspective of its extreme body size. Relationships between muscle metabolism and body mass were fibre-type specific. The 'sprinter' profile of the fin whale swimming muscle, particularly of its superficial compartment, supports physiological demands during both high-speed swimming and the lunge, when energy expenditure reaches maximal or supramaximal levels. Comparatively, the slower and more oxidative profile of the deep compartment of this muscle seems to be well designed for sustained, low-intensity muscle activity during routine swimming.


Assuntos
Tamanho Corporal , Metabolismo Energético , Baleia Comum/fisiologia , Fibras Musculares Esqueléticas/fisiologia , Natação/fisiologia , Animais , Cadáver , Feminino , Masculino
13.
Echocardiography ; 35(7): 905-914, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29600555

RESUMO

BACKGROUND: Prior studies have shown that both heart failure (HF) and atrial fibrillation (AF) are factors that impact left atrial function and structure. However, right atrial (RA) function measured as RA emptying fraction (RAEF) on echocardiography has not been analyzed systematically in a chronic HF population. The aim of this study was to assess RA volume index (RAVI) and RAEF in patients with chronic HF and patients with hypertension (HTN) and to relate these findings to other cardiopulmonary ultrasound parameters and 12-month outcomes. METHODS AND RESULTS: In this prospective observational study, we identified 119 patients with chronic HF (64 patients without a history of AF [HF without AF], 55 with AF [HF with AF]), and 127 patients with HTN but without important cardiac disease who underwent routine outpatient transthoracic echocardiography. We found that RAEF was impaired in patients with HF without AF compared to patients with HTN (35% ±2 vs 50% ±1, P < .001), whereas RAVI did not differ between these two groups. Lower RAEF was associated with larger RAVI and higher estimated RA pressures but not with a higher degree of pulmonary congestion by lung ultrasound. Both lower RAEF and higher RAVI were associated with an increased risk of 12-month HF hospitalizations or all-cause death (age, sex, and AF adjusted HR: 4.07, 95% CI: 1.69-9.79; P = .002, vs 2.74, 95% CI: 1.15-6.54, P = .023). CONCLUSIONS: In an outpatient HF cohort, both lower RAEF and increased RAVI were associated with other markers of impaired cardiac function and 12-month adverse events.


Assuntos
Função do Átrio Direito/fisiologia , Volume Cardíaco/fisiologia , Átrios do Coração/diagnóstico por imagem , Insuficiência Cardíaca/complicações , Hipertensão/complicações , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Ecocardiografia , Feminino , Seguimentos , Átrios do Coração/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
14.
J Immunoassay Immunochem ; 39(1): 30-42, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29144197

RESUMO

Congenital hypothyroidism is one of the most common preventable causes of mental retardation. The Center of Immunoassay has developed the UMELISA® T4 NEONATAL and UMELISA® T4 to determine neonatal T4 levels in dried blood and serum samples. Both reagent kits use the same polystyrene plates coated with anti-thyroxine (T4) polyclonal antibodies as solid phase. This work shows the re-standardization of the UMELISA® T4 NEONATAL and UMELISA® T4 using plates coated with anti-T4 monoclonal antibodies (T4Mabs). Polystyrene plates of the modified assays were firstly coated with polyclonal IgG sheep-anti-mouse IgG for 18 hours. T4Mabs were added to the plates and incubated for 2 hours at room temperature. Different performance parameters were evaluated and correlation studies with the commercial kits done. Using polystyrene plates coated with T4Mabs increases the slope of the calibration curve in the clinical interest zone. The assay conjugates work twice diluted in respect to the ones of the commercial kits. Recovery percentages (90.8-110.7 for UMELISA® T4 NEONATAL and 92.1-109.3 for UMELISA® T4) and intra (7.2-7.6 for UMELISA® T4 NEONATAL and 6.9-7.2 for UMELISA® T4) and inter (7.4-8.5 for UMELISA® T4 NEONATAL and 7.1-8.5 for UMELISA® T4) coefficients of variation were similar to the ones described for the commercial kits. Limits of detection and quantification were 9.0 and 21.1 nmol/L for UMELISA® T4 NEONATAL, and 8.9 and 20.5 nmol/L for UMELISA® T4, respectively. The results also showed high overall concordance between assays (n = 244, r = 0.92, ρc = 0.91 for UMELISA® T4 NEONATAL and n = 492, r = 0.92, ρc = 0.9 for UMELISA® T4). The analytical sensibility of UMELISA® T4 NEONATAL and UMELISA® T4 is improved by using polystyrene plates coated with T4Mabs, without affecting the precision and accuracy of the results. ABBREVIATIONS: T4: L-Thyroxine; ELISA: Enzyme-linked immunosorbent assay; SUMA: Ultra Micro Analytic System; UMELISA: Ultramicro enzyme-linked immunosorbent assay; TSH: Thyroid-stimulating hormone.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/imunologia , Ensaio de Imunoadsorção Enzimática/instrumentação , Ensaio de Imunoadsorção Enzimática/normas , Poliestirenos/química , Tiroxina/imunologia , Ensaio de Imunoadsorção Enzimática/métodos , Humanos
15.
Rev Esp Enferm Dig ; 109(8): 609, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28715902

RESUMO

Within the functional tests, the High Resolution Manometry has been a great improvement in the diagnosis of esophageal motor disorders, especially those that cause obstruction or difficulty for the normal progress of the alimentary content. We present the case of a patient with dysphagia to which a manometry is performed in the diagnostic process, where the presence of two types of Acalasia is present in the same tracing.


Assuntos
Acalasia Esofágica/diagnóstico , Adulto , Deglutição , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/etiologia , Acalasia Esofágica/complicações , Acalasia Esofágica/fisiopatologia , Transtornos da Motilidade Esofágica , Feminino , Humanos , Manometria
16.
Bull World Health Organ ; 94(2): 147-52, 2016 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-26908964

RESUMO

PROBLEM: New drugs for infectious diseases often need to be evaluated in low-resource settings. While people working in such settings often provide high-quality care and perform operational research activities, they generally have less experience in conducting clinical trials designed for drug approval by stringent regulatory authorities. APPROACH: We carried out a capacity-building programme during a multi-centre randomized controlled trial of delamanid, a new drug for the treatment of multidrug-resistant tuberculosis. The programme included: (i) site identification and needs assessment; (ii) achieving International Conference on Harmonization - Good Clinical Practice (ICH-GCP) standards; (iii) establishing trial management; and (iv) increasing knowledge of global and local regulatory issues. LOCAL SETTING: Trials were conducted at 17 sites in nine countries (China, Egypt, Estonia, Japan, Latvia, Peru, the Philippines, the Republic of Korea and the United States of America). Eight of the 10 sites in low-resource settings had no experience in conducting the requisite clinical trials. RELEVANT CHANGES: Extensive capacity-building was done in all 10 sites. The programme resulted in improved local capacity in key areas such as trial design, data safety and monitoring, trial conduct and laboratory services. LESSONS LEARNT: Clinical trials designed to generate data for regulatory approval require additional efforts beyond traditional research-capacity strengthening. Such capacity-building approaches provide an opportunity for product development partnerships to improve health systems beyond the direct conduct of the specific trial.


Assuntos
Antituberculosos/uso terapêutico , Fortalecimento Institucional/organização & administração , Cooperação Internacional , Nitroimidazóis/uso terapêutico , Oxazóis/uso terapêutico , Projetos de Pesquisa , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Fortalecimento Institucional/normas , Protocolos Clínicos , Documentação , Aprovação de Drogas , Humanos
17.
Am J Physiol Renal Physiol ; 309(7): F638-47, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26246512

RESUMO

This study describes fiber-type adaptations in hindlimb muscles, the interaction of sex, and the role of hypoxia on this response in 12-wk ⅚ nephrectomized rats (Nx). Contractile, metabolic, and morphological features of muscle fiber types were assessed in the slow-twitch soleus and the fast-twitch tibialis cranialis muscles of Nx rats, and compared with sham-operated controls. Rats of both sexes were considered in both groups. A slow-to-fast fiber-type transformation occurred in the tibialis cranialis of Nx rats, particularly in males. This adaptation was accomplished by impaired oxidative capacity and capillarity, increased glycolytic capacity, and no changes in size and nuclear density of muscle fiber types. An oxidative-to-glycolytic metabolic transformation was also found in the soleus muscle of Nx rats. However, a modest fast-to-slow fiber-type transformation, fiber hypertrophy, and nuclear proliferation were observed in soleus muscle fibers of male, but not of female, Nx rats. Serum testosterone levels decreased by 50% in male but not in female Nx rats. Hypoxia-inducible factor-1α protein level decreased by 42% in the tibialis cranialis muscle of male Nx rats. These data demonstrate that 12 wk of Nx induces a muscle-specific adaptive response in which myofibers do not change (or enlarge minimally) in size and nuclear density, but acquire markedly different contractile and metabolic characteristics, which are accompanied by capillary rarefaction. Muscle function and sex play relevant roles in these adaptations.


Assuntos
Membro Posterior/citologia , Membro Posterior/fisiologia , Fibras Musculares de Contração Rápida/fisiologia , Fibras Musculares de Contração Lenta/fisiologia , Nefrectomia , Animais , Peso Corporal/fisiologia , Capilares/citologia , Capilares/fisiologia , Ingestão de Alimentos/fisiologia , Feminino , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Hipóxia/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Testes de Função Renal , Masculino , Fibras Musculares de Contração Rápida/ultraestrutura , Fibras Musculares de Contração Lenta/ultraestrutura , Cadeias Pesadas de Miosina/metabolismo , Tamanho do Órgão/fisiologia , Ratos , Ratos Wistar , Caracteres Sexuais , Succinato Desidrogenase/metabolismo , Testosterona/metabolismo , Uremia/patologia
18.
N Engl J Med ; 366(23): 2151-60, 2012 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-22670901

RESUMO

BACKGROUND: Delamanid (OPC-67683), a nitro-dihydro-imidazooxazole derivative, is a new antituberculosis medication that inhibits mycolic acid synthesis and has shown potent in vitro and in vivo activity against drug-resistant strains of Mycobacterium tuberculosis. METHODS: In this randomized, placebo-controlled, multinational clinical trial, we assigned 481 patients (nearly all of whom were negative for the human immunodeficiency virus) with pulmonary multidrug-resistant tuberculosis to receive delamanid, at a dose of 100 mg twice daily (161 patients) or 200 mg twice daily (160 patients), or placebo (160 patients) for 2 months in combination with a background drug regimen developed according to World Health Organization guidelines. Sputum cultures were assessed weekly with the use of both liquid broth and solid medium; sputum-culture conversion was defined as a series of five or more consecutive cultures that were negative for growth of M. tuberculosis. The primary efficacy end point was the proportion of patients with sputum-culture conversion in liquid broth medium at 2 months. RESULTS: Among patients who received a background drug regimen plus 100 mg of delamanid twice daily, 45.4% had sputum-culture conversion in liquid broth at 2 months, as compared with 29.6% of patients who received a background drug regimen plus placebo (P=0.008). Likewise, as compared with the placebo group, the group that received the background drug regimen plus 200 mg of delamanid twice daily had a higher proportion of patients with sputum-culture conversion (41.9%, P=0.04). The findings were similar with assessment of sputum-culture conversion in solid medium. Most adverse events were mild to moderate in severity and were evenly distributed across groups. Although no clinical events due to QT prolongation on electrocardiography were observed, QT prolongation was reported significantly more frequently in the groups that received delamanid. CONCLUSIONS: Delamanid was associated with an increase in sputum-culture conversion at 2 months among patients with multidrug-resistant tuberculosis. This finding suggests that delamanid could enhance treatment options for multidrug-resistant tuberculosis. (Funded by Otsuka Pharmaceutical Development and Commercialization; ClinicalTrials.gov number, NCT00685360.).


Assuntos
Antituberculosos/uso terapêutico , Nitroimidazóis/uso terapêutico , Oxazóis/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Antituberculosos/efeitos adversos , Antituberculosos/farmacocinética , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/isolamento & purificação , Nitroimidazóis/efeitos adversos , Nitroimidazóis/farmacocinética , Oxazóis/efeitos adversos , Oxazóis/farmacocinética , Escarro/microbiologia , Análise de Sobrevida , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto Jovem
19.
Am J Emerg Med ; 33(11): 1552-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26123928

RESUMO

OBJECTIVES: Pulmonary edema is a common sign of heart failure and can be quantified by counting vertical artifacts (B-lines) on lung ultrasound (LUS). The primary aim of this study was to compare a pocket size ultrasound device to high-end ultrasound systems on the measured number of B-lines. We also compared the impact of different-length ultrasound clips on the measured number of B-lines. METHODS AND RESULTS: We studied 21 hospitalized patients with heart failure (81% men; median age, 73; 71% Caucasian) who underwent concurrent 8- and 4-zone LUS using both a pocket ultrasound device and a high-end ultrasound system. For the 4-zone scanning method, the median B line number was 2 (interquartile range, 1-4) for the pocket device and 3 (1-5) for the high-end system (P = .67). For the 8-zone method, the median B-line number was 4 (2-7) for the pocket device and 5 (3-7) for the high-end system (P = .18). A higher number of B-lines was identified on the 4- vs 2-second LUS clips (P < .001 for 4 zones, P = .001 for 8 zones), and on the 6- vs 4-second LUS clips (P=0.057 for 4 zones, P=0.018 for 8 zones). CONCLUSIONS: Our findings suggest significant differences based on LUS clip duration rather than the type of ultrasound device used, with respect to the number of B-lines detectable in patients with heart failure. These factors should be considered in the design and reporting of LUS studies and in longitudinal assessments of heart failure patients.


Assuntos
Insuficiência Cardíaca/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Edema Pulmonar/diagnóstico por imagem , Ultrassonografia/instrumentação , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Edema Pulmonar/etiologia , Ultrassonografia/métodos
20.
Echocardiography ; 31(2): 133-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24028294

RESUMO

PURPOSE: Lung ultrasound (LUS) represents a novel, noninvasive method in the assessment of extravascular lung water. We investigated the utility of LUS in ambulatory subjects with dyspnea or prior heart failure (HF). METHODS: We studied 81 ambulatory subjects with HF history or dyspnea who underwent transthoracic echocardiography (TTE) with LUS of 8 zones. Subjects with heart transplantation or pulmonary conditions known to interfere with LUS were excluded. A reviewer blinded to the clinical data performed echocardiographic measurements and quantified B-lines (reverberation artifacts arising from the pleural line). RESULTS: Of 81 subjects, 74 (91%) (median age 66 years, 39% men, median left ventricular ejection fraction [LVEF] 54%, 39% with prior HF) had adequate LUS images of all 8 zones and were included in the analysis. The number of B-lines ranged from 0-12 (median 2). Increased B-lines, analyzed by tertiles, were associated with larger left ventricular (LV) end-diastolic (P = 0.036) and end-systolic diameters (P = 0.026), septal wall thickness (P = 0.009), LV mass index (P = 0.001), left atrial (LA) volume index (P = 0.005), tricuspid regurgitation (TR) velocity (P = 0.005) and estimated pulmonary artery systolic pressure (PASP) (P = 0.003). In a secondary analysis associations between B-lines (not grouped by tertiles) and LV mass index, LA volume index, TR velocity and PASP remained stable after adjustment for age, gender, BMI and HF history. CONCLUSIONS: Sonographic B-lines from LUS are related to measures of LV and LA structure and right ventricular pressure in ambulatory patients with dyspnea or prior HF. The added clinical and prognostic utility of this imaging modality in ambulatory patients warrants further investigation.


Assuntos
Dispneia/fisiopatologia , Ecocardiografia/métodos , Água Extravascular Pulmonar/diagnóstico por imagem , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Idoso , Assistência Ambulatorial/métodos , Pressão Sanguínea , Dispneia/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco , Sensibilidade e Especificidade , Método Simples-Cego , Volume Sistólico
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