Local anesthetics (LAs), such as lidocaine and mexiletine, inhibit bronchoconstriction in asthmatics, but adverse effects limit their use for this specific clinical application. In this study, we ...describe the anti-spasmodic properties of the mexiletine analog 2-(2-aminopropoxy)-3,5-dimethyl, 4-Br-benzene (JME-173), which was synthesized and screened for inducing reduced activity on Na
+
channels. The effectiveness of JME-173 was assessed using rat tracheal rings, a GH3 cell line and mouse cardiomyocytes to access changes in smooth muscle contraction, and Na
+
, and Ca
++
ionic currents, respectively. Bronchospasm and airway hyper-reactivity (AHR) were studied using whole-body barometric plethysmography in A/J mice. We observed that the potency of JME-173 was 653-fold lower than mexiletine in inhibiting Na
+
currents, but 12-fold higher in inhibiting L-type Ca
++
currents. JME-173 was also more potent than mexiletine in inhibiting tracheal contraction by carbachol, allergen, extracellular Ca
++
, or sodium orthovanadate provocations. The effect of JME-173 on carbachol-induced tracheal contraction remained unaltered under conditions of de-epithelized rings, β
2
-receptor blockade or adenylate cyclase inhibition. When orally administered, JME-173 and theophylline inhibited methacholine-induced bronchospasm at time points of 1 and 3 h post-treatment, while only JME-173 remained active for at least 6 h. In addition, JME-173 also inhibited AHR in a mouse model of lipopolysaccharide (LPS)-induced lung inflammation. Thus, the mexiletine analog JME-173 shows highly attenuated activity on Na
+
channels and optimized anti-spasmodic properties, in a mechanism that is at least in part mediated by regulation of Ca
++
inflow toward the cytosol. Thus, JME-173 is a promising alternative for the treatment of clinical conditions marked by life-threatening bronchoconstriction.
A solitary dilated duct visualized by mammography is a rare event. According to the latest edition of BI-RADSR it is classified as category 4. This series of cases shows complementary ultrasound of a ...solitary dilated duct can reduce false-positive results on mammography. Keywords: breast, duct, mammography, ultrasound
We tested the hypothesis that exercise training would attenuate metabolic impairment in a model of severe cancer cachexia.
We used multiple in vivo and in vitro methods to explore the mechanisms ...underlying the beneficial effects induced by exercise training in tumor-bearing rats.
Exercise training improved running capacity, prolonged lifespan, reduced oxidative stress, and normalized muscle mass and contractile function in tumor-bearing rats. An unbiased proteomic screening revealed COP9 signalosome complex subunit 2 (COPS2) as one of the most downregulated proteins in skeletal muscle at the early stage of cancer cachexia. Exercise training normalized muscle COPS2 protein expression in tumor-bearing rats and mice. Lung cancer patients with low endurance capacity had low muscle COPS2 protein expression as compared to age-matched control subjects. To test whether decrease in COPS2 protein levels could aggravate or be an intrinsic compensatory mechanism to protect myotubes from cancer effects, we performed experiments in vitro using primary myotubes. COPS2 knockdown in human myotubes affected multiple cellular pathways, including regulation of actin cytoskeleton. Incubation of cancer-conditioned media in mouse myotubes decreased F-actin expression, which was partially restored by COPS2 knockdown. Direct repeat 4 (DR4) response elements have been shown to positively regulate gene expression. COPS2 overexpression decreased the DR4 activity in mouse myoblasts, and COPS2 knockdown inhibited the effects of cancer-conditioned media on DR4 activity.
These studies demonstrated that exercise training may be an important adjuvant therapy to counteract cancer cachexia and uncovered novel mechanisms involving COPS2 to regulate myotube homeostasis in cancer cachexia.
•Exercise training prolongs lifespan, reduces oxidative stress, and improves skeletal muscle function in tumor-bearing rats.•Muscle COP9 signalosome complex subunit 2 (COPS2) protein is downregulated in cancer cachexia.•Exercise training restores COPS2 protein expression to control levels.•Cancer-conditioned media decreased F-actin expression in myotubes, which is partially restored by COPS2 knockdown.•COPS2 overexpression decreases DR4 activity and COPS2 knockdown inhibits cancer-conditioned media effects on DR4 activity.
INTRODUÇÃO: O câncer de pulmão (CP) é um relevante problema de saúde pública no Brasil e no mundo, dada sua alta incidência e mortalidade. Assim, objetiva-se analisar a distribuição do tabagismo e da ...carga tabágica segundo características sociodemográficas e disparidades no acesso, no tratamento e na mortalidade por CP no Brasil, em 2013 e 2019. MÉTODO: Estudo retrospectivo de triangulação de fontes de dados de abrangência nacional: a) análise da distribuição do tabagismo, baseada na Pesquisa Nacional de Saúde (PNS); b) investigação dos registros de CP, via Registros Hospitalares de Câncer (RHC); e c) distribuição da mortalidade por CP, no Sistema de Informação sobre Mortalidade (SIM). RESULTADOS: Verificou-se redução do percentual de pessoas que nunca fumaram de 2013 (68,5%) para 2019 (60,2%), assim como da carga tabágica (anos-maço). Esta foi observada maior em homens em pessoas de faixas etárias mais avançadas e de menor escolaridade. Em relação aos pacientes registrados no RHC, a entrada no serviço de saúde se dá a partir de 50 anos, e apenas 19% nunca fumaram. Ao passo que os fumantes na população são majoritariamente pardos, os pacientes no RHC são em maioria brancos. Quanto ao estadiamento inicial (I e II), é mais frequente em pessoas brancas e que nunca fumaram. A taxa de mortalidade apresentou variação de 1,00, para pessoas com ensino superior, a 3,36, entre pessoas sem instrução, assim como pessoas brancas têm uma taxa de mortalidade três vezes maior que a de pessoas negras e pardas. CONCLUSÃO: Este artigo apontou relevantes disparidades sociodemográficas no acesso ao diagnóstico, tratamento e mortalidade do CP. Assim, recomenda-se: fortalecer o Registro de Câncer de Base Populacional; desenvolver e implementar estratégia de screening de CP no Brasil, uma vez que a realização de estratégias de prevenção e diagnóstico precoce combinadas funcionam melhor no controle da mortalidade pela doença; e investimento contínuo nas políticas de prevenção e controle do tabagismo.
INTRODUCTION: Lung cancer (LC) is a relevant public health problem in Brazil and worldwide, given its high incidence and mortality. Thus, the objective of this study is to analyze the distribution of smoking and smoking status according to sociodemographic characteristics and disparities in access, treatment, and mortality due to LC in Brazil in 2013 and 2019. METHOD: Retrospective study of triangulation of national data sources: a) analysis of the distribution of smoking, based on the National Survey of Health (PNS); b) investigation of LC records via Hospital-based Cancer Registry (HCR); and c) distribution of mortality due to LC in the Mortality Information System (SIM). RESULTS: There was a decrease in the percentage of people who had never smoked from 2013 (68.5%) to 2019 (60.2%) and in smoking history (pack-years). This was observed to be greater in men, people of older age groups, and those with less education. Concerning patients registered in the HCR, entry into the healthcare service occurs at the age of 50, and only 19% have never smoked. While smokers in the population are mainly Mixed-race, patients in the HCR are primarily White. As for the initial stage (I and II), it is more common in White people and people who have never smoked. The mortality rate varied from 1.00 for people with higher education to 3.36 for people without education. Furthermore, White people have a mortality rate three times higher than that of Black and mixed-race people. CONCLUSION: This article highlighted relevant sociodemographic disparities in access to LC diagnosis, treatment, and mortality. Therefore, the recommendation is to strengthen the Population-Based Cancer Registry and develop and implement a nationwide LC screening strategy in Brazil since combined prevention and early diagnosis strategies work better in controlling mortality from the disease and continued investment in tobacco prevention and control policies.
Up to 40% of patients with primary biliary cholangitis (PBC) will have a suboptimal biochemical response to ursodeoxycholic acid (UDCA), which can be improved by the addition of fibrates. This ...exploratory study aims to evaluate the long-term real-life biochemical response of different fibrates, including ciprofibrate, in subjects with UDCA-unresponsive PBC.
The Brazilian Cholestasis Study Group multicenter database was reviewed to assess the response rates to UDCA plus fibrates in patients with UDCA-unresponsive PBC 1 and 2 years after treatment initiation by different validated criteria.
In total, 27 patients (100% women, mean age 48.9 ± 9.2 years) with PBC were included. Overall response rates to fibrates by each validated criterion varied from 39 to 60% and 39-76% at 12 and 24 months after treatment combination, respectively. Combination therapy resulted in a significant decrease in ALT and ALP only after 2 years, while GGT significantly improved in the first year of treatment. Treatment response rates at 1 and 2 years appear to be comparable between ciprofibrate and bezafibrate using all available criteria.
Our findings endorse the efficacy of fibrate add-on treatment in PBC patients with suboptimal response to UDCA. Ciprofibrate appears to be at least as effective as bezafibrate and should be assessed in large clinical trials as a possibly new, cheaper, and promising option for treatment of UDCA-unresponsive PBC patients.
Malignant extracranial germ cell tumors (GCTs) are rare in pediatric patients and are usually extremely sensitive to chemotherapy. Relapsed or refractory tumors, although rare, established the need ...for second-line therapies, including high-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT). However, there are few data on its use in children with GCTs. We present a retrospective analysis of all patients diagnosed with extracranial GCTs who received HDCT/ASCT at two Brazilian pediatric cancer centers from May 1999 to December 2019. We identified a total of 34 patients with a median age at diagnosis of 2.8 years (range, 0 to 18.8), who received HDCT/ASCT. Most patients (73%) received carboplatin, etoposide and melphalan (CEM) as a HDCT regimen. Fourteen patients received a second-line conventional dose chemotherapy (CDCT), 14 received a third-line CDCT and five received even a fourth-line CDCT prior to HDCT/ASCT. After a median follow-up of 22.7 months (range, 0.3 to 198.1), 16 patients had died after tumor relapse/progression and 2 patients died from HDCT/ASCT toxicity. We observed a 5-year OS of 47.1% and 5-year EFS of 44.1%. The 5-year OS for patients referred for HDCT/ASCT with progressive disease was 10% compared to 62.5% for those who achieved disease control before HDCT/ASCT (p = 0.001). In our experience, heavily pretreated children and adolescents with extracranial GCTs achieved considerable survival rates with HDCT/ASCT since, at least, partial control of their disease was possible before starting HDCT/ASCT. The role of HDCT/ASCT in pediatric patients with GCTs should be investigated in prospective trials.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The present study investigates the evolution of the residual stresses in TWIP steels induced by manufacturing chain for the production of automotive body-in-white. Two different manufacturing routes ...were considered. The first route encompassed a plastic deformation prior to the welding stage, whereas the second involved the spot welding followed by a baking treatment. A convergent approach was adopted to isolate the effects of the first and final manufacturing steps. The findings showed that the plastic deformation prior to the welding stage is not annihilated by the welding thermomechanical cycle. Abrupt hardness gradients along small material fractions are observed. The residual stresses state changes, although its profile is still defined by the welding stage. The post-weld bake treatment showed to promote slight residual stresses relaxation, but it is not effective in inducing the same post-weld residual stresses state for different RSW parameters set.
Organizing pneumonia: chest HRCT findings Faria, Igor Murad; Zanetti, Gláucia; Barreto, Miriam Menna ...
Jornal Brasileiro de Pneumologia,
06/2015, Letnik:
41, Številka:
3
Journal Article
Recenzirano
Odprti dostop
To determine the frequency of HRCT findings and their distribution in the lung parenchyma of patients with organizing pneumonia.
This was a retrospective review of the HRCT scans of 36 adult patients ...(26 females and 10 males) with biopsy-proven organizing pneumonia. The patients were between 19 and 82 years of age (mean age, 56.2 years). The HRCT images were evaluated by two independent observers, discordant interpretations being resolved by consensus.
The most common HRCT finding was that of ground-glass opacities, which were seen in 88.9% of the cases. The second most common finding was consolidation (in 83.3% of cases), followed by peribronchovascular opacities (in 52.8%), reticulation (in 38.9%), bronchiectasis (in 33.3%), interstitial nodules (in 27.8%), interlobular septal thickening (in 27.8%), perilobular pattern (in 22.2%), the reversed halo sign (in 16.7%), airspace nodules (in 11.1%), and the halo sign (in 8.3%). The lesions were predominantly bilateral, the middle and lower lung fields being the areas most commonly affected.
Ground-glass opacities and consolidation were the most common findings, with a predominantly random distribution, although they were more common in the middle and lower thirds of the lungs.
O presente estudo teve como objetivo investigar as estratégias de pacing utilizadas por homens e mulheres na Maratona de Berlim entre os anos de 2004 e 2019. Foram analisados os registros dos 20 ...primeiros atletas no masculino e feminino. A amostra foi dividida em sete grupos: recorde mundial, grupo dos campeões (masculino e feminino), grupo do 2 ao 5 colocado (masculino e feminino) e grupo do 6 ao 20 colocado (masculino e feminino). O tempo realizado nas oito parciais de 5 km e na parcial de 2.195 km foram convertidos em segundos para cálculo de velocidade em metros por segundos. Para análise da estratégia de pacing a velocidade em cada parcial foi normalizada pela velocidade média na prova. Utilizou-se ANOVA de um fator para verificar possíveis diferenças entre os grupos em cada parcial, e para a análise da estratégia de pacing de cada grupo, foi utilizada a ANOVA de medidas repetidas intra-grupo. Os homens recordistas mundiais utilizaram estratégia de pacing constante (p= 0.98). Os grupos de campeões, masculino e feminino, também utilizaram estratégia de pacing constante (p> 0.108). Os grupos do 2 ao 5 colocados, de ambos os sexos, apresentaram estratégia de pacing positiva (homens p= 0.001-0.007; mulheres p = 0.001-0.04). Do mesmo modo, os atletas dos grupos do 6 à 20 colocados masculino e feminino também apresentaram estratégia de pacing positiva (homens p< 0.001; mulheres p< 0.001). Não foram encontradas diferenças na estratégia de pacing entre homens e mulheres vencedores. Conclui-se que a estratégia de pacing constante é aquela que possibilitou melhor êxito na Maratona de Berlim, tanto os recordistas quanto os campeões a utilizaram.
The main goal of this work is related to a study of the maintenance of equipment in a food industry located in Säo Paulo state, Brazil, using statistical methodology. Several factors can affect the ...performance of each equipment, for example, type of equipment, fault code, the reason for failure, site installation and technical knowledge of the maintenance workers. From a statistical approach, the maintenance times of the equipments are analyzed under different statistical modeling. The results of this analysis can be of great interest to managers and industry leaders regarding planning on the use of the equipment, detection of the greatest risks in the use of the equipment and to minimize the maintenance stopping times. All these results are of great importance under the production engineering approach in the optimization of its resources.
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