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1.
Plants (Basel) ; 13(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38592756

RESUMO

The use of remotely piloted aircraft (RPA) to spray pesticides currently occurs, but knowledge about this technology is lacking due to the different locations, targets, and products applied. The objective of this study was to evaluate the control of Urochloa decumbens with glyphosate applied using an RPA (10 L ha-1) equipped with different spray nozzles (XR 11001 and AirMix 11001). For the purpose of comparison, ground application was also performed (100 L ha-1). The deposition was evaluated by means of the quantification of a tracer by spectrophotometry, the droplet spectrum was evaluated with water-sensitive paper, and the control efficiency was evaluated based on visual measurements with percentage scores. Statistical process control was used to analyse the quality of the deposition in the area. The results showed that the application via RPA presented a greater amount of tracer on the leaves than the ground application, suggesting that the former is a good option for application, even providing a lower coverage and number of droplets per area. Both application methods were effective at controlling Urochloa decumbens. The nozzles showed potential for use in applications, with control efficiency higher than 84% from 21 days after application. The percentage of droplets smaller than 100 µm in the applications was less than 5%. No nonrandom behaviour was observed during deposition, indicating a high-quality process.

2.
Nat Prod Res ; : 1-14, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676413

RESUMO

Inflammation is a complex and necessary mechanism of an organ's response to biological, chemical and/or physical stimuli. In recent years, investigations on natural compounds with therapeutic actions for the treatment of different diseases have increased. Among these compounds, bromelain is highlighted, as a cysteine protease isolated from the Ananas comosus (pineapple) stem. This review aimed to evaluate the anti-inflammatory activity of bromelain, as well as its pathways on inflammatory mediators, through a systematic review with in vitro studies on different cell lines. The search was performed in PubMed, Science Direct, Scopus, Cochrane Library and Web of Science databases. Bromelain reduced IL-1ß, IL-6 and TNF-α secretion when immune cells were already stimulated in an overproduction condition by proinflammatory cytokines, generating a modulation in the inflammatory response through prostaglandins reduction and activation of a cascade reactions that trigger neutrophils and macrophages, in addition to accelerating the healing process.

3.
Pharmaceuticals (Basel) ; 17(1)2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38256905

RESUMO

This study aims to evaluate the hepatoprotective, hypolipidemic and aortic morphometric effects of fish oil rich in omega-3 in hypercholesterolemic BALB/c mice. This is an experimental model that included 16 male BALB/c mice (Mus musculus) divided into three groups (G1 (standard commercial chow and 0.9% saline solution), G2 (hypercholesterolemic diet and 0.9% saline solution) and G3 (hypercholesterolemic diet and fish oil)) for 8 weeks. There was no significant difference in the treatment with omega-3-rich fish oil in the lipid profile (p > 0.05). In the histological analysis, group G2 detected the presence of hepatitis and liver tissue necrosis, but this was not observed in group G3. As for the morphometry in the light area of the vessel, the G1 group had a higher score (2.62 ± 0.36 mm2) when compared to G2 (2.10 ± 0.16 mm2) and G3 (2.26 ± 0.25 mm2) (p < 0.05). The vessel wall thickness did not differ between the groups (p > 0.05). It is concluded that supplementation with fish oil rich in omega-3 carried out in this study may have a protective effect on liver tissue, but it has not yet improved the lipid and morphometric profile. Despite this research being preliminary, it is a relevant study with future prospects for improving the doses of EPA and DHA in order to better elucidate the benefits of fish oil in models of dyslipidemia.

4.
Drug Chem Toxicol ; : 1-9, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-36912194

RESUMO

Alpha-terpineol is a monoterpene alcohol found in essential oils from medicinal plants with some well-known pharmacological activities and widely used in cosmetics. However, the toxicological effects and additional pharmacological activities need to be clarified. Thus, the study evaluated the toxic, cytotoxic, genotoxic, hemolytic, and oxidative potential of alpha-terpineol in non-clinical bioassays. Different concentrations of alpha-terpineol were used in bioassays, including MTT (50, 100, 200, and 400 µg/mL), Artemia salina (6.25-400 µg/mL), Allium cepa (10, 50, and 100 µg/mL), comet assay (100, 200, and 500 µg/mL), cytokinesis-block micronucleus (100, 250, and 500 µg/mL), confocal microscopy for apoptosis quantification (100 and 500 µg/mL), hemolysis and Saccharomyces cerevisiae central disk test (10, 35, and 75 µg/mL). For the MTT test, alpha-terpineol was more cytotoxic on melanoma murine B16-F10 cells rather than macrophages. For A. salina test, alpha-terpineol showed LC50 of 68.29 and 76.36 µg/mL for 24 h and 48 h of exposure time, respectively. Meanwhile, alpha-terpineol was also cytotoxic to meristematic cells, which revealed inhibition of cellular division and mutagenic action by formation of bridges and delayed anaphases. The compound increased damage index and frequency of damage corroborated by the presence of micronuclei, bridges and nuclear buds at 500 µg/mL, but it caused neither hemolysis, oxidative damage on the S. cerevisiae nor cell death in normal fibroblasts. The findings indicate alpha-terpineol has cytotoxic potential by cytogenetic and molecular mechanisms associated with apoptosis and probable target effects against melanoma cells.

5.
World J Clin Cases ; 11(8): 1761-1770, 2023 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-36970001

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a major health concern worldwide. In that context, the understanding of epidemiological and clinical features associated with the disease and its severity is crucial for the establishment of strategies aimed at disease control and remedy. AIM: To describe epidemiological features, signs, symptoms, and laboratory findings among severely ill COVID-19 patients from an intensive care unit in northeastern Brazil as well as to evaluate predictor factors for disease outcomes. METHODS: This is a prospective single-center study that evaluated 115 patients admitted to the intensive care unit in a northeastern Brazilian hospital. RESULTS: The patients had a median age of 65.60 ± 15.78 years. Dyspnea was the most frequent symptom, affecting 73.9% of the patients, followed by cough (54.7%). Fever was reported in approximately one-third of patients and myalgia in 20.8% of the patients. At least two comorbidities were found in 41.7% of the patients, and hypertension was the most prevalent (57.3%). In addition, having two or more comorbidities was a predictor of mortality, and lower platelet count was positively associated with death. Nausea and vomiting were two symptoms that were predictors of death, and the presence of a cough was a protective factor. CONCLUSION: This is the first report of a negative correlation between cough and death in severely ill severe acute respiratory syndrome coronavirus 2-infected individuals. The associations between comorbidities, advanced age, and low platelet count and the outcomes of the infection were similar to the results of previous studies, highlighting the relevance of these features.

6.
Clin Cosmet Investig Dermatol ; 16: 375-385, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36798538

RESUMO

Purpose: Tretinoin is a topical gold standard for photoaging treatment. However, patient adherence can be impaired by local tolerability in the first 1-2 weeks of treatment. Mineral 89 Probiotic Fractions® (M89PF) containing Vichy volcanic mineralizing water®, probiotic fractions, hyaluronic acid, niacinamide and tocopherol was developed to fulfill the need for adjunctive products that can reinforce skin barrier and manage retinoid induced irritation. Patients and Methods: The study included 38 women, aged 44-60 years, phototype II-VI, applying 0.025% tretinoin gel once nightly for 84 days. For 28 days, one hemi face was treated with M89PF and sunscreen SPF 50+ while other hemi face received sunscreen only. Then, M89PF application was changed to full face. Evaluations were performed at days 0, 7, 28 and 84. Erythema, dryness, fine lines, skin tone, radiance and pore appearance were assessed by a dermatologist. Tolerability was evaluated through self-assessment questionnaire. Skin hydration levels, inflammatory and oxidative stress biomarkers were analyzed by immunological assay: Interleukin(IL)-8, IL1-alpha, IL1-Receptor Antagonist (IL-1Ra), Prostaglandin E2 (PGE2), Catalase and Superoxide Dismutase (SOD). Results: Hemiface analysis showed that erythema, fine lines, skin tone, radiance, pore appearance, hydration, tightness, dryness, burning, itching and stinging sensations were improved (p<0.05) on the M89PF side. At full face analysis on D84, erythema, fine lines, skin tone, radiance and pore appearance were improved compared to D0 (p<0.001). Tightness, dryness, burning, itching and stinging were reduced when compared to D7 (p<0.05). Dermatology Life Quality Index (DLQI) and Skindex 16 showed improvement in quality of life (p<0.05). IL-1RA increased at D28 (p=0.003) and PGE2 decreased at D28 and D84 compared to D0 (p<0.01). Conclusion: M89PF reduced retinoid induced irritation with a good tolerability profile and, used as an adjunct to topical tretinoin, significantly improved skin hydration, erythema, fine lines, skin tone, radiance and pore appearance.

7.
Int J Mol Sci ; 24(2)2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36675244

RESUMO

Sleeve gastrectomy (SG) successfully recovers metabolic homeostasis in obese humans and rodents while also resulting in the normalization of insulin sensitivity and insulinemia. Reduced insulin levels have been attributed to lower insulin secretion and increased insulin clearance in individuals submitted to SG. Insulin degradation mainly occurs in the liver in a process controlled, at least in part, by the insulin-degrading enzyme (IDE). However, research has yet to explore whether liver IDE expression or activity is altered after SG surgery. In this study, C57BL/6 mice were fed a chow (CTL) or high-fat diet (HFD) for 10 weeks. Afterward, the HFD mice were randomly assigned to two groups: sham-surgical (HFD-SHAM) and SG-surgical (HFD-SG). Here, we confirmed that SG improves glucose-insulin homeostasis in obese mice. Additionally, SG reduced insulinemia by reducing insulin secretion, assessed by the analysis of plasmatic C-peptide content, and increasing insulin clearance, which was evaluated through the calculation of the plasmatic C-peptide:insulin ratio. Although no changes in hepatic IDE activity were observed, IDE expression was higher in the liver of HFD-SG compared with HFD-SHAM mice. These results indicate that SG may be helpful to counteract obesity-induced hyperinsulinemia by increasing insulin clearance, likely through enhanced liver IDE expression.


Assuntos
Hiperinsulinismo , Resistência à Insulina , Humanos , Camundongos , Animais , Insulina/metabolismo , Camundongos Obesos , Peptídeo C , Camundongos Endogâmicos C57BL , Redução de Peso , Obesidade/etiologia , Obesidade/cirurgia , Insulina Regular Humana , Hiperinsulinismo/etiologia , Gastrectomia/métodos , Dieta Hiperlipídica/efeitos adversos
8.
Sci Adv ; 8(12): eabm1444, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35333571

RESUMO

As blood oxygenation decreases (hypoxemia), mammals mount cardiorespiratory responses, increasing oxygen to vital organs. The carotid bodies are the primary oxygen chemoreceptors for breathing, but sympathetic-mediated cardiovascular responses to hypoxia persist in their absence, suggesting additional high-fidelity oxygen sensors. We show that spinal thoracic sympathetic preganglionic neurons are excited by hypoxia and silenced by hyperoxia, independent of surrounding astrocytes. These spinal oxygen sensors (SOS) enhance sympatho-respiratory activity induced by CNS asphyxia-like stimuli, suggesting they bestow a life-or-death advantage. Our data suggest the SOS use a mechanism involving neuronal nitric oxide synthase 1 (NOS1) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX). We propose NOS1 serves as an oxygen-dependent sink for NADPH in hyperoxia. In hypoxia, NADPH catabolism by NOS1 decreases, increasing availability of NADPH to NOX and launching reactive oxygen species-dependent processes, including transient receptor potential channel activation. Equipped with this mechanism, SOS are likely broadly important for physiological regulation in chronic disease, spinal cord injury, and cardiorespiratory crisis.

9.
Biology (Basel) ; 11(2)2022 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-35205069

RESUMO

Atherosclerosis is a cardiovascular disease associated with abnormalities of vascular functions. The consumption of mono- and polyunsaturated fatty acids can be considered a strategy to reduce clinical events related to atherosclerosis. In the present study, we investigated the effects of supplementation with 310 mg of ω-3 PUFAs (2:1 eicosapentaenoic/docosahexaenoic acids) for 56 days on rats with hypercholesterolemia induced by a diet containing cholesterol (0.1%), cholic acid (0.5%), and egg yolk. Serum biochemical parameters were determined by the enzymatic colorimetric method. Assessment of vascular effects was performed by analysis of histological sections of the heart and aortic arch stained with hematoxylin and eosin and vascular reactivity of the aorta artery. We observed that treatment with ω-3 PUFAs did not promote alterations in lipid profile. On the other hand, we documented a favorable reduction in liver biomarkers, as well as contributions to the preservation of heart and aortic arch morphologies. Interestingly, the vascular reactivity of rat thoracic aortic preparations was improved after treatment with ω-3 PUFAs, with a decrease in hyperreactivity to phenylephrine and increased vasorelaxation promoted by acetylcholine. Our findings suggest that the supplementation of hypercholesterolemic rats with ω-3 PUFAs promoted improvement in liver and vascular endothelial function as well as preserving heart and aortic tissue, reinforcing the early health benefits of ω-3 PUFAs in the development of atherosclerotic plaque and further related events.

10.
Cardiovasc Res ; 118(15): 3052-3070, 2022 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-34734981

RESUMO

The autonomic nervous system maintains homeostasis of cardiovascular, respiratory, gastrointestinal, urinary, immune, and thermoregulatory function. Homeostasis involves a variety of feedback mechanisms involving peripheral afferents, many of which contain molecular receptors sensitive to mechanical deformation, termed mechanosensors. Here, we focus on the molecular identity of mechanosensors involved in the baroreflex control of the cardiovascular system. Located within the walls of the aortic arch and carotid sinuses, and/or astrocytes in the brain, these mechanosensors are essential for the rapid moment-to-moment feedback regulation of blood pressure (BP). Growing evidence suggests that these mechanosensors form a co-existing system of peripheral and central baroreflexes. Despite the importance of these molecules in cardiovascular disease and decades of research, their precise molecular identity remains elusive. The uncertainty surrounding the identity of these mechanosensors presents a major challenge in understanding basic baroreceptor function and has hindered the development of novel therapeutic targets for conditions with known arterial baroreflex impairments. Therefore, the purpose of this review is to (i) provide a brief overview of arterial and central baroreflex control of BP, (ii) review classes of ion channels currently proposed as the baroreflex mechanosensor, namely Transient Receptor Potential (TRP), Epithelial Sodium Channel (ENaC), Acid Sensing Ion Channel (ASIC), and Piezo, along with additional molecular candidates that serve mechanotransduction in other organ systems, and (iii) summarize the potential clinical implications of impaired baroreceptor function in the pathophysiology of cardiovascular disease.


Assuntos
Canais Iônicos Sensíveis a Ácido , Doenças Cardiovasculares , Humanos , Canais Iônicos Sensíveis a Ácido/genética , Canais Epiteliais de Sódio/genética , Mecanotransdução Celular
11.
Behav Brain Res ; 417: 113588, 2022 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-34547341

RESUMO

The monoamine neurotransmitter serotonin (5-HT) modulates anxiety by its activity on 5-HT2C receptors (5-HT2CR) expressed in the dorsal periaqueductal gray (dPAG). Here, we investigated the presence of 5-HT3A receptors (5-HT3AR) in the dPAG, and the interplay between 5-HT2CR and 5-HT3AR in the dPAG in mediating anxiety-like behavior in mice. We found that 5-HT3AR is expressed in the dPAG and the blockade of these receptors using intra-dPAG infusion of ondansetron (5-HT3AR antagonist; 3.0 nmol) induced an anxiogenic-like effect. The activation of 5-HT3ABR by the infusion of mCPBG [1-(m-Chlorophenyl)-biguanide; 5-HT3R agonist] did not alter anxiety-like behaviors. In addition, blockade of 5-HT3AR (1.0 nmol) prevented the anxiolytic-like effect induced by the infusion of the 5-HT2CR agonist mCPP (1-(3-chlorophenyl) piperazine; 0.03 nmol). None of the treatment effects on anxiety-like behaviors altered the locomotor activity levels. The present results suggest that the anxiolytic-like effect exerted by serotonin activity on 5-HT2CR in the dPAG is modulated by 5-HT3AR expressed in same region.


Assuntos
Ansiedade/fisiopatologia , Biguanidas/metabolismo , Ondansetron/farmacologia , Substância Cinzenta Periaquedutal/metabolismo , Receptor 5-HT2C de Serotonina/metabolismo , Receptores 5-HT3 de Serotonina/metabolismo , Serotonina/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Masculino , Camundongos , Ondansetron/antagonistas & inibidores , Piperazinas
12.
World J Clin Oncol ; 12(10): 845-867, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34733609

RESUMO

Cancer is the second leading cause of death worldwide and epidemiological projections predict growing cancer mortality rates in the next decades. Cancer has a close relationship with the immune system and, although Th17 cells are known to play roles in the immune response against microorganisms and in autoimmunity, studies have emphasized their roles in cancer pathogenesis. The Th17 immune response profile is involved in several types of cancer including urogenital, respiratory, gastrointestinal, and skin cancers. This type of immune response exerts pro and antitumor functions through several mechanisms, depending on the context of each tumor, including the protumor angiogenesis and exhaustion of T cells and the antitumor recruitment of T cells and neutrophils to the tumor microenvironment. Among other factors, the paradoxical behavior of Th17 cells in this setting has been attributed to its plasticity potential, which makes possible their conversion into other types of T cells such as Th17/Treg and Th17/Th1 cells. Interleukin (IL)-17 stands out among Th17-related cytokines since it modulates pathways and interacts with other cell profiles in the tumor microenvironment, which allow Th17 cells to prevail in tumors. Moreover, the IL-17 is able to mediate pro and antitumor processes that influence the development and progression of various cancers, being associated with variable clinical outcomes. The understanding of the relationship between the Th17 immune response and cancer as well as the singularities of carcinogenic processes in each type of tumor is crucial for the identification of new therapeutic targets.

13.
An Acad Bras Cienc ; 93(4): e20200884, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34495204

RESUMO

To assess the effect of vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) on the esophageal and intestinal morphology of western diet (WD)-obese rats and to characterize the stomach histopathology of WD rats submitted to VSG. Male Wistar rats received WD from 2-4 months of age, to induce obesity, before randomly submitting them to pseudo (WD-SHAM), VSG (WD-VSG) or RYGB (WD-RYGB) surgeries. Gastrointestinal histomorphometry was performed at 3-months post-surgery. The upper esophagus of VSG and RYGB rats increased luminal area, while reductions in the keratin layer of the mucosa and the tunica muscularis were observed only in the RYGB animals. In the lower esophagus, both surgeries increased keratin layer thickness, but reduced the mucosal mucus content, while RYGB increased the thickness of the tunica mucosa and muscularis. The glandular region of the stomach of WD-VSG rats exhibited hypotrophy, epithelial erosion, fibrosis and moderate inflammatory infiltration. VSG and RYGB increased the villi height in the ileum, and the thickness of the tunica muscularis in the jejunum and ileum of WD rats; furthermore, RYGB augmented the ileal villi height. Thus both approaches induced histomorphological alterations in the esophagus and intestine and VSG damaged the gastric mucosa, even over the long-term.


Assuntos
Derivação Gástrica , Animais , Dieta Ocidental , Gastrectomia , Masculino , Obesidade/cirurgia , Ratos , Ratos Wistar
14.
Exp Neurol ; 345: 113813, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34284029

RESUMO

Thyroid hormones (THs) are essential for foetal brain development. Because the gestating mother is the main source of THs to the foetus, maternal hypothyroidism and/or premature birth compromise neurological outcomes in the offspring. Respiratory instability and recurrent apneas due to immaturity of the respiratory control network are major causes of morbidity in infants. Inadequate TH supply may be sufficient to delay perinatal maturation of the respiratory control system; however, this hypothesis remains untested. To address this issue, maternal hypothyroidism was induced by adding methimazole (MMI; 0.02% w/v) to the drinking water of pregnant dams from conception to postpartum day 4 (P4). The effect of TH supplementation on respiratory function was tested by injecting levothyroxine (L-T4) in newborns at P1. Respiratory function was assessed by plethysmography (in vivo) and recording of phrenic output from medullary preparations (in vitro). By comparison with controls, TH deficiency increased the frequency of apneas and decreased basal ventilation in vivo and prevented the age-dependent increase in phrenic burst frequency normally observed in vitro. The effects of TH deficiency on GABAergic modulation of respiratory activity were measured by bath application of muscimol (GABAA agonist) or bicuculline (GABAA antagonist). The phrenic burst frequency responses to GABAergic agents were consistently greater in preparations from TH deficient pups. L-T4 supplementation reversed part of the respiratory anomalies related to MMI treatment in vitro. We conclude that TH deficiency during the perinatal period is sufficient to delay maturation of the respiratory control network development. Excessive GABAergic inhibition may contribute to this effect.


Assuntos
Antitireóideos/farmacologia , Rede Nervosa/metabolismo , Nervo Frênico/metabolismo , Mecânica Respiratória/fisiologia , Hormônios Tireóideos/deficiência , Animais , Animais Recém-Nascidos , Feminino , Antagonistas de Receptores de GABA-A/farmacologia , Masculino , Metimazol/farmacologia , Rede Nervosa/efeitos dos fármacos , Nervo Frênico/efeitos dos fármacos , Pletismografia/métodos , Gravidez , Ratos , Ratos Sprague-Dawley , Respiração/efeitos dos fármacos , Mecânica Respiratória/efeitos dos fármacos
15.
Compr Physiol ; 11(3): 2097-2134, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34107062

RESUMO

As our understanding of respiratory control evolves, we appreciate how the basic neurobiological principles of plasticity discovered in other systems shape the development and function of the respiratory control system. While breathing is a robust homeostatic function, there is growing evidence that stress disrupts respiratory control in ways that predispose to disease. Neonatal stress (in the form of maternal separation) affects "classical" respiratory control structures such as the peripheral O2 sensors (carotid bodies) and the medulla (e.g., nucleus of the solitary tract). Furthermore, early life stress disrupts the paraventricular nucleus of the hypothalamus (PVH), a structure that has emerged as a primary determinant of the intensity of the ventilatory response to hypoxia. Although underestimated, the PVH's influence on respiratory function is a logical extension of the hypothalamic control of metabolic demand and supply. In this article, we review the functional and anatomical links between the stress neuroendocrine axis and the medullary network regulating breathing. We then present the persistent and sex-specific effects of neonatal stress on respiratory control in adult rats. The similarities between the respiratory phenotype of stressed rats and clinical manifestations of respiratory control disorders such as sleep-disordered breathing and panic attacks are remarkable. These observations are in line with the scientific consensus that the origins of adult disease are often found among developmental and biological disruptions occurring during early life. These observations bring a different perspective on the structural hierarchy of respiratory homeostasis and point to new directions in our understanding of the etiology of respiratory control disorders. © 2021 American Physiological Society. Compr Physiol 11:1-38, 2021.


Assuntos
Privação Materna , Respiração , Animais , Animais Recém-Nascidos , Feminino , Hipóxia , Masculino , Sistemas Neurossecretores , Ratos
17.
World J Clin Oncol ; 12(2): 69-94, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33680875

RESUMO

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm and was the first neoplastic disease associated with a well-defined genotypic anomaly - the presence of the Philadelphia chromosome. The advances in cytogenetic and molecular assays are of great importance to the diagnosis, prognosis, treatment, and monitoring of CML. The discovery of the breakpoint cluster region (BCR)-Abelson murine leukemia (ABL) 1 fusion oncogene has revolutionized the treatment of CML patients by allowing the development of targeted drugs that inhibit the tyrosine kinase activity of the BCR-ABL oncoprotein. Tyrosine kinase inhibitors (known as TKIs) are the standard therapy for CML and greatly increase the survival rates, despite adverse effects and the odds of residual disease after discontinuation of treatment. As therapeutic alternatives, the subsequent TKIs lead to faster and deeper molecular remissions; however, with the emergence of resistance to these drugs, immunotherapy appears as an alternative, which may have a cure potential in these patients. Against this background, this article aims at providing an overview on CML clinical management and a summary on the main targeted drugs available in that context.

18.
Transl Psychiatry ; 10(1): 394, 2020 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-33173029

RESUMO

Panic disorder (PD) is ~2 times more frequent in women. An excessive ventilatory response to CO2 inhalation is more likely during the premenstrual phase. While ovarian hormones appear important in the pathophysiology of PD, their role remains poorly understood as female animals are rarely used in pre-clinical studies. Using neonatal maternal separation (NMS) to induce a "PD-like" respiratory phenotype, we tested the hypothesis that NMS disrupts hormonal regulation of the ventilatory response to CO2 in female rats. We then determined whether NMS attenuates the inhibitory actions of 17-ß estradiol (E2) on orexin neurons (ORX). Pups were exposed to NMS (3 h/day; postnatal day 3-12). The ventilatory response to CO2-inhalation was tested before puberty, across the estrus cycle, and following ovariectomy. Plasma E2 and hypothalamic ORXA were measured. The effect of an ORX1 antagonist (SB334867; 15 mg/kg) on the CO2 response was tested. Excitatory postsynaptic currents (EPSCs) were recorded from ORX neurons using whole-cell patch-clamp. NMS-related increase in the CO2 response was observed only when ovaries were functional; the largest ventilation was observed during proestrus. SB334867 blocked this effect. NMS augmented levels of ORXA in hypothalamus extracts. EPSC frequency varied according to basal plasma E2 levels across the estrus cycle in controls but not NMS. NMS reproduces developmental and cyclic changes of respiratory manifestations of PD. NMS disrupts the inhibitory actions of E2 on the respiratory network. Impaired E2-related inhibition of ORX neurons during proestrus is a novel mechanism in respiratory manifestations of PD in females.


Assuntos
Privação Materna , Transtorno de Pânico , Animais , Animais Recém-Nascidos , Dióxido de Carbono , Estradiol/farmacologia , Feminino , Neurônios , Orexinas , Ventilação Pulmonar , Ratos , Ratos Sprague-Dawley , Maturidade Sexual
19.
Braz Dent J ; 31(4): 353-359, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32901709

RESUMO

The aim of this prospective, randomized, clinical study was to analyze the influence of occlusal adjustment on the prevalence of postoperative pain after endodontic treatment. Seventy-eight patients, diagnosed with symptomatic irreversible pulpitis with indication for endodontic treatment, were selected to participate in the study. The participants were randomized and divided into two groups: in the occlusal adjustment group (OAG), endodontic treatment was performed with subsequent occlusal adjustment. In the control group (CG), endodontic treatment was performed without occlusal adjustment. Treatments were performed by the same operator. Pain occurrence and intensity were recorded on two scales: the verbal rating scale (VRS) and numerical rating scale (NRS). Pain assessment was carried out by a second examiner, blinded to the experiment, 6, 24 and 72 h after endodontic treatment. Data were analyzed using Mann-Whitney, chi-squared, and Fisher's exact tests. In the occlusal adjustment group, 71.1% reported postoperative pain and 67.5% reported pain in the control group. At the 6-hour assessment, 21 individuals reported pain in the occlusal adjustment group and 24 in the control group (p=0.672). At the 24-hour assessment, 18 and 19 individuals reported pain (p=0.991) and at the 72-hour assessment, 8 and 4 reported pain (p=0.219), respectively. Occlusal adjustment did not influence the prevalence of postoperative pain of endodontically treated teeth with symptomatic irreversible pulpitis.


Assuntos
Cavidade Pulpar , Tratamento do Canal Radicular , Humanos , Ajuste Oclusal , Dor Pós-Operatória , Estudos Prospectivos
20.
Braz. dent. j ; 31(4): 353-359, July-Aug. 2020. tab, graf
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-1132317

RESUMO

Abstract The aim of this prospective, randomized, clinical study was to analyze the influence of occlusal adjustment on the prevalence of postoperative pain after endodontic treatment. Seventy-eight patients, diagnosed with symptomatic irreversible pulpitis with indication for endodontic treatment, were selected to participate in the study. The participants were randomized and divided into two groups: in the occlusal adjustment group (OAG), endodontic treatment was performed with subsequent occlusal adjustment. In the control group (CG), endodontic treatment was performed without occlusal adjustment. Treatments were performed by the same operator. Pain occurrence and intensity were recorded on two scales: the verbal rating scale (VRS) and numerical rating scale (NRS). Pain assessment was carried out by a second examiner, blinded to the experiment, 6, 24 and 72 h after endodontic treatment. Data were analyzed using Mann-Whitney, chi-squared, and Fisher's exact tests. In the occlusal adjustment group, 71.1% reported postoperative pain and 67.5% reported pain in the control group. At the 6-hour assessment, 21 individuals reported pain in the occlusal adjustment group and 24 in the control group (p=0.672). At the 24-hour assessment, 18 and 19 individuals reported pain (p=0.991) and at the 72-hour assessment, 8 and 4 reported pain (p=0.219), respectively. Occlusal adjustment did not influence the prevalence of postoperative pain of endodontically treated teeth with symptomatic irreversible pulpitis.


Resumo O objetivo deste estudo prospectivo, randomizado e clínico foi analisar a influência do ajuste oclusal na prevalência de dor pós-operatória após o tratamento endodôntico. Setenta e oito pacientes, diagnosticados com pulpite irreversível sintomática com indicação de tratamento endodôntico, foram selecionados para participar do estudo. Os participantes foram randomizados e divididos em dois grupos: no grupo de ajuste oclusal (GAO), foi realizado tratamento endodôntico com posterior ajuste oclusal. No grupo controle (GC), o tratamento endodôntico foi realizado sem ajuste oclusal. Os tratamentos foram realizados pelo mesmo operador. A ocorrência e a intensidade da dor foram registradas em duas escalas: a escala de classificação verbal (VRS) e a escala de classificação numérica (NRS). A avaliação da dor foi realizada por um segundo examinador, cego para o experimento, 6, 24 e 72 horas após o tratamento endodôntico. Os dados foram analisados utilizando testes de Mann-Whitney, qui-quadrado e exato de Fisher. No grupo de ajuste oclusal, 71,1% relataram dor pós-operatória e 67,5% relataram dor no grupo controle. Na avaliação de 6 horas, 21 indivíduos relataram dor no grupo de ajuste oclusal e 24 no grupo controle (p=0,672). Na avaliação de 24 horas, 18 e 19 indivíduos relataram dor (p=0,991) e, na avaliação de 72 horas, 8 e 4 relataram dor (p=0,219), respectivamente. O ajuste oclusal não influenciou a prevalência de dor pós-operatória após o tratamento endodôntico em dentes com pulpite irreversível sintomática.


Assuntos
Humanos , Tratamento do Canal Radicular , Cavidade Pulpar , Dor Pós-Operatória , Estudos Prospectivos , Ajuste Oclusal
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