Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
1.
Rev. bras. cir. plást ; 39(2): 1-6, abr.jun.2024. ilus
Artigo em Inglês, Português | LILACS-Express | LILACS | ID: biblio-1556475

RESUMO

Introdução: A fissura labiopalatina é a deformidade congênita mais comum, com uma incidência de 1,53/1000 nascidos vivos e o tratamento predominantemente realizado no Sistema Único de Saúde (SUS). Em 1999, o Sistema de Informações sobre Nascidos Vivos (SINASC) implantou a lacuna para preenchimento referente a deformidade congênita. Trabalhos vêm demostrando a subnotificação importante da fissura no SINASC. Método: Foi levantado o número de crianças nascidas por ano no Brasil entre 2012 e 2018 nas respectivas regiões, projetando o número de fissurados nascidos por ano usando a proporção 1,53/1000 nascidos vivos. A partir destes dados, observado o número de fissurados notificados no sistema SUS e comparado com a projeção feita observando uma estimativa de notificação por região. Verificada também a evolução dos gastos governamentais por região com cirurgia de fissura labiopalatina no período de 2012 a 2018. Resultados: Houve uma notificação de 54,1% a 36,7% das crianças nascidas com fissura, sendo a Região Sudeste com melhor índice e o Nordeste com o índice mais baixo de notificação. Os gastos federais em cirurgia de fissura labiopalatina diminuíram entre 2012 e 2018, frente ao número de nascimentos com fissuras, que se manteve estável neste período. Conclusão: Apesar do SINASC ser uma ferramenta importante, as subnotificações expressivas desta afecção impactam nas políticas públicas, pois utilizam dados inconsistentes com a realidade. Outra preocupação é a diminuição dos gastos federais com cirurgias de fissurados, o que demostra que mais crianças estão deixando de receber tratamento adequado.


Introduction: Cleft lip and palate is the most common congenital deformity, with an incidence of 1.53/1000 live births, and treatment is predominantly carried out in the Unified Health System (Sistema Único de Saúde SUS). In 1999, the Live Birth Information System (Sistema de Informações sobre Nascidos Vivos SINASC) implemented the gap to be filled in regarding congenital deformities. Studies have demonstrated the significant underreporting of the fissure in SINASC. Method: The number of children born per year in Brazil between 2012 and 2018 was surveyed in the respective regions, projecting the number of cleft children born per year using the proportion 1.53/1000 live births. From these data, the number of cleft patients notified in the SUS system was observed and compared with the projection made by observing an estimate of notification by region. The evolution of government spending by region on cleft lip and palate surgery in the period from 2012 to 2018 was also verified. Results: There was a notification of 54.1% to 36.7% of children born with cleft, with the Southeast Region having the best rate and the Northeast with the lowest notification rate. Federal spending on cleft lip and palate surgery decreased between 2012 and 2018, compared to the number of births with clefts, which remained stable during this period. Conclusion: Although SINASC is an important tool, the significant underreporting of this condition impacts public policies, as it uses data inconsistent with reality. Another concern is the decrease in federal spending on cleft surgery, which shows that more children are failing to receive adequate treatment.

2.
Gynecol Oncol ; 186: 53-60, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38599112

RESUMO

OBJECTIVES: To identify predictors of referral and completion of germline genetic testing among newly diagnosed ovarian cancer patients, with a focus on geographic social deprivation, oncologist-level practices, and time between diagnosis and completion of testing. METHODS: Clinical and sociodemographic data were abstracted from medical records of patients newly diagnosed with ovarian cancer between 2014 and 2019 in the University of North Carolina Health System. Factors associated with referral for genetic counseling, completion of germline testing, and time between diagnosis and test results were identified using multivariable regression. RESULTS: 307/459 (67%) patients were referred for genetic counseling and 285/459 (62%) completed testing. The predicted probability of test completion was 0.83 (95% CI: 0.77-0.88) for patients with a referral compared to 0.27 (95% CI: 0.18-0.35) for patients without a referral. The predicted probability of referral was 0.75 (95% CI: 0.69-0.82) for patients at the 25th percentile of ZIP code-level Social Deprivation Index (SDI) and 0.67 (0.60-0.74) for patients at the 75th percentile of SDI. Referral varied by oncologist, with predicted probabilities ranging from 0.47 (95% CI: 0.32-0.62) to 0.93 (95% CI: 0.85-1.00) across oncologists. The median time between diagnosis and test results was 137 days (IQR: 55-248 days). This interval decreased by a predicted 24.46 days per year (95% CI: 37.75-11.16). CONCLUSIONS: We report relatively high germline testing and a promising trend in time from diagnosis to results, with variation by oncologist and patient factors. Automated referral, remote genetic counseling and sample collection, reduced out-of-pocket costs, and educational interventions should be explored.


Assuntos
Aconselhamento Genético , Testes Genéticos , Mutação em Linhagem Germinativa , Neoplasias Ovarianas , Encaminhamento e Consulta , Humanos , Feminino , Encaminhamento e Consulta/estatística & dados numéricos , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/diagnóstico , Pessoa de Meia-Idade , Testes Genéticos/estatística & dados numéricos , Testes Genéticos/métodos , Aconselhamento Genético/estatística & dados numéricos , Adulto , Idoso , North Carolina , Institutos de Câncer/estatística & dados numéricos , Estudos Retrospectivos
4.
JAMA Netw Open ; 6(10): e2335941, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37782500

RESUMO

Importance: Patients with early breast cancer must choose between undergoing breast conservation surgery or mastectomy. This decision is often difficult as there are trade-offs between breast conservation and adverse effects, and women with higher decisional conflict have a harder time choosing the therapy that suits their preferences. Objective: To study the impact of a decision aid with a patient preference assessment tool for surgical decision-making on patients' decisional conflict scale (DCS) score. Design, Setting, and Participants: This 3-group randomized clinical trial was conducted between June 2017 and December 2019 at a single high-volume tertiary care cancer center in Mumbai, India. A research questionnaire comprising 16 questions answered on a Likert scale (from 1, strongly agree, to 5, strongly disagree) was used to measure DCS scores and other secondary psychological variables, with higher scores indicating more decisional conflict. The Navya Patient Preference Tool (Navya-PPT) was developed as a survey-based presentation of evidence in an adaptive, conjoint analysis-based module for and trade-offs between cosmesis, adverse effects of radiotherapy, and cost of mandatory radiation following breast-conserving surgery. Adult patients with histologically proven early breast cancer (cT1-2, N0-1) who were eligible for breast-conserving surgery as per clinicoradiological assessment were included. Those who were pregnant or unable to read the research questionnaire or who had bilateral breast cancer were excluded. Data were analyzed from January to June 2020. Interventions: Patients were randomized 1:1:1 to study groups: standard care including clinical explanation about surgery (control), standard care plus the Navya-PPT provided to the patient alone (solo group), and standard care plus the Navya-PPT provided to the patient and a caregiver (joint group). Main Outcomes and Measures: The primary end point of the study was DCS score. The study was 80% powered with 2-sided α = .01 to detect an effect size of 0.25 measured by Cohen d, F test analysis of variance, and fixed effects. Results: A total of 245 female patients (median [range] age, 48 [23-76] years) were randomized (82 to control, 83 to the solo group, and 80 to the joint group). The median (range) pathological tumor size was 2.5 (0-6) cm. A total of 153 participants (62.4%) had pN0 disease, 185 (75.5%) were hormone receptor positive, 197 (80.4%) were human epidermal growth factor receptor 2 negative, 144 (58.6%) were of middle or lower socioeconomic status, and 114 (46.5%) had an education level lower than a college degree. DCS score was significantly reduced in the solo group compared with control (1.34 vs 1.66, respectively; Cohen d, 0.50; SD, 0.31; P < .001) and the joint group compared with control (1.31 vs 1.66, respectively; Cohen d, 0.54; SD, 0.31; P < .001). Conclusions and Relevance: The results of this study demonstrated lower decisional conflict as measured by DCS score following use of the online, self-administered Navya-PPT among patients with early breast cancer choosing between breast-conserving surgery vs mastectomy. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/11/010480.


Assuntos
Neoplasias da Mama , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Adulto , Gravidez , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/cirurgia , Mastectomia , Mama , Técnicas de Apoio para a Decisão
5.
Viruses ; 15(6)2023 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-37376604

RESUMO

INTRODUCTION: Although fewer children have been affected by the severe form of the coronavirus disease 2019 (COVID-19), community-acquired pneumonia (CAP) continues to be the leading global cause of child hospitalizations and deaths. AIM: This study investigated the incidence of respiratory syncytial virus (RSV) as well its subtypes (RSV A and B), adenovirus (ADV), rhinovirus (HRV), metapneumovirus (HMPV), coronavirus (NL63, OC43, 229E and HKU1), parainfluenza virus subtypes (PI1, PI2 and PI3), bocavirus and influenza A and B viruses (FluA and FluB) in children diagnosed with CAP during the COVID-19 pandemic. METHODS: A total of 200 children with clinically confirmed CAP were initially recruited, of whom 107 had negative qPCR results for SARS-CoV-2 and were included in this study. Viral subtypes were identified using a real-time polymerase chain reaction in the nasopharyngeal swab samples. RESULTS: Viruses were identified in 69.2% of the patients. RSV infections were the most frequently identified (65.4%), with type RSV B being the most prevalent (63.5%). In addition, HCoV 229E and HRV were detected in 6.5% and 3.7% of the patients, respectively. RSV type B was associated with severe acute respiratory infection (ARI) and a younger age (less than 24 months). CONCLUSIONS: New strategies for preventing and treating viral respiratory infections, particularly RSV infections, are necessary.


Assuntos
COVID-19 , Infecções Comunitárias Adquiridas , Pneumonia , Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Humanos , Criança , Lactente , Pré-Escolar , Incidência , Brasil/epidemiologia , Pandemias , COVID-19/epidemiologia , SARS-CoV-2 , Vírus Sincicial Respiratório Humano/genética , Pneumonia/epidemiologia , Infecções por Vírus Respiratório Sincicial/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia
6.
Food Chem Toxicol ; 177: 113852, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37244598

RESUMO

The ostrich oil (OO) has been topically used for decades to treat skin diseases. Its oral use has been encouraged through e-commerce advertising several health benefits to OO without scientific evidence on its safety or effectiveness. This study presents the chromatographic profile of a commercially available OO and its acute and 28-day repeated dose in vivo toxicological profiles. OO anti-inflammatory and antinociceptive effects were also investigated. Omega-9 (ω-9; oleic acid; 34.6%) and -6 (linoleic acid; 14.9%) were detected as OO main constituents. A high single dose of the OO (2 g/kg of ω-9) demonstrated no or low acute toxicity. However, when orally treated with OO (30-300 mg/kg of ω-9) for 28 consecutive days, mice exhibited altered locomotor and exploratory activities, hepatic damage, and increased hindpaw sensitivity accompanied by increased levels of cytokine and brain-derived neurotrophic factor in their spinal cords and brains. Lack of anti-inflammatory or antinociceptive activities was also evidenced in 15-day-OO treated mice. These results indicate that chronic consumption of OO induces hepatic injury, in addition to neuroinflammation and subsequent hypersensitivity and behavioural changes. Thus, there is no evidence to support OO use to treating illness in humans.


Assuntos
Struthioniformes , Humanos , Animais , Camundongos , Azeite de Oliva/química , Doenças Neuroinflamatórias , Testes de Toxicidade , Analgésicos/toxicidade
7.
Drug Discov Today ; 28(7): 103626, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37224998

RESUMO

Antineoplastic treatment induces a type of gastrointestinal toxicity known as mucositis. Findings in animal models are usually easily reproducible, and standardized treatment regimens are often used, thus supporting translational science. Essential characteristics of mucositis, including intestinal permeability, inflammation, immune and oxidative responses, and tissue repair mechanisms, can be easily investigated in these models. Given the effects of mucositis on the quality of life of patients with cancer, and the importance of experimental models in the development of more effective new therapeutic alternatives, this review discusses progress and current challenges in using experimental models of mucositis in translational pharmacology research.


Assuntos
Antineoplásicos , Mucosite , Animais , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Roedores , Qualidade de Vida , Antineoplásicos/toxicidade , Desenvolvimento de Medicamentos , Mucosa Intestinal
8.
Nutr Cancer ; 75(5): 1382-1398, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36974004

RESUMO

Gastrointestinal toxicity, including diarrhea and inflammation, is commonly observed with the use of 5-fluorouracil (5-FU). Several studies have shown that polysaccharides are interesting bioactive macromolecules for the treatment or prevention of gastrointestinal diseases. Therefore, in this study, the effect of a polysaccharide fraction from a mixture of two Guavira species (Campomanesia adamantium and Campomanesia pubescens), referred to here as CPW, on the development of intestinal mucositis was investigated. Intestinal mucositis was induced by a single injection of 5-FU (450 mg/kg), and various doses of CPW (3-100 mg/kg) were tested. CPW attenuated disease development and prevented small bowel dysmotility and colon shortening. CPW prevented the increase in villi width, crypt depth, and mucosal thickness in the duodenum, but not in the colon. Preservation of mucus, reduction of oxidative stress, inflammation, and prevention of the 5-FU-induced enlargement and swelling of the spleen were observed. In conclusion, this study demonstrated for the first time that CPW alleviates the intestinal damage induced by 5-FU and could be used as an adjuvant strategy during chemotherapy.


Assuntos
Fluoruracila , Mucosite , Camundongos , Animais , Fluoruracila/toxicidade , Mucosite/induzido quimicamente , Mucosite/tratamento farmacológico , Mucosite/prevenção & controle , Antimetabólitos Antineoplásicos/toxicidade , Mucosa Intestinal , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Polissacarídeos/farmacologia
9.
Braz. oral res. (Online) ; 36: e011, 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS, BBO - Odontologia | ID: biblio-1355932

RESUMO

Abstract Mucopolysaccharidosis (MPS) is a heterogeneous group of rare, chronic, progressive and systemic inherited disorders resulting from deficiency or lack of lysosomal enzymes responsible for the degradation of glycosaminoglycans. Products of nitrosative stress have been previously detected in blood and urine samples of patients with MPS. However, it is unclear whether they are present in the saliva of MPS patients and also if they correlate with salivary parameters such as flow and pH. This study compared the salivary levels of NOX (NO2- + NO3-), nitrite (NO2-), protein (albumin), erythrocyte and leukocyte numbers, as well as the salivary flow rate and pH values of samples obtained from 10 MPS patients and 10 healthy subjects. MPS patients exhibited higher salivary levels of NOX and NO2- when compared to healthy subjects (p < 0.05). Albumin was only detected in six saliva samples of MPS patients and, erythrocytes and leukocytes were detected in 60% and 40% of the MPS patients, respectively. In addition, salivary flow rate and pH averages were statistically lower in this group when compared to healthy samples (p < 0.05). Overall, the data indicates that the salivary levels of NO products can be used in combination with other heath indicators to monitor MPS disorders.

10.
Front Physiol ; 12: 714846, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366901

RESUMO

Intestinal mucositis is a clinically relevant side effect of anticancer therapies. It is experienced by 60-100% of patients undergoing treatment with high doses of chemotherapy, radiation therapy, and bone marrow transplantation. Intestinal mucositis can manifest as pain, weight loss, inflammation, diarrhea, rectal bleeding, and infection; affecting normal nutritional intake and intestinal function. It often impacts adherence to anticancer therapy as it frequently limits patient's ability to tolerate treatment, causing schedule delays, interruptions, or premature discontinuation. In some cases, local and systemic secondary infections are observed, increasing the costs toward medical care and hospitalization. Several strategies for managing mucositis are available which do not always halt this condition. In this context, new therapeutic strategies are under investigation to prevent or treat intestinal mucositis. Polysaccharides from natural resources have recently become promising molecules against intestinal damage due to their ability to promote mucosal healing and their anti-inflammatory actions. These effects are associated with the protection of intestinal mucosa and regulation of microbiota and immune system. This review aims to discuss the recent advances of polysaccharides from natural resources as potential therapies for intestinal mucositis. The source, species, doses, treatment schedules, and mechanisms of action of polysaccharides will be discussed in detail.

11.
Nutrients ; 13(6)2021 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-34200897

RESUMO

Purpose: To review the effects of polysaccharides and their proposed mechanisms of action in breast cancer experimental models. Data sources, selection, and extraction: Articles were selected by using PubMed, ScienceDirect, Scopus, and Medline, assessed from 1 May 2019 to 1 July 2020. The systematic review was registered in the International Prospective Register of Systematic Reviews (Prospero) under the number CRD42020169103. Results: Most of the studies explore algae polysaccharides (43.2%), followed by mushrooms (13.5%), plants (13.5%), fruits (10.8%), fungus (2.7%), bacteria, (2.7%), and sea animals (2.7%). A total of 8.1% investigated only in vitro models, 62.1% evaluated only in vivo models, and 29.7% evaluated in vitro and in vivo models. The mechanism of action involves apoptosis, inhibition of cellular proliferation, angiogenesis, and antimetastatic effects through multiple pathways. Conclusions: Findings included here support further investigations on the anti-tumor effect of polysaccharides. Some polysaccharides, such as fucoidan and ß-glucans, deserve detailed and structured studies aiming at translational research on breast tumors, since they are already used in the clinical practice of other proposals of human health.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Polissacarídeos/uso terapêutico , Animais , Feminino , Humanos , Viés de Publicação , Risco
12.
Eur J Pharmacol ; 890: 173636, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33053380

RESUMO

Inflammatory arthritis, such as rheumatoid arthritis (RA), stands out as one of the main sources of pain and impairment to the quality of life. The use of hemopressin (PVNFKFLSH; Hp), an inverse agonist of type 1 cannabinoid receptor, has proven to be effective in producing analgesia in pain models, but its effect on neuro-inflammatory aspects of RA is limited. In this study, antigen-induced arthritis (AIA) was evoked by the intraarticular (i.art.) injection of methylated bovine serum albumin (mBSA) in male Sprague Dawley rats. Phosphate buffered saline (PBS)-injected ipsilateral knee joints or AIA contralateral were used as control. Nociceptive and inflammatory parameters such as knee joint oedema and leukocyte influx and histopathological changes were carried out in addition to the local measurement of interleukins (IL) IL-6, IL-1ß, tumor necrosis factor-α and the immunoreactivity of the neuropeptides substance P (SP) and calcitonin gene related peptide (CGRP) in the spinal cord (lumbar L3-5 segments) of AIA rats. For 4 days, AIA rats were treated daily with a single administration of saline, Hp injected (10 or 20 µg/day, i.art.), Hp given orally (20 µg/Kg, p.o.) or indomethacin (Indo; 5 mg/Kg, i.p.). In comparison to the PBS control group, the induction of AIA produced a significant and progressive mono-arthritis condition. The degree of AIA severity progressively compromised the normal walking pattern and impaired mobility over the next four days in relation to PBS-injected rats or contralateral knee joints. In AIA rats, the reduction of the distance between footprints and disturbances of gait evidenced signs of nociception. This response worsened at day 4, and a loss of footprint from the ipsilateral hind paw was evident. Daily treatment of the animals with Hp either i.art. (10 and 20 µg/knee) or p.o. (20 µg/Kg) as well as Indo (5 mg/Kg, i.p.) ameliorated the impaired mobility in a time-dependent manner (P < 0.05). In parallel, the AIA-injected ipsilateral knee joints reach a peak of swelling 24 h after AIA induction, which persisted over the next four days in relation to PBS-injected rats or contralateral knee joints. There was a significant but not dose-dependent inhibitory effect produced by all dosages and routes of Hp treatments on AIA-induced knee joint swelling (P < 0.05). In addition, the increased synovial levels of MPO activity, total leukocytes number and IL-6, but not IL-1ß, were significantly reduced by the lower i.art. dose of Hp. In conclusion, these results successfully demonstrate that Hp may represent a novel therapeutic strategy to treat RA, an effect which is unrelated to the proinflammatory actions of the neuropeptides CGRP and SP.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Hemoglobinas/farmacologia , Dor Nociceptiva/prevenção & controle , Fragmentos de Peptídeos/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Citocinas/metabolismo , Edema/tratamento farmacológico , Marcha/efeitos dos fármacos , Hemoglobinas/administração & dosagem , Inflamação/tratamento farmacológico , Injeções Intra-Articulares , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Leucócitos/efeitos dos fármacos , Masculino , Fragmentos de Peptídeos/administração & dosagem , Ratos Sprague-Dawley , Receptores de Peptídeo Relacionado com o Gene de Calcitonina/metabolismo , Substância P/metabolismo
13.
Br J Pharmacol ; 177(14): 3127-3146, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32352155

RESUMO

Taxane-derived drugs are antineoplastic agents used for the treatment of highly common malignancies. Paclitaxel and docetaxel are the most commonly used taxanes; however, other drugs and formulations have been used, such as cabazitaxel and nab-paclitaxel. Taxane treatment is associated with neurotoxicity, a well-known and relevant side effect, very prevalent amongst patients undergoing chemotherapy. Painful peripheral neuropathy is the most dose-limiting side effect of taxanes, affecting up to 97% of paclitaxel-treated patients. Central neurotoxicity is an emerging side effect of taxanes and it is characterized by cognitive impairment and encephalopathy. Besides impairing compliance to chemotherapy treatment, taxane-induced neurotoxicity (TIN) can adversely affect the patient's life quality on a long-term basis. Despite the clinical relevance, not many reviews have comprehensively addressed taxane-induced neurotoxicity when they are used therapeutically. This article provides an up-to-date review on the pathophysiology of TIN and the novel potential therapies to prevent or treat this side effect.


Assuntos
Antineoplásicos , Taxoides , Antineoplásicos/efeitos adversos , Hidrocarbonetos Aromáticos com Pontes/efeitos adversos , Docetaxel , Humanos , Paclitaxel , Taxoides/efeitos adversos
14.
Cancers (Basel) ; 12(2)2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32098292

RESUMO

Phosphodiesterases (PDEs) form a superfamily of enzymes that catalyze the hydrolysis of cyclic nucleotides adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) to their inactive 5' monophosphates. cAMP plays a critical role as a second messenger in endocrine tissues, and activation of cAMP signaling has been reported in endocrine tumors. Germline variants in PDEs have been associated with benign cortisol-secreting adrenocortical adenomas and testicular germ cell cancer but not adrenocortical carcinoma. We performed whole genome sequencing (WGS) and whole exome sequencing (WES) of paired blood and tumor samples from 37 pediatric adrenocortical tumors (ACTs). Germline inactivating variants in PDEs were observed in 9 of 37 (24%) patients. Tumor DNA analysis revealed loss of heterozygosity, with maintenance of the mutated allele in all cases. Our results suggest that germline variants in PDEs and other regulators of the cAMP-signaling pathway may contribute to pediatric adrenocortical tumorigenesis, perhaps by cooperating with germline hypomorphic mutant TP53 alleles and uniparental disomy of chromosome 11p15 (Beckwith-Wiedemann syndrome).

16.
Molecules ; 24(8)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027179

RESUMO

Wound healing can be delayed following colonization and infection with the common bacterium Pseudomonas aeruginosa. While multiple therapies are used for their treatment, these are ineffective, expensive, and labour-intensive. Thus, there is an enormous unmet need for the treatment of infected wounds. Cinnamaldehyde, the major component of cinnamon oil, is well known for its antimicrobial properties. Herein, we investigated the effects of sub-inhibitory concentrations of cinnamaldehyde in the virulence of P. aeruginosa. We also assessed its healing potential in P. aeruginosa-infected mouse skin wounds and the mechanisms involved in this response. Sub-inhibitory concentrations of cinnamaldehyde reduced P. aeruginosa metabolic rate and its ability to form biofilm and to cause haemolysis. Daily topical application of cinnamaldehyde on P. aeruginosa-infected skin wounds reduced tissue bacterial load and promoted faster healing. Lower interleukin-17 (IL-17), vascular endothelial growth factor (VEGF) and nitric oxide levels were detected in cinnamaldehyde-treated wound samples. Blockage of transient receptor potential ankyrin 1, the pharmacological target of cinnamaldehyde, abrogated its healing activity and partially reversed the inhibitory actions of this compound on VEGF and IL-17 generation. We suggest that topical application of sub-inhibitory concentrations of cinnamaldehyde may represent an interesting approach to improve the healing of P. aeruginosa-infected skin wounds.


Assuntos
Acroleína/análogos & derivados , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , Pele/microbiologia , Cicatrização/efeitos dos fármacos , Acroleína/uso terapêutico , Animais , Anti-Infecciosos/uso terapêutico , Biofilmes/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Interleucina-17/metabolismo , Camundongos , Infecções por Pseudomonas/tratamento farmacológico , Canal de Cátion TRPA1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Neuropharmacology ; 151: 136-143, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30991054

RESUMO

Painful peripheral neuropathy is the most dose-limiting side effect of paclitaxel (PTX), a widely used anti-cancer drug to treat solid tumours. The understanding of the mechanisms involved in this side effect is crucial to the development of new therapeutic approaches. CXCL1 chemokine and its receptor CXCR2 have been pointed as promising targets to treat chronic pain. Herein, we sought to evaluate the possible involvement of CXCL1 and CXCR2 in the pathogenesis of PTX-induced neuropathic pain in mice. PTX treatment led to increased levels of CXCL1 in both dorsal root ganglion and spinal cord samples. Systemic treatment with the anti-CXCL1 antibody (10 µg/kg, i.v.) or the selective CXCR2 antagonist (SB225002, 3 mg/kg, i.p.) had minor effect on PTX-induced mechanical hypersensitivity. On the other hand, the intrathecal (i.t.) treatment with anti-CXCL1 (1 ng/site) or SB225002 (10 µg/site) consistently inhibited the nociceptive responses of PTX-treated mice. Similar results were obtained by inhibiting the PI3Kγ enzyme a downstream pathway of CXCL1/CXCR2 signalling with either the selective AS605240 (5 µg/site, i.t.) or the non-selective wortmannin PI3K inhibitor (0.4 µg/site, i.t.). Overall, the data indicates that the up-regulation of CXCL1 is important for the development and maintenance of PTX-induced neuropathic pain in mice. Therefore, the spinal blockage of CXCL1/CXCR2 signalling might be a new innovative therapeutic approach to treat this clinical side effect of PTX.


Assuntos
Antineoplásicos Fitogênicos/efeitos adversos , Quimiocina CXCL1/antagonistas & inibidores , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Receptores de Interleucina-8B/antagonistas & inibidores , Medula Espinal/efeitos dos fármacos , Animais , Quimiocina CXCL1/metabolismo , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Compostos de Fenilureia/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Quinoxalinas/farmacologia , Receptores de Interleucina-8B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Medula Espinal/metabolismo , Tiazolidinedionas/farmacologia
18.
J Craniofac Surg ; 29(6): 1457-1462, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30028395

RESUMO

OBJECTIVE: Evaluate treatment of patients with bilateral cleft lip operated during the last 10 years, using the methodology of Mortier and Anastassov. METHODS: A total of 84 patients were evaluated using a preoperative score assessing fissure severity and a postsurgical score assessing of uncorrected or secondary deformities. A pre- and postcorrelation analysis was performed to evaluate the gain and identify the main postoperative alterations, using Spearman's statistical test (P < 0.001). RESULTS: About 89.3% underwent surgery between 4 and 7 months. Surgical techniques used Millard 65.5% and Mulliken 34.5%. Presurgical evaluation classified fissures as mild (0%), moderate (2.4%), severe (19.1%), or very severe (78.6%). Postoperative evaluation classified results as poor (24%), satisfactory (12%), good (15, 6%), very good (34.6%), or excellent (14.3%). The postoperative changes on the lip were the notch in the vermilion and the defect in the edge of the vermilion, and in the bow of the wide cupid; in the nose, the most frequent were deficiency in the upper nasal nostril, insufficient rotation of the alar base, broad tip, and short columella; in the scar and alveolar portion, the most frequent were alveolar cleft, premaxilla protrusion, and poor scar. Spearman correlation of preoperative and postoperative was positive of 0.43. CONCLUSION: The proposed measurement method is technically simple and can be performed without equipment allowing pre- and postoperative evaluation to identify the main alterations to be corrected.


Assuntos
Fenda Labial/cirurgia , Deformidades Adquiridas Nasais , Administração dos Cuidados ao Paciente/métodos , Planejamento de Assistência ao Paciente , Procedimentos de Cirurgia Plástica , Complicações Pós-Operatórias , Brasil , Face/cirurgia , Assimetria Facial/diagnóstico , Assimetria Facial/etiologia , Feminino , Humanos , Lactente , Masculino , Deformidades Adquiridas Nasais/diagnóstico , Deformidades Adquiridas Nasais/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Tempo para o Tratamento
19.
Surg. cosmet. dermatol. (Impr.) ; 10(3): 256-259, Jul.-Set. 2018. ilus.
Artigo em Inglês, Português | LILACS | ID: biblio-969832

RESUMO

A esclerose sistêmica (ES) é doença autoimune do tecido conjuntivo de etiologia desconhecida, caracterizada pela esclerose (fibrose), que afeta a pele, vasos sanguíneos e órgãos internos. O diagnóstico é firmado pelo quadro clínico compatível, pesquisa de autoanticorpos e capilaroscopia do leito ungueal. Destaca-se neste relato a importância do médico dermatologista frente ao diagnóstico de doenças sistêmicas. Na observação da pele, visível e palpável em todas as suas dimensões e na interpretação de todos os seus sinais, conclui-se que é possível revelar precocemente problemas internos que poderiam evoluir de forma oculta.


Systemic sclerosis (SE) is an autoimmune disease of the connective tissue. Of unknown etiology, it is characterized by sclerosis (fibrosis), which affects the skin, blood vessels and internal organs. The diagnosis is confirmed by a compatible clinical picture, autoantibody research and capillaroscopy of the nail bed. The present report highlights the importance of the dermatologist physician in the diagnosis of systemic diseases. Based on the observation of the skin ­ which is visible and palpable in all of its dimensions ­ and in the interpretation of all its signs, it is possible to conclude that it can reveal early internal disorders that could develop unnoticeably.


Assuntos
Doenças Autoimunes , Escleroderma Sistêmico , Esclerose
20.
J Immunol Res ; 2018: 6879183, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29675437

RESUMO

The hydroalcoholic extract of Punica granatum (pomegranate) leaves was previously demonstrated to be anti-inflammatory in a rat model of lipopolysaccharide- (LPS-) induced acute peritonitis. Here, we investigated the anti-inflammatory effects of the ethyl acetate fraction obtained from the pomegranate leaf hydroalcoholic extract (EAFPg) on the LPS-induced acute lung injury (ALI) mouse model. Male Swiss mice received either EAFPg at different doses or dexamethasone (per os) prior to LPS intranasal instillation. Vehicle-treated mice were used as controls. Animals were culled at 4 h after LPS challenge, and the bronchoalveolar lavage fluid (BALF) and lung samples were collected for analysis. EAFPg and kaempferol effects on NO and cytokine production by LPS-stimulated RAW 264.7 macrophages were also investigated. Pretreatment with EAFPg (100-300 mg/kg) markedly reduced cell accumulation (specially neutrophils) and collagen deposition in the lungs of ALI mice. The same animals presented with reduced lung and BALF TNF-α and IL-1ß expression in comparison with vehicle controls (p < 0.05). Additionally, incubation with either EAFPg or kaempferol (100 µg/ml) reduced NO production and cytokine gene expression in cultured LPS-treated RAW 264.7 macrophages. Overall, these results demonstrate that the prophylactic treatment with EAFPg attenuates acute lung inflammation. We suggest this fraction may be useful in treating ALI.


Assuntos
Lesão Pulmonar Aguda/terapia , Macrófagos/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Pneumonia/terapia , Acetatos/química , Lesão Pulmonar Aguda/imunologia , Animais , Modelos Animais de Doenças , Humanos , Interleucina-1beta/metabolismo , Lipopolissacarídeos/imunologia , Lythraceae/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Óxido Nítrico/metabolismo , Extratos Vegetais/química , Folhas de Planta , Pneumonia/imunologia , Células RAW 264.7 , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA