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1.
J Biochem Mol Toxicol ; 34(2): e22433, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31916655

RESUMO

Colorectal cancer (CRC) is the third most common fatal cancer. Indomethacin, a nonsteroidal anti-inflammatory drug, is known to reduce the occurrence of CRC. This study evaluated the potential anticolon cancer effects of juglone (5-hydroxy-1,4-naphthoquinone) in combination with indomethacin. Human colon adenocarcinoma cells (HT29) were subjected to treatment with indomethacin, juglone, and a combination of both. Morphological analysis, cell cycle regulation, and dual staining using acridine orange and ethidium bromide in control and treated cells revealed the apoptotic potential of these compounds. Bcl2 and inflammatory molecules (tumor necrosis factor-α, nuclear factor kappa B, and Cox-2) were found to be decreased with a concomitant increase in the expression of proapoptotic molecules (Bad, Bax, cytochrome c, and PUMA) as a result of the molecular regulation of Wnt, Notch, and peroxisome proliferator-activated receptor-γ signaling. Treatment with juglone was not as effective as with indomethacin; however, a combination of both was shown to be more effective, suggesting that juglone may be considered for therapeutic intervention of colon cancer.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/metabolismo , Indometacina/farmacologia , Mediadores da Inflamação/metabolismo , Naftoquinonas/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos/uso terapêutico , Proteínas Reguladoras de Apoptose/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Sinergismo Farmacológico , Células HT29 , Humanos , Indometacina/uso terapêutico , Concentração Inibidora 50 , Naftoquinonas/uso terapêutico , PPAR gama/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Via de Sinalização Wnt
2.
J Stroke Cerebrovasc Dis ; 28(12): 104443, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31611169

RESUMO

We herein report the case of a 45-year-old woman who developed a continuous hemicranial headache subsequent to vertebral artery dissection (VAD). After remission of VAD, the patient repeatedly experienced right forehead and temporal region throbbing headache, accompanied by nausea, ocular hyperemia and lacrimation of the right eye, nasal congestion, and rhinorrhea. Magnetic resonance angiography did not reveal the recurrence of dissection. Daily use of indomethacin (190.8 mg/day) showed an excellent effect on the headache, suggesting that the patient had developed hemicrania continua subsequent to VAD.


Assuntos
Cefaleia/etiologia , Dissecação da Artéria Vertebral/complicações , Inibidores de Ciclo-Oxigenase/uso terapêutico , Feminino , Cefaleia/diagnóstico , Cefaleia/tratamento farmacológico , Humanos , Indometacina/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento , Dissecação da Artéria Vertebral/diagnóstico por imagem
3.
Medicine (Baltimore) ; 98(40): e17359, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577731

RESUMO

INTRODUCTION: The clinical and genetic characteristics of nephrogenic diabetes insipidus (NDI) were described via assessing 2 cases of NDI patients from a Chinese family. PATIENT CONCERNS: Two patients who manifest polyuria and polydipsia were admitted to hospital for definite diagnosis. DIAGNOSIS: Water deprivation-vasopressin tests showed that the patients may possess renal-origin diabetes insipidus. All the levels of thyroid-stimulating hormone, luteinizing hormone, follicle stimulation hormone, adrenocorticotropic hormone, prolactin, and growth hormone in both patients were normal. These results were certified that both patients possess a nephropathy-type diabetes insipidus. B-mode ultrasonography and urinalysis test demonstrated that the patient's diabetes insipidus is unlikely to originate from renal organic disease. Remarkably, by nucleotide sequencing, we found a novel mutation c.414_418del in arginine-vasopressin receptor 2 (AVPR2) was related to the disease of NDI. INTERVENTIONS: Two patients were treated with oral hydrochlorothiazide and indomethacin. In addition, low salt diet and potassium supplementation throughout the patients' treatment. OUTCOMES: The clinical symptoms of 2 patients were significantly reduced after targeted therapy. CONCLUSION: A mutation in AVPR2 was discovered to be associated with NID. It provides a new target for molecular diagnosis of NDI, enabling families to undergo genetic counseling and obtain prenatal diagnoses.


Assuntos
Diabetes Insípido Nefrogênico/genética , Receptores de Vasopressinas/genética , Grupo com Ancestrais do Continente Asiático , Diabetes Insípido Nefrogênico/diagnóstico , Diabetes Insípido Nefrogênico/tratamento farmacológico , Humanos , Hidroclorotiazida/uso terapêutico , Indometacina/uso terapêutico
4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(4): 562-565, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31484622

RESUMO

Acute pancreatitis(AP)is an inflammatory condition of the pancreas following the activationt of pancreatic enzymes induced by a variety of factors,with or without other organ dysfunction.The production and release of inflammatory factors is generally considered as a key link during pathogenesis.Non-steroidal anti-inflammatory drugs(NSAIDs)are the most commonly applied agents for inflammatory diseases.Many studies have proved that indomethacin can reduce the risk of pancreatitis after endoscopic retrograde cholangiopancreatography;however,few high-quality evidences have demonstrated the roles of NSAIDs in treating,rather than preventing AP.Most animal experiments have shown that NSAIDs can protect organs,although the currently available findings remained inconsistent.Randomized controlled trials with large sample sizes are warranted to elucidate the roles of NSAIDs in treating AP.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Pancreatite/tratamento farmacológico , Animais , Colangiopancreatografia Retrógrada Endoscópica , Humanos , Indometacina/uso terapêutico
5.
Ital J Pediatr ; 45(1): 107, 2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31439021

RESUMO

BACKGROUND: The treatment of patent ductus arteriosus (PDA) in very low birth weight (VLBW) infants remains a challenge. The ability to predict which infants will respond to indomethacin could spare some from the risks of unnecessary medications. Our objective was to determine if indicators of acid-base homeostasis could predict response to indomethacin treatment for ductal closure, and thus help guide treatment decisions. METHODS: We performed a retrospective analysis of medical records of VLBW (< 1500 g) neonates with hemodynamically significant PDA born at our institution between January 2009 and December 2012; all infants included in the study were treated with indomethacin for ductal closure within the first 2 weeks of life. We extracted data for a number of clinical variables including gestational age, birth weight, blood chemistries, surfactant use, hematocrit, and blood gas parameters. Our primary outcome measure was successful closure of PDA following the first round of indomethacin. Using variables that were significant on initial testing, we created multivariable regression models to determine the independent association of selected variables with indomethacin response. RESULTS: Of the 91 infants included in the study, 62 (68%) responded to the first course of indomethacin with successful ductal closure. Multivariable regression modeling revealed that both base excess and hematocrit were independently associated with indomethacin response; odds of PDA closure increased with increasing base excess (OR [odds ratio]: 1.81; 95% confidence interval [CI]: 1.36-2.60) and increasing hematocrit (OR: 1.21; 95% CI: 1.01-1.45). The optimal cutoff value for base excess was - 4.56, with a sensitivity of 96.8% (95% CI: 89-100) and specificity of 79.3% (95% CI: 60-92); optimal cutoff value for hematocrit was 40, with 69.4% sensitivity (95% CI: 56-80) and 65.5% specificity (95% CI: 46-82). CONCLUSIONS: Base excess and hematocrit may be independent predictors of indomethacin response in VLBW infants with PDA. Low-cost and readily accessible, acid-base indicators such as base excess could help guide treatment decisions.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Permeabilidade do Canal Arterial/tratamento farmacológico , Permeabilidade do Canal Arterial/metabolismo , Indometacina/uso terapêutico , Equilíbrio Ácido-Base , Feminino , Hematócrito , Humanos , Recém-Nascido , Recém-Nascido de muito Baixo Peso , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
6.
Int J Pharm Compd ; 23(4): 324-331, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31315084

RESUMO

Indomethacin is used for off-label prescription for the treatment of patent ductus arteriosus in premature infants. In Argentina, indomethacin is only available as a suppository, dermic cream, injectable ampules, and delayed-release capsules. Aiming to improve pediatric treatment and minimize the risk associated with improper dosage, this work focused on the development of an extemporaneous 0.2% indomethacin oral suspension, starting from the commercially injectable formulation. Two 150-mL batches of suspension were prepared using Generally Recognized as Safe excipients. The suspensions were stored for 17 days at room temperature. Physical stability, morphological analysis of suspended particles, sedimentation volume, easy re-suspension, and dynamic viscosity were studied. The indomethacin content, dissolution studies, and microbiological attributes of nonsterile pharmaceutical products were also evaluated. After 17 days of storage, the suspension was easily re-dispersed after 15 seconds of the hand-shaking technique. There were no detectable changes in color, odor, and/or flavor. The suspension showed minimal changes in pH, viscosity, shape, and mean size of the suspended indomethacin particles. The content uniformity and drug dissolution remained within the acceptable range during storage. This oral liquid suspension is an interesting alternative to be prepared by hospital pharmacy services for optimizing the pediatric treatment of patent ductus arteriosus.


Assuntos
Indometacina , Recém-Nascido Prematuro , Administração Oral , Estabilidade de Medicamentos , Humanos , Indometacina/uso terapêutico , Lactente , Recém-Nascido , Suspensões
7.
BMJ Case Rep ; 12(7)2019 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-31345829

RESUMO

Multifocal bone Langerhans cell histiocytosis (LCH) is usually treated with prednisolone and vinblastine. We present a case conservatively treated with indomethacin with good clinical and radiological response. A 7-year-old achondroplastic boy presented with worsening thoracic back pain and leg weakness. An admission MRI spine showed a pathological T1 vertebrae fracture with posterior soft tissue extension compressing and distorting the spinal cord. A CT guided biopsy revealed an LCH. Steroids were avoided to reduce osteopenia risk and further vertebral fragility. Considering the risk of a thoracic surgical approach in a child with this background, he was managed conservatively with indomethacin and a Sternal Occipital Mandibular Immobilizer (SOMI) Brace. Pain resolved completely within 6 months and the brace was discontinued. Serial follow-up scans showed progressive resolution of the pathological T1 fracture and complete resolution of the spinal cord compression.


Assuntos
Acondroplasia/fisiopatologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Dor nas Costas/etiologia , Histiocitose de Células de Langerhans/fisiopatologia , Indometacina/uso terapêutico , Compressão da Medula Espinal/fisiopatologia , Vértebras Torácicas/patologia , Acondroplasia/complicações , Dor nas Costas/diagnóstico por imagem , Dor nas Costas/tratamento farmacológico , Braquetes , Criança , Tratamento Conservador , Histiocitose de Células de Langerhans/diagnóstico por imagem , Histiocitose de Células de Langerhans/tratamento farmacológico , Humanos , Imagem por Ressonância Magnética , Masculino , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/tratamento farmacológico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Cardiol Young ; 29(7): 893-897, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31218973

RESUMO

BACKGROUND: Vascular endothelial growth factor is critically involved in ductus arteriosus closure. Polymorphisms in the vascular endothelial growth factor gene have been associated with several diseases in neonates and adults. AIM: Herein, we investigated if vascular endothelial growth factor polymorphism rs2010963 status is associated with patent ductus arteriosus incidence and/or pharmacological treatment success. METHODS: We assessed rs2010963 status in 814 preterm infants (<1500 g birth weight) by means of restriction fragment length polymorphism analysis. DNA samples were obtained from dry-spot cards used for the German national newborn screening program. Clinical data were obtained by retrospective chart review. RESULTS: We could not find any statistically significant difference in the incidence of patent ductus arteriosus depending on vascular endothelial growth factor rs2010963 polymorphism status. Furthermore, no statistically significant associations between vascular endothelial growth factor polymorphism rs2010963 status and cyclooxygenase inhibitor treatment success were observed. CONCLUSION: Our results indicate that there is no association between vascular endothelial growth factor polymorphism rs2010963 status and the occurrence of patent ductus arteriosus or the response to cyclooxygenase inhibitor treatment in a large cohort of preterm infants. Additional studies are needed to determine the role of genetic factors on patent ductus arteriosus incidence and treatment response.


Assuntos
Inibidores de Ciclo-Oxigenase/uso terapêutico , Permeabilidade do Canal Arterial/tratamento farmacológico , Permeabilidade do Canal Arterial/genética , Doenças do Prematuro/genética , Polimorfismo Genético/genética , Fator A de Crescimento do Endotélio Vascular/genética , Estudos de Casos e Controles , Permeabilidade do Canal Arterial/epidemiologia , Feminino , Humanos , Ibuprofeno/uso terapêutico , Incidência , Indometacina/uso terapêutico , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/tratamento farmacológico , Doenças do Prematuro/epidemiologia , Masculino , Resultado do Tratamento
9.
Pediatr Int ; 61(8): 792-796, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31199535

RESUMO

BACKGROUND: Video-assisted thoracoscopic surgery for patent ductus arteriosus (VATS-PDA) is an alternative surgical procedure to open chest surgery, even in premature infants. This study investigated whether the timing of VATS-PDA has a prognostic impact in premature infants whose operative indication was determined according to the symptomatic PDA and the ineffectiveness of or contraindication to indomethacine therapy. METHODS: We studied 49 infants born at or before 28 weeks of gestation who were admitted to the neonatal intensive care unit between January 2004 and June 2016, and who underwent VATS-PDA. The patients were divided into two groups according to median age at the time of surgery (early group, 24 infants who underwent surgery at ≤ 24 days of life; late group, 25 infants who underwent surgery at ≥ 25 days of life). RESULTS: No significant differences were found in bodyweight at 30 days of age and 40 weeks of corrected gestational age between the groups. The timing of surgery did not affect the operative procedure or postoperative complications. In addition, no differences were observed between the early and late groups in terms of complications associated with prematurity, including intraventricular hemorrhage, incidence and severity of bronchopulmonary dysplasia, and necrotizing enteropathy. CONCLUSION: Video-assisted thoracoscopic surgery for patent ductus arteriosus can be safely performed in premature infants without a preferential timing for the intervention, suggesting that this procedure allows for an elective basis approach after heart failure management with conservative and/or drug therapy in premature infants with PDA.


Assuntos
Permeabilidade do Canal Arterial/cirurgia , Lactente Extremamente Prematuro , Doenças do Prematuro/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Fatores Etários , Fármacos Cardiovasculares/uso terapêutico , Permeabilidade do Canal Arterial/tratamento farmacológico , Feminino , Humanos , Indometacina/uso terapêutico , Recém-Nascido , Doenças do Prematuro/tratamento farmacológico , Masculino , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
10.
J Med Case Rep ; 13(1): 173, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31167644

RESUMO

BACKGROUND: Kikuchi-Fujimoto disease, which was originally described in young women, is a benign condition characterized by necrotizing lymphadenitis and fever. Even though the clinical course is usually self-limiting, it can be associated with recurrences and rarely can be associated with systemic lupus erythematosus or can be complicated with hemophagocytic lymphohistiocytosis. We report the case of a 17-year-old Sri Lankan Sinhalese schoolboy who presented with fever and cervical lymphadenopathy diagnosed as Kikuchi-Fujimoto disease and was complicated with hemophagocytic lymphohistiocytosis subsequently. Later he fulfilled the criteria for systemic lupus erythematosus. CASE PRESENTATION: A 17-year-old previously healthy Sinhalese schoolboy presented with high-grade fever associated with chills and rigors associated with loss of appetite and loss of weight for more than 40 days. On examination, he had bilateral firm matted tender cervical lymphadenopathy and firm hepatomegaly. An excision biopsy of his right cervical lymph node revealed necrotizing lymphadenitis and immunohistochemistry of a lymph node biopsy favored Kikuchi disease. Initial antinuclear antibody and anti-double-stranded deoxyribonucleic acid tests were negative and his C3 and C4 levels were normal. An infections screening was negative. He was treated with steroids. While in hospital he developed hemophagocytic lymphohistiocytosis and renal impairment. Later his antinuclear antibody titer became positive in 1:160 and fulfilled the diagnostic criteria for systemic lupus erythematosus. He was managed with steroids and immune suppressive drugs and showed remarkable improvement. CONCLUSION: Although Kikuchi-Fujimoto disease is uncommon in male patients, it needs to be considered in patients with lymphadenopathy and fever. The disease can be complicated with hemophagocytic lymphohistiocytosis and the patients need continuous monitoring for the possible development of systemic lupus erythematosus later in the course.


Assuntos
Linfadenite Histiocítica Necrosante/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Linfo-Histiocitose Hemofagocítica/diagnóstico , Adolescente , Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Medula Óssea/patologia , Glucocorticoides/uso terapêutico , Linfadenite Histiocítica Necrosante/complicações , Linfadenite Histiocítica Necrosante/tratamento farmacológico , Linfadenite Histiocítica Necrosante/patologia , Humanos , Hidroxicloroquina/uso terapêutico , Indometacina/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Linfonodos/patologia , Linfo-Histiocitose Hemofagocítica/tratamento farmacológico , Linfo-Histiocitose Hemofagocítica/etiologia , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Metilprednisolona/uso terapêutico , Pancitopenia/diagnóstico , Pancitopenia/etiologia , Prednisolona/uso terapêutico
11.
Med Sci Monit ; 25: 3668-3675, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31100058

RESUMO

BACKGROUND Neutrophil gelatinase-associated lipocalin plays an important role in renal dysfunctions. The objective of this study was to test the hypothesis that indomethacin used in treating patent ductus arteriosus protects infants from renal dysfunction. MATERIAL AND METHODS This prospective cohort study assessed data on urine prostaglandin metabolites, urinary neutrophil gelatinase-associated lipocalin, and the renal functions of preterm infants with confirmed patent ductus arteriosus who had been injected with indomethacin (n=144, ID group) or acetaminophen (n=144, AP group). RESULTS A reduction of neutrophil gelatinase-associated lipocalin in urine samples was found in the ID group (993±48 µG/L vs. 103±5 µG/L, p<0.0001). The reduction in prostaglandin (673±32 pg/mL vs. 139±7 pg/mL, p<0.0001) and the closure of ductus (2.64±0.89 mm vs. 2.31±0.81 mm, p=0.001) were found in the ID group after the first dose of indomethacin, but the closure of ductus (2.47±0.54 mm vs. 2.32±0.55 mm, p=0.02) and prostaglandin reduction (667±31 pg/mL vs. 129±7 pg/mL, p<0.0001) were found after the second dose of acetaminophen. Indomethacin had greater effect in reducing the risk of acute kidney injury than did acetaminophen (p=0.042). CONCLUSIONS Indomethacin treatment used in treating patent ductus arteriosus protects infants from renal dysfunction.


Assuntos
Lesão Renal Aguda/prevenção & controle , Permeabilidade do Canal Arterial/tratamento farmacológico , Indometacina/uso terapêutico , Acetaminofen/uso terapêutico , China , Estudos de Coortes , Feminino , Humanos , Indometacina/farmacologia , Recém-Nascido , Recém-Nascido Prematuro/metabolismo , Doenças do Prematuro/tratamento farmacológico , Lipocalina-2/análise , Lipocalina-2/urina , Masculino , Estudos Prospectivos , Prostaglandinas/análise , Prostaglandinas/urina , Resultado do Tratamento
12.
Medicine (Baltimore) ; 98(20): e15742, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096538

RESUMO

BACKGROUND AND AIMS: The before-procedure or after-procedure rectal indomethacin administration was shown to be useful in preventing post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. We designed this prospective randomized study to compare the efficacy of single-dose and double-dose rectal indomethacin administration in preventing post-ERCP pancreatitis (PEP). METHODS: We enrolled patients who underwent the ERCP in Taipei Mackay Memorial Hospital from 2016 June to 2017 November. Patients were randomly assigned to 2 groups: single and double-dose groups. The primary endpoint was the frequency of post-ERCP pancreatitis. RESULTS: A total 162 patients participated in this study, and there were 87 patients randomly assigned to the single-dose group, and 75 patients were assigned to the double-dose group. In the high-risk patients, the incidence of PEP was lower in double-dose patients (4.8%) than the single-dose patients (9.5%), but there was no significant difference (P =.24). Difficult cannulation was the only 1 risk factor for PEP after rectal indomethacin treatment. CONCLUSIONS: Single-dose rectal indomethacin administration immediately after ERCP in general population is good enough to prevent PEP, but difficult cannulation could induce the PEP frequency up to 15.4% even under rectal indomethacin use.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Indometacina/administração & dosagem , Pancreatite/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Administração Retal , Adulto , Idoso , Cateterismo/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Incidência , Indometacina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Pancreatite/epidemiologia , Pancreatite/etiologia , Complicações Pós-Operatórias/epidemiologia , Distribuição Aleatória
13.
Clin Perinatol ; 46(2): 311-325, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31010562

RESUMO

Neonatal brain injury (NBI) remains a major contributor to neonatal mortality and long-term neurodevelopmental morbidity. Although therapeutic hypothermia is the only proven treatment to minimize brain injury caused by neonatal encephalopathy in term neonates, it provides incomplete neuroprotection. There are no specific drugs yet proven to prevent NBI in preterm neonates. This review discusses the scientific and emerging clinical trial data for several neuroprotective drugs in development, examining potential efficacy and safety concerns. Drugs with the highest likelihood of success and closest to clinical application include erythropoietin for term and preterm neonates and antenatal magnesium for preterm neonates.


Assuntos
Hemorragia Cerebral Intraventricular/prevenção & controle , Hipóxia-Isquemia Encefálica/prevenção & controle , Leucomalácia Periventricular/prevenção & controle , Neuroproteção , Corticosteroides/uso terapêutico , Alopurinol/uso terapêutico , Anestésicos Inalatórios/uso terapêutico , Anticonvulsivantes/uso terapêutico , Antioxidantes/uso terapêutico , Hemorragia Cerebral Intraventricular/tratamento farmacológico , Inibidores de Ciclo-Oxigenase/uso terapêutico , Darbepoetina alfa/uso terapêutico , Eritropoetina/uso terapêutico , Depuradores de Radicais Livres/uso terapêutico , Hematínicos/uso terapêutico , Humanos , Hipotermia Induzida , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Indometacina/uso terapêutico , Recém-Nascido , Leucomalácia Periventricular/tratamento farmacológico , Magnésio/uso terapêutico , Melatonina/uso terapêutico , Cuidado Pré-Natal , Topiramato/uso terapêutico , Xenônio/uso terapêutico
14.
J Cancer Res Ther ; 15(1): 157-163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30880773

RESUMO

Aim of Study: Cholangiocarcinoma (CCA) is an aggressive cancer with considerable metastatic potential. Various cytokines secreted by tumor cells or cells in the tumor environment can promote the metastasis of CCA. The aim of the present study was to investigate the effect of myricetin on the inhibition of cytokine-induced migration and invasion and the associated cellular mechanisms in human CCA cells. Materials and Methods: CCA KKU-100 cells were treated with a pro-inflammatory cytokine mixture consisting of interleukin-6, interferon-γ, and tumor necrosis factor-α. The migratory and invasive ability of KKU-100 cells were determined using a wound-healing assay and transwell invasion assay. The effect of myricetin on cytokine-induced STAT3 activation in CCA cells was determined using Western blot analysis. The real-time polymerase chain reaction was performed to determine messenger RNA expression. Results: Myricetin significantly inhibited cytokine-induced migration and invasion of KKU-100 cells. Detailed molecular analyses revealed that myricetin suppressed the activation of the STAT3 pathway, evidently by a decrease of the active phospho-STAT3 protein expression after myricetin treatment. The cytokine-mediated upregulation of metastasis- and inflammatory-associated genes, which are downstream genes of STAT3 including the intercellular adhesion molecule-1, matrix metalloproteinase-9, inducible nitric oxide synthase, and cyclo-oxygenase 2 (COX-2), were also significantly abolished by myricetin treatment. Moreover, the anti-migratory and anti-invasive activities of a widely prescribed COX inhibitor, indomethacin, were also revealed. Conclusion: This finding reveals the anti-metastatic effect of myricetin against CCA cells which is mediated partly through suppression of the STAT3 pathway. This compound could be potentially useful as a therapeutic agent against CCA.


Assuntos
Neoplasias dos Ductos Biliares/tratamento farmacológico , Colangiocarcinoma/tratamento farmacológico , Flavonoides/farmacologia , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Colangiocarcinoma/patologia , Citocinas/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/uso terapêutico , Humanos , Indometacina/farmacologia , Indometacina/uso terapêutico , Invasividade Neoplásica/patologia , Invasividade Neoplásica/prevenção & controle
15.
Am J Gastroenterol ; 114(2): 339-347, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30730860

RESUMO

INTRODUCTION: Rectal indomethacin and topical spray of epinephrine have separately shown efficacy in the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) in randomized controlled trials. We hypothesized that the combination of indomethacin and topical spray of epinephrine on the duodenal papillae would further reduce PEP than when indomethacin was used alone. METHODS: We conducted a comparative effectiveness, multicenter, double-blinded, randomized trial of rectal indomethacin alone vs a combination of rectal indomethacin and topical spray of epinephrine for the prevention of PEP in high-risk patients. The primary outcome was the incidence of PEP and the secondary outcome was the severity of PEP. A 2-tailed Fisher's exact test was used to analyze the difference in the proportion of patients with PEP in the indomethacin alone vs the combination group. RESULTS: A total of 960 patients (mean age 52.33 ± 14.96 years; 551 [57.4%] females) were randomized and 959 completed follow-up. The baseline demographic and clinical characteristics were similar between the 2 groups. Women <50 years of age (25.4%) and difficult cannulation (84.9%) were the most common PEP risk factors. The incidence of PEP was 6.4% in the indomethacin alone group (n = 482) compared to 6.7% in the combination group (n = 477; P = 0.87). Severe PEP was found in 5 (12%) and 7 (16%) patients in the indomethacin alone and combination groups, respectively (P = 0.88). The overall mortality was 0.6%, which was unrelated to the primary outcome. CONCLUSIONS: The combination of rectal indomethacin and topical spray of epinephrine does not reduce the incidence of PEP compared to rectal indomethacin alone in high-risk patients; https://clinicaltrials.gov/ct2/show/NCT02116309.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Inibidores de Ciclo-Oxigenase/uso terapêutico , Epinefrina/uso terapêutico , Indometacina/uso terapêutico , Pancreatite/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Vasoconstritores/uso terapêutico , Administração Retal , Administração Tópica , Adulto , Idoso , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco
16.
Congenit Heart Dis ; 14(1): 65-68, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30811794

RESUMO

The ductus arteriosus is a lifeline for the developing fetus prior to delivery, allowing the circulation of oxygen-rich blood from the placenta to bypass the lungs and perfuse the body. However, when the ductus fails to close after birth, the pressures can cause blood to shunt from the aorta back into the lungs, causing pulmonary edema. This is called a left-to-right shunt. The patent ductus arteriosus (PDA) can also shunt blood from the pulmonary arteries to the aorta, bypassing the lungs and causing oxygen-poor blood to mix with the oxygen-rich blood circulating to the body. This is called a right-to-left shunt. Too much shunting in either direction can cause significant long-term problems for the neonate. These three case studies compare the outcomes of patients with PDAs closed using different treatment techniques. The first patient's ductus arteriosus closed >2 months after birth following pharmacologic treatment. The second was closed by surgical ligation. The third was closed by transcatheter device closure.


Assuntos
Cateterismo Cardíaco/métodos , Procedimentos Cirúrgicos Cardíacos/métodos , Permeabilidade do Canal Arterial/cirurgia , Furosemida/uso terapêutico , Glucocorticoides/uso terapêutico , Indometacina/uso terapêutico , Dispositivo para Oclusão Septal , Inibidores de Ciclo-Oxigenase , Diuréticos/uso terapêutico , Permeabilidade do Canal Arterial/diagnóstico , Permeabilidade do Canal Arterial/tratamento farmacológico , Ecocardiografia , Feminino , Seguimentos , Humanos , Recém-Nascido , Ligadura/métodos , Masculino
17.
Am J Emerg Med ; 37(6): 1009-1012, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30126672

RESUMO

INTRODUCTION: Renal colic is a prevalent cause of abdominal pain in the emergency department. Although non-steroidal anti-inflammatory drugs and opioids are used for the treatment of renal colic, some adverse effects have been reported. Therefore, desmopressin -a synthetic analogue of vasopressin- has been proposed as another treatment choice. In the present study, indomethacin in combination with nasal desmopressin was compared with indomethacin alone in the management of renal colic. METHODS: Included in the study were 124 patients with initial diagnosis of renal colic and randomized to receive indomethacin suppository (100 mg) with either desmopressin intranasal spray (4 puffs, total dose of 40 micrograms) and or placebo intranasal spray. RESULTS: All the included patients were finally diagnosed with renal colic. There was no difference between the two groups in pain at the baseline (p = 0.4) and both treatments reduced pain successfully (p < 0.001). There was no significant difference between the two groups in pain reduction (p = 0.35). CONCLUSIONS: While there was significant pain reduction in both patients groups, pain reduction of NSAIDs (e.g. indomethacin) in renal colic, does not significantly improve when given in combination with desmopressin.


Assuntos
Desamino Arginina Vasopressina/normas , Indometacina/normas , Manejo da Dor/normas , Segurança do Paciente/normas , Adulto , Distribuição de Qui-Quadrado , Desamino Arginina Vasopressina/uso terapêutico , Método Duplo-Cego , Combinação de Medicamentos , Feminino , Humanos , Indometacina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Manejo da Dor/métodos , Manejo da Dor/estatística & dados numéricos , Medição da Dor/métodos , Segurança do Paciente/estatística & dados numéricos , Placebos , Estudos Prospectivos , Cólica Renal/complicações , Cólica Renal/tratamento farmacológico , Cólica Renal/psicologia
18.
Rheumatol Int ; 39(3): 569-576, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30343406

RESUMO

Fibrodysplasia ossificans progressiva (FOP), is a rare autosomal dominant connective tissue disease with a prevalence of 1 in 2 million. It is characterized by congenital foot deformities and multiple heterotopic ossifications in fibrous tissue. It usually starts with painful soft tissue swellings occurring with attacks at the ages of three or four. The attacks develop spontaneously or after minor trauma, and gradually turn into heterotopic ossifications that cause joint limitations, growth defects, skeletal deformities and chronic pain. The average life expectancy is forthy, and most of the patients are lost due to pulmonary complications. FOP is often misdiagnosed as fibromatosis, desmoid tumour or cancer, bunion, myositis, arthritis and rheumatic diseases. After clinical suspicion, confirmatory genetic analysis should be used for the diagnosis. The treatment of FOP is currently supportive. An effective, proven method has not yet been established. Herein, we present an 18-year-old female patient with FOP who underwent different treatment modalities in a 5-year period. This case-based review reveals all available treatment approaches with at least 6-month follow-up for FOP in the literature.


Assuntos
Anti-Inflamatórios/uso terapêutico , Conservadores da Densidade Óssea/uso terapêutico , Miosite Ossificante/terapia , Modalidades de Fisioterapia , Radioterapia , Adolescente , Exercícios Respiratórios , Síndrome de Cushing/induzido quimicamente , Feminino , Humanos , Indometacina/uso terapêutico , Exercícios de Alongamento Muscular , Miosite Ossificante/diagnóstico por imagem , Miosite Ossificante/fisiopatologia , Prednisolona/uso terapêutico , Amplitude de Movimento Articular , Ácido Risedrônico/uso terapêutico , Vitamina D/uso terapêutico , Adulto Jovem , Ácido Zoledrônico/uso terapêutico
19.
J Pediatr ; 205: 41-48.e6, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30340932

RESUMO

OBJECTIVE: To compare early routine pharmacologic treatment of moderate-to-large patent ductus arteriosus (PDA) at the end of week 1 with a conservative approach that requires prespecified respiratory and hemodynamic criteria before treatment can be given. STUDY DESIGN: A total of 202 neonates of <28 weeks of gestation age (mean, 25.8 ± 1.1 weeks) with moderate-to-large PDA shunts were enrolled between age 6 and 14 days (mean, 8.1 ± 2.2 days) into an exploratory randomized controlled trial. RESULTS: At enrollment, 49% of the patients were intubated and 48% required nasal ventilation or continuous positive airway pressure. There were no differences between the groups in either our primary outcome of ligation or presence of a PDA at discharge (early routine treatment [ERT], 32%; conservative treatment [CT], 39%) or any of our prespecified secondary outcomes of necrotizing enterocolitis (ERT, 16%; CT, 19%), bronchopulmonary dysplasia (BPD) (ERT, 49%; CT, 53%), BPD/death (ERT, 58%; CT, 57%), death (ERT,19%; CT, 10%), and weekly need for respiratory support. Fewer infants in the ERT group met the rescue criteria (ERT, 31%; CT, 62%). In secondary exploratory analyses, infants receiving ERT had significantly less need for inotropic support (ERT, 13%; CT, 25%). However, among infants who were ≥26 weeks gestational age, those receiving ERT took significantly longer to achieve enteral feeding of 120 mL/kg/day (median: ERT, 14 days [range, 4.5-19 days]; CT, 6 days [range, 3-14 days]), and had significantly higher incidences of late-onset non-coagulase-negative Staphylococcus bacteremia (ERT, 24%; CT,6%) and death (ERT, 16%; CT, 2%). CONCLUSIONS: In preterm infants age <28 weeks with moderate-to-large PDAs who were receiving respiratory support after the first week, ERT did not reduce PDA ligations or the presence of a PDA at discharge and did not improve any of the prespecified secondary outcomes, but delayed full feeding and was associated with higher rates of late-onset sepsis and death in infants born at ≥26 weeks of gestation. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958320.


Assuntos
Acetaminofen/uso terapêutico , Tratamento Conservador , Inibidores de Ciclo-Oxigenase/uso terapêutico , Permeabilidade do Canal Arterial/terapia , Ibuprofeno/uso terapêutico , Indometacina/uso terapêutico , Pressão Positiva Contínua nas Vias Aéreas , Permeabilidade do Canal Arterial/classificação , Feminino , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Masculino , Estudos Prospectivos , Método Simples-Cego , Resultado do Tratamento
20.
Ultrasound Obstet Gynecol ; 53(6): 841-846, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30381862

RESUMO

A circular shunt (CS) is a life-threatening condition involving massive shunting of systemic arterial blood via the ductus arteriosus to the left ventricle without traversing the lungs. In the prenatal setting, it occurs mainly in fetuses with severe forms of Ebstein's anomaly (EA) owing to unrestricted ductal flow and significant pulmonary and tricuspid regurgitation. We aimed to improve the fetal hemodynamics and chances of survival of affected fetuses by inducing ductal constriction using transplacental non-steroidal anti-inflammatory drugs (NSAIDs). Following initiation of treatment between 26 and 34 weeks' gestation, three (75%) of four fetuses with EA/CS responded with sustained ductal constriction and improved hemodynamic function, which allowed continuation of pregnancy for 3-7 weeks and elective delivery. All successfully treated cases underwent neonatal surgery immediately after birth to eliminate the CS and survived. This included two neonates that underwent single-ventricle palliation surgery that required postoperative extracorporeal membrane oxygenation and hemofiltration for transient respiratory and renal failure. The one case that did not respond to treatment with NSAIDs was delivered prematurely for progressive fetal compromise and died shortly after birth. Transplacental treatment with NSAIDs represents a novel approach to controlling fetal CS, avoiding in-utero death and prolonging the pregnancy to a more advanced gestational age, thereby potentially increasing the chances of neonatal survival. This treatment should be considered and initiated at an early stage of systemic steal to prevent brain injury due to hypoperfusion. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Permeabilidade do Canal Arterial/tratamento farmacológico , Anomalia de Ebstein/complicações , Indometacina/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Permeabilidade do Canal Arterial/complicações , Permeabilidade do Canal Arterial/cirurgia , Anomalia de Ebstein/cirurgia , Feminino , Idade Gestacional , Humanos , Indometacina/administração & dosagem , Gravidez , Resultado da Gravidez
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