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1.
Medicine (Baltimore) ; 99(40): e22598, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019480

RESUMO

BACKGROUND: Early diagnosis and treatment of the osteonecrosis of the femoral head (ONFH), a refractory disease, is imperative to prevent femoral head collapse; however, the existing solutions remain controversial. This study assessed the safety and efficacy of extracorporeal shock wave therapy (ESWT) combined with multiple drilling and intramedullary drug injection, a novel cocktail therapy, as a randomized controlled trial (RCT) model to postulate an alternative therapy for patients with early-stage ONFH. METHODS: Femoral head necrosis patients aged 20 to 60 years with stage ARCO I-II were recruited. One hundred twenty eligible participants were randomized into four groups in a 1:1:1:1 ratio: extracorporeal shock wave therapy combined with multiple drilling and intramedullary drug injection (group EMI), extracorporeal shock wave therapy (group E), multiple drilling combined with intramedullary drug injection (group MI), and multiple drilling ("positive" control group; group M). The primary outcomes included effective rate, subchondral collapse rate of the femoral head, lesion size, and grade of bone marrow edema. Secondary outcomes included the Harris Hip Score and the visual analog scale. All outcomes were measured at the screening visit (baseline) and at the planned time intervals during treatment and follow-up, and the efficacy was statistically analyzed according to the intention-to-treat sub-populations and per-protocol sub-populations. OBJECTIVES: To examine the clinical efficacy of ESWT combined with multiple drilling and intramedullary drug injection to provide a safe and more effective method for treating early-stage ONFH. TRIAL REGISTRATION NUMBER: ChiCTR1900020888; Pre-results.


Assuntos
Tratamento por Ondas de Choque Extracorpóreas/métodos , Necrose da Cabeça do Fêmur/terapia , Cabeça do Fêmur/patologia , Infusões Intraósseas/instrumentação , Adulto , Artroplastia Subcondral/efeitos adversos , Artroplastia Subcondral/métodos , Doenças da Medula Óssea/patologia , Protocolos Clínicos , Terapia Combinada/métodos , Diagnóstico Precoce , Edema/induzido quimicamente , Feminino , Cabeça do Fêmur/efeitos dos fármacos , Necrose da Cabeça do Fêmur/classificação , Seguimentos , Humanos , Infusões Intraósseas/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Segurança , Resultado do Tratamento , Escala Visual Analógica
2.
N Engl J Med ; 383(10): 944-957, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32877583

RESUMO

BACKGROUND: Among patients with non-small-cell lung cancer (NSCLC), MET exon 14 skipping mutations occur in 3 to 4% and MET amplifications occur in 1 to 6%. Capmatinib, a selective inhibitor of the MET receptor, has shown activity in cancer models with various types of MET activation. METHODS: We conducted a multiple-cohort, phase 2 study evaluating capmatinib in patients with MET-dysregulated advanced NSCLC. Patients were assigned to cohorts on the basis of previous lines of therapy and MET status (MET exon 14 skipping mutation or MET amplification according to gene copy number in tumor tissue). Patients received capmatinib (400-mg tablet) twice daily. The primary end point was overall response (complete or partial response), and the key secondary end point was response duration; both end points were assessed by an independent review committee whose members were unaware of the cohort assignments. RESULTS: A total of 364 patients were assigned to the cohorts. Among patients with NSCLC with a MET exon 14 skipping mutation, overall response was observed in 41% (95% confidence interval [CI], 29 to 53) of 69 patients who had received one or two lines of therapy previously and in 68% (95% CI, 48 to 84) of 28 patients who had not received treatment previously; the median duration of response was 9.7 months (95% CI, 5.6 to 13.0) and 12.6 months (95% CI, 5.6 to could not be estimated), respectively. Limited efficacy was observed in previously treated patients with MET amplification who had a gene copy number of less than 10 (overall response in 7 to 12% of patients). Among patients with MET amplification and a gene copy number of 10 or higher, overall response was observed in 29% (95% CI, 19 to 41) of previously treated patients and in 40% (95% CI, 16 to 68) of those who had not received treatment previously. The most frequently reported adverse events were peripheral edema (in 51%) and nausea (in 45%); these events were mostly of grade 1 or 2. CONCLUSIONS: Capmatinib showed substantial antitumor activity in patients with advanced NSCLC with a MET exon 14 skipping mutation, particularly in those not treated previously. The efficacy in MET-amplified advanced NSCLC was higher in tumors with a high gene copy number than in those with a low gene copy number. Low-grade peripheral edema and nausea were the main toxic effects. (Funded by Novartis Pharmaceuticals; GEOMETRY mono-1 ClinicalTrials.gov number, NCT02414139.).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Imidazóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Triazinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Edema/induzido quimicamente , Éxons , Feminino , Dosagem de Genes , Humanos , Imidazóis/efeitos adversos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-met/genética , Triazinas/efeitos adversos
3.
Wilderness Environ Med ; 31(3): 332-336, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32800447

RESUMO

We report a case of a 42-y-old female patient who sustained a sting to the neck from a Trachinus draco fish. She subsequently developed complications including arytenoid membrane edema secondary to either the local anesthetic agent administered to the wound or the dracotoxin itself. The patient was examined in the emergency department after the sting. Local anesthesia with lidocaine was administered to the areas of injury at another hospital before presenting to our hospital emergency department. The patient reported that her pain partially decreased but hoarseness developed and she had difficulty breathing after the local anesthetic was administered. Laryngeal examination by our hospital's otolaryngologist revealed edema of the patient's right arytenoid membrane without evidence of vocal cord swelling. Computed tomography of the neck revealed edema in the right arytenoid membrane on the side of the neck where the local anesthetic had been injected. The patient, who was given supplementary treatment, was discharged without any complications on the seventh day of hospitalization. The principle treatment for these types of stings includes immersion in hot water, analgesic therapy, and observation for signs of local and systemic envenomation. We recommend using caution when injecting local anesthetic agents in the neck because of underlying vital structures.


Assuntos
Analgésicos/efeitos adversos , Mordeduras e Picadas/patologia , Edema/tratamento farmacológico , Venenos de Peixe/efeitos adversos , Manejo da Dor , Prega Vocal/patologia , Adulto , Analgésicos/uso terapêutico , Animais , Mordeduras e Picadas/tratamento farmacológico , Edema/induzido quimicamente , Edema/diagnóstico , Feminino , Peixes , Humanos , Injeções Subcutâneas
4.
Toxicon ; 186: 126-140, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-32805296

RESUMO

Freshwater stingrays are cartilaginous fish with stingers at the base of their tail. The stinger is covered with an epithelium containing mucous and venom glands. Human envenomation usually occurs when a person steps on a stingray hiding in the sand and the fish sinks its stinger into the victim, causing an extremely painful wound which generally leads to tissue necrosis. Medical treatment is based on the use of painkillers, anti-inflammatory drugs and antibiotics, as there is to date no specific antidote for envenomation by freshwater stingrays. The aim of this study was therefore to investigate whether sera containing anti-P. motoro antibodies can neutralize the edema-forming and myotoxic activities of Potamotrygon motoro venom. To this end, two protocols were used: seroneutralization and vaccination of mice. The seroneutralization protocol involved intramuscular injection of the P. motoro venom in the mice gastrocnemius followed by administration of hyperimmune mouse serum anti P. motoro dorsal extract and stinger extract via the ophthalmic venous plexus. The vaccination protocol involved immunizing the mice with dorsal or stinger extract adsorbed to aluminum hydroxide followed by intramuscular challenge with the P. motoro venom. The gastrocnemii of all the animals were removed for histopathological and stereological analyses, and blood was collected via the ophthalmic venous plexus to measure IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, C-reactive protein and total creatine kinase. Protocols did not neutralize the edema-forming or local myotoxic induced by P. motoro venom under the experimental conditions tested. But systemic rhabdomyolysis was only completely neutralized in animals vaccinated with the stinger extract. Cytokine analysis revealed that under the experimental conditions used here, seroneutralization induced release of Th1, Th2, Th17 and Treg cytokines whereas vaccination induced a Th1 response.


Assuntos
Elasmobrânquios , Venenos de Peixe/toxicidade , Miotoxicidade , Animais , Antivenenos , Edema/induzido quimicamente , Imunoglobulinas
5.
Am J Cardiol ; 129: 1-4, 2020 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-32540170

RESUMO

Ranolazine is approved for patients with chronic stable angina but has not been formally studied in patients with refractory angina pectoris (RAP). Patients with RAP have limited therapeutic options and significant limitations in their quality of life. The Ranolazine Refractory Angina Registry was designed to evaluate the safety, tolerability, and effectiveness of ranolazine in RAP patients in order to expand treatment options for this challenging patient population. Using an extensive prospective database, we enrolled 158 consecutive patients evaluated in a dedicated RAP clinic. Angina class, medications, major adverse cardiac events including death, myocardial infarction, and revascularization were obtained at 12, 24, and 36 months. At 3 years, 95 (60%) patients remained on ranolazine. A ≥2 class improvement in angina was seen in 48% (38 of 80 patients with known Canadian Cardiovascular Society class) of those who remained on ranolazine. Discontinuation due to side effects, ineffectiveness, cost, and progression of disease were the principle reasons for discontinuation, but primarily occurred within the first year. In conclusion, ranolazine is an effective antianginal therapy at 3-year follow-up in patients with RAP and may reduce cardiac readmission.


Assuntos
Angina Pectoris/tratamento farmacológico , Fármacos Cardiovasculares/uso terapêutico , Ranolazina/uso terapêutico , Idoso , Angina Pectoris/epidemiologia , Angina Pectoris/fisiopatologia , Fármacos Cardiovasculares/economia , Constipação Intestinal/induzido quimicamente , Desprescrições , Diabetes Mellitus/epidemiologia , Progressão da Doença , Tontura/induzido quimicamente , Custos de Medicamentos , Dislipidemias/epidemiologia , Edema/induzido quimicamente , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Mortalidade , Infarto do Miocárdio/epidemiologia , Revascularização Miocárdica/estatística & dados numéricos , Náusea/induzido quimicamente , Ranolazina/economia , Sistema de Registros , Fumar/epidemiologia , Falha de Tratamento , Resultado do Tratamento
6.
Enferm. nefrol ; 23(2): 207-210, abr.-jun. 2020. ilus
Artigo em Espanhol | IBECS | ID: ibc-194139

RESUMO

CASO CLÍNICO: Paciente que inició un Síndrome de Dress tras la colocación del catéter peritoneal. En la literatura se han reportado un número muy escaso de casos de reacción alérgica al catéter peritoneal e inicialmente se sospechó como causa un antibiótico profiláctico utilizado en el quirófano, pero tras sufrir en su domicilio una exacerbación de la sintomatología a la semana de la implantación, se planteó la posibilidad de que el catéter fuera el origen del cuadro, por lo que el paciente ingresó para monitorización y administración de medicación con una mejoría clínica significativa. El Plan de Cuidados se centraba en la resolución aguda del proceso alérgico y asistir al paciente en la técnica hasta que pudo realizarla autónomamente. Finalmente, el cuadro clínico se atribuyó a un Síndrome de Dress provocado por alopurinol. CONCLUSIONES: Tras una revisión bibliográfica y ante la falta de evidencia, se decidió no retirar el catéter y tratar el cuadro, que se solucionó, pudiendo iniciar el paciente la técnica en domicilio de forma autónoma


CLINICAL CASE: Patient suffering from Dress Syndrome after placement of the peritoneal catheter. A very few cases of allergic reaction to the peritoneal catheter have been reported in the literature. Initially, the use of a prophylactic antibiotic used in the operating room was suspected as a cause, but after suffering an exacerbation of symptoms one week after implantation at the patient's home, the possibility that the catheter was the origin of the condition was raised. Then, the patient was admitted for monitoring and administration of medication with significant clinical improvement. The care plan was focused on the acute resolution of the allergic process and on assisting the technique until the patient was able to perform it autonomously. Finally, the clinical picture was attributed to a Dress Syndrome caused by allopurinol. CONCLUSIONS: After a bibliographic review and in the absence of evidence, it was decided not to remove the catheter and treat the clinical picture, which was resolved, and the patient could start the technique at home autonomously


Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Síndrome de Hipersensibilidade a Medicamentos/diagnóstico , Diálise Peritoneal/efeitos adversos , Cateteres/efeitos adversos , Hipersensibilidade a Drogas/complicações , Alopurinol/efeitos adversos , Edema/induzido quimicamente , Síndrome de Hipersensibilidade a Medicamentos/enfermagem , Cefazolina/administração & dosagem , Antibioticoprofilaxia , Corticosteroides , Administração Tópica
7.
N Engl J Med ; 383(10): 931-943, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32469185

RESUMO

BACKGROUND: A splice-site mutation that results in a loss of transcription of exon 14 in the oncogenic driver MET occurs in 3 to 4% of patients with non-small-cell lung cancer (NSCLC). We evaluated the efficacy and safety of tepotinib, a highly selective MET inhibitor, in this patient population. METHODS: In this open-label, phase 2 study, we administered tepotinib (at a dose of 500 mg) once daily in patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation. The primary end point was the objective response by independent review among patients who had undergone at least 9 months of follow-up. The response was also analyzed according to whether the presence of a MET exon 14 skipping mutation was detected on liquid biopsy or tissue biopsy. RESULTS: As of January 1, 2020, a total of 152 patients had received tepotinib, and 99 patients had been followed for at least 9 months. The response rate by independent review was 46% (95% confidence interval [CI], 36 to 57), with a median duration of response of 11.1 months (95% CI, 7.2 to could not be estimated) in the combined-biopsy group. The response rate was 48% (95% CI, 36 to 61) among 66 patients in the liquid-biopsy group and 50% (95% CI, 37 to 63) among 60 patients in the tissue-biopsy group; 27 patients had positive results according to both methods. The investigator-assessed response rate was 56% (95% CI, 45 to 66) and was similar regardless of the previous therapy received for advanced or metastatic disease. Adverse events of grade 3 or higher that were considered by investigators to be related to tepotinib therapy were reported in 28% of the patients, including peripheral edema in 7%. Adverse events led to permanent discontinuation of tepotinib in 11% of the patients. A molecular response, as measured in circulating free DNA, was observed in 67% of the patients with matched liquid-biopsy samples at baseline and during treatment. CONCLUSIONS: Among patients with advanced NSCLC with a confirmed MET exon 14 skipping mutation, the use of tepotinib was associated with a partial response in approximately half the patients. Peripheral edema was the main toxic effect of grade 3 or higher. (Funded by Merck [Darmstadt, Germany]; VISION ClinicalTrials.gov number, NCT02864992.).


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Mutação , Piperidinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Piridazinas/uso terapêutico , Pirimidinas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/genética , Edema/induzido quimicamente , Éxons , Feminino , Humanos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Proteínas Proto-Oncogênicas c-met/genética , Piridazinas/efeitos adversos , Pirimidinas/efeitos adversos
8.
AAPS PharmSciTech ; 21(5): 145, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-32430787

RESUMO

The present study demonstrates the solubility and dissolution of flufenamic acid (FLF)/ß-cyclodextrin (ß-CD)/Soluplus® supramolecular ternary inclusion complex. The binary and ternary inclusion complexes were prepared using solvent evaporation and the microwave irradiation method. The prepared inclusion complexes were evaluated for physicochemical characterization and anti-inflammatory activity using a murine paw edema mol. The phase solubility studies demonstrated 4.59-fold and 17.54-fold enhancements in FLF solubility with ß-CD alone and ß-CD:Soluplus® combination compared with pure FLF, respectively. The in vitro drug release results revealed a significant improvement (P < 0.05) in the release pattern compared with pure FLF. Maximum release was found with flufenamic acid binary and ternary complexes prepared using the microwave irradiation method, i.e., 75.23 ± 3.12% and 95.36 ± 3.23% in 60 min, respectively. The physicochemical characterization results showed complex formation and conversion of the crystalline form of FLF to an amorphous form. The SEM study revealed the presence of a more agglomerated and amorphous structure of the solid particles, which confirmed the formation of complexes. The anti-inflammatory effect of the complex was higher than pure FLF. Therefore, the FLF:ß-CD:Soluplus® inclusion complex may be a very valuable formulation with improved solubility, dissolution, and anti-inflammatory effect.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Ácido Flufenâmico/química , Ácido Flufenâmico/farmacologia , Polietilenoglicóis/química , Polivinil/química , beta-Ciclodextrinas/química , Animais , Varredura Diferencial de Calorimetria , Carragenina , Cristalização , Composição de Medicamentos , Edema/induzido quimicamente , Edema/patologia , Excipientes , Masculino , Micro-Ondas , Ratos , Ratos Wistar , Solubilidade , beta-Ciclodextrinas/farmacologia
9.
PLoS One ; 15(4): e0231244, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32298274

RESUMO

BACKGROUND: Quantifying dose-dependent ultra-early edema and ultrastructural changes in the myocyte after drug delivery is important for the development of new mixed calcium channel blockers (CCBs). MATERIALS AND METHODS: Arterial cannulation was used to measure mean arterial pressure in real time; simultaneously, magnetic resonance imaging proton density mapping was used to quantify edema 5-55 min after the delivery of L-type CCBs, T- and L-type CCBs, and solvent to a spontaneously hypertensive rat model. Transmission electron microscopy was used to show ultrastructural changes in the myocyte. RESULTS: Analysis of variance showed significant differences among the three groups in mean arterial pressure reduction (F = 246.36, P = 5.75E-25), ultra-early level of edema (ULE) (F = 175.49, P = 5.62E-22), and dose-dependent level of edema (DLE) (F = 199.48, P = 4.28E-23). Compared with the solvent's mean arterial pressure reduction (2.65±6.56±1.64), ULE (1.16±0.09±0.02), and DLE (0.0010±0.0001±0.0000), post hoc tests showed that T- and L-type CCBs had better mean arterial pressure reduction (90.67±11.58±2.90, P = 1.06E-24 vs. 68.34±15.19±3.80, P = 1.76E-12), lower ULE (1.53±0.14±0.04, P = 4.74E-9 vs. 2.08±0.18±0.04, P = 2.68E-22), and lower DLE (0.0025±0.0004±0.0001, P = 1.14E-11 vs. 0.0047±0.0008±0.0002, P = 2.10E-11) than L- type CCBs. Transmission electron microscopy showed that T- and L-type CCBs caused fewer ultrastructural changes in the myocytes after drug delivery than L-type CCBs. CONCLUSION: T- and L-type CCBs produced less ultra-early and dose-dependent edema, fewer ultrastructural changes in the myocyte, and a greater antihypertensive effect. Proton density mapping combined with arterial cannulation and transmission electron microscopy allowed for quantification of ultra-early and dose-dependent edema, antihypertensive efficacy, and ultrastructural changes in the myocyte. This is important for the evaluation of induced vasodilatory edema.


Assuntos
Anti-Hipertensivos/farmacologia , Artérias/efeitos dos fármacos , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/farmacologia , Edema/diagnóstico , Hipertensão/tratamento farmacológico , Células Musculares/efeitos dos fármacos , Animais , Anti-Hipertensivos/administração & dosagem , Artérias/fisiopatologia , Bloqueadores dos Canais de Cálcio/administração & dosagem , Canais de Cálcio Tipo L/metabolismo , Canais de Cálcio Tipo T/metabolismo , Edema/induzido quimicamente , Ratos , Ratos Endogâmicos SHR
10.
An Acad Bras Cienc ; 92(1): e20181120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32321020

RESUMO

the focus ofthis study was to testthe hypothesisthatthere would be no difference betweenthe biocompatibility of silicon dioxide nanofilms used as antimicrobial agents. Sixty male Wistar rats were divided into 4 groups (n=15): Group C (Control,Polyethylene), Group AR (Acrylic Resin), Group NP (Acrylic Resin coated with NP-Liquid), Group BG (Acrylic Resin coated with Bacterlon).the animals were sacrificed with 7,15 and 30 days and tissues analyzed as regardsthe events of inflammatory infiltrate, edema, necrosis, granulation tissue, mutinucleated giant cells, fibroblasts and collagen. Kruskal-Wallis and Dunn tests was used (P<0.05). Intense inflammatory infiltrate was shown mainly in Groups BG and AR, with significant difference from Control Group inthe time interval of 7days (P=0.004). Necrosis demonstrated significant difference between Group BG and Control Group (P<0.05) inthe time intervals of 7 days. For collagen fibers,there was significant difference betweenthe Control Group and Groups AR and BG inthe time interval of 7 days (P=0.006), and between BG and Control Groups inthe time intervals of 15 days (P=0.010).the hypothesis was rejected. Bacterlon demonstratedthe lowest level, and NP-Liquid Glassthe highest level of tissue compatibility, and best cell repair.the coating with NP-Liquid Glass was demonstrated to be highly promising for clinical use.


Assuntos
Resinas Acrílicas/farmacologia , Materiais Biocompatíveis/farmacologia , Edema/induzido quimicamente , Necrose/induzido quimicamente , Dióxido de Silício/farmacologia , Tela Subcutânea/patologia , Resinas Acrílicas/química , Animais , Materiais Biocompatíveis/química , Edema/patologia , Masculino , Teste de Materiais , Modelos Animais , Necrose/patologia , Ratos , Ratos Wistar , Dióxido de Silício/química , Tela Subcutânea/efeitos dos fármacos
11.
Chemosphere ; 254: 126808, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32339801

RESUMO

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has adverse effects on the development and function of the heart in zebrafish eleutheroembryos (embryos and larvae). We previously reported that TCDD reduced blood flow in the mesencephalic vein of zebrafish eleutheroembryos long before inducing pericardial edema. In the present study, we compared early edema (pre-cardiac edema), reduction of deduced cardiac output and reduction of blood flow in the dorsal aorta and cardinal vein caused by TCDD. In the same group of eleutheroembryos, TCDD (1.0 ppb) caused pre-cardiac edema and circulation failure at the cardinal vein in the central trunk region with the similar time courses from 42 to 54 h post fertilization (hpf), while the same concentration of TCDD did not significantly affect aortic circulation in the central trunk region or cardiac output. The dependence of pre-cardiac edema on TCDD concentration (0-2.0 ppb) at 55 hpf correlated well with the dependence of blood flow through the cardinal vein on TCDD concentration. Several treatments that markedly inhibited TCDD-induced pre-cardiac edema such as knockdown of aryl hydrocarbon receptor nuclear translocator-1 (ARNT1) and treatment with ascorbic acid, an antioxidant, did not significantly prevent the reduction of cardiac output at 55 hpf caused by 2.0 ppb TCDD. TCDD caused hemorrhage and extravasation of Evans blue that was intravascularly injected with bovine serum albumin, suggesting an increase in endothelium permeability to serum protein induced by TCDD. The results suggest that the blood vessels are primary targets of TCDD in edema formation in larval zebrafish.


Assuntos
Dibenzodioxinas Policloradas/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Ácido Ascórbico , Edema/induzido quimicamente , Edema Cardíaco/induzido quimicamente , Embrião não Mamífero/efeitos dos fármacos , Larva/efeitos dos fármacos , Dibenzodioxinas Policloradas/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Poluentes Químicos da Água/metabolismo , Peixe-Zebra/metabolismo , Proteínas de Peixe-Zebra/metabolismo
13.
Phytomedicine ; 69: 153194, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32146299

RESUMO

BACKGROUND: The frequency of allergic diseases is constantly rising. Dysregulated production of isotype E immunoglobulins is one of the key factors behind allergic reactions and its modulation is therefore an important target for pharmacological intervention. Natural products of the pseurotin family were reported to be inhibitors of IgE production in B-cells. Mechanistic details underlying these effects are however not well understood. PURPOSE: In the present study, we synthesized new analogs of natural pseurotins and extensively investigated their inhibitory effects on activation, proliferation and differentiation of B-cells, as well as on the production of IgE. STUDY DESIGN: Effects of two natural pseurotins (pseurotins A and D) and a collection of fully synthetic pseurotin analogs were studied on mouse B-cells stimulated by the combination of IL-4 and E. coli lipopolysaccharide. The IgE production was determined along with cell viability and cell proliferation. The phosphorylation of selected members of the STAT transcription factor family was subsequently investigated. Finally, the in vivo effect of pseurotin D on the ovalbumin-induced delayed type hypersensitivity response was tested in mice. RESULTS: We discovered that several fully synthetic pseurotin analogs were able to decrease the production of IgE in stimulated B-cells with potency comparable to that of pseurotins A and D. We found that the two natural pseurotins and the active synthetic analogs inhibited the phosphorylation of STAT3, STAT5 and STAT6 proteins in stimulated B-cells, resulting in the inhibition of B-cell proliferation and differentiation into the plasma cells. In vivo, pseurotin D decreased ovalbumin-induced foot pad edema. CONCLUSION: Our results advance the current mechanistic understanding of the pseurotin-induced inhibition of IgE production in B-cells by linking the effect to STAT signaling, and associated modulation of B-cell proliferation and differentiation. Together with our finding that structurally simpler pseurotin analogs were able to reproduce the effects of natural pseurotins, the presented work has implications for the future research on these secondary metabolites in the context of allergic diseases.


Assuntos
Linfócitos B/efeitos dos fármacos , Imunoglobulina E/metabolismo , Plasmócitos/citologia , Pirrolidinonas/química , Pirrolidinonas/farmacologia , Animais , Linfócitos B/citologia , Linfócitos B/fisiologia , Diferenciação Celular/efeitos dos fármacos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Escherichia coli/química , Imunoglobulina E/sangue , Imunoglobulina M/sangue , Imunoglobulina M/metabolismo , Lipopolissacarídeos/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Ovalbumina/toxicidade , Fosforilação/efeitos dos fármacos , Plasmócitos/fisiologia , Fatores de Transcrição STAT/metabolismo
15.
PLoS One ; 15(3): e0230645, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210452

RESUMO

Houttuynia cordata Thunb. has been used as a traditional medicine to treat a variety of ailments in Asian countries such as China, Japan, South Korea, and Thailand. In Thailand, H. cordata fermentation products (HCFPs) are commercially produced and popularly consumed throughout the country without experimental validation. Anti-inflammatory activity of H. cordata fresh leaves or aerial parts has previously been reported, however, the anti-inflammatory activity of the commercially available HCFPs produced by the industrialized process has not yet been investigated. The aim of this study was to evaluate in vitro and in vivo anti-inflammatory potential of the selected industrialized HCFP. LPS-induced RAW264.7 and carrageenan-induced paw edema models were used to evaluate the anti-inflammatory activity of HCFP. The phenolic acid components of HCFP aqueous and methanolic extracts were investigated using HPLC analysis. In RAW264.7 cells, the HCFP aqueous and methanolic extracts reduced NO production and suppressed LPS-stimulated expression of PGE2, iNOS, IL-1ß, TNF-α and IL-6 levels in a concentration-dependent manner, however, less effect on COX-2 level was observed. In Wistar rats, 3.08 and 6.16 mL/kg HCFP reduced paw edema after 2 h carrageenan stimulation, suggesting the second phase anti-edematous effect similar to diclofenac (150 mg/kg). Whereas, 6.16 mL/kg HCFP also reduced paw edema after 1 h carrageenan stimulation, suggesting the first phase anti-edematous effect. Quantitative HPLC revealed the active phenolic compounds including syringic, vanillic, p-hydroxybenzoic and ferulic acids, which possess anti-inflammatory activity. Our results demonstrated for the first time the anti-inflammatory activity of the industrialized HCFP both in vitro and in vivo, thus validating its promising anti-inflammation potential.


Assuntos
Anti-Inflamatórios/farmacologia , Suplementos Nutricionais/análise , Houttuynia/metabolismo , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Sobrevivência Celular/efeitos dos fármacos , Edema/induzido quimicamente , Edema/tratamento farmacológico , Houttuynia/química , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Lipopolissacarídeos/toxicidade , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Camundongos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fenóis/análise , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Folhas de Planta/metabolismo , Células RAW 264.7 , Ratos , Ratos Wistar
16.
Chem Biol Interact ; 319: 108984, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32061742

RESUMO

OBJECTIVES: As one of the main active ingredients of Chinese herbal medicine Andrographis paniculate, andrographolide is used in domestic clinical treatment for respiratory infections and inflammation. This study was designed to investigate the effects of andrographolide as an antioxidant on the level of oxidative stress, neutrophil accumulation and infiltration in joints and synovial tissue of arthritis rats induced by complete freund's adjuvant. METHODS: A rat model of rheumatoid arthritis was induced by subcutaneous injection of complete Freund's adjuvant in the footpad. The model was established 14 days after induction. The treatment was performed from 14th day to 35th day with different doses of andrographolide (25, 50, 100 mg/kg) and positive control methotrexate (3 mg/kg). The effects of andrographolide on oxidative stress, neutrophil accumulation and infiltration were measured by the paw swelling, arthritis score, the hot plate test, biochemical analysis, and histology. RESULTS: The medium and high-dose andrographolide (50, 100 mg/kg) group declined the levels of tumor necrosis factor-α, interleukin-6 and CXC chemokine ligand2, articular elastase and myeloperoxidase, and increased the levels of antioxidant enzymes superoxide dismutase, catalase, and glutathione. The activity of malondialdehyde and nitrite/nitrate in andrographolide (50, 100 mg/kg) group was weakened than the model group. The degree of swelling and arthritis score of andrographolide group was lower than the model group. The results of hot plate test showed that high dose of andrographolide significantly improved the anti-injury ability of rats; Radiological and histological results showed that the joint osteoporosis, inflammatory cell infiltration, synovial hyperplasia and other phenomena in the andrographolide group were significantly improved. CONCLUSIONS: Andrographolide acts as a protective agent for the treatment of complete freund's adjuvant induced rheumatoid arthritis by inhibiting lipid peroxidation and nitrite/nitrate levels in a dose-dependent manner, enhancing antioxidant enzyme activity, reducing levels of chemokines and inflammatory factors, preventing neutrophil accumulation and infiltration.


Assuntos
Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Diterpenos/farmacologia , Adjuvante de Freund/farmacologia , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Artrite Experimental/metabolismo , Artrite Reumatoide/induzido quimicamente , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Catalase/metabolismo , Modelos Animais de Doenças , Edema/induzido quimicamente , Edema/tratamento farmacológico , Edema/metabolismo , Glutationa/metabolismo , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Articulações/efeitos dos fármacos , Articulações/metabolismo , Masculino , Metotrexato/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismo , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
18.
Plast Reconstr Surg ; 145(3): 661-667, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32097303

RESUMO

BACKGROUND: Nonsurgical rhinoplasty with injectable dermal fillers has become an increasingly popular alternative to surgical procedures, in view of its relative low cost, convenience and rapid recovery, and low risk profile. The safety and efficacy of nonsurgical rhinoplasty remains a relatively contentious and ambiguous matter, given that there are few large-scale series reporting results or complications. This study reports the experience of a single clinician performing nonsurgical rhinoplasty in the largest cohort to date. METHODS: Patient demographics, indications, treatment details, and outcomes of patients treated between March of 2016 and January of 2019 were reviewed. The nonsurgical rhinoplasty technique described previously by Harb was used using hyaluronic acid dermal filler. RESULTS: Nonsurgical rhinoplasty was performed in 5000 patients. The commonest indication was dorsal hump (44 percent). Swelling and erythema were self-limiting side effects encountered in approximately half of patients. Infection was seen in two patients, and localized skin necrosis was observed in three patients. CONCLUSIONS: Nonsurgical rhinoplasty is a safe procedure with positive aesthetic results when performed by an experienced clinician. Knowledge of nasal anatomy, comprehensive training, and use of appropriate materials are key in ensuring safety and results. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.


Assuntos
Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/administração & dosagem , Nariz/anatomia & histologia , Rinoplastia/métodos , Adolescente , Adulto , Idoso , Preenchedores Dérmicos/efeitos adversos , Edema/induzido quimicamente , Edema/epidemiologia , Eritema/induzido quimicamente , Eritema/epidemiologia , Estética , Feminino , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Masculino , Pessoa de Meia-Idade , Necrose/induzido quimicamente , Necrose/epidemiologia , Satisfação do Paciente , Estudos Retrospectivos , Rinoplastia/efeitos adversos , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento , Adulto Jovem
20.
J Ethnopharmacol ; 252: 112565, 2020 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-31935495

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Aerial parts of Vincetoxicum arnottianum (Wight) Wight (Family Apocynaceae) are used by local communities for inflammation, healing of wound and injuries and also for urticaria. AIM OF STUDY: Extract/fractions of V. arnottianum were evaluated for potential anti-inflammatory activity in rat. METHODS: Methanol extract of aerial parts of V. arnottianum (VAM) was partitioned on polarity for n-hexane (VAH), ethyl acetate (VAE), butanol (VAB) and aqueous (VAA) fractions. The extract/fractions were evaluated during in vitro assay for protection against heat induced protein denaturation and Carrageenan induced paw inflammation in rat. VAM and VAE were evaluated for anti-inflammatory potential against formalin and Freund's complete adjuvant (FCA) induced inflammation in paw of rat while croton oil induced inflammation in ear of rat, respectively. The level of inflammatory mediators; IL-17, IL-1ß, IL-6, TNF-α and nitric oxide (NO) was estimated in serum of rat. RESULTS: All the extract/fractions used in this study exhibited anti-inflammatory activity. However, VAE (300 mg/kg) exhibited potential anti-inflammatory activity in carrageenan (78.06 ± 4.6%), formalin (54.71 ± 0.34%) and croton oil (73.12 ± 1.9%) induced edema in rat. In FCA induced inflammation model VAM and VAE showed admiring proficiencies against alteration of body weight and organ weight indices, paw edema and histological studies. In serum increased level of pro-inflammatory cytokines (IL-1ß, TNF-α, IL-6, IL-17) and NO during adjuvant-induced inflammation were more efficiently restored with VAE treatment to rat. Presence of polyphenolics; rutin, gallic acid, caffeic acid, apigenin, myricetin and quercetin was indicated in VAE. CONCLUSION: The results suggest the presence of anti-inflammatory constituents in V. arnottianum.


Assuntos
Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Vincetoxicum , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/toxicidade , Carragenina , Óleo de Cróton , Citocinas/imunologia , Edema/induzido quimicamente , Edema/imunologia , Formaldeído , Adjuvante de Freund , Masculino , Óxido Nítrico/imunologia , Estresse Oxidativo/efeitos dos fármacos , Componentes Aéreos da Planta , Extratos Vegetais/farmacologia , Extratos Vegetais/toxicidade , Ratos Sprague-Dawley , Testes de Toxicidade Aguda
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