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1.
Photodiagnosis Photodyn Ther ; 33: 102196, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33515763

RESUMO

Many oral signs and symptoms related to the novel coronavirus disease (COVID-19) have been reported; however, both prevalence and etiology are still undetermined. Since the clinical features of the oral lesions seen in COVID-19 are highly heterogeneous and the treatments differ considerably in the literature, the present study aimed to report a clinical case in which a combination of antimicrobial photodynamic therapy (aPDT) and photobiomodulation therapy (PBMT) was used for extensive lip lesions in a patient suffering from COVID-19. Within 4 days and without any systemic drug administration, after two sessions of aPDT and one session of PBMT, the lip lesions were completely healed, and the patient recovered her orofacial functions satisfactorily. According to the current case report and taking into consideration the evident lack of information about many aspects of COVID-19 infection, this combination of phototherapy modalities seems to be a promising tool for managing COVID-19-related lip lesions; however, more studies are necessary.


Assuntos
/patologia , Lábio/efeitos dos fármacos , Lábio/patologia , Terapia com Luz de Baixa Intensidade/métodos , Fotoquimioterapia/métodos , Feminino , Humanos , Azul de Metileno/uso terapêutico , Pessoa de Meia-Idade , Fármacos Fotossensibilizantes/uso terapêutico
2.
Cell Death Dis ; 11(12): 1070, 2020 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-33318476

RESUMO

Lack of effective treatments for aggressive breast cancer is still a major global health problem. We have previously reported that photodynamic therapy using methylene blue as photosensitizer (MB-PDT) massively kills metastatic human breast cancer, marginally affecting healthy cells. In this study, we aimed to unveil the molecular mechanisms behind MB-PDT effectiveness and specificity towards tumor cells. Through lipidomics and biochemical approaches, we demonstrated that MB-PDT efficiency and specificity rely on polyunsaturated fatty acid-enriched membranes and on the better capacity to deal with photo-oxidative damage displayed by non-tumorigenic cells. We found out that, in tumorigenic cells, lysosome membrane permeabilization is accompanied by ferroptosis and/or necroptosis. Our results also pointed at a cross-talk between lysosome-dependent cell death (LDCD) and necroptosis induction after photo-oxidation, and contributed to broaden the understanding of MB-PDT-induced mechanisms and specificity in breast cancer cells. Therefore, we demonstrated that efficient approaches could be designed on the basis of lipid composition and metabolic features for hard-to-treat cancers. The results further reinforce MB-PDT as a therapeutic strategy for highly aggressive human breast cancer cells.


Assuntos
Neoplasias da Mama/patologia , Luz , Antioxidantes/farmacologia , Neoplasias da Mama/tratamento farmacológico , Carcinogênese/efeitos dos fármacos , Carcinogênese/patologia , Carcinogênese/efeitos da radiação , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Linhagem Celular Tumoral , Feminino , Ferroptose/efeitos dos fármacos , Ferroptose/efeitos da radiação , Humanos , Lipídeos/química , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Lisossomos/efeitos da radiação , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Modelos Biológicos , Necroptose/efeitos dos fármacos , Necroptose/efeitos da radiação , Oxirredução , Fotoquimioterapia , Neoplasias de Mama Triplo Negativas/patologia
3.
Cir. pediátr ; 33(4): 166-171, oct. 2020. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-195126

RESUMO

OBJETIVOS: Evaluar un programa de corrección toracoscópica de atresia de esófago comparándola con una cohorte histórica de pacientes. MATERIAL Y MÉTODOS: Estudio de cohortes retrospectivas. Grupo intervención: pacientes intervenidos por vía toracoscópica; grupo con-trol: pacientes con corrección abierta, con peso y edad gestacional en el mismo rango que la cohorte intervención. El peso mínimo para la cirugía toracoscópica fue de 1.700 g. Los efectos adversos se registraron mediante la clasificación de Clavien-Dindo. Se calculó la odds ratio del evento complicación. Una p < 0,05 se consideró estadísticamente significativa. RESULTADOS: Entre enero de 2006 y diciembre de 2019 se registraron 40 casos de atresia de esófago (tipo C de Gross). Diez pacientes se excluyeron del análisis, analizándose 12 pacientes en el grupo intervención y 18 en el grupo control. Los grupos fueron comparables respecto a sexo, edad gestacional y peso al nacimiento. En el grupo intervención el tiempo quirúrgico medio fue significativamente superior (146 min vs. 213 min; t test = -4,76; p = 0,0001) y se correlacionó con el número de caso (Rho de Spearman: -0,853; p = 0,0001).Dieciséis pacientes (52%) desarrollaron 19 complicaciones: 3 (16%) grado I, 8 (42%) grado II, 5 (26,5%) grado IIIa, 1 (5%) grado IIIb y 2 (10,5%) grado IVa, con una distribución similar entre grupos (Chi cua-drado:1,98; p = 0,73). La odds ratio para la presentación de un efecto adverso no mostró diferencias (OR: 2,4; IC 95%: 0,48-11,93; p = 0,44), incluso cuando se excluyeron los pacientes con complicación grado I aislada (OR: 1,4; IC 95%: 0,32-6,10; p = 0,72). Las complicaciones en el grupo intervención se concentraron en los primeros cinco casos. CONCLUSIONES: En el abordaje toracoscópico la morbilidad asociada a la curva de aprendizaje parece limitada al tiempo operatorio y a una tasa de complicaciones similar a la de la cirugía abierta


OBJECTIVES: To evaluate a thoracoscopic esophageal atresia repair program by comparing it with a historic patient cohort. MATERIALS AND METHODS: Retrospective cohort study. Surgery group: thoracoscopic surgery patients. CONTROL GROUP: open repair patients, with weight and gestational age in the same range as the surgery cohort. Minimal weight for thoracoscopic surgery was 1,700 g. Adverse effects were recorded using Clavien-Dindo classification. Complication odds ratio was calculated. Statistical significance was established at p < 0.05. RESULTS: From January 2006 to December of 2019, 40 cases of esophageal atresia (Gross type C) were recorded, 10 of which were excluded. The study consisted of 12 patients in the surgery group and 18 patients in the control group. Groups were similar in terms of sex, gestational age, and weight at birth. In the surgery group, mean operating time was significantly longer (146 min vs. 213 min.; T test = -4.76; p = 0.0001) and it was correlated with the case number (Spearman's Rho: -0.853; p = 0.0001).16 patients (52%) developed 19 complications: 3 (16%) grade I complications, 8 (42%) grade II complications, 5 (26.5%) grade IIIa complications, 1 (5%) grade IIIb complication, and 2 (10.5%) IVa complications, with a similar distribution between groups (Chi square: 1.98; p = 0.73). Odds ratio for adverse effect occurrence showed no differences (OR: 2.4; 95% CI: 0.48-11.93; p = 0.44) even when ex-cluding patients with isolated grade I complication (OR: 1.4; 95% CI: 0.32-6.10; p = 0.72). Complications in the surgery group occurred in the first 5 cases only. CONCLUSIONS: In the thoracoscopic approach, learning curve associ-ated morbidity seems limited to operating time and has a complication rate similar to that of open surgery


Assuntos
Humanos , Criança , Atresia Esofágica/cirurgia , Complicações Pós-Operatórias/classificação , Toracoscopia/métodos , Curva de Aprendizado , Índice de Gravidade de Doença , Estudos de Coortes , Atresia Esofágica/complicações , Estudos Retrospectivos , Razão de Chances , Fístula Traqueoesofágica/complicações , Fístula Traqueoesofágica/cirurgia , Idade Gestacional , Azul de Metileno/uso terapêutico , Anastomose Cirúrgica
4.
A A Pract ; 14(9): e01287, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32909713

RESUMO

Methemoglobinemia is a rare disorder of the blood in which there is an increase in methemoglobin, which occurs when hemoglobin is present in the oxidized form. Methemoglobin impairs hemoglobin's ability to transport oxygen, produces functional anemia, and leads to tissue hypoxia. We report the successful management of a case of refractory hypoxia due to acutely acquired methemoglobinemia in a patient undergoing treatment for coronavirus disease 2019 (COVID-19) pneumonia. The cause of methemoglobinemia in this patient remains unknown. Hypoxia and methemoglobinemia did not respond to methylene blue and required administration of packed red blood cell transfusions.


Assuntos
Infecções por Coronavirus/complicações , Hipóxia/etiologia , Metemoglobinemia/complicações , Pneumonia Viral/complicações , Insuficiência Respiratória/etiologia , Lesão Renal Aguda/complicações , Lesão Renal Aguda/terapia , Idoso , Anticorpos Monoclonais Humanizados/uso terapêutico , Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Betacoronavirus , Infecções por Coronavirus/tratamento farmacológico , Corynebacterium , Infecções por Corynebacterium/complicações , Infecções por Corynebacterium/terapia , Síndrome da Liberação de Citocina/complicações , Inibidores Enzimáticos/uso terapêutico , Transfusão de Eritrócitos , Hematínicos/uso terapêutico , Humanos , Hidroxocobalamina/uso terapêutico , Hidroxicloroquina/uso terapêutico , Hipóxia/terapia , Masculino , Metemoglobinemia/terapia , Azul de Metileno/uso terapêutico , Pandemias , Pneumonia Bacteriana/complicações , Pneumonia Bacteriana/terapia , Pneumonia Viral/tratamento farmacológico , Terapia de Substituição Renal , Insuficiência Respiratória/terapia , Choque Séptico/complicações
5.
Emerg Med Clin North Am ; 38(4): 841-856, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32981621
7.
Eur J Pharmacol ; 885: 173494, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32828741

RESUMO

COVID-19 is a global catastrophic event that causes severe acute respiratory syndrome. The mechanism of the disease remains unclear, and hypoxia is one of the main complications. There is no currently approved protocol for treatment. The microbial threat as induced by COVID-19 causes the activation of macrophages to produce a huge amount of inflammatory molecules and nitric oxide (NO). Activation of macrophages population into a pro-inflammatory phenotype induces a self-reinforcing cycle. Oxidative stress and NO contribute to this cycle, establishing a cascade inflammatory state that can kill the patient. Interrupting this vicious cycle by a simple remedy may save critical patients' lives. Nitrite, nitrate (the metabolites of NO), methemoglobin, and prooxidant-antioxidant-balance levels were measured in 25 ICU COVID-19 patients and 25 healthy individuals. As the last therapeutic option, five patients were administered methylene blue-vitamin C-N-acetyl Cysteine (MCN). Nitrite, nitrate, methemoglobin, and oxidative stress were significantly increased in patients in comparison to healthy individuals. Four of the five patients responded well to treatment. In conclusion, NO, methemoglobin and oxidative stress may play a central role in the pathogenesis of critical COVID-19 disease. MCN treatment seems to increase the survival rate of these patients. Considering the vicious cycle of macrophage activation leading to deadly NO, oxidative stress, and cytokine cascade syndrome; the therapeutic effect of MCN seems to be reasonable. Accordingly, a wider clinical trial has been designed. It should be noted that the protocol is using the low-cost drugs which the FDA approved for other diseases. TRIAL REGISTRATION NUMBER: NCT04370288.


Assuntos
Acetilcisteína/uso terapêutico , Ácido Ascórbico/uso terapêutico , Ensaios Clínicos Fase I como Assunto , Infecções por Coronavirus/tratamento farmacológico , Estado Terminal , Azul de Metileno/uso terapêutico , Pneumonia Viral/tratamento farmacológico , Ensaios de Uso Compassivo , Infecções por Coronavirus/complicações , Feminino , Humanos , Hipóxia/complicações , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/complicações
8.
Am J Med Sci ; 360(4): 329-337, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32631574

RESUMO

Methylene blue (MB) is considered to be the first synthetic medication ever used in humans. There are many indications for MB, including vasoplegic shock. Nitric oxide (NO), the central mediator of sepsis, promotes vasoplegia by enhancing the guanylate cyclase cyclic guanosine monophosphate second messenger system, the effect of which is attenuated by MB. Therefore, the use of MB represents a unique pharmacologic approach towards treating the underlying pathophysiology of vasoplegia in sepsis. There are numerous reports of the successful use of MB in refractory shock in the literature. This manuscript describes the historical aspects of the identification of NO as the endothelial derived relaxation factor and its role in the pathogenesis of vasoplegia in septic shock. An analysis of the existing evidence for the use of MB as an inhibitor of NO in vasodilatory shock is provided. The adverse effects associated with the use of MB and an approach to optimal dosing in septic shock are also addressed.


Assuntos
Azul de Metileno/uso terapêutico , Óxido Nítrico/antagonistas & inibidores , Choque Séptico/tratamento farmacológico , Vasoplegia/tratamento farmacológico , Humanos , Azul de Metileno/administração & dosagem , Azul de Metileno/efeitos adversos , Choque Séptico/complicações , Choque Séptico/metabolismo , Vasodilatação/efeitos dos fármacos , Vasoplegia/etiologia , Vasoplegia/metabolismo
9.
Medicine (Baltimore) ; 99(14): e19429, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32243363

RESUMO

It is known that the presence of orthodontic brackets predisposes for a change in the biofilm, facilitating the development of gingivits. The sites are difficult to access with a toothbrush and periodontal curette, worsening inflammation, in addition, a gingival hyperplasia is associated with poor hygiene. The objective of this study is to evaluate the impact of photodinamyc therapy (PDT) as an adjuvant treatment, considering clinical immunoregulatory and microbiological parameters. This randomized, controlled, double-blind clinical study will include 34 patients, both genders, having used fixed appliance for more than 12 months, with gingivitis. Participants will be divided into two groups: G1 (n = 17)- Scaling and Root Planing + PDT placebo and G2 (n = 17)- Scaling and Root Planing + PDT. In G2 the following dosimetric parameters will be used: methylene blue 0.005%, λ= 660 nanometers (nm), 9 Joules (J) per site, irradiance= 3.5Watts (W)/ centimeters (cm), radiant exposure= 318J/cm. All participants will receive oral hygiene guidance prior the curetes scaling. The clinical periodontal data to be analyzed are plaque index, gingival index and probing depth. Crevicular fluid, from 4 pre-determined sites and saliva, will be collected and analysed for IL-6, IL-1ß, IL-8, TNF-α and IL-10 cytokines using ELISA (Enzyme immunoabsorption assay) method. Total Bacteria count will also be performed, by qPCR and Universal16SrRNA gene. All analysis will be realized using in the baseline (T0), 7 (T1) and 21 (T2) days after treatment. Oral health-related quality of life will be assessed using the OHIP-14 questionnaire at times T0 and T2. If sample distribution is normal, the Student T-test will be applied if it is not normal, the Mann-Whitney test will be used. The data will be presented in terms of ±â€ŠPD and The significance level will be set at p < 0.05. Our results may improve quality of life and add data to establish a therapeutic alternative for gingivitis during the orthodontic treatment. Registration: clinicaltrials.gov NCT04037709. https://clinicaltrials.gov/ct2/show/NCT04037709 - Registered in July 2019.


Assuntos
Gengivite/terapia , Mediadores da Inflamação/metabolismo , Azul de Metileno/uso terapêutico , Aparelhos Ortodônticos Fixos , Fotoquimioterapia/métodos , Adolescente , Adulto , Criança , Terapia Combinada , Raspagem Dentária/métodos , Método Duplo-Cego , Ensaio de Imunoadsorção Enzimática , Feminino , Gengivite/tratamento farmacológico , Gengivite/microbiologia , Humanos , Masculino , Índice Periodontal , Qualidade de Vida , Adulto Jovem
10.
Expert Opin Pharmacother ; 21(6): 619-627, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32037892

RESUMO

INTRODUCTION: Alzheimer's disease (AD) is a major cause of morbidity worldwide and its prevalence is expected to rise. Previous studies involving compounds that target the accumulation of amyloid ß protein have been unsuccessful, renewing interest in therapies directed against intracellular deposits of tau proteins. Derived from methylene blue, hydromethylthionine is a tau aggregation inhibitor that recently emerged as a promising disease-modifying treatment for AD. AREAS COVERED: Herein, the authors cover the chemistry, pharmacodynamics and pharmacokinetics of hydromethylthionine and its oxidized form methylthionine chloride (MTC) that was first studied, as well as clinical efficacy and safety of hydromethylthionine in the treatment of mild to moderate AD. EXPERT OPINION: Randomized clinical trials with hydromethylthionine failed to show any impact of the doses used on the disease course. Data analysis from a non-randomized cohort showed that a smaller dose of the drug previously thought to be ineffective and used as placebo, prescribed as monotherapy rather than as add-on to AD approved symptomatic therapies may slow cognitive decline. This finding was further confirmed by a pharmacokinetic analysis study showing a dose/response relationship with doses around 16 mg daily. Future trials need to study the pharmacological properties of hydromethylthionine and ascertain the optimal safe and effective dose to be used.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Disfunção Cognitiva/prevenção & controle , Azul de Metileno/análogos & derivados , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Animais , Estudos de Coortes , Progressão da Doença , Relação Dose-Resposta a Droga , Humanos , Azul de Metileno/efeitos adversos , Azul de Metileno/farmacocinética , Azul de Metileno/uso terapêutico , Agregados Proteicos/efeitos dos fármacos , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Proteínas tau/metabolismo
11.
Crit Care ; 24(1): 36, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32019600

RESUMO

Vasoplegic syndrome is a common occurrence following cardiothoracic surgery and is characterized as a high-output shock state with poor systemic vascular resistance. The pathophysiology is complex and includes dysregulation of vasodilatory and vasoconstrictive properties of smooth vascular muscle cells. Specific bypass machine and patient factors play key roles in occurrence. Research into treatment of this syndrome is limited and extrapolated primarily from that pertaining to septic shock, but is evolving with the expanded use of catecholamine-sparing agents. Recent reports demonstrate potential benefit in novel treatment options, but large clinical trials are needed to confirm.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Vasoplegia/tratamento farmacológico , Vasoplegia/fisiopatologia , Corticosteroides/uso terapêutico , Angiotensina II/uso terapêutico , Ácido Ascórbico/uso terapêutico , Procedimentos Cirúrgicos Cardíacos/métodos , Dopamina/uso terapêutico , Inibidores Enzimáticos/uso terapêutico , Epinefrina/uso terapêutico , Humanos , Azul de Metileno/uso terapêutico , Norepinefrina/uso terapêutico , Fenilefrina/uso terapêutico , Simpatomiméticos/uso terapêutico , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologia , Vasoconstritores/uso terapêutico , Vasoplegia/etiologia , Vasopressinas/uso terapêutico
12.
Sci Rep ; 10(1): 1828, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32020043

RESUMO

Hemodynamic effectiveness of methylene blue (MB) was tested in patients with refractory distributive shock. A retrospective analysis of 20 critically-ill patients who developed refractory shock was performed. Patients were divided into two study groups as responders with positive hemodynamic response to MB administration (defined as 10% decrease of norepinephrine dose) and non-responders. Hemodynamic, outcome data and baseline tissue hypoxia-related parameters including ratio of central venous-to-arterial carbon dioxide tension to arterio-venous oxygen content (P(v-a)CO2/C(a-v)O2) were compared between the groups. There were 9 (45%) responders and 11 (55%) non-responders to single bolus of MB administration. Dose of MB did not differ between responders and non-responders (1.3 ± 0.5 vs. 1.3 ± 0.4 mg/kg respectively, P = 0.979). MB responders had lower baseline P(v-a) CO2/C(a-v)O2 (1.79 ± 0.73 vs. 3.24 ± 1.18, P = 0.007), higher pH (7.26 ± 0.11 vs. 7.16 ± 0.10, P = 0.037) and lower lactate levels at 12 hours post MB administration (3.4 ± 2.7 vs. 9.9 ± 2.2 mmol/L, P = 0.002) compared to non-responders. Methylene blue represents a non-adrenergic vasopressor with only limited effectiveness in patients with refractory distributive shock. Profound tissue hypoxia with high degree of anaerobic metabolism was associated with the loss of hemodynamic responsiveness to its administration.


Assuntos
Azul de Metileno/uso terapêutico , Choque/tratamento farmacológico , Vasoconstritores/uso terapêutico , Idoso , Pressão Sanguínea/efeitos dos fármacos , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Norepinefrina/uso terapêutico , Oxigênio/sangue , Estudos Retrospectivos , Choque/mortalidade , Análise de Sobrevida , Resultado do Tratamento
13.
Medicine (Baltimore) ; 99(6): e18854, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028395

RESUMO

BACKGROUND: The elimination of the pathogenic microorganisms of the periodontal pocket is one of the main points for success in periodontal treatment. The objective of this study is to investigate the clinical and antimicrobial effect of papain-mediated photodynamic therapy in the clinical treatment of periodontal disease. METHODS: Twenty patients with chronic periodontitis will be selected. Patients will be randomly divided into 2 groups (n = 10). Group 1 will receive conventional periodontal treatment and group 2 will receive conventional treatment and antimicrobial photodynamic therapy (PACT). Conventional treatment will consist of oral hygiene guidance, with brushing technique instructions and recommendation of daily flossing. The calculus deposits on the teeth will be removed with ultrasound equipment and curettes for scraping and root planning. The PACT will be performed at the end of each periodontal treatment session, at sites with bags ≥4 mm. PapaMblue photosensitizer will be deposited in the periodontal pockets with a syringe and a pre-irradiation time of 1 minute will be adopted. Then, the laser emitting wavelength of 660 nm, with power of 100 mW, for 2 minutes, radiant exposure of 30 J/cm and power density of 250 mW/cm will be applied. Patients will undergo clinical evaluations before treatment (day 1) at 30, 60, and 90 days after the end of treatment; and microbiological evaluations before and immediately after treatment. The distribution of the data within each group and the homogeneity of the variances will be verified. With this information, the most appropriate statistical test in each evaluation will be used. The sample calculation is based on the literature and the significance level of 5% will be adopted. DISCUSSION: The combination of PACT with methylene blue in a papain gel and the conventional treatment may increase the reduction of bacteria in periodontal pockets.


Assuntos
Anti-Infecciosos/uso terapêutico , Periodontite Crônica/terapia , Azul de Metileno/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Adulto , Anti-Infecciosos/administração & dosagem , Terapia Combinada , Método Duplo-Cego , Feminino , Humanos , Masculino , Azul de Metileno/administração & dosagem , Fotoquimioterapia , Fármacos Fotossensibilizantes/administração & dosagem , Resultado do Tratamento
14.
BMJ Case Rep ; 13(1)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31969408

RESUMO

Methaemoglobinaemia is an extremely rare condition with multiple causes, both genetic and acquired. We present a severe case of methaemoglobinaemia occurring in a Brazilian hairdresser working in the UK. She presented after several days of preparing popular 'Brazilian blowdry' treatments for customers at a hair salon. She had been exposed to multiple volatile chemicals, including formaldehyde, without any respiratory protection, and we postulate that this may have caused her illness. If so, this would be the first published case of methaemoglobinaemia caused by exposure to the volatile components of beauty products.


Assuntos
Poluentes Ocupacionais do Ar/efeitos adversos , Preparações para Cabelo/efeitos adversos , Metemoglobinemia/induzido quimicamente , Metemoglobinemia/tratamento farmacológico , Azul de Metileno/uso terapêutico , Exposição Ocupacional/efeitos adversos , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Pessoa de Meia-Idade
16.
Lasers Med Sci ; 35(1): 79-85, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31081523

RESUMO

Chagas disease is endemic in Latin America and increasingly found in non-endemic countries. Its treatment is limited due to the variable efficacy and several side effects of benznidazole. Photodynamic antimicrobial chemotherapy (PACT) may be an attractive approach for treating Chagas disease. Here, the trypanocidal activity of PACT was investigated in vitro using phenothiazine derivatives. The cytotoxicity of both, methylene blue (MB) and toluidine blue (TBO), was determined on macrophages cultures using AlamarBlue method. The trypanocidal activity of the two photosensitizers was initially evaluated by determining their IC50 values against trypomastigote forms. After this, the trypanocidal effect was evaluated in cultures of infected macrophages using an automatized image analysis protocol. All experiments were performed in the dark and in the clear phase (after a photodynamic exposure). The compounds showed no cytotoxicity in both phases at the tested concentrations. The IC50 values for the sole use of MB and TBO were 2.6 and 1.2 µM, respectively. The photoactivation of the compounds using a fixed energy density (J/cm2) caused a reduction of the IC50 values to 1.0 and 0.9 µM, respectively. It was found that, on infected macrophage, the use of TBO significantly reduced the number of infected cells and parasitic load, and this effect was increased in the presence of light. The results of the present study are indicative that PACT may be considered as both selective and effective therapeutic intervention for treating Chagas disease.


Assuntos
Antiparasitários/farmacologia , Fenotiazinas/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Anti-Infecciosos/farmacologia , Antiparasitários/uso terapêutico , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Doença de Chagas/tratamento farmacológico , Humanos , Luz , Azul de Metileno/química , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Camundongos Endogâmicos BALB C , Carga Parasitária , Fenotiazinas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Cloreto de Tolônio/química , Cloreto de Tolônio/farmacologia , Cloreto de Tolônio/uso terapêutico , Trypanosoma cruzi/efeitos da radiação
17.
Clin Toxicol (Phila) ; 58(6): 495-497, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31446806

RESUMO

Background: Acetaminophen is a common pharmaceutical ingestion reported to US poison centers. In overdose, toxic metabolites are known to cause hepato- and nephrotoxicity. While G6PD deficiency may be a risk factor for methemoglobin production in the setting of acetaminophen overdose, it is rarely reported in patients who do not have this condition.Methods: We present two cases of methemoglobinemia following massive acetaminophen ingestion with no known history of G6PD deficiency or other substances known to induce methemoglobinemia. The two cases had peak methemoglobin measurements of 32% and 12% respectively, and both were treated with methylene blue.Discussion: A number of mechanisms may be involved in production of methemoglobin in the setting of massive acetaminophen ingestion including NAPQI-induced oxidation, depletion of glutathione stores, and production of oxidant-metabolites including paraaminophenol. While it is unlikely that the majority of acetaminophen overdoses result in any clinically significant methemoglobinemia, massive acetaminophen overdose may be complicated by development of methemoglobinemia.Conclusion: Physicians should be aware of the possibility that massive acetaminophen ingestion may be complicated by methemoglobinemia in rare instances. Further studies should aim to characterize the metabolic pathways leading to possible methemoglobinemia in humans after large acetaminophen ingestions.


Assuntos
Acetaminofen/envenenamento , Overdose de Drogas/etiologia , Metemoglobinemia/induzido quimicamente , Acetaminofen/sangue , Acetaminofen/urina , Overdose de Drogas/sangue , Overdose de Drogas/terapia , Overdose de Drogas/urina , Evolução Fatal , Feminino , Humanos , Masculino , Metemoglobina/análise , Metemoglobinemia/sangue , Metemoglobinemia/terapia , Metemoglobinemia/urina , Azul de Metileno/uso terapêutico , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Acta Neuropathol Commun ; 7(1): 210, 2019 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-31843022

RESUMO

Activated Caspase-6 (Casp6) is associated with age-dependent cognitive impairment and Alzheimer disease (AD). Mice expressing human Caspase-6 in hippocampal CA1 neurons develop age-dependent cognitive deficits, neurodegeneration and neuroinflammation. This study assessed if methylene blue (MB), a phenothiazine that inhibits caspases, alters Caspase-6-induced neurodegeneration and cognitive impairment in mice. Aged cognitively impaired Casp6-overexpressing mice were treated with methylene blue in drinking water for 1 month. Methylene blue treatment did not alter Caspase-6 levels, assessed by RT-PCR, western blot and immunohistochemistry, but inhibited fluorescently-labelled Caspase-6 activity in acute brain slice intact neurons. Methylene blue treatment rescued Caspase-6-induced episodic and spatial memory deficits measured by novel object recognition and Barnes maze, respectively. Methylene blue improved synaptic function of hippocampal CA1 neurons since theta-burst long-term potentiation (LTP), measured by field excitatory postsynaptic potentials (fEPSPs) in acute brain slices, was successfully induced in the Schaffer collateral-CA1 pathway in methylene blue-treated, but not in vehicle-treated, Caspase-6 mice. Increased neuroinflammation, measured by ionized calcium binding adaptor molecule 1 (Iba1)-positive microglia numbers and subtypes, and glial fibrillary acidic protein (GFAP)-positive astrocytes, were decreased by methylene blue treatment. Therefore, methylene blue reverses Caspase-6-induced cognitive deficits by inhibiting Caspase-6, and Caspase-6-mediated neurodegeneration and neuroinflammation. Our results indicate that Caspase-6-mediated damage is reversible months after the onset of cognitive deficits and suggest that methylene blue could benefit Alzheimer disease patients by reversing Caspase-6-mediated cognitive decline.


Assuntos
Envelhecimento/metabolismo , Caspase 6/metabolismo , Inibidores de Caspase/uso terapêutico , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/enzimologia , Azul de Metileno/uso terapêutico , Envelhecimento/efeitos dos fármacos , Envelhecimento/patologia , Animais , Inibidores de Caspase/farmacologia , Disfunção Cognitiva/patologia , Feminino , Humanos , Inflamação/tratamento farmacológico , Inflamação/enzimologia , Inflamação/patologia , Masculino , Azul de Metileno/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos
19.
Niger J Clin Pract ; 22(12): 1654-1661, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31793470

RESUMO

Background: Incomplete eradication of plaque bacteria from the plaque retentive sites and the emerging problem of antibiotic resistance led the scientific community to explore new antimicrobial strategies for improved results and shun antibiotic resistance. Objective: The purpose of this in-vitro study was to evaluate the antimicrobial effect of a novel light based therapy and to assess the susceptibility of oral plaque bacteria to light based technologies with and without photosensitizers. Materials and Methods: Four oral plaque bacterial strains were isolated from the dental plaque sample collected from the patients and exposed to various light based technologies and photodynamic therapy (PDT) with and without photosensitizers. The cultures were analysed for viable colony forming unit (CFU) counts. One-way analysis of variance was used to statistically analyse differences and the Student-Newman-Keuls method to perform multiple comparison procedures. Results: All groups showed remarkable reduction in the CFUs as compared to control group with use of light based technologies and PDT in this study. The difference of antimicrobial effect between all tested groups either with light based technologies and PDT with control group showed significant reduction in CFUs. Conclusions: From the results of this study, we concluded that light based technologies and PDT could be a valuable alternative therapy to mechanical debridement in the prevention of growth and recolonisation of oral plaque bacteria.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Placa Dentária/microbiologia , Placa Dentária/terapia , Bolsa Periodontal/microbiologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Bactérias/classificação , Bactérias/isolamento & purificação , Carga Bacteriana/efeitos dos fármacos , Placa Dentária/tratamento farmacológico , Cavidade Pulpar/efeitos dos fármacos , Cavidade Pulpar/microbiologia , Humanos , Técnicas In Vitro , Azul de Metileno/administração & dosagem , Azul de Metileno/uso terapêutico , Bolsa Periodontal/terapia , Fármacos Fotossensibilizantes/administração & dosagem , Fármacos Fotossensibilizantes/uso terapêutico , Titânio
20.
JAAPA ; 32(12): 28-30, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31770301

RESUMO

Methemoglobinemia is a rare and potentially life-threatening medical emergency that can be overlooked when evaluating a patient in respiratory distress. Without early recognition, patients may develop respiratory failure and die. This article describes a teenager who presented to the ED for dyspnea and lightheadedness and failed to respond to supplemental oxygen. She was eventually diagnosed with methemoglobinemia.


Assuntos
Hipóxia/diagnóstico , Metemoglobinemia/diagnóstico , Adolescente , Dispneia/etiologia , Inibidores Enzimáticos/uso terapêutico , Feminino , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Metemoglobinemia/complicações , Metemoglobinemia/terapia , Azul de Metileno/uso terapêutico , Oxigenoterapia
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