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1.
J Intensive Care Med ; 35(8): 797-804, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30021499

RESUMO

Ubiquinol is a fundamental component of cellular metabolism. Low ubiquinol levels have been associated with mortality. This was a substudy of a randomized trial in patients undergoing coronary artery bypass grafting. We drew blood before and after surgery. Ubiquinol or placebo was added to peripheral blood mononuclear cells for oxygen consumption (OCR) measurements. In vivo ubiquinol levels were lower postsurgery compared to presurgery (0.16 µmol/L [quartiles: 0.02-0.39], P = .01), although the difference disappeared when adjusting for hemoglobin levels (P = .30). There was no difference in presurgical basal (1.0 mL/min/mg [95% confidence interval [CI]: -0.9 to 2.2], P = .08) and maximal (0.5 mL/min/mg [95% CI: -4.3 to 7.3], P = .56) OCR in cells receiving ubiquinol or placebo. There was a difference in postsurgical basal (1.1 mL/min/mg [95% CI: 0.9-1.6], P < .001) and maximal (4.2 mL/min/mg [95% CI: 0.3-7.0], P = .01) OCR between the groups. We found no association between ubiquinol and OCR levels (all P > .05).


Assuntos
Ponte de Artéria Coronária , Leucócitos Mononucleares/metabolismo , Consumo de Oxigênio/efeitos dos fármacos , Ubiquinona/análogos & derivados , Idoso , Método Duplo-Cego , Feminino , Humanos , Masculino , Período Pós-Operatório , Período Pré-Operatório , Ensaios Clínicos Controlados Aleatórios como Assunto , Ubiquinona/administração & dosagem , Ubiquinona/sangue
2.
Molecules ; 23(6)2018 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-29914147

RESUMO

(1) Background: Thiamine is an important cofactor for multiple metabolic processes. Its role in cancer has been debated for years. Our aim is to determine if thiamine can convert the cellular metabolic state of breast cancer cells from anaerobic to aerobic, thus reducing their growth. (2) Methods: Breast cancer (MCF7) and non-tumorigenic (MCF10A) cell lines were treated with various doses of thiamine and assessed for changes in cell growth. The mechanism of this relationship was identified through the measurement of enzymatic activity and metabolic changes. (3) Results: A high dose of thiamine reduced cell proliferation in MCF7 (63% decrease, p < 0.0001), but didn't affect apoptosis and the cell-cycle profile. Thiamine had a number of effects in MCF7; it (1) reduced extracellular lactate levels in growth media, (2) increased cellular pyruvate dehydrogenase (PDH) activities and the baseline and maximum cellular oxygen consumption rates, and (3) decreased non-glycolytic acidification, glycolysis, and glycolytic capacity. MCF10A cells preferred mitochondrial respiration instead of glycolysis. In contrast, MCF7 cells were more resistant to mitochondrial respiration, which may explain the inhibitory effect of thiamine on their proliferation. (4) Conclusions: The treatment of MCF7 breast cancer cells with 1 µg/mL and 2 µg/mL of thiamine for 24 h significantly reduced their proliferation. This reduction is associated with a reduction in glycolysis and activation of the PDH complex in breast cancer cells.


Assuntos
Glicólise/efeitos dos fármacos , Ácido Láctico/metabolismo , Complexo Piruvato Desidrogenase/metabolismo , Tiamina/farmacologia , Anaerobiose/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7
3.
Am J Emerg Med ; 35(10): 1500-1502, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28460805

RESUMO

BACKGROUND: Variceal hemorrhage is associated with high morbidity and mortality. A balloon tamponade device (BTD), such as the Sengstaken-Blakemore or Minnesota tube, may be used in cases of variceal hemorrhage. While these devices may be effective at controlling acute bleeding, the effect on patient outcomes remains less clear. We sought to describe the number of patients with variceal hemorrhage and a BTD who survive to discharge, survive to one-year, and develop complications related to a BTD. METHODS: In this retrospective study, we identified patients at a single, tertiary care center who underwent placement of a BTD for upper gastrointestinal hemorrhage between 2003 and 2014. Patient characteristics and outcomes were summarized using descriptive statistics. RESULTS: 34 patients with a BTD were identified. Median age was 57.5 (IQR 47-63) and 76% (26/34) were male. Approximately 59% (20/34) of patients survived to discharge, and 41% (13/32) were alive after one year. Two patients were lost to follow-up. Of those surviving to discharge, 95% (19/20) had undergone transjugular intrahepatic portosystemic shunt (TIPS), while 36% (5/14) of patients who did not survive to discharge had TIPS (p<0.01). One complication, an esophageal perforation, was identified and managed conservatively. CONCLUSION: In this cohort of patients undergoing BTD placement for variceal hemorrhage, approximately 59% of patients were alive at discharge and 41% were alive after one year. Placement of a BTD as a temporizing measure in the management of acute variceal hemorrhage may be helpful, particularly when utilized as a bridge to more definitive therapy.


Assuntos
Oclusão com Balão/métodos , Varizes Esofágicas e Gástricas/terapia , Hemorragia Gastrointestinal/terapia , Idoso , Endoscopia do Sistema Digestório , Varizes Esofágicas e Gástricas/diagnóstico , Varizes Esofágicas e Gástricas/mortalidade , Feminino , Seguimentos , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/mortalidade , Humanos , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento
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