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J Int Soc Sports Nutr ; 18(1): 60, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34503541


BACKGROUND: Numerous studies have demonstrated the efficacy of creatine supplementation for improvements in exercise performance. Few studies, however, have examined the effects of phosphocreatine supplementation on exercise performance. Furthermore, while polyphenols have antioxidant and anti-inflammatory properties, little is known regarding the influence of polyphenol supplementation on muscular strength, power, and endurance. Thus, the purpose of the present study was to compare the effects of 28 days of supplementation with phosphocreatine disodium salts plus blueberry extract (PCDSB), creatine monohydrate (CM), and placebo on measures of muscular strength, power, and endurance. METHODS: Thirty-three men were randomly assigned to consume either PCDSB, CM, or placebo for 28 days. Peak torque (PT), average power (AP), and percent decline for peak torque (PT%) and average power (AP%) were assessed from a fatigue test consisting of 50 maximal, unilateral, isokinetic leg extensions at 180°·s- 1 before and after the 28 days of supplementation. Individual responses were assessed to examine the proportion of subjects that exceeded a minimal important difference (MID). RESULTS: The results demonstrated significant (p < 0.05) improvements in PT for the PCDSB and CM groups from pre- (99.90 ± 22.47 N·m and 99.95 ± 22.50 N·m, respectively) to post-supplementation (119.22 ± 29.87 N·m and 111.97 ± 24.50 N·m, respectively), but no significant (p = 0.112) change for the placebo group. The PCDSB and CM groups also exhibited significant improvements in AP from pre- (140.18 ± 32.08 W and 143.42 ± 33.84 W, respectively) to post-supplementation (170.12 ± 42.68 W and 159.78 ± 31.20 W, respectively), but no significant (p = 0.279) change for the placebo group. A significantly (p < 0.05) greater proportion of subjects in the PCDSB group exceeded the MID for PT compared to the placebo group, but there were no significant (p > 0.05) differences in the proportion of subjects exceeding the MID between the CM and placebo groups or between the CM and PCDSB groups. CONCLUSIONS: These findings indicated that for the group mean responses, 28 days of supplementation with both PCDSB and CM resulted in increases in PT and AP. The PCDSB, however, may have an advantage over CM when compared to the placebo group for the proportion of individuals that respond favorably to supplementation with meaningful increases in muscular strength.

Força Muscular/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Fosfocreatina/farmacologia , Resistência Física/efeitos dos fármacos , Extratos Vegetais/farmacologia , Mirtilos Azuis (Planta)/química , Creatina , Suplementos Nutricionais , Método Duplo-Cego , Humanos , Masculino , Torque , Adulto Jovem
Proc Natl Acad Sci U S A ; 110(40): 16127-32, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-24043769


Stabilization of p53 in erythroid precursors in response to nucleosomal stress underlies the hypoplastic anemia in myelodysplastic syndromes (MDS) with chromosome 5q deletion [del(5q)]. We investigated whether cenersen, a clinically active 20-mer antisense oligonucleotide complementary to TP53 exon10, could suppress p53 expression and restore erythropoiesis in del(5q) MDS. Cenersen treatment of ribosomal protein S-14-deficient erythroblasts significantly reduced cellular p53 and p53-up-regulated modulator of apoptosis expression compared with controls, accompanied by a significant reduction in apoptosis and increased cell proliferation. In a two-stage erythroid differentiation assay, cenersen significantly suppressed nuclear p53 in bone marrow CD34+ cells isolated from patients with del(5q) MDS, whereas erythroid burst recovery increased proportionally to the magnitude of p53 suppression without evidence of del(5q) clonal suppression (r = -0.6; P = 0.005). To explore the effect of p53 suppression on erythropoiesis in vivo, dexamethasone, a glucocorticoid receptor-dependent p53 antagonist, was added to lenalidomide treatment in eight lower-risk, transfusion-dependent, del(5q) MDS patients with acquired drug resistance. Transfusion independence was restored in five patients accompanied by expansion of erythroid precursors and decreased cellular p53 expression. We conclude that targeted suppression of p53 could support effective erythropoiesis in lenalidomide-resistant del(5q) MDS.

Eritropoese/efeitos dos fármacos , Síndromes Mielodisplásicas/metabolismo , Oligonucleotídeos/farmacologia , Proteína Supressora de Tumor p53/antagonistas & inibidores , Sequência de Bases , Dexametasona , Resistência a Medicamentos/fisiologia , Células Precursoras Eritroides/efeitos dos fármacos , Citometria de Fluxo , Imunofluorescência , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Lenalidomida , Dados de Sequência Molecular , Síndromes Mielodisplásicas/genética , Oligonucleotídeos/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Estatísticas não Paramétricas , Talidomida/análogos & derivados , Resultado do Tratamento , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
Leuk Lymphoma ; 53(2): 218-24, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21827374


Patients with chronic lymphocytic leukemia (CLL) with deletion or mutation of TP53 have exceedingly poor clinical outcomes. Cenersen, an oligonucleotide targeting TP53, has been shown to abrogate the activity of TP53 gain-of-function mutants and to increase sensitivity of lymphoma cells to cytotoxic chemotherapy in vitro. We combined cenersen with fludarabine, cyclophosphamide and rituximab (FCR) as treatment for patients with high-risk CLL. The purpose of this phase II study was to determine the overall response rate, response duration and toxicity of cenersen administered in combination with FCR. Twenty patients with relapsed or high-risk CLL were evaluated. Nineteen patients were previously treated. The complete response rate was 18%; the overall response rate was 53%. Median progression-free and overall survival was 5.3 and 10.6 months, respectively. The most common serious adverse events were neutropenia and thrombocytopenia. In this single arm phase II study, cenersen combined with FCR yielded clinical responses with acceptable toxicity in patients with high-risk CLL.

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Oligonucleotídeos/uso terapêutico , Proteína Supressora de Tumor p53/antagonistas & inibidores , Idoso , Anticorpos Monoclonais Murinos/administração & dosagem , Ciclofosfamida/administração & dosagem , Feminino , Seguimentos , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação/genética , Prognóstico , Fatores de Risco , Rituximab , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genética , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
J Nat Prod ; 74(9): 1833-41, 2011 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-21875098


Two trimeric proanthocyanidins, cinnamtannin B-1 (1) and cinnamtannin D-1 (2), have been isolated from the bark of Cinnamomum cassia along with the known tetramer parameritannin A-1 (3) and a previously unreported tetramer, named cassiatannin A (4). The structures of 1-4 were elucidated on the basis of 1D and 2D NMR, MS, and CD analyses and compared to the reported data. Proanthocyanidins (1-4) possess significant in vitro inhibitory activity against cyclooxygenase-2 (COX-2) at micromolar concentrations.

Cinnamomum aromaticum/química , Inibidores de Ciclo-Oxigenase 2/isolamento & purificação , Inibidores de Ciclo-Oxigenase 2/farmacologia , Proantocianidinas/isolamento & purificação , Proantocianidinas/farmacologia , Inibidores de Ciclo-Oxigenase 2/química , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Casca de Planta/química , Proantocianidinas/química