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1.
Nephron ; 143(2): 77-85, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31117088

RESUMO

BACKGROUND: Enarodustat (JTZ-951) is an orally available hypoxia-inducible factor prolyl hydroxylase inhibitor that increases endogenous erythropoietin levels in the treatment of anemia associated with chronic kidney disease (CKD). OBJECTIVE: A phase 2b study of enarodustat to assess the hemoglobin (Hb) response, safety, and maintenance dosage was conducted in Japanese anemic patients with hemodialysis-dependent CKD. METHODS: Subjects receiving a stable dose of an erythropoiesis-stimulating agent were randomized to receive once-daily enarodustat at a dose of 2, 4, or 6 mg or placebo in a double-blind manner for 6 weeks (Period 1) followed by 24-week open treatment with enarodustat, adjusted in the range of 2-8 mg to maintain Hb within a target range (10.0-12.0 g/dL; Period 2). RESULTS: Change in Hb from baseline increased with enarodustat dose in Period 1. In Period 2, the proportion of subjects who maintained their Hb level within the target range at the end of treatment was 65.1%. To maintain Hb levels within the target range over the course of Period 2, approximately 80% of subjects required 2 dose adjustments or fewer. Enarodustat decreased hepcidin and ferritin levels, increased total iron-binding capacity, and was generally well tolerated. CONCLUSIONS: Enarodustat corrected and maintained Hb levels in anemic patients with hemodialysis-dependent CKD. Phase 3 studies of enarodustat are currently ongoing.


Assuntos
Anemia/tratamento farmacológico , Anemia/etiologia , Glicinas N-Substituídas/administração & dosagem , Piridinas/administração & dosagem , Diálise Renal , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/terapia , Triazóis/administração & dosagem , Idoso , Anemia/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/efeitos adversos , Feminino , Ferritinas/sangue , Hemoglobinas/metabolismo , Hepcidinas/sangue , Humanos , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Glicinas N-Substituídas/efeitos adversos , Piridinas/efeitos adversos , Insuficiência Renal Crônica/sangue , Triazóis/efeitos adversos
2.
Am J Nephrol ; 49(2): 165-174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30699415

RESUMO

BACKGROUND: Enarodustat (JTZ-951) is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor that mimics adaptive responses to hypoxic conditions and may provide a new therapeutic approach for managing anemia in patients with chronic kidney disease (CKD). We evaluated the efficacy, safety, and maintenance dose of enarodustat in anemic patients with CKD not on dialysis. METHODS: Erythropoiesis-stimulating agent (ESA) naïve patients (correction group) and patients on a stable dose of ESA (conversion group) were randomized to receive 2, 4, or 6 mg of enarodustat or placebo once daily for 6 weeks in a double-blind manner (Period 1) followed by 24 weeks of open enarodustat treatment to maintain their hemoglobin (Hb) levels within a target range of 10.0-12.0 g/dL in reference to a dose adjustment algorithm (Period 2). RESULTS: In the correction group, Hb level increase rate per week increased in a dose-response manner. The proportion of subjects in the conversion group who maintained Hb levels within ± 1.0 g/dL of baseline did not differ between each enarodustat arm and placebo arm during Period 1. Over 70% of subjects in both groups maintained Hb levels within the target range at the end of treatment in Period 2. The mean prescribed doses were 3.58 and 3.74 mg/day in the correction group and the conversion group, respectively. Enarodustat was associated with decreases in hepcidin and ferritin and increased total iron-binding capacity and was generally well tolerated. CONCLUSIONS: Enarodustat corrects and maintains Hb levels in anemic patients with CKD not on dialysis.


Assuntos
Anemia/tratamento farmacológico , Hematínicos/administração & dosagem , Prolina Dioxigenases do Fator Induzível por Hipóxia/antagonistas & inibidores , Glicinas N-Substituídas/administração & dosagem , Piridinas/administração & dosagem , Insuficiência Renal Crônica/complicações , Triazóis/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anemia/sangue , Anemia/etiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eritropoetina/sangue , Eritropoetina/metabolismo , Feminino , Ferritinas/sangue , Seguimentos , Hematínicos/efeitos adversos , Hemoglobinas/análise , Hepcidinas/sangue , Humanos , Japão , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Glicinas N-Substituídas/efeitos adversos , Placebos/administração & dosagem , Placebos/efeitos adversos , Piridinas/efeitos adversos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/metabolismo , Fatores de Tempo , Resultado do Tratamento , Triazóis/efeitos adversos
3.
Neuropsychol Rehabil ; 20(4): 624-36, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20467963

RESUMO

Several cognitive therapies have been developed for patients with schizophrenia. However, little is known about the outcomes of these therapies in terms of non-verbal/visuospatial working memory, even though this may affect patients' social outcomes. In the present pilot study, we investigated the effect of a structured floral arrangement (SFA) programme, where participants were required to create symmetrical floral arrangements. In this programme, the arrangement pattern and the order of placing each of the natural materials was predetermined. Participants have to identify where to place each material, and memorise the position temporarily to complete the floral arrangement. The schizophrenic patients who participated in this programme showed significant improvement in their scores for a block-tapping task backward version; whereas, non-treated control patients did not show such an improvement. The present results suggest that the SFA programme may positively stimulate visuospatial working memory in patients.


Assuntos
Terapia Cognitivo-Comportamental/métodos , Transtornos da Memória/etiologia , Transtornos da Memória/reabilitação , Memória de Curto Prazo/fisiologia , Esquizofrenia/complicações , Comportamento Espacial/fisiologia , Adulto , Feminino , Flores , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Desempenho Psicomotor/fisiologia
4.
J Telemed Telecare ; 14(4): 215-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18534958

RESUMO

We conducted videophone conversations with elderly adults living in a nursing home to discover whether their verbal ability was improved by repeated remote conversations. The control group comprised five elderly adults. The experimental group comprised six elderly adults, including three patients with dementia. They took part in three videophone conversations and their verbal ability was measured before and after the conversations. During the sessions, the participants and volunteers talked about themselves and participated in a quiz. In the experimental group, the mean number of words generated increased from 4.8 to 6.5 after the session (P < 0.05); this increase was not observed in the control group. The experimental group also showed an improvement in words generated after indirect conversations. Videophone conversations appear to have some positive effects on verbal ability and may be beneficial in the cognitive rehabilitation of elderly adults.


Assuntos
Comunicação , Comportamento Verbal/fisiologia , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/reabilitação , Feminino , Idoso Fragilizado/psicologia , Humanos , Masculino , Projetos Piloto , Comunicação por Videoconferência/estatística & dados numéricos
5.
J Neurol Sci ; 225(1-2): 143-8, 2004 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-15465098

RESUMO

A 69-year-old woman developed subacute cerebellar ataxia and tremors in all four limbs in April 1996. Laboratory examination showed elevated antibodies against Ro and La. Head magnetic resonance imaging showed T(2) high-intensity lesions in the cerebellar white matter bilaterally and later in the pons. In April 2000, she died of multiple organ failure with incidental colon cancer. The autopsy showed atrophic parotid glands with an accumulation of lymphocytes around the ducts, confirming the diagnosis of Sjogren's syndrome histopathologically. The neuropathological examination revealed severe necrotic lesions in the cerebellar white matter bilaterally with several foci of perivenous demyelination in the periphery of the lesions and similar demyelinated areas in the pons. Immunohistochemistry with anti-JC virus antibody demonstrated no positive inclusions. A single focus of granulomatous arteritis was observed in one subarachnoid artery. The combination of Sjogren's syndrome, granulomatous angitis, and foci of perivenous demyelination suggests that an autoimmune mechanism played an important role in causing the necrotic lesions in the cerebellar white matter in this case.


Assuntos
Cerebelo/patologia , Doenças Desmielinizantes/patologia , Síndrome de Sjogren/patologia , Idoso , Autopsia/métodos , Córtex Cerebelar , Doenças Desmielinizantes/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Necrose , Estudos Retrospectivos , Síndrome de Sjogren/complicações , Coloração e Rotulagem/métodos
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