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1.
Sci Adv ; 5(8): eaax1387, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31457100

RESUMO

Adenosine and its receptors play a key role in bone homeostasis and regeneration. Extracellular adenosine is generated from CD39 and CD73 activity in the cell membrane, through conversion of adenosine triphosphate to adenosine monophosphate (AMP) and AMP to adenosine, respectively. Despite the relevance of CD39/CD73 to bone health, the roles of these enzymes in bona fide skeletal disorders remain unknown. We demonstrate that CD39/CD73 expression and extracellular adenosine levels in the bone marrow are substantially decreased in animals with osteoporotic bone loss. Knockdown of estrogen receptors ESR1 and ESR2 in primary osteoprogenitors and osteoclasts undergoing differentiation showed decreased coexpression of membrane-bound CD39 and CD73 and lower extracellular adenosine. Targeting the adenosine A2B receptor using an agonist attenuated bone loss in ovariectomized mice. Together, these findings suggest a pathological association of purine metabolism with estrogen deficiency and highlight the potential of A2B receptor as a target to treat osteoporosis.

2.
Molecules ; 24(14)2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31340614

RESUMO

Photoreactions of acetonitrile solutions of 3,3-diaryl-1,1-dicyano-2-methylprop-1-enes (1a-c) with allyltrimethylsilane (2) in the presence of phenanthrene as a photoredox catalyst and acetic acid as a proton source formed photoallylation (3) and photoreduction (4) products via photoinduced electron transfer pathways. When (S)-mandelic acid was used as the proton source, the reactions proceeded with 3.4 and 4.8 %ee for formation of 3 and 4, respectively. The results of studies of the effect of aryl ring substituents and several chiral carboxylic acids suggested that the enantioselectivities of the reactions are governed by steric controlled proton transfer in intermediate complexes formed by π-π and OH-π interactions of anion radicals derived from 1a-c and chiral carboxylic acids.


Assuntos
Ácidos Carboxílicos/química , Nitrilos/química , Fenantrenos/química , Prótons , Compostos de Trimetilsilil/química , Ácido Acético/química , Alcenos/química , Ânions , Catálise , Radicais Livres , Hidrogenação , Luz , Processos Fotoquímicos , Estereoisomerismo
3.
Chemistry ; 21(37): 12927-39, 2015 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-26212577

RESUMO

Heterometal arrays in molecular aggregations were obtained by the spontaneous and ultrasound-induced gelation of organic liquids containing the chiral, clothespin-shaped trans-bis(salicylaldiminato) d8 transition-metal complexes 1. Heterometallic mixtures of complexes 1 a (Pd) and 1 b (Pt) underwent strict heterochiral aggregation entirely due to the organic shell structure of the clothespin shape, with no effect of the metal cores. This phenomenon provides an unprecedented means of generating highly controlled heterometallic arrangements such as alternating sequences [(+)-Pd(-)-Pt(+)-Pd(-)-Pt⋅⋅⋅] as well as a variety of single metal-enriched arrays (e.g., [(+)-Pt(-)-Pd(+)-Pd(-)-Pd(+)-Pd(-)-Pd⋅⋅⋅] and [(+)-Pd(-)-Pt(+)-Pt(-)-Pt(+)-Pt(-)-Pt⋅⋅⋅]) upon the introduction of an optically active masquerading unit with a different metal core in the heterochiral single-metal sequence. The present method can be applied to form various new aggregates with optically active Pd and Pt units, to allow 1) tuning of the gelation ultrasound sensitivity based on the different hearing abilities of the metal units; 2) aggregation-induced chirality transfer between heterometallic species; and 3) aggregation-induced chirality enhancement. A mechanistic rationale is proposed for these molecular aggregations based on the molecular structures of the units and the morphologies of the aggregates.

4.
Hepatol Res ; 43(5): 459-66, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23046471

RESUMO

AIM: To test if the treatment adherence to branched-chain amino acid (BCAA) granules influences the serum albumin level and prognosis in prospective 2984 patients with decompensated liver cirrhosis who were prescribed BCAA granules containing 952 mg of L-isoleucine, 1904 mg of L-leucine and 1144 mg of L-valine at 4.15 g/sachet three times a day after meals. METHODS: The primary end-point was the time to the event defined as "hospital admission due to progression of hepatic failure", and factors affecting this outcome were explored. Changes in serum albumin level were evaluated as the secondary end-point. RESULTS: Patients were divided into the good adherence group (those who reported to have taken "nearly all" prescribed doses) and the poor adherence group (those who reported to have taken "approximately half" or "less" doses), because such stratification was validated by treatment responses in plasma BCAA/tyrosine ratio. Factors related to the primary end-point were age, drug adherence during 6 months of study treatment, previous hepatic cancer, current clinical manifestations, previous clinical manifestations, baseline serum albumin level, platelet count and total bilirubin level. The cumulative event-free survival was significantly higher in the good adherence group. Increase in the serum albumin level was also greater in the good adherence group. CONCLUSION: Higher BCAA treatment adherence better raised the serum albumin level, leading to improvement of event-free survival. These results indicate the importance of patient instruction for the adequate use of BCAA granules.

5.
Biologicals ; 40(6): 421-5, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23041594

RESUMO

RD-114 virus is a feline endogenous retrovirus that exists in the genome of all cats. It can be assumed that feline and canine live vaccines manufactured by culturing cells of feline origin are contaminated with the virus. The current study is attempted to develop a product enhanced reverse transcriptase (PERT) assay to detect replication-competent RD-114 virus. Since culture supernatants of Crandell-Rees feline kidney (CRFK) cells do not have detectable reverse transcriptase activity in case of do not passage on other cell lines, these results raise the possibility that RD-114 virus grow efficiently in other retrovirus producing cell lines. For the PERT assay, RD-114 virus isolated from CRFK cells may need to be passaged more than four times on 293T cells to be expressed at appreciable levels. The PERT assay described here provides an accurate method for determining the presence of RD-114 in culture supernatants and will help monitor live vaccines produced in endogenous virus producing cell lines.


Assuntos
Retrovirus Endógenos/metabolismo , DNA Polimerase Dirigida por RNA/metabolismo , Animais , Sequência de Bases , Gatos , Linhagem Celular , Primers do DNA , Retrovirus Endógenos/enzimologia , Células HEK293 , Humanos , Reação em Cadeia da Polimerase em Tempo Real
6.
J Am Chem Soc ; 133(40): 16054-61, 2011 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-21894951

RESUMO

Instant and precise control of phosphorescent emission can be performed by ultrasound-induced gelation of organic liquids with chiral, clothespin-shaped trans-bis(salicylaldiminato)Pt(II) complexes, anti-1. Nonemissive solutions of racemic, short-linked anti-1a (n = 5) and optically pure, long-linked anti-1c (n = 7) in organic liquids are transformed immediately into stable phosphorescent gels upon brief irradiation of low-power ultrasound. Emission from the gels can be controlled by sonication time, linker length, and optical activity of the complexes. Several experimental results indicated that structure-dependent homo- and heterochiral aggregations and ultrasound-control of the aggregate morphology are key factors for emission enhancement.


Assuntos
Géis/química , Substâncias Luminescentes/química , Compostos Organoplatínicos/química , Ultrassom
7.
J Gastroenterol ; 38(3): 278-82, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-12673452

RESUMO

We describe a case of biliary cystadenocarcinoma that showed a longterm clinical course. A 69-year-old Japanese man was admitted to our hospital because of abdominal discomfort. The patient had been diagnosed with benign cystadenoma of the liver at another hospital in 1987 and had been followed up for 10 years. Abdominal ultrasonography (US) and computed tomography (CT) scan demonstrated a unilocular cystic lesion, which included multiple conspicuous papillary protrusions in the left hepatic lobe. Left lateral segmentectomy was performed, and intraoperative cholangiography revealed a communication between the cystic tumor and intrahepatic bile duct. The tumor contained clear mucinous fluid and enfolded multiple yellowish papillary projections on the cystic wall. Histological examination showed the tumor to be biliary cystadenocarcinoma. The patient is doing well 4 years after the operation.


Assuntos
Neoplasias dos Ductos Biliares/diagnóstico , Cistadenocarcinoma/diagnóstico , Cistadenoma/diagnóstico , Erros de Diagnóstico , Ducto Hepático Comum , Neoplasias Hepáticas/diagnóstico , Abdome/diagnóstico por imagem , Idoso , Neoplasias dos Ductos Biliares/cirurgia , Cistadenocarcinoma/cirurgia , Cistadenoma/cirurgia , Artéria Hepática/diagnóstico por imagem , Ducto Hepático Comum/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/cirurgia , Imagem por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , Ultrassonografia
8.
J Clin Gastroenterol ; 34(1): 77-80, 2002 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11743251

RESUMO

BACKGROUND: Although biliary expandable metallic stents (EMS) improve patency, they are unsuitable for primary biliary stenting. Although plastic tube stents without side holes (PWOS) are also reported to prolong patency, their efficacy remains controversial. GOALS: To evaluate clinical utility and relative advantages, we reviewed clinical results of three types of stents: plastic tube stents with side holes (PS), PWOS, and EMS. STUDY: The 130 patients comprised 56 with pancreatic cancers, 26 with gallbladder cancers, 21 with bile duct cancers, and 27 with other malignant diseases. Plastic tube stents with side holes (10 French [Fr]), PWOS (10 Fr), and EMS (30 Fr) were inserted in 64, 28, and 38 cases, respectively. RESULTS: Overall cumulative stent patency rates for EMS and PWOS groups were significantly higher than that of PS. This was also the case with middle and lower biliary tract strictures and with pancreas cancers. In Japan, medical costs with endoscopic retrograde cholangiopancreatography ($631.00) divided by the mean patent period with PS, PWOS, and EMS were $8.80/d, $4.60/d, and $20.40/d, respectively. CONCLUSION: We recommend PWOS for primary biliary stenting of middle and lower biliary strictures, especially those caused by pancreatic cancer, based on its lower price and sufficient patency without replacement after diagnosis of inoperability.


Assuntos
Doenças dos Ductos Biliares/cirurgia , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças dos Ductos Biliares/etiologia , Distribuição de Qui-Quadrado , Constrição Patológica/cirurgia , Análise Custo-Benefício , Drenagem/instrumentação , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polietilenos , Estudos Retrospectivos , Stents/economia , Resultado do Tratamento
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