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1.
J Reprod Dev ; 69(3): 163-169, 2023 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-37045747

RESUMO

Lysophosphatidic acid (LPA) has been implicated in the uterine endometrial functions of implantation and decidualization; however, not much is known about its myometrial contractile function. Herein we characterized the uterotonic effects of LPA in non-pregnant (estrus) and peri-parturient rats in vitro. LPA dose-dependently (0.01-10 µM) stimulated the amplitude and integral, but not the frequency, of the uterine strip contraction of estrous rats. The stimulatory effect of LPA was enhanced 1 day before parturition but was lost 1 day postpartum. LPA did not cause the de novo synthesis of prostaglandin (PG) F2α but stimulated contractions cooperatively with the PG. LPA-induced contractions were significantly inhibited by an LPA1/2/3 antagonist in the uteri of estrous rats but not in term rats. This study characterized the uterotonic effect of a natural LPA that occurs at physiological concentrations, changes with reproductive states, and is independent of mediation by the newly synthesized PG.


Assuntos
Contração Uterina , Útero , Gravidez , Feminino , Ratos , Animais , Lisofosfolipídeos/farmacologia , Endométrio , Receptores de Ácidos Lisofosfatídicos
2.
Chem Pharm Bull (Tokyo) ; 64(6): 650-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27250800

RESUMO

We investigated the kinetics of in vitro transformation of a dichlorinated propyl paraben (2-propyl 3,5-dichloro-4-hydroxybenzoate; Cl2PP) by the rat liver S9 fraction and assessed the aryl hydrocarbon receptor (AhR) agonist activity of the metabolite products identified in HPLC and GC/MS analysis and by metabolite syntheses. The results indicated that the chlorination of Cl2PP reduced its degradation rate by approximately 40-fold. Two hydroxylated metabolite products showed AhR agonist activity of up to 39% of that of the parent Cl2PP when assessed in a yeast (YCM3) reporter gene assay. The determination of the metabolic properties of paraben bioaccumulation presented here provides further information on the value of risk assessments of chlorinated parabens as a means to ensure human health and environmental safety.


Assuntos
Microssomos Hepáticos/metabolismo , Parabenos/farmacologia , Receptores de Hidrocarboneto Arílico/agonistas , Animais , Cinética , Microssomos Hepáticos/química , Estrutura Molecular , Parabenos/química , Parabenos/metabolismo , Ratos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
3.
Gan To Kagaku Ryoho ; 42(5): 617-9, 2015 May.
Artigo em Japonês | MEDLINE | ID: mdl-25981658

RESUMO

Here, we report about a 60-year-old woman with metastatic breast cancer who was successfully treated for paclitaxelinduced peripheral neuropathy with duloxetine. She was administered trastuzumab plus paclitaxel(PTX)combination therapy that was ultimately discontinued because of grade 3 peripheral neuropathy detected on day 15, according to the CTCAE (v4.0). She was administered duloxetine on day 90 after the end of the previous therapy because of the peripheral neuropathy. Thereafter, the peripheral neuropathy decreased to grade 1, which enabled PTX administration on her request. Further trials are required to confirm the efficacy of duloxetine.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/efeitos adversos , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Tiofenos/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/patologia , Cloridrato de Duloxetina , Feminino , Humanos , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Trastuzumab
4.
J Steroid Biochem Mol Biol ; 103(3-5): 222-6, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17207991

RESUMO

1alpha,25-Dihydroxy-2beta-(3-hydroxypropoxy)vitamin D(3) (ED-71), an analog of active vitamin D(3), 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], possesses a hydroxypropoxy substituent at the 2beta-position of 1,25(OH)(2)D(3). ED-71 has potent biological effects on bone and is currently under phase III clinical studies for bone fracture prevention. It is well-known that the synthesis and secretion of parathyroid hormone (PTH) is regulated by 1,25(OH)(2)D(3). Interestingly, during clinical development of ED-71, serum intact PTH in osteoporotic patients did not change significantly upon treatment with ED-71. The reason remains unclear, however. Brown et al. reported that 3-epi-1,25(OH)(2)D(3), an epimer of 1,25(OH)(2)D(3) at the 3-position, shows equipotent and prolonged activity compared to 1,25(OH)(2)D(3) at suppressing PTH secretion. Since ED-71 has a bulky hydroxypropoxy substituent at the 2-position, epimerization at the adjacent and sterically hindered 3-position might be prevented, which may account for its weak potency in PTH suppression observed in clinical studies. We have significant interest in ED-71 epimerization at the 3-position and the biological potency of 3-epi-ED-71 in suppressing PTH secretion. In the present studies, synthesis of 3-epi-ED-71 and investigations of in vitro suppression of PTH using bovine parathyroid cells are described. The inhibitory potency of vitamin D(3) analogs were found to be 1,25(OH)(2)D(3)>ED-71> or =3-epi-1,25(OH)(2)D(3)>>3-epi-ED-71. ED-71 and 3-epi-ED-71 showed weak activity towards PTH suppression in our assays.


Assuntos
Calcitriol/análogos & derivados , Animais , Calcitriol/síntese química , Calcitriol/química , Calcitriol/farmacologia , Bovinos , Células Cultivadas , Humanos , Estrutura Molecular , Glândulas Paratireoides/efeitos dos fármacos , Glândulas Paratireoides/metabolismo , Vitamina D/análogos & derivados
5.
Bioorg Med Chem ; 14(23): 8050-6, 2006 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-16908172

RESUMO

A 3-position diastereomer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71, 2), 3-epi-ED-71 (4), was synthesized by the convergent method coupling the A-ring fragment (5) with the C/D-ring fragment (6). As the results of preliminary in vitro biological evaluation of 3-epi-ED-71 (4), the inhibition of parathyroid hormone secretion in bovine parathyroid cells and binding affinity to human recombinant vitamin D receptor and to human vitamin D binding protein in comparison with ED-71 (2), 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, 1), and 3-epi-1,25(OH)2D3 (3) are described.


Assuntos
Colecalciferol/síntese química , Colecalciferol/farmacologia , Animais , Bovinos , Colecalciferol/química , Glândulas Paratireoides/citologia , Hormônio Paratireóideo/antagonistas & inibidores , Hormônio Paratireóideo/metabolismo , Ligação Proteica , Receptores de Calcitriol/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade
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