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1.
J Pharm Pharmacol ; 67(11): 1512-8, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26285918

RESUMO

OBJECTIVES: Objectives of this study are investigating the initial dissolution kinetics of the cocrystal of carbamazepine (CBZ) with nicotinamide (NIC) and understanding its initial dissolution process. METHODS: Cocrystal solids of CBZ with NIC were prepared by co-milling and solvent evaporation methods. The formation of cocrystal solid was verified via X-ray diffraction measurement. Dissolution tests of the solids were performed using an original flow cell and ultraviolet-visible spectroscopic detector. The spectra monitored in situ were analyzed to determine the dissolved compounds separately using the classical least squares regression method. The initial dissolution profiles were interpreted using simultaneous model of dissolution and phase changes. KEY FINDINGS: In the initial dissolution, CBZ in the cocrystal structure dissolved in water and it was suggested that CBZ reached a metastable intermediate state simultaneously with dissolution. The cocrystal solid prepared by solvent evaporation provided a higher rate constant of the phase change than that prepared by co-milling. Our results thus support the use of evaporation as the method of choice to produce ordered cocrystal structures. CONCLUSION: We suggest that CBZ forms dihydrate during the dissolution process; however, during the initial phase of dissolution, CBZ changes to a metastable intermediate phase.


Assuntos
Carbamazepina/química , Química Farmacêutica/métodos , Niacinamida/química , Cristalização , Cinética , Análise dos Mínimos Quadrados , Solubilidade , Espectrofotometria Ultravioleta , Difração de Raios X
2.
Int J Emerg Ment Health ; 15(3): 181-96, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24558747

RESUMO

International Medical Corps and TELL, a local mental health non-profit organization in Japan, collaborated to develop localized Psychological First Aid (PFA) training of welfare and volunteer organizations supporting survivors of the Japan March 11, 2011 triple disaster The trainings significantly increased participants 'perceived competency in applying PFA principles and in interacting with the disaster affected populations in a safe manner The collaboration between International Medical Corps and TELL in developing, implementing and evaluating the training has potential to inform PFA activities in other disaster affected settings.


Assuntos
Intervenção em Crise/educação , Desastres , Conhecimentos, Atitudes e Prática em Saúde , Competência Profissional , Autoimagem , Sobreviventes/psicologia , Adulto , Terremotos , Acidente Nuclear de Fukushima , Humanos , Japão , Organizações/organização & administração , Tsunamis , Recursos Humanos
3.
Nat Immunol ; 12(1): 37-44, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21102435

RESUMO

The poly(ADP-ribose) polymerases (PARPs) participate in many biological and pathological processes. Here we report that the PARP-13 shorter isoform (ZAPS), rather than the full-length protein (ZAP), was selectively induced by 5'-triphosphate-modified RNA (3pRNA) and functioned as a potent stimulator of interferon responses in human cells mediated by the RNA helicase RIG-I. ZAPS associated with RIG-I to promote the oligomerization and ATPase activity of RIG-I, which led to robust activation of IRF3 and NF-κB transcription factors. Disruption of the gene encoding ZAPS resulted in impaired induction of interferon-α (IFN-α), IFN-ß and other cytokines after viral infection. These results indicate that ZAPS is a key regulator of RIG-I signaling during the innate antiviral immune response, which suggests its possible use as a therapeutic target for viral control.


Assuntos
Infecções por Avulavirus/metabolismo , RNA Helicases DEAD-box/metabolismo , Vírus da Doença de Newcastle/fisiologia , Infecções por Orthomyxoviridae/metabolismo , Orthomyxoviridae/fisiologia , Poli(ADP-Ribose) Polimerases/metabolismo , Isoformas de Proteínas/metabolismo , Infecções por Avulavirus/imunologia , Proteína DEAD-box 58 , RNA Helicases DEAD-box/imunologia , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/imunologia , Células HEK293 , Humanos , Imunidade Inata , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Vírus da Doença de Newcastle/patogenicidade , Orthomyxoviridae/patogenicidade , Infecções por Orthomyxoviridae/imunologia , Poli I-C/imunologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/imunologia , Isoformas de Proteínas/genética , Isoformas de Proteínas/imunologia , RNA Interferente Pequeno/genética , Proteínas de Ligação a RNA , Receptores Imunológicos , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Replicação Viral/genética
4.
Microbiol Immunol ; 53(11): 595-602, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19903259

RESUMO

Sixty Gram-negative bacterial isolates were collected from Palestinian hospitals in 2006. Thirty-two (53.3%) isolates showed multidrug resistance phenotypes. PCR and DNA sequencing were used to characterize integrons and antimicrobial resistance genes. PCR screening showed that 19 (31.7%) and five (8.3%) isolates were positive for class 1 and class 2 integrons, respectively. DNA-sequencing results for the captured antimicrobial resistance gene cassettes within class 1 integrons identified the following genes: dihydrofolate reductases, dfrA1, dfrA5, dfrA7, dfrA12, dfrA17 and dfrA25; aminoglycoside adenyltransferases, aadA1, aadA2, aadA5, aadA12 and aadB; aminoglycoside acetyltransferase, aac(6')-Ib; and chloramphenicol resistance gene, cmlA1. ESBL were identified in 25 (41.7%) isolates. The identified ESBL were bla(CTX-M-15), bla(CTX-M-56), bla(OXA-1), bla(SHV-1), bla(SHV-12), bla(SHV-32) and bla(TEM-1) genes. Moreover, we characterized the plasmid-mediated quinolone resistance genes, aac(6')-Ib-cr and qnrB2, which were detected in seven (11.7%) and two (3.3%) isolates, respectively. In this study various types of antibiotic resistance genes have been identified in Gram-negative bacteria from Palestinian hospitals, many of which are reported in the Middle East area for the first time.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Genes Bacterianos , Bactérias Gram-Negativas/genética , Hospitais , Integrons , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Oriente Médio , Plasmídeos , Quinolonas/farmacologia , beta-Lactamases/genética
5.
Acta Vet Scand ; 51: 46, 2009 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-19930691

RESUMO

Imported animals, especially those from developing countries, may constitute a potential hazard to native animals and to public health. In this study, a new flock of lesser flamingos imported from Tanzania to Hiroshima Zoological Park were screened for multidrug-resistant Gram-negative bacteria, integrons and antimicrobial resistance genes. Thirty-seven Gram-negative bacterial isolates were obtained from the flamingos. Seven isolates (18.9%) showed multidrug resistance phenotypes, the most common being against: ampicillin, streptomycin, tetracycline, trimethoprim/sulfamethoxazole and nalidixic acid. Molecular analyses identified class 1 and class 2 integrons, beta-lactamase-encoding genes, blaTEM-1 and blaCTX-M-2 and the plasmid-mediated quinolone resistance genes, qnrS and qnrB. This study highlights the role of animal importation in the dissemination of multidrug-resistant bacteria, integrons and antimicrobial resistance genes from one country to another.


Assuntos
Animais de Zoológico/microbiologia , Doenças das Aves/microbiologia , Bactérias Gram-Negativas/fisiologia , Infecções por Bactérias Gram-Negativas/veterinária , Animais , Anti-Infecciosos/farmacologia , Aves , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Farmacorresistência Bacteriana Múltipla/genética , Genes MDR/genética , Bactérias Gram-Negativas/classificação , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/microbiologia , Japão , Tanzânia
6.
Appl Environ Microbiol ; 73(20): 6686-90, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17720829

RESUMO

A total of 232 isolates of gram-negative bacteria were recovered from mammals, reptiles, and birds housed at Asa Zoological Park, Hiroshima prefecture, Japan. Forty-nine isolates (21.1%) showed multidrug resistance phenotypes and harbored at least one antimicrobial resistance gene. PCR and DNA sequencing identified class 1 and class 2 integrons and many beta-lactamase-encoding genes, in addition to a novel AmpC beta-lactamase gene, bla(CMY-26). Furthermore, the plasmid-mediated quinolone resistance genes qnr and aac(6')-Ib-cr were also identified.


Assuntos
Animais de Zoológico/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Integrons , Animais , Bactérias Gram-Negativas/genética , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA , beta-Lactamases/genética
7.
Eur J Pharmacol ; 559(2-3): 155-60, 2007 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-17258195

RESUMO

Most atypical antipsychotic drugs increase acetylcholine release in the prefrontal cortex, but the detailed mechanism is still unknown. The present study examined the role of serotonin (5-HT)1A receptors in risperidone-induced increases in acetylcholine release in rat prefrontal cortex. Systemic administration of risperidone at doses of 1 and 2 mg/kg increased acetylcholine release in the prefrontal cortex in a dose-dependent manner. This increase was antagonized by systemic administration of high doses (1 and 3 mg/kg) of N-{2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl}-N-(2-pyridinyl)cyclohexanecarboxamide (WAY100635), a 5-HT1A receptor antagonist/dopamine D4 receptor agonist, but not by a low dose (0.1 mg/kg) of the antagonist which antagonizes preferentially presynaptic 5-HT1A autoreceptors. Furthermore, local application of WAY100635 into the prefrontal cortex also attenuated risperidone-induced increases in acetylcholine release. WAY100635 alone did not affect acetylcholine release in the prefrontal cortex. On the other hand, local application of risperidone (3 and 10 microM), the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (1 and 10 microM), and the dopamine D4 receptor antagonist 3-(4-(4-iodophenyl)piperazine-1-yl)methyl-1H-pyrrolo[2,3-b]pyridine (1 and 10 microM) into the cortex did not affect acetylcholine release in the prefrontal cortex. These results suggest that risperidone increases acetylcholine release in the prefrontal cortex through a complex mechanism which is enhanced by prefrontal 5-HT1A receptor activation.


Assuntos
Acetilcolina/metabolismo , Antipsicóticos/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Risperidona/farmacologia , Antagonistas da Serotonina/farmacologia , Sinapses/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Masculino , Microdiálise , Piperazinas/farmacologia , Córtex Pré-Frontal/metabolismo , Piridinas/farmacologia , Ratos , Ratos Wistar , Receptor 5-HT1A de Serotonina/metabolismo , Sinapses/metabolismo , Fatores de Tempo
8.
J Pharmacol Sci ; 102(4): 419-22, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17130670

RESUMO

We have shown that coadministration of sulpiride and fluvoxamine preferentially increases the release of dopamine in the prefrontal cortex. To study the possible role of the cortical cholinergic system in this effect, we combined several other antipsychotic drugs with fluvoxamine and examined the effects on acetylcholine release in rat prefrontal cortex. Risperidone and clozapine significantly increased the release of acetylcholine but sulpiride did not, and fluvoxamine did not enhance the effects of the antipsychotics. These results further support the previous suggestion that the cortical dopamine system plays an important role in the effects of antipsychotic drugs administered in combination with fluvoxamine.


Assuntos
Acetilcolina/metabolismo , Antipsicóticos/farmacologia , Fluvoxamina/farmacologia , Córtex Pré-Frontal/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Antipsicóticos/uso terapêutico , Depressão/tratamento farmacológico , Interações Medicamentosas , Quimioterapia Combinada , Fluvoxamina/uso terapêutico , Loxapina/farmacologia , Masculino , Microdiálise , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Wistar , Risperidona/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sulpirida/farmacologia , Fatores de Tempo
9.
Glycobiology ; 16(12): 1194-206, 2006 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16899492

RESUMO

Protein O-linked fucosylation is an unusual glycosylation associated with many important biological functions such as Notch signaling. Two fucosylation pathways synthesizing O-fucosylglycans have been reported on cystein-knotted proteins, that is, on epidermal growth factor-like (EGF-like) domains and on thrombospondin Type 1 repeat (TSR) domains. We report here the molecular cloning and characterization of a novel beta1,3-glucosyltransferase (beta3Glc-T) that synthesizes a Glcbeta1,3Fucalpha- structure on the TSR domain. We found a novel glycosyltransferase gene with beta1,3-glycosyltransferase (beta3GT) motifs in databases. The recombinant enzyme expressed in human embryonic kidney 293T (HEK293T) cells exhibited glucosyltransferase activity toward fucose-alpha-para-nitrophenyl (Fucalpha-pNp). Thin-layer chromatography (TLC) analysis revealed that the product of the recombinant enzyme migrated to the same position as did the product of endogenous beta3Glc-T of Chinese hamster ovary (CHO) cells. The two products could be digested by beta-glucosidase from almond and by exo-1,3-beta-glucanase from Trichoderma sp. These results strongly suggested that the product has the structure of Glcbeta1-3Fuc. Therefore, we named this novel enzyme beta3Glc-T. Immunostaining revealed that FLAG-tagged beta3Glc-T is an enzyme residing in the endoplasmic reticulum (ER) via retention signal, "REEL," which is a KDEL-like sequence, at the C-terminus. The TSR domain expressed in Escherichia coli was first fucosylated by the recombinant protein O-fucosyltransferase 2 (POFUT2), after which it became an acceptor substrate for the recombinant beta3Glc-T, which could apparently transfer Glc to the fucosylated TSR domain. Our results suggest that a novel glycosyltransferase, beta3Glc-T, contributes to the elongation of O-fucosylglycan and that this occurs specifically on TSR domains.


Assuntos
Retículo Endoplasmático/enzimologia , Glucosiltransferases/química , Trombospondina 1/metabolismo , Sequência de Aminoácidos , Animais , Células Cultivadas , Clonagem Molecular , Cricetinae , Cricetulus , DNA Complementar/genética , Escherichia coli/genética , Fucose/metabolismo , Fucosiltransferases/biossíntese , Galactosiltransferases , Glucosiltransferases/análise , Glucosiltransferases/genética , Glicosilação , Humanos , Dados de Sequência Molecular , Polissacarídeos/metabolismo , Processamento de Proteína Pós-Traducional , Estrutura Terciária de Proteína , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Análise de Sequência de DNA , Especificidade por Substrato , Trombospondina 1/química
10.
J Neurosci ; 25(44): 10252-61, 2005 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-16267233

RESUMO

Alzheimer's disease (AD) is the most common cause of dementia. Humanin (HN) is a short bioactive peptide abolishing neuronal cell death induced by various familial AD (FAD)-causative genes and amyloid-beta (Abeta) in vitro. It has been shown that HN suppresses memory impairment of mice induced by intracerebroventricular administration of Abeta. To potentiate the neuroprotective effect of HN, we synthesized a hybrid peptide named Colivelin composed of activity-dependent neurotrophic factor (ADNF) C-terminally fused to AGA-(C8R)HNG17, a potent HN derivative. Colivelin completely suppresses death induced by overexpressed FAD-causative genes and Abeta1-43 at a concentration of 100 fM, whereas AGA-(C8R)HNG17 does so at a concentration of 10 pM. Colivelin-induced neuroprotection has been confirmed to occur via two neuroprotective pathways: one mediated by Ca2+/calmodulin-dependent protein kinase IV, triggered by ADNF, and one mediated by signal transducer and activator of transcription 3, triggered by HN. In vivo animal studies have further indicated that intracerebroventricular administration of Colivelin not only completely suppresses impairment in spatial working memory induced by repetitive intracerebroventricular injection of Abeta25-35 or Abeta1-42, but also it antagonizes neuronal loss in the CA1 region of hippocampus induced by hippocampal injection of Abeta1-42. In addition, intraperitoneally administered Colivelin suppresses memory impairment caused by a muscarinic acetylcholine receptor antagonist, 3-quinuclidinyl benzilate, indicating that a substantial portion of intraperitoneally administered Colivelin passes through the blood-brain barrier and suppresses functional memory deficit. Thus, Colivelin might serve as a novel drug candidate for treatment of AD.


Assuntos
Doença de Alzheimer/prevenção & controle , Peptídeos e Proteínas de Sinalização Intracelular/administração & dosagem , Proteínas do Tecido Nervoso/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Fragmentos de Peptídeos/administração & dosagem , Peptídeos/síntese química , Doença de Alzheimer/patologia , Sequência de Aminoácidos , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/fisiologia , Linhagem Celular , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Proteínas do Tecido Nervoso/química , Proteínas do Tecido Nervoso/genética , Fármacos Neuroprotetores/química , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Peptídeos/administração & dosagem , Peptídeos/genética , Ratos
11.
Proc Natl Acad Sci U S A ; 102(35): 12365-70, 2005 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-16116085

RESUMO

In the early development of the central nervous system, neural progenitor cells divide in an asymmetric manner and migrate along the radial glia cells. The radial migration is an important process for the proper lamination of the cerebral cortex. Recently, a new mode of the radial migration was found at the intermediate zone where the neural progenitor cells become multipolar and reduce the migration rate. However, the regulatory signals for the radial migration are unknown. Using the migration assay in vitro, we examined how neural progenitor cell migration is regulated. Neural progenitor cells derived from embryonic mouse telencephalon migrated on laminin-coated dishes. Endothelin (ET)-1 inhibited the neural progenitor cell migration. This ET-1 effect was blocked by BQ788, a specific inhibitor of the ETB receptor, and by the expression of a carboxyl-terminal peptide of Galpha q but not Galpha i. The expression of constitutively active mutant of Galpha q, Galpha qR183C, inhibited the migration of neural progenitor cells. Moreover, the inhibitory effect of ET-1 was suppressed by the c-Jun N-terminal kinase (JNK) inhibitor SP600125 and the expression of the JNK-binding domain of JNK-interacting protein-1, a specific inhibitor of the JNK pathway. Using the slice culture system of embryonic brain, we demonstrated that ET-1 and the constitutively active mutant of Galpha q caused the retention of the neural progenitor cells in the intermediate zone and JNK-binding domain of JNK-interacting protein-1 abrogated the effect of ET-1. These results indicated that G protein-coupled receptor signaling negatively regulates neural progenitor cell migration through Gq and JNK.


Assuntos
Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Células-Tronco Multipotentes/metabolismo , Neurônios/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Antracenos/farmacologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Endotelina-1/farmacologia , Inibidores Enzimáticos/farmacologia , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/genética , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Camundongos , Camundongos Endogâmicos ICR , Células-Tronco Multipotentes/citologia , Células-Tronco Multipotentes/efeitos dos fármacos , Mutação , Neurônios/citologia , Neurônios/efeitos dos fármacos , Receptor de Endotelina B/metabolismo , Transdução de Sinais , Técnicas de Cultura de Tecidos
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