Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 12 de 12
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Can J Physiol Pharmacol ; 100(1): 61-67, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34793682

RESUMO

Trimethylamine N-oxide (TMAO), a metabolite of gut microbiota, is involved in the regulation of lipid metabolism and inflammatory response; however, the role of TMAO in hyperlipidemia acute pancreatitis (HAP) is not clear. In this study, HAP mice were used as an animal model to explore the effects and possible mechanism of TMAO on HAP, which may provide new ideas for the treatment of HAP. Results found that the levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, nonestesterified fatty acid, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, α-amylase, TMAO, and flavin-containing monooxygenase 3 were significantly increased, the levels of high-density lipoprotein cholesterol and insulin were significantly decreased, and there was an obvious pancreatic injury and inflammatory response in the model group. The choline analogue 3,3-dimethyl-1-butanol (DMB) treatment reversed the changes of serum biochemical parameters, alleviated the pancreatic tissue injury, and reduced the levels of inflammatory cytokines. Further studies of toll-like receptor (TLR)/p-glycoprotein 65 (p65) pathway found that the expressions of TLR2, TLR4, and p-p65/p65 in the model group were significantly increased, which was more obvious after Escherichia coli (Migula) Castellani & Chalmers treatment, while activation of the TLR/p65 pathway was inhibited by DMB. The results indicated that TMAO promotes HAP by promoting inflammatory response through TLR/p65 signaling pathway, suggesting that TMAO may be a potential target of HAP.


Assuntos
Hiperlipidemias/etiologia , Metilaminas/efeitos adversos , Pancreatite/etiologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Microbioma Gastrointestinal/fisiologia , Hexanóis/farmacologia , Hexanóis/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Inflamação , Mediadores da Inflamação/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metilaminas/metabolismo , Camundongos Endogâmicos C57BL , Terapia de Alvo Molecular , Pancreatite/tratamento farmacológico , Pancreatite/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptores Toll-Like/metabolismo
2.
Front Immunol ; 12: 735913, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34512670

RESUMO

Identifying signaling pathways that induce B cell response can aid functional cure strategies for chronic hepatitis B infection (CHB). TLR8 activation with ssRNA was shown to enhance follicular helper T cell (TFH) function leading to improved B cell responses in vitro. We investigated whether this mechanism can rescue an exhausted immune response in CHB infection. Effect of TLR8 agonism on supporting cytokines and TFH and B cells were evaluated using ex vivo and in vitro assays. The ability of an oral TLR8 agonist to promote TFH and B cell response was tested in samples from phase 1b clinical trial. TLR8 agonism induced TFH polarizing cytokine IL-12 in monocytes. Treatment of peripheral blood mononuclear cells (PBMCs) from CHB patients with TLR8 agonists induced cytokine IL-21 by TFH cells with enhanced IL-21+BCL-6+ and ICOS+BCL-6+ co-expression. Mechanistically, incubation of isolated naïve CD4+ T cells with TLR8 triggered monocytes resulted in their differentiation into IL-21+ICOS+BCL-6+ TFH in an IL-12 dependent manner. Furthermore, co-culture of these IL-21 producing TFH with autologous naïve B cells led to enhanced memory (CD19+CD27+) and plasma B cell generation (CD19+CD27++CD38+) and IgG production. Importantly, in TFH from CHB patients treated with an oral TLR8 agonist, HBsAg-specific BCL-6, ICOS, IL-21 and CD40L expression and rescue of defective activation induced marker (AIM) response along with partial restoration of HBsAg-specific B cell ELISPOT response was evident. TLR8 agonism can thus enhance HBV-specific B cell responses in CHB patients by improving monocyte-mediated TFH function and may play a role in achieving HBV functional cure.


Assuntos
Antivirais/uso terapêutico , Linfócitos B/efeitos dos fármacos , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/tratamento farmacológico , Hexanóis/uso terapêutico , Pirimidinas/uso terapêutico , Células T Auxiliares Foliculares/efeitos dos fármacos , Receptor 8 Toll-Like/agonistas , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos B/virologia , Ligante de CD40/metabolismo , Estudos de Casos e Controles , Células Cultivadas , ELISPOT , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/imunologia , Hepatite B Crônica/metabolismo , Hepatite B Crônica/virologia , Interações Hospedeiro-Patógeno , Humanos , Proteína Coestimuladora de Linfócitos T Induzíveis/metabolismo , Interleucinas/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , Transdução de Sinais , Células T Auxiliares Foliculares/imunologia , Células T Auxiliares Foliculares/metabolismo , Células T Auxiliares Foliculares/virologia , Receptor 8 Toll-Like/metabolismo , Resultado do Tratamento
3.
Hepatology ; 74(4): 1737-1749, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33704806

RESUMO

BACKGROUND AND AIMS: In patients with chronic hepatitis B (CHB) infection, activation of toll-like receptor 8 may induce antiviral immunity and drive functional cure. Selgantolimod, a toll-like receptor 8 agonist, was evaluated in patients with CHB who were virally suppressed on oral antiviral treatment or viremic and not on oral antiviral treatment. APPROACH AND RESULTS: In this phase 1b study, patients were randomized 4:1 to receive either selgantolimod or placebo once weekly. Virally suppressed patients received either 1.5 mg (for 2 weeks) or 3 mg (for 2 weeks or 4 weeks). Viremic patients received 3 mg for 2 weeks. The primary endpoint was safety, as assessed by adverse events (AEs), laboratory abnormalities, and vital sign examination. Pharmacokinetic and pharmacodynamic parameters were assessed by plasma analysis. A total of 38 patients (28 virally suppressed, 10 viremic) were enrolled from six sites in Australia, New Zealand, and South Korea. Twenty patients (53%) experienced an AE and 32 (84%) had laboratory abnormalities, all of which were mild or moderate in severity. The most common AEs were headache (32%), nausea (24%), and dizziness (13%). With a half-life of 5 hours, no accumulation of selgantolimod was observed with multiple dosing. Selgantolimod induced transient dose-dependent increases in serum cytokines, including IL-12p40 and IL-1RA, which are important for the expansion and activity of multiple T- cell subsets and innate immunity. CONCLUSION: Selgantolimod was safe and well-tolerated in virally suppressed and viremic patients with CHB and elicited cytokine responses consistent with target engagement. Further studies with longer durations of selgantolimod treatment are required to evaluate efficacy.


Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hexanóis/uso terapêutico , Pirimidinas/uso terapêutico , Receptor 8 Toll-Like/agonistas , Adulto , Tontura/induzido quimicamente , Relação Dose-Resposta a Droga , Feminino , Cefaleia/induzido quimicamente , Hepatite B Crônica/sangue , Hexanóis/farmacologia , Humanos , Proteína Antagonista do Receptor de Interleucina 1/sangue , Subunidade p40 da Interleucina-12/sangue , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Pirimidinas/farmacologia , Resposta Viral Sustentada
4.
Hepatology ; 74(1): 55-71, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33368377

RESUMO

BACKGROUND AND AIMS: GS-9688 (selgantolimod) is a toll-like receptor 8 agonist in clinical development for the treatment of chronic hepatitis B (CHB). Antiviral activity of GS-9688 has previously been evaluated in vitro in HBV-infected hepatocytes and in vivo in the woodchuck model of CHB. Here we evaluated the potential of GS-9688 to boost responses contributing to viral control and to modulate regulatory mediators. APPROACH AND RESULTS: We characterized the effect of GS-9688 on immune cell subsets in vitro in peripheral blood mononuclear cells of healthy controls and patients with CHB. GS-9688 activated dendritic cells and mononuclear phagocytes to produce IL-12 and other immunomodulatory mediators, inducing a comparable cytokine profile in healthy controls and patients with CHB. GS-9688 increased the frequency of activated natural killer (NK) cells, mucosal-associated invariant T cells, CD4+ follicular helper T cells, and, in about 50% of patients, HBV-specific CD8+ T cells expressing interferon-γ. Moreover, in vitro stimulation with GS-9688 induced NK-cell expression of interferon-γ and TNF-α, and promoted hepatocyte lysis. We also assessed whether GS-9688 inhibited immunosuppressive cell subsets that might enhance antiviral efficacy. Stimulation with GS-9688 reduced the frequency of CD4+ regulatory T cells and monocytic myeloid-derived suppressor cells (MDSCs). Residual MDSCs expressed higher levels of negative immune regulators, galectin-9 and programmed death-ligand 1. Conversely, GS-9688 induced an expansion of immunoregulatory TNF-related apoptosis-inducing ligand+ NK cells and degranulation of arginase-I+ polymorphonuclear MDSCs. CONCLUSIONS: GS-9688 induces cytokines in human peripheral blood mononuclear cells that are able to activate antiviral effector function by multiple immune mediators (HBV-specific CD8+ T cells, CD4+ follicular helper T cells, NK cells, and mucosal-associated invariant T cells). Although reducing the frequency of some immunoregulatory subsets, it enhances the immunosuppressive potential of others, highlighting potential biomarkers and immunotherapeutic targets to optimize the antiviral efficacy of GS-9688.


Assuntos
Antivirais/farmacologia , Hepatite B Crônica/tratamento farmacológico , Hexanóis/farmacologia , Pirimidinas/farmacologia , Receptor 8 Toll-Like/antagonistas & inibidores , Adulto , Idoso , Animais , Antivirais/uso terapêutico , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Modelos Animais de Doenças , Feminino , Voluntários Saudáveis , Células Hep G2 , Hepatite B Crônica/imunologia , Hepatite B Crônica/virologia , Hexanóis/uso terapêutico , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/imunologia , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares , Masculino , Marmota , Pessoa de Meia-Idade , Cultura Primária de Células , Pirimidinas/uso terapêutico , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Receptor 8 Toll-Like/metabolismo , Adulto Jovem
5.
Hepatology ; 73(1): 53-67, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32246499

RESUMO

BACKGROUND AND AIMS: GS-9688 (selgantolimod) is an oral selective small molecule agonist of toll-like receptor 8 in clinical development for the treatment of chronic hepatitis B. In this study, we evaluated the antiviral efficacy of GS-9688 in woodchucks chronically infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to hepatitis B virus. APPROACH AND RESULTS: WHV-infected woodchucks received eight weekly oral doses of vehicle, 1 mg/kg GS-9688, or 3 mg/kg GS-9688. Vehicle and 1 mg/kg GS-9688 had no antiviral effect, whereas 3 mg/kg GS-9688 induced a >5 log10 reduction in serum viral load and reduced WHV surface antigen (WHsAg) levels to below the limit of detection in half of the treated woodchucks. In these animals, the antiviral response was maintained until the end of the study (>5 months after the end of treatment). GS-9688 treatment reduced intrahepatic WHV RNA and DNA levels by >95% in animals in which the antiviral response was sustained after treatment cessation, and these woodchucks also developed detectable anti-WHsAg antibodies. The antiviral efficacy of weekly oral dosing with 3 mg/kg GS-9688 was confirmed in a second woodchuck study. The antiviral response to GS-9688 did not correlate with systemic GS-9688 or cytokine levels but was associated with transient elevation of liver injury biomarkers and enhanced proliferative response of peripheral blood mononuclear cells to WHV peptides. Transcriptomic analysis of liver biopsies taken prior to treatment suggested that T follicular helper cells and various other immune cell subsets may play a role in the antiviral response to GS-9688. CONCLUSIONS: Finite, short-duration treatment with a clinically relevant dose of GS-9688 is well tolerated and can induce a sustained antiviral response in WHV-infected woodchucks; the identification of a baseline intrahepatic transcriptional signature associated with response to GS-9688 treatment provides insights into the immune mechanisms that mediate this antiviral effect.


Assuntos
Antivirais/uso terapêutico , Vírus da Hepatite B da Marmota/efeitos dos fármacos , Vírus da Hepatite B da Marmota/genética , Hepatite B Crônica/tratamento farmacológico , Hexanóis/uso terapêutico , Pirimidinas/uso terapêutico , Receptor 8 Toll-Like/agonistas , Animais , Antivirais/farmacologia , DNA Viral/sangue , Modelos Animais de Doenças , Anticorpos Anti-Hepatite/sangue , Antígenos de Hepatite/sangue , Vírus da Hepatite B da Marmota/imunologia , Hepatite B Crônica/complicações , Hepatite B Crônica/imunologia , Hexanóis/farmacologia , Humanos , Marmota , Pirimidinas/farmacologia , Replicação Viral/efeitos dos fármacos
6.
Mol Med Rep ; 20(1): 779-786, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180562

RESUMO

Myocardial infarction (MI) is a common cause of chronic heart failure (HF). Increasing evidence has revealed that trimethylamine N­oxide (TMAO), a gut­microbiota­derived metabolite, contributes to the pathogenesis of cardiovascular disease by promoting inflammation. Elevated levels of circulating TMAO have been reported in patients following MI and were associated with unfavorable outcomes. The present study examined whether reductions in circulating TMAO could attenuate the progression of HF in rats following MI. Sprague­Dawley rats underwent coronary ligation to induce MI or a sham operation. Echocardiography confirmed MI and cardiac dysfunction one day following coronary ligation. MI and sham rats were then treated with either vehicle (tap water) or 1.0% 3,3­dimethyl­1­butanol (DMB, a trimethylamine formation inhibitor) in tap water, for 8 weeks. At the end of the experiment, TMAO plasma levels were markedly elevated in vehicle­treated MI rats compared with vehicle­treated sham rats; however, TMAO plasma levels were reduced in DMB­treated MI rats compared with vehicle­treated MI rats. Both MI groups exhibited cardiac hypertrophy, lung congestion, left ventricular remodeling and impaired cardiac function, according to the results of anatomical analysis, echocardiography and left ventricular hemodynamics; however, these manifestations of MI­induced HF were significantly improved in DMB­treated MI rats compared with vehicle­treated MI rats. The plasma levels of the chemokine interleukin (IL)­8, and cardiac expression of IL­8 and its receptors were significantly increased in vehicle­treated MI rats compared with vehicle­treated sham rats; however, these were normalized in DMB­treated MI rats. In addition, elevated TMAO plasma level was positively correlated with increased IL­8 plasma level in MI groups. Notably, DMB treatment of sham rats also reduced plasma TMAO, but did not alter other parameters. These results indicated that reducing circulating TMAO may ameliorate the development of chronic HF following MI in rats, potentially by inhibiting IL­8 secretion. The results from the present study suggested that inhibition of TMAO synthesis may be considered as a novel therapeutic approach for the prevention and treatment of patients with chronic MI­induced HF.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Hexanóis/uso terapêutico , Metilaminas/antagonistas & inibidores , Infarto do Miocárdio/tratamento farmacológico , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/microbiologia , Interleucina-8/sangue , Masculino , Metilaminas/sangue , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Infarto do Miocárdio/microbiologia , Ratos , Ratos Sprague-Dawley
7.
Biosci Rep ; 38(1)2018 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-29358310

RESUMO

The 7-nitro-2,1,3-nitrobenzoxadiazole (NBD) derivatives are a series of compounds containing the NBD scaffold that are not glutathione (GSH) peptidomimetics, and result in a strong inhibition of glutathione S-transferases (GSTs). Growing evidences highlight their pivotal roles and outstanding anticancer activity in different tumor models. In particular, 6-(7-nitro-2,1,3-benzoxadiazol-4-ylthio) hexanol (NBDHEX) is extensively studied, which is a very efficient inhibitor of GSTP1-1. It triggers apoptosis in several tumor cell lines and this cytotoxic activity is observed at micro and submicromolar concentrations. Importantly, studies have shown that NBDHEX acts as an anticancer drug by inhibiting GSTs catalytic activity, avoiding inconvenience of the inhibitor extrusion from the cell by specific pumps and disrupting the interaction between the GSTP1-1 and key signaling effectors. Additionally, some researchers also have discovered that NBDHEX can act as late-phase autophagy inhibitor, which opens new opportunities to fully exploit its therapeutic potential. In this review, we summarize the advantages, anticancer mechanisms, and analogs of this compound, which will establish the basis on the usage of NBDHEX in clinical applications in future.


Assuntos
Antineoplásicos/química , Glutationa S-Transferase pi/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Oxidiazóis/química , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Azóis/química , Azóis/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Glutationa S-Transferase pi/química , Hexanóis/química , Hexanóis/uso terapêutico , Humanos , Neoplasias/patologia , Nitrobenzenos/química , Nitrobenzenos/uso terapêutico , Oxidiazóis/uso terapêutico
8.
Parasitol Int ; 60(4): 488-92, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21924377

RESUMO

Malaria is one of the world's deadliest diseases and is becoming an increasingly serious problem as malaria parasites develop resistance to most of the antimalarial drugs used today. We previously reported the in vitro and in vivo antimalarial potencies of 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) and 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against Plasmodium falciparum and Plasmodium berghei parasites. To improve water-solubility for synthetic peroxides, a variety of cyclic peroxides having carboxyl functionality was prepared based on the antimalarial candidate, N-251, and their antimalarial activities were determined. The reactions of N-89 and its derivatives with Fe(II) demonstrated a highly efficient formation of the corresponding carbon radical which may be suspected as a key for the antiparasitic activity.


Assuntos
Antimaláricos/administração & dosagem , Hexanóis/administração & dosagem , Malária Falciparum/tratamento farmacológico , Malária/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Compostos de Espiro/administração & dosagem , Animais , Antimaláricos/síntese química , Antimaláricos/uso terapêutico , Carbono/química , Carbono/metabolismo , Ácidos Carboxílicos/química , Avaliação Pré-Clínica de Medicamentos , Compostos Ferrosos/metabolismo , Radicais Livres/química , Radicais Livres/metabolismo , Hexanóis/síntese química , Hexanóis/uso terapêutico , Humanos , Concentração Inibidora 50 , Malária/parasitologia , Malária Falciparum/parasitologia , Camundongos , Camundongos Endogâmicos ICR , Oxirredução , Peróxidos/química , Peróxidos/metabolismo , Plasmodium berghei/crescimento & desenvolvimento , Plasmodium falciparum/crescimento & desenvolvimento , Compostos de Espiro/síntese química , Compostos de Espiro/uso terapêutico , Relação Estrutura-Atividade
9.
Parasitol Int ; 60(3): 270-3, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21501696

RESUMO

Plasmodium falciparum, the major causative parasite for the disease, has acquired resistance to most of the antimalarial drugs used today, presenting an immediate need for new antimalarial drugs. Here, we report the in vitro and in vivo antimalarial activities of 6-(1,2,6,7-tetraoxaspiro[7.11]nonadec-4-yl)hexan-1-ol (N-251) against P. falciparum and Plasmodium berghei parasites. The N-251 showed high antimalarial potencies both in the in vitro and the in vivo tests (EC(50) 2.3×10(-8) M; ED(50) 15 mg/kg (per oral)). The potencies were similar to that of artemisinin in vitro and greater than artemisinin's activity in vivo (p.o.). In addition, N-251 has little toxicity: a single oral administration at 2000 mg/kg to a rat gave no health problems to it. Administration of N-251 to mice bearing 1% of parasitemia (per oral 68 mg/kg, 3 times a day for 3 consecutive days) resulted in a dramatic decrease in the parasitemia: all the 5 mice given N-251 were cured without any recurrence, with no diarrhea or weight loss occurring in the 60 days of experiment. N-251 deserves more extensive clinical evaluation, desirably including future trials in the human.


Assuntos
Antimaláricos/farmacologia , Artemisininas/farmacologia , Compostos Heterocíclicos com 2 Anéis/farmacologia , Hexanóis/farmacologia , Malária Falciparum/tratamento farmacológico , Plasmodium berghei/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Compostos de Espiro/farmacologia , Administração Oral , Animais , Antimaláricos/química , Antimaláricos/uso terapêutico , Artemisininas/uso terapêutico , Linhagem Celular Tumoral , Quimioterapia Combinada , Eritrócitos/efeitos dos fármacos , Eritrócitos/parasitologia , Compostos Heterocíclicos com 2 Anéis/síntese química , Compostos Heterocíclicos com 2 Anéis/uso terapêutico , Hexanóis/química , Hexanóis/uso terapêutico , Humanos , Malária/tratamento farmacológico , Malária/parasitologia , Malária Falciparum/parasitologia , Camundongos , Camundongos Endogâmicos ICR , Estrutura Molecular , Parasitemia/tratamento farmacológico , Testes de Sensibilidade Parasitária , Ratos , Compostos de Espiro/síntese química , Compostos de Espiro/química , Compostos de Espiro/uso terapêutico , Análise de Sobrevida , Tetraoxanos
10.
Physiol Behav ; 103(5): 547-56, 2011 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-21515296

RESUMO

Green odor (GO), a mixture of cis-3-hexenol and trans-2-hexenal, attenuates stress responses and anxiety to psychological stressors in rodents; however, it remains unknown whether GO affects behavioral and stress responses to risk-related olfactory stimuli and actual noxious stimuli. The present study investigated the effects of green odor on behavioral and plasma adrenocorticotropic hormone (ACTH) responses to 2,5-dihydro-2,4,5-trimethylthiazoline (TMT), a component of fox feces, and electric footshock (FS) stress. When rats were simultaneously exposed to TMT and GO, they showed decreases in immobility and plasma ACTH levels compared with TMT alone. GO exposure after TMT increased immobility, but blocked the elevation of plasma ACTH levels compared with rats exposed to distilled water after TMT. This means that GO presentation during TMT attenuated the TMT-induced behavioral response and GO presentation during and after TMT inhibited TMT-induced elevation of plasma ACTH levels. Furthermore, electric FS-induced plasma ACTH elevations were attenuated by simultaneous GO and FS exposure. GO presentation after FS attenuated plasma ACTH elevations and fecal responses. These findings reveal that GO has alleviating effects on olfactory stimulus- and noxious stimulus-induced behavioral and endocrinal responses.


Assuntos
Hormônio Adrenocorticotrópico/sangue , Aldeídos/farmacologia , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Hexanóis/farmacologia , Estresse Psicológico/tratamento farmacológico , Tiazóis/farmacologia , Aldeídos/administração & dosagem , Aldeídos/uso terapêutico , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/induzido quimicamente , Ansiedade/complicações , Modelos Animais de Doenças , Quimioterapia Combinada , Estimulação Elétrica/métodos , Comportamento Excretor Animal/efeitos dos fármacos , Hexanóis/administração & dosagem , Hexanóis/uso terapêutico , Masculino , Percepção Olfatória/efeitos dos fármacos , Ratos , Ratos Wistar , Estresse Psicológico/induzido quimicamente , Estresse Psicológico/complicações
11.
Behav Brain Res ; 166(2): 247-52, 2006 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-16214236

RESUMO

In the present study, the effect of (Z)-3-hexenol, one of the main constituent of green odor, on the anxiety-related behavior of mouse and the content of 5-hydroxytryptamine (5-HT), dopamine and their metabolites in the brain were investigated. Evaluation of anxiety-related animal behavior was performed by measuring the percent of time spent on the open arms and the percent of open-arm entries as conventional anxiety indices. The number of times displaying risk-assessment from a closed arm was also measured as an ethological anxiety index. Diazepam, an anxiolytic agent, enhanced the percent of time spent on the open arms and the percent of open-arm entries. The number of times displaying risk-assessment was not affected by diazepam in the present study. The percent of time on the open arms were depressed, and the number of times displaying risk-assessment were stimulated by 1-(3-trifluoromethylphenyl)piperazine (TFMPP), indicating that TFMPP acts as an anxiogenic agent. (Z)-3-Hexenol revealed anxiolytic activity and increased the percent of time spent on the open arms and decreased the number of times displaying risk-assessment. In the neurochemical study, diazepam had no effect on the content of 5-HT and its metabolite in the brain cortex or hippocampus. On the other hand, TFMPP inhibited the 5-HT turnover rate accompanied by the elevation of the 5-HT content and reduction of the 5-HIAA content in the brain cortex and hippocampus. (Z)-3-Hexenol significantly increased the 5-HT content without affecting the 5-HIAA content or the 5-HT turnover rate in the brain cortex or hippocampus. Changes in serotonergic activity in the cortex and hippocampus were suggested to be involved in the anxiolytic effect of (Z)-3-hexenol observed in the elevated plus-maze test.


Assuntos
Ansiolíticos/farmacologia , Aminas Biogênicas/metabolismo , Encéfalo/efeitos dos fármacos , Hexanóis/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Comportamento Animal , Química Encefálica/efeitos dos fármacos , Diazepam/uso terapêutico , Relação Dose-Resposta a Droga , Hexanóis/uso terapêutico , Masculino , Camundongos , Piperazinas/uso terapêutico , Agonistas do Receptor de Serotonina/uso terapêutico , Fatores de Tempo
12.
Chin Med J (Engl) ; 113(1): 27-30, 2000 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11775204

RESUMO

OBJECTIVE: To investigate whether albumin can be substituted by mannitolum in cirrhotic patients with tense ascites treated by paracentesis. METHODS: Sixty-eight patients admitted to this therapeutic procedure were randomly assigned to receive intravenous albumin (36 patients) and mannitolum (32 patients) infusion. In repeated large-volume paracentesis (3-6 L/day), intravenous albumin 20 g or intravenous 20% mannitolum 250 ml were added. RESULTS: In 24 and 48 hours after paracentesis the mean value of electrolytes, liver and renal functions and various indicators of systemic circulation either in Group 1 or in Group 2 cases were found without changes (P > 0.05). As compared with that before paracentesis, the diameter of spleen vein was increased significantly (P < 0.05). The complications occurring after paracentesis were similar in both groups. CONCLUSIONS: It was suggested that paracentesis with intravenous infusion of mannitolum is an effective and safe method in treating cirrhotic patients with tense ascites.


Assuntos
Ascite/terapia , Hexanóis/uso terapêutico , Cirrose Hepática/terapia , Paracentese , Substitutos do Plasma/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...