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1.
Sci Rep ; 9(1): 8666, 2019 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-31209282

RESUMO

5-aminolevulinic acid (5-ALA) has recently been employed for photodynamic diagnosis (ALA-PDD) and photodynamic therapy (ALA-PDT) of various types of cancer because hyperproliferating tumor cells do not utilize oxidative phosphorylation and do not efficiently produce heme; instead, they accumulate protoporphyrin IX (PpIX), which is a precursor of heme that is activated by violet light irradiation that results in the production of red fluorescence and singlet oxygen. The efficiencies of ALA-PDD and ALA-PDT depend on the efficient cellular uptake of 5-ALA and the inefficient excretion of PpIX. We employed the JFCR39 cell panel to determine whether tumor cells originating from different tissues can produce and accumulate PpIX. We also investigated cellular factors/molecules involved in PpIX excretion by tumor cells with the JFCR39 cell panel. Unexpectedly, the expression levels of ABCG2, which has been considered to play a major role in PpIX extracellular transport, did not show a strong correlation with PpIX excretion levels in the JFCR39 cell panel, although an ABCG2 inhibitor significantly increased intracellular PpIX accumulation in several tumor cell lines. In contrast, the expression levels of dynamin 2, which is a cell membrane-associated molecule involved in exocytosis, were correlated with the PpIX excretion levels. Moreover, inhibitors of dynamin significantly suppressed PpIX excretion and increased the intracellular levels of PpIX. This is the first report demonstrating the causal relationship between dynamin 2 expression and PpIX excretion in tumor cells.

2.
Oncotarget ; 9(80): 35141-35161, 2018 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-30416685

RESUMO

Treatment of patients with advanced sarcoma remains challenging due to lack of effective medicine, with the development of novel drugs being of keen interest. A pan-PI3K inhibitor, ZSTK474, has been evaluated in clinical trials against a range of advanced solid tumors, with clinical benefit shown in sarcoma patients. In the present study, we developed a panel of 14 human sarcoma cell lines and investigated the antitumor effect of 24 anticancer agents including ZSTK474, other PI3K inhibitors, and those clinically used for sarcoma treatment. ZSTK474 exhibited a similar antiproliferative profile to other PI3K inhibitors but was clearly different from the other drugs examined. Indeed, ZSTK474 inhibited PI3K-downstream pathways, in parallel to growth inhibition, in all cell lines examined, showing proof-of-concept of PI3K inhibition. In addition, ZSTK474 induced apoptosis selectively in Ewing's sarcoma (RD-ES and A673), alveolar rhabdomyosarcoma (SJCRH30) and synovial sarcoma (SYO-1, Aska-SS and Yamato-SS) cell lines, all of which harbor chromosomal translocation and resulting oncogenic fusion genes, EWSR1-FLI1, PAX3-FOXO1 and SS18-SSX, respectively. Finally, animal experiments confirmed the antitumor activity of ZSTK474 in vivo, with superior efficacy observed in translocation-positive cells. These results suggest that ZSTK474 could be a promising drug candidate for treating sarcomas, especially those harboring chromosomal translocation.

3.
Infant Behav Dev ; 43: 66-74, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-27155926

RESUMO

Previous studies have mainly examined how maternal behaviors influence infants during holding. However it is unclear how infants influence maternal holding. This current study investigated how infants' emotional states influence maternal holding behaviors, and whether maternal holding behaviors are also influenced by the mothers' parenting stress. We manipulated infants' emotional states and videotaped mothers' holding behaviors. The mothers also completed a questionnaire about their parental stress. Results showed that mothers varied their holding behaviors depending on their infants' emotional states. When infants were comfortable, mothers rocked them horizontally and quietly. When infants were uncomfortable, mothers rocked them vertically at a high frequency. Furthermore, some types of parenting stress were related to several types of maternal behaviors in the context of holding. These findings suggest that maternal holding behaviors are influenced by both the infants' emotional states and the mothers' parenting stress.


Assuntos
Comportamento do Lactente/psicologia , Cuidado do Lactente/psicologia , Comportamento Materno/psicologia , Mães/psicologia , Estresse Psicológico/psicologia , Adulto , Emoções , Feminino , Humanos , Lactente , Cuidado do Lactente/métodos , Masculino , Relações Mãe-Filho , Poder Familiar/psicologia , Inquéritos e Questionários
4.
Cancer Sci ; 106(2): 171-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25483727

RESUMO

Drug resistance often critically limits the efficacy of molecular targeted drugs. Although pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) is an attractive therapeutic strategy for cancer therapy, molecular determinants for efficacy of PI3K inhibitors (PI3Kis) remain unclear. We previously identified that overexpression of insulin-like growth factor 1 receptor (IGF1R) contributed to the development of drug resistance after long-term exposure to PI3Kis. In this study, we examined the involvement of basal IGF1R expression in intrinsic resistance of drug-naïve cancer cells to PI3Kis and whether inhibition of IGF1R overcomes the resistance. We found that cancer cells highly expressing IGF1R showed resistance to dephosphorylation of Akt and subsequent antitumor effect by ZSTK474 treatment. Knockdown of IGF1R by siRNAs facilitated the dephosphorylation and enhanced the drug efficacy. These cells expressed tyrosine-phosphorylated insulin receptor substrate 1 at high levels, which was dependent on basal IGF1R expression. In these cells, the efficacy of ZSTK474 in vitro and in vivo was improved by its combination with the IGF1R inhibitor OSI-906. Finally, we found a significant correlation between the basal expression level of IGF1R and the inefficacy of ZSTK474 in an in vivo human cancer panel, as well as in vitro. These results suggest that basal IGF1R expression affects intrinsic resistance of cancer cells to ZSTK474, and IGF1R is a promising target to improve the therapeutic efficacy. The current results provide evidence of combination therapy of PI3Kis with IGF1R inhibitors for treating IGF1R-positive human cancers.


Assuntos
Resistencia a Medicamentos Antineoplásicos/genética , Receptor IGF Tipo 1/genética , Triazinas/farmacologia , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/genética , Proteínas Proto-Oncogênicas c-akt/genética
5.
Phytother Res ; 28(5): 685-91, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23873581

RESUMO

Bisabololoxide A (BSBO), main constituents in German chamomile extract, is responsible for antipruritic effect. In previous study, the incubation with 30-100 µM BSBO for 24 h exerted cytotoxic and proapoptotic effects on rat thymocytes. To further characterize BSBO cytotoxicity, the effect on the cells suffering from calcium overload by calcium ionophore A23187 was examined. A23187 induced Ca(2+) -dependent cell death. Contrary to our expectation, 1-10 µM BSBO inhibited A23187-induced increase in cell lethality of rat thymocytes. BSBO attenuated A23187-induced increases in populations of shrunken living cells, phosphatidylserine-exposed living cells, and dead cells, without affecting the increase in intracellular Ca(2+) concentration and the Ca(2+) -dependent hyperpolarization. The effect of BSBO on A23187-treated cells may be unique because the activation of Ca(2+) -dependent K(+) channels is required for cell shrinkage, externalization of phosphatidylserine, and cell death in some cells. The cell death induced by A23187 was not inhibited by Z-VAD-FMK, a pan-inhibitor of caspases. Thus, the cell death may be a necrosis with some features observed during an early stage of apoptosis. These results suggest that BSBO at low micromolar concentrations is cytoprotective against calcium overload.


Assuntos
Apoptose/efeitos dos fármacos , Cálcio/efeitos adversos , Matricaria/química , Extratos Vegetais/farmacologia , Sesquiterpenos/farmacologia , Timócitos/efeitos dos fármacos , Clorometilcetonas de Aminoácidos , Animais , Calcimicina/farmacologia , Células Cultivadas , Ratos , Ratos Wistar
6.
J Toxicol Sci ; 38(1): 49-55, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23358139

RESUMO

It was recently reported that triclocarban was absorbed significantly from soap used during showering in human subjects and that its C(max) in their whole blood ranged from 23 nM to 530 nM. We revealed that a nanomolar concentration (300 nM) of triclocarban potentiated the cytotoxicity of 300 µM H(2)O(2) in rat thymocytes by using cytometric techniques with appropriate fluorescent probes. Although 300 nM triclocarban did not itself increase the population of dead cells (cell lethality), it facilitated the process of cell death induced by H(2)O(2), resulting in a further increase in the population of dead cells. Nanomolar concentrations (300 nM or higher) of triclocarban significantly decreased the cellular content of nonprotein thiol (glutathione), which has a protective role against oxidative stress. Triclocarban at 300 nM or higher increased the cell vulnerability to oxidative stress. The results may suggest that nanomolar concentration (300 nM or higher) of triclocarban affects some cellular functions although there is no evidence for adverse effects of triclocarban in humans at present.


Assuntos
Anti-Infecciosos Locais/toxicidade , Carbanilidas/toxicidade , Timócitos/efeitos dos fármacos , Animais , Morte Celular/efeitos dos fármacos , Peróxido de Hidrogênio , Estresse Oxidativo/efeitos dos fármacos , Ratos , Compostos de Sulfidrila/metabolismo , Timócitos/metabolismo
7.
Cancer Sci ; 103(11): 1955-60, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22925034

RESUMO

Acquired resistance is a major obstacle for conventional cancer chemotherapy, and also for some of the targeted therapies approved to date. Long-term treatment using protein tyrosine kinase inhibitors (TKIs), such as gefitinib and imatinib, gives rise to resistant cancer cells carrying a drug-resistant gatekeeper mutation in the kinase domain of the respective target genes, EGFR and BCR-ABL. As for the phosphatidylinositol 3-kinase inhibitors (PI3Kis), little is known about their acquired resistance, although some are undergoing clinical trials. To address this issue, we exposed 11 human cancer cell lines to ZSTK474, a PI3Ki we developed previously, for a period of more than 1 year in vitro. Consequently, we established ZSTK474-resistant cells from four of the 11 cancer cell lines tested. The acquired resistance was not only to ZSTK474 but also to other PI3Kis. None of the PI3Ki-resistant cells, however, contained any mutation in the kinase domain of the PIK3CA gene. Instead, we found that insulin-like growth factor 1 receptor (IGF1R) was overexpressed in all four resistant cells. Interestingly, targeted knockdown of IGF1R expression using specific siRNAs or inhibition of IGF1R using IGF1R-TKIs reversed the acquired PI3Ki resistance. These results suggest that long-term treatment with PI3Kis may cause acquired resistance, and targeting IGF1R is a promising strategy to overcome the resistance.


Assuntos
Antineoplásicos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Triazinas/farmacologia , Linhagem Celular Tumoral , Classe I de Fosfatidilinositol 3-Quinases , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Mutação/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Receptores de Somatomedina/genética
8.
Arch Toxicol ; 84(1): 45-52, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19834689

RESUMO

German chamomile (Matricaria recutita L.), one of the popular ingredients in herbal teas, has been traditionally used for medicinal purposes. Bisabololoxide A (BSBO) is one of the main constituents in this herb. BSBO is supposed to be principle in some bioactivities of German chamomile such as anti-inflammatory, gastrointestinal, and antipruritic actions. Although the use of German chamomile has spread, the information related to toxicity of BSBO is very limited. In present study, the cytotoxic effect of micromolar BSBO was cytometrically examined on rat thymocytes by using appropriate fluorescent dyes. When the cells were incubated with BSBO for 24 h, BSBO at concentrations of 30 microM or more significantly increased populations of dead cells, shrunken cells, and cells with phosphatidylserine exposed on membrane surface. Both cell shrinkage and externalization of membrane phosphatidylserine are general features in an early stage of apoptosis. In addition, BSBO significantly increased population of cells containing hypodiploid DNA, and the increase was completely attenuated by Z-VAD-FMK, a pan-inhibitor for caspases, indicating an involvement of caspase activation. Thus, it is likely that the type of cell death induced by BSBO is apoptosis. The significant changes in cellular parameters of rat thymocytes by BSBO were not observed when the concentration was 10 microM or less. Furthermore, the short incubation (3 h) of cells even with 30-100 microM BSBO did not significantly affect the cells. Therefore, it may be suggested that BSBO is practically safe when German chamomile is conventionally used.


Assuntos
Apoptose/efeitos dos fármacos , Flores/química , Matricaria/química , Sesquiterpenos/toxicidade , Linfócitos T/efeitos dos fármacos , Timo/efeitos dos fármacos , Animais , Anexina A5/metabolismo , Inibidores de Caspase , Membrana Celular/metabolismo , Tamanho Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Diploide , Relação Dose-Resposta a Droga , Fosfatidilserinas/metabolismo , Extratos Vegetais/química , Ratos , Ratos Wistar , Propriedades de Superfície/efeitos dos fármacos , Linfócitos T/citologia , Timo/citologia , Fatores de Tempo
9.
Toxicol In Vitro ; 23(6): 1092-9, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19497362

RESUMO

Thimerosal (TMR), an ethylmercury-containing preservative in pharmaceutical products, was recently reported to increase intracellular Zn(2+) concentration. Therefore, some health concerns about the toxicity of TMR remain because of physiological and pathological roles of Zn(2+). To reveal the property of TMR-induced increase in intracellular Zn(2+) concentration, the effect of TMR on FluoZin-3 fluorescence, an indicator of intracellular Zn(2+), of rat thymocytes was examined. TMR at concentrations ranging from 0.3 microM to 10 microM increased the intensity of FluoZin-3 fluorescence in a concentration-dependent manner under external Ca(2+)- and Zn(2+)-free condition. The threshold concentration was 0.3-1 microM. The increase in the intensity was significant when TMR concentration was 1 microM or more. N,N,N',N'-Tetrakis(2-pyridylmethyl)ethylenediamine (TPEN), a chelator for intracellular Zn(2+), completely attenuated the TMR-induced augmentation of FluoZin-3 fluorescence. Hydrogen peroxide (H(2)O(2)) and N-ethylmaleimide, reducing cellular thiol content, significantly increased FluoZin-3 fluorescence intensity and decreased 5-chloromethylfluorescein (5-CMF) fluorescence intensity, an indicator for cellular thiol. The correlation coefficient between TMR-induced augmentation of FluoZin-3 fluorescence and attenuation of 5-CMF fluorescence was -0.882. TMR also attenuated the 5-CMF fluorescence in the presence of TPEN. Simultaneous application of H(2)O(2) and TMR synergistically augmented the FluoZin-3 fluorescence. It is suggested that TMR increases intracellular Zn(2+) concentration via decreasing cellular thiol content.


Assuntos
Estresse Oxidativo/efeitos dos fármacos , Conservantes Farmacêuticos/toxicidade , Timerosal/toxicidade , Zinco/metabolismo , Animais , Relação Dose-Resposta a Droga , Corantes Fluorescentes , Peróxido de Hidrogênio/toxicidade , Masculino , Compostos Policíclicos , Conservantes Farmacêuticos/administração & dosagem , Ratos , Ratos Wistar , Compostos de Sulfidrila/metabolismo , Timerosal/administração & dosagem , Timo/citologia
10.
Toxicol In Vitro ; 23(4): 610-6, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19490836

RESUMO

Econazole, one of imidazole antifungals, has been reported to exhibit an inhibitory action on Mycobacterium tuberculosis and its multidrug-resistant strains under in vitro and ex vivo conditions. There is a chemotherapeutic potential of econazole against tuberculosis. We have revealed that Zn(2+) at micromolar concentrations potentiates the cytotoxicity of imidazole antifungals by increasing membrane Zn(2+) permeability. It is reminiscent of a possibility that econazole exhibits harmful action on human in the presence of Zn(2+) at a physiological range when the agent is systemically administered. Because it is necessary to characterize the cytotoxic action of econazole in the presence of Zn(2+), we have cytometrically examined the effects of econazole, ZnCl(2), and their combination on rat thymocytes. ZnCl(2) at concentrations ranging from 1 microM to 30 microM significantly increased the lethality induced by 10 microM econazole in a concentration-dependent manner. Econazole at a sublethal concentration of 1 microM significantly augmented the intensity of side scatter in the presence of micromolar ZnCl(2), suggesting the change in an intracellular circumstance by the combination of econazole and ZnCl(2). Econazole at 0.3 microM or more in the presence of ZnCl(2) increased the intensity of Fluo-3 fluorescence, an indicator for intracellular Ca(2+). Furthermore, the intensity of FluoZin-3 fluorescence, an indicator for intracellular Zn(2+), was also augmented by econazole at 0.1 microM or more in the presence of ZnCl(2). Results suggest that the combination of submicromolar econazole with micromolar ZnCl(2) may increase the intracellular concentration of Ca(2+) and Zn(2+), leading to disturbance of intracellular Ca(2+) and Zn(2+) homeostasis that triggers cytotoxic action.


Assuntos
Antifúngicos/farmacologia , Cálcio/metabolismo , Econazol/farmacologia , Linfócitos T/efeitos dos fármacos , Zinco/farmacologia , Animais , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Homeostase/efeitos dos fármacos , Bicamadas Lipídicas/metabolismo , Masculino , Ratos , Ratos Wistar , Linfócitos T/metabolismo , Zinco/metabolismo
11.
Basic Clin Pharmacol Toxicol ; 104(6): 455-62, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19389048

RESUMO

The chemopreventive and chemotherapeutic actions of polyphenols and related phenolics have received considerable attention since these compounds induce apoptosis in several types of cancer cells in vitro. A plausible criterion for the use of such compounds is that they should not exert any toxic effect on normal cells. However, information about the toxicity of polyphenols and related phenolics to normal cells is limited. In this study, the effects of polyphenols and related phenolics on rat thymocytes were examined by flow cytometric analysis with appropriate fluorescent probes. The compounds examined in this study were caffeic acid, rosmarinic acid, chlorogenic acid, (+)-catechin, 6-gingerol, sesamol, resveratrol, and eugenol. Of these, resveratrol was the most cytotoxic on rat thymocytes incubated for 24 hrs with 100 microM of this compound. Resveratrol at a concentration of 10 microM or more (up to 100 microM) led to a significant dose-dependent increase in the population of dead cells, shrunken living cells, annexin V-positive cells and cells with hypodiploidal DNA. In the presence of benzyloxycarbonyl-Val-Ala-Asp (OMe) fluoromethylketone (Z-VAD-FMK), a pan-inhibitor of caspases, the resveratrol-induced increase in the population of cells with hypodiploidal DNA was partially inhibited. Overall, it is suggested that resveratrol at a concentration of 10 microM or more induces apoptosis in normal cells as well as cancer cells (previously reported elsewhere). Thus, at concentrations that are suitable for chemopreventive and chemotherapeutic actions, resveratrol may exert a cytotoxic effect on normal cells.


Assuntos
Flavonoides/toxicidade , Fenóis/toxicidade , Timo/efeitos dos fármacos , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Citometria de Fluxo , Técnicas In Vitro , Masculino , Polifenóis , Ratos , Ratos Wistar , Resveratrol , Estilbenos/toxicidade , Timo/citologia
12.
Nihon Rinsho ; 67(1): 16-22, 2009 Jan.
Artigo em Japonês | MEDLINE | ID: mdl-19177747

RESUMO

Japan has witnessed the rise of STDs, and the increase in the number of HIV cases infected through sexual contact in the last decade. Background of these trends will be the exceptionally high prevalence of paid sex in Japan among developed countries and the diversified unprotected sexual behaviors that have prevailed among general population since 1990s. STDs are also increasing and HIV infection through sexual contact has resumed to increase among other developed countries in the same period of time. Coordinated research among developed countries is becoming increasingly important to clarify the specific and general causes of such phenomena and thus to explore the possibility of coordinated responses toward these global challenges.


Assuntos
Doenças Sexualmente Transmissíveis/epidemiologia , Países Desenvolvidos/estatística & dados numéricos , Europa (Continente)/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Japão/epidemiologia , Masculino , Comportamento Sexual , Doenças Sexualmente Transmissíveis/prevenção & controle , Doenças Sexualmente Transmissíveis/transmissão , Fatores de Tempo , Estados Unidos/epidemiologia
13.
Toxicol In Vitro ; 23(2): 338-45, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19124067

RESUMO

A23187, a calcium ionophore, is used to induce Ca(2+)-dependent cell death by increasing intracellular Ca(2+) concentration ([Ca(2+)](i)) under in vitro condition. Since this ionophore also increases membrane permeability of metal divalent cations such as Zn(2+) and Fe(2+) rather than Ca(2+), trace metal cations in cell suspension may affect Ca(2+)-dependent cell death induced by A23187. Therefore, the effects of chelators for divalent metal cations, EDTA and TPEN, on the A23187-induced cytotoxicity were cytometrically examined in rat thymocytes. The cytotoxicity of A23187 was attenuated by 1mM EDTA while it was augmented by 50 microM EDTA and 10 microM TPEN. These changes were statistically significant. The A23187-induced increase in Fluo-3 fluorescence intensity, a parameter for [Ca(2+)](i), was significantly reduced by 1mM EDTA while it was not the case for 50 microM EDTA and 10 microM TPEN. The intensity of FluoZin-3 fluorescence, a parameter for [Zn(2+)](i), increased by A23187 was respectively reduced by 50 microM EDTA and 10 microM TPEN. It is suggested that the attenuation of A23187-induced cytotoxicity by 1mM EDTA is due to the chelation of extracellular Ca(2+) and Zn(2+) while the augmentation by 50 microM ETDA or 10 microM TPEN is due to the chelation of extracellular Zn(2+). The Tyrode's solution without thymocytes contained 32.4 nM of zinc while it was 216.9 nM in the cell suspension. In conclusion, trace Zn(2+), derived from cell preparation, partly attenuates the Ca(2+)-dependent cell death induced by A23187.


Assuntos
Calcimicina/farmacologia , Compostos de Cálcio/metabolismo , Ionóforos/farmacologia , Timo/efeitos dos fármacos , Compostos de Zinco/metabolismo , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Ácido Edético/farmacologia , Etilenodiaminas/farmacologia , Ratos , Timo/metabolismo , Timo/patologia
14.
Sex Transm Dis ; 35(12): 990-6, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-18836392

RESUMO

BACKGROUND: Sexually transmitted infections (STIs) increased rapidly in Japan during the 1990s. METHODS: To determine the epidemiologic characteristics of STI patients, male cases (n = 765) from 21 clinics across Japan and controls from the general population (n = 1,167), both aged 18 to 59 years, were compared using two datasets of nationwide sexual behavior surveys conducted in 1999. RESULTS: Male STI patients were more likely to be <40 years of age (OR = 3.94, 95% CI: 2.17, 7.15), unmarried (OR = 2.65, 95% CI: 1.80, 3.91), and at least college/university educated (OR = 2.03, 95% CI: 1.45, 2.83). They were also more likely to have had multiple partnerships in the previous year (OR = 3.33, 95% CI: 2.20, 5.05 for 2-3 partners, OR = 6.29, 95% CI: 3.81, 10.37 for >or=4 partners), unprotected vaginal sex with regular partners (OR = 2.70, 95% CI: 1.75, 4.17), unprotected vaginal and/or oral sex with casual partners (OR = 2.14, 95% CI: 1.40, 3.26), and unprotected vaginal (OR = 2.64, 95% CI: 1.46, 4.80) and oral sex with paid partners (OR = 4.72, 95% CI: 3.04, 7.32) in the previous year. CONCLUSIONS: These results suggest that male STI patients in Japan are highly educated and have a diverse occupational background, and that STI risks exist universally for various types of sex and sexual partnerships.


Assuntos
Demografia , Comportamento Sexual , Doenças Sexualmente Transmissíveis/epidemiologia , Adolescente , Adulto , Estudos de Casos e Controles , Escolaridade , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Assunção de Riscos , Parceiros Sexuais , Doenças Sexualmente Transmissíveis/etiologia , Inquéritos e Questionários , Sexo sem Proteção , Adulto Jovem
15.
Life Sci ; 83(5-6): 164-9, 2008 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-18586279

RESUMO

Quercetin is known to protect the cells suffering from oxidative stress. The oxidative stress elevates intracellular Ca(2+) concentration, one of the phenomena responsible for cell death. Therefore, we hypothesized that quercetin would protect the cells suffering from overload of intracellular Ca(2+). To test the hypothesis, the effects of quercetin on the cells suffering from oxidative stress and intracellular Ca(2+) overload were examined by using a flow cytometer with appropriate fluorescence probes (propidium iodide, fluo-3-AM, and annexin V-FITC) and rat thymocytes. The concentrations (1-30 microM) of quercetin to protect the cells suffering from intracellular Ca(2+) overload by A23187, a calcium ionophore, were similar to those for the cells suffering from oxidative stress by H(2)O(2). The cell death respectively induced by H(2)O(2) and A23187 was significantly suppressed by removal of external Ca(2+). Furthermore, quercetin greatly delayed the process of Ca(2+)-dependent cell death although it did not significantly affect the elevation of intracellular Ca(2+) concentration by H(2)O(2) and A23187, respectively. It is concluded that quercetin can protect the cells from oxidative injury in spite of increased concentration of intracellular Ca(2+). Results suggest that quercetin is also used for protection of cells suffering from overload of intracellular Ca(2+).


Assuntos
Antioxidantes/farmacologia , Cálcio/metabolismo , Citoproteção , Quercetina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Calcimicina/farmacologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
16.
Toxicology ; 248(2-3): 142-50, 2008 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-18468760

RESUMO

The use of zinc as a nutritional supplement has become common in many countries. Since zinc has diverse actions, it may be difficult to predict its synergistic and/or antagonistic action in simultaneous presence of drug(s). The combination of imidazole antifungals, but not triazole antifungals, with 3-30 microM ZnCl2 significantly increased the lethality of rat thymocytes. Since intracellular Zn2+ exerts various actions on the process of cell death, there is a possibility that imidazole antifungals, but not triazole antifungals, increases concentration of intracellular Zn2+ ([Zn2+]i). To test the possibility, we examined the effects of imidazole and triazole antifungals on [Zn2+]i of rat thymocytes in absence and presence of extracellular Zn2+ by the use of FluoZin-3, a fluorescent Zn2+ indicator. Imidazole antifungals (clotrimazole, econazole, and oxiconazole) increased the [Zn2+]i in the presence of extracellular Zn2+ while it was not the case for triazole antifungals (itraconazole and fluoconazole). Thus, it is suggested that imidazole antifungals increase the membrane permeability of Zn2+. The potency order in the augmentation of FluoZin-3 fluorescence by imidazole antifungals in the presence of extracellular Zn2+ was the same as that in their cytotoxic action. Therefore, the cytotoxic action of imidazole antifungals may be related to their action on membrane Zn2+ permeability.


Assuntos
Antifúngicos/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Cloretos/metabolismo , Imidazóis/farmacologia , Timo/efeitos dos fármacos , Triazóis/farmacologia , Compostos de Zinco/metabolismo , Animais , Antifúngicos/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Clotrimazol/química , Clotrimazol/toxicidade , Relação Dose-Resposta a Droga , Fluconazol/química , Fluconazol/toxicidade , Imidazóis/química , Imidazóis/toxicidade , Itraconazol/química , Itraconazol/toxicidade , Masculino , Ratos , Ratos Wistar , Relação Estrutura-Atividade , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Linfócitos T/patologia , Timo/metabolismo , Timo/patologia , Triazóis/química
17.
Toxicol In Vitro ; 22(4): 1002-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18356015

RESUMO

Quercetin, a flavonoid found in fruits and vegetables, exerts beneficial effects that contribute to human health. Therefore, quercetin preparation is expected as complementary or alternative medicine used by general population. The plausible criterion for such medicines is to exert no toxic action on normal cells. In this study, the effects of quercetin on normal cells were examined using rat thymocytes in RPMI-1640 medium. Significant cytotoxic actions of quercetin were observed at 30 microM. Quercetin increased the populations of propidium-stained cells, shrunken cells, annexin V-positive cells, and the cells with hypodiploidal DNA. Thus, the type of cell death induced by quercetin was apoptosis. Z-VAD-FMK, a pan-inhibitor for caspases, partly attenuated the process of quercetin-induced apoptosis. It can be suggested that plasma concentration of quercetin should be below 30 microM after the digestion when quercetin preparation as complementary or alternative medicine is used.


Assuntos
Apoptose/efeitos dos fármacos , Flavonoides/toxicidade , Quercetina/toxicidade , Timo/efeitos dos fármacos , Animais , Anexina A5/metabolismo , DNA/metabolismo , Diploide , Relação Dose-Resposta a Droga , Flavonoides/administração & dosagem , Masculino , Quercetina/administração & dosagem , Ratos , Ratos Wistar , Coloração e Rotulagem , Timo/citologia
18.
BMC Int Health Hum Rights ; 7: 8, 2007 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-17919330

RESUMO

BACKGROUND: Little is known about the HIV/AIDS epidemic in the Indian Ocean region, including Mauritius. National records suggest a prevalence of HIV in Mauritius of < 1% in the general population, which is one of the lowest prevalence rates in southern Africa. However, HIV-positive cases have been increasing recently in Mauritius. We conducted a cross-sectional survey in January 2003 to assess the prevalence of HIVrelated sexual behaviors and their correlates among young people aged 15-24 years in Mauritius. METHODS: We identified 1200 participants using two-stage cluster sampling. Demographic, social, sexual, and knowledge of HIV/AIDS data were obtained in face-to-face interviews using a structured questionnaire administered by trained interviewers. The prevalence of sexual behaviors was described in relation to gender, and the correlates of ever having had sex and nonuse of condom at last sex were analyzed using logistic regression. RESULTS: In the target population, 30.9% of males and 9.7% of females reported a history of sexual intercourse. Of the currently sexually active participants, 50.6% of men and 71.2% of women did not use condoms at their last sexual encounter. Logistic regression revealed that work experience and marijuana use were significantly associated with men's sexual experience, whereas being out of school and drinking experience were significantly associated with women's sexual experience. For both men and women, being Christian and visiting nightclubs were associated with having ever had sexual intercourse (P < 0.05). In addition, not using a condom at the first sexual encounter and lack of exposure to a nongovernmental organization (NGO) dealing with HIV/AIDS were associated with the nonuse of condoms at the last sexual encounter (P < 0.05). CONCLUSION: Young people in Mauritius are at risk of a future HIV epidemic because behaviors predisposing to HIV infection are prevalent among sexually experienced youth. A focused prevention program targeting young people should be reinforced as part of the National AIDS Control Program, taking into account the predictors of sexual behaviors identified here.

19.
Toxicol In Vitro ; 21(6): 1113-20, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17544615

RESUMO

Fluoride is found in the atmosphere, water, soil, coal, food, dental and industrial uses. There were some case reports concerning acute fluoride poisoning in workplaces and laboratories. However, there is limited information concerning the mechanism of fluoride-induced cell death. To study the cytotoxicity of fluoride, the effect of sodium fluoride (NaF) on rat thymocytes has been examined by using a flow cytometer with appropriate fluorescence probes for membrane and cellular parameters. The cytotoxicity of NaF under nominal Ca2+-free condition was significantly lower than that under control condition. NaF also increased intracellular Ca2+ concentration. NaF significantly increased the population of shrunken cells and the cells positive to annexin V. Both are known to be parameters for early stage of apoptosis. However, NaF decreased the population of cells with hypodiploidal DNA, indicating that NaF apparently attenuated spontaneous apoptosis in rat thymocytes. It may be suggested that NaF induces necrosis, associated with some apoptotic characteristics.


Assuntos
Fluoreto de Sódio/toxicidade , Linfócitos T/efeitos dos fármacos , Animais , Cálcio/metabolismo , Morte Celular , Células Cultivadas , Masculino , Ratos , Ratos Wistar , Linfócitos T/metabolismo , Linfócitos T/patologia
20.
Toxicol Lett ; 171(3): 138-45, 2007 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-17583447

RESUMO

In our previous study, the application of clotrimazole, an antifungal drug, with CdCl(2) or PbCl(2) significantly increased cell lethality of rat thymocytes, even though their individual concentrations were ineffective in affecting the viability. This observation prompted us to study the case for the combination of clotrimazole and ZnCl(2) because the use of zinc as a nutritional supplement has become common. Their combination induced very potent cytotoxic action on rat thymocytes with "bell-shape" dose-response relation. An acceleration of apoptotic process by the combination was suggested for the mechanism. The present result may provide a new insight into toxicological characteristics of clotrimazole.


Assuntos
Antifúngicos/toxicidade , Clotrimazol/toxicidade , Linfócitos T/efeitos dos fármacos , Zinco/toxicidade , Animais , Anexina A5/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Indicadores e Reagentes , Masculino , Microscopia de Fluorescência , Fosfatidilserinas/metabolismo , Propídio , Ratos , Ratos Wistar
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