RESUMO
Oxidation hair-dyes, which are the principal hair-dyes, sometimes induce painful sensory irritation of the scalp caused by the combination of highly reactive substances, such as hydrogen peroxide and alkali agents. Although many cases of severe facial and scalp dermatitis have been reported following the use of hair-dyes, sensory irritation caused by contact of the hair-dye with the skin has not been reported clearly. In this study, we used a self-assessment questionnaire to measure the sensory irritation in various regions of the body caused by two model hair-dye bases that contained different amounts of alkali agents without dyes. Moreover, the occipital region was found as an alternative region of the scalp to test for sensory irritation of the hair-dye bases. We used this region to evaluate the relationship of sensitivity with skin properties, such as trans-epidermal water loss (TEWL), stratum corneum water content, sebum amount, surface temperature, current perception threshold (CPT), catalase activities in tape-stripped skin and sensory irritation score with the model hair-dye bases. The hair-dye sensitive group showed higher TEWL, a lower sebum amount, a lower surface temperature and higher catalase activity than the insensitive group, and was similar to that of damaged skin. These results suggest that sensory irritation caused by hair-dye could occur easily on the damaged dry scalp, as that caused by skin cosmetics reported previously.
Assuntos
Álcalis/efeitos adversos , Tinturas para Cabelo/efeitos adversos , Irritantes/efeitos adversos , Pele/efeitos dos fármacos , Adulto , Amônia/efeitos adversos , Humanos , Peróxido de Hidrogênio/efeitos adversos , MasculinoRESUMO
BACKGROUND: Skin pigmentation by ultraviolet (UV) B radiation is caused in part by inflammation mediated by chemokines and cytokines secreted by keratinocytes in the irradiated area. However, such inflammatory processes have not been well documented. OBJECTIVES: To elucidate the inflammation processes caused by UVB irradiation using skin-lightening agents that suppress melanin synthesis after UVB irradiation. METHODS: Utilizing a three-dimensional (3D) skin model, agents that suppressed formation of sunburn cells (SBC) after UVB irradiation were screened. Molecules whose expression was upregulated by UVB irradiation and attenuated by pretreatment with the agent were then screened by gene microarray to explore the mechanism of UVB irradiation. Messenger RNA expression of the molecules identified to be responsible for melanin biosynthesis was knocked down with a Tet-off shRNA lentivirus construct to confirm the involvement of the molecule in the pigmentation pathway following UVB irradiation. RESULTS: Paeonia suffruticosa Andrews (PSA) pretreatment suppressed SBC formation in the 3D skin model, and erythema formation and pigmentation in volunteers exposed to UVB irradiation. Comprehensive gene analysis after UVB irradiation showed upregulation of CXCR3 and its ligands, CXCL9/monokine induced by interferon (IFN)-γ (MIG), CXCL10/10-kDa IFN-γ-induced protein (IP-10) and CXCL11/inducible T-cell α-chemoattractant (I-TAC). Upregulation of these genes was partially suppressed by PSA pretreatment. Melanin biosynthesis increased upon stimulation of CXCR3 ligands (MIG, IP-10 or I-TAC) and decreased following CXCR3 downregulation by shRNA knockdown. CONCLUSIONS: UVB irradiation activates CXCR3-mediated signalling that leads to melanin synthesis. PSA pretreatment shows a lightening effect partly by attenuating CXCR3-mediated signalling at the transcriptional level.
Assuntos
Dermatite/metabolismo , Eritema/prevenção & controle , Receptores CXCR3/antagonistas & inibidores , Pigmentação da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Células Cultivadas/metabolismo , Quimiocina CXCL10/metabolismo , Quimiocina CXCL11/metabolismo , Dermatite/fisiopatologia , Eritema/genética , Regulação da Expressão Gênica , Humanos , Interferon gama/farmacologia , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Melaninas/biossíntese , Melaninas/genética , Análise em Microsséries , Paeonia , Preparações de Plantas/farmacologia , RNA Mensageiro/metabolismo , Receptores CXCR/metabolismo , Receptores CXCR3/genética , Receptores CXCR3/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/irrigação sanguínea , Pele/patologia , Pigmentação da Pele/genética , Queimadura Solar , Regulação para CimaAssuntos
Cateterismo , Endoscopia Gastrointestinal , Divertículo Ileal/diagnóstico , Adolescente , Coristoma/diagnóstico , Coristoma/patologia , Coristoma/cirurgia , Mucosa Gástrica , Humanos , Doenças do Íleo/diagnóstico , Doenças do Íleo/patologia , Doenças do Íleo/cirurgia , Íleo/patologia , Laparoscopia , Masculino , Divertículo Ileal/patologia , Divertículo Ileal/cirurgia , Melena/etiologia , Úlcera/diagnóstico , Úlcera/patologiaRESUMO
BACKGROUND AND PURPOSE: Parabens are commonly added in pharmaceutical, cosmetic and food products because of their wide antibacterial properties, low toxicity, inertness and chemical stability, although the molecular mechanism of their antibacterial effect is not fully understood. Some agonists of the transient receptor potential (TRP) A1 channels are known to have strong antibacterial activities. Therefore, a series of experiments was conducted to find out the effects of parabens on TRP channels expressed in sensory neurons, particularly the TRPA1 channels. EXPERIMENTAL APPROACH: Effects of parabens, especially of methyl p-hydroxybenzoate (methyl paraben) on TRP channel activities were examined using Ca(2+)-imaging and patch-clamp methods. In addition, an involvement of methyl paraben in the development of pain-related behavior in mice was investigated. KEY RESULTS: Methyl paraben specifically activated TRPA1 in both HEK293 cells expressing TRPA1 and in mouse sensory neurons with an EC(50) value of 4.4 mM, an attainable concentration in methyl paraben-containing products. Methyl paraben caused pain-related behavior in mice similar to that caused by allyl isothiocyanate, which was blocked by the TRP channel blocker, ruthenium red. CONCLUSIONS AND IMPLICATIONS: Our data indicate that methyl paraben is able to activate TRPA1 channels and can cause pain sensation. As such, methyl paraben provides a useful tool for investigating TRPA1 function and development of antinociceptive agents acting on TRPA1 channels.
Assuntos
Canais de Cálcio/efeitos dos fármacos , Proteínas de Membrana/efeitos dos fármacos , Proteínas do Tecido Nervoso/efeitos dos fármacos , Dor/induzido quimicamente , Parabenos/farmacologia , Canais de Potencial de Receptor Transitório/efeitos dos fármacos , Animais , Cálcio/metabolismo , Canais de Cálcio/fisiologia , Células Cultivadas , Relação Dose-Resposta a Droga , Humanos , Masculino , Proteínas de Membrana/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/fisiologia , Canal de Cátion TRPA1 , Canais de Potencial de Receptor Transitório/fisiologiaRESUMO
BACKGROUND: The epidemiology and pathophysiology of non-erosive gastro-oesophageal reflux disease differs from erosive gastro-oesophageal reflux disease. There is a possibility that non-erosive gastro-oesophageal reflux disease treatment requires a different regimen/approach but it is not yet acknowledged. AIM: To investigate the efficacy of famotidine and omeprazole in the treatment of gastro-oesophageal reflux disease, especially non-erosive gastro-oesophageal reflux disease. PATIENTS AND METHODS: A randomized, open-label trial was conducted. Fifty-four gastro-oesophageal reflux disease patients were assigned to treatment with famotidine at a dosage of 20 mg twice daily; or omeprazole, 20 mg once daily, for a period of 8 weeks. The Short Form-36 Health Survey and Gastrointestinal Symptom Rating Scale administered at baseline and after 8 weeks of treatment as well as a symptom questionnaire were conducted daily. RESULTS: Short Form-36 revealed that gastro-oesophageal reflux disease has severe impact on health-related quality of life. Thirty-nine subjects (77%) were endoscopically diagnosed as non-erosive gastro-oesophageal reflux disease. The mean Gastrointestinal Symptom Rating Scale abdominal pain, and indigestion score of non-erosive gastro-oesophageal reflux disease significantly improved in famotidine-treated patients (P < 0.05), but not in the omeprazole. There was no significant change regarding improved heartburn symptoms of non-erosive gastro-oesophageal reflux disease between treatments in the daytime or night-time. CONCLUSION: Famotidine and omeprazole were both effective in improving symptoms of gastro-oesophageal reflux disease, particularly non-erosive gastro-oesophageal reflux disease.
Assuntos
Antiulcerosos/administração & dosagem , Famotidina/administração & dosagem , Refluxo Gastroesofágico/tratamento farmacológico , Omeprazol/administração & dosagem , Análise de Variância , Quimioterapia Combinada , Feminino , Azia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e Questionários , Resultado do TratamentoAssuntos
Salas Cirúrgicas , Atitude do Pessoal de Saúde , Previsões , Humanos , Processamento de Imagem Assistida por Computador/instrumentação , Laparoscopia , Microcomputadores , Procedimentos Cirúrgicos Minimamente Invasivos/instrumentação , Enfermagem de Centro Cirúrgico , Auxiliares de Cirurgia/psicologia , Médicos/psicologia , Equipamentos Cirúrgicos , Telecomunicações/instrumentação , Televisão , Cirurgia Vídeoassistida/instrumentaçãoRESUMO
This study evaluated the efficacy of a novel hyaluronic acid (HA) gel for preventing adhesions in a rat caecal model. The gel was manufactured from an acidic HA solution using a freezing procedure. HA gel films with four different half-lives (50-200 h) in physiological buffered saline at 37 degrees C were prepared, by regulating the freezing time, and tested. The HA gel film was applied as a barrier on the injured caecal surface after standardized treatment with a rotary abrasion apparatus. A control group of 20 animals were abraded in the same way but not treated. Seven days after the initial operation, the incidence and severity of any adhesions were recorded. Application of the HA gel film significantly reduced the incidence and severity of adhesion formation in all treatment groups compared with the control group. This novel HA gel film is effective for reducing post-operative adhesions in this rat model and the resorption rate is optimum for adhesion prevention on the caecal surface.
Assuntos
Ácido Hialurônico/farmacologia , Aderências Teciduais/prevenção & controle , Animais , Ceco/patologia , Ceco/cirurgia , Feminino , Géis , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/prevenção & controle , Ratos , Ratos Wistar , Aderências Teciduais/patologiaRESUMO
The antitumor effects of human tumor necrosis factor-alpha (TNF) mutant RGD-V29 (code no. F4614), that includes the cell adhesive sequence (4)Arg-(5)Gly-(6)Asp and (29)Arg-->Val substitution, were evaluated. The therapeutic index, a measure of the extent of the therapeutically-effective range, using three constitutive administrations of RGD-V29 in Meth A-bearing mice was 4.8, whereas that of recombinant human TNF (rhTNF) ((1)SSS(4)RTPSDK...(29)RR...(155)L) was 2.8, clearly indicating that the effective RGD-V29 dose-range was extended. Furthermore, RGD-V29 showed potent antitumor activity against human lung cancer Mqnu-1 xenografted nude mice without severe gastrointestinal and other organ toxicities, even when administered at the maximal tolerated dose (MTD). In contrast, rhTNF induced severe toxicity at the MTD. Direct cytotoxicity of RGD-V29 against Mqnu-1 cells was similar to that of rhTNF. In addition, a cytotoxicity assay using a tumor-derived endothelial-like cell (tEC)/normal endothelial cell (nEC) system used to study TNF antitumor effects on tumor-associated endothelial cells, suggested that RGD-V29 showed preferential cytotoxicity toward tumor-associated endothelial cells compared with rhTNF. Thus, RGD-V29 appears to be a low-toxicity mutant of rhTNF that shows preferential activity towards tumors, and therefore merits further investigation in pre-clinical and clinical studies.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Fator de Necrose Tumoral alfa/uso terapêutico , Sequência de Aminoácidos , Substituição de Aminoácidos , Animais , Antineoplásicos/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Proteínas Recombinantes/farmacologia , Proteínas Recombinantes/uso terapêutico , Fatores de Tempo , Transplante Heterólogo , Células Tumorais Cultivadas , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
KM871 is a chimeric antibody recognizing ganglioside GD3, which is one of the major gangliosides expressed on the cell surface of human tumors of neuroectodermal origin. This study demonstrates the antitumor activity of KM871 against human melanoma xenografts in nude mice, and analyzes the effector function operating in mice. In a well-established tumor model, KM871 showed antitumor activity against H-15 and SK-MEL-28 human melanoma but not against H-187 and G361 human melanoma when administered intravenously 5 days/week for 2 weeks. The G361 tumor became sensitive when KM871 was first administered on the day of tumor inoculation. In this assay, it was observed that almost all the mice were tumor-free, but a few mice developed tumors. Therefore, we examined the amount and expression pattern of GD3 antigen on G361 tumors escaping from KM871 treatment, but no change was observed. Next we examined the optimal administration schedule for KM871 in mice, using H-15 melanoma. KM871 showed antitumor activity when administered intravenously either 5 days/week for 2 weeks or three biweekly doses. However, the effect of the former schedule was stronger than three biweekly doses. To compare the effector function in humans and mice, we studied the complement-mediated cytotoxicity, antibody-dependent cell-mediated cytotoxicity and antibody-dependent macrophage-mediated cytotoxicity of KM871 using complement or effector cells prepared from humans and mice. It was found that the antibody-dependent cell-mediated cytotoxicity exerted by polymorphonuclear cells and antibody-dependent macrophage-mediated cytotoxicity were the only antitumor mechanism of KM871 in mice. However their action was very weak compared with that in humans, and complement-mediated cytotoxicity, which was strong in humans, was not observed in mice. Therefore, the antitumor activity of KM871 against human melanomas evaluated by the nude mouse model might be underestimated. These results indicate that KM871 shows good antitumor activity against GD3-positive human melanoma and the antitumor activity expected in humans might be superior to that of the nude mouse model.
Assuntos
Anticorpos/uso terapêutico , Gangliosídeos/imunologia , Imunoglobulina G/farmacologia , Imunoglobulina G/uso terapêutico , Melanoma Experimental/imunologia , Melanoma Experimental/terapia , Animais , Peso Corporal/imunologia , Morte Celular/imunologia , Cromatografia em Camada Fina , DNA Complementar/metabolismo , Relação Dose-Resposta Imunológica , Humanos , Imunização Passiva , Leucócitos Mononucleares/imunologia , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Fatores de Tempo , Células Tumorais CultivadasRESUMO
To determine arterial oxygen tension (PaO2) in mechanically ventilated patients, we repeatedly measured arterial blood gas (ABG) to examine changes in PaO2 until equilibration following alteration of fractional concentrations of oxygen in inspired gas (FIO2). Forty anesthetized patients with normal arterial oxygenation were randomly assigned to one of four groups. Group 1 (n = 10): Arterial blood samples were drawn every one minute during a 15-min period of equilibration after change of FIO2 from 1.0 to 0.21. Then FIO2 was returned to 1.0 and the similar sampling was repeated. Group 2 (n = 10): The protocol was same as in Group 1 except for FIO2 targeted for 0.8 and 0.4. Group 3 (n = 10): Blood sampling was every two minutes during a 14-min period and repeated while FIO2 was altered as in Group 1. Group 4 (n = 10): The protocol was same as in Group 3 except for the target FIO2 similar to Group 2. PaO2 was stabilized in 4 min at earliest and in 6 min at latest after change of FIO2 in every settings of this study. In mechanically ventilated patients with normal arterial oxygenation, PaO2 could be stabilized after a 6-min period of equilibration following alteration of FIO2.
Assuntos
Oxigênio/sangue , Troca Gasosa Pulmonar/fisiologia , Respiração Artificial , Gasometria , Testes Respiratórios , Humanos , Oxigênio/análise , Pressão Parcial , Fatores de TempoRESUMO
TZT-1027 was evaluated for its antitumor effects in sixteen human tumors xenografted in nude mice from gastric (H-81, H-106, H-30, H-154), breast (H-31, H-62), colon (H-110, H-143), lung (LC-376, H-74, Mqnu-1, LC-351), liver (H-181), renal cell (H-12) and ovarian (H-OC-3, SOC-4) cancer lines. In the latter three and lung (Mqnu-1, LC-351) cancers the results were compared with those obtained with CPT-11, VCR, CDDP, ADM. TZT-1027 showed effective antitumor activity (IR > or = 58%) against fifteen of the tumor lines, all but LC-351, and showed markedly effective activity (IR > or = 80%) against twelve tumor lines, including drug-resistant colon (H-110), lung (H-74) and ovarian (SOC-4) cancer lines. The complete regression was shown in five H-OC-3 tumor-bearing mice out of seven. Moreover, TZT-1027 was shown to be more potent in three cancer models (Mqnu-1, H-81, SOC-4) than CPT-11, and to have markedly effective antitumor activity in two cancers (H-12, H-OC-3) in which VCR was ineffective and in ovarian cancer (SOC-4) in which CPT-11, CDDP and ADM were ineffective. The administration of TZT-1027 induced fewer side effects; transient reduction of body weight was observed in four lines out of sixteen tested. These results suggest that TZT-1027 is an excellent candidate for clinical trials for the treatment of cancer.
Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Oligopeptídeos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Animais , Peso Corporal/efeitos dos fármacos , Humanos , Camundongos , Camundongos Nus , Transplante de NeoplasiasRESUMO
Factors that influence the relation between extraversion and pleasant affect were examined in 6 studies. In Studies 1 through 5, the authors used structural equation modeling techniques to test whether different extraversion and pleasant affect scales and the use of multiple methods of assessment influenced the strength of the relation. In Study 6, the authors conducted a meta-analysis of previous literature to calculate an average effect size and to assess the influence of moderator variables. Results from both the structural equation models and the meta-analysis showed that with only a few exceptions, the use of different extraversion and affect scales resulted in moderate to strong correlations. The use of "on-line" methods of mood assessment (moment reports or daily-diary reports) resulted in lower and more homogeneous correlations than did the use of global, retrospective measures of mood.
Assuntos
Afeto , Extroversão Psicológica , Adulto , Feminino , Humanos , Masculino , Determinação da Personalidade , Estudantes/psicologiaRESUMO
BACKGROUND: Mutations in the adenomatous polyposis coli (APC) tumour suppressor gene are implicated in the genesis of colorectal cancers. The product of the APC gene forms a complex with beta-catenin, glycogen synthase kinase 3beta (GSK-3beta) and Axin/conductin, and induces the degradation of beta-catenin. RESULTS: We have identified a novel Drosophila homologue of APC, E-APC, which is similar to but differs in several respects from D-APC. The E-APC cDNA encodes a protein of predicted 1067 amino acids, with seven armadillo repeats, two copies of the 15-amino acid repeat, five copies of the 20-amino acid repeat, and one Axin/conductin binding site. E-APC directly interacts with D-Axin and Armadillo (Arm, the Drosophila homologue of beta-catenin) in vitro, destabilizes intracellular beta-catenin, and suppresses beta-catenin/TCF-regulated transcription in APC-/- colon cancer cells. The E-APC mRNA is ubiquitously expressed throughout all developmental stages in Drosophila. CONCLUSION: Our findings suggest that E-APC may be universally involved in the regulation of the Wingless signalling pathway by down-regulating the level of Arm in Drosophila.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas do Citoesqueleto/química , Proteínas do Citoesqueleto/genética , Proteínas de Drosophila , Transativadores , Proteína da Polipose Adenomatosa do Colo , Sequência de Aminoácidos , Animais , Proteínas do Domínio Armadillo , Proteína Axina , Proteínas de Transporte/metabolismo , Clonagem Molecular , Proteínas do Citoesqueleto/metabolismo , DNA Complementar/análise , Proteínas de Ligação a DNA/metabolismo , Drosophila/genética , Humanos , Proteínas de Insetos/metabolismo , Fator 1 de Ligação ao Facilitador Linfoide , Modelos Genéticos , Dados de Sequência Molecular , Plasmídeos/metabolismo , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas , Técnicas do Sistema de Duplo-Híbrido , beta CateninaRESUMO
Wnt/Wingless directs many cell fates during development. Wnt/Wingless signaling increases the amount of beta-catenin/Armadillo, which in turn activates gene transcription. Here the Drosophila protein D-Axin was shown to interact with Armadillo and D-APC. Mutation of d-axin resulted in the accumulation of cytoplasmic Armadillo and one of the Wingless target gene products, Distal-less. Ectopic expression of d-axin inhibited Wingless signaling. Hence, D-Axin negatively regulates Wingless signaling by down-regulating the level of Armadillo. These results establish the importance of the Axin family of proteins in Wnt/Wingless signaling in Drosophila.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas de Transporte/metabolismo , Proteínas de Drosophila , Drosophila/embriologia , Proteínas/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Repressoras , Transdução de Sinais , Transativadores , Fatores de Transcrição , Proteína da Polipose Adenomatosa do Colo , Animais , Proteínas do Domínio Armadillo , Proteína Axina , Padronização Corporal , Proteínas de Transporte/química , Proteínas de Transporte/genética , Mapeamento Cromossômico , Citoplasma/metabolismo , Proteínas do Citoesqueleto/metabolismo , Regulação para Baixo , Drosophila/genética , Drosophila/metabolismo , Embrião não Mamífero/metabolismo , Extremidades/embriologia , Regulação da Expressão Gênica no Desenvolvimento , Genes de Insetos , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Hibridização In Situ , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Dados de Sequência Molecular , Mutação , Fenótipo , Proteínas/química , Proteínas/genética , Proteínas Recombinantes de Fusão/metabolismo , Asas de Animais/embriologia , Asas de Animais/metabolismo , Proteína Wnt1RESUMO
We investigated the effects of the presence or absence of N2O in propofol anesthesia using a laryngeal mask on the incidence of postoperative sore throat. In the N2O-combined anesthesia group (n = 25), score 0 (no sore throat) was observed in 11 patients; score 1 (slight pain and discomfort that improved on the next day of operation) in 9; and score 2 (persistent pain on the next day) in 5. In the non-N2O-combined anesthesia group (n = 25), score 0 was observed in 21 patients, score 1 in 3; and score 2 in 1, showing a significantly lower incidence of sore throat and milder sore throat than in the N2O-combined anesthesia group. These results suggest that propofol anesthesia using a laryngeal mask not combined with N2O reduces the incidence of postoperative sore throat.
Assuntos
Ar , Anestesia por Inalação , Anestésicos Intravenosos , Máscaras Laríngeas/efeitos adversos , Oxigênio , Faringite/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Propofol , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nitroso/efeitos adversosRESUMO
The effect of life events on subjective well-being (SWB) was explored in a 2-year longitudinal study of 115 participants. It was found that only life events during the previous 3 months influenced life satisfaction and positive and negative affect. Although recent life events influenced SWB even when personality at Time 1 was controlled, distal life events did not correlate with SWB. SWB and life events both showed a substantial degree of temporal stability. It was also found that good and bad life events tend to covary, both between individuals and across periods of the lives of individuals. Also, when events of the opposite valence were controlled, events correlated more strongly with SWB. The counterintuitive finding that good and bad events co-occur suggests an exciting avenue for explorations of the structure of life events.
Assuntos
Acontecimentos que Mudam a Vida , Satisfação Pessoal , Adulto , Afeto , Feminino , Humanos , Estudos Longitudinais , Masculino , PersonalidadeRESUMO
CGP 41251 (4'-N-benzoyl staurosporine, CAS 120685-11-2) has been shown to exert increased selectivity for the inhibition of protein kinase C (PKC) activity. In the present study the effect of CGP 41251 formulated in gelucire as an antitumor agent was studied in various types of murine and human tumor models. When administered at a dose of 75 mg/kg 3 times daily for 9 days, CGP 41251 prolonged the life span of the mice bearing B16 melanoma (ILS = 36%). CGP 41251, administered orally at doses of 25-225 mg/kg once daily for 9 days, however, did not show distinct efficacy in four kinds of murine tumor models (B16 melanoma, colon 26, colon 38 and M5076). In s.c.inoculated human tumor xenograft models, CGP 41251, administered orally at a dose of 200 mg/kg once daily for 4 weeks showed a broad antitumor spectrum. CGP 41251 inhibited the growth of gastric cancer (H-55), colorectal cancer (H-26), breast cancer (H-31) and lung cancer (H-74 and LC-376) with inhibition rates of 58-80%. In a histopathologic study, increase in central necrosis and condensed nuclei and vacuolar degeneration were observed, but there was no structural destruction by the treatment of CGP 41251. In addition, CGP 41251 decreased the number of PCNA (proliferating cell nuclear antigen) immunoreactive cells in human tumor cells H-55, H-26 and H-74. These results indicate that CGP 41251 shows a broad antitumor spectrum against human tumors, and it is suggested that CGP 41251 is a promising oral antitumor agent which has a novel mechanism of action.
Assuntos
Antineoplásicos/farmacologia , Neoplasias Experimentais/tratamento farmacológico , Proteína Quinase C/antagonistas & inibidores , Estaurosporina/análogos & derivados , Animais , Antineoplásicos/uso terapêutico , Dieta , Feminino , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Transplante de Neoplasias , Neoplasias Experimentais/patologia , Estaurosporina/farmacologia , Células Tumorais CultivadasRESUMO
The covariation of resources such as money, family support, social skills, and intelligence with subjective well-being (SWB) was assessed in 195 college students. Informant ratings provided an index of resources. Self-reports, daily experience sampling, and informant reports were used to measure SWB. The authors concluded that resources taken together are moderately strong predictors of SWB. This conclusion, however, was qualified by the fact that life satisfaction was more closely related to resources than was affective well-being and that social and personal resources were in general more strongly related to SWB than were material resources. The findings also supported the hypothesis that resources correlate more strongly with SWB when they are relevant to an individual's idiographic personal strivings. A tendency was found for people to choose personal strivings for which they have relevant resources, and the degree of congruence of individuals' goals with resources was predictive of SWB.
Assuntos
Logro , Fatores Socioeconômicos , Afeto , Feminino , Objetivos , Humanos , Masculino , Personalidade , Fatores SexuaisRESUMO
One of the problems in the treatment of cancer is the development of resistance to anti-tumor agents when used repeatedly. We described the induction of resistance, cross-resistance to cisplatin (CDDP) or vindesine (VDS) and the side effects of gemcitabine, a new Ara-C derivative, in human lung cancers, Mqnu-1 or H-74 xenografted in nude mice. We investigated the effects of 4-week observation period. Gemcitabine was effective and did not show the acquired resistance when given repeatedly. In contrast, CDDP but not VDS, when given repeatedly, showed a decrease of the anti-tumor effect in the second course. Gemcitabine was still effective to the large tumor grown after CDDP or VDS therapy. Thus, gemcitabine may not develop resistance nor show cross-resistance to CDDP or VDS. In addition, repeated treatment with gemcitabine was much safer than CDDP or VDS. These results suggest that gemcitabine is a candidate for the first choice drug in cancer treatment.