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1.
Chemistry ; 29(1): e202203884, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36592161

RESUMO

Invited for the cover of this issue are Kentaro Tanaka at Nagoya University and co-workers. The image depicts three isomers of a terbium(III) phthalocyanine double-decker complex made from C4h symmetrically substituted phthalocyanines and their magnetic properties. Read the full text of the article at 10.1002/chem.202203272.

2.
Chemistry ; 29(1): e202203272, 2023 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-36448188

RESUMO

A C4h symmetrically substituted phthalocyanine, 1,8,15,22-tertrakis(2,4-dimethylpent-3-oxy)phthalocyanine (H2 TdMPPc), was used to synthesize Tb3+ -phthalocyanine double-decker complexes ([Tb(TdMPPc)2 ]s). Because H2 TdMPPc has C4h symmetry, S,S, R,R, and meso isomers of [Tb(TdMPPc)2 ] were obtained depending on the difference in the direction of the coordination plane of two C4h -type phthalocyanines with respect to a central Tb3+ ion. We investigated the physical properties of these [Tb(TdMPPc)2 ] isomers, including their single-ion magnetic properties, and found that the spin-reversal energy barrier (Ueff ) of the meso isomer was apparently higher than that of the enantiomers. Detailed crystal structural analyses indicated that the meso isomer has a more symmetrical structure than do the enantiomers, thereby suggesting that the higher Ueff of the meso isomer originated from the more highly symmetrical structure.

3.
Skin Res Technol ; 28(4): 582-595, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35723085

RESUMO

BACKGROUND: Skin transparency is a cosmetic asset highly considered by Asian women. Resulting from complex light interactions within the skin, but still not fully understood, there is no simple method to measure it objectively. In this study, skin parameters from digital images were analysed to build a model predicting transparency. MATERIALS AND METHODS: Initially, 71 Japanese women (between ages 50 and 60 years) were recruited. This group was then extended to 262 women (between ages 21 and 60 years). Pictures of their faces were taken with the Colorface® under diffuse light and different polarisation angles. Experts graded their transparency using pictures. Pictures were also used to compute 958 skin colour and surface parameters from different regions of the face. RESULTS: In the initial group of 71 subjects, 109 parameters correlated with transparency. Half of them are from the cheek and relate to colour or colour homogeneity. If the cheek presented the largest proportion of correlated parameters, best correlations were usually found in other facial regions. Multiple regressions from some cheek parameters can predict up to 80% of transparency. Stepwise regression on parameters from 262 subjects led to a six-parameter model, which is highly correlated (R = 84.1%) with transparency. It combines skin texture, colour, colour homogeneity and gloss parameters. If half of them are from the cheek, the others are from the tear trough, the full face and the cheekbone. CONCLUSION: Using parameters from digital pictures exclusively, we propose a model that accurately reflects transparency. Including parameters previously shown to relate to transparency, this model should be useful for future dermatology and cosmetic research.


Assuntos
Envelhecimento da Pele , Pigmentação da Pele , Adulto , Bochecha , Face/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Pele/diagnóstico por imagem , Adulto Jovem
4.
Int J Mol Sci ; 22(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669634

RESUMO

Little is known about the effects on hyaluronan (HA) metabolism of UVA radiation. This study demonstrates that the secretion of HA by human dermal fibroblasts (HDFs) is downregulated by UVA, accompanied by the down- and upregulation of mRNA and protein levels of the HA-synthesizing enzyme (HAS2) and the HA-degrading protein, HYaluronan Binding protein Involved in HA Depolymerization(HYBID), respectively. Signaling analysis revealed that the exposure distinctly elicits activation of the p38/MSK1/CREB/c-Fos/AP-1 axis, the JNK/c-Jun axis, and the p38/ATF-2 axis, but downregulates the phosphorylation of NF-kB and JAK/STAT3. A signal inhibition study demonstrated that the inhibition of p38 significantly abrogates the UVA-accentuated mRNA level of HYBID. Furthermore, the inhibition of STAT3 significantly downregulates the level of HAS2 mRNA in non-UVA exposed HDFs. Analysis using siRNAs demonstrated that transfection of ATF-2 siRNA but not c-Fos siRNA abrogates the increased protein level of HYBID in UVA-exposed HDFs. An inhibitor of protein tyrosine phosphatase but not of protein serine/threonine phosphatase restored the diminished phosphorylation level of STAT3 at Tyr 705, accompanied by a significant abolishing effect on the decreased mRNA expression level of HAS2. Silencing with a protein tyrosine phosphatase PTP-Meg2 siRNA revealed that it abrogates the decreased phosphorylation of STAT3 at Tyr 705 in UVA-exposed HDFs. These findings suggest that the UVA-induced decrease in HA secretion by HDFs is attributable to the down- and upregulation of HAS2 and HYBID expression, respectively, changes that are mainly ascribed to the inactivated signaling of the STAT3 axis due to the activated tyrosine protein phosphatase PTP-Meg2 and the activated signaling of the p38/ATF2 axis, respectively.


Assuntos
Regulação para Baixo/efeitos da radiação , Fibroblastos/efeitos da radiação , Hialuronan Sintases/metabolismo , Ácido Hialurônico/metabolismo , Hialuronoglucosaminidase/metabolismo , Transdução de Sinais/efeitos da radiação , Raios Ultravioleta , Regulação para Cima/efeitos da radiação , Fator 2 Ativador da Transcrição/metabolismo , Morte Celular/efeitos dos fármacos , Morte Celular/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Derme/citologia , Regulação para Baixo/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Janus Quinase 2/metabolismo , Masculino , Modelos Biológicos , Peso Molecular , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT3/metabolismo , Regulação para Cima/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
5.
Chemotherapy ; 62(4): 239-245, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28472787

RESUMO

We retrospectively evaluated clinical data from patients with advanced non-small-cell lung cancer (NSCLC) treated with third-generation chemotherapy agents prior to treatment, to determine a reliable method for predicting prognosis in such patients. We analyzed 100 patients who received third-generation agents (paclitaxel, docetaxel, gemcitabine, irinotecan, and vinorelbine) for the treatment of advanced NSCLC. Factors significantly related to prognosis were evaluated using the Cox regression model, and the prognostic index (PI) was determined by combining these factors. The mean follow-up duration was 12.6 months (0.2-67.0 months). Multivariate analysis identified pleural effusion, absolute neutrophil count (ANC), and C-reactive protein (CRP) level as significant factors that independently contribute to prognosis in patients with advanced NSCLC treated with third-generation agents (p < 0.05). The PI was calculated using these 3 factors, according to the following formula: PI = 0.581 × pleural effusion + 0.125 × ANC + 0.105 × CRP. The death rate in the group with the highest PI scores was significantly higher than in the group with the lowest scores (p < 0.001). Pleural effusion, ANC, and CRP level were the most important factors that contributed to prognosis following chemotherapy with third-generation agents in patients with advanced NSCLC. The PI is suggested to be an appropriate index to predict the prognosis of patients with NSCLC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Feminino , Humanos , Leucócitos/citologia , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de Sobrevida , Taxoides/administração & dosagem , Vimblastina/administração & dosagem , Vimblastina/análogos & derivados , Vinorelbina , Gencitabina
6.
Cytokine ; 73(2): 184-97, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25777483

RESUMO

BACKGROUND: Paracrine interactions between keratinocytes and melanocytes via cytokines play an essential role in regulating pigmentation in epidermal hyperpigmentary disorders. There is an urgent need for a human epidermal model in which melanogenic paracrine interactions between UVB-exposed keratinocytes and melanocytes can be precisely evaluated because human epidermal equivalents consisting of multilayered keratinocytes and melanocytes have significant limitations in this respect. OBJECTIVE: To resolve this challenge, we established a co-culture system with cell inserts using human keratinocytes and human melanocytes that serves as an appropriate new model for UVB-induced hyperpigmentation. Using that new model, we examined the blocking effects of two natural chemicals, astaxanthin and withaferin A, on paracrine cytokine interactions between UVB-exposed keratinocytes and melanocytes and characterized their mechanisms of action. METHODS AND RESULTS: RT-PCR analysis showed that co-culture of human keratinocytes that had been exposed to UVB significantly stimulated human melanocytes to increase their expression of genes encoding microphthalmia-associated transcription factor, tyrosinase and tyrosinase-related protein 1. The catalytic activity of tyrosinase was also increased. ELISA assays revealed that UVB significantly increased the secretion of interleukin-1α, interleukin-6/8, granulocyte macrophage stimulatory factor and endothelin-1 but not α-melanocyte stimulating hormone. The addition of an endothelin-1 neutralizing antibody significantly abrogated the increase of tyrosinase activity. Post-irradiation treatment with astaxanthin or withaferin A significantly abolished the up-regulation of tyrosinase activity induced by UVB. Treatment with astaxanthin or withaferin A significantly reduced the increased levels of interleukin-1α, interleukin-6/8, granulocyte macrophage stimulatory factor and endothelin-1. Withaferin A but not astaxanthin also significantly abrogated the endothelin-1-stimulated activity of tyrosinase in melanocytes. Western blot analysis of intracellular signaling factors revealed that withaferin A but not astaxanthin significantly abolished the endothelin-1-stimulated phosphorylation of Raf-1, MEK, ERK, MITF and CREB in human melanocytes. CONCLUSIONS: These results demonstrate that this co-culture system is an appropriate model to characterize melanogenic paracrine interactions and that astaxanthin and withaferin A serve as potent inhibitors of those interactions. Their effects are caused not only by down-regulating the increased secretion of an intrinsic melanogenic cytokine, endothelin-1, by UVB-exposed human keratinocytes, but also by interrupting the endothelin-1-triggered downstream intracellular signaling between protein kinase C and Raf-1 in human melanocytes (only for withaferin A).


Assuntos
Endotelina-1/metabolismo , Queratinócitos/metabolismo , Melanócitos/metabolismo , Comunicação Parácrina/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Raios Ultravioleta , Vitanolídeos/farmacologia , Anticorpos/farmacologia , Cálcio/metabolismo , Linhagem Celular Tumoral , Técnicas de Cocultura , Citocinas/metabolismo , Ditiotreitol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Espaço Intracelular/metabolismo , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Melanócitos/efeitos dos fármacos , Melanócitos/efeitos da radiação , Melanoma/metabolismo , Melanoma/patologia , Monofenol Mono-Oxigenase/metabolismo , Comunicação Parácrina/efeitos da radiação , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Transdução de Sinais/efeitos da radiação , Xantofilas/farmacologia
7.
Int J Mol Sci ; 16(4): 7776-95, 2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-25856676

RESUMO

Our previous studies strongly indicated that the up-regulated activity of skin fibroblast-derived elastase plays a pivotal role in wrinkling and/or sagging of the skin via the impairment of elastic fiber configuration and the subsequent loss of skin elasticity. Fortunately, we succeeded in identifying human skin fibroblast-derived elastase as a previously known enzyme, neprilysin or neutral endopeptidase (NEP). We have also characterized epithelial-mesenchymal paracrine cytokine interactions between UVB-exposed-keratinocytes and dermal fibroblasts and found that interleukin-1α and granulocyte macrophage colony stimulatory factor (GM-CSF) are intrinsic cytokines secreted by UVB-exposed keratinocytes that stimulate the expression of neprilysin by fibroblasts. On the other hand, direct UVA exposure of human fibroblasts significantly stimulates the secretion of IL-6 and also elicits a significant increase in the gene expression of matrix metallo-protease(MMP)-1 as well as neprilysin (to a lesser extent), which is followed by distinct increases in their protein and enzymatic activity levels. Direct UVA exposure of human keratinocytes also stimulates the secretion of IL-6, IL-8 and GM-CSF but not of IL-1 and endothelin-1. These findings suggest that GM-CSF secreted by UVA-exposed keratinocytes as well as IL-6 secreted by UVA-exposed dermal fibroblasts play important and additional roles in UVA-induced sagging and wrinkling by up-regulation of neprilysin and MMP-1, respectively, in dermal fibroblasts.


Assuntos
Neprilisina/genética , Envelhecimento da Pele/patologia , Envelhecimento da Pele/efeitos da radiação , Pele/patologia , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Citocinas/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibroblastos/efeitos da radiação , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Queratinócitos/metabolismo , Queratinócitos/patologia , Queratinócitos/efeitos da radiação , Pele/metabolismo , Envelhecimento da Pele/genética
8.
J Parasitol ; 110(2): 159-169, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38629270

RESUMO

Dicyemids (phylum Dicyemida) are the most common and most characteristic endosymbionts in the renal sacs of benthic cephalopod molluscs: octopuses and cuttlefishes. Typically, 2 or 3 dicyemid species are found in a single specimen of the host, and most dicyemids have high host specificity. Host-specific parasites are restricted to a limited range of host species by ecological barriers that impede dispersal and successful establishment; therefore, phylogenies of interacting groups are often congruent due to repeated co-speciation. Most frequently, however, host and parasite phylogenies are not congruent, which can be explained by processes such as host switching and other macro-evolutionary events. Here, the history of dicyemids and their host cephalopod associations were studied by comparing their phylogenies. Dicyemid species were collected from 8 decapodiform species and 12 octopodiform species in Japanese waters. Using whole mitochondrial cytochrome c oxidase subunit 1 (COI) sequences, a phylogeny of 37 dicyemid species, including 4 genera representing the family Dicyemidae, was reconstructed. Phylogenetic trees derived from analyses of COI genes consistently suggested that dicyemid species should be separated into 3 major clades and that the most common genera, Dicyema and Dicyemennea, are not monophyletic. Thus, morphological classification does not reflect the phylogenetic relationships of these 2 genera. Divergence (speciation) of dicyemid species seems to have occurred within a single host species. Possible host-switching events may have occurred between the Octopodiformes and Decapodiformes or within the Octopodiformes or the Decapodiformes. Therefore, the mechanism of dicyemid speciation may be a mixture of host switching and intra-host speciation. This is the first study in which the process of dicyemid diversification involving cephalopod hosts has been evaluated with a large number of dicyemid species and genera.


Assuntos
Octopodiformes , Parasitos , Animais , Filogenia , Invertebrados/anatomia & histologia , Invertebrados/genética , Decapodiformes/parasitologia
9.
Phys Rev Lett ; 110(15): 155001, 2013 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-25167276

RESUMO

We demonstrate that, from a 10-µm metal wire irradiated by a 10(19) W/cm2 laser pulse, fast electrons form a nearly perfect circular beam around the wire and propagate along it. The total charge and diameter of the electron beam are maintained over a propagation distance of 1 m. Moreover, the electron beam can be guided along a slightly bent wire. Numerical simulations suggest that a relatively weak steady electric field, which does not decay for several nanoseconds, is generated around the wire and plays a key role in the long-distance guidance.

10.
Biochem J ; 443(1): 297-305, 2012 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-22417750

RESUMO

We recently reported that overexpression of the elastase NEP (neutral endopeptidase) by fibroblasts plays a pivotal role in the mechanism of UVB-induced skin wrinkling by degrading dermal elastic fibres. Since UVB does not penetrate to the dermis, we hypothesized that factors secreted by UVB-exposed keratinocytes in the epidermis trigger fibroblasts in the dermis to increase their expression of NEP which then degrades the elastic fibres. In the present study, we characterized the epithelial-mesenchymal interaction between keratinocytes and fibroblasts which leads to increased expression of NEP. Human fibroblasts co-cultured with UVB-exposed human keratinocytes in cell inserts significantly increased their expression of NEP at the transcriptional, translational and enzymatic levels. Neutralizing antibodies to IL (interleukin)-1α or GM-CSF (granulocyte/macrophage colony-stimulating factor) significantly abolished the increased expression of NEP at the enzymatic levels in human fibroblasts co-cultured with UVB-exposed human keratinocytes, whereas neutralizing antibodies to IL-6, IL-8 or TNFα (tumour necrosis factor α) had no such effect. The addition of IL-1α or GM-CSF, but not TNFα, IL-6 or IL-8, at concentrations ranging from 1 to 10 nM, significantly stimulated the expression of NEP in human fibroblasts at the transcriptional and translational levels. These findings suggest that IL-1α and GM-CSF are intrinsic cytokines secreted by UVB-exposed keratinocytes that stimulate expression of NEP by fibroblasts.


Assuntos
Fibroblastos/enzimologia , Queratinócitos/efeitos da radiação , Neprilisina/genética , Raios Ultravioleta , Regulação para Cima/efeitos da radiação , Células Cultivadas , Técnicas de Cocultura , Citocinas/farmacologia , Citocinas/fisiologia , Células Epidérmicas , Prepúcio do Pênis/citologia , Expressão Gênica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/fisiologia , Humanos , Interleucina-1alfa/metabolismo , Interleucina-1alfa/farmacologia , Interleucina-1alfa/fisiologia , Queratinócitos/metabolismo , Masculino , Neprilisina/metabolismo , Comunicação Parácrina
11.
Neurosurgery ; 92(3): 574-580, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36512845

RESUMO

BACKGROUND: Follow-up of aneurysms treated with stent-assisted coil embolization has been performed using digital subtraction angiography (DSA) because in time-of-flight magnetic resonance angiography, metal artifacts from the stent often affect visualization. OBJECTIVE: To confirm whether ultrashort echo time (TE) MRA may be an alternative for DSA during follow-up. METHODS: Patients with unruptured aneurysms initially treated with stent-assisted coil embolization between April 2019 and March 2021 were enrolled. After 3 months of treatment, follow-up DSA and ultrashort TE MRA were performed. All images were independently reviewed by neurosurgeons to evaluate in-stent flow and rated from 1 (not visible) to 4 (excellent). Aneurysmal embolization status was assessed as complete obliteration, residual neck, or residual aneurysm. Ultrashort TE MRA findings were classified as evaluative or nonevaluative state based on the presence of metal artifacts. We investigated the types of aneurysms that were evaluative and the agreement between ultrashort TE and DSA. RESULTS: Overall, 89 aneurysms were examined, of which 74% (n = 66) were classified as evaluative on ultrashort TE. Significant differences were observed in size and stent type. Evaluative cases had an aneurysm size of <7 mm ( P = .0007) and a higher rate of Neuroform Atlas ( P = .0006). The rate of agreement between ultrashort TE with evaluative state and DSA was 95%. CONCLUSION: Ultrashort TE MRA could evaluate an embolization status treated with stenting, and the findings are in excellent agreement with those of DSA. Aneurysms measuring <7 mm and treated with Neuroform Atlas are evaluative on ultrashort TE, and DSA might not be necessary.


Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Humanos , Seguimentos , Aneurisma Intracraniano/terapia , Aneurisma Intracraniano/cirurgia , Angiografia por Ressonância Magnética/métodos , Angiografia Digital/métodos , Stents , Embolização Terapêutica/métodos , Resultado do Tratamento , Angiografia Cerebral/métodos
12.
Cytokine ; 59(1): 166-75, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22507381

RESUMO

BACKGROUND: We recently reported that over-expression of skin fibroblast-derived elastase (SFE) plays a pivotal role in the mechanism of UVB-induced skin wrinkling. Since UVB penetrates only modestly to the dermis, we hypothesized that factors secreted by UVB-exposed keratinocytes in the epidermis trigger fibroblasts in the dermis to increase their expression of SFE which then degrades the elastic fibers. OBJECTIVE: In this study, we characterized the paracrine interaction between human keratinocytes (HK) and human fibroblasts (HF) which leads to increased expression of SFE. METHODS AND RESULTS: Medium conditioned by UVB-exposed HK contained increased levels of IL-1α, GM-CSF, IL-6, TNFα and IL-8. While HF cultured with those conditioned medium slightly down-regulated the gene expression of collagen and elastin, they significantly increased their expression of SFE at the transcriptional, translational and enzymatic levels. Neutralizing antibodies to IL-1α or GM-CSF significantly abolished the increased expression of SFE at the translational and/or enzymatic levels in HF cultured with those conditioned medium, while neutralizing antibodies to IL-6, IL-8 or TNFα had no such effect. The addition of IL-1α or GM-CSF, but not TNFα, IL-6 or IL-8, at concentrations ranging from 1 to 10nm, significantly stimulated the enzymatic levels of SFE in HF. CONCLUSIONS: The sum of these findings suggests that IL-1α and GM-CSF are intrinsic cytokines secreted by UVB-exposed HK that stimulate expression of SFE by HF, leading to UVB-induced wrinkle formation.


Assuntos
Citocinas/metabolismo , Fibroblastos/enzimologia , Fibroblastos/efeitos da radiação , Queratinócitos/efeitos da radiação , Neprilisina/metabolismo , Comunicação Parácrina/efeitos da radiação , Raios Ultravioleta , Adulto , Anticorpos Neutralizantes , Linhagem Celular , Células Cultivadas , Colagenases/genética , Colagenases/metabolismo , Meios de Cultivo Condicionados/farmacologia , Derme/citologia , Células Epidérmicas , Feminino , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos da radiação , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Masculino , Neprilisina/genética , Comunicação Parácrina/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
13.
Exp Dermatol ; 21 Suppl 1: 11-7, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22626465

RESUMO

To elucidate the effects of redox balance regulation on cutaneous inflammation, we used the potent antioxidant astaxanthin (AX) to assess its effect on the UVB-induced secretion of PGE(2) and IL-8 in human keratinocytes and analysed its biological mechanism of action. The addition of AX (at 8 µm) to human keratinocytes even after UVB irradiation significantly down-regulated the increased secretion of PGE(2) or IL-8. Those suppressive effects were accompanied by significantly decreased expression of genes encoding COX-2 or IL-8 as well as COX-2 protein. Analysis using a specific NF-κB tanslocation inhibitor demonstrated that the UVB-stimulated secretion of PGE(2) and IL-8 was significantly abolished by its treatment prior to UVB irradiation. Western blotting of phosphorylated signalling molecules revealed that UVB irradiation (80 mJ/cm(2) ) significantly stimulated the phosphorylation of p38, ERK and JNK, which was not suppressed by treatment with AX after irradiation. In contrast, AX significantly inhibited the UVB-increased phosphorylation of mitogen- and stress-activated protein kinase (MSK)-1, NF-kBp65 or CREB even when treated postirradiation. Further, the MSK1 inhibitor H89 significantly down-regulated the increased secretion of PGE(2) and IL-8 in UVB-exposed human keratinocytes, following post-irradiation treatment. These findings suggests that AX attenuates the auto-phosphorylation of MSK1 required for its activation, which results in the decreased phosphorylation of NF-kBp65, which in turn probably leads to a deficiency of NF-kB DNA binding activity. This may be associated with the significant suppression of PGE(2) /IL-8 secretion via the down-regulated expression of COX-2 and IL-8 at the gene and/or protein levels.


Assuntos
Dinoprostona/metabolismo , Interleucina-8/metabolismo , Queratinócitos/citologia , Proteínas Quinases S6 Ribossômicas 90-kDa/metabolismo , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Inibidores Enzimáticos/farmacologia , Humanos , Isoquinolinas/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/efeitos da radiação , Microscopia Confocal/métodos , Modelos Biológicos , Fosforilação , Espécies Reativas de Oxigênio , Transdução de Sinais , Sulfonamidas/farmacologia , Raios Ultravioleta , Xantofilas/farmacologia
14.
Anim Sci J ; 93(1): e13763, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35946783

RESUMO

The concentration of inosine 5'-monophosphate (IMP) in beef is an important factor contributing to beef palatability. A previous study suggested that single nucleotide polymorphisms (SNPs) in the ecto-5'-nucleotidase (NT5E) gene strongly affect the concentration of IMP under postmortem conditions by regulating NT5E enzymatic activity in beef. Genotyping of the NT5E gene is performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or real-time PCR assay. However, these conventional laboratory assays require large installed instruments. They also involve complicated procedures and are time-consuming. Here, the PCR primers and probes for the NT5E gene (rs42508588 SNP) were designed and synthesized, and we examined the rapid genotyping of the NT5E gene using a PicoGene PCR 1100 mobile PCR device. The results showed that this system enabled rapid amplification of each allele at approximately 19.4 s per cycle, with a total run time of 13 min 36 s. This device is portable and does not require a power supply, which facilitates its use not only in specific laboratories but also in meat production farms and distribution stages of beef.


Assuntos
Inosina Monofosfato , Polimorfismo de Nucleotídeo Único , Animais , Bovinos/genética , Primers do DNA/genética , Genótipo , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária
15.
Phytother Res ; 25(9): 1398-411, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21678520

RESUMO

Redox imbalances have been shown to be closely linked to a variety of altered cellular responses and profoundly affect intracellular signaling pathways, especially the PKC/MAPK pathway which is a major pathway involved in regulating melanogenesis within human melanocytes. To elucidate the effects of redox balance regulation on epidermal hyperpigmentary disorders, an antioxidant-rich herb extract of Withania somnifera was used to assess its effect on endothelin-1 (EDN1)-stimulated pigmentation in human epidermis equivalents and its biological mechanisms analysed. Addition of the Withania somnifera extract (10 µg/mL) elicited a marked depigmenting effect on EDN1 (10 nm)-stimulated pigmentation which was accompanied by a significant decrease in eumelanin content. Real-time RT-PCR and western blotting revealed that the stimulated expression of melanocyte-specific mRNAs and proteins, including microphthalmia associated transcription factor (MITF), was significantly suppressed at days 7-10 of culture by the Withania somnifera extract (10 µg/mL), suggesting an impairment in intracellular signaling upstream of gene expression. Signaling analysis revealed that in Withania somnifera extract (10 µg/mL)-treated human melanoma cells in culture, there was a marked deficiency in EDN1 (10 nm)-stimulated phosphorylation of Raf-1, MEK, ERK, MITF and Cyclic AMP responsive element binding protein (CREB) at 15 min after EDN1 treatment. Consistently, treatment with withaferin A, a major component of the Withania somnifera extract, at concentrations of 10-50 µm also significantly down-regulated the EDN1 stimulated phosphorylation of Raf-1, MEK, ERK, MITF and CREB at 15 min after EDN1 treatment. Since Raf-1 is phosphorylated by protein kinase C (PKC) activity, these findings indicate that the Withania somnifera extract attenuates EDN1-stimulated pigmentation by preferentially inhibiting EDN1-triggered PKC activity.


Assuntos
Melanócitos/efeitos dos fármacos , Pigmentação/efeitos dos fármacos , Extratos Vegetais/farmacologia , Proteína Quinase C/metabolismo , Withania/química , Linhagem Celular Tumoral , Endotelina-1/farmacologia , Humanos , Melaninas/metabolismo , Melanoma/metabolismo , Fator de Transcrição Associado à Microftalmia/metabolismo , Fosforilação , Transdução de Sinais
16.
Gan To Kagaku Ryoho ; 38(9): 1499-502, 2011 Sep.
Artigo em Japonês | MEDLINE | ID: mdl-21918349

RESUMO

We report a hemodialysis patient with extensive small-cell lung cancer who was administered CPT-11(50mg/m2)chemotherapy and achieved a partial response after four courses of chemotherapy. Hemodialysis was performed 24 hours after the first course of CPT-11 was completed. Because the patient developed thrombocytopenia and pneumonia, hemodialysis was performed 4 hours following the second course of chemotherapy, after which grade III bone marrow suppression was observed. The plasma concentrations of CPT-11 and its metabolic products(SN-38 and SN-38G)were measured during both courses. A pharmacokinetic study showed that the plasma concentration of CPT-11 after the first course was relatively high, and that the kinetics was similar to that in a non-dialysis case. However, 4 hours after hemodialysis, the concentrations of CPT-11 and SN-38G were re-elevated, and showed a sustained level higher than that obtained 24 hours after hemodialysis. Further study is needed to determine the optimal dosages of CPT-11, and the best time to conduct hemodialysis for chronic cancer patients requiring it.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Diálise Renal/métodos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Idoso , Antineoplásicos Fitogênicos/sangue , Camptotecina/sangue , Camptotecina/uso terapêutico , Ensaios Clínicos Fase I como Assunto , Humanos , Irinotecano , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/complicações , Masculino , Carcinoma de Pequenas Células do Pulmão/sangue , Carcinoma de Pequenas Células do Pulmão/complicações
17.
Allergol Int ; 59(1): 33-41, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19946198

RESUMO

BACKGROUND: This study investigated the variations in the clinical efficacy and drug cost following the introduction of the Asthma Prevention and Management Guidelines in Japan (JGL2003). METHODS: The medical charts of fifty outpatients treated continuously for asthma, aged 16-50 years, from October 2002 to October 2004 at Showa University Hospital were analyzed for physicians' compliance with asthma guidelines, symptom severity, episodes in various occasions, prescriptions and drug costs. RESULTS: Physicians' compliance with the guidelines, which were defined as the number of patient visits treated in conformity with the JGL over the total number of patient visits, was found to be high before (89.4%) and after (90.3%) the introduction of JGL2003, without a statistical difference. On the other hand, the distribution of asthma symptom severity varied significantly (P<0.0001). Fewer patients were recognized as having more severe asthma symptoms after the introduction of JGL2003. Significantly more patients with severe asthma symptoms were detected in the physicians' noncompliant group than in the compliant group (P<0.0001). The number of patients prescribed with oral corticosteroids, long-acting beta2-agonists containing patches, long-acting oral beta2-agonists, short-acting inhaled beta2-agonists, sustained-released theophylline and leukotriene receptor antagonists decreased after the introduction of JGL2003. Furthermore, the total annual drug cost per patient decreased significantly by an average of 16,259 yen (P=0.006). CONCLUSIONS: The JGL2003 was judged to have improved criteria, which thus resulted in the high compliance of physicians with the guidelines, in the remission of asthma symptoms and in the reduction in the total annual drug cost per patient.


Assuntos
Asma/tratamento farmacológico , Custos de Medicamentos , Fidelidade a Diretrizes , Adolescente , Adulto , Asma/economia , Asma/fisiopatologia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Prescrições/economia , Resultado do Tratamento
18.
J Vet Sci ; 21(6): e86, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33263233

RESUMO

BACKGROUND: Dicyemids are parasites found in the renal sac of cephalopods. The first species of dicyemid was found from kidneys of the Korean common octopus Callistoctopus minor. OBJECTIVES: This study aimed to identify the dicyemid and investigate the effect on renal sac of host. METHODS: In this study, we compared the morphological characteristics of isolate to dicyemids (Dicyema sphyrocephalum, Dicyema clavatum, and Dicyema dolichocephalum) reported from C. minor in Japan. We compared the 18S ribosomal RNA (rDNA) and cytochrome c oxidase subunit I (COI) sequences of isolate to the sequences of D. shyrocephalum and D. clavatum. The infected octopuses renal tissues were histologically compared with the tissues of uninfected individuals. RESULTS: The morphological characteristic of this isolated species corresponds to D. sphyrocephalum. The sequences similarities of 18S rDNA and COI gene of isolate are 99.7% and 98.1% with D. sphyrocephalum. We observed morphological changes in the epithelia folds of kidney at the dicyemids attached areas. CONCLUSIONS: The present study identified the isolate as D. sphyrocephalum and this is the first report of dicyemid species from Republic of Korea. Further studies on the effects of dicyemids on growth and health status of cephalopods will be needed.


Assuntos
Distribuição Animal , Invertebrados/fisiologia , Octopodiformes/parasitologia , Animais , Complexo IV da Cadeia de Transporte de Elétrons/análise , Invertebrados/genética , Rim/parasitologia , Filogenia , RNA Ribossômico 18S/análise , República da Coreia
19.
Biochem Genet ; 47(5-6): 397-411, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19291389

RESUMO

Eight novel and four known mutations were detected in the coding sequence of the bovine fatty acid synthase (FASN) gene of an F2 population from Japanese Black and Limousin cattle. Two mutations, g.16024A>G and g.16039T>C, detected in exon 34, which determine amino acid substitutions of threonine (T) to alanine (A) and tryptophan (W) to arginine (R), were clearly separated in the parental breeds. The haplotypes (TW and AR) segregated in F2 individuals and had a significant effect on the fatty acid composition of backfat, intermuscular fat, and intramuscular fat. The TW haplotype was associated with increasing C18:0 and C18:1 content and the ratio of monounsaturated to saturated fatty acids, and decreasing C14:0, C14:1, C16:0, and C16:1 content. The two mutations were screened in two commercial Japanese Black half-sibling populations and similarly determined the contribution to the fatty acid composition of intramuscular fat. The frequency of the TW haplotype was markedly higher in Japanese Black (0.67) than in Holstein (0.17), Angus (0.02), and Hereford (0.07). We conclude that these mutations may contribute to the characteristic fatty acid composition of Japanese Black beef.


Assuntos
Bovinos/genética , Ácido Graxo Sintases/genética , Ácidos Graxos/análise , Carne/análise , Mutação , Alelos , Sequência de Aminoácidos , Animais , Bovinos/classificação , Análise Mutacional de DNA , Ácido Graxo Sintases/metabolismo , Ácidos Graxos/metabolismo , Feminino , Frequência do Gene , Genótipo , Haplótipos , Japão , Masculino , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Homologia de Sequência de Aminoácidos , Especificidade da Espécie
20.
Nihon Kokyuki Gakkai Zasshi ; 46(5): 404-10, 2008 May.
Artigo em Japonês | MEDLINE | ID: mdl-18517018

RESUMO

During a 54-year-old woman's visit to a hot-spring resort, she suffered a fever and became dizzy and unable to speak clearly. She was admitted to our hospital due to serious pneumonia and respiratory failure type I. She was treated with antibiotics, but her condition became worse and developed into acute respiratory distress syndrome (ARDS). She was intubated and received artificial ventilation. Her blood pressure gradually decreased and she suffered septic shock probably due to endotoxin with gram negative coccus infection. Subsequently, she was treated with a direct hemoperfusion using a polymyxin B immobilized fiber column (PMX-DHP), which resulted in an improvement of oxygenation. However, her pneumonia led to the development of septic shock with gram negative coccus infection, and PMX-DHP treatment was resumed. After PMX-DHP re-treatment, she recovered gradually in intensive care including prone positioning ventilation.


Assuntos
Antibacterianos/administração & dosagem , Hemoperfusão/métodos , Polimixina B/administração & dosagem , Síndrome do Desconforto Respiratório/terapia , Feminino , Infecções por Bactérias Gram-Negativas/terapia , Humanos , Pessoa de Meia-Idade , Decúbito Ventral/fisiologia , Respiração Artificial , Choque Séptico/terapia , Resultado do Tratamento
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