894 research outputs found

    Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma

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    Melanoma cells express the platelet-activating factor receptor (PAFR) and, thus, respond to PAF, a bioactive lipid produced by both tumour cells and those in the tumour microenvironment such as macrophages. Here, we show that treatment of a human melanoma SKmel37 cell line with cisplatin led to increased expression of PAFR and its accumulation. In the presence of exogenous PAF, melanoma cells were significantly more resistant to cisplatin-induced cell death. Inhibition of PAFR-dependent signalling pathways by a PAFR antagonist (WEB2086) showed chemosensitisation of melanoma cells in vitro. Nude mice were inoculated with SKmel37 cells and treated with cisplatin and WEB2086. Animals treated with both agents showed significantly decreased tumour growth compared to the control group and groups treated with only one agent. PAFR accumulation and signalling are part of a prosurvival program of melanoma cells, therefore constituting a promising target for combination therapy for melanomas

    Expression of PAFR as Part of a Prosurvival Response to Chemotherapy: A Novel Target for Combination Therapy in Melanoma

    Get PDF
    Melanoma cells express the platelet-activating factor receptor (PAFR) and, thus, respond to PAF, a bioactive lipid produced by both tumour cells and those in the tumour microenvironment such as macrophages. Here, we show that treatment of a human melanoma SKmel37 cell line with cisplatin led to increased expression of PAFR and its accumulation. In the presence of exogenous PAF, melanoma cells were significantly more resistant to cisplatin-induced cell death. Inhibition of PAFR-dependent signalling pathways by a PAFR antagonist (WEB2086) showed chemosensitisation of melanoma cells in vitro. Nude mice were inoculated with SKmel37 cells and treated with cisplatin and WEB2086. Animals treated with both agents showed significantly decreased tumour growth compared to the control group and groups treated with only one agent. PAFR accumulation and signalling are part of a prosurvival program of melanoma cells, therefore constituting a promising target for combination therapy for melanomas

    O Conflito Político. Alguns Aspectos da sua Modelação

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    Objective: Sports practice alters the homeostasis of athletes. To achieve homeostatic equilibrium, the integrated action of the neuroendocrine and immune systems is necessary. Here we studied the relation between cytokines, hormones and mood states in marathon runners. Methods: A total of 20 male recreational marathon runners (mean age = 35.7 ± 9 years) and 20 male sedentary individuals (mean age = 35.5 ± 7 years) were recruited. We compared the serum levels of growth hormone (GH), cortisol and interleukins 8 and 10 and the amounts of these two cytokines spontaneously produced by peripheral blood mononuclear cells. Blood samples of the sedentary group were collected at rest. Blood from the marathon runners was collected at rest (baseline: 24 h before the race), immediately after a marathon and 72 h after a marathon. Mood state analysis in both groups was performed using the 24-item Brunel Mood Scale (BRUMS). Results: Our results showed that, at rest, levels of interleukins 8 and 10 in the supernatant of culture cells, the serum concentration of GH, and tension and vigour (evaluated using the BRUMS), were significantly higher in athletes compared to sedentary people. Immediately after the race all serum parameters analysed were statistically higher than baseline values. At 72 h after the marathon, serum levels of hormones and interleukins returned to values at rest, but the concentrations of interleukins in the supernatant of culture cells showed a significant reduction compared to values at rest. Conclusion: The higher serum levels of GH in athletes at rest and the higher production of cytokines in culture without previous stimulus suggest that marathon runners present mechanisms that may be associated with preparing the body to perform prolonged strenuous exercise, such as a marathon

    Peripheral antinociceptive action of mangiferin in mouse models of experimental pain: Role of endogenous opioids, KATP-channels and adenosine

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    AbstractThis study aimed to assess the possible systemic antinociceptive activity of mangiferin and to clarify the underlying mechanism, using the acute models of chemical (acetic acid, formalin, and capsaicin) and thermal (hot-plate and tail-flick) nociception in mice. Mangiferin at oral doses of 10 to 100mg/kg evidenced significant antinociception against chemogenic pain in the test models of acetic acid-induced visceral pain and in formalin- and capsaicin-induced neuro-inflammatory pain, in a naloxone-sensitive manner, suggesting the participation of endogenous opiates in its mechanism. In capsaicin test, the antinociceptive effect of mangiferin (30mg/kg) was not modified by respective competitive and non-competitive transient receptor potential vanilloid 1 (TRPV1) antagonists, capsazepine and ruthenium red, or by pretreatment with l-NAME, a non-selective nitric oxide synthase inhibitor, or by ODQ, an inhibitor of soluble guanylyl cyclase. However, mangiferin effect was significantly reversed by glibenclamide, a blocker of KATP channels and in animals pretreated with 8-phenyltheophylline, an adenosine receptor antagonist. Mangiferin failed to modify the thermal nociception in hot-plate and tail-flick test models, suggesting that its analgesic effect is only peripheral but not central. The orally administered mangiferin (10–100mg/kg) was well tolerated and did not impair the ambulation or the motor coordination of mice in respective open-field and rota-rod tests, indicating that the observed antinociception was unrelated to sedation or motor abnormality. The findings of this study suggest that mangiferin has a peripheral antinociceptive action through mechanisms that involve endogenous opioids, KATP-channels and adenosine receptors

    Hysteresis loops in CuO

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    Hysteresis loops at room temperature have been observed and investigated in nanostructures and nanoparticles ofCupric Oxide (CuO) with same average grain size. Morphological and structural properties of the studied sampleswere characterized using x-ray diffraction (XRD) and scanning electron microscopy (SEM). Energy-dispersive X-rayspectroscopy (EDS) was employed to analyze the possible presence of impurities. Mean crystallite diameter sizeswere determined using Rietveld refinement analysis of the diffraction patterns. The results suggest that hysteresisloops morphology depend on the process to obtain each sample, which not only affect grain size, but also mayinduce anisotropic forms and residual microstrains.Lazos de histéresis a temperatura ambiente han sido observados y estudiados en nanoestructuras y nanopartículas de óxido cúprico (CuO) con el mismo tamaño promedio de cristalito. Las propiedades morfológicas y estructurales de las muestras fueron caracterizadas usando difracción de rayos X y microscopía electrónica de barrido (SEM). La presencia de impurezas ha sido descartada a partir de resultados de espectrometría de dispersión de energía de rayos X (EDS). El tamaño promedio de los cristalitos ha sido determinado usando el método de refinamiento de Rietveld de los patrones de difracción. Los resultados sugieren que las características de los lazos de histéresis dependen del proceso de obtención de las muestras, el que no sólo influye en el tamaño de grano sino también puede inducir formas y micro tensiones residuales anisotrópicas.Instituto de Física La PlataFacultad de IngenieríaConsejo Nacional de Investigaciones Científicas y Técnica

    Hysteresis loops in CuO

    Get PDF
    Hysteresis loops at room temperature have been observed and investigated in nanostructures and nanoparticles ofCupric Oxide (CuO) with same average grain size. Morphological and structural properties of the studied sampleswere characterized using x-ray diffraction (XRD) and scanning electron microscopy (SEM). Energy-dispersive X-rayspectroscopy (EDS) was employed to analyze the possible presence of impurities. Mean crystallite diameter sizeswere determined using Rietveld refinement analysis of the diffraction patterns. The results suggest that hysteresisloops morphology depend on the process to obtain each sample, which not only affect grain size, but also mayinduce anisotropic forms and residual microstrains.Lazos de histéresis a temperatura ambiente han sido observados y estudiados en nanoestructuras y nanopartículas de óxido cúprico (CuO) con el mismo tamaño promedio de cristalito. Las propiedades morfológicas y estructurales de las muestras fueron caracterizadas usando difracción de rayos X y microscopía electrónica de barrido (SEM). La presencia de impurezas ha sido descartada a partir de resultados de espectrometría de dispersión de energía de rayos X (EDS). El tamaño promedio de los cristalitos ha sido determinado usando el método de refinamiento de Rietveld de los patrones de difracción. Los resultados sugieren que las características de los lazos de histéresis dependen del proceso de obtención de las muestras, el que no sólo influye en el tamaño de grano sino también puede inducir formas y micro tensiones residuales anisotrópicas.Instituto de Física La PlataFacultad de IngenieríaConsejo Nacional de Investigaciones Científicas y Técnica

    Health for sale: the medicinal plant markets in Trujillo and Chiclayo, Northern Peru

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    Traditional methods of healing have been beneficial in many countries with or without access to conventional allopathic medicine. In the United States, these traditional practices are increasingly being sought after for illnesses that cannot be easily treated by allopathic medicine. More and more people are becoming interested in the knowledge maintained by traditional healers and in the diversity of medicinal plants that flourish in areas like Northern Peru. While scientific studies of medicinal plants are underway, concern has arisen over the preservation of both the large diversity of medicinal plants and the traditional knowledge of healing methods that accompanies them. To promote further conservation work, this study attempted to document the sources of the most popular and rarest medicinal plants sold in the markets of Trujillo (Mayorista and Hermelinda) and Chiclayo (Modelo and Moshoqueque), as well as to create an inventory of the plants sold in these markets, which will serve as a basis for comparison with future inventories. Individual markets and market stalls were subjected to cluster analysis based on the diversity of the medicinal plants they carry. The results show that markets were grouped based on the presence of: (1) common exotic medicinal plants; (2) plants used by laypeople for self-medication related to common ailments ("everyday remedies"); (3) specialized medicinal plants used by curanderos or traditional healers; and (4) highly "specialized" plants used for magical purposes. The plant trade in the study areas seems to correspond well with the specific health care demands from clientele in those areas. The specific market patterns of plant diversity observed in the present study represent a foundation for comparative market research in Peru and elsewhere

    Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report.

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    We identified a PSEN1 (presenilin 1) mutation carrier from the world's largest autosomal dominant Alzheimer's disease kindred, who did not develop mild cognitive impairment until her seventies, three decades after the expected age of clinical onset. The individual had two copies of the APOE3 Christchurch (R136S) mutation, unusually high brain amyloid levels and limited tau and neurodegenerative measurements. Our findings have implications for the role of APOE in the pathogenesis, treatment and prevention of Alzheimer's disease
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