RESUMO
BACKGROUND: Hysterectomy is a gynaecological surgical procedure in which the uterus is removed as a treatment for both malignant and benign gynaecological diseases. A hysterectomy is also performed to minimise risks in women with problems related to the uterus. This study aimed to estimate the prevalence of reported hysterectomy and associated risk factors in Brazilian women aged 50 and older. METHODS: A cross-sectional study using data from the Brazilian Longitudinal Study of Ageing (ELSI-Brazil) was conducted. A total of 5,293 women aged 50 and over who participated in the ELSI-Brazil study in 2015 and 2016 were included. The prevalence rate of hysterectomy was estimated and the main reasons for performing the surgery were identified. The bivariate analyses utilised the chi-square test, while multivariate analyses employed Poisson regression with a robust estimator. RESULTS: The reported prevalence of hysterectomy was 17.8%. The most prevalent reason for the surgery was the presence of uterine myoma. Significant and independent associations were observed in women aged 63 and older, married, having undergone preventive exams, hormonal treatment, had up to three deliveries and having a private health plan. CONCLUSION: The main objective of the study was achieved. The prevalence of hysterectomy in Brazilian women aged 50 and older was 17.8%. Significant associations were observed with participants' sociodemographic and clinical characteristics reinforcing the importance of considering the reproductive characteristics of women as indicators of health status.
Assuntos
Histerectomia , Humanos , Feminino , Histerectomia/estatística & dados numéricos , Brasil/epidemiologia , Pessoa de Meia-Idade , Estudos Longitudinais , Estudos Transversais , Idoso , Prevalência , Fatores de RiscoRESUMO
The potential to regenerate a damaged body part is expressed to a different extent in animals. Echinoderms, in particular starfish, are known for their outstanding regenerating potential. Differently, humans have restricted abilities to restore organ systems being dependent on limited sources of stem cells. In particular, the potential to regenerate the central nervous system is extremely limited, explaining the lack of natural mechanisms that could overcome the development of neurodegenerative diseases and the occurrence of trauma. Therefore, understanding the molecular and cellular mechanisms of regeneration in starfish could help the development of new therapeutic approaches in humans. In this study, we tackle the problem of starfish central nervous system regeneration by examining the external and internal anatomical and behavioral traits, the dynamics of coelomocyte populations, and neuronal tissue architecture after radial nerve cord (RNC) partial ablation. We noticed that the removal of part of RNC generated several anatomic anomalies and induced behavioral modifications (injured arm could not be used anymore to lead the starfish movement). Those alterations seem to be related to defense mechanisms and protection of the wound. In particular, histology showed that tissue patterns during regeneration resemble those described in holothurians and in starfish arm tip regeneration. Flow cytometry coupled with imaging flow cytometry unveiled a new coelomocyte population during the late phase of the regeneration process. Morphotypes of these and previously characterized coelomocyte populations were described based on IFC data. Further studies of this new coelomocyte population might provide insights on their involvement in radial nerve cord regeneration.
Assuntos
Nervo Radial , Pepinos-do-Mar , Animais , Humanos , Nervo Radial/fisiologia , Estrelas-do-Mar/fisiologia , Regeneração Nervosa/fisiologiaRESUMO
Glioblastomas are tumors that present a high mortality rate. Artemether (ART) is a lactone with antitumor properties, demonstrating low bioavailability and water solubility. In the present study, we developed lipid-core nanocapsules (LNC) containing pequi oil (Caryocar brasiliense Cambess) as the oily core for ART-loaded LNCs (LNCART) and evaluated their effect on human glioblastoma cells (U-87 MG). LNCs were developed by interfacial deposition of a preformed polymer, followed by physicochemical characterization. LNCART revealed a diameter of 0.216 µm, polydispersity index of 0.161, zeta potential of -12.0 mV, and a pH of 5.53. Furthermore, mitochondrial viability, proliferation, total antioxidant status, and antioxidant enzyme activity were evaluated. ART reduced cell viability after 24 h and proliferation after 48 h of treatment at concentrations equal to or above 40 µg . mL-1. LNCART, at 1.25 µg . mL-1, reduced these parameters after 24 h of treatment. Furthermore, superoxide dismutase (SOD) activity was elevated, while glutathione reductase (GR) activity was reduced. These findings suggest that ART loaded into LNC may be a promising alternative to improve its pharmacological action and possible application as a therapeutic agent for glioblastoma.
Assuntos
Glioblastoma , Nanocápsulas , Humanos , Nanocápsulas/química , Antioxidantes/farmacologia , Artemeter , Sobrevivência Celular , Glioblastoma/tratamento farmacológico , Lipídeos/química , PolímerosRESUMO
BACKGROUND: ESGO (European Society of Gynaecological Oncology) and partners are continually improving the developmental opportunities for gynaecological oncology fellows. The objectives of this survey were to evaluate the progress in the infrastructure of the training systems in Europe over the past decade. We also evaluated training and assessment techniques, the perceived relevance of ENYGO (European Network of Young Gynaecological Oncologists) initiatives, and unmet needs of trainees. METHODOLOGY: National representatives of ENYGO from 39 countries were contacted with an electronic survey. A graduation in well/moderately/loosely-structured training systems was performed. Descriptive statistical analysis and frequency tables, as well as two-sided Fisher's exact test, were used. RESULTS: National representatives from 33 countries answered our survey questionnaire, yielding a response rate of 85%. A national fellowship is offered in 22 countries (66.7%). A logbook to document progress during training is mandatory in 24 (72.7%) countries. A logbook of experience is only utilized in a minority of nations (18%) for assessment purposes. In 42.4% of countries, objective assessments are recognized. Trainees in most countries (22 (66.7%)) requested additional training in advanced laparoscopic surgery. 13 (39.4%) countries have a loosely-structured training system, 11 (33.3%) a moderately-structured training system, and 9 (27.3%) a well-structured training system. CONCLUSION: Since the last publication in 2011, ENYGO was able to implement new activities, workshops, and online education to support training of gynaecological oncology fellows, which were all rated by the respondents as highly useful. This survey also reveals the limitations in establishing more accredited centers, centralized cancer care, and the lack of laparoscopic training.
Assuntos
Ginecologia/educação , Oncologistas/educação , Europa (Continente) , Feminino , HumanosRESUMO
BACKGROUND: Numerous studies have shown that the external nasal dilator (END) increases the cross sectional area of the nasal valve, thereby reducing nasal resistance, transnasal inspiratory pressure, stabilizing the lateral nasal vestibule, and preventing its collapse during final inhalation. OBJECTIVES: Our objective was to carry out a systematic review of the literature and meta-analysis on the effects of the END during physical exercise. METHODS: After selecting articles in the PubMed, Cochrane Library and EMBASE databases, 624 studies were identified. However, after applying the inclusion and exclusion criteria, 19 articles were considered eligible for review. RESULTS: Those studies included in the meta-analysis, the maximal oxygen uptake (VO2max.) outcome was assessed in 168 participants in which no statistically significant difference was found, MD (95% CI) = 0.86 [- 0.43, 2.15], p = 0.19, and I2 = 0%. The heart rate (HR) outcome was assessed in 138 participants in which no statistically significant difference was found, MD (95% CI) = 0.02 [- 3.19, 3.22], p = 0.99, and I2 = 0%. The rating of perceived exertion (RPE) outcome was assessed in 92 participants in which no statistically significant difference was found, MD (95% CI) = - 0.12 [- 0.52, 0.28], p = 0.56, and I2 = 27%. CONCLUSIONS: The external nasal dilator strip showed no improvement in VO2max., HR and RPE outcomes in healthy individuals during exercise.
Assuntos
Cavidade Nasal , Nariz , Dilatação , Exercício Físico , Frequência Cardíaca , HumanosRESUMO
The link between mitochondrial dysfunction, redox impairment, and inflammation leads to increased rates of brain cells loss in neurodegenerative diseases and in affective disorders. Carvacrol (CAR) is a component of essential oils found in Labiatae. CAR exerts antioxidant and anti-inflammatory effects in different cell types, as assessed in both in vitro and in vivo experimental designs. Nonetheless, it was not previously investigated whether and how CAR would prevent mitochondrial impairment in human cells exposed to a pro-oxidant challenge. Therefore, we analyzed here whether a pretreatment (for 4 h) with CAR (10-1000 µM) would promote mitochondrial protection in the human neuroblastoma cells SH-SY5Y exposed to hydrogen peroxide (H2O2). We found that CAR at 100 µM prevented the H2O2-induced decline in the activity of the complexes I and V, as well as on the levels of adenosine triphosphate (ATP). CAR also prevented the H2O2-elicited decrease in the activity of the mitochondrial enzymes aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. Moreover, CAR induced an antioxidant action by decreasing the levels of lipid peroxidation, protein carbonylation, and protein nitration in the mitochondrial membranes. Interestingly, CAR prevented the pro-inflammatory action of H2O2 by downregulating the transcription factor nuclear factor-κB (NF-κB). The inhibition of the heme oxygenase-1 (HO-1) enzyme by zinc protoporphyrin IX (ZnPP IX, 10 µM) suppressed the preventive effects caused by CAR regarding mitochondrial function and inflammation. Thus, it is suggested that CAR caused cytoprotective effects by an HO-1-dependent manner in SH-SY5Y cells exposed to H2O2.
Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Heme Oxigenase-1/metabolismo , Peróxido de Hidrogênio/toxicidade , Mitocôndrias/enzimologia , Monoterpenos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Cimenos , Citoproteção/efeitos dos fármacos , Citoproteção/fisiologia , Relação Dose-Resposta a Droga , Humanos , Mitocôndrias/efeitos dos fármacosRESUMO
The aim of this study was investigate the effects of a low-protein, high-carbohydrate (LPHC) diet introduced to rats soon after weaning. The animals were distributed in the following groups: LPHC45: fed an LPHC diet (6%-protein, 74%-carbohydrate) for 45 days; C45: fed a control (C) diet (17%-protein, 63%-carbohydrate) for 45 days; R (Reverse): fed with LPHC for 15 days followed by C diet for 30 days. The LPHC45 group showed alterations in the energetic balance with an increase in brown adipose tissue, and in glucose tolerance, and lower final body weight, muscle mass and total protein in blood when compared with C45 group. The HOMA-IR index was similar between LPHC45 and C45 groups, but this parameter was lower in LPHC45 compared with R groups. Serum adiponectin was higher in LPHC45 group than C45 and R groups. The R group presented higher fed insulin than C45 and LPHC45 and higher T4 compared with C45 group. Total cholesterol in R group was higher when compared with LPHC45 group. Thus, the data show that the change of the diet LPHC for a balanced diet led to different metabolic evolution and suggest that the different response can be due to different levels of adiponectin.
Assuntos
Adiponectina/sangue , Glicemia/metabolismo , Dieta com Restrição de Proteínas , Carboidratos da Dieta/metabolismo , Homeostase/fisiologia , Animais , Masculino , Ratos , Ratos WistarRESUMO
Naringenin (NGN; 5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one; C15H12O5), a flavanone, is found in citrus fruits and has been viewed as an antioxidant and anti-inflammatory agent. NGN is a potent inducer of the nuclear factor erythroid 2-related factor 2 (Nrf2) and upregulates the expression of heme oxygenase-1 (HO-1), an enzyme exhibiting both antioxidant and anti-inflammatory effects. The complete mechanism by which NGN exerts anti-inflammatory actions is not completely understood yet. Therefore, we investigated here whether NGN would be able to reduce the inflammation induced by paraquat (PQ) in SH-SY5Y cells. Additionally, we analyzed the mechanism associated with the NGN-induced anti-inflammatory effect. We found that a pretreatment with NGN at 80 µM for 2 h decreased the levels of pro-inflammatory cytokines interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in PQ-treated SH-SY5Y cells. The production of nitric oxide (NO·) and levels of cyclooxygenase-2 (COX-2) and of the inducible isoform of nitric oxide synthase (iNOS) were downregulated by NGN in the cells exposed to PQ. Moreover, NGN downregulated the activation of the nuclear factor-κB (NF-κB) in PQ-treated cells. The anti-apoptotic and anti-inflammatory effects promoted by NGN were abolished by ZnPP IX (a specific inhibitor of HO-1) or by knockdown of Nrf2 by small interfering RNA (siRNA). Therefore, NGN induced anti-inflammatory effects in PQ-treated SH-SY5Y cells by a mechanism associated with the Nrf2/HO-1 signaling pathway.
Assuntos
Anti-Inflamatórios/farmacologia , Flavanonas/farmacologia , Heme Oxigenase-1/antagonistas & inibidores , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Paraquat/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Heme Oxigenase-1/metabolismo , Herbicidas/toxicidade , Humanos , Fator 2 Relacionado a NF-E2/metabolismoRESUMO
PURPOSE: To investigate salivary parameters of caries susceptibility in men and women in order to identify potential variations due to sexual dimorphism. MATERIALS AND METHODS: A total of 46 female and 24 male patients, aged 18-40 years, participated in this study. Unstimulated saliva was collected for the evaluation of flow rate, pH, secretory IgA, Snyder test scores, and Streptococcus mutans counts (confirmed by PCR assay). Statistical analysis included the Mann-Whitney, Kruskal-Wallis and Bonferroni tests, one-way ANOVA, and the Spearman correlation at a 5% significance level, followed by a general linear model and multiple linear regressions. RESULTS: Female participants presented lower salivary pH values compared to males (p < 0.05), and different patterns of correlation among salivary parameters were found in men (p < 0.05) and women (p < 0.001). When comparing the variables according to Snyder test scores in men and women, there was a significant difference for S. mutans levels in the male group, and for pH and IgA in the female group (p < 0.05). Gender was found to be a predictor of salivary flow (R2 = 0.05; p < 0.05) and pH (R2 = 0.16; p < 0.001). In the female group, multiple regression showed several predictors for salivary flow rate, pH, IgA and Snyder test scores (p < 0.05), whereas no predictor was found in the male group (p > 0.05). CONCLUSION: Different salivary patterns were observed in men and women, thus the implications of such findings for caries susceptibility require further investigation.
Assuntos
Cárie Dentária , Suscetibilidade a Doenças , Saliva , Adolescente , Adulto , Feminino , Humanos , Concentração de Íons de Hidrogênio , Imunoglobulina A/metabolismo , Masculino , Saliva/química , Saliva/metabolismo , Saliva/microbiologia , Fatores Sexuais , Streptococcus mutans/isolamento & purificação , Adulto JovemRESUMO
Plant specialized metabolism often presents a complex cell-specific compartmentation essential to accomplish the biosynthesis of valuable plant natural products. Hence, the disclosure and potential manipulation of such pathways may depend on the capacity to isolate and characterize specific cell types. Catharanthus roseus is the source of several medicinal terpenoid indole alkaloids, including the low-level anticancer vinblastine and vincristine, for which the late biosynthetic steps occur in specialized mesophyll cells called idioblasts. Here, the optical, fluorescence, and alkaloid-accumulating properties of C. roseus leaf idioblasts are characterized, and a methodology for the isolation of idioblast protoplasts by fluorescence-activated cell sorting is established, taking advantage of the distinctive autofluorescence of these cells. This achievement represents a crucial step for the development of differential omic strategies leading to the identification of candidate genes putatively involved in the biosynthesis, pathway regulation, and transmembrane transport leading to the anticancer alkaloids from C. roseus.
Assuntos
Catharanthus/metabolismo , Separação Celular/métodos , Citometria de Fluxo/métodos , Alcaloides de Triptamina e Secologanina/metabolismo , Vimblastina/metabolismo , Catharanthus/citologia , Células do Mesofilo/citologia , Células do Mesofilo/metabolismo , Folhas de Planta/citologia , Folhas de Planta/metabolismoRESUMO
Mitochondria are the major site of ATP production in mammalian cells. Furthermore, these organelles are a source and a target of reactive oxygen species (ROS), such as radical anion superoxide (O2-·) and hydrogen peroxide (H2O2). The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is the master regulator of the mammalian redox biology and controls the expression of antioxidant and phase II detoxifying enzymes in several cell types. Naringenin (NGN, 5,7-dihydroxy-2-(4-hydroxyphenyl)-2,3-dihydrochromen-4-one), a flavanone, exhibits cytoprotective effects by acting as an antioxidant and anti-inflammatory agent. NGN is a potent activator of Nrf2. Nonetheless, it was not examine yet whether NGN would induce mitochondrial protection in cells under redox stress. Therefore, we investigate here whether Nrf2 would be involved in the mitochondrial protection elicited by NGN in SH-SY5Y cells exposed to H2O2. We observed that a pretreatment with NGN at 80 µM for 2 h reduced the levels of lipid peroxidation, protein carbonylation, and protein nitration in the membranes of mitochondria obtained from H2O2-treated SH-SY5Y cells. Additionally, NGN prevented the H2O2-induced impairment in the function of the enzymes aconitase, α-ketoglutarate dehydrogenase, and succinate dehydrogenase. The activites of the complexes I and V, as well as the production of ATP, were restored by NGN. NGN also suppressed the H2O2-induced mitochondria-related apoptosis. Interestingly, NGN promoted an increase in the levels of both total and mitochondrial glutathione (GSH). Silencing of Nrf2 abolished the protective effects induced by NGN. Overall, NGN induced mitochondrial protection by an Nrf2-dependent mechanism in H2O2-treated SH-SY5Y cells.
Assuntos
Flavanonas/farmacologia , Peróxido de Hidrogênio/toxicidade , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular Tumoral , HumanosRESUMO
OBJECTIVE: Demonstration of surgical steps of a Boari Flap ureteroneocystostomy in an oncological context. METHODS: Clinical case of a 66-year-old woman diagnosed with a left-pelvic recurrence of a high-grade serous ovarian carcinoma, involving the left ureter. After transection of 5cm of ureteral length, up to the level of the bifurcation of common iliac vessels, it was decided to perform a Boari Flap for ureteral reimplantation. RESULTS: Through the tubularization of a bladder flap, the extension of the ureter to the bladder is possible. After mobilization and psoas fixation, the bladder is opened on its anterior surface, in a rhomboid incision, and a full thickness bladder flap is extended cranially and tubularized for anastomosis of the proximal ureteral segment. The ureter is reimplanted after creation of an anti-reflux system with a submucosal tunnel between the mucosa and the detrusor. To finish the procedure, the bladder is closed in two layers with a running monofilament absorbable suture. CONCLUSIONS: Boari Flap ureteroneocystostomy is an uncommon urinary reconstruction, useful to correct distal ureteric defects caused by traumatic, oncological or iatrogenic injuries [1]. The success rate of ureteral reimplantation can be higher than 85% [2]. This technique is suitable for anastomosis of lumbar ureteral segments, allowing the better correction of higher and more extensive defects than the Psoas-Hitch technique. The flap length should compensate the ureteric defect and enable a tension free anastomosis.
Assuntos
Cistostomia/métodos , Neoplasias Ovarianas/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Retalhos Cirúrgicos , Ureter/cirurgia , Idoso , Feminino , HumanosRESUMO
BACKGROUND: Numerous studies have demonstrated the benefit of devices delivering altered auditory feedback (AAF) as a therapeutic alternative for those who stutter. AIMS: The effectiveness of a device delivering AAF (SpeechEasy®) was compared with behavioural techniques in the treatment of stuttering in a randomized clinical trial. METHODS & PROCEDURES: Two groups of adults who stutter participated: group 1 consisted of 10 men and one woman aged 21-42 years (mean = 30.0). Group 2 consisted of six men and one woman aged 20-50 years (mean = 35.6). Participants in group 1 were fit with a SpeechEasy® device and were not given any additional training (i.e., supplementary fluency enhancing techniques). Participants used the device daily for 6 months. Participants in group 2 received treatment in the form of a 12-week fluency promotion protocol with techniques based on both fluency shaping and stuttering modification. OUTCOMES & RESULTS: There were no statistically significant differences (p > .05) between groups in participants' stuttered syllables following treatment. That is, both therapeutic protocols achieved approximately 40% reduction in number of stuttered syllables from baseline measures, with no significant relapse after 3 or 6 months post-treatment. CONCLUSIONS & IMPLICATIONS: The results suggest that the SpeechEasy® device can be a viable option for the treatment of stuttering.
Assuntos
Retroalimentação Sensorial , Fonoterapia , Gagueira/terapia , Adulto , Feminino , Humanos , Masculino , Fala , Resultado do Tratamento , Adulto JovemRESUMO
Context Ethnopharmacological studies have demonstrated that plants of the Combretum genus presented antidiabetic activity, including Combretum lanceolatum Pohl ex Eichler (Combretaceae). Objective This study investigated the hepatic mechanisms of action of C. lanceolatum flowers ethanol extract (ClEtOH) related to its antihyperglycaemic effect in streptozotocin-diabetic rats. Materials and methods Male Wistar rats were divided into normal (N) and diabetic control (DC) rats treated with vehicle (water); diabetic rats treated with 500 mg/kg metformin (DMet) or 500 mg/kg ClEtOH (DT500). After 21 d of treatment, hepatic glucose and urea production were investigated through in situ perfused liver with l-glutamine. Changes in the phosphoenolpyruvate carboxykinase (PEPCK) levels and in the activation of adenosine monophosphate-activated protein kinase (AMPK) and insulin-signalling intermediates were also investigated. Results Similar to DMet, DT500 rats showed a reduction in the rates of hepatic production of glucose (46%) and urea (22%) in comparison with DC. This reduction was accompanied by a reduction in the PEPCK levels in liver of DT500 (28%) and DMet (43%) when compared with DC. AMPK phosphorylation levels were higher in the liver of DT500 (17%) and DMet (16%) rats. The basal AKT phosphorylation levels were increased in liver of DT500 rats, without differences in the insulin-stimulated AKT phosphorylation and in the insulin receptor levels between DC and DT500 rats. Discussion and conclusion The antidiabetic activity of ClEtOH can be attributed, at least in part, to inhibition of hepatic gluconeogenesis, probably due to the activation of both AMPK and AKT effectors and reduction in the PEPCK levels.
Assuntos
Combretum , Diabetes Mellitus Experimental/tratamento farmacológico , Etanol/química , Gluconeogênese/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Solventes/química , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Combretum/química , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/induzido quimicamente , Flores , Hipoglicemiantes/isolamento & purificação , Insulina/sangue , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fígado/metabolismo , Masculino , Metformina/farmacologia , Fosfoenolpiruvato Carboxiquinase (GTP)/metabolismo , Fosforilação , Fitoterapia , Extratos Vegetais/isolamento & purificação , Plantas Medicinais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar , Receptor de Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina , Ureia/metabolismoRESUMO
The activation of hepatic stellate cell (HSC), from a quiescent cell featuring cytoplasmic lipid droplets to a proliferative myofibroblast, plays an important role in liver fibrosis development. The GRX line is an activated HSC model that can be induced by all-trans-retinol to accumulate lipid droplets. Resveratrol is known for activating Sirtuin1 (SIRT1), a NAD(+)-dependent deacetylase that suppresses the activity of peroxisome proliferator-activated receptor gamma (PPARγ), an important adipogenic transcription factor involved in the quiescence maintenance of HSC. We evaluated the effects of 0.1 µM of resveratrol in retinol-induced GRX quiescence by investigating the interference of SIRT1 and PPARγ on cell lipogenesis. GRX lipid accumulation was evaluated through Oil-red O staining, triacylglycerides quantification, and [(14)C] acetate incorporation into lipids. mRNA expression and protein content of SIRT1 and PPARγ were measured by RT-PCR and immunoblotting, respectively. Resveratrol-mediated SIRT1 stimuli did not induce lipogenesis and reduced the retinol-mediated fat-storing capacity in GRX. In order to support our results, we established a cell culture model of transgenic super expression of PPARγ in GRX cells (GRXPγ). Resveratrol reduced lipid droplets accumulation in GRXPγ cells. These results suggest that the PPARγ/SIRT1 ratio plays an important role in the fate of HSC. Thus, whenever the PPARγ activity is greater than SIRT1 activity the lipogenesis is enabled.
Assuntos
Fibrose/genética , Gotículas Lipídicas/metabolismo , PPAR gama/biossíntese , Sirtuína 1/biossíntese , Animais , Proliferação de Células , Fibrose/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células Estreladas do Fígado/metabolismo , Humanos , Células de Kupffer/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Mioblastos/metabolismo , PPAR gama/metabolismo , RNA Mensageiro/biossíntese , Resveratrol , Sirtuína 1/metabolismo , Estilbenos/administração & dosagem , Vitamina A/metabolismoRESUMO
BACKGROUND: Prostate cancer is a leading cause of death among men due to the limited number of treatment strategies available for advanced disease. γ-oryzanol is a component of rice bran, rich in phytosterols, known for its antioxidant, anti-carcinogenic and endocrinological effects. It is known that γ-oryzanol may affect prostate cancer cells through the down regulation of the antioxidant genes and that phytosterols have anti-proliferative and apoptotic effects. There are evidences showing that some of the components of γ-oryzanol can modulate genes involved in the development and progression of prostate cancer, as caveolin-1 (Cav-1) and prostate specific androgen-regulated gene (PCGEM1). METHODS: To determine the effects of γ-oryzanol on prostate cancer cell survival we evaluated the cell viability and biomass by MTT and sulforhodamine B assays, respectively. Cell death, cell cycle and pERK1/2 activity were assessed by flow cytometry. The changes in gene expression involved in the survival and progression of prostate cancer cav-1 and PCGEM1 genes were evaluated by quantitative real time reverse transcriptase polymerase chain reaction (RT-PCR) and cav-1 protein by immunofluorescence followed by confocal microscopy analysis. RESULTS: We found that γ-oryzanol decreases cell viability and culture biomass by apoptosis and/or necrosis death in androgen unresponsive (PC3 and DU145) and responsive (LNCaP) cell lines, and signals through pERK1/2 in LNCaP and DU145 cells. γ-oryzanol also appears to block cell cycle progression at the G2/M in PC3 and LNCaP cells and at G0/G1 in DU145 cells. These effects were accompanied by a down regulation in the expression of the cav-1 in both androgen unresponsive cell lines and PCGEM1 gene in DU145 and LNCaP cells. CONCLUSION: In summary, we used biochemical and genetics approaches to demonstrate that γ-oryzanol show a promising adjuvant role in the treatment of prostate cancer.
Assuntos
Caveolina 1/antagonistas & inibidores , Caveolina 1/biossíntese , Regulação Neoplásica da Expressão Gênica , Fenilpropionatos/farmacologia , Neoplasias da Próstata/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/biossíntese , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Masculino , Fenilpropionatos/uso terapêutico , Neoplasias da Próstata/tratamento farmacológicoRESUMO
The use of flow cytometry in malaria research has increased over the last decade. Most approaches use nucleic acid stains to detect parasite DNA and RNA and require complex multi-color, multi-parameter analysis to reliably detect infected red blood cells (iRBCs). We recently described a novel and simpler approach to parasite detection based on flow cytometric measurement of scattered light depolarization caused by hemozoin (Hz), a pigment formed by parasite digestion of hemoglobin in iRBCs. Depolarization measurement by flow cytometry was described in 1987; however, patent issues restricted its use to a single manufacturer's hematology analyzers until 2009. Although we recently demonstrated that depolarization measurement of Hz, easily implemented on a bench top flow cytometer (Cyflow), provided useful information for malaria work, doubts regarding its application and utility remain in both the flow cytometry and malaria communities, at least in part because instrument manufacturers do not offer the option of measuring depolarized scatter. Under such circumstances, providing other researchers with guidance as to how to do this seemed to offer the most expeditious way to resolve the issue. We accordingly examined how several commercially available flow cytometers (CyFlow SL, MoFLo, Attune and Accuri C6) could be modified to detect depolarization due to the presence of free Hz on solution, or of Hz in leukocytes or erythrocytes from rodent or human blood. All were readily adapted, with substantially equivalent results obtained with lasers emitting over a wide wavelength range. Other instruments now available may also be modifiable for Hz measurement. Cytometric detection of Hz using depolarization is useful to study different aspects of malaria. Adding additional parameters, such as DNA content and base composition and RNA content, can demonstrably provide improved accuracy and sensitivity of parasite detection and characterization, allowing malaria researchers and eventually clinicians to benefit from cytometric technology.
Assuntos
Citometria de Fluxo/métodos , Hemeproteínas/isolamento & purificação , Malária/diagnóstico , Animais , Eritrócitos/metabolismo , Eritrócitos/parasitologia , Hemeproteínas/metabolismo , Humanos , Leucócitos/metabolismo , Leucócitos/parasitologia , Luz , Malária/metabolismo , Malária/parasitologiaRESUMO
Pelvic endometriosis may infiltrate somatic nerves causing severe neuropathic symptoms with a high impact on quality of life. It is a medical condition poorly known, and few published data about involvement of femoral nerve are available. We report an isolated unilateral endometriosis lesion of the left lumbar region infiltrating the femoral nerve in a 38-year-old woman. She described severe dysmenorrhea, dyspareunia, dischezia, and chronic pelvic pain with irradiation to the anterior part of the left thigh. After investigation, it was identified as a 5-centimeter endometriotic nodule involving the femoral nerve and the psoas muscle. The patient was treated by two laparoscopic surgeries with neurolysis of the involved somatic nerve by a multidisciplinary team, with improvement of the symptoms. Laparoscopic neurolysis is the first approach advocated in these cases, leading to relief of neurological symptoms resulting from nerve infiltration by endometriosis.
Assuntos
Endometriose , Nervo Femoral/cirurgia , Laparoscopia , Adulto , Endometriose/complicações , Endometriose/fisiopatologia , Endometriose/cirurgia , Feminino , Humanos , Dor/etiologia , Dor/cirurgia , Músculos Psoas/cirurgiaRESUMO
This study examined syntactic assignment for predicates and reflexives as well as working memory effects in the sentence comprehension of children with Specific Language Impairment (SLI), Down syndrome (DS), high functioning Autism (HFA) and Typical Language Development (TLD). Fifty-seven children (35 boys and 22 girls) performed a computerised picture-selection sentence comprehension task. Predicate attachment and reflexive antecedent assignment (with working memory manipulations) were investigated. The results showed that SLI, HFA and DS children exhibited poorer overall performance than TLD children. Children with SLI exhibited similar performance to the DS and HFA children only when working memory demands were higher. We conclude that children with SLI, HFA and DS differ from children with TLD in their comprehension of predicate and reflexive structures where the knowledge of syntactic assignment is required. Working memory manipulation had different effects on syntactic comprehension depending on language disorder. Intelligence was not an explanatory factor for the differences observed in performance.