Questionário Patient's Awareness in Psoriasis: adaptação transcultural para o português brasileiro e avaliação de propriedades psicométricas / Patient's Awareness in Psoriasis Questionnaire: cross-cultural adaptation to brazilian portuguese and assessment of psychometric properties

Objetivo: Traduzir e realizar a adaptação transcultural do questionário Patient's Awareness in Psoriasis (Conhecimento do Paciente sobre Psoríase) para o contexto e idioma português do Brasil e avaliar suas propriedades psicométricas. Métodos: Este trabalho foi realizado por meio de um estudo transversal. O delineamento do estudo foi correspondente à derivação de um questionário para a vigilância e controle em saúde, seguindo metodologia sugerida pela Sociedade Internacional para Farmacoeconomia e Pesquisa de Resultados - Grupo de Trabalho para Tradução e Adaptação Cultural. Primeiro, um questionário piloto foi aplicado a 10 pacientes com psoríase para avaliar compreensibilidade. Depois, outros 115 pacientes foram caracterizados e responderam ao questionário de forma autorreferida. Trinta e um pacientes responderam ao questionário mais uma vez, uma semana mais tarde. Foi avaliado: o coeficiente de correlação intraclasse, o coeficiente alfa de Cronbach, o erro padrão de medição e feita análise fatorial exploratória. Resultados: O coeficiente de correlação intraclasse foi 0,91 (0,82 - 0,96) e o alfa de Cronbach global foi 0,79. Todos participantes responderam 'não' à questão n.º 10 (suprimida nas avaliações psicométricas). A análise fatorial indicou três fatores principais: 1. Evolução clínica, 2. Aspectos clínicos e Qualidade de vida e 3. Expectativa de cura e tratamento (itens distribuídos com cargas > 0,400 ). Conclusões: O estudo resultou em uma versão do questionário que contribui com o desenvolvimento de estudos, com futuros que objetivarem aprimorar a avaliação clínica dos pacientes e a tomada de decisões relacionadas à vigilância e controle da psoríase no Brasil.

Objective: To translate and perform the cross-cultural adaptation of the Patient's Awareness in Psoriasis questionnaire to the Brazilian context in Brazilian Portuguese idiom and assess its psychometric properties. Methods: This assignment was conducted within a cross-sectional study. The study design corresponded to the derivation of a questionnaire for health surveillance and control, following the methodology suggested by the International Society for Pharmacoeconomics and Outcomes Research - Task Force for Translation and Cultural Adaptation. First, a pilot questionnaire was given to 10 psoriasis patients to assess comprehensibility. Then, another 115 patients were characterized and responded to it (self-reported manner). Thirty-one patients retook the questionnaire a week later. The intraclass correlation coefficient, Cronbach's alpha, standard error of measurement, and the exploratory factor analysis were determined. Results: The intraclass correlation coefficient was 0.91 (0.82 - 0.96). Overall, Cronbach's alpha was 0.79. All participants answered 'no' to question #10, which was restrained in the psychometric assessments. Factor analysis indicated three main factors: 1. Clinical evolution, 2. Clinical aspects and quality of life and 3. Healing and treatment (items distributed with loads > 0.400). Conclusions: The study resulted in a version of the questionnaire that contributes to the development of future studies, to the clinical evaluation of patients and to decision-making related to the surveillance and control of psoriasis in Brazil.

Aquatic exercise and Far Infrared (FIR) modulates pain and blood cytokines in fibromyalgia patients: A double-blind, randomized, placebo-controlled pilot study.

Fibromyalgia (FM) has an inflammatory component, as elevated serum levels of inflammatory biomarkers are associated with its diagnosis. Treatments decreased pain, body temperature, improved quality of life and reduced serum levels of IL-6 in both groups; however, these beneficial effects were more pronounced in aquatic exercise (AE) + Far-Infrared (FIR) group. The findings of the present study suggest that the association of AE to FIR increases the benefits of aquatic exercise in patients with FM.

Dietary supplementation with procyanidin-rich Pinus pinaster extract is associated with attenuated Ehrlich tumor development in mice.

Inflammation and oxidative stress are related to cancer initiation and progression. We hypothesized that dietary supplementation with a procyanidin-rich Pinus pinaster extract (Pyc) with known antioxidant and anti-inflammatory effects could induce systemic protection, thereby attenuating tumor development. To test our hypothesis, mice were subjected to long-term supplementation (20 days, every 24 h) with saline, 25 mg/kg resveratrol or 100 mg/kg Pyc. Pyc was administered at a maximum tolerated oral dose, previously determined using toxicity indicators. Ten days after Ehrlich ascites tumor induction, weight gain and abdominal circumference increase were calculated. Ascitic fluid from six mice/group was evaluated by determining total volume; tumor packed cell volume; cell viability; tumor cell death type; inflammatory infiltrate; and levels of tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), carbonyl proteins, lipid peroxidation, cyclooxigenase-2 (COX-2) expression and Akt phosphorylation (p-Akt). Ten mice/group were monitored to evaluate survival. Pyc and resveratrol were associated with reduced weight gain (>30%), abdominal circumference and ascitic volume. Tumor packed cell volume was reduced in Pyc-supplemented mice (26%), which had the largest tumor cell count reduction (>35%), increased ascitic fluid apoptosis rates (20%) and the longest survival (>2-fold). Pyc and resveratrol treatment both reduced inflammatory infiltrate and levels of TNF-α, IL-1ß, carbonyl proteins, lipid peroxidation (~ 30%) and p-Akt (up to 4-fold). Only Pyc significantly inhibited COX-2. Pyc attenuated oxidative and inflammation mediators and impaired tumor development, supporting our hypothesis and suggesting Pyc as a candidate for future studies in multitargeted dietary-based cancer prevention approaches.

Healing effect of Dillenia indica fruit extracts standardized to betulinic acid on ultraviolet radiation-induced psoriasis-like wounds in rats.

CONTEXT: Dillenia indica Linn. (Dilleniaceae) is traditionally used to treat skin inflammation. OBJECTIVE: This study evaluated the healing effect of Dillenia indica fruit extracts on induced psoriasis-like wounds in Wistar rats. MATERIALS AND METHODS: Extracts were standardized to betulinic acid, including an aqueous ethanolic extract (AEE), ethyl acetate extract (EAE) and petroleum ether extract. Effects against lipid peroxidation were assessed in vitro. Wounds were created at rat tails (n = 12). Topical treatments were applied once daily for 7 days (1 mL of AEE or EAE at 5 or 50 mg/mL). Maximal dose was defined by the extract solubility. A 10-fold lower dose was also tested. Positive and negative controls were treated with clobetasol (0.5 mg/mL) or excipient. Half of each group was euthanized for histology. The remaining animals were observed for 20 days for wound measurements. RESULTS: Yields of AEE and EAE were 4.3 and 0.7%, respectively. Betulinic acid concentrations in AEE and EAE were 4.6 and 107.6 mg/g. Extracts neutralized lipid peroxidation in vitro at 0.02 µg/mL, accelerating healing at 50 mg/mL. Complete healing in mice treated with AEE occurred 16 days after wound induction. This time was 14 and 12 days in mice treated with EAE and clobetasol. Compared to orthokeratosis, parakeratosis was reduced by AEE (25%), EAE (45%) and clobetasol (55%). EAE caused superior protection against biomolecules oxidation of skin compared to AEE. DISCUSSION AND CONCLUSION: EAE exhibited activity closer to that of clobetasol. Betulinic acid may be an active constituent, which should be assessed in future studies.

Piper nigrum ethanolic extract rich in piperamides causes ROS overproduction, oxidative damage in DNA leading to cell cycle arrest and apoptosis in cancer cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Ayurvedic and Chinese traditional medicine and tribal people use herbal preparations containing Piper nigrum fruits for the treatment of many health disorders like inflammation, fever, asthma and cancer. In Brazil, traditional maroon culture associates the spice Piper nigrum to health recovery and inflammation attenuation. AIMS OF THE STUDY: The aim of the current work was to evaluate the relationship between reactive oxygen species (ROS) overproduction, DNA fragmentation, cell cycle arrest and apoptosis induced by Piper nigrum ethanolic extract and its antitumor activity. METHODS: The plant was macerated in ethanol. Extract constitution was assessed by TLC, UV-vis and ESI-IT-MS/MS spectrometry. The cytotoxicity, proliferation and intracellular ROS generation was evaluated in MCF-7 cells. DNA damage effects were evaluated through intercalation into CT-DNA, plasmid DNA cleavage and oxidative damage in CT-DNA. Tumor growth inhibition, survival time increase, apoptosis, cell cycle arrest and oxidative stress were assessed in Ehrlich ascites carcinoma-bearing mice. RESULTS: Extraction yielded 64mg/g (36% piperine and 4.2% piperyline). Treatments caused DNA damage and reduced cell viability (EC50=27.1±2.0 and 80.5±6.6µg/ml in MCF-7 and HT-29 cells, respectively), inhibiting cell proliferation by 57% and increased ROS generation in MCF-7 cells (65%). Ehrlich carcinoma was inhibited by the extract, which caused reduction of tumor growth (60%), elevated survival time (76%), cell cycle arrest and induced apoptosis. The treatment with extract increased Bax and p53 and inhibited Bcl-xL and cyclin A expression. It also induced an oxidative stress in vivo verified as enhanced lipid peroxidation and carbonyl proteins content and increased activities of glutathione reductase, superoxide dismutase and catalase. GSH concentration was decreased in tumor tissue from mice. CONCLUSION: The ethanolic extract has cytotoxic and antiproliferative effect on MCF-7 cells and antitumor effect in vivo probably due to ROS overproduction that induced oxidative stress affecting key proteins involved in cell cycle arrest at G1/S and triggering apoptosis. Finally, the overall data from this study are well in line with the traditional claims for the antitumor effect of Piper nigrum fruits.

Inhibition of tumor proliferation associated with cell cycle arrest caused by extract and fraction from Casearia sylvestris (Salicaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia sylvestris is a tree found in tropical America. In Brazil it is known mainly as Guaçatonga. Literature reports suggest that the leaves and other plant parts have been used by indigenous populations from South America in preparations, mainly aqueous or hydroethanolic macerations or decoctions, most times taken orally for the primary treatment of several diseases, including cancer. AIM OF THE STUDY: This article reports the results of an investigation about the antiproliferative effects of Casearia sylvestris on tumor cells in vitro and in vivo. MATERIAL AND METHODS: Aqueous ethanolic maceration and column chromatography were done to obtain a crude aqueous ethanolic extract (CAE) and a chloroform fraction (f-CHCl3). The human breast cancer cell line MCF-7 was used in culture. In vitro, non-cytotoxic concentrations were determined by MTT assay and the antiproliferative effect was assessed by the colony forming unit assay using non-cytotoxic concentrations. Effects on the cell cycle were observed through flow cytometry using a propidium iodide kit. Casearin C was identified in f-CHCl3 by chromatography and H(1) nuclear magnetic resonance. The effect on some key proteins of DNA damage (phosphorylation on the histone H2AX) and cell cycle control (p53, p16, cdk2) was evaluated through immunoblot. Antiproliferative effects in vivo were measured in tumor tissue from Ehrlich ascites-bearing mice through the (3)H-thymidine uptake assay and the trypan blue exclusion method. RESULTS: In vitro, EC50 values found at 24 h on MCF-7 cells were 141 µg/mL for CAE and 66 µg/mL for f-CHCl3. Inhibition on proliferation was recorded at concentrations as low as 4 µg/mL in the case of the f-CHCl3 (up to 40%) and up to 50% when CAE was added at 9 µg/mL. The cell cycle arrest was demonstrated by the reduction in terms of number of cells in phases G2/M and S, up to 38.9% and 51.9% when cells were treated with CAE, and 53.9% and 66.2%, respectively, when cells were treated with f-CHCl3. The number of cells in G1 was increased when the cells were treated with CAE (21.4%) or f-CHCl3 (27.8%). Key proteins of cell cycle control were affected. The treatments caused activation of p53, p16 and DNA damage found by the appearance of bands corresponding to γ-H2AX. The treatments caused inhibition of cdk2. CAE and particularly f-CHCl3 caused significant inhibition on tumor growth in mice (40% and 60%, respectively). Uptake of (3)H-thymidine, thus proliferation was reduced in tumor cells from mice treated with CAE (>30%) or f-CHCl3 (up to 50%) compared to cells from control animals. Data from the trypan blue assay indicating a lower number of tumor cells in treated animals. From the overall, data from this study are in line with the traditional claims for the antitumor effect of Casearia sylvestris. CONCLUSIONS: This investigation suggests that whether the extracts from Casearia sylvestris are cytotoxic at high concentrations, lower concentrations have antiproliferative effect and could be useful to complement conventional cytotoxic chemotherapy, and should be evaluated further.

Substituted 3­acyl­2­phenylamino­1,4­naphthoquinones intercalate into DNA and cause genotoxicity through the increased generation of reactive oxygen species culminating in cell death.

Naphthoquinones interact with biological systems by generating reactive oxygen species (ROS) that can damage cancer cells. The cytotoxicity and the antitumor activity of 3­acyl­2­phenylamino­1,4­naphthoquinones (DPB1­DPB9) were evaluated in the MCF7 human breast cancer cell line and in male Ehrlich tumor­bearing Balb/c mice. DPB4 was the most cytotoxic derivative against MCF7 cells (EC50 15 µM) and DPB6 was the least cytotoxic one (EC50 56 µM). The 1,4­naphthoquinone derivatives were able to cause DNA damage and promote DNA fragmentation as shown by the plasmid DNA cleavage assay (FII form). In addition, 1,4­naphthoquinone derivatives possibly interacted with DNA as intercalating agents, which was demonstrated by the changes caused in the fluorescence of the DNA­ethidium bromide complexes. Cell death of MCF7 cells induced by 3­acyl­2­phenylamino­1,4­naphthoquinones was mostly due to apoptosis. The DNA fragmentation and subsequent apoptosis may be correlated to the redox potential of the 1,4­naphthoquinone derivatives that, once present in the cell nucleus, led to the increased generation of ROS. Finally, certain 1,4­naphthoquinone derivatives and particularly DPB4 significantly inhibited the growth of Ehrlich ascites tumors in mice (73%).

Sodium orthovanadate associated with pharmacological doses of ascorbate causes an increased generation of ROS in tumor cells that inhibits proliferation and triggers apoptosis.

Pharmacological doses of ascorbate were evaluated for its ability to potentiate the toxicity of sodium orthovanadate (Na(3)VO(4)) in tumor cells. Cytotoxicity, inhibition of cell proliferation, generation of ROS and DNA fragmentation were assessed in T24 cells. Na(3)VO(4) was cytotoxic against T24 cells (EC(50)=5.8 µM at 24 h), but in the presence of ascorbate (100 µM) the EC(50) fell to 3.3 µM. Na(3)VO(4) plus ascorbate caused a strong inhibition of cell proliferation (up to 20%) and increased the generation of ROS (4-fold). Na(3)VO(4) did not directly cleave plasmid DNA, at this aspect no synergism was found occurring between Na(3)VO(4) and ascorbate once the resulting action of the combination was no greater than that of both substances administered separately. Cells from Ehrlich ascites carcinoma-bearing mice were used to determine the activity of antioxidant enzymes, the extent of the oxidative damage and the type of cell death. Na(3)VO(4) alone, or combined with ascorbate, increased catalase activity, but only Na(3)VO(4) plus ascorbate increased superoxide dismutase activity (up to 4-fold). Oxidative damage on proteins and lipids was higher due to the treatment done with Na(3)VO(4) plus ascorbate (2-3-fold). Ascorbate potentiated apoptosis in tumor cells from mice treated with Na(3)VO(4). The results indicate that pharmacological doses of ascorbate enhance the generation of ROS induced by Na(3)VO(4) in tumor cells causing inhibition of proliferation and apoptosis. Apoptosis induced by orthovanadate and ascorbate is closer related to inhibition on Bcl-xL and activation of Bax. Our data apparently rule out a mechanism of cell demise p53-dependent or related to Cdk2 impairment.

Brazilian Bidens pilosa Linné yields fraction containing quercetin-derived flavonoid with free radical scavenger activity and hepatoprotective effects.

Bidens pilosa is a plant used by Amazonian and Asian folks for some hepatopathies. The hydroethanol crude extract and three fractions were assessed for antioxidant and hepatoprotective effects. Higher levels of scavenger activity on the 1,1-diphenyl-2-picrylhydrazyl radical, inhibition of deoxyribose oxidation and lipid peroxidation in vitro were detected for the ethyl acetate fraction (IC(50)~4.3-32.3 µg/ml) followed by the crude extract (IC(50)~14.2-98.0 µg/ml). The ethyl acetate fraction, again followed by the crude extract, showed high contents of total soluble polyphenols (3.6±0.2 and 2.1±0.2 GAE/mg, respectively) and presence of a quercetin-derived flavonoid identified as quercetin 3,3'-dimethyl ether 7-O-ß-D-glycopyranoside. Both products were assayed for hepatoprotector effects against CCl(4)-induced liver injury in mice. Markers of oxidative stress and hepatic injury were evaluated. The results showed that the 10-day pretreatments (15 mg/kg, p.o.) protected the livers against injury by blocking CCl(4)-induced lipid peroxidation and protein carbonylation and the DNA fragmentation was decreased (~60%). The pretreatments avoided the loss of the plasma ferric reducing/antioxidant power and the elevation of serum transaminases and lactate dehydrogenase activities. The results suggest that the main constituents responsible for the hepatoprotective effects with free radical scavenger power associated are well extracted by performing fractionation with ethyl acetate. The findings support the Brazilian traditional use of this plant and justify further evaluations for the therapeutic efficacy and safety of the constituents of the ethyl acetate fraction to treat some liver diseases.

Study of the antitumor potential of Bidens pilosa (Asteraceae) used in Brazilian folk medicine.

AIM OF THE STUDY: Bidens pilosa (L.) (Asteraceae) is a medicinal plant traditionally used in Brazil for treating conditions that can be related to cancer. Therefore the present study was carried out to evaluate the antitumor activity of extracts obtained from the aerial parts of this plant species. MATERIALS AND METHODS: The crude hydroalcoholic extract (HAE) (water:alcohol, 6:4) and solvent fractions (chloroform=CHCl3,ethyl acetate=EtOAc, methanol=MeOH) were assessed for cytotoxicity assay by the brine shrimp and hemolytic, MTT and NRU assays. The antiproliferative potential of the crude extract and fractions was investigated in vivo using the Ehrlich ascites carcinoma (EAC) in isogenic Balb/c mice that were administered intraperitoneally 150 and 300 mg/kg body weight per day for nine days beginning 24 h after tumor inoculation. RESULTS: In in vitro cytotoxicity using Ehrlich ascites carcinoma cell line assay CHCl3 extract proved to be more toxic than the crude HAE with an IC(50) of 97+/-7.2 and 83+/-5.2 microg/mL to NRU and MTT, respectively. Histomorphological evaluations indicated that the treatment with CHCl3 and HAE extracts significantly reduced (P<0.05) body weight, abdominal circumference, tumor volume, packed cell volume and viable cell count, when compared to EAC control group. Furthermore, nonviable tumor cell count increased significantly (P<0.01) only under treatment with CHCl3 or HAE, and this was accompanied by a marked percentage increase in life span (54.2 and 41.7%, respectively). Biochemical assays revealed that CHCl3 and HAE extracts were also able to decrease serum LDH activity (39.5 and 30.6%) and GSH concentration (94.6 and 50.7%) in ascitic fluid, respectively. CONCLUSION: The chloroform fraction showed the best and methanolic the worst antitumor activity.