Oleocanthal, a phenolic derived from virgin olive oil: a review of the beneficial effects on inflammatory disease

Virgin olive oil (VOO) is credited as being one of many healthful components of the Mediterranean diet. Mediterranean populations experience reduced incidence of chronic inflammatory disease states and VOO is readily consumed as part of an everyday dietary pattern. A phenolic compound contained in VOO, named oleocanthal, shares unique perceptual and anti-inflammatory characteristics with Ibuprofen. Over recent years oleocanthal has become a compound of interest in the search for naturally occurring compounds with pharmacological qualities. Subsequent to its discovery and identification, oleocanthal has been reported to exhibit various modes of action in reducing inflammatory related disease, including joint-degenerative disease, neuro-degenerative disease and specific cancers. Therefore, it is postulated that long term consumption of VOO containing oleocanthal may contribute to the health benefits associated with the Mediterranean dietary pattern. The following paper summarizes the current literature on oleocanthal, in terms of its sensory and pharmacological properties, and also discusses the beneficial, health promoting activities of oleocanthal, in the context of the molecular mechanisms within various models of disease.

Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses

The genesis of severe fatigue and disability in people following acute pathogen invasion involves the activation of Toll-like receptors followed by the upregulation of proinflammatory cytokines and the activation of microglia and astrocytes. Many patients suffering from neuroinflammatory and autoimmune diseases, such as multiple sclerosis, Parkinson's disease and systemic lupus erythematosus, also commonly suffer from severe disabling fatigue. Such patients also present with chronic peripheral immune activation and systemic inflammation in the guise of elevated proinflammtory cytokines, oxidative stress and activated Toll-like receptors. This is also true of many patients presenting with severe, apparently idiopathic, fatigue accompanied by profound levels of physical and cognitive disability often afforded the non-specific diagnosis of chronic fatigue syndrome.

Auranofin: repurposing an old drug for a golden new age

Drug discovery, development and registration is an expensive and time-consuming process associated with a high failure rate [Pessetto et al. (Mol Cancer Ther 12:1299-1309, 2013), Woodcock and Woosley (Annu Rev Med 59:1-12, 2008)]. Drug 'repurposing' is the identification of new therapeutic purposes for already approved drugs and is more affordable and achievable than novel drug discovery [Pessetto et al. (Mol Cancer Ther 12:1299-1309, 2013)]. Auranofin is a drug that is approved for the treatment of rheumatoid arthritis but is being investigated for potential therapeutic application in a number of other diseases including cancer, neurodegenerative disorders, HIV/AIDS, parasitic infections and bacterial infections [Tejman-Yarden et al. (Antimicrob Agents Chemother 57:2029-2035, 2013)]. The main mechanism of action of auranofin is through the inhibition of reduction/oxidation (redox) enzymes that are essential for maintaining intracellular levels of reactive oxygen species. Inhibition of these enzymes leads to cellular oxidative stress and intrinsic apoptosis [Pessetto et al. (Mol Cancer Ther 12:1299-1309, 2013), Fan et al. (Cell Death Dis 5:e1191, 2014), Fiskus et al. (Cancer Res 74:2520-2532, 2014), Marzano et al. (Free Radic Biol Med 42:872-881, 2007)]. Drugs such as auranofin that have already been approved for human use [Tejman-Yarden et al. (Antimicrob Agents Chemother 57:2029-2035, 2013)] can be brought into clinical use for other diseases relatively quickly and for a fraction of the cost of new drugs.

The neuro-immune pathophysiology of central and peripheral fatigue in systemic immune-inflammatory and neuro-immune diseases

Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue. The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders. This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways.

Dissecting ADAMTS proteoglycanase biology in development and disease

 This research was focused upon members of the ADAMTS family of 'proteinases', proteins that have enzymatic activity. Their dysregulation can cause developmental defects and disease. This thesis describes the expression and regulation of ADAMTS15, as well as new developmental functions and inhibition of ADAMTS5 in arthritis.

Positive changes in self-management and disease severity following climate therapy in people with psoriasis

The aim of this study was to investigate the impact of climate therapy on self-management in people with psoriasis. This was a prospective study of 254 adults with chronic psoriasis who participated in a 3-week climate therapy (CT) programme. The 8-scale Health Education Impact Questionnaire (heiQ) was completed at baseline, after 3 weeks of CT, and 3 months later. Change was assessed using paired sample t-tests mean (95% confidence interval) change scores (range 1-4). All heiQ scales showed statistically significant improvement after 3 weeks of CT. The greatest improvement was in Health-directed activity, followed by Emotional distress, and Skill and technique acquisition. At the 3-month follow-up, only the Emotional distress scale remained improved. In addition, disease severity (self-administered PASI; SAPASI) improved significantly from before CT to 3 weeks and 3 months after CT. This study suggests that CT provides a range of benefits that are important to people with psoriasis, particularly in the short term. A challenge is how to achieve long-term benefits.

The epidemiology of dry eye in Melbourne, Australia

OBJECTIVE: To describe the epidemiology of dry eye in the adult population of Melbourne, Australia. DESIGN: A cross-sectional prevalence study. PARTICIPANTS: Participants were recruited by a household census from two of nine clusters of the Melbourne Visual Impairment Project, a population-based study of age-related eye disease in the 40 and older age group of Melbourne, Australia. Nine hundred and twenty-six (82.3% of eligible) people participated; 433 (46.8%) were male. They ranged in age from 40 to 97 years, with a mean of 59.2 years. MAIN OUTCOME MEASURES: Self-reported symptoms of dry eye were elicited by an interviewer-administered questionnaire. Four objective assessments of dry eye were made: Schirmer's test, tear film breakup time, rose bengal staining, and fluorescein corneal staining. A standardized clinical slit-lamp examination was performed on all participants. Dry eye for the individual signs or symptoms was defined as: rose bengal > 3, Schirmers < 8, tear film breakup time < 8, > 1/3 fluorescein staining, and severe symptoms (3 on a scale of 0 to 3). RESULTS: Dry eye was diagnosed as follows: 10.8% by rose bengal, 16.3% by Schirmer's test, 8.6% by tear film breakup time, 1.5% by fluorescein staining, 7.4% with two or more signs, and 5.5% with any severe symptom not attributed to hay fever. Women were more likely to report severe symptoms of dry eye (odds ratio [OR] = 1.85; 95% confidence limits [CL] = 1.01, 3.41). Risk factors for two or more signs of dry eye include age (OR = 1.04; 95% CL = 1.01, 1.06), and self-report of arthritis (OR = 3.27; 95% CL = 1.74, 6.17). These results were not changed after excluding the 21 people (2.27%) who wore contact lenses. CONCLUSIONS: These are the first reported population-based data of dry eye in Australia. The prevalence of dry eye varies by sign and symptom.

Physical health comorbidities in women with personality disorder: data from the Geelong osteoporosis study

BACKGROUND: Associations between common psychiatric disorders, psychotic disorders and physical health comorbidities are frequently investigated. The complex relationship between personality disorders (PDs) and physical health is less understood, and findings to date are varied. This study aims to investigate associations between PDs with a number of prevalent physical health conditions. METHODS: This study examined data collected from women (n=765;≥25years) participating in a population-based study located in south-eastern Australia. Lifetime history of psychiatric disorders was assessed using the semi-structured clinical interviews (SCID-I/NP and SCID-II). The presence of physical health conditions (lifetime) were identified via a combination of self-report, medical records, medication use and clinical data. Socioeconomic status, and information regarding medication use, lifestyle behaviors, and sociodemographic information was collected via questionnaires. Logistic regression models were used to investigate associations. RESULTS: After adjustment for sociodemographic variables (age, socioeconomic status) and health-related factors (body mass index, physical activity, smoking, psychotropic medication use), PDs were consistently associated with a range of physical health conditions. Novel associations were observed between Cluster A PDs and gastro-oesophageal reflux disease (GORD); Cluster B PDs with syncope and seizures, as well as arthritis; and Cluster C PDs with GORD and recurrent headaches. CONCLUSIONS: PDs were associated with physical comorbidity. The current data contribute to a growing evidence base demonstrating associations between PDs and a number of physical health conditions independent of psychiatric comorbidity, sociodemographic and lifestyle factors. Longitudinal studies are now required to investigate causal pathways, as are studies determining pathological mechanisms.

Avaliação da adesão ao acompanhamento ambulatorial dos pacientes em profilaxia secundária da febre reumática no Hospital de Clínicas de Porto Alegre

A Febre Reumática (FR) é uma doença com significativa prevalência na população de pacientes em idade escolar. Constitui-se na principal causa de cardiopatia crônica em adultos jovens em países em desenvolvimento. A prevenção é de fácil manejo terapêutico, embora com reduzido índice de adesão. Até o momento, a melhor forma de evitarmos as seqüelas cardíacas é através da identificação e tratamento precoces e a manutenção de uma adequada profilaxia secundária. São raras as publicações referentes ao acompanhamento da profilaxia secundária após a alta hospitalar. O objetivo deste trabalho é avaliar a adesão ao acompanhamento dos pacientes com FR internados no Hospital de Clínicas de Porto Alegre, no período de janeiro de 1977 a junho de 1999. A coorte foi constituída de 112 indivíduos com FR que tinham indicação de retorno ao ambulatório após a alta. Quarenta pacientes (35,7%) foram atendidos no primeiro episódio de FR. A maioria apresentou seqüelas cardíacas (52,7%), ocorrendo registro de casos a partir de 8 anos de idade. As manifestações clínicas nos 40 pacientes atendidos no primeiro episódio de FR foram: 21 (52,5%) com cardite, 30 (75%) com artrite e 14 (35%) com coréia. Apenas 77 (68,7%) retornaram ao ambulatório após a alta e somente 13 (21% pelo método de Kaplan-Meier) mantiveram acompanhamento por no mínimo 5 anos. A idade menor ou igual a 16 anos foi fator preditivo de maior tempo de acompanhamento. Local de procedência, presença de seqüelas e renda familiar não mostraram associação significante. A interrupção do acompanhamento pela maioria dos pacientes e a verificação do pior prognóstico cardíaco nos pacientes com recidivas sugere a necessidade da adoção de um programa de orientação e busca para garantir a efetividade da profilaxia secundária.

Um estudo piloto sobre os aspectos psicológicos associados a artrite reumatoide

A presente dissertação de Mestrado em Psicologia Social e da Personalidade caracterizou-se por um Estudo Piloto concernente aos aspectos psicológicos relacionados a Artrite Reumatóide (AR), realizado através de uma investigação exploratória de campo no Hospital Universitário Clementino Fraga Filho (HUCFF), Ambulatório de Reumatologia, na qual treze (13) pacientes reumatóides foram entrevista dos. O grupo amostral foi constituído de dez (lO) casos do sexo feminino e três (3) do sexo masculino com diagnóstico apenas desse tipo de patologia. O foco de interesse desta pesquisa foram os aspectos psicológicos que precederam e desempenharam algum tipo de influência no começo e progressão da AR, a partir do ponto de vista psicossomático. Os resultados obtidos parecem evidenciar um background psicodinâmico, uma vez que os relatos de história de vida giraram em torno de temas que sugeriram uma influência parental restritiva na primeira infância; hostilidade e agressividade contidas; inibição; auto-estima baixa; sentimentos de inferioridade e tendência a repressão e controle dos sentimentos. A nível manifesto essas pessoas procuram demonstrar externa mente o oposto do que são ou como se sentem internamente (‘necessidade se serem ativos'). Assim, parece existir uma relação psicodinâmica entre os aspectos somáticos e psíquicos influenciando o processo da Artrite Reumatóide. Os efeitos psicológicos advindos da doença, tais como: grande preocupação acerca do processo da enfermidade em si e de suas consequências; ansiedade gerada pelo desconhecimento parcial do real significado da doença; menor comunicação tanto no meio intra como extra familiar, também foram enfatizados. Os resultados deste estudo não são conclusivos e o pesquisa dor admite que o grupo amostral foi muito reduzido e o método empregado diferiu dos comumente aplicados a este tipo de pesquisa. Entre tanto, os mesmos pouco divergiram dos de outras investigações.

Efeito do Fucoidam de Fucus vesiculosus em um modelo experimental de artrite reumatóide

Rheumatoid arthritis (RA) is systemic auto imune disorder. It is caracterized by chronic inflammation of joints leading to progressive erosion of cartilage and bone. We investigated the effect of the administration of fucoidan, sulfated polysaccharides, from algae Fucus vesiculosus in the acute (6h) in zymosan-induced arthritis (AZy). Wistar rats (180-230 g) were used for all groups experimental. Non-treated animals received just intraarticular injection of 1 mg the zymosan, control group received intraarticular injection of 50 µL the saline, groups received either fucoidan of Fucus vesiculosus (15, 30, 50 or 70 mg/Kg) or parecoxib (1 mg/Kg) 1 hour after injection of zymosan. After 6 h, the articular exudates were collected for evaluation of the cell influx and nitrite (Griess reaction) release. The sinovial membranes and articular cartilages were excised for histopathological analysis and by determination of the glycosaminoglycan (GAG), respectively. ZyA led to increased NO and cell influx into the joints. Therapeutic administration of the fucoidan or parecoxib did significantly inhibited the cell influx and the synovitis, as compared to non-treated rats (p<0,05), though being able to reduced NO release. Representative agarose gel electrophoresis of the GAGs, the content of condroitin-sulphate was observed during the process. These findings suggest that the fucoidan from Fucus vesiculosus has potential anti-inflammatory activity

Avaliação demográfica, clinico-laboratorial e genética de indivíduos com lupus eritematoso sistêmico e artrite reumatóide residentes em região tropical

The aetiology of autoimmunes disease is multifactorial and involves interactions among environmental, hormonal and genetic factors. Many different genes may contribute to autoimmunes disease susceptibility. The major histocompatibility complex (MHC) genes have been extensively studied, however many non-polymorphic MHC genes have also been reported to contribute to autoimmune diseases susceptibility. The aim of the present study was to evaluate the influence of SLC11A1 gene in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Ninety-six patients with SLE, 37 with RA and 202 controls enrolled in this case-control study, were evaluated with regard to demographic, genetic, laboratorial and clinical data. SLE mainly affects females in the ratio of 18 women for each man, 88,3% of the patients aged from 15 to 45 years old and it occurs with similar frequency in whites and mulattos. The rate of RA between women and men was 11:1, with 77,1% of the cases occurring from 31 to 60 years. The genetic analysis of the point mutation -236 of the SLC11A1 gene by SSCP did not show significant differences between alleles/genotypes in patients with SLE or RA when compared to controls. The most frequent clinical manifestations in patients with SLE were cutaneous (87%) and joint (84.9%). In patients with RA, the most frequent out-joint clinical manifestation were rheumatoid nodules (13,5%). Antinuclear antibodies were present in 100% of the patients with SLE. There was no significant relation between activity of disease and presence of rheumatoid factor in patients with RA, however 55,6% of patients with active disease presented positive rheumatoid factor. Significant association between alleles/genotypes of point mutation -236 and clinical manifestations was not found

Efeito de frações obtidas da fucoidana de Fucus vesiculosus em modelo experimental de artrite induzida por Zymosan

The fucoidan from Fucus vesiculosus is known for having diverse biological properties. This study analyzed the therapeutic action of populations of commercial fucoidan (F. vesiculosus) on zymosan-induced arthritis. Three populations of fucoidan were obtained after acetone fractionation; these were denominated F1 (52.3%), F2 (36.7%) and F3 (10.7%). Chemical analyses showed that F1 contained the largest amount of sulfate ion. The electrophoretic profile shows that the commercial or total fucoidan (TF), different from the other fucoidans and from glycosaminoglycan patterns, is quite polydisperse, which indicates that it is composed of a mixture of sulfate polysaccharides. On the other hand, the fucoidans obtained from TF showed only an electrophoretic band with much lower polydispersion than that observed for TF. Fucoidan F2 showed a migration between fucoidans F1 and F3. Owing to the small amount of mass obtained from F3, we used only fucoidans F1 and F2 in the induced arthritis tests. After 1 hour of induction, we administered F1 or F2 (10, 25 and 50 mg/kg i.p.) or diclofenac sodium (10 mg/kg i.p.) or lumiracoxib (5 mg/kg o.a.) or L-NAME (30 mg/kg i.p.). After 6 hours, we performed analyses of cell influx and nitrite levels in addition to histopathological analysis. Fucoidans F1 and F2 were more potent both in decreasing the number of leukocytes and the amount of nitric oxide found in the synovial fluid. This indicates that the anti-inflammatory mechanism of these fucoidans is not only related to selectin block, but also to nitric oxide synthesis inhibition

Inhibition of Neurotoxic Secretory Phospholipases A(2) Enzymatic, Edematogenic, and Myotoxic Activities by Harpalycin 2, an Isoflavone Isolated from Harpalyce brasiliana Benth

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Harpalycin 2 inhibits the enzymatic and platelet aggregation activities of PrTX-III, a D49 phospholipase A(2) from Bothrops pirajai venom

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)