Antioxidant properties of hydroxycinnamic acids: a review of structure- activity relationships

Hydroxycinnamic acids (HCAs) are important phytochemicals possessing significant biological properties. Several investigators have studied in vitro antioxidant activity of HCAs in detail. In this review, we have gathered the studies focused on the structure-activity relationships (SARs) of these compounds that have used medicinal chemistry to generate more potent antioxidant molecules. Most of the reports indicated that the presence of an unsaturated bond on the side chain of HCAs is vital to their activity. The structural features that were reported to be of importance to the antioxidant activity were categorized as follows: modifications of the aromatic ring, which include alterations in the number and position of hydroxy groups and insertion of electron donating or withdrawing moieties as well as modifications of the carboxylic function that include esterification and amidation process. Furthermore, reports that have addressed the influence of physicochemical properties including redox potential, lipid solubility and dissociation constant on the antioxidant activity were also summarized. Finally, the pro-oxidant effect of HCAs in some test systems was addressed. Most of the investigations concluded that the presence of ortho-dihydroxy phenyl group (catechol moiety) is of significant importance to the antioxidant activity, while, the presence of three hydroxy groups does not necessarily improve the activity. Optimization of the structure of molecular leads is an important task of modern medicinal chemistry and its accomplishment relies on the careful assessment of SARs. SAR studies on HCAs can identify the most successful antioxidants that could be useful for management of oxidative stress-related diseases.

Mammography in asymptomatic women aged 40-49 years

OBJECTIVE To assess findings of mammography of and interventions resulting from breast cancer screening in women aged 40-49 years with no increased risk (typical risk) of breast cancer. METHODS This cross-sectional study evaluated women aged 40-49 years who underwent mammography screening in a mastology reference center in Recife, PE, Northeastern Brazil, between January 2010 and October 2011. Women with breast-related complaints, positive findings in the physical examination, or high risk of breast cancer were excluded. RESULTS The 1,000 mammograms performed were classified into the following Breast Imaging-Reporting and Data System (BI-RADS) categories BI-RADS 0, 232; BI-RADS 1, 294; BI-RADS 2, 294; BI-RADS 3, 16; BI-RADS 4A, 2; BI-RADS 5, 1. There was one case of grade II invasive ductal carcinoma and various interventions, including 469 ultrasound scans, 53 referrals to mastologists, 11 cytological examinations, and 8 biopsies. CONCLUSIONS Mammography screening in women aged 40-49 years with typical risk of breast cancer led to the performance of other interventions. However, it also resulted in increased costs without demonstrable efficacy in decreasing mortality.

Nanotechnology and antioxidant therapy: An emerging approach for neurodegenerative diseases

The efficacy, cellular uptake and specific transport of dietary antioxidants to target organs, tissues and cells remains the most important setback for their application in the treatment of oxidative-stress related disorders and in particular in neurodegenerative diseases, as brain targeting remains a still unsolved challenge. Nanotechnology based delivery systems can be a solution for the above mentioned problems, specifically in the case of targeting dietary antioxidants with neuroprotective activity. Nanotechnology-based delivery systems can protect antioxidants from degradation, improve their physicochemical drug-like properties and in turn their bioavailability. The impact of nanomedicine in the improvement of the performance of dietary antioxidants, as protective agents in oxidative- stress events, specifically through the use of drug delivery systems, is highlighted in this review as well as the type of nanomaterials regularly used for drug delivery purposes. From the data one can conclude that the research combining (dietary) antioxidants and nanotechnology, namely as a therapeutic solution for neurodegenerative diseases, is still in a very early stage. So, a huge research area remains to be explored that hopefully will yield new and effective neuroprotective therapeutic agents in a foreseeable future.

Feasibility and acceptability of an exergame intervention for schizophrenia

Objectives To evaluate the feasibility and acceptability of an exergame intervention as a tool to promote physical activity in outpatients with schizophrenia. Design Feasibility/Acceptability Study and Quasi-Experimental Trial. Method Sixteen outpatients with schizophrenia received treatment as usual and they all completed an 8-week exergame intervention using Microsoft Kinect® (20 min sessions, biweekly). Participants completed pre and post treatment assessments regarding functional mobility (Timed Up and Go Test), functional fitness performance (Senior Fitness Test), motor neurological soft signs (Brief Motor Scale), hand grip strength (digital dynamometer), static balance (force plate), speed of processing (Trail Making Test), schizophrenia-related symptoms (Positive and Negative Syndrome Scale) and functioning (Personal and Social Performance Scale). The EG group completed an acceptability questionnaire after the intervention. Results Attrition rate was 18.75% and 69.23% of the participants completed the intervention within the proposed schedule. Baseline clinical traits were not related to game performance indicators. Over 90% of the participants rated the intervention as satisfactory and interactive. Most participants (76.9%) agreed that this intervention promotes healthier lifestyles and is an acceptable alternative to perform physical activity. Repeated-measures MANOVA analyses found no significant multivariate effects for combined outcomes. Conclusion This study established the feasibility and acceptability of an exergame intervention for outpatients with schizophrenia. The intervention proved to be an appealing alternative to physical activity. Future trials should include larger sample sizes, explore patients' adherence to home-based exergames and consider greater intervention dosage (length, session duration, and/or frequency) in order to achieve potential effects.

Exploring cinnamic acid scaffold: development of promising neuroprotective lipophilic antioxidants

New lipophilic hydroxycinnamic acid based derivatives were designed and synthesized and their antioxidant and neuroprotective activities evaluated. The chemical modification introduced in the cinnamic acid scaffold leads to compounds with amplified lipophilicity and in general with increased antioxidant activity when compared to natural models (caffeic and ferulic acids). The compounds did not display cytotoxicity and present a significant neuroprotective effect against 6-OH-DA induced damage to SH-SY5Y cells. Compound 6 stands out as an efficient radical scavenger and iron(II) chelator that ensures drug-like properties. Moreover, neuroprotection against oxidative damage was observed even at low concentration (1 μM). Therefore, compound 6 developed by a biology-oriented approach displays a combination of important features for a further optimization process that will generate a new effective antioxidant with therapeutic application for oxidative-stress-related events, namely neurodegenerative diseases.

PROTEIN FOLDING AND DISEASE THE MITOCHONDRIAL PROTEIN FRATAXIN

This dissertation focuses on the study of frataxin, a small mitochondrial protein whose deficiency is associated with the neurodegenerative disease Friedreich's ataxia (FRDA). Aiming at a better understanding of frataxin conformational and functional properties, two lines of research were followed: first, the effect of FRDA-related mutations in human frataxin (FXN) were studied and the role of oxidative stress related modification addressed; second, yeast frataxin (Yfh1) orthologue was used to explore the conformational and functional properties of the protein.(...)

Anti-Toxocara antibodies detected in children attending elementary school in Vitoria, State of Espírito Santo, Brazil: prevalence and associated factors

INTRODUCTION: The aim of this study was to evaluate the frequency of anti-Toxocara antibodies in serum from 7-year-old children attending elementary school in Vitória-ES, Brazil and to correlate these antibodies with socio-demographic factors, the presence of intestinal helminths, blood eosinophil numbers, past history of allergy or asthma, and clinical manifestations of helminth infections. METHODS: The detection of anti-Toxocara antibodies was performed using an ELISA (Cellabs Pty Ltd)on serum from 391 children who had already been examined by fecal examination and blood cell counts. Data from clinical and physical examinations were obtained for all children. RESULTS: The prevalence of anti-Toxocara antibodies was 51.6%, with no gender differences. No significant differences were observed between positive serology and the presence or absence of intestinal worms (60.3 and 51.7%, respectively; p = 0.286). The only variables significantly related to positive serology were onycophagy and the use of unfiltered water. Although eosinophilia (blood eosinophil count higher than 600/mm³) was significantly related to the presence of a positive ELISA result, this significance disappeared when we considered only children without worms or without a past history of allergy or asthma. No clinical symptoms related to Toxocara infection were observed. CONCLUSIONS: There is a high prevalence of anti-Toxocara antibodies in children attending elementary schools in Vitória, which may be partially related to cross-reactivity with intestinal helminths or to a high frequency of infection with a small number of Toxocara eggs.

Good vibrations

The work reported in this thesis addresses the research question of when and how positive psychological states impact positive behavior and positive organizational development. We present two theoretical essays and three empirical studies to find possible answers to this question and we use a multitude of methodologies with different epistemological assumptions, including quantitative correlation analysis, social network analysis and qualitative grounded theory analysis. In the whole, our work shows that positive psychological states are fundamental to promote individual and organizational higher-levels of performance and well-being. It also points that the capability to induce positive psychological states in others (an “alter-positive” approach) is a powerful way to develop outstanding individuals and organizations. In a broader sense, it stresses the need to promote good vibrations as a fundamental route to create a better world.

MAP kinase pathways in UV-induced apoptosis of retinal pigment epithelium ARPE19 cells.

The retinal pigment epithelium (RPE) is constantly exposed to external injuries which lead to degeneration, dysfunction or loss of RPE cells. The balance between RPE cells death and proliferation may be responsible for several diseases of the underlying retina, including age-related macular degeneration (AMD) and proliferative vitreoretinopathy (PVR). Signaling pathways able to control cells proliferation or death usually involve the MAPK (mitogen-activated protein kinases) pathways, which modulate the activity of transcription factors by phosphorylation. UV exposure induces DNA breakdown and causes cellular damage through the production of reactive oxygen species (ROS) leading to programmed cell death. In this study, human retinal pigment epithelial cells ARPE19 were exposed to 100 J/m(2) of UV-C and MAPK pathways were studied. We first showed the expression of the three major MAPK pathways. Then we showed that activator protein-1 (AP-1) was activated through phosphorylation of cJun and cFos, induced by JNK and p38, respectively. Specific inhibitors of both kinases decreased their respective activities and phosphorylation of their nuclear targets (cJun and cFos) and reduced UV-induced cell death. The use of specific kinases inhibitors may provide excellent tools to prevent RPE apoptosis specifically in RPE diseases involving ROS and other stress-related compounds such as in AMD.

Preconditioning with Triiodothyronine Improves the Clinical Signs and Acute Tubular Necrosis Induced by Ischemia/Reperfusion in Rats.

BACKGROUND Renal ischemia/reperfusion (I/R) injury is manifested by acute renal failure (ARF) and acute tubular necrosis (ATN). The aim of this study was to evaluate the effectiveness of preconditioning with 3, 3, 5 triiodothyronine (T3) to prevent I/R renal injury. METHODOLOGY/PRINCIPAL FINDINGS THE RATS WERE DIVIDED INTO FOUR GROUPS: sham-operated, placebo-treated (SO-P), sham-operated T3- treated (SO- T3), I/R-injured placebo-treated (IR-P), and I/R-injured T3-treated (IR- T3) groups. At 24 h before ischemia, the animals received a single dose of T3 (100 μg/kg). Renal function and plasma, urinary, and tissue variables were studied at 4, 24, and 48 h of reperfusion, including biochemical, oxidative stress, and inflammation variables, PARP-1 immunohistochemical expression, and ATN morphology. In comparison to the SO groups, the IR-P groups had higher plasma urea and creatinine levels and greater proteinuria (at all reperfusion times) and also showed: increased oxidative stress-related plasma, urinary, and tissue variables; higher plasma levels of IL6 (proinflammatory cytokine); increased glomerular and tubular nuclear PARP-1 expression; and a greater degree of ATN. The IR-T3 group showed a marked reduction in all of these variables, especially at 48 h of reperfusion. No significant differences were observed between SO-P and SO-T3 groups. CONCLUSIONS This study demonstrates that preconditioning rats with a single dose of T3 improves the clinical signs and ATN of renal I/R injury. These beneficial effects are accompanied by reductions in oxidative stress, inflammation, and renal PARP-1 expression, indicating that this sequence of factors plays an important role in the ATN induced by I/R injury.

Light-induced retinal degeneration correlates with changes in iron metabolism gene expression, ferritin level, and aging.

PURPOSE: Retinal degeneration is associated with iron accumulation in several rodent models in which iron-regulating proteins are impaired. Oxidative stress is catalyzed by unbound iron. METHODS: The role of the heavy chain of ferritin, which sequesters iron, in regulating the thickness of the photoreceptor nuclear layer in the 4- and 16-month-old wild-type H ferritin (HFt(+/+)) and heterozygous H ferritin (HFt(+/-)) mice was investigated, before and 12 days after exposure to 13,000-lux light for 24 hours. The regulation of gene expression of the various proteins involved in iron homeostasis, such as transferrin, transferrin receptor, hephaestin, ferroportin, iron regulatory proteins 1 and 2, hepcidin, ceruloplasmin, and heme-oxygenase 1, was analyzed by quantitative (q)RT-PCR during exposure (2, 12, and 24 hours) and 24 hours after 1 day of exposure in the 4-month-old HFt(+/+) and HFt(+/-) mouse retinas. RESULTS: Retinal degeneration in the 4-month-old HFt(+/-) mice was more extensive than in the HFt(+/+) mice. Yet, it was more extensive in both of the 16-month-old mouse groups, revealing the combined effect of age and excessive light. Injury caused by excessive light modified the temporal gene expression of iron-regulating proteins similarly in the HFt(+/-) and HFt(+/+) mice. CONCLUSIONS: Loss of one allele of H ferritin appears to increase light-induced degeneration. This study highlighted that oxidative stress related to light-induced injury is associated with major changes in gene expression of iron metabolism proteins.

O efeito do sorriso na percepção psicológica da pessoa

O objectivo do estudo foi o de verificar o efeito do sorriso na percepção psicológica da pessoa em jovens, adultos, idosos e jovens negros. Pretendia-se verificar se o sorriso contribui para os traços diferenciais entre os grupos humanos em estudo e se o mesmo era descritor de género. O estudo envolveu um delineamento transversal analítico ou estudo não-experimental, também classificado por estudo pós-facto, estudo de observação passiva ou estudo correlacional e de observação, de comparação entre grupos, mediante o juízo ou julgamento psicológico da face neutra e do tipo de sorriso contrastados, de matriz factorial 4 x 2 x 2 (face neutra, sorriso fechado, sorriso superior, sorriso largo; género dos estímulos; género dos respondentes) e a sua finalidade foi descrever a percepção psicológica do sorriso em função das variáveis género do estímulo, género do respondente e grupo étnico, na Escala de Percepção do Sorriso (EPS), em formato diferenciador semântico, com 19 itens bipolares opostos, tendo a avaliação sido feita numa escala ordinal de 1 a 7 pontos, nas dimensões Avaliação (12 itens) e Movimento Expressivo (7 itens) resultante dos estudos preliminares sobre a atractividade facial (estudo preliminar 1) e a escolha de dípolos de adjectivos preditores para percepção psicológica da face neutra (estudo preliminar 2). Nos estudos principais 1, 2 e 3 foram utilizados 24 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (12 do estímulo mulher e 12 do estímulo homem) referentes aos três grupos etários (18-25 anos, 40-50 anos e 60-70 anos) e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 480 participantes portugueses de ambos os géneros (240 mulheres e 240 homens) distribuídos por grupos etários de jovens (80 mulheres e 80 homens, média: 22.2 anos), adultos (80 mulheres e 80 homens, média: 43.1 anos) e idosos (80 mulheres e 80 homens, média: 65.0 anos) No estudo principal 4, foram utilizados 8 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (4 do estímulo mulher e 4 do estímulo homem) de universitários de Cabo Verde, a estudar em Portugal, e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 160 participantes de ambos os géneros (80 mulheres e 80 homens) e estudantes universitários portugueses (média: 21.8 anos). Os resultados revelam e confirmam o efeito do sorriso na percepção psicológica da pessoa, à semelhança de outros estudos, isto é, sorrir torna a percepção psicológica mais positiva ou negativa e verifica-se que tal sucede em função do género do estímulo e do género do respondente. As diferenças significativas na percepção da face neutra e tipo de sorriso contrastados são justificadas pela pertença de género de quem os percepciona e pela pertença do género de quem é percepcionado. Tal apenas não sucede no factor Avaliação do grupo dos adultos. Os resultados obtidos indicam que, quer no factor Avaliação quer no factor Movimento Expressivo, os tipos de sorriso largo e superior são os que registam médias ponderadas mais elevadas. Pelo contrário, a face neutra e o sorriso fechado registam valores menos elevados na percepção. A análise da percepção da pessoa em função da face neutra e tipo de sorriso contrastados revelou uma correspondência entre a expressão facial, o género do estímulo e o género do respondente. No factor Avaliação, a mulher é percepcionada mais positivamente que o homem, verificando-se o inverso no factor Movimento Expressivo no grupo dos adultos e dos idosos. Verificou-se efeito do sorriso na percepção psicológica dos estímulos de cor negra. No grupo dos jovens que percepcionaram estímulos de cor negra, o homem é considerado mais positivo que a mulher em ambos os factores. O efeito significativo do género revela que a sua percepção é condicionada pelo seu próprio género. Os resultados apontam ainda para a configuração pronunciada de uma hierarquização ascendente da face neutra e tipo de sorriso contrastados em dois conjuntos bem delimitados e distinguindo diferentes formas topográficas de sorrir: a face neutra e o sorriso fechado e o sorriso superior e o sorriso largo.

O efeito do sorriso na percepção psicológica da pessoa

O objectivo do estudo foi o de verificar o efeito do sorriso na percepção psicológica da pessoa em jovens, adultos, idosos e jovens negros. Pretendia-se verificar se o sorriso contribui para os traços diferenciais entre os grupos humanos em estudo e se o mesmo era descritor de género. O estudo envolveu um delineamento transversal analítico ou estudo não-experimental, também classificado por estudo pós-facto, estudo de observação passiva ou estudo correlacional e de observação, de comparação entre grupos, mediante o juízo ou julgamento psicológico da face neutra e do tipo de sorriso contrastados, de matriz factorial 4 x 2 x 2 (face neutra, sorriso fechado, sorriso superior, sorriso largo; género dos estímulos; género dos respondentes) e a sua finalidade foi descrever a percepção psicológica do sorriso em função das variáveis género do estímulo, género do respondente e grupo étnico, na Escala de Percepção do Sorriso (EPS), em formato diferenciador semântico, com 19 itens bipolares opostos, tendo a avaliação sido feita numa escala ordinal de 1 a 7 pontos, nas dimensões Avaliação (12 itens) e Movimento Expressivo (7 itens) resultante dos estudos preliminares sobre a atractividade facial (estudo preliminar 1) e a escolha de dípolos de adjectivos preditores para percepção psicológica da face neutra (estudo preliminar 2). Nos estudos principais 1, 2 e 3 foram utilizados 24 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (12 do estímulo mulher e 12 do estímulo homem) referentes aos três grupos etários (18-25 anos, 40-50 anos e 60-70 anos) e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 480 participantes portugueses de ambos os géneros (240 mulheres e 240 homens) distribuídos por grupos etários de jovens (80 mulheres e 80 homens, média: 22.2 anos), adultos (80 mulheres e 80 homens, média: 43.1 anos) e idosos (80 mulheres e 80 homens, média: 65.0 anos) No estudo principal 4, foram utilizados 8 estímulos fotográficos apresentando o tipo de sorriso (fechado, superior e largo) e a face neutra (4 do estímulo mulher e 4 do estímulo homem) de universitários de Cabo Verde, a estudar em Portugal, e a Escala de Percepção do Sorriso (EPS) foi aplicada a uma amostra não probabilística ou intencional do tipo homogénea de 160 participantes de ambos os géneros (80 mulheres e 80 homens) e estudantes universitários portugueses (média: 21.8 anos). Os resultados revelam e confirmam o efeito do sorriso na percepção psicológica da pessoa, à semelhança de outros estudos, isto é, sorrir torna a percepção psicológica mais positiva ou negativa e verifica-se que tal sucede em função do género do estímulo e do género do respondente. As diferenças significativas na percepção da face neutra e tipo de sorriso contrastados são justificadas pela pertença de género de quem os percepciona e pela pertença do género de quem é percepcionado. Tal apenas não sucede no factor Avaliação do grupo dos adultos. Os resultados obtidos indicam que, quer no factor Avaliação quer no factor Movimento Expressivo, os tipos de sorriso largo e superior são os que registam médias ponderadas mais elevadas. Pelo contrário, a face neutra e o sorriso fechado registam valores menos elevados na percepção. A análise da percepção da pessoa em função da face neutra e tipo de sorriso contrastados revelou uma correspondência entre a expressão facial, o género do estímulo e o género do respondente. No factor Avaliação, a mulher é percepcionada mais positivamente que o homem, verificando-se o inverso no factor Movimento Expressivo no grupo dos adultos e dos idosos. Verificou-se efeito do sorriso na percepção psicológica dos estímulos de cor negra. No grupo dos jovens que percepcionaram estímulos de cor negra, o homem é considerado mais positivo que a mulher em ambos os factores. O efeito significativo do género revela que a sua percepção é condicionada pelo seu próprio género. Os resultados apontam ainda para a configuração pronunciada de uma hierarquização ascendente da face neutra e tipo de sorriso contrastados em dois conjuntos bem delimitados e distinguindo diferentes formas topográficas de sorrir: a face neutra e o sorriso fechado e o sorriso superior e o sorriso largo.

Cognitive errors assessed by observer ratings in bipolar affective disorder: relationship with symptoms and therapeutic alliance

The construct of cognitive errors is clinically relevant for cognitive therapy of mood disorders. Beck's universality hypothesis postulates the relevance of negative cognitions in all subtypes of mood disorders, as well as positive cognitions for manic states. This hypothesis has rarely been empirically addressed for patients presenting bipolar affective disorder (BD). In-patients (n = 30) presenting with BD were interviewed, as were 30 participants of a matched control group. Valid and reliable observer-rater methodology for cognitive errors was applied to the session transcripts. Overall, patients make more cognitive errors than controls. When manic and depressive patients were compared, parts of the universality hypothesis were confirmed. Manic symptoms are related to positive and negative cognitive errors. These results are discussed with regard to the main assumptions of the cognitive model for depression; thus adding an argument for extending it to the BD diagnostic group, taking into consideration specificities in terms of cognitive errors. Clinical implications for cognitive therapy of BD are suggested.

The impact of triathlon training and racing on athletes' general health.

Although the sport of triathlon provides an opportunity to research the effect of multi-disciplinary exercise on health across the lifespan, much remains to be done. The literature has failed to consistently or adequately report subject age group, sex, ability level, and/or event-distance specialization. The demands of training and racing are relatively unquantified. Multiple definitions and reporting methods for injury and illness have been implemented. In general, risk factors for maladaptation have not been well-described. The data thus far collected indicate that the sport of triathlon is relatively safe for the well-prepared, well-supplied athlete. Most injuries 'causing cessation or reduction of training or seeking of medical aid' are not serious. However, as the extent to which they recur may be high and is undocumented, injury outcome is unclear. The sudden death rate for competition is 1.5 (0.9-2.5) [mostly swim-related] occurrences for every 100,000 participations. The sudden death rate is unknown for training, although stroke risk may be increased, in the long-term, in genetically susceptible athletes. During heavy training and up to 5 days post-competition, host protection against pathogens may also be compromised. The incidence of illness seems low, but its outcome is unclear. More prospective investigation of the immunological, oxidative stress-related and cardiovascular effects of triathlon training and competition is warranted. Training diaries may prove to be a promising method of monitoring negative adaptation and its potential risk factors. More longitudinal, medical-tent-based studies of the aetiology and treatment demands of race-related injury and illness are needed.