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Bisphenol A (BPA) may adversely affect human health by inducing oxidative stress and irreversible damage to cells. Bioactive compounds found in some functional foods, individually or in combination, can attenuate the negative effects of BPA exposure; an example is the multi-supplement containing guarana (Gua), selenium (Se), and L-carnitine (LC) -GSC- which has already demonstrated antioxidant, genoprotective, and immunomodulatory activities. This study aimed to determine the effect of GSC and its constituents on oxidative and genotoxic alterations triggered by BPA exposure in the retinal epithelial cell line. The cells exposed to BPA (0.001, 0.01, 0.1, 1, 3, and 10 µM) to determine the lowest concentration required to induce cyto-genotoxicity. ARPE-19 cells were then concomitantly exposed to the selected BPA concentration, GSC, and its components (Gua, 1.07 mg/mL; Se, 0.178 µg/mL; and LC, 1.43 mg/mL). Flow cytometry, biochemical assays, qRT-PCR, genotoxicity, apoptosis, and cellular proliferation. Based on our results, 10 µM of BPA could induce cyto-genotoxic and oxidative alterations. BPA did not alter the Bcl-2/BAX expression ratio but induced Casp3 and Casp8 overexpression, suggesting that apoptosis was induced mainly via the extrinsic pathway. GSC partially reversed the alterations triggered by BPA in ARPE-19 cells. However, Se had unexpected negative effects on ARPE-19 cells. The multi-supplement GSC may attenuate changes in oxidative and genotoxic markers related to exposure of ARPE-19 cells to BPA. our results revealed that the antioxidant, anti-apoptotic, and genoprotective properties of GSC were not universally shared by its individual, once Se did not exhibit any positive impact.

Background: This study aimed to analyze the trend of occupational noise-induced hearing loss (ONIHL) in Brazilian workers at a metallurgical plant with a hearing conservation program (HCP), which has been addressed in a previous study., Methods: All 152 workers in this time series (20032018) participated in the HCP and used personal protective equipment. All annual audiometry records in the company's software were collected from the electronic database. The trend of ONIHL was analyzed with the joinpoint regression model. The hearing thresholds of ONIHL cases at the end of the series were compared with those found in a national reference study., Results: The binaural mean hearing thresholds at 3, 4, and 6 kHz at the end of the series were higher for ages ≥50 years, exposures ≥85 dB (A), time since admission >20 years, and maintenance workers. Significance was found only in the group divided by age. There was an increasing time trend of ONIHL, though with a low percentage variation for the period (AAPC = 3.5%; p  = 0.01). Hearing thresholds in this study differed from the reference one., Conclusion: Despite the unmet expectation of a stationary trend in the study period, the time pace of ONIHL evolution did not follow what was expected for a population exposed to noise. These findings signal to the scientific community and public authorities that good ONIHL control is possible when HCP is well implemented., (© 2024 Occupational Safety and Health Research Institute. Published by Elsevier B.V. on behalf of Institute, Occupational Safety and Health Research Institute, Korea Occupational Safety and Health Agency.)

Introduction  The voice and hearing can be affected to different degrees by aging, which can cause communication difficulties for elderly people. Vocal production requires effective temporal auditory processing at central levels within the nervous system, which can be compromised by the aging process. Objective  To analyze the correlation between voice and temporal auditory processing in older adults. Materials and Methods  A total of 40 elderly people aged 60 years or older were subdivided into 2 groups according to the presence or absence of vocal symptoms measured by the Voice Symptom Scale. All of the participants were submitted to auditory temporal tests, vocal self-assessment, and acoustic and perceptual auditory analyses of voice. Results  Most of the subjects assessed had decreased voice intensity and normal variability in terms of vocal quality. The performance was normal in the Pitch Pattern Sequence test and altered in the Random Gap Detection test. In the Masking Period Pattern test, the detection thresholds for the target signal were increased in the presence of masking in different temporal target signal positions. Only pitch differed between the two groups. There were differences between the genders regarding frequency, shimmer, the overall severity of the alteration, and roughness. There was a correlation regarding temporal resolution ability and the overall severity of the alteration and roughness of the voice. Conclusion  There is a central auditory impairment in temporal resolution which is correlated with vocal alterations in the elderly., Competing Interests: Conflict of Interests The authors have no conflict of interests to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Chronic exposure to stress is a non-adaptive situation that is associated with mitochondrial dysfunction and the accumulation of reactive oxygen species (ROS), especially superoxide anion (SA). This accumulation of ROS produces damage-associated molecular patterns (DAMPs), which activate chronic inflammatory states and behavioral changes found in several mood disorders. In a previous study, we observed that an imbalance of SA triggered by rotenone (Ro) exposure caused evolutionarily conserved oxi-inflammatory disturbances and behavioral changes in Eisenia fetida earthworms. These results supported our hypothesis that SA imbalance triggered by Ro exposure could be attenuated by lithium carbonate (LC), which has anti-inflammatory properties. The initial protocol exposed earthworms to Ro (30 nM) and four different LC concentrations. LC at a concentration of 12.85 mg/L decreased SA and nitric oxide (NO) levels and was chosen to perform complementary assays: (1) neuromuscular damage evaluated by optical and scanning electron microscopy (SEM), (2) innate immune inefficiency by analysis of Eisenia spp. extracellular neutrophil traps (eNETs), and (3) behavioral changes. Gene expression was also evaluated involving mitochondrial (COII, ND1), inflammatory (EaTLR, AMP), and neuronal transmission (nAchR α5). LC attenuated the high melanized deposits in the circular musculature, fiber disarrangement, destruction of secretory glands, immune inefficiency, and impulsive behavior pattern triggered by Ro exposure. However, the effects of LC and Ro on gene expression were more heterogeneous. In summary, SA imbalance, potentially associated with mitochondrial dysfunction, appears to be an evolutionary component triggering oxidative, inflammatory, and behavioral changes observed in psychiatric disorders that are inhibited by LC exposure., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Rotenone (Ro), causes superoxide imbalance by inhibiting complex I of the mitochondrial electron transport chain, being able to serve as a model for functional skin aging by inducing cytofunctional changes in dermal fibroblasts prior to proliferative senescence. To test this hypothesis, we conducted an initial protocol to select a concentration of Ro (0.5, 1, 1.5, 2, 2.5, and 3 μM) that would induce the highest levels of the aging marker beta-galactosidase (β-gal) in human dermal HFF-1 fibroblasts after 72 h of culture, as well as a moderate increase in apoptosis and partial G1 arrestment. We evaluated whether the selected concentration (1 μM) differentially modulated oxidative and cytofunctional markers of fibroblasts. Ro 1.0 μM increased β-gal levels and apoptosis frequency, decreased the frequency of S/G2 cells, induced higher levels of oxidative markers, and presented a genotoxic effect. Fibroblasts exposed to Ro showed lower mitochondrial activity, extracellular collagen deposition, and fewer fibroblast cytoplasmic connections than controls. Ro triggered overexpression of the gene associated with aging (MMP-1), downregulation genes of collagen production (COL1A, FGF-2), and cellular growth/regeneration (FGF-7). The 1 μM concentration of Ro could serve as an experimental model for functional aging fibroblasts prior to replicative senescence. It could be used to identify causal aging mechanisms and strategies to delay skin aging events., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest. The authors alone are responsible for the content and writing of the article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The aim of this study is to analyze the political action of the Brazilian Health Care Reform Movement (MRSB, Movimento da Reforma Sanitária Brasileira), particularly Cebes and Abrasco, during the COVID-19 pandemic. The data were obtained through the documental review of publications from the abovementioned entities, which describe their positions on government actions implemented between January 2020 and June 2021. The results show that the performance of these entities included several actions, most of them reactive and critical of the Federal Government's role in the pandemic. Moreover, they led the creation of "Frente pela Vida", an organization that brought together several scientific entities and civil society organizations, whose highlight was the preparation and dissemination of the "Frente pela Vida Plan", a document that contains a comprehensive analysis of the pandemic and its social determinants, as well as a set of proposals to face the pandemic and its effects on the population's living and health conditions. It is concluded that the performance of the MRSB entities reveals alignment with the original project of the Brazilian Health Care Reform (RSB, Reforma Sanitária Brasileira), emphasizing the relationship between health and democracy, the defense of the universal right to health and the expansion and strengthening of the Brazilian Unified Health System - SUS (Sistema Único de Saúde).

The study aim is to analyze the performance of the Brazilian federal government (FG) in the COVID-19 pandemic, seeking to identify tensions and conflicts between actors and institutions of the three branches of the government and the FG with state governors. Data production included a review of articles, publications and documents that analyze the pandemic evolution and record announcements, decisions, actions, debates and controversies between these actors in the period of 2020 to 2021. The results include the characterization of the action style of the central Actor and the analysis of conflicts between the Presidency, the Ministry of Health, ANVISA, state governments, the House of Representatives and the Senate and the Federal Supreme Court, seeking to correlate them with the debate around the political projects for health in dispute under the current circumstances. It is concluded that the central actor largely used a communicative action aimed at his supporters and strategic action characterized by imposition, coercion and confrontation in the relationships he maintained with other institutional actors, especially when they diverged from his viewpoints about how to face the health crisis, consistently with his connection to the ultra-neoliberal and authoritarian political project of the FG, which includes the deconstruction of the Brazilian Unified Health System.

Relapsing-remitting multiple sclerosis (RRMS) is the most common clinical course of multiple sclerosis (MS), characterized by a chronic inflammatory state and elevated levels of oxidative markers. Food supplements with potential anti-inflammatory, antioxidant and neuroprotective effects have been tested as possible adjuvants in the treatment of MS. In this sense, this pilot study was carried out with the aim of verifying whether a minimum daily dose of a guarana, selenium and l-carnitine (GSC) based multi supplement, mixed in cappuccino-type coffee, administered for 12 weeks to 28 patients with RRMS could differentially modulate oxidative blood markers (lipoperoxidation, protein carbonylation and DNA oxidation) and inflammatory blood markers (protein levels of cytokines IL-1β, IL-6, TNF-α, IFN-γ, IL-10, gene expression of these cytokines, and NLRP3 and CASP-1 molecules, and C-reactive protein levels). The results indicate that a low concentration of GSC is capable of decreasing the plasma levels of oxidized DNA and pro-inflammatory cytokines of RRMS patients. The results support further research into the action of GSC on clinical symptoms, not only in patients with MS, but also with other neurological conditions., Competing Interests: Declarations of Competing Interest none., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: To analyze the effect of masking on the Cortical Auditory Evoked Potential with speech stimulus in young adults., Methods: Fourteen individuals aged between 19 and 28 years of both sexes with no hearing loss participated in the study. The Cortical Auditory Evoked Potential examination was performed with synthetic speech stimulus /ba/ simultaneous to Speech Shaped Noise presented under three conditions: steady noise with a 30 dB SPLep intensity (weak steady noise), steady noise with a 65 dB SPLep intensity o (strong steady noise) and modulated noise with 30 dB SPLep and 65 dB SPLep intensities at 25Hz and modulation period of 40 ms., Results: Higher latencies were observed in the cortical components, except P2, in the condition of strong steady noise and more meaningful measures of amplitude of the cortical components P1, N1 and P2 in the condition of modulated noise with statistically significant difference in comparison to the strong steady noise condition. There was worse wave morphology in the condition of strong steady noise, when compared to the other records. The average electrophysiological thresholds for the conditions of strong steady noise and modulated noise were 60 dB SPLep and 49 dB SPLep, respectively, showing a 11.7 dB mean difference., Conclusion: We could infer that there was a lower masking effect of modulated noise when compared to the strong steady noise condition, in the amplitude measurements of the cortical components and an average difference of 11.7 dB between the electrophysiological thresholds (interpreted as the measure of the Masking Release).

Background: Some studies have suggested that mitochondrial dysfunction and a superoxide imbalance could increase susceptibility to chronic stressful events, contributing to the establishment of chronic inflammation and the development of mood disorders. The mitochondrial superoxide imbalance induced by some molecules, such as rotenone, could be evolutionarily conserved, causing behavioral, immune, and neurological alterations in animals with a primitive central nervous system., Objective: Behavioral, immune, and histological markers were analyzed in Eisenia fetida earthworms chronically exposed to rotenone for 14 days., Methods: Earthworms were placed in artificial soil containing 30 nM of rotenone distributed into a plastic cup that allowed the earthworms to leave and return freely into the ground. Since these organisms prefer to be buried, the model predicted that the earthworms would necessarily have to return to the rotenone-contaminated medium, creating a stressful condition. The effect on survival behavior in the immune and histological body wall and ventral nervous ganglia (VNG) structures, as well as gene expression related to inflammation and mitochondrial and neuromuscular changes., Results: Rotenone-induced loss of earthworm escape behavior and immune alterations indicated a chronic inflammatory state. Some histological changes in the body wall and VNG indicated a possible earthworm reaction aimed at protecting against rotenone. Overexpression of the nicotinic acetylcholine receptor gene (nAChR α5) in neural tissues could also help earthworms reduce the degenerative effects of rotenone on dopaminergic neurons., Conclusion: These data suggest that mitochondrial dysfunction could be an evolutionarily conserved element that induces inflammatory and behavioral changes related to chronic stress., Competing Interests: Conflicts of interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background: Previous studies have suggested that guarana ( Paullinia cupana ) and açai ( Euterpe oleracea ) have antioxidant, anti-inflammatory, and proliferative properties, indicating their potential therapeutic action in wound healing. We produced a conjugated guarana-açai (GA) extract and tested its healing action on earthworms ( Eisenia fetida ) subjected to tail amputation by surgical incision., Methods: Extract from roasted guarana seeds and fresh açai seed berries was produced. The antioxidant and genoprotective capacity of GA extract was tested. The concentration with the most remarkable healing potential was used in subsequent tests. The last three posterior segments of the clitellate earthworm tail reared under standardized conditions were surgically amputated. Next, topical PBS or GA extract was applied to the surgical wound. The rate of cell migration and tissue regeneration at the local wound site was histologically evaluated after the procedure. Expression of the SOX4 gene that acts in epithelial-to-mesenchymal transition was determined by RT-qPCR., Results: Sixteen bioactive molecules, including some previously described substances, were identified. All tested concentrations exhibited antioxidant and genoprotective effects. The GA extract accelerated the healing processes as observed through macroscopic and histological analyses and increased expression of SOX4., Conclusion: The GA extract has a potential role in the healing of surgically induced wounds., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022 Fellipe D. Felin et al.)

Superoxide-hydrogen peroxide (S-HP), triggered by Val16Ala-SOD2 human polymorphism, may influence the risk of depression. Therefore, it is plausible that higher basal S-anion levels and chronic inflammatory states associated with the VV-SOD2 genotype can negatively modulate the stress response associated with resilience in various species, from primitive species to humans. To test this hypothesis, Eisenia fetida earthworms were exposed for 24 h to 30 nM rotenone, which causes mitochondrial dysfunction by generating high S-anion levels (known as the "VV-like phenotype"), and 10 μM porphyrin, a SOD2-like compound, which generates elevated HP levels (known as the "AA-like phenotype"). The results suggested that both S-anion and HP acted as signaling molecules, differentially altering the immune function and acute hydric stressful response. Although the AA-like phenotype improved the immune and stress response efficiencies, the VV-like phenotype showed a downregulated expression of the toll-like receptor (EaTLR, JX898685) and antimicrobial peptide (AMP) (AF060552) genes, which triggered the impairment of encapsulation and earthworms extracellular trap (EET) processes used by earthworms to trap and destroy microorganisms. When exposed to adverse environments and dangerous hydric stress, VV-like earthworms exhibited an impulsive behavior and failed to quickly identify and migrate to a protected environment, unlike control earthworms and AA-like earthworms. All results corroborated that the S-anion imbalance could concomitantly induce alterations in immune function and stress behavior related to earthworm survival. From a human perspective, this information may corroborate the potential specific role of superoxide anion in the modulation of the stress response, resilience, and risk of depression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier Ltd.)

Neurodegenerative diseases are associated with chronic inflammatory states. There is evidence to support the design of novel supplements based on guarana (G) (Paullinia cupana), selenium (S), and L-carnitine (C), the use of which, potentially attenuates neuro oxi-inflammatory conditions. Therefore, this study analyzed the cytotoxic and redox effects of GSC on human leucocytes, the inflammatory activation of microglia BV-2 cells, and effect on mortality, oxidative metabolism, and the immune modulation of red earthworms (Eisenia fetida). The GSC concentrations tested in cell culture were in the range of 0.04-2.1 mg/mL. All the GSC-supplemented samples tested, reverted H 2 O 2 oxidation in DNA molecules, suggesting its genoprotective potential. GSC did not induce mortality in leucocyte cultures. On the contrary, a reduction in the levels of oxidation of lipids, proteins, and cell apoptosis was observed, via downregulation of caspase 3 and 8 genes. GSC showed a dual effect on microglia, decreasing the cellular proliferation at lower concentrations (<0.24 mg/mL) and increasing the cellular proliferation mainly at concentrations > 1.0 mg/mL. GSC did not have a toxic effect on red earthworms, but induced an increase in amoebocyte cells and in brown body formation, indicating immune response activation. The results suggest that GSC could be safe for human consumption., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Chronic psycho-environmental stress can induce neurological dysfunction due to an increase in cortisol levels. It is possible that some food supplements could attenuate its negative impact, such as avocado oil (AO), which is rich in fatty acids with beneficial effects on the brain. This hypothesis was tested by an in vitro model using undifferentiated neuroblastoma cells (SH-SY5Y) exposed to hydrocortisone (HC), an active cortisol molecule with and without AO-supplementation. Cortisol can induce oxidative stress, apoptosis events, and a lowering effect on brain-derived neurotrophic factor (BDNF), a neurogenic molecule. As AO protective effects on HC-exposed cells could involve these routes, some markers of these routes were compared among neuroblastoma cultures. In the first assay, the range concentrations of HC exposure that trigger cell mortality and range AO-concentrations that could revert the HC effect. AO at all concentrations tested (2-30 µg/ml) did not present a cytotoxic effect on SH-SY5Y cells, whereas HC at 0.3-10 ng/ml had a dose-dependent cytotoxic effect on these cells. From these results, HC at 10 ng/ml and AO at 5 µg/ml were chosen for mechanistic analysis. AO was able to decrease the oxidative molecules; however, both AO- and HC-induced differential and varied gene expression modulation of these enzymes. AO partially reverted the protein and gene expression of apoptotic markers that were higher in HC-exposed cells. AO also increases the BDNF levels, which are lower HC-exposed cultures. The results indicate that AO could be a beneficial supplement in situations where cortisol levels are elevated, including chronic psycho-environmental stress. PRACTICAL APPLICATIONS: Psychological chronic stress that induces high cortisol exposure has been linked to premature aging and decreased healthy life expectancy. Neurobiological models involving cortisol have suggested a neurotoxic effect of this molecule, increasing the risk of psychiatric and other CNTDs. This effect can have a high impact mainly in infants and elderly people. In child abuse situations, chronic cortisol exposure could induce extensive apoptosis events, causing impairment in synaptogenesis. In both age groups, chronic cortisol exposure increased the risk of psychiatric conditions, especially anxiety and major depression. However, it is possible that the negative effects associated with chronic cortisol exposure could be attenuated by some food supplements. This is the case for molecules acquired through diet, such as polyunsaturated fatty acids (PUFAs), including omega-3. As inadequate omega-3 levels in the brain can increase the risk factor for neuropsychiatric disorders, it is possible to infer that some from food supplements, such as avocado oil, could attenuate the neurotoxic effects of chronic cortisol exposure. This hypothesis was tested using an exploratory in vitro protocol, and the results suggested that avocado oil could be used as a cytoprotective food supplement by decreasing the oxidative stress and apoptotic events induced by cortisol., (© 2021 Wiley Periodicals LLC.)

Quetiapine is an antipsychotic drug that is used to treat psychiatric and neurological disorders. Despite its efficiency and low-toxicity, quetiapine administration has been associated with undesirable side effects such as the development of low-grade inflammatory disorders and neutropenia states. As the liver rapidly metabolizes quetiapine to metabolites, the non-metabolized part of this molecule might play a role in immune alterations. In an in vitro study, this hypothesis was tested by exposing activated and inactivated RAW-264.7 macrophages and human neutrophils to unmetabolized quetiapine (u-QUE). Based on our findings, u-QUE was not cytotoxic to these cells. u-QUE differentially modulates macrophages according to their activation states. In inactivated macrophages, u-QUE induced a proinflammatory state as observed by an increase in cellular proliferation; increased levels of oxidative molecules (nitric oxide and superoxide), protein levels, and gene overexpression of proinflammatory cytokines (IL-1β, IL-6, and TNF-α); and decreased levels of IL-10, an anti-inflammatory cytokine. Conversely, on phytohemagglutinin (PHA)-activated macrophages, u-QUE exerted an anti-inflammatory effect. u-QUE induced neutrophil extracellular trap (NET) formation and increased the sensitivity of the neutrophils previously activated by exposure to dead yeast cells for NET formation. These results confirm the effect of quetiapine on macrophage and neutrophil function, which may be associated with the side effects of this psychopharmaceutical agent., (Copyright © 2020. Published by Elsevier Masson SAS.)

Background: Low-level laser therapy (LLLT) has several clinical applications; however, its benefits are not universal. Therefore, combination therapy with LLLT and extracts from the guarana (Paullinia cupana) plant may improve its effectiveness as guarana extracts exhibit anti-aging properties., Objectives: To evaluate the antioxidant, anti-inflammatory, anti-apoptotic, and proliferative effects of combined LLLT and guarana extract therapy on human dermal fibroblasts., Methods: Human dermal fibroblasts (HFF-1) were cultured and initially exposed to several concentrations (1, 3, 5, 10, 30 µg/mL) of guarana extract. The experimental concentration of guarana extract was selected by analyzing cytokine levels, DNA oxidation, and apoptotic markers in LLLT-exposed (4 J/cm 2 ) and LLLT-unexposed fibroblast cultures. After 72 hours, the cells were analyzed using spectrophotometric, fluorimetric, immunological, and gene expression (qRT-PCR) assays. Flow cytometry was used to evaluate the effect of each treatment on cell cycle., Results: Fibroblasts treated with guarana (5 µg/mL) exhibited anti-inflammatory and anti-apoptotic properties been used in complementary protocols. Combined guarana and LLLT treatment significantly decreased protein carbonylation, lipoperoxidation, and DNA oxidation, downregulated the mRNA and protein expression of pro-inflammatory molecules, and upregulated IL-10 gene and protein expression. Guarana plus LLLT also decreased the levels of caspases 1, 3, and 8, increased the percentage of S-phase cells, and decreased FGF-1 and KGF-1 levels. Some of these changes were also observed after treatment with guarana or LLLT alone., Conclusions: Our results suggest that concomitant treatment with guarana and LLLT may promote fibroblast biostimulation and thus is clinically relevant., (© 2019 Wiley Periodicals, Inc.)

Ethnopharmacological Relevance: The fruit of Astrocaryum aculeatum G.Mey. (tucumã) is highly consumed by riverside communities in the Amazonian region. These communities have recently been shown to have increased longevity and reduced prevalence of age-related morbidity. Tucumã, which is locally used in their diet and traditional medicine may contribute to these features., Aim of the Study: To investigate the anti-inflammatory and antioxidant properties of A. aculeatum extract against phytohemagglutinin-induced inflammation in cell cultures., Materials and Methods: Cell viability and cytotoxicity assays, gene expression of interleukins IL-1β, IL-6, IL-10, levels of reactive oxygen species (ROS), nitric oxide (NO) and thiols were employed, as well as the activities of antioxidant enzymes in RAW 264.7 cells stimulated with phytohemagglutinin to mimic inflammation., Results: The extract of A. aculeatum fruit inhibited macrophage proliferation (P < 0.05), arrested the cell cycle in G0/G1 phase (P < 0.001), increased antioxidant defenses (P < 0.01), reduced oxidative stress (P < 0.01), and modulated genes related to the inflammatory response (P < 0.001)., Conclusion: Our results demonstrate that A. aculeatum fruit has anti-inflammatory and antioxidant capacities. These beneficial effects of tucumã on cells are also likely to be seen in vivo, thereby suggesting that its extract is a suitable therapeutic adjuvant in the prevention or treatment of inflammatory diseases., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Pyridostigmine bromide (PB), an acetylcholinesterase (AChE) enzyme inhibitor. Experimental evidence showed that when combined with other drugs or exercise, PB caused extensive neural and/or systemic oxidative stress. However, no studies have been conducted on the genetic influence associated with basal oxidative superoxide-hydrogen peroxide (S-HP) imbalance, such as that triggered by Val16Ala-SOD2 single nucleotide polymorphism (SNP, rs4880). This SNP, (homozygous genotypes) has been associated with several chronic degenerative disorders. Therefore, we evaluated whether the SOD-SNP could alter cyto-genotoxic effects triggered by different PB-concentrations in peripheral blood mononuclear cells (PBMCs). PBMCs were obtained from volunteers carrying different SOD2-genotypes and were cultured with various concentrations of PB. PB effects in quantity of enzyme AChE, mortality rate, oxidative stress markers, and DNA damage were assessed. Protein and gene expression of antioxidant enzymes, apoptotic markers and DNA repair enzyme, were evaluated in 24 h cultures. In general, PB up-regulated expression of antioxidant enzymes, and did not trigger apoptotic events. However, AA-PBMCs seemed more sensitive to PB exposure, in a protein decrease of the enzyme AChE by 10%, cell-mortality at concentrations of 20 and 40 ng/mL, protein carbonylation, and DNA damage, as analyzed by the Comet assay. Contrarily, PB demonstrated cyto-genoprotective effects on V-allele cells. These results indicated that genetic factors that increase HP-release may affect PB efficiency and safety., (Copyright © 2019. Published by Elsevier Ltd.)

Skin aging is a complex biological process induced by intrinsic and extrinsic factors which is characterized by clinical and cellular changes, especially dermal fibroblasts. It is possible that, some procedures, such as low-level laser therapy (LLLT), could decelerate this process. To test this hypothesis, this study evaluated the in vitro LLLT on dermal fibroblast cell line (HFF-1) with premature senescence H 2 O 2 -induced. HFF-1 cells were cultured in standardized conditions, and initially H 2 O 2 exposed at different concentrations. Fibroblasts were also just exposed at different LLLT (660 nm) doses. From these curves, the lowest H 2 O 2 concentration that induced indicators of premature senescence and the lowest LLLT doses that triggered fibroblast proliferation were used in all assays. Cellular mortality, proliferation, and the levels of oxidative, inflammatory cytokines, apoptotic markers, and of two growth signaling molecules (FGF-1 and KGF) were compared among treatments. The H 2 O 2 at 50 μM concentration induced some fibroblast senescence markers and for LLLT, the best dose for treatment was 4 J (p < 0.001). The interaction between H 2 O 2 at 50 μM and LLLT at 4 J showed partially reversion of the higher levels of DNA oxidation, CASP 3, CASP 8, IL-1B, IL-6, and INFy induced by H 2 O 2 exposure. LLLT also trigger increase of IL-10 anti-inflammatory cytokine, FGF-1 and KGF levels. Cellular proliferation was also improved when fibroblasts treated with H 2 O 2 were exposed to LLLT (p < 0.001). These results suggest that in fibroblast with some senescence characteristics H 2 O 2 -induced, the LLLT presented an important protective and proliferative action, reverting partially or totally negative effects triggering by H 2 O 2 .

Brazil has changed a lot since the enactment of the 1988 Federal Constitution. Although substantial advances have occurred in the health sector, old problems persist and new ones arise. The main goal of ensuring the universal right to health has not been achieved. The 16th National Health Conference will be held in 2019, an opportune moment to analyze the history, the present moment and the announcing trends. This text seeks to contribute to this analysis based on the results of studies on the developing health conditions of the population and the Brazilian health system in the last 30 years. It identifies the strengthening of the private sector and capital in the health sector, to the detriment of the public interest and the SUS. Finally, it discusses the strategies of the struggle for the right to health necessary and possible in the current context.

Background: Olanzapine (OLZ) is a second-generation antipsychotic drug used for treatment of schizophrenia, bipolar disorder, and other neuropsychiatric conditions. Undesirable side effects of OLZ include metabolic alterations associated with chronic oxidative-inflammation events. It is possible that lithium (Li), a mood modulator that exhibits anti-inflammatory properties may attenuate OLZ-induced oxi-inflammatory effects., Methodology: To test this hypothesis we activated RAW 264.7 immortalized macrophages with OLZ and evaluated oxidation and inflammation at the gene and protein levels. Li and OLZ concentrations were determined using estimated plasma therapeutic concentrations., Results: OLZ triggered a significant increase in macrophage proliferation at 72 h. Higher levels of oxidative markers and proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6, with a concomitant reduction in IL-10, were observed in OLZ-exposed macrophages. Lithium (Li) exposure triggered a short and attenuated inflammatory response demonstrated by elevation of superoxide anion (SA), reactive oxygen species (ROS), IL-1β, and cellular proliferation followed by elevation of anti-inflammatory IL-10 levels. Li treatment of OLZ-supplemented macrophages was able to reverse elevation of oxidative and inflammatory markers and increase IL-10 levels., Conclusions: Despite methodological limitations related to in vitro protocols, results suggested that Li may attenuate OLZ-induced oxidative and inflammatory responses that result from metabolic side effects associated with OLZ., Competing Interests: The authors have declared that no competing interests exist.

There are some genes associated to the risk of chronic diseases that present potential nutrigenetic response, such as the human manganese-dependent superoxide dismutase gene (Val16Ala-SOD2, rs4880) for which homozygous genotypes (VV and AA) are associated with higher basal superoxide (S) and hydrogen peroxide (HP) levels, respectively. It is possible that the VV- and AA-imbalance could be attenuated by selenium(Se)-rich foods such as Brazil nut (BN). To test this hypothesis, we conducted an in vitro protocol triggering a chemical S-HP imbalance by exposure of dermal fibroblast cells (HFF-1) to paraquat, which generates high S levels (VV-like treatment) and porphyrin (MnTBAP), which generates high HP levels (AA-like treatment). Modulation of cell growth and pro-oxidative and antioxidant markers were evaluated. BN aqueous extract (BNAE) most effective concentration which increased cell growth and decreased oxidative metabolism indicators of imbalanced cells was 75 ng Se/mL. However, this effect was not directly affected by the S-HP imbalance: in AA-SOD2-like cells, thioredoxin reductase (TrxR-1) gene was upregulated and in VV-SOD2-like cells an upregulation of glutathione peroxidase (GPx-1) gene expression was observed, however, this regulation occured in a homeostatic manner. These results suggest that BNAE was able to minimize negative effects in both directions of the S-HP imbalance, by modulation of different oxidative-metabolic pathways., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Barbatimão ( Stryphnodendron adstringens , Mart.) is a native Brazilian species used in traditional medicine and some commercial preparations owing to its strong wound-healing activity. However, controversy regarding its use due to safety concerns over the potential genotoxic effect of this plant remains. In order to clarify this issue, the effect of hydroalcoholic extract of barbatimão in vitro on cell viability, DNA damage, and induction of apoptosis in two commercial cell lines of keratinocytes (HaCaT) and fibroblasts (HFF-1) was evaluated. Barbatimão stem bark hydroalcoholic extract (70% ethanol) was obtained and lyophilized for subsequent use in all experiments. The main bioactive molecules quantified by HPLC were gallic acid, caffeic acid, quercetin, catechin, and epigallocatechin gallate (EGCG). Barbatimão (0.024 to 1.99 mg/mL) was found to decrease cellular mortality as compared to the control group. GEMO assay, a noncellular DNA protocol that uses H 2 O 2 -exposed calf thymus DNA, revealed not only a genotoxic effect of barbatimão, but also a potential genoprotective action against H 2 O 2 -triggered DNA fragmentation . These results indicated that barbatimão at concentrations of 0.49 and 0.99 mg/mL, which are near to the levels found in commercial preparations, exerted an in vitro genoprotective effect on cells by decreasing the levels of DNA oxidation quantified by 8-hydroxy-2'-deoxyguanosine (8-OHdG) and reactive oxygen species (ROS) levels. Gene and protein apoptotic markers, quantified by qRT-PCR ( BAX/Bcl-2 genes) and immunoassays (Caspases 3 and 8), respectively, also indicated a decrease in apoptotic events in comparison with control cells. Collectively, the results suggest that barbatimão could exert genoprotective and antiapoptotic effects on human keratinocytes and fibroblasts.

Jaboticaba peel powder (JPP) is rich in bioactive compounds, mainly soluble and insoluble polyphenols with great antioxidant properties. The aim of this study is to evaluate the effects of JPP supplementation on the oxidative stress and hepatic damage in a rat model of type 2 diabetes mellitus (T2DM). Diabetic rats received vehicle or JPP at 2.7 (JPP-I), 5.4 (JPP-II), or 10.8 (JPP-III) g/L in drinking water during 8 weeks. JPP-III attenuated hyperglycaemia and dyslipidemia increased by 86% the liver content of nonprotein thiol groups and by 90% the GSH/GSSG ratio by activating glutathione synthesis. Accordingly, JPP supplementation prevented the loss of activity of the sulfhydryl-dependent enzyme δ -aminolaevulinic acid dehydratase and attenuated hepatic injury assessed by the reduction of serum aspartate aminotransferase activity and liver hypertrophy. Our results support that JPP supplementation to T2DM rats decreases hepatic damage most likely by increasing glutathione synthesis and modulating the thiol/disulfide redox balance.

Antipsychotic drugs are used to treat schizophrenia and other psychiatric disorders. However, most of these drugs present side effects causing obesity and other serious metabolic alterations that correlate with grade of chronic inflammation. In contrast, ziprasidone's (ZIP) metabolic side effects are attenuated relative to those of other antipsychotic drugs, but some reports suggest that this drug could cause allergic, hypersensitive reactions in susceptible patients. At present, the mechanism of ZIP's effect on peripheral inflammatory metabolism is not well characterized. We conducted an in vitro study to evaluate the effect of ZIP on a macrophage cell line (RAW 264.1). Our results showed that in non-activated macrophage cells, ZIP exposure initiated macrophage spreading; increased cellular proliferation, as evaluated by MTT and flow cytometry assays; and presented higher levels of oxidant molecules involved in the inflammatory response (nitric oxide, superoxide, reactive oxygen species), and proinflammatory cytokines (IL-1, IL-6, TNFα, INFγ). Levels of IL-10, an anti-inflammatory cytokine were lower in ZIP-exposed cells. These effects were less potent than those caused by the positive control for inflammation induction (phytohemagglutinin), and more intense than the effects of lithium (LI), which was used as an anti-inflammatory molecule. ZIP also modulated cytokine gene expression. Taken together, these data suggest that ZIP can produce a peripheral inflammatory response, and this response may explain the allergen-inflammatory response observed in some patients treated with this antipsychotic drug., (Copyright © 2017. Published by Elsevier Ltd.)

Trypanosoma rangeli is a protozoan parasite that infects mammals and triatomines, causing different levels of pathogenicity in its invertebrate vectors, particularly those from the genus Rhodnius. We have recently shown that temperature can modulate T. rangeli growth during in vitro culture, as well as its in vivo pathogenicity to R. prolixus. In the present study, we investigated colonization of R. prolixus by T. rangeli and assessed the role of temperature and vector nutrition on parasite development and multiplication. We infected nymphs and either assessed parasite density in the first hours after the ingestion of the infected blood or maintained the nymphs for up to 60 days at different temperatures (21, 24, 27, and 30 °C) and under different blood-feeding schedules (either every 15 days, or on day 30 post infection only), with parasite development and multiplication measured on days 15, 30, and 60 post infection. In the first hours after ingesting infected blood, epimastigogenesis not only occurred in the anterior midgut, but a stable parasite population also established in this intestinal region. T. rangeli subsequently colonized all intestinal regions examined, but with fewer parasites being found in the rectum. The number of parasites was only affected by higher temperatures (27 and 30 °C) during the beginning of the infection (15 days post infection). Nutritional status of the vector also had a significant effect on parasite development, as reduced blood-feeding decreased infection rates by approximately 30%.

Introduction: Lithium (Li), a mood stabilizer used to treat bipolar disorder (BP) symptoms has important anti-inflammatory effects by downregulation of glycogen synthase kinase-3 beta (GSK-3β). However, sometime Li effect is not efficient in some patients suggesting genetic interference. Previous investigations described association between a genetic superoxide‑hydrogen (S-HP) imbalance caused by a superoxide dismutase manganese dependent gene polymorphism (Val16Ala-SOD2 SNP, rs4880) and differential anti-inflammatory response of some drugs and bioactive molecules. Therefore, we postulated here that S-HP imbalance could present some effect on GSK-3β modulation by Li., Methods: to test this hypothesis, a genetic and a pharmacological S-HP imbalance protocols were performed. In the two protocols, immune cells were activated by phythohemaglutin (PHA). The first one, used peripheral blood mononuclear cells (PBMCs) cultures carrying different Val16Ala-SOD2 genotypes, and the second used a commercial macrophage cell line RAW 264.7. Macrophages were exposed to paraquat to induce high S levels (VV-like cells) or porphyrin, that is a SOD2-like molecule that increase dismutation of S into HP (AA-like cells). In both protocols the Li effects on GSK-3β gene and protein modulation as evaluated in 24 h cultures. The inflammatory activation was also analyzed by cellular proliferation in 72 h cell cultures., Results: as expected PHA exposure triggered a strong upregulation of GSK-3β gene expression (p ≤ 0.001), and Li exposure showed GSK-3β gene downregulation from 0.7 mEq/L concentrations. However, Li modulatory effects on GSk-3β gene and protein expression was directly influenced by basal S-HP balance. Presence of high S-basal levels (VV genotype and VV-like cells) induced attenuated Li anti-inflammatory effects in comparison with balanced and AA and AA-like cells (p < 0.001). Despite methodological limitations related to in vitro assays, the whole of results suggested that Li anti-inflammatory effects is influenced by S-HP basal state and is plausible that its influence could contributes to resistance of some patients to Li treatment or to increase of intensity of some side effects Li-associated., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The trophodynamics of halogenated flame retardants (HFRs) including polybrominated diphenyl ethers (PBDEs) and alternative HFRs were investigated in the terrestrial, vegetation-caribou-wolf food chain in the Bathurst Region of northern Canada. The greatest concentrations in vegetation (geometric mean of lichens, moss, grasses, willow, and mushrooms) were of the order 2,4,6-tribromophenyl allyl ether (TBP-AE) (10 ng g -1 lw) > BDE47 (5.5 ng g -1 lw) > BDE99 (3.9 ng g -1 lw) > BDE100 (0.82 ng g -1 lw) > 1,2,3,4,5-pentabromobenzene (PBBz) (0.72 ng g -1 lw). Bioconcentration among types of vegetation was consistent, though it was typically greatest in rootless vegetation (lichens, moss). Biomagnification was limited in mammals; only BDE197, BDE206-208 and ∑PBDE biomagnified to caribou from vegetation [biomagnification factors (BMFs) = 2.0-5.1]. Wolves biomagnified BDE28/33, BDE153, BDE154, BDE206, BDE207, and ∑PBDE significantly from caribou (BMFs = 2.9-17) but neither mammal biomagnified any alternative HFRs. Only concentrations of BDE28/33, BDE198, nonaBDEs, and ∑PBDE increased with trophic level, though the magnitude of biomagnification was low relative to legacy, recalcitrant organochlorine contaminants [trophic magnification factors (TMFs) = 1.3-1.8]. Despite bioaccumulation in vegetation and mammals, the contaminants investigated here exhibited limited biomagnification potential and remained at low parts per billion concentrations in wolves.

Radiation therapy is commonly applied in breast cancer (BC) patients. However, radioresistance and side effects are limiting factors of this practice. Therefore, studying substances that can enhance the radiation effect and, at the same time, protect normal cells is very relevant. Thus, the aim of this work was to assess the radiosensitizer effect of resveratrol (RV) on BC cells (MCF-7). A high cytotoxic and antiproliferative effect was observed in the treatment with 10 μM of RV + 3 Gy ionizing radiation (IR). Our results indicate that, 24 h after the exposition of cell cultures to RV + IR, an induction of necrosis/senescence has occurred. Furthermore, was observed the activation of extrinsic apoptosis pathway through a decrease of the Bax/Bcl-2 ratio and a high activity of caspase 8. Moreover, our data show that this treatment affected the oxidative cell metabolism, increasing oxidative protein, lipid and membrane damage and also acted to decrease the antioxidant enzymes activity. The antiproliferative effect on 72 h cultures may be associated with a high expression of p53 and an interruption of cell cycle in the S phase. Therefore, our results suggest that RV is a potential radiosensitizer of MCF-7 BC cells., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Pyridostigmine bromide (PB) is a reversible acetylcholinesterase (AChE) inhibitor and the first-choice for the treatment of symptoms associated with myasthenia gravis and other neuromuscular junction disorders. However, evidence suggested that PB could be associated with the Gulf War Illness characterised by the presence of fatigue, headaches, cognitive dysfunction, and musculoskeletal respiratory and gastrointestinal disturbances. Given that a potential neurotoxic effect of PB has not yet been completely elucidated, the present investigation used neural SH-SY5Y cells to evaluate the effect of PB on the cellular viability, cell apoptosis, modulation of the cell cycle, oxidative stress, and genotoxicity variables, which indicate neurodegeneration. As expected, a PB concentration curve based on the therapeutic dose of the drug showed an inhibition of the AChE activity. However, this effect was transient and did not involve differential AChE gene regulation by PB. These results confirmed that undifferentiated SH-SY5Y cells can be used as a cholinergic in vitro model. In general, PB did not trigger oxidative stress, and at a slightly higher PB concentration (80ng/mL), higher levels of protein carbonylation and DNA damage were detected, as determined by the marker 8-deoxyguanosine. The PB genotoxic effects at 80ng/mL were confirmed by the upregulation of the p53 and DNA methyltransferase 1 (DNMT1) genes, which are associated with cellular DNA repair. PB at 40ng/mL, which is the minimal therapeutic dose, led to higher cell proliferation and mitochondrial activity compared with the control group. The effects of PB were corroborated by the upregulation of the telomerase gene. In summary, despite the methodological constrains related to the in vitro protocols, our results suggested that exposure of neural cells to PB, without other chemical and physical stressors did not cause extensive toxicity or indicate any neurodegeneration patterns., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To analyze the performance of family health teams toward the suspicion and identification of child hearing loss., Methods: This is a case study. Data were collected in three focus groups with three family health teams of a health district in the metropolitan area of Recife, Brazil. All data were transcribed and analyzed based on the interview analysis model of condensation of meanings., Results: The family health professionals investigated made use of some resources to assess child reaction to sound stimuli, but they were mostly unaware of risk indicators for hearing loss and presented doubts about conducting referrals. Regarding child monitoring, the family health professionals reported that the lack of counter-reference by other professionals precludes the effective monitoring of children in the family health units., Conclusion: Despite their potential in assisting child health, the role of family health teams is still permeated by weaknesses that hinder their performance with respect to hearing health.

Lithium (Li) is a chemical element used for treating and preventing bipolar disorder (BD) and exerts positive effects such as anti-inflammatory effects as well as undesirable side effects. These effects of Li can be influenced by interaction with some nutritional elements. Therefore, we investigated the potential effects of xanthine (caffeine and theobromine) and catechin molecules present in some food beverages broadly consumed worldwide, such as coffee and tea, on Li-induced anti-inflammatory effects. In the present study, we concomitantly exposed RAW 264.7 macrophages to Li, isolated xanthine and catechin molecules, and a xanthine-catechin mixture (XC mixture). We evaluated the effects of these treatments on cell proliferation, cell cycle progression, oxidative and antioxidant marker expression, cytokine levels, gene expression, and GSK-3 β enzyme expression. Treatment with the XC mixture potentialized Li-induced anti-inflammatory effects by intensification of the following: GSK-3 β inhibitory action, lowering effect on proinflammatory cytokines (IL-1 β , IL-6, and TNF α ), and increase in the levels of IL-10 that is an anti-inflammatory cytokine. Despite the controversial nature of caffeine consumption by BD patients, these results suggested that consumption of caffeine, in low concentrations, mixed with other bioactive molecules along with Li may be safe.

The venom of Micrurus lemniscatus, a coral snake of wide geographical distribution in South America, was fractionated by reverse-phase HPLC and the fractions screened for phospholipase A2 (PLA2) activity. The major component of the venom, a PLA2, here referred to as 'Lemnitoxin', was isolated and characterized biochemically and toxicologically. It induces myotoxicity upon intramuscular or intravenous injection into mice. The amino acid residues Arg15, Ala100, Asn108, and a hydrophobic residue at position 109, which are characteristic of myotoxic class I phospholipases A2, are present in Lemnitoxin. This PLA2 is antigenically related to M. nigrocinctus nigroxin, Notechis scutatus notexin, Pseudechis australis mulgotoxin, and Pseudonaja textilis textilotoxin, as demonstrated with monoclonal and polyclonal antibodies. Lemnitoxin is highly selective in its targeting of cells, being cytotoxic for differentiated myotubes in vitro and muscle fibers in vivo, but not for undifferentiated myoblasts or endothelial cells. Lemnitoxin is not lethal after intravenous injection at doses up to 2μg/g in mice, evidencing its lack of significant neurotoxicity. Lemnitoxin displays anticoagulant effect on human plasma and proinflammatory activity also, as it induces paw edema and mast cell degranulation. Thus, the results of this work demonstrate that Lemnitoxin is a potent myotoxic and proinflammatory class I PLA2., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

This study contributes new data on the spatial variability of persistent organic pollutants in the Indian-Pacific sector of the Southern Ocean and represents the first empirical data obtained from this region in 25 years. Paired high-volume atmospheric and seawater samples were collected along a transect between Australia and Antarctica to investigate the latitudinal dependence of the occurrence and distribution of legacy organochlorine pesticides (OCPs) and the current use pesticide chlorpyrifos in the Southern Ocean. Dissolved ΣHCH and dieldrin concentrations decreased linearly with increasing latitude from 7.7 to 3.0 and from 1.0 to 0.6 pg·L(-1), respectively. There was no consistent trend observed in the latitudinal profile of atmospheric samples; however, some compounds (such as dieldrin) showed reduced concentrations from 7.5-3.4 to 2.7-0.65 pg·m(-3) at the highest latitudes south of the Polar Front. Chlorpyrifos was found in samples from this area for the first time. Estimated air-seawater fugacity ratios and fluxes indicate a current net deposition between -3600 and -900, -6400 and -400, and -1400 and -200 (pg·m(-2)·d(-1)) for γ-HCH, dieldrin, and chlorpyrifos, respectively. These findings suggest that, under current climatic conditions, the Southern Ocean reservoir in the Indian-Pacific sector serves as an environmental sink rather than a source of OCPs to the atmosphere.

Introduction: One of the problems observed in pure-tone audiometry tonal has been the variation in test results of a same individual, particularly at frequencies of 4kHz, 6kHz and/or 8kHz. Improper placement of headphones is one of the factors that can cause alterations in results., Objective: To compare differences in auditory thresholds using earphones positioned by the examiner and by the worker., Methods: Clinical and experimental study conducted in 2009, with 324 workers aged between 19 and 61 years, with a mean of 33.29 years and mean exposure time of 7.67 years. All subjects were familiar with audiometry procedures. Auditory thresholds were obtained at frequencies of 0.25-8kHz, with earphones positioned by the examiners, and at frequencies of 4, 6 and 8kHz, with earphones placed by workers in a comfortable position, following the examiner's instructions. The thresholds obtained in these two situations were compared., Results: The three frequencies exhibited better responses with earphones placed by the workers themselves (p<0.001). At a frequency of 8kHz a greater difference was found (p<0.001), with a mean of 13.89dB and standard deviation of 6.07dB., Conclusion: Earphone placement by the workers themselves under supervision of the examiner results in improved mean auditory thresholds at frequencies of 4, 6 and 8kHz, the last one significantly higher than the other two., (Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Resveratrol is an molecule that provides both anti-inflammatory and antioxidant properties. However, it is unclear whether the basal oxidative state of the cell has any influence on the effects of this compound. In humans, a single nucleotide polymorphism (SNP) is present in the enzyme manganese superoxide dismutase (SOD2), localized in codon 16 (rs4880), which can either be an alanine (A) or valine (V). This SNP causes an imbalance in the cellular levels of SOD2, where AA- and VV-genotypes result in higher or lower enzymatic activity, respectively. Furthermore, the VV-genotype has been associated with high levels of inflammatory cytokines. Here, we examined the effects of a range of resveratrol concentrations on the in vitro activation of human peripheral blood mononuclear cells (PBMCs) carrying different Ala16Val-SOD2 genotypes. Cell proliferation, several oxidative biomarkers and cytokines (IL-1β, IL-6, TNFα, Igγ and IL-10) were analyzed. In addition, the effects of resveratrol on the expression of the sirt1 gene were evaluated by qRT-PCR. After 24 h exposure to resveratrol, A-genotype PBMCs displayed a decrease in cell proliferation, whilst VV-cells contrasted; At 10 µM resveratrol, there was a significant decrease in the production of inflammatory cytokines in A-allele cells; however, VV-cells generally displayed a subtle decrease in these, except for TNFα, which was not affected. In all SOD2 genotypes cells exposed to resveratrol resulted in an upregulation of Sirt1 levels. Together, these results suggest that the effect of resveratrol on human PBMC activation is not universal and is dependent on the Ala16Val-SOD2 SNP.

This work aimed to investigate mechanisms underlying the inflammatory response caused by Potamotrygon motoro stingray venom (PmV) in mouse paws. Pre-treatment of animals with a mast cell degranulation inhibitor (cromolyn) diminished edema (62% of inhibition) and leukocyte influx into the site of PmV injection. Promethazine (histamine type 1 receptor antagonist) or thioperamide (histamine type 3 and 4 receptor antagonist) also decreased edema (up to 30%) and leukocyte numbers, mainly neutrophils (40-50 %). Cimetidine (histamine type 2 receptor antagonist) had no effect on PmV-induced inflammation. In the RBL-2H3 lineage of mast cells, PmV caused proper cell activation, in a dose-dependent manner, with release of PGD2 and PGE2. In addition, the role of COXs products on PmV inflammatory response was evaluated. Indomethacin (COX-1/COX-2 inhibitor) or etoricoxib (COX-2 inhibitor) partially diminished edema (around 20%) in PmV-injected mice. Indomethacin, but not etoricoxib, modulated neutrophil influx into the site of venom injection. In conclusion, mast cell degranulation and histamine, besides COXs products, play an important role in PmV-induced reaction. Since PmV mechanism of action remains unknown, hindering accurate treatment, clinical studies can be performed to validate the prescription of antihistaminic drugs, besides NSAIDs, to patients injured by freshwater stingrays., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

This article analyzes the process of government planning in health in the state of Bahia in the 2007-2010 period based on the formulation of the State Health Plan. The benchmark adopted involved adaptation of the theoretical model of the cycle of public policy, including analysis of context, characterization of the actors involved, operations conducted in decision making and the strategic means used. The production of information was through the analysis of documents organized in institutional portfolios and records of the planning process in the organization studied. The analysis of results reveals that the political game included "concessions" and "negotiations" regarding changes in the management and organization of the health system, highlighting the discussion on the problems facing the state management of the Unified Health System (SUS) during the period, and the search for alternatives and solutions to these problems. It also reveals the institutional learning acquired, involving managers and technicians who broadened and reinforced their capacity to analyze and formulate proposals around the government agenda.

This article describes and analyzes the political and institutional context and the process of implementation of the Interdisciplinary Bachelor's degree in Health (IBH) during the 2006-2011 period. The methodology included document review and analysis of personnel records of the researchers involved. By using the concepts of "window of opportunity" and "hypercomplex organization," it was revealed that managerial and organizational structures were created and master-documents were prepared. In addition to this, actions for implementation of the course, related to the structure of the faculty and the academic council, preparation of the pedagogical project, planning, implementation and monitoring of the teaching-learning process in the various curriculum components offered since 2009 was conducted. Analysis of the challenges and prospects of the course indicates that the major problem is the tension between the traditional model of vocational and discipline-based higher education existing hitherto and the interdisciplinary model proposed by IBH. This tension can be overcome by the full implementation of learning cycles with the institutionalization of IBH as the first cycle of professional health education.

The diagnosis of schistosomiasis is problematic in low-intensity transmission areas because parasitological methods lack sensitivity and molecular methods are neither widely available nor extensively validated. Helmintex is a method for isolating eggs from large faecal samples. We report preliminary results of a comparative evaluation of the Helmintex and Kato-Katz (KK) methods for the diagnosis of schistosomiasis in a low-intensity transmission area in Bandeirantes, Paraná, southern Brazil. Eggs were detected by both methods in seven patients, whereas only Helmintex yielded positive results in four individuals. The results confirm the previously demonstrated higher sensitivity of the Helmintex method compared with the KK method.

The objective of this study is to characterize Brazilian/Latin American scientific output in the "field" of health and on health systems management specifically, based on work registered on the Lilacs database in the period from 1987 to 2009. The terms "health management" and "health systems", identified in the BVS/Bireme "Health Science Descriptors" were used and 1,544 works were identified, of which 298 were selected (19.3%). The reading and analysis of these abstracts enabled the identification of a set of variables processed with the use of Epi-Info software, such as: year of publication of the work; type of document; object of the study; type of study; theoretical bases and methodological approach/nature. The results point to an irregular, albeit increasing trend, in the volume of the output in the area from the year 1988 onwards, with the emergence of studies and research in sub-areas that reveal the influence of the process of construction of the Brazilian Unified Health System in the 1990s and thereafter. The fact that very few abstracts made reference to the theoretical bases used is noticeable. From a methodological point of view it is seen that when they are declared in abstracts, descriptive studies with a qualitative approach are predominant.

The construction of Brazil's Unified National Health System (SUS) has raised a set of challenges for the health sector's administrators and personnel, including issues of work management and continuing education for health workers, in view of the financial, political, and organizational constraints in the process of changing the healthcare model. The current study aimed to analyze the process of formulating the Health Work and Education Management Policy by the Bahia State Health Department. Public policy cycle was used as the theoretical framework. The study analyzed data from institutional documents and records of participant observation by one of the authors. The results include mapping the governmental and nongovernmental stakeholders that participated in the process. The analysis highlights a series of problems in the SUS in Bahia related to work management and health workers' profile, taken as the point of departure for priority-setting in the State Strategic Agenda and Health Plan for 2008-2011.

The object of this article is the planning process of the Health Secretariat of State of Bahia from January 2007 to July 2009. It describes and analyses this process, discussing the difficulties and the advances to build the planning practice in this institution. It was used documental analyses and systematic registers of lived experience by the authors to do it. The process points for an approach between theory and practice articulating the Strategic-situational focus and the Communicative Action, including the principle of the Social Participation. The analyses explain that the process occurs in a pool of dialogic movements enlaced by the explicative, normative, strategic and tactic-operative moments that finished with the construction of the Health Secretariat of State of Bahia. There is a powerful planning revealed in plurality and multiplicity of approaches used to build a collective "vision of future" in organizations that adopted "plans" like instruments to qualify Government actions.

Analysis of the effects of cyclosporine A (25-28 mgkg(-1)) and/or methotrexate (0.1 mgkg(-1)) treatments on dipeptidyl peptidase IV (DPPIV) and prolyl oligopeptidase (POP) activities and on algesic response in two distinct status of murine macrophages (Mphis) was undertaken. In resident Mphis, DPPIV and POP were affected by neither individual nor combined treatments. In thioglycolate-elicited Mphis, methotrexate increased DPPIV (99-110%) and POP (60%), while cyclosporine inhibited POP (21%). Combined treatment with both drugs promoted a rise (51-84%) of both enzyme activities. Only cyclosporine decreased (42%) the tolerance to algesic stimulus. Methotrexate was revealed to exert prevalent action over that of cyclosporine on proinflammatory Mphi POP. The opposite effects of methotrexate and cyclosporine on POP activity might influence the availability of the nociceptive mediators bradykinin and substance P in proinflammatory Mphis. The exacerbated response to thermally induced algesia observed in cyclosporine-treated animals could be related to upregulation of those mediators.