88 results on '"Reis HJ"'
Search Results
2. Metabotropic glutamate receptor 5 positive allosteric modulators are neuroprotective in a mouse model of Huntington's disease.
- Author
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Doria, JG, Silva, FR, Souza, JM, Vieira, LB, Carvalho, TG, Reis, HJ, Pereira, GS, Dobransky, T, and Ribeiro, FM
- Subjects
GLUTAMATE receptors ,ALLOSTERIC regulation ,NEUROPROTECTIVE agents ,HUNTINGTON disease ,NEURODEGENERATION ,GENETIC disorders ,LABORATORY mice - Abstract
Background and Purpose Huntington's disease ( HD) is an autosomal dominant neurodegenerative disorder caused by a polyglutamine expansion in the huntingtin protein. We have previously demonstrated that the cell signalling of the metabotropic glutamate receptor 5 ( mGluR5) is altered in a mouse model of HD. Although mGluR5-dependent protective pathways are more activated in HD neurons, intracellular Ca
2+ release is also more pronounced, which could contribute to excitotoxicity. In the present study, we aim to investigate whether mGluR5 positive allosteric modulators ( PAMs) could activate protective pathways without triggering high levels of Ca2+ release and be neuroprotective in HD. Experimental Approach We performed a neuronal cell death assay to determine which drugs are neuroprotective, Western blot and Ca2+ release experiments to investigate the molecular mechanisms involved in this neuroprotection, and object recognition task to determine whether the tested drugs could ameliorate HD memory deficit. Key Results We find that mGluR5 PAMs can protect striatal neurons from the excitotoxic neuronal cell death promoted by elevated concentrations of glutamate and NMDA. mGluR5 PAMs are capable of activating Akt without triggering increased intracellular Ca2+ concentration ([Ca2+ ]i ); and Akt blockage leads to loss of PAM-mediated neuroprotection. Importantly, PAMs' potential as drugs that may be used to treat neurodegenerative diseases is highlighted by the neuroprotection exerted by mGluR5 PAMs on striatal neurons from a mouse model of HD, BACHD. Moreover, mGluR5 PAMs can activate neuroprotective pathways more robustly in BACHD mice and ameliorate HD memory deficit. Conclusions and Implications mGluR5 PAMs are potential drugs that may be used to treat neurodegenerative diseases, especially HD. [ABSTRACT FROM AUTHOR]- Published
- 2013
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3. Coronary artery bypass surgery provokes Alzheimer's disease-like changes in the cerebrospinal fluid.
- Author
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Palotás A, Reis HJ, Bogáts G, Babik B, Racsmány M, Engvau L, Kecskeméti E, Juhász A, Vieira LB, Teixeira AL, Mukhamedyarovi MA, Rizvanov AA, Yalvaç ME, Guimaraes MM, Ferreira CN, Zefirov AL, Kiyasov AP, Wang L, Janka Z, and Kálmán J
- Abstract
Several biomarkers are used in confirming the diagnosis of cognitive disorders. This study evaluates whether the level of these markers after heart surgery correlates with the development of cognitive dysfunction, which is a frequent complication of cardiac interventions. Concentrations of amyloid-β peptide, tau, and S100β in the cerebro-spinal fluid were assessed, as well as cognitive functions were evaluated before and after coronary artery bypass grafting, utilizing immuno-assays and psychometric tests, respectively. A drastic rise in the level of S100β was observed one week after the surgery, a mark of a severe generalized cerebral injury. The level of amyloid-β peptide significantly decreased, whereas the concentration of tau markedly increased six months postoperatively. Gradual cognitive decline was also present. These findings clearly demonstrate post-surgical cognitive impairment associated with changes in biomarkers similar to that seen in Alzheimer's disease, suggesting a unifying pathognomic factor between the two disorders. A holistic approach to coronary heart disease and Alzheimer's type dementia is proposed. [ABSTRACT FROM AUTHOR]
- Published
- 2010
4. Downregulation of CAMP/PKA pathway and DARPP-32 expression in PC12 cells overexpressing NCS-1
- Author
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Souza, Br, Matta, Bs, Caetano, Fs, Rosa, Dv, Souza, Rp, Reis, Hj, Guimaraes, Mm, Jeromin, A., and Marco Romano-Silva
5. Different inflammatory biomarker patterns in the cerebro-spinal fluid following heart surgery and major non-cardiac operations
- Author
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Reis, Hj, Mauro Teixeira, and Kalman, J.
6. In the Name of Science: Don't Tamper with the Deceptive Truth
- Author
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Reis, H.J., Mukhamedyarov, M.A., Rizvanov, A.A., Palotás, A., Reis, HJ, Mukhamedyarov, MA, Rizvanov, AA, Palotas, A, Yeditepe Üniversitesi, Reis, H.J., Mukhamedyarov, M.A., Rizvanov, A.A., and Palotás, A.
- Abstract
Werner Heisenberg (1901-1976) is one of the most controversial, most ambivalent and most important figures in the history of modern science. The debate surrounding him with respect to nuclear weapons and National Socialism appears unending. Even though Heisenberg's uncertainty principle of the quantum system and his involvement in the Nazi atomic bomb project have been thoroughly discussed in various journals over the past decades, no communication has ever been published at a holistic level of his greatest Nobel-prize winning achievement in theoretical physics. In order to fill up this hole, this piece explicitly communicates the Heisenberg's paradox at all levels of science. © 2009 Bentham Science Publishers Ltd.
- Published
- 2009
7. Molecular Mechanisms Linking Osteoarthritis and Alzheimer's Disease: Shared Pathways, Mechanisms and Breakthrough Prospects.
- Author
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Umoh IO, Dos Reis HJ, and de Oliveira ACP
- Subjects
- Humans, Aged, Amyloid beta-Peptides genetics, Cross-Sectional Studies, Multimorbidity, Inflammation, Alzheimer Disease metabolism, Neurodegenerative Diseases, Osteoarthritis
- Abstract
Alzheimer's disease (AD) is a progressive neurodegenerative disease mostly affecting the elderly population. It is characterized by cognitive decline that occurs due to impaired neurotransmission and neuronal death. Even though deposition of amyloid beta (Aβ) peptides and aggregation of hyperphosphorylated TAU have been established as major pathological hallmarks of the disease, other factors such as the interaction of genetic and environmental factors are believed to contribute to the development and progression of AD. In general, patients initially present mild forgetfulness and difficulty in forming new memories. As it progresses, there are significant impairments in problem solving, social interaction, speech and overall cognitive function of the affected individual. Osteoarthritis (OA) is the most recurrent form of arthritis and widely acknowledged as a whole-joint disease, distinguished by progressive degeneration and erosion of joint cartilage accompanying synovitis and subchondral bone changes that can prompt peripheral inflammatory responses. Also predominantly affecting the elderly, OA frequently embroils weight-bearing joints such as the knees, spine and hips leading to pains, stiffness and diminished joint mobility, which in turn significantly impacts the patient's standard of life. Both infirmities can co-occur in older adults as a result of independent factors, as multiple health conditions are common in old age. Additionally, risk factors such as genetics, lifestyle changes, age and chronic inflammation may contribute to both conditions in some individuals. Besides localized peripheral low-grade inflammation, it is notable that low-grade systemic inflammation prompted by OA can play a role in AD pathogenesis. Studies have explored relationships between systemic inflammatory-associated diseases like obesity, hypertension, dyslipidemia, diabetes mellitus and AD. Given that AD is the most common form of dementia and shares similar risk factors with OA-both being age-related and low-grade inflammatory-associated diseases, OA may indeed serve as a risk factor for AD. This work aims to review literature on molecular mechanisms linking OA and AD pathologies, and explore potential connections between these conditions alongside future prospects and innovative treatments.
- Published
- 2024
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8. Association between TAFI and PAI-1 polymorphisms with biochemical and hemostatic parameters in polycystic ovary syndrome.
- Author
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Albuquerque JC, Luz NMC, Ribeiro THO, Costa LBX, Candido AL, Reis FM, Reis HJ, Silva FS, Silva IFO, Gomes KB, and Ferreira CN
- Subjects
- Female, Humans, Plasminogen Activator Inhibitor 1 genetics, Polymorphism, Genetic, Polycystic Ovary Syndrome genetics, Hemostatics
- Published
- 2023
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9. Evaluation of New Potential Inflammatory Markers in Patients with Nonvalvular Atrial Fibrillation.
- Author
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Martins GL, Duarte RCF, Vieira ÉLM, Rocha NP, Figueiredo EL, Silveira FR, Caiaffa JRS, Lanna RP, Carvalho MDG, Palotás A, Ferreira CN, and Reis HJ
- Subjects
- Humans, Middle Aged, Aged, Aged, 80 and over, Interleukin-10, Interleukin-6, Interferon-gamma, Chemokine CXCL10, Interleukin-4, Tumor Necrosis Factor-alpha, Atrial Fibrillation
- Abstract
Atrial fibrillation (AF), the most common arrhythmia in clinical practice, is associated with an increase in mortality and morbidity due to its high potential to cause stroke and systemic thromboembolism. Inflammatory mechanisms may play a role in the pathogenesis of AF and its maintenance. We aimed to evaluate a range of inflammatory markers as potentially involved in the pathophysiology of individuals with nonvalvular AF (NVAF). A total of 105 subjects were enrolled and divided into two groups: patients with NVAF (n = 55, mean age 72 ± 8 years) and a control group of individuals in sinus rhythm (n = 50, mean age 71 ± 8 years). Inflammatory-related mediators were quantified in plasma samples by using Cytometric Bead Array and Multiplex immunoassay. Subjects with NVAF presented significantly elevated values of interleukin (IL)-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF), interferon-gamma, growth differentiation factor-15, myeloperoxidase, as well as IL-4, interferon-gamma-induced protein (IP-10), monokine induced by interferon-gamma, neutrophil gelatinase-associated lipocalin, and serum amyloid A in comparison with controls. However, after multivariate regression analysis adjusting for confounding factors, only IL-6, IL-10, TNF, and IP-10 remained significantly associated with AF. We provided a basis for the study of inflammatory markers whose association with AF has not been addressed before, such as IP-10, in addition to supporting evidence about molecules that had previously been associated with the disease. We expect to contribute to the discovery of markers that can be implemented in clinical practice hereafter., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.
- Published
- 2023
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10. Role of Oxysterols in the Activation of the NLRP3 Inflammasome as a Potential Pharmacological Approach in Alzheimer's Disease.
- Author
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Martins GL, Ferreira CN, Palotás A, Rocha NP, and Reis HJ
- Subjects
- Humans, Inflammasomes metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Inflammation drug therapy, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, Oxysterols
- Abstract
Alzheimer's disease (AD), the most prevalent form of dementia, is a complex clinical condition with multifactorial origin posing a major burden to health care systems across the world. Even though the pathophysiological mechanisms underlying the disease are still unclear, both central and peripheral inflammation has been implicated in the process. Piling evidence shows that the nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated in AD. As dyslipidemia is a risk factor for dementia, and cholesterol can also activate the inflammasome, a possible link between lipid levels and the NLRP3 inflammasome has been proposed in Alzheimer's. It is also speculated that not only cholesterol but also its metabolites, the oxysterols, may be involved in AD pathology. In this context, mounting data suggest that NLRP3 inflammasome activity can be modulated by different peripheral nuclear receptors, including liver-X receptors, which present oxysterols as endogenous ligands. In light of this, the current review explores whether the activation of NLRP3 by nuclear receptors, mediated by oxysterols, may also be involved in AD and could serve as a potential pharmacological avenue in dementia., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Published
- 2023
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11. Evaluation of serum haptoglobin levels and Hp1-Hp2 polymorphism in the haptoglobin gene in patients with atrial fibrillation.
- Author
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Costa LBX, Martins GL, Duarte RCF, Rocha PL, Figueiredo EL, Silveira FR, das Graças Carvalho M, Reis HJ, Gomes KB, and Ferreira CN
- Subjects
- Genotype, Hemoglobins, Humans, Polymorphism, Genetic, Atrial Fibrillation genetics, Haptoglobins chemistry, Haptoglobins genetics
- Abstract
Background: Atrial fibrillation (AF) is an arrhythmia that involves structural and electrophysiological abnormalities. Many of the AF-related clinical conditions are associated with an increase in inflammatory and oxidative factors. Haptoglobin (Hp) is an acute phase protein whose biological role is to promote clearance of free hemoglobin (Hb). In addition, for being considered an inflammatory marker, Hp represents a protective mechanism against the oxidative effects of Hb. The Hp1-Hp2 polymorphism at Hp locus can lead to three phenotypes related to structural and functional differences in the protein. The objective of this study were to evaluate Hp levels and Hp1-Hp2 polymorphism at Hp locus in patients with AF compared to a control group., Methods and Results: This study included 65 patients with AF and 54 individuals without the arrhythmia. Biochemical parameters were determined using Vitros system, plasma levels of Hp were measured in serum samples by using ELISA method and polymorphisms were verified by PCR technique. Plasma Hp levels, as well as allelic and genotypic frequency, were not associated with AF. The levels of Hp also did not differ among the genotypes according to the applied models., Conclusions: The results suggest that Hp levels and Hp1-Hp2 polymorphism are not associated to AF., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)
- Published
- 2022
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12. Metabotropic glutamate receptor 5 knockout rescues obesity phenotype in a mouse model of Huntington's disease.
- Author
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Santos RPM, Ribeiro R, Ferreira-Vieira TH, Aires RD, de Souza JM, Oliveira BS, Lima ALD, de Oliveira ACP, Reis HJ, de Miranda AS, Vieira EML, Ribeiro FM, and Vieira LB
- Subjects
- Animals, Mice, Mice, Knockout, Neurons metabolism, Obesity complications, Obesity genetics, Obesity metabolism, Phenotype, Receptor, Metabotropic Glutamate 5 genetics, Receptor, Metabotropic Glutamate 5 metabolism, Huntington Disease metabolism
- Abstract
Obesity represents a global health problem and is characterized by metabolic dysfunctions and a low-grade chronic inflammatory state, which can increase the risk of comorbidities, such as atherosclerosis, diabetes and insulin resistance. Here we tested the hypothesis that the genetic deletion of metabotropic glutamate receptor 5 (mGluR5) may rescue metabolic and inflammatory features present in BACHD mice, a mouse model of Huntington's disease (HD) with an obese phenotype. For that, we crossed BACHD and mGluR5 knockout mice (mGluR5
-/- ) in order to obtain the following groups: Wild type (WT), mGluR5-/- , BACHD and BACHD/mGluR5-/- (double mutant mice). Our results showed that the double mutant mice present decreased body weight as compared to BACHD mice in all tested ages and reduced visceral adiposity as compared to BACHD at 6 months of age. Additionally, 12-month-old double mutant mice present increased adipose tissue levels of adiponectin, decreased leptin levels, and increased IL-10/TNF ratio as compared to BACHD mice. Taken together, our preliminary data propose that the absence of mGluR5 reduce weight gain and visceral adiposity in BACHD mice, along with a decrease in the inflammatory state in the visceral adipose tissue (VAT), which may indicate that mGluR5 may play a role in adiposity modulation., (© 2022. The Author(s).)- Published
- 2022
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13. Cannabidiol prevents lipopolysaccharide-induced sickness behavior and alters cytokine and neurotrophic factor levels in the brain.
- Author
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Tito PAL, Bernardino TCS, Bellozi PMQ, da Silva MCM, de Miranda AS, Vieira ÉLM, Moreira FA, Palotás A, de Oliveira ACP, and Reis HJ
- Subjects
- Animals, Antidepressive Agents pharmacology, Behavior, Animal drug effects, Brain metabolism, Brain-Derived Neurotrophic Factor metabolism, Cytokines metabolism, Depressive Disorder, Major physiopathology, Disease Models, Animal, Lipopolysaccharides, Male, Mice, Mice, Inbred C57BL, Nerve Growth Factor metabolism, Neuroinflammatory Diseases drug therapy, Neuroinflammatory Diseases physiopathology, Brain drug effects, Cannabidiol pharmacology, Depressive Disorder, Major drug therapy, Illness Behavior drug effects
- Abstract
Background: Major depressive disorder (MDD) affects millions of people worldwide. While the exact pathogenesis is yet to be elucidated, the role of neuro-immune signaling has recently emerged. Despite major advances in pharmacotherapy, antidepressant use is marred by limited efficacy and potential side effects. Cannabidiol (CBD), a phytocannabinoid, exerts antidepressant-like effects in experimental animals. This study investigated the impact of CBD on sickness behavior (SB), a measure of depressive-like response, and neuro-immune changes induced by lipopolysaccharides (LPS) in mice., Methods: Socially isolated rodents were administered with LPS to trigger SB. and treated with CBD or its vehicle. Animals were submitted to forced swimming test, to evaluate depressive-like behavior, and to open field test, to evaluate locomotory activity. Immediately after behavioral analyses, animals were euthanized and had their hypothalamus, prefrontal cortex and hippocampus dissected, to proceed neurotrophins and cytokines analyses. ELISA was used to detect IL-1β, BDNF and NGF; and cytometric beads array to measure IL-2, IL-4, IL-6, IFN-γ, TNF-α and IL-10 levels., Results: CBD effectively prevented SB-induced changes in the forced swim test without altering spontaneous locomotion. This phytocannabinoid also partially reversed LPS-evoked IL-6 increase in both the hypothalamus and hippocampus. In addition, CBD prevented endotoxin-induced increase in BDNF and NGF levels in the hippocampus of SB animals., Conclusions: Apparently, CBD prevents both behavioral and neuro-immunological changes associated with LPS-induced SB, which reinforces its potential use as an antidepressant which modulates neuroinflammation. This opens up potentially new therapeutic avenues in MDD., (© 2021. Maj Institute of Pharmacology Polish Academy of Sciences.)
- Published
- 2021
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14. Neurochemical abnormalities in the hippocampus of male rats displaying audiogenic seizures, a genetic model of epilepsy.
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Dos Santos RR, Bernardino TC, da Silva MCM, de Oliveira ACP, Drumond LE, Rosa DV, Massensini AR, Moraes MFD, Doretto MC, Romano-Silva MA, and Reis HJ
- Subjects
- Animals, Calcium metabolism, Glutamic Acid metabolism, Male, Neuronal Calcium-Sensor Proteins metabolism, Neuropeptides metabolism, Rats, Rats, Wistar, Synaptosomes metabolism, gamma-Aminobutyric Acid metabolism, Hippocampus metabolism, Seizures metabolism
- Abstract
Background: Epilepsy is a disorder characterized by recurrent seizures that affects 1% of the population. However, the neurochemical alterations observed in epilepsy are not fully understood. There are different animal models of epilepsy, such as genetic or drug induced. In the present study, we utilize Wistar Audiogenic Rats (WAR), a murine strain that develops seizures in response to high intensity audio stimulation, in order to investigate abnormalities in glutamatergic and GABAergic systems., Methods: Synaptosomes and glial plasmalemmal vesicles were prepared from hippocampus and cortex, respectively. Glutamate and GABA release and uptake were assayed by monitoring the fluorescence and using L-[
3 H]-radiolabeled compounds. Glutamate and calcium concentration in the synaptosomes were also measured. The expression of neuronal calcium sensor 1 (NCS-1) was determined by western blot., Results: Glutamate and GABA release evoked by KCl was decreased in WAR compared to control Wistar rats. Calcium independent release was not considerably different in both groups. The total amount of glutamate of synaptosomes, as well as glutamate uptake by synaptosomes and GPV were also decreased in WAR in comparison with the controls. In addition, [Ca2+ ]i of hippocampal synaptosomes, as well as NCS-1 expression in the hippocampus, were increased in WAR in comparison with controls., Conclusion: In conclusion, our results suggest that WAR have important alterations in the glutamatergic and GABAergic pathways, as well as an increased expression of NCS-1 in the hippocampus and inferior colliculus. These alterations may be linked to the spreading of hyperexcitability and recruitment of various brain regions., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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15. Serotonin and dopamine receptors profile on peripheral immune cells from patients with temporal lobe epilepsy.
- Author
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Vieira ÉLM, da Silva MCM, Gonçalves AP, Martins GL, Teixeira AL, de Oliveira ACP, and Reis HJ
- Subjects
- Adult, Epilepsy, Temporal Lobe metabolism, Female, Granulocytes metabolism, Humans, Male, Middle Aged, Monocytes metabolism, Receptors, Dopamine metabolism, Receptors, Serotonin metabolism, Epilepsy, Temporal Lobe immunology, Granulocytes immunology, Monocytes immunology, Receptors, Dopamine immunology, Receptors, Serotonin immunology
- Abstract
The role of inflammation and immune cells has been demonstrated in neurological diseases, including epilepsy. Leukocytes, as well as inflammatory mediators, contribute to abnormal processes that lead to a reduction in seizure threshold and synaptic reorganization. In this sense, identifying different phenotypes of circulating immune cells is essential to understanding the role of these cells in epilepsy. Immune cells can express a variety of surface markers, including neurotransmitter receptors, such as serotonin and dopamine. Alteration in these receptors expression patterns may affect the level of inflammatory mediators and the pathophysiology of epilepsy. Therefore, in the current study, we evaluated the expression of dopamine and serotonin receptors on white blood cells from patients with temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). Blood samples from 17 patients with TLE-HS and 21 controls were collected. PBMC were isolated and stained ex vivo for flow cytometry. We evaluated the expression of serotonin (5-HT
1A , 5-HT1B , 5-HT2 , 5-HT2B , 5-HT2C , 5-HT3 , 5-HT4 ), and dopamine receptors (D1 , D2 , D3 , D4 , and D5 ) on the cell surface of lymphocytes and innate immune cells (monocytes and granulocytes). Our results demonstrated that innate cells and lymphocytes from patients with TLE-HS showed high mean fluorescent intensity (MFI) for 5-HT1A , 5-HT1B , 5-HT2A, and 5-HT4 compared to controls. No difference was observed for 5-HT2B . For dopamine receptors, the expression of D1 , D2 , D4, and D5 receptors was higher on innate cells from patients with TLE-HS when compared to controls for the MFI. Regarding lymphocytes population, D2 expression was increased in patients with TLE-HS. In conclusion, there are alterations in the expression of serotonin and dopamine receptors on immune blood cells of patients with TLE-HS. Although the biological significance of these findings still needs to be further investigated, these changes may contribute to the understanding of TLE-HS pathophysiology., (Copyright © 2021 Elsevier B.V. All rights reserved.)- Published
- 2021
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16. Negative Modulation of the Metabotropic Glutamate Receptor Type 5 as a Potential Therapeutic Strategy in Obesity and Binge-Like Eating Behavior.
- Author
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Oliveira TPD, Gonçalves BDC, Oliveira BS, de Oliveira ACP, Reis HJ, Ferreira CN, Aguiar DC, de Miranda AS, Ribeiro FM, Vieira EML, Palotás A, and Vieira LB
- Abstract
Obesity is a multifactorial disease, which in turn contributes to the onset of comorbidities, such as diabetes and atherosclerosis. Moreover, there are only few options available for treating obesity, and most current pharmacotherapy causes severe adverse effects, while offering minimal weight loss. Literature shows that metabotropic glutamate receptor 5 (mGluR5) modulates central reward pathways. Herein, we evaluated the effect of VU0409106, a negative allosteric modulator (NAM) of mGluR5 in regulating feeding and obesity parameters. Diet-induced obese C57BL/6 mice were treated for 14 days with VU0409106, and food intake, body weight, inflammatory/hormonal levels, and behavioral tests were performed. Our data suggest reduction of feeding, body weight, and adipose tissue inflammation in mice treated with high-fat diet (HFD) after chronic treatment with VU0409106. Furthermore, a negative modulation of mGluR5 also reduces binge-like eating, the most common type of eating disorder. Altogether, our results pointed out mGluR5 as a potential target for treating obesity, as well as related disorders., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Oliveira, Gonçalves, Oliveira, de Oliveira, Reis, Ferreira, Aguiar, de Miranda, Ribeiro, Vieira, Palotás and Vieira.)
- Published
- 2021
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17. Thrombin Generation and other hemostatic parameters in patients with atrial fibrillation in use of warfarin or rivaroxaban.
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Duarte RCF, Rios DRA, Figueiredo EL, Caiaffa JRS, Silveira FR, Lanna R, Alves LCV, Martins GL, Reis HJ, Reis EA, Ferreira CN, Sternick EB, Campos FMF, and das Graças Carvalho M
- Subjects
- Aged, Aged, 80 and over, Atrial Fibrillation blood, Blood Coagulation drug effects, Factor Xa Inhibitors therapeutic use, Female, Hemostasis drug effects, Humans, Male, Anticoagulants therapeutic use, Atrial Fibrillation drug therapy, Rivaroxaban therapeutic use, Thrombin analysis, Warfarin therapeutic use
- Abstract
Patients with atrial fibrillation (AF) present hyperactivation of both platelets and coagulation leading to a hypercoagulable state which contributes to an increased risk of thromboembolism. Therefore, one of the main strategies for treatment of AF is prevention of these events through the use of oral anticoagulants (OAC). The aim of this study was to evaluate hemostasis as a whole in patients with non-valvular AF undergoing warfarin or rivaroxaban by thrombin generation test (TGT), in addition to monocyte-platelet aggregates (MPA), glycoprotein IIb/IIIa (GPIIb/IIIa), and platelet (PMP) and endothelium (EMP) microparticles, compared to age and sex matched controls. PT/INR for OAC use was also determined. In patients taking OAC, compared to control group, a decrease in TGT (p = 0.000 for all parameters) were observed. Patients taking warfarin showed to be more hypocoagulable, presenting lower levels of ETP (p = 0.000) and peak (p = 0.002) than patients using rivaroxaban. Patients on warfarin use with INR > 3 had also lower levels of ETP (p = 0.01) and peak (p = 0.006). A decrease in ETP (p = 0.03) and peak (p = 0.02) values was also observed in patients using rivaroxaban with PT > 21.4 s. Patients using warfarin (p = 0.000) and rivaroxaban (p = 0.000) presented lower levels of MPA in relation to control group. It was also observed in patients using warfarin, lower GPIIb/IIIa levels in relation to control group (p = 0.011). Patients taking rivaroxaban (p = 0.003) and warfarin (p = 0.001) had higher PMP levels compared to control group. There was no difference in levels of EMP between the groups (p = 0.0536). The present study reinforces the usefulness of OAC in AF, which decisively contribute to a better management of the disease preventing possible complications.
- Published
- 2021
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18. Comparison of Inflammatory Mediators in Patients With Atrial Fibrillation Using Warfarin or Rivaroxaban.
- Author
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Martins GL, Duarte RCF, Vieira ÉLM, Rocha NP, Figueiredo EL, Silveira FR, Caiaffa JRS, Lanna RP, Carvalho MDG, Palotás A, Ferreira CN, and Reis HJ
- Abstract
Background: Atrial fibrillation (AF) is the most common arrhythmia associated with high risk of venous thromboembolism. Inflammatory mechanisms may be involved in the pathophysiology of AF and in the AF-related thrombogenesis, and patients with AF might benefit from the use of anticoagulants with anti-inflammatory properties. However, the evidence is still scarce, and it points out the need of trials seeking to investigate the levels of inflammatory mediators in patients with AF under different anticoagulant therapies. Therefore, this study was designed to define whether patients with AF treated either with an activated coagulation factor X (FXa) inhibitor (rivaroxaban) or with a vitamin K inhibitor (warfarin) present changes in peripheral levels of inflammatory mediators, mainly cytokines and chemokines. Methods: A total of 127 subjects were included in this study, divided into three groups: patients with non-valvular atrial fibrillation (NVAF) using warfarin ( N = 42), patients with NVAF using rivaroxaban ( N = 29), and controls ( N = 56). Plasma levels of inflammatory mediators were quantified by immunoassays. Results: Patients with AF (both warfarin and rivaroxaban groups) presented increased levels of inflammatory cytokines in comparison with controls. The use of rivaroxaban was associated with decreased levels of inflammatory cytokines in comparison with warfarin. On the other hand, patients with AF using rivaroxaban presented increased levels of the chemokines (MCP-1 in comparison with warfarin users; MIG and IP-10 in comparison with controls). Conclusions: AF is associated with an inflammatory profile that was less pronounced in patients on rivaroxaban in comparison with warfarin users. Further studies are necessary to assess the clinical implications of our results and whether patients with AF would benefit from rivaroxaban anti-inflammatory effects., (Copyright © 2020 Martins, Duarte, Vieira, Rocha, Figueiredo, Silveira, Caiaffa, Lanna, Carvalho, Palotás, Ferreira and Reis.)
- Published
- 2020
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19. Inflammatory and Infectious Processes Serve as Links between Atrial Fibrillation and Alzheimer's Disease.
- Author
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Martins GL, Duarte RCF, Mukhamedyarov MA, Palotás A, Ferreira CN, and Reis HJ
- Subjects
- Dementia physiopathology, Humans, Models, Biological, Risk Factors, Alzheimer Disease physiopathology, Atrial Fibrillation physiopathology, Cognitive Dysfunction physiopathology, Infections physiopathology, Inflammation physiopathology, Stroke physiopathology
- Abstract
Atrial fibrillation (AF) is one of the most prevalent forms of arrhythmia that carries an increased risk of stroke which, in turn, is strongly associated with cognitive decline. The majority of dementia cases are caused by Alzheimer's disease (AD) with obscure pathogenesis. While the exact mechanisms are unknown, the role of inflammatory processes and infectious agents have recently been implicated in both AD and AF, suggesting a common link between these maladies. Here, we present the main shared pathways underlying arrhythmia and memory loss. The overlapping predictive biomarkers and emerging joint pharmacological approaches are also discussed.
- Published
- 2020
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20. Evaluation of Brain Cytokines and the Level of Brain-Derived Neurotrophic Factor in an Inflammatory Model of Depression.
- Author
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Horita JKHA, da Silva MCM, Ferrari CZ, Vieira ELM, Moreira FA, de Oliveira ACP, and Reis HJ
- Subjects
- Animals, Behavior, Animal, Brain metabolism, Cytokines metabolism, Depression drug therapy, Hippocampus metabolism, Lipopolysaccharides toxicity, Male, Mice, Brain-Derived Neurotrophic Factor metabolism, Depressive Disorder, Major drug therapy
- Abstract
Introduction: Major depressive disorder is considered a global public health problem. Inflammatory processes are likely involved in its pathophysiology, but the underlying mechanisms have remained uncertain.Here, we used the model of systemic lipopolysaccharide (LPS) injection to test the hypothesis that depressive-like behaviors occur along with changes in the levels of cytokines and brain-derived neurotrophic factor (BDNF) in the hippocampus (HC), prefrontal cortex (PFC), and hypothalamus (HT), and can be prevented by dexamethasone administration., Methods: Adult C57Bl/6 male mice were first isolated for 10 days, and thereafter received an injection of dexamethasone (6 mg/kg, intraperitoneal [i.p.]), saline followed by LPS (0.83 mg/kg, i.p.), or saline. After 6 h, animals were subjected to the forced-swim test (FST) and open-field tests. Immediately after the behavioral tests, they were euthanized and their brains were collected for the biochemical analyses., Results: LPS increased the immobility time and reduced the distance travelled in the FST and open-field test, respectively. Dexamethasone increased the immobility time in saline-treated mice but reduced this behavior in the LPS group. LPS increased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6 and interferon (IFN)-γ in most of the regions evaluated. Dexamethasone prevented LPS-induced IL-6 in the HC, PFC, and HT. Interestingly, dexamethasone increased IL-4 and IL-10 levels in both the LPS- and saline-treated groups. Although dexamethasone reduced BDNF in saline-treated mice, it prevented LPS-induced reduction in this neurotrophic factor., Conclusion: In summary, dexamethasone decreased proinflammatory and increased anti-inflammatory levels of cytokines and prevented a reduction in BDNF levels induced by the inflammatory stimulus. Thus, the attenuation of depressive-like behavior induced by dexamethasone may be related to the effects on these parameters., (© 2020 S. Karger AG, Basel.)
- Published
- 2020
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21. Effects of Transplanted Umbilical Cord Blood Mononuclear Cells Overexpressing GDNF on Spatial Memory and Hippocampal Synaptic Proteins in a Mouse Model of Alzheimer's Disease.
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Petukhova EO, Mukhamedshina YO, Salafutdinov II, Garanina EE, Kaligin MS, Leushina AV, Rizvanov AA, Reis HJ, Palotás A, Zefirov AL, and Mukhamedyarov MA
- Subjects
- Alzheimer Disease genetics, Animals, Disks Large Homolog 4 Protein biosynthesis, Disks Large Homolog 4 Protein genetics, Female, Glial Cell Line-Derived Neurotrophic Factor genetics, HEK293 Cells, Humans, Mice, Mice, Transgenic, Pregnancy, Synaptophysin biosynthesis, Synaptophysin genetics, Alzheimer Disease metabolism, Alzheimer Disease therapy, Cord Blood Stem Cell Transplantation methods, Disease Models, Animal, Glial Cell Line-Derived Neurotrophic Factor biosynthesis, Hippocampus metabolism, Spatial Memory physiology
- Abstract
Background/objective: Alzheimer's disease (AD) is a progressive incurable neurodegenerative disorder. Glial cell line-derived neurotrophic factor (GDNF) is a prominent regulator of brain tissue and has an impressive potential for use in AD therapy. While its metabolism is still not fully understood, delivering neuropeptides such as GDNF via umbilical cord blood mononuclear cells (UCBMCs) to the sites of neurodegeneration is a promising approach in the development of innovative therapeutic avenues., Methods: UCBMCs were transduced with adenoviral vectors expressing GDNF and injected into AD transgenic mice. Various parameters including homing and survival of transplanted cells, expression of GDNF and synaptic proteins, as well as spatial memory were evaluated., Results: UCBMCs were observed in the hippocampus and cortex several weeks after transplantation, and their long-term presence was associated with improved spatial memory. Post-synaptic density protein 95 (PSD-95) and synaptophysin levels in the hippocampus were also effectively restored following the procedure in AD mice., Conclusions: Our data indicate that gene-cell therapy with GDNF-overexpressing UCBMCs may produce long-lasting neuroprotection and stimulation of synaptogenesis. Such adenoviral constructs could potentially possess a high therapeutic potential for the treatment of AD.
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- 2019
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22. Circulating levels of neurotrophic factors are unchanged in patients with Parkinson's disease.
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Rocha NP, Ferreira JPS, Scalzo PL, Barbosa IG, Souza MS, Christo PP, Reis HJ, and Teixeira AL
- Subjects
- Aged, Biomarkers blood, Case-Control Studies, Cohort Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Nerve Growth Factors blood, Parkinson Disease blood
- Abstract
There is great evidence linking neurotrophic factor (NF) dysfunction with Parkinson's disease (PD) pathophysiology. This study was conducted to evaluate plasma levels of NFs and their possible associations with clinical symptoms in PD. For this purpose, 40 PD patients and 25 controls were subjected to a clinical evaluation and peripheral blood draw. Plasma levels of brain-derived neurotrophic factor (BDNF), pro-BDNF, neurotrophin 3, neurotrophin 4, nerve growth, glial cell line-derived neurotrophic factor and ciliary neurotrophic factor were measured by enzyme-linked immunosorbent assay. There was no significant difference between PD patients and controls regarding the plasma levels of the evaluated NFs. In addition, NF levels were not associated with disease duration, degree of motor or functional impairment, cognitive performance or severity of depressive symptoms. In conclusion, although NFs may play relevant roles in the pathophysiology of PD, the circulating levels of these molecules are not necessarily changed in patients with PD.
- Published
- 2018
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23. Inflammation as a Possible Link Between Dyslipidemia and Alzheimer's Disease.
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Oliveira BCL, Bellozi PMQ, Reis HJ, and de Oliveira ACP
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- Animals, Humans, Alzheimer Disease metabolism, Dyslipidemias metabolism, Inflammation metabolism
- Abstract
Alzheimer's disease (AD) is the leading cause of dementia worldwide. This pathological condition is characterized not only by Aβ and tau accumulation in the central nervous system (CNS), but also by inflammation, processes that can lead to neurodegeneration. Besides that, other factors may contribute to the development of AD, such as dyslipidemias. Changes in lipid levels can either influence the activity of enzymes related to the protein deposition that occurs in this pathological condition, or enhance the peripheral and CNS immune responses. Furthermore, cholesterol-associated genes are frequently associated with AD. Here, we extensively reviewed the literature and, based on the existing evidences, we suggest inflammation as an important link between dyslipidemias and AD., (Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Published
- 2018
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24. Evaluation of PCSK9 levels and its genetic polymorphisms in women with polycystic ovary syndrome.
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Xavier LB, Sóter MO, Sales MF, Oliveira DK, Reis HJ, Candido AL, Reis FM, Silva IO, Gomes KB, and Ferreira CN
- Subjects
- Adult, Brazil, Case-Control Studies, Cholesterol, LDL genetics, Dyslipidemias genetics, Female, Gene Frequency genetics, Genotype, Humans, Lipids genetics, Receptors, LDL genetics, Genetic Predisposition to Disease genetics, Polycystic Ovary Syndrome genetics, Polymorphism, Single Nucleotide genetics, Proprotein Convertase 9 genetics
- Abstract
Dyslipidemia is one of the common metabolic disorders in Polycystic Ovary Syndrome (PCOS). Proprotein convertase subtilisin kexin type 9 (PCSK9) is a new component of lipid metabolism and correlated to the development of dyslipidemia and atherosclerosis. This protein acts by preventing the recycling of LDL receptors (LDL-r) back to the cell surface and thus generates higher levels of LDLc. The objective of this study was to evaluate the PCSK9 polymorphisms rs505151 (c.2009A>G), rs562556 (c.1420A>G) and rs11206510 (T>C) and plasma PCSK9 levels in PCOS. A group of women with PCOS (n=97), and a group of healthy women (control, n=99) were selected. Biochemical parameters were determined by using Vitros system and polymorphisms were assessed by TaqMan SNP Genotyping Assays. Plasma PCSK9 levels or PCSK9 polymorphisms were not associated with PCOS. The genotype rs11206510TT was associated with higher levels of PCSK9 in both groups. The population investigated (PCOS+control groups) with the rs505151AA genotype presented higher HDLc levels. The GG genotype regarding rs562556 polymorphism was associated with higher HDLc in PCOS group, while the AA genotype carriers had higher plasma testosterone levels when evaluated all women in a same group. The results were the same by comparing recessive and dominant model despite PCOS or both groups altogether. Our results suggest that PCSK9 is not altered specifically in PCOS, but it could be associated with in lipid and androgen metabolism in Brazilian women., (Copyright © 2017 Elsevier B.V. All rights reserved.)
- Published
- 2018
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25. Reduced Activated T Lymphocytes (CD4+CD25+) and Plasma Levels of Cytokines in Parkinson's Disease.
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Rocha NP, Assis F, Scalzo PL, Vieira ÉLM, Barbosa IG, de Souza MS, Christo PP, Reis HJ, and Teixeira AL
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- Aged, Antiparkinson Agents pharmacology, Female, Humans, Immunophenotyping, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Levodopa pharmacology, Male, Middle Aged, Pramipexole pharmacology, CD4-Positive T-Lymphocytes cytology, Cytokines blood, Parkinson Disease blood
- Abstract
Parkinson's disease (PD) is the second most common neurodegenerative disease. The cause of neurodegeneration in PD is not completely understood, and evidence has shown that inflammatory/immune changes may be involved in PD pathophysiology. Herein, we aimed to determine the profile of the peripheral immune system in patients with PD in comparison with controls. Forty patients with PD and 25 age- and gender-matched controls were enrolled in this study. From these, 23 PD patients and 21 controls were included in the immunophenotyping analyses. Peripheral blood was drawn on the same day of the clinical assessment and submitted to plasma separation for enzyme-linked immunosorbent assay or cytometric bead array. Immunophenotyping analyses of the peripheral blood were performed by flow cytometry. We found that patients with PD presented peripheral immune changes evidenced by decreased percentage of T lymphocytes (CD3+ cells), especially activated T lymphocytes (CD4+CD25+ cells), when compared with controls. In line with these results, we also found decreased plasma levels of the cytokines IL-4, IL-6, IL-10, TNF, IFN-γ, and IL-17A in the PD group. In vitro experiments demonstrated that the production of cytokines by peripheral blood mononuclear cells harvested from healthy young donors was reduced after exposure to the anti-parkinsonian drugs levodopa and pramipexole. Our data corroborate the hypothesis that immunological mechanisms are involved in PD. It is not clear whether the differences that we have found are due to adaptive mechanisms or to changes associated with PD, including pharmacological treatment, or even directly related to the disease pathophysiology. Future studies are needed in this regard.
- Published
- 2018
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26. Effectiveness of an early mobilization program on functional capacity after coronary artery bypass surgery: A randomized controlled trial protocol.
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da Costa Torres D, Dos Santos PM, Reis HJ, Paisani DM, and Chiavegato LD
- Abstract
Background: Muscle atrophy and prolonged inactivity are associated with an increased sensation of fatigue and reduced functional capacity in the postoperative period in patients undergoing coronary artery bypass grafting. Cardiac rehabilitation after hospital discharge is highly recommended and contributes to improvement in functional capacity and quality of life. However, few studies have evaluated the effectiveness of early mobilization protocols during hospitalization on the patterns of physical activity and functional capacity after coronary artery bypass grafting., Objective: To investigate the effectiveness of an early mobilization program on the functional capacity of patients undergoing coronary artery bypass grafting in the short and long term., Methods: This is a prospective, randomized, controlled, single-blind trial protocol that will evaluate 66 consecutive patients undergoing coronary artery bypass grafting. Patients will be randomized into two training groups: the control group (N = 33), which will perform breathing exercises and the intervention group (N = 33), which will perform breathing exercises and aerobic exercises. The groups will receive treatment from first to the seventh postoperative day, twice daily. In the preoperative period, the following outcomes will be assessed: physical activity level (Baecke Questionnaire), Functional Independence Measure, and functional capacity (6-min walking test). Functional capacity will be reassessed after the 7th and 60th postoperative day. Pulmonary complications and length of hospital stay will also be evaluated. Statistical analysis will be calculated using linear mixed models and will be based on intention-to-treat. The level of significance will be set at α = 5%., Competing Interests: Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2016
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27. Transcriptional Analysis of Blood Lymphocytes and Skin Fibroblasts, Keratinocytes, and Endothelial Cells as a Potential Biomarker for Alzheimer's Disease.
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Mukhamedyarov MA, Rizvanov AA, Yakupov EZ, Zefirov AL, Kiyasov AP, Reis HJ, Teixeira AL, Vieira LB, Lima LM, Salafutdinov II, Petukhova EO, Khaiboullina SF, Schlauch KA, Lombardi VC, and Palotás A
- Subjects
- Aged, Alzheimer Disease diagnosis, Biomarkers metabolism, Female, Humans, Male, Pilot Projects, Transcription, Genetic physiology, Alzheimer Disease blood, Alzheimer Disease genetics, Endothelial Cells metabolism, Fibroblasts metabolism, Keratinocytes metabolism, Lymphocytes metabolism
- Abstract
Alzheimer's disease (AD) is a devastating and progressive form of dementia that is typically associated with a build-up of amyloid-β plaques and hyperphosphorylated and misfolded tau protein in the brain. Presently, there is no single test that confirms AD; therefore, a definitive diagnosis is only made after a comprehensive medical evaluation, which includes medical history, cognitive tests, and a neurological examination and/or brain imaging. Additionally, the protracted prodromal phase of the disease makes selection of control subjects for clinical trials challenging. In this study we have utilized a gene-expression array to screen blood and skin punch biopsy (fibroblasts, keratinocytes, and endothelial cells) for transcriptional differences that may lead to a greater understanding of AD as well as identify potential biomarkers. Our analysis identified 129 differentially expressed genes from blood of dementia cases when compared to healthy individuals, and four differentially expressed punch biopsy genes between AD subjects and controls. Additionally, we identified a set of genes in both tissue compartments that showed transcriptional variation in AD but were largely stable in controls. The translational products of these variable genes are involved in the maintenance of the Golgi structure, regulation of lipid metabolism, DNA repair, and chromatin remodeling. Our analysis potentially identifies specific genes in both tissue compartments that may ultimately lead to useful biomarkers and may provide new insight into the pathophysiology of AD.
- Published
- 2016
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28. Peripheral levels of angiotensins are associated with depressive symptoms in Parkinson's disease.
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Rocha NP, Scalzo PL, Barbosa IG, de Campos-Carli SM, Tavares LD, de Souza MS, Christo PP, Reis HJ, Simões E Silva AC, and Teixeira AL
- Subjects
- Aged, Case-Control Studies, Female, Humans, Male, Middle Aged, Peptidyl-Dipeptidase A blood, Psychiatric Status Rating Scales, Statistics as Topic, Angiotensins blood, Depressive Disorder blood, Depressive Disorder etiology, Parkinson Disease complications
- Abstract
Background: The pathogenesis of PD remains elusive. The renin-angiotensin-system (RAS) has recently been implicated in the degeneration of dopaminergic neurons. This study aimed to compare plasma levels of components of the RAS of individuals with PD with controls. We also investigated the association between these circulating markers and motor, depressive and cognitive parameters., Methods: Thirty PD patients and twenty controls were subjected to clinical evaluation, including cognitive and depressive symptoms assessment. Plasma levels of Angiotensin (Ang) I, Ang II, Ang- (1-7), angiotensin-converting enzyme (ACE) and ACE2 were measured by Enzyme-Linked Immunosorbent Assay (ELISA)., Results: PD patients presented lower plasma levels of Ang I, Ang II and Ang- (1-7) than control individuals. Among PD patients, lower circulating levels of angiotensins were associated with increased severity of depressive symptoms., Conclusions: This is the first study showing that peripheral levels of RAS components are changed in PD and associated with depressive symptoms., (Copyright © 2016. Published by Elsevier B.V.)
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- 2016
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29. Human adipose-derived stem cells stimulate neuroregeneration.
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Masgutov RF, Masgutova GA, Zhuravleva MN, Salafutdinov II, Mukhametshina RT, Mukhamedshina YO, Lima LM, Reis HJ, Kiyasov AP, Palotás A, and Rizvanov AA
- Subjects
- Animals, Disease Models, Animal, Ganglia, Spinal pathology, Humans, Immunohistochemistry, Microscopy, Confocal, Microscopy, Fluorescence, Rats, Sciatic Nerve pathology, Treatment Outcome, Adipose Tissue, Nerve Regeneration, Peripheral Nerve Injuries therapy, Sciatic Nerve injuries, Stem Cell Transplantation, Stem Cells physiology, Transplantation, Heterologous
- Abstract
Traumatic brain injuries and degenerative neurological disorders such as Alzheimer's dementia, Parkinson's disease, amyotrophic lateral sclerosis and many others are characterized by loss of brain cells and supporting structures. Restoring microanatomy and function using stem cells is a promising therapeutic approach. Among the many various sources, adipose-derived stem cells (ADSCs) are one of the most easily harvested alternatives, they multiply rapidly, and they demonstrate low immunogenicity with an ability to differentiate into several cell types. The objective of this study was to evaluate the effect of xenotransplanted human ADSCs on post-traumatic regeneration of rat sciatic nerve. Peripheral reconstruction following complete sciatic transection and autonerve grafting was complemented by intra-operative injection of hADSCs into the proximal and distal stumps. The injury caused gliosis and apoptosis of sensory neurons in the lumbar 5 (L5) ganglia in the control rodents; however, animals treated with hADSCs demonstrated a smaller amount of cellular loss. Formation of amputation neuroma, which hinders axonal repair, was less prominent in the experimental group, and immunohistochemical analysis of myelin basic protein showed good myelination 65 days after surgery. At this point, control groups still exhibited high levels of microglia/macrophage-specific marker Iba-1 and proliferating cell nuclear antigen, the mark of an ongoing inflammation and incomplete axonal growth 2 months after the injury. This report demonstrates that hADSCs promote neuronal survival in the spinal ganglion, fuel axonal repair and stimulate the regeneration of peripheral nerves.
- Published
- 2016
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30. Construction of recombinant adenovirus containing picorna-viral 2A-peptide sequence for the co-expression of neuro-protective growth factors in human umbilical cord blood cells.
- Author
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Garanina EE, Mukhamedshina YO, Salafutdinov II, Kiyasov AP, Lima LM, Reis HJ, Palotás A, Islamov RR, and Rizvanov AA
- Subjects
- Adenoviridae genetics, Amyotrophic Lateral Sclerosis genetics, Animals, Cysteine Endopeptidases genetics, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Fetal Blood cytology, Fibroblast Growth Factor 2 genetics, Genetic Vectors physiology, HEK293 Cells, Humans, Male, Mice, Mice, Transgenic, Mutation genetics, Recombinant Proteins genetics, Recombinant Proteins metabolism, Superoxide Dismutase-1 genetics, Transfection, Vascular Endothelial Growth Factor A genetics, Viral Proteins genetics, Amyotrophic Lateral Sclerosis therapy, Blood Cells metabolism, Blood Cells transplantation, Cysteine Endopeptidases metabolism, Fibroblast Growth Factor 2 metabolism, Vascular Endothelial Growth Factor A metabolism, Viral Proteins metabolism
- Abstract
Study Design: Experimental study., Objective: Several neuro-degenerative disorders such as Alzheimer's dementia, Parkinson's disease and amyotrophic lateral sclerosis (ALS) are associated with genetic mutations, and replacing or disrupting defective sequences might offer therapeutic benefits. Single gene delivery has so far failed to achieve significant clinical improvements in humans, leading to the advent of co-expression of multiple therapeutic genes. Co-transfection using two or more individual constructs might inadvertently result in disproportionate delivery of the products into the cells. To prevent this, and in order to rule out interference among the many promoters with varying strength, expressing multiple proteins in equimolar amounts can be achieved by linking open reading frames under the control of only one promoter., Setting: Kazan, Russian Federation., Methods: Here we describe a strategy for adeno-viral co-expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2) interconnected through picorna-viral 2A-amino-acid sequence in transfected human umbilical cord blood mono-nuclear cells (hUCB-MCs)., Results: Presence of both growth factors, as well as absence of immune response to 2A-antigen, was demonstrated after 28-52 days. Following injection of hUCB-MCs into ALS transgenic mice, co-expression of VEGF and FGF2, as well as viable xeno-transplanted cells, were observed in the spinal cord after 1 month., Conclusion: These results suggest that recombinant adeno-virus containing 2A-sequences could serve as a promising alternative in regenerative medicine for the delivery of therapeutic molecules to treat neurodegenerative diseases, such as ALS.
- Published
- 2016
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31. Neuroprotective effects of the anticancer drug NVP-BEZ235 (dactolisib) on amyloid-β 1-42 induced neurotoxicity and memory impairment.
- Author
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Bellozi PM, Lima IV, Dória JG, Vieira ÉL, Campos AC, Candelario-Jalil E, Reis HJ, Teixeira AL, Ribeiro FM, and de Oliveira AC
- Subjects
- Animals, Cell Survival drug effects, Cells, Cultured, Imidazoles pharmacology, Mice, Neurons drug effects, Neurons physiology, Neuroprotective Agents pharmacology, Quinolines pharmacology, Amyloid beta-Peptides toxicity, Hippocampus drug effects, Hippocampus pathology, Imidazoles administration & dosage, Memory Disorders prevention & control, Neuroprotective Agents administration & dosage, Quinolines administration & dosage
- Abstract
Alzheimer's Disease (AD) is a progressive neurodegenerative disease and the main cause of dementia. Substantial evidences indicate that there is over-activation of the PI3K/Akt/mTOR axis in AD. Therefore, the aim of the present study was to investigate the effects of NVP-BEZ235 (BEZ; dactolisib), a dual PI3K/mTOR inhibitor that is under phase I/II clinical trials for the treatment of some types of cancer, in hippocampal neuronal cultures stimulated with amyloid-β (Aβ) 1-42 and in mice injected with Aβ 1-42 in the hippocampus. In cell cultures, BEZ reduced neuronal death induced by Aβ. BEZ, but not rapamycin, a mTOR inhibitor, or LY294002, a PI3K inhibitor that also inhibits mTOR, reduced the memory impairment induced by Aβ. The effect induced by Aβ was also prevented in PI3Kγ(-/-) mice. Neuronal death and microgliosis induced by Aβ were reduced by BEZ. In addition, the compound increased IL-10 and TNF-α levels in the hippocampus. Finally, BEZ did not change the phosphorylation of Akt and p70s6K, suggesting that the involvement of PI3K and mTOR in the effects induced by BEZ remains controversial. Therefore, BEZ represents a potential strategy to prevent the pathological outcomes induced by Aβ and should be investigated in other models of neurodegenerative conditions.
- Published
- 2016
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32. Wistar Audiogenic Rats (WAR) exhibit altered levels of cytokines and brain-derived neurotrophic factor following audiogenic seizures.
- Author
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de Souza Bernardino TC, Teixeira AL, Miranda AS, Guidine PM, Rezende G, Doretto MC, Castro GP, Drummond L, Moraes MF, Tito PA, de Oliveira AC, and Reis HJ
- Subjects
- Acoustic Stimulation, Animals, Brain metabolism, Interleukin-1beta metabolism, Male, Rats, Wistar, Seizures etiology, Tumor Necrosis Factor-alpha metabolism, Brain-Derived Neurotrophic Factor metabolism, Cytokines metabolism, Seizures metabolism
- Abstract
Increasing body of evidence suggests that inflammatory and neurotrophic factors might be important for epileptogenesis. Most animal studies demonstrated altered levels of these mediators in drug-induced models of seizures and epilepsy. In the present study, we investigated the production of cytokines and a neurotrophin in the brain of Wistar Audiogenic Rats (WAR), a genetic model of epilepsy, stimulated with high-intensity sound. Four hours after stimulation, animals were decapitated and the hippocampus, inferior colliculus, striatum and cortex were removed for evaluation of the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α and brain derived neurotrophic factor (BDNF). All the cytokines and BDNF levels were increased in the cortex. Increased levels of TNF-α and IL-6 were also observed in the striatum. Finally, TNF-α also increased in the inferior colliculus after the seizures induced by high-intensity sound. Although different studies have demonstrated that the levels of cytokines and BDNF increase in animal models of epilepsy induced by chemical stimuli, we provided here evidence that these mediators are also increased in WAR, a genetic model of epilepsy. Thus, the observed increase in these mediators might be involved in the pathophysiology of epilepsy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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33. Neuroinflammation and Neurodegeneration: Pinpointing Pathological and Pharmacological Targets.
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de Oliveira AC, Candelario-Jalil E, Fiebich BL, Santos Mda S, Palotás A, and dos Reis HJ
- Subjects
- Animals, Humans, Inflammation complications, Nerve Degeneration complications, Neurodegenerative Diseases drug therapy, Neurodegenerative Diseases pathology, Inflammation drug therapy, Inflammation pathology, Nerve Degeneration drug therapy, Nerve Degeneration pathology, Nervous System pathology
- Published
- 2015
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34. Apolipoprotein polymorphism is associated with pro-thrombotic profile in non-demented dyslipidemic subjects.
- Author
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Ferreira CN, Carvalho MG, Gomes KB, Reis HJ, Fernandes AP, Palotás A, and Sousa MO
- Subjects
- Adult, Apolipoprotein A-V, Dementia epidemiology, Dementia genetics, Female, Humans, Male, Middle Aged, Apolipoproteins A genetics, Apolipoproteins E genetics, Dyslipidemias complications, Genetic Predisposition to Disease, Polymorphism, Genetic, Thrombosis epidemiology, Thrombosis genetics
- Abstract
Apolipoprotein gene polymorphism has an important role in lipid metabolism and in the development of cerebro- and cardio-vascular disease (CCVD), including dementia. Dyslipidemia and hemostatic abnormalities are key risk factors associated with athero-sclerotic events preceding CCVD. The aim of this study was to evaluate the possible relationships of various apolipoprotein-species with hemostatic parameters and cognitive function. Lipid profile, gene polymorphism, coagulation markers, and mini-mental state examination (MMSE) scores were assessed in 109 dys-lipidemic subjects and in 107 healthy control volunteers. Thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels were significantly higher in apolipoprotein-E2 (apoE2) patients when compared to other apoE forms. The apoA5 -1131T>C polymorphism was associated with elevated D-dimer concentration in dyslipidemic TT homozygous individuals. MMSE did not correlate with lipid or coagulation profile. These data suggest that apoE and apoA5 variants have an effect on hemostatic parameters, but they neither influence nor predict cognitive performance in non-demented individuals., (© 2014 by the Society for Experimental Biology and Medicine.)
- Published
- 2015
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35. Hyper-coagulable profile with elevated pro-thrombotic biomarkers and increased cerebro- and cardio-vascular disease risk exist among healthy dyslipidemic women.
- Author
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Ferreira CN, Carvalho MG, Reis HJ, Gomes KB, Sousa MO, and Palotás A
- Subjects
- Adult, Coronary Artery Disease complications, Dyslipidemias complications, Enzyme-Linked Immunosorbent Assay, Female, Fibrin Fibrinogen Degradation Products analysis, Humans, Intracranial Arteriosclerosis complications, Male, Middle Aged, Peptide Fragments, Prothrombin, Risk Factors, Biomarkers blood, Coronary Artery Disease blood, Dyslipidemias blood, Intracranial Arteriosclerosis blood, Thrombophilia complications
- Abstract
Dyslipidemia is one of the pathognomonic elements of athero-genesis, as well as cerebro- and cardio-vascular disease (CCVD). Hemostatic factors are also involved in athero-sclerosis and ischemic changes, however their relationship with disrupted lipid homeostasis is not well characterized. The aim of this study was to determine the coagulation state of dyslipidemic patients and to evaluate their association with CCVD risk factors. Biochemical and hematological parameters, as well as neuro-psychiatric profile of 109 dyslipidemic subjects and 107 normo-lipidic healthy volunteers were assessed. Serum bio-marker levels and cognitive performance generally did not differ in the groups, but prothrombin fragment 1+2 (F1+2) and D-dimer concentrations were markedly higher among women. Hyper-coagulability was not associated with dyslipidemia, but was correlated with the female gender, which might pose an increased thromboembolic risk in asymptomatic women.
- Published
- 2014
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36. The astrocyte marker Aldh1L1 does not reliably label enteric glial cells.
- Author
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Boesmans W, Rocha NP, Reis HJ, Holt M, and Vanden Berghe P
- Subjects
- Aldehyde Dehydrogenase genetics, Aldehyde Dehydrogenase 1 Family, Aldehyde Dehydrogenase, Mitochondrial, Animals, Biomarkers metabolism, Enteric Nervous System cytology, Female, Male, Mice, Transgenic, Myenteric Plexus cytology, Myenteric Plexus enzymology, Neurons enzymology, Promoter Regions, Genetic, Aldehyde Dehydrogenase metabolism, Astrocytes enzymology, Enteric Nervous System enzymology, Neuroglia enzymology
- Abstract
Enteric glial cells are increasingly acknowledged as important partners of enteric neurons in the control of gastrointestinal function. They share morphological features and expression of antigenic markers with astrocytes of the central nervous system. Recently, aldehyde dehydrogenase 1 family member L1 (Aldh1L1) has been proposed as a novel and specific marker for astrocytes. Taking the known similarities between astrocytes and enteric glia into account, we sought to investigate whether enteric glial cells also express Aldh1L1. To this end, we performed immunostaining on preparations of myenteric plexus obtained from adult Aldh1L1-eGFP bacterial artificial chromosome (BAC) transgenic mice and found that the Aldh1L1 promoter is indeed active in enteric glia, albeit mainly in cells residing outside the myenteric ganglia. Apart from enteric glia, we also observed eGFP expression in interstitial cells of Cajal. Furthermore, myenteric ganglia of the large intestine contained eGFP positive neurons. Taken together, our data indicate that Aldh1L1 is not a suitable marker for enteric glial cells., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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37. Circulating levels of adipokines in Parkinson's disease.
- Author
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Rocha NP, Scalzo PL, Barbosa IG, de Sousa MS, Morato IB, Vieira EL, Christo PP, Reis HJ, and Teixeira AL
- Subjects
- Aged, Biomarkers blood, Female, Humans, Male, Middle Aged, Adipokines blood, Body Mass Index, Parkinson Disease blood, Parkinson Disease diagnosis
- Abstract
Introduction: Adipokines are adipocyte-derived secretory factors, which have functions in satiety, energetic homeostasis, insulin sensitivity, vascular disease and also immune response. Parkinson's disease (PD) has been associated with unintended weight loss and reduced prevalence of cardiovascular risk factors. In addition, inflammation has been proposed as one of the factors contributing to PD pathophysiology. Therefore, we sought to investigate if adipokine levels - adiponectin, leptin and resistin - are altered in PD patients. Also, we aimed to evaluate association between adipokine levels and clinical variables in PD., Methods: Forty PD patients and twenty-five age-, gender- and body mass index-matched controls were enrolled in this study. Peripheral blood was drawn and plasma levels of adiponectin, leptin and resistin were measured by Enzyme-Linked Immunosorbent Assay., Results: There was no significant difference between PD patients and controls regarding plasma levels of the evaluated adipokines. In PD patients, higher leptin levels were associated with increased age and body mass index. No other correlation was found between adipokine levels and clinical or demographic data., Conclusions: Although adipokines play important roles in inflammation, it seems that they are not implicated in the inflammatory response associated with PD., (Copyright © 2014 Elsevier B.V. All rights reserved.)
- Published
- 2014
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38. Plasma levels of soluble tumor necrosis factor receptors are associated with cognitive performance in Parkinson's disease.
- Author
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Rocha NP, Teixeira AL, Scalzo PL, Barbosa IG, de Sousa MS, Morato IB, Vieira EL, Christo PP, Palotás A, and Reis HJ
- Subjects
- Aged, Biomarkers blood, Cognition Disorders blood, Cognition Disorders complications, Executive Function physiology, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Parkinson Disease complications, Cognition physiology, Cognition Disorders diagnosis, Parkinson Disease blood, Parkinson Disease psychology, Receptors, Tumor Necrosis Factor blood
- Abstract
Inflammatory mechanisms have been implicated in a series of neuropsychiatric conditions, including behavioral disturbances, cognitive dysfunction, and affective disorders. Accumulating evidence also strongly suggests their involvement in the pathophysiology of Parkinson's disease (PD). This study aimed to evaluate plasma levels of inflammatory biomarkers, and their association with cognitive performance and other non-motor symptoms of PD. PD patients and control individuals were subjected to various psychometric tests, including the Mini-Mental State Examination (MMSE), Frontal Assessment Battery (FAB), and Beck's Depression Inventory (BDI). Biomarker plasma levels were measured by enzyme-linked immunosorbent assay (ELISA). PD patients exhibited worse performance on MMSE and the programming task of FAB, and presented higher soluble tumor necrosis factor receptor (sTNFR) plasma levels than control individuals. Among PD patients, increased sTNFR1 and sTNFR2 concentrations were associated with poorer cognitive test scores. After multiple linear regression, sTNFR1 and education remained a significant predictor for FAB scores. Our data suggest that PD is associated with a proinflammatory profile, and sTNFRs are putative biomarkers of cognitive performance, with elevated sTNFR1 levels predicting poorer executive functioning in PD patients., (© 2013 International Parkinson and Movement Disorder Society.)
- Published
- 2014
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39. Use of evidence-based interventions in acute coronary syndrome - Subanalysis of the ACCEPT registry.
- Author
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Wang R, Neuenschwander FC, Lima Filho A, Moreira CM, Santos ES, Reis HJ, Romano ER, Mattos LA, Berwanger O, and Andrade JP
- Subjects
- Adrenergic beta-Antagonists therapeutic use, Aged, Analysis of Variance, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Aspirin therapeutic use, Brazil, Female, Fibrinolytic Agents therapeutic use, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Male, Middle Aged, Myocardial Infarction drug therapy, Myocardial Reperfusion, Platelet Aggregation Inhibitors therapeutic use, Purinergic P2Y Receptor Antagonists therapeutic use, Time Factors, Treatment Outcome, Acute Coronary Syndrome drug therapy, Drug Prescriptions statistics & numerical data, Evidence-Based Medicine standards, Practice Guidelines as Topic standards
- Abstract
Background: The recommendations in guidelines are based on evidence; however, there is a gap between recommendations and clinical practice., Objective: To describe the practice of prescribing evidence-based treatments for patients with acute coronary syndrome in Brazil., Methods: This study carried out a subanalysis of the ACCEPT registry, assessing epidemiological data and the prescription rate of acetylsalicylic acid, p2y12 inhibitors, antithrombotic drugs, beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (IAT1RB), and statins. In addition, the quality of myocardial reperfusion in ST-segment elevation myocardial infarction was evaluated., Results: This study assessed 2,453 patients. The prescription rates of acetylsalicylic acid, p2y12 inhibitors, antithrombotic drugs, beta-blockers, angiotensin-converting enzyme inhibitors/IAT1RB, and statins were as follows: in 24 hours - 97.6%, 89.5%, 89.1%, 80.2%, 67.9% and 90.6%; and at six months - 89.3%, 53.6%, 0%, 74.4%, 57.6% and 85.4%, respectively. Regarding ST-segment elevation myocardial infarction, only 35.9% and 25.3% of the patients underwent primary angioplasty and thrombolysis, respectively, within the recommended times., Conclusion: This registry showed high initial prescription rates of antiplatelet drugs, antithrombotic drugs, and statins, and lower prescription rates of beta-blockers and angiotensin-converting enzyme inhibitors/IAT1RB. Independently of the class, the use of all drugs decreased by six months. Most patients with ST-segment elevation myocardial infarction did not undergo myocardial reperfusion within the time recommended.
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- 2014
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40. Reduced frequency of T lymphocytes expressing CTLA-4 in frontotemporal dementia compared to Alzheimer's disease.
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Santos RR, Torres KC, Lima GS, Fiamoncini CM, Mapa FC, Pereira PA, Rezende VB, Martins LC, Bicalho MA, Moraes EN, Reis HJ, Teixeira AL, and Romano-Silva MA
- Subjects
- Antigens, CD metabolism, B-Lymphocytes metabolism, Brazil, Female, HLA-DR Antigens metabolism, Humans, Male, Alzheimer Disease pathology, CTLA-4 Antigen metabolism, Frontotemporal Dementia pathology, T-Lymphocytes metabolism
- Abstract
Studies suggest that inflammation is involved in the neurodegenerative cascade of dementias. Immunological mechanisms may be part of the pathophysiological process in frontotemporal dementia (FTD), but up till now only vague evidence of such mechanisms has been presented. The B7- CD28/CTLA-4 pathway is an important immunological signaling pathway involved in modulation of T cell activation. The aim of this study was to compare the expression of molecules associated with co-stimulatory signaling in peripheral blood mononuclear cells (PBMC) of FTD to Alzheimer disease (AD) and control groups. Our results confirm the previous demonstrated increased expression of CD80 in CD14+ Alzheimer patients T cells but show, for the first time, a reduction in the expression of CTLA-4 in CD4+ FTD cells. As CTLA-4 is the most potent negative regulators of T-cell activation we speculated that peripheral T lymphocytes in FTD are more activated and this could be involved in the neurodegeneration observed in this dementia., (© 2013 Elsevier Inc. All rights reserved.)
- Published
- 2014
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41. Cognitive Status Correlates with CXCL10/IP-10 Levels in Parkinson's Disease.
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Rocha NP, Scalzo PL, Barbosa IG, Souza MS, Morato IB, Vieira EL, Christo PP, Teixeira AL, and Reis HJ
- Abstract
Cognitive impairment and depressive symptoms are of great interest in Parkinson's disease (PD), since they are very common and lead to increased disability with poor quality of life. Inflammatory mechanisms have been implicated in PD and its nonmotor symptoms. In the current pilot study, we aimed to evaluate plasma levels of chemokines in PD patients and to analyze the putative association of chemokines with depressive symptoms and cognitive performance. We hypothesized that higher chemokines levels are associated with worse cognitive performance and increased depressive symptoms in PD. For this purpose, 40 PD patients and 25 age- and gender-matched controls were subjected to a clinical evaluation including cognitive and mood tests. Peripheral blood was drawn and plasma levels of CCL2/MCP-1, CCL11/eotaxin, CCL24/eotaxin-2, and CXCL10/IP-10 were measured by enzyme-linked immunosorbent assay. PD patients and control individuals presented comparable plasma concentrations of all the evaluated chemokines. In PD patients, CXCL10/IP-10 plasma levels correlated positively with Hoehn and Yahr staging scale. In addition, the higher CXCL10/IP-10 levels, the worse performance on cognitive tests. Although there was no significant difference between PD patients and control individuals regarding chemokines levels, our preliminary results showed that CXCL10/IP-10 may be associated with cognitive status in PD.
- Published
- 2014
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42. Depression and cognitive impairment in Parkinson's disease: a role for inflammation and immunomodulation?
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Pessoa Rocha N, Reis HJ, Vanden Berghe P, and Cirillo C
- Subjects
- Animals, Humans, Parkinson Disease complications, Cognition Disorders immunology, Depression immunology, Immunomodulation immunology, Inflammation immunology, Parkinson Disease immunology
- Abstract
The etiology of Parkinson's disease (PD) is complex and not fully understood, most probably because of the multiplicity of factors involved. Inflammatory and abnormal immune responses have been hypothesized to play a crucial role in PD. Not only in the brain, but also peripherally, inflammation is believed to contribute to the onset and progression of the neurodegenerative process seen in PD. Furthermore, increased inflammatory responses have been described both in the brain and peripheral blood of PD subjects. Although PD is considered a motor disorder, nonmotor symptoms are extremely frequent and disabling. Cognitive impairment and mood alterations are such symptoms that deserve increased attention since on the one hand they can appear even before typical motor disturbances are recognized, and on the other hand they are associated with high morbidity and mortality. A growing body of evidence suggests the existence of a link between inflammatory-immune responses and the occurrence of depression and cognitive impairment in PD patients. However, not all data are equally conclusive and are sometimes even conflicting. The aim of this brief review is to give an overview of the possible role that inflammation and immunomodulation may play in PD together with their putative impact on mood and cognitive alterations. What clearly emerges from this work is the fact that studies performed until now lack standardized and comparable methods to analyze both clinical and biological parameters. It is thus difficult to conclusively link mood and cognitive changes to underlying pathological mechanisms. Additional studies in this direction are warranted to convincingly establish or refute any causative relation., (© 2014 S. Karger AG, Basel.)
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- 2014
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43. Human cognitive and neuro-psychiatric bio-markers in the cardiac peri-operative patient.
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Reis HJ, de Oliveira AC, Mukhamedyarov MA, Zefirov AL, Rizvanov AA, Yalvaç ME, Teixeira AL, Janka Z, Hussain A, Vieira LB, and Palotás A
- Subjects
- Animals, Biomarkers metabolism, Cognition Disorders etiology, Delirium etiology, Heart Diseases metabolism, Humans, Perioperative Period, Risk Factors, Cardiac Surgical Procedures adverse effects, Cognition Disorders metabolism, Delirium metabolism, Heart Diseases surgery
- Abstract
Some of the complexities of surgical interventions include neurological and psychiatric disturbances. Prompt identification and early treatment of these complications are pivotal in achieving excellent clinical results. Recognizing major adverse events such as stroke, seizure or delirium is usually straight-forward, however the discovery of less frequent or more subtle post-operative changes such as cognitive dysfunction might be delayed due to lack of appropriate diagnostic tools. This review summarizes biological markers that can be utilized as surrogates in evaluating surgery-related neuro-psychiatric disorders.
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- 2014
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44. Acute coronary syndrome behavior: results of a Brazilian registry.
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Piegas LS, Avezum A, Guimarães HP, Muniz AJ, Reis HJ, Santos ES, Knobel M, and Souza Rd
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- Acute Coronary Syndrome complications, Acute Coronary Syndrome diagnosis, Adult, Age Distribution, Aged, Aged, 80 and over, Brazil epidemiology, Disease Management, Epidemiologic Methods, Female, Hospital Mortality, Hospitalization statistics & numerical data, Humans, Male, Medical Records statistics & numerical data, Middle Aged, Risk Factors, Sex Distribution, Young Adult, Acute Coronary Syndrome mortality, Acute Coronary Syndrome therapy, Registries statistics & numerical data
- Abstract
Background: Brazil lacks published multicenter registries of acute coronary syndrome., Objective: The Brazilian Registry of Acute Coronary Syndrome is a multicenter national study aiming at providing data on clinical aspects, management and hospital outcomes of acute coronary syndrome in our country., Methods: A total of 23 hospitals from 14 cities, participated in this study. Eligible patients were those who came to the emergency wards with suspected acute coronary syndrome within the first 24 hours of symptom onset, associated with compatible electrocardiographic alterations and/or altered necrosis biomarkers. Follow-up lasted until hospital discharge or death, whichever occurred first., Results: Between 2003 and 2008, 2,693 ACS patients were enrolled, of which 864 (32.1%) were females. T he final diagnosis was unstable angina in 1,141 patients, (42.4%), with a mortality rate of 3.06%, non-ST elevation acute myocardial infarction (AMI) in 529 (19.6%), with mortality of 6.8%, ST-elevation AMI 950 (35.3%), with mortality of 8.1% and non-confirmed diagnosis 73 (2.7%), with mortality of 1.36%. The overall mortality was 5.53%. The multiple logistic regression model identified the following as risk factors for death regarding demographic factors and interventions: female gender (OR=1.45), diabetes mellitus (OR=1.59), body mass index (OR=1.27) and percutaneous coronary intervention (OR=0.70). A second model for death due to major complications identified: cardiogenic shock/acute pulmonary edema (OR=4.57), reinfarction (OR=3.48), stroke (OR=21.56), major bleeding (OR=3.33), cardiopulmonary arrest (OR=40.27) and Killip functional class (OR=3.37)., Conclusion: The Brazilian Registry of Acute Coronary Syndrome data do not differ from other data collected abroad. The understanding of their findings may help promote better planning and management of acute coronary syndrome care in public and private health services.
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- 2013
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45. Chemokines in bipolar disorder: trait or state?
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Barbosa IG, Rocha NP, Bauer ME, de Miranda AS, Huguet RB, Reis HJ, Zunszain PA, Horowitz MA, Pariante CM, and Teixeira AL
- Subjects
- Adult, Affect physiology, Case-Control Studies, Disease Progression, Enzyme-Linked Immunosorbent Assay, Female, Humans, Logistic Models, Male, Middle Aged, Bipolar Disorder immunology, Chemokines immunology, Inflammation immunology
- Abstract
Recent evidence has suggested that inflammatory and immune mechanisms may play a role in the pathophysiology of bipolar disorder (BD). Only a few studies have assessed the profile of chemokines, a family of chemotactic cytokines related to the recruitment of leukocytes, in BD. The objective of our study was to evaluate the plasma levels of chemokines in BD patients in different mood states in comparison with healthy controls. Seventy BD type I patients (35 in euthymia and 35 in mania), and 50 healthy controls matched by age, gender, and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatry Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of CCL2, CCL3, CCL11, CCL24, CXCL8, and CXCL10 were measured by enzyme-linked immunosorbent assay. BD patients presented higher plasma levels of CCL11 (1.69-fold increase; p < 0.001), CCL24 (1.40-fold increase; p = 0.02), CXCL10 (1.45-fold increase; p < 0.001) and decreased plasma levels of CXCL8 (8.68-fold decrease p < 0.001). Logistic regression stressed the main effect of increased plasma levels of CXCL10 (OR = 1.009, 95 % CI = 1.000-1.018, p = 0.042) and CCL11 (OR = 1.002, 95 % CI = 1.001-1.003, p = 0.003) and decreased plasma levels of CXCL8 (OR = 0.995, 95 % CI = 0.990-0.999, p = 0.013) to BD. This study reinforces the view that BD is associated with an immune dysfunction.
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- 2013
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46. Increased BDNF levels in long-term bipolar disorder patients.
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Barbosa IG, Rocha NP, Miranda AS, Huguet RB, Bauer ME, Reis HJ, and Teixeira AL
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- Age Factors, Biomarkers blood, Bipolar Disorder physiopathology, Case-Control Studies, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Neuropsychological Tests, Time Factors, Bipolar Disorder blood, Brain-Derived Neurotrophic Factor blood
- Abstract
Introduction: Bipolar disorder (BD) is a prevalent, chronic and progressive illness. There is a growing body of evidence indicating that brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of BD., Objective: The aim of this study was to evaluate BDNF plasma levels in BD patients with long term illness in comparison with controls., Methods: 87 BD type I patients and 58 controls matched by age, gender and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of BDNF were measured by ELISA., Results: On average, patients had suffered from BD for 23.4 years. In comparison with controls, BD patients with mania presented a 1.90-fold increase in BDNF plasma levels (p = .001), while BD patients in remission presented a 1.64-fold increase in BDNF plasma levels (p = .03). BDNF plasma levels were not influenced by age, length of illness or current medications., Conclusions: The present study suggests that long-term BD patients exhibit increased circulating levels of BDNF.
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- 2013
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47. Clinical outcomes at 30 days in the Brazilian Registry of Acute Coronary Syndromes (ACCEPT).
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Piva e Mattos LA, Berwanger O, Santos ES, Reis HJ, Romano ER, Petriz JL, Sousa AC, Neuenschwander FC, Guimarães JI, and Andrade JP
- Subjects
- Acute Coronary Syndrome therapy, Age Distribution, Aged, Brazil epidemiology, Female, Humans, Male, Middle Aged, Myocardial Revascularization statistics & numerical data, Prospective Studies, Risk Factors, Sex Distribution, Time Factors, Treatment Outcome, Acute Coronary Syndrome epidemiology, Medical Records statistics & numerical data, Registries statistics & numerical data
- Abstract
Background: There are few registries documenting clinical practice in Brazilian patients with acute coronary syndrome., Objectives: Demography description, occurrence of major clinical adverse events and comparative analysis in patients submitted or not to an invasive strategy (coronary angiography and myocardial revascularization) in a Brazilian multicenter registry of acute coronary syndrome., Methods: The ACCEPT/SBC registry prospectively collected data on acute coronary syndrome patients from 47 Brazilian hospitals. The current analysis reports the occurrence of major clinical outcomes and according to the performance or not of a procedure for myocardial revascularization at the end of 30 day follow-up., Results: Between August 2010 and December 2011, 2.485 patients were enrolled in this registry. Of these, 31.6% had unstable angina, 34.9% and 33.4% had acute coronary syndrome without and with ST-segment elevation. At 30 days, the performance of a myocardial revascularization procedure was progressively higher according to the severity of clinical presentation (38.7% vs. 53.6% vs. 77.7%, p < 0.001). Cardiac mortality among those submitted or not to myocardial revascularization procedure was 1.0% vs. 2.3% (p = 0.268), 1.9% vs. 4.2% (p = 0.070) and 2.0% vs. 8.1% (p < 0.001), in those with unstable angina, acute coronary syndrome without and with ST-segment elevation, respectively., Conclusions: The prescription of a myocardial revascularization procedure was progressively more frequent according to the severity of clinical presentation; for those treated during acute coronary syndrome without and with ST-segment elevation, there was a trend and significant decrease in mortality rate at 30 day of follow-up, respectively.
- Published
- 2013
- Full Text
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48. Andes-virus-induced cytokine storm is partially suppressed by ribavirin.
- Author
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Khaiboullina SF, Rizvanov AA, Lombardi VC, Morzunov SP, Reis HJ, Palotás A, and St Jeor S
- Subjects
- Animals, Chemokine CCL5 metabolism, Chlorocebus aethiops, Dose-Response Relationship, Drug, Gene Expression Regulation, Orthohantavirus physiology, Human Umbilical Vein Endothelial Cells cytology, Human Umbilical Vein Endothelial Cells drug effects, Human Umbilical Vein Endothelial Cells virology, Humans, Interleukin-6 genetics, Interleukin-6 metabolism, NF-kappa B metabolism, Tumor Necrosis Factor-alpha metabolism, Vero Cells, Viral Load drug effects, Antiviral Agents pharmacology, Chemokine CCL5 genetics, Orthohantavirus drug effects, NF-kappa B genetics, Ribavirin pharmacology, Tumor Necrosis Factor-alpha genetics
- Abstract
Background: Microbe-induced over-activation of cytokines, especially tumour necrosis factor (TNF)-α, is key to the pathogenesis of hantavirus infection leading to severe inflammation with high mortality rate. Although ribavirin showed promise in inhibiting viral replication in vitro, its clinical efficacy remains controversial., Methods: Various concentrations of ribavirin were used to determine its effect on cytokine activation in our infectious model system., Results: Ribavirin decreased the virus load and dose-dependently inhibited the accumulation of RANTES messenger RNA in Andes-virus (ANDV)-infected human endothelial cells, but failed to suppress TNF-α-induced activation of RANTES and interleukin-6 in ANDV-inoculated cultures. This report also shows, for the first time, that the deleterious over-stimulation by TNF-α is mediated by nuclear factor-κB, and describes the effect of ribavirin on cytokine production following ANDV infection., Conclusions: Although highly effective in preventing ANDV replication and suppressing activation of select inflammatory mediators, the therapeutic efficacy of ribavirin is limited due to its inability to fully inhibit cytokine outburst triggered by hantavirus infection.
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- 2013
- Full Text
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49. Disease-specific expression of the serotonin-receptor 5-HT(2C) in natural killer cells in Alzheimer's dementia.
- Author
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Martins LC, Rocha NP, Torres KC, Dos Santos RR, França GS, de Moraes EN, Mukhamedyarov MA, Zefirov AL, Rizvanov AA, Kiyasov AP, Vieira LB, Guimarães MM, Yalvaç ME, Teixeira AL, Bicalho MA, Janka Z, Romano-Silva MA, Palotás A, and Reis HJ
- Subjects
- Aged, Aged, 80 and over, B-Lymphocytes metabolism, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Depression metabolism, Female, Humans, Leukocytes, Mononuclear metabolism, Male, Receptors, Dopamine D3 biosynthesis, Receptors, Dopamine D4 biosynthesis, Receptors, Serotonin biosynthesis, Alzheimer Disease metabolism, Killer Cells, Natural metabolism, Receptor, Serotonin, 5-HT2C biosynthesis
- Abstract
Alzheimer's dementia (AD) is a degenerative brain disorder characterized mainly by cholinergic failure, but other neuro-transmitters are also deficient especially at late stages of the disease. Misfolded β-amyloid peptide has been identified as a causative agent, however inflammatory changes also play a pivotal role. Even though the most prominent pathology is seen in the cognitive functions, specific abnormalities of the central nervous system (CNS) are also reflected in the periphery, particularly in the immune responses of the body. The aim of this study was to characterize the dopaminergic and serotonergic systems in AD, which are also markedly disrupted along with the hallmark acetyl-choline dysfunction. Peripheral blood mono-nuclear cells (PBMCs) from demented patients were judged against comparison groups including individuals with late-onset depression (LOD), as well as non-demented and non-depressed subjects. Cellular sub-populations were evaluated by mono-clonal antibodies against various cell surface receptors: CD4/CD8 (T-lymphocytes), CD19 (B-lymphocytes), CD14 (monocytes), and CD56 (natural-killer (NK)-cells). The expressions of dopamine D(3) and D(4), as well as serotonin 5-HT(1A), 5-HT(2A), 5-HT(2B) and 5-HT(2C) were also assessed. There were no significant differences among the study groups with respect to the frequency of the cellular sub-types, however a unique profound increase in 5-HT(2C) receptor exclusively in NK-cells was observed in AD. The disease-specific expression of 5-HT(2C), as well as the NK-cell cyto-toxicity, has been linked with cognitive derangement in dementia. These changes not only corroborate the existence of bi-directional communication between the immune system and the CNS, but also elucidate the role of inflammatory activity in AD pathology, and may serve as potential biomarkers for less invasive and early diagnostic purposes as well., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
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50. Differential effects of swimming training on neuronal calcium sensor-1 expression in rat hippocampus/cortex and in object recognition memory tasks.
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Drumond LE, Mourão FA, Leite HR, Abreu RV, Reis HJ, Moraes MF, Pereira GS, and Massensini AR
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- Animals, Immunoblotting, Male, Rats, Rats, Wistar, Swimming, Cerebral Cortex metabolism, Hippocampus metabolism, Memory physiology, Neuronal Calcium-Sensor Proteins biosynthesis, Neuropeptides biosynthesis, Physical Conditioning, Animal physiology, Recognition, Psychology physiology
- Abstract
Physical activity has been proposed as a behavioral intervention that improves learning and memory; nevertheless, the mechanisms underlying these health benefits are still not well understood. Neuronal Calcium Sensor-1 (NCS-1) is a member of a superfamily of proteins that respond to local Ca(2+) changes shown to have an important role in learning and memory. The aim of the present study was to investigate the effects of swimming training on NCS-1 levels in the rat brain after accessing cognitive performance. Wistar rats were randomly assigned to sedentary (SG) or exercised groups (EG). The EG was subject to forced swimming activity, 30 min/day, 5 days/week, during 8 weeks. Progressive load trials were performed in the first and last week in order to access the efficiency of the training. After the 8 week training protocol, memory performance was evaluated by the novel object preference and object location tasks. NCS-1 levels were measured in the cortex and hippocampus using immunoblotting. The EG performed statistically better for the spatial short-term memory (0.73 ± 0.01) when compared to the SG (0.63 ± 0.02; P<0.05). No statistically significant exercise-effect was observed in the novel object preference task (SG 0.65 ± 0.02 and EG 0.68 ± 0.02; p>0.05). In addition, chronic exercise promoted a significant increase in hippocampal NCS-1 levels (1.8 ± 0.1) when compared to SG (1.17 ± 0.08; P<0,05), but had no effect on cortical NCS-1 levels (SG 1.6 ± 0.1 and EG 1.5 ± 0.1; p>0.05). Results suggest that physical exercise would modulate the state of the neural network regarding its potential for plastic changes: physical exercise could be modulating NCS-1 in an activity dependent manner, for specific neural substrates, thus enhancing the cellular/neuronal capability for plastic changes in these areas; which, in turn, would differentially effect ORM task performance for object recognition and displacement., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2012
- Full Text
- View/download PDF
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