BENEFÍCIOS DA FACILITAÇÃO NEUROMUSCULAR PROPRIOCEPTIVA EM MULHERES MASTECTOMIZADAS: UM ESTUDO PILOTO

O carcinoma mamário pode ser tratado de diversas formas, incluindo a mastectomia. A mastectomia é caracterizada como uma cirurgia total ou parcial da mama, podendo ou não ser associada à excisão dos gânglios linfáticos axilares. Podem aparecer sequelas e complicações no período pós-operatório. A facilitação neuromuscular proprioceptiva (FNP) é uma técnica de abordagem global em que procedimentos básicos da facilitação permitem ao terapeuta ajudar seus pacientes a atingir o máximo da sua função motora eficiente. O objetivo deste estudo foi avaliar os efeitos do Método de FNP em mulheres pós mastectomizadas. No estudo foram utilizadas quatro pacientes pós-mastectomizadas, tratadas com a técnica de FNP. Foram realizadas 10 sessões de 30 minutos. Na primeira e última sessão foram aplicadas as técnicas de avaliação: perimetria (linfedema), dinamometria (força muscular) e goniometria (amplitude articular). Os resultados da avaliação do linfedema demonstram que pode haver redução do edema com a aplicação da técnica de FNP, os quais demonstraram diferença apenas em membro superior direito. Nenhum dos testes apresentou diferença significativa. Porém, mais estudos são necessários para verificar os efeitos da técnica FNP em mulheres mastectomizadas.Palavras-chave: Carcinoma mamário; FNP; fisioterapia

Synthesis of Novel Selenocyanates and Evaluation of Their Effect in Cultured Mouse Neurons Submitted to Oxidative Stress

Herein, we report the synthesis of novel selenocyanates and assessment of their effect on the oxidative challenge elicited by hydrogen peroxide (H2O2) in cultured mouse neurons. First, α-methylene-β-hydroxy esters were prepared as precursors of allylic bromides. A reaction involving the generated bromides and sodium selenocyanate was conducted to produce the desired selenocyanates (3a-f). We next prepared cultures of neurons from 7-day-old mice (n=36). H2O2 (10-5 M) was added into the culture flasks as an oxidative stress inducer, alone or combined with one of each designed compounds. (PhSe)2 was used as a positive control. It was carried out assessment of lipid (thiobarbituric acid reactive species, 4-hydroxy-2′-nonenal, 8-isoprostane), DNA (8-hydroxy-2′-deoxyguanosine), and protein (carbonyl) modification parameters. Finally, catalase and superoxide dismutase activities were also evaluated. Among the compounds, 3b, 3d, and 3f exhibited the most pronounced pattern of antioxidant activity, similar to (PhSe)2. These novel aromatic selenocyanates could be promising to be tried in most sophisticated in vitro studies or even at the preclinical level

Synthesis of Novel Selenocyanates and Evaluation of Their Effect in Cultured Mouse Neurons Submitted to Oxidative Stress

Herein we report the synthesis of novel selenocyanates and assessment of their effect on the oxidative challenge elicited by hydrogen peroxide (H2O2) in cultured mouse neurons. First, α-methylene-β-hydroxy esters were prepared as precursors of allylic bromides. A reaction involving the generated bromides and sodium selenocyanate was conducted to produce the desired selenocyanates (3a-f). We next prepared cultures of neurons from 7-day-old-mice (n = 36). H2O2 (10⁻5 M) was added into the culture flasks as an oxidative stress inducer, alone or combined with one of each designed compounds. PhSe)2 was used as positive control. It was carried out assessment of lipid (thiobarbituric acid reactive species, 4-hydroxy-2’-nonenal, 8-isoprostane), DNA (8-hydroxy-2’-deoxyguanosine) and protein (carbonyl) modification parameters. Finally, catalase and superoxide dismutase activities were also evaluated. Among the compounds, 3b, 3d and 3f exhibited the most pronounced pattern of antioxidant activity, similar to (PhSe)2. These novel aromatic selenocyanates could be promising to be tried in most sophisticated in vitro studies or even at preclinical level.</p

HDAC inhibitors reverse mania-like behavior and modulate epigenetic regulatory enzymes in an animal model of mania induced by Ouabain

Background: The etiology of bipolar disorder (BD) is multifactorial, involving both environmental and genetic factors. Current pharmacological treatment is associated with several side effects, which are the main reason patients discontinue treatment. Epigenetic alterations have been studied for their role in the pathophysiology of BD, as they bridge the gap between gene and environment. Objective: Evaluate the effects of histone deacetylase inhibitors on behavior and epigenetic enzymes activity in a rat model of mania induced by ouabain. Methods: Adult male rats were subjected to a single intracerebroventricular injection of ouabain (10 M) followed by 7 days of valproate (200 mg/kg) or sodium butyrate (600 mg/kg) administration. Locomotor and exploratory activities were evaluated in the open-field test. Histone deacetylase, DNA methyltransferase, and histone acetyltransferase activity were assessed in the frontal cortex, hippocampus, and striatum. Results: Ouabain induced hyperactivity in rats, which was reversed by valproate and sodium butyrate treatment. Ouabain did not alter the activity of any of the enzymes evaluated. However, valproate and sodium butyrate decreased the activity of histone deacetylase and DNA methyltransferase. Moreover, there was a positive correlation between these two enzymes. Conclusion: These results suggest that targeting epigenetic mechanisms may play an important role in mania-like behavior management

Effects of co-administration of lithium and celecoxib on inflammatory parameters in an animal model of mania induced by amphetamine

Artigo apresentado como requisito parcial para obtenção do grau de Bacharel, no Curso de Medicina, da Universidade do Extremo Sul Catarinense- UNESC.It is observed alterations in levels of inflammatory mediatorsin Bipolar Disorder (BD) patients.Celecoxib (Cel) is an anti-inflammatory drug and can reduce levels of pro-inflammatory cytokines. The present study aimed to evaluate the effects of co-administration of lithium(Li) and Cel on inflammatory parameters in an animal model of mania induced by amphetamine. Were used Wistar rats, 60 days old (250–350g). The animals (n=10 per group) received D-amph (2mg/kg) or Sal intraperitoneally once a day, during 14 days. From the day 8–14, the animals from D-amph and Sal groups received via gavage Li (24 mg/kg), Cel (20 mg/kg), Li + Cel or water. The behavioral analyses were evaluated through Open Field test. Furthermore, were evaluated the levels of IL-1β, IL-4, IL-10, and TNF-α. The administration of D-amph induced hyperactivity in the rats and treatment with Li plus Cel reversed these alterations. The administration of D-amph increased the IL-4, IL-10, and TNF-α levels in the serum, frontal cortex, and striatum of rats, and treatment with Li plus Cel reversed these alterations in all tissue evaluated. The treatment with Li plus Celshowed very effective against inflammation induced by D-amph. However, more studies are necessaries to elucidate these mechanisms

Effects of co-administration of lithium and celecoxib on inflammatory parameters in an animal model of mania induced by amphetamine

Artigo apresentado como requisito parcial para obtenção do grau de Bacharel, no Curso de Medicina, da Universidade do Extremo Sul Catarinense- UNESC.It is observed alterations in levels of inflammatory mediatorsin Bipolar Disorder (BD) patients.Celecoxib (Cel) is an anti-inflammatory drug and can reduce levels of pro-inflammatory cytokines. The present study aimed to evaluate the effects of co-administration of lithium(Li) and Cel on inflammatory parameters in an animal model of mania induced by amphetamine. Were used Wistar rats, 60 days old (250–350g). The animals (n=10 per group) received D-amph (2mg/kg) or Sal intraperitoneally once a day, during 14 days. From the day 8–14, the animals from D-amph and Sal groups received via gavage Li (24 mg/kg), Cel (20 mg/kg), Li + Cel or water. The behavioral analyses were evaluated through Open Field test. Furthermore, were evaluated the levels of IL-1β, IL-4, IL-10, and TNF-α. The administration of D-amph induced hyperactivity in the rats and treatment with Li plus Cel reversed these alterations. The administration of D-amph increased the IL-4, IL-10, and TNF-α levels in the serum, frontal cortex, and striatum of rats, and treatment with Li plus Cel reversed these alterations in all tissue evaluated. The treatment with Li plus Celshowed very effective against inflammation induced by D-amph. However, more studies are necessaries to elucidate these mechanisms

The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization: implications to the animal model of bipolar disorder

Background: Bipolar disorder (BD) and substance use disorders share common symptoms, such as behavioral sensitization. Amphetamine-induced behavioral sensitization can serve as an animal model of BD. Neurotrophic factors have an important role in BD pathophysiology. This study evaluated the effects of amphetamine sensitization on behavior and neurotrophic factor levels in the brains of rats.Methods: Wistar rats received daily intraperitoneal (i.p) injections of dextroamphetamine (D-AMPH) 2 mg/kg or saline for 14 days. After seven days of withdrawal, the animals were challenged with D-AMPH (0.5 mg/kg, i.p) and locomotor behavior was assessed. In a second protocol, rats were similarly treated with D-AMPH (2 mg/kg, i.p) for 14 days. After withdrawal, without D-AMPH challenge, depressive-and anxiety-like behaviors were evaluated through forced swimming test and elevated plus maze. Levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), neurotrophin 4/5 (NT-4/5) and glial-derived neurotrophic factor (GDNF) were evaluated in the frontal cortex, hippocampus, and striatum.Results: D-AMPH for 14 days augmented locomotor sensitization to a lower dose of D-AMPH (0.5 mg/kg) after the withdrawal. D-AMPH withdrawal induced depressive-and anxious-like behaviors. BDNF, NGF, and GDNF levels were decreased, while NT-3 and NT-4 levels were increased in brains after D-AMPH sensitization.Limitations: Although D-AMPH induces manic-like behavior, the mechanisms underlying these effects can also be related to phenotypes of drug abuse.Conclusions: Together, vulnerability to mania-like behavior following D-AMPH challenge and extensive neurotrophic alterations, suggest amphetamine-induced behavioral sensitization is a good model of BD pathophysiology

Role of epigenetic regulatory enzymes in animal models of mania induced by amphetamine and paradoxical sleep deprivation

It is known that bipolar disorder has a multifactorial aetiology where the interaction between genetic and environmental factors is responsible for its development. Because of this, epigenetics has been largely studied in psychiatric disorders. The present study aims to evaluate the effects of histone deacetylase inhibitors on epigenetic enzyme alterations in rats or mice submitted to animal models of mania induced by dextro-amphetamine or sleep deprivation, respectively. Adult male Wistar rats were subjected to 14\ua0days of dextro-amphetamine administration, and from the eighth to the fourteenth day, the animals were treated with valproate and sodium butyrate in addition to dextro-amphetamine injections. Adult C57BL/6 mice received 7\ua0days of valproate or sodium butyrate administration, being sleep deprived at the last 36\ua0hr of the protocol. Locomotor and exploratory activities of rats and mice were evaluated in the open-field test, and histone deacetylase, DNA methyltransferase, and histone acetyltransferase activities were assessed in the frontal cortex, hippocampus, and striatum. Dextro-amphetamine and sleep deprivation induced hyperactivity and increased histone deacetylase and DNA methyltransferase activities in the animal's brain. Valproate and sodium butyrate were able to reverse hyperlocomotion induced by both animal models, as well as the alterations on histone deacetylase and DNA methyltransferase activities. There was a positive correlation between enzyme activities and number of crossings for both models. Histone deacetylase and DNA methyltransferase activities also presented a positive correlation between theirselves. These results suggest that epigenetics can play an important role in BD pathophysiology as well as in its treatment

Efficacy of folic acid as an adjunct to lithium therapy on manic-like behaviors, oxidative stress and inflammatory parameters in an animal model of mania

Evaluate the efficacy of folic acid (FA) as a therapeutic adjunct to lithium (Li) on the manic-like behaviors as well as parameters of oxidative stress and inflammation in an animal model of mania induced by m-amphetamine (m-AMPH). Wistar rats first received m-AMPH or saline (NaCl 0.9%, Sal) for 14\ua0days. Between the 8th and 14th day, rats were treated with water, Li, FA or a combination of thereof drugs (Li + FA). Manic-like behaviors were assessed in the open-field test. Oxidative stress and inflammation parameters were assessed in the frontal cortex, striatum, and hippocampus. Administration of m-AMPH in rats significantly enhanced the exploratory and locomotor behaviors, as well as the risk-taking and stereotypic behaviors. Li + FA reversed these behavioral alterations elicited by m-AMPH. Administration of this psychostimulant also increased oxidative damage to lipids and proteins, whereas Li + FA reversed these oxidative damages. m-AMPH also induced an increase in the glutathione peroxidase (GPx) activity and a decrease in the glutathione reductase (GR) activity. Li + FA reversed the alteration in GR activity, but not in GPx activity. In addition, m-AMPH increased the IL-1β and TNF-α levels in the rat brain; Li + FA combined therapy reversed the alterations on these inflammatory parameters. FA administration per se reduced the increased TNF-α content induced by m-AMPH. Present study provides evidence that FA is effective as an adjunct to Li standard therapy on manic-like behaviors, oxidative stress and inflammatory parameters in a model of mania induced by m-AMPH

The Effects of Histone Deacetylase Inhibition on the Levels of Cerebral Cytokines in an Animal Model of Mania Induced by Dextroamphetamine

Studies have suggested the involvement of inflammatory processes in the physiopathology of bipolar disorder. Preclinical evidences have shown that histone deacetylase inhibitors may act as mood-stabilizing agents and protect the brain in models of mania and depression. The aim of the present study was to evaluate the effects of sodium butyrate (SB) and valproate (VPA) on behavioral changes, histone deacetylase activity, and the levels of cytokines in an animal model of mania induced by dextroamphetamine (d-AMPH). Wistar rats were first given d-AMPH or saline (Sal) for a period of 14 days, and then, between the 8th and 14th days, the rats were treated with SB, VPA, or Sal. The activity of histone deacetylase and the levels of cytokines (interleukin (IL) IL-4, IL-6, and IL-10 and tumor necrosis factor-alpha (TNF-alpha)) were evaluated in the frontal cortex and striatum of the rats. The administration of d-AMPH increased the activity of histone deacetylase in the frontal cortex. Administration of SB or VPA decreased the levels of histone deacetylase activity in the frontal cortex and striatum of rats. SB per se increased the levels of cytokines in both of the brain structures evaluated. AMPH increased the levels of cytokines in both of the brain structures evaluated, and VPA reversed this alteration. The effects of SB on d-AMPH-induced cytokine alterations were dependent on the brain structure and the cytokine evaluated. Despite VPA and SB having a similar mechanism of action, both being histone deacetylase inhibitors, they showed different effects on the levels of cytokines. The present study reinforces the need for more research into histone deacetylase inhibitors being used as a possible target for new medications in the treatment of bipolar disorder.Univ Southern Santa Catarina UNESC Univ, Hlth Sci Unit, Grad Program Hlth Sci, Lab Neuronal Signaling & Psychopharmacol, Criciuma, SC, BrazilUniv Southern Santa Catarina UNESC, Hlth Sci Unit, Grad Program Hlth Sci, Lab Neurosci, Criciuma, SC, BrazilUniv Fed Ceara, Translat Psychiat Res Grp, Fac Med, Fortaleza, Ceara, BrazilUniv Fed Ceara, Fac Med, Dept Clin Med, Fortaleza, Ceara, BrazilUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, BrazilHCPA, Lab Mol Psychiat, Bipolar Disorder Program, Porto Alegre, RS, BrazilUniv Texas Hlth Sci Ctr Houston UTHlth, Sch Med, Translat Psychiat Program, Dept Psychiat & Behav Sci, Houston, TX USAUniv Texas Hlth Sci Ctr Houston UTHlth, Sch Med, Ctr Excellence Mood Disorders, Dept Psychiat & Behav Sci, Houston, TX USAUniv Texas Houston, Grad Sch Biomed Sci, Neurosci Grad Program, Houston, TX USAUniv Fed Sao Paulo, Dept Psicobiol, Sao Paulo, BrazilWeb of Scienc