A novel antiplasmodial compound: integration of in silico and in vitro assays.

Malaria is a disease caused by Plasmodium genus. which P. falciparum is responsible for the most severe form of the disease, cerebral malaria. In 2018, 405,000 people died of malaria. Antimalarial drugs have serious adverse effects and limited efficacy due to multidrug-resistant strains. One way to overcome these limitations is the use of computational approaches for prioritizing candidates to phenotypic assays and/or in vitro assays against validated targets. Plasmodium falciparum Enoyl-ACP reductase (PfENR) is noteworthy because it catalyzes the rate-limiting step of the biosynthetic pathway of fatty acid. Thus, the study aimed to identify potential PfENR inhibitors by ligand (2D molecular similarity and pharmacophore models) and structure-based virtual screening (molecular docking). 2D similarity-based virtual screening using Tanimoto Index (> 0.45) selected 29,236 molecules from natural products subset available in ZINC database (n = 181,603). Next, 10 pharmacophore models for PfENR inhibitors were generated and evaluated based on the internal statistical parameters from GALAHAD™ and ROC/AUC curve. These parameters selected a suitable pharmacophore model with one hydrophobic center and two hydrogen bond acceptors. The alignment of the filtered molecules on best pharmacophore model resulted in the selection of 10,977 molecules. These molecules were directed to the docking-based virtual screening by AutoDock Vina 1.1.2 program. These strategies selected one compound to phenotypic assays against parasite. ZINC630259 showed EC50 = 0.12 ± 0.018 µM in antiplasmodial assays and selective index similar to other antimalarial drugs. Finally, MM/PBSA method showed stability of molecule within PfENR binding site (ΔGbinding=-57.337 kJ/mol).Communicated by Ramaswamy H. Sarma.

Use of psychotropic agents to treat agitation and aggression in Brazilian patients with Alzheimer's disease: A naturalistic and multicenter study.

We assessed psychotropic prescribing patterns in the clinical treatment of agitation and aggressive behavior in patients with Alzheimer's disease (AD) treated at specialist outpatient clinics in the Federal District of Brazil. This was a naturalistic, observational, multicenter study of a convenience sample of patients with AD (according to DSM-5) who had behavioral symptoms of aggression and/or agitation at outpatient visits, as assessed by the Neuropsychiatric Inventory (NPI), and required pharmacologic intervention. Participants were recruited in 2018-2019 from 11 AD treatment centers. Sociodemographic and clinical data were collected during routine visits. The sample consisted of 369 older adults with a mean age of 82.3 (SD, 7.7) years. The medications most commonly used in patients with behavioral disorders were antidepressants (79.1%), antipsychotics (70.2%), benzodiazepines (10.6%), and mood stabilizers (9.5%). Quetiapine was the most frequently prescribed antipsychotic medication (48.5%), at a mean dose of 57.4 (SD, 40.7) mg. Citalopram was the most widely used antidepressant medication (32.0%), at a mean daily dose of 24.1 (SD, 8.1) mg. In this sample, two or more pharmacologic agents were frequently used together to control aggression and agitation. Benzodiazepine was not frequently used.

Prevalência e fatores associados à síndrome da fragilidade no idoso do Distrito Federal / Prevalence and factors associated with the frailty syndrome in older adults in the Brazilian Federal District

INTRODUÇÃO: A síndrome da fragilidade no idoso (SFI) tem sido reconhecida como uma condição de vulnerabilidade fisiológica associada ao envelhecimento, resultante de uma reserva homeostática reduzida e da dificuldade do organismo em responder adequadamente ao estresse, característica altamente preditiva de uma variedade de desfechos clínicos adversos associados, que incluem declínio funcional, institucionalização e mortalidade. OBJETIVO: Identificar a prevalência e os fatores associados à SFI em população assistida por uma unidade ambulatorial de atenção secundária em centro especializado de atendimento em geriatria e gerontologia do Distrito Federal. MÉTODOS: Trata-se de um estudo observacional, descritivo, transversal e analítico realizado com idosos atendidos no centro especializado em geriatria e gerontologia da Secretaria de Saúde do Distrito Federal (SES/DF). Na avaliação dos idosos, foram coletados dados para identificação do perfil, capacidade funcional, informações referentes às multimorbidades e desfechos clínicos, como quedas. Os idosos também foram classificados na SFI pelos critérios de Fried. Para a análise estatística, utilizaram-se o teste de χ2 e a regressão de Poisson. RESULTADOS: No presente estudo, 24% da amostra total foi considerada frágil, 32,9% pré-frágil e 42,1% não frágil. Com relação aos aspectos sociodemográficos, houve associação de fragilidade com maior faixa etária e menor nível educacional. Diabetes, hipertensão arterial sistêmica, incontinência urinária, polifarmácia, depressão, quedas e alteração cognitiva tiveram associação com maior risco de fragilidade. CONCLUSÃO: Mediante os resultados obtidos, será possível definir medidas e estratégias para prevenção de morbimortalidade e proporcionar melhor qualidade de vida para os idosos.

INTRODUCTION: Frailty syndrome (FS) in older adults has been recognized as a physiological vulnerability condition associated with aging, resulting from reduced homeostatic reserve and a difficulty of the body to respond adequately to stress, a highly predictive feature of a variety of adverse clinical outcomes including functional decline, institutionalization, and mortality. OBJECTIVE: To identify the prevalence and factors associated with FS in a population assisted by an outpatient geriatric unit at a specialized geriatric and gerontological care center in the Brazilian Federal District. METHODS: This is an observational, descriptive, cross-sectional and analytical study conducted with older people who were assisted at the specialized center for geriatrics and gerontology of the Brazilian Federal District Health Department. In the baseline evaluation of the participants, data were collected to identify the profile, functional capacity, multimorbidities and clinical outcomes such as falls, as well as the level of frailty, which was classified according to Fried's criteria. Statistical analysis was performed using the chi-square test and Poisson's regression. RESULTS: In the present study, 24% of the total sample was considered frail, 32.9% pre-frail and 42.1%, non-frail. Regarding sociodemographic aspects, there was an association of frailty with the higher age group and with lower educational level. Diabetes, systemic arterial hypertension, incontinence, polypharmacy, depression, falls, and cognitive impairment were directly related to higher risk of frailty. CONCLUSION: The results obtained were useful to help define measures and strategies to prevent morbidity and mortality as well as to provide better quality of life for older adults.

Identification of new promising Plasmodium falciparum superoxide dismutase allosteric inhibitors through hierarchical pharmacophore-based virtual screening and molecular dynamics.

Malaria is the world's most widespread protozoan infection, being responsible for more than 445,000 annual deaths. Among the malaria parasites, Plasmodium falciparum is the most prevalent and lethal. In this context, the search for new antimalarial drugs is urgently needed. P. falciparum superoxide dismutase (PfSOD) is an important enzyme involved in the defense mechanism against oxidative stress. The goal of this study was to identify through hierarchical screening on pharmacophore models and molecular dynamics (MD), promising allosteric PfSOD inhibitors that do not show structural requirements for human inhibition. MD simulations of 1000 ps were performed on PfSOD using GROMACS 5.1.2. For this, the AMBER99SB-ILDN force field was adapted to describe the metal-containing system. The simulations indicated stability in the developed system. Therefore, a covariance matrix was generated, in which it was possible to identify residues with correlated and anticorrelated movements with the active site. These results were associated with the results found in the predictor of allosteric sites, AlloSitePro, which affirmed the ability of these residues to delimit an allosteric site. Then, after successive filtering of the Sigma-Aldrich® compounds database for HsSOD1 and PfSOD pharmacophores, 152 compounds were selected, also obeying Lipinski's rule of 5. Further filtering of those compounds based on molecular docking results, toxicity essays, availability, and price filtering led to the selection of a best compound, which was then submitted to MD simulations of 20,000 ps on the allosteric site. The study concludes that the ZINC00626080 compound could be assayed against SODs. Graphical Abstract Plasmodium falciparum superoxide dismutase.

Reduced Systolic Volume: Main Pathophysiological Mechanism in Patients with Orthostatic Intolerance?

BACKGROUND: Orthostatic intolerance patients' pathophysiological mechanism is still obscure, contributing to the difficulty in their clinical management. OBJECTIVE: To investigate hemodynamic changes during tilt test in individuals with orthostatic intolerance symptoms, including syncope or near syncope. METHODS: Sixty-one patients who underwent tilt test at - 70° in the phase without vasodilators were divided into two groups. For data analysis, only the first 20 minutes of tilting were considered. Group I was made up of 33 patients who had an increase of total peripheral vascular resistance (TPVR) during orthostatic position; and Group II was made up of 28 patients with a decrease in TPVR (characterizing insufficient peripheral vascular resistance). The control group consisted of 24 healthy asymptomatic individuals. Hemodynamic parameters were obtained by a non-invasive hemodynamic monitor in three different moments (supine position, tilt 10' and tilt 20') adjusted for age. RESULTS: In the supine position, systolic volume (SV) was significantly reduced in both Group II and I in comparison to the control group, respectively (66.4 ±14.9 ml vs. 81.8±14.8 ml vs. 101.5±24.2 ml; p<0.05). TPVR, however, was higher in Group II in comparison to Group I and controls, respectively (1750.5± 442 dyne.s/cm5 vs.1424±404 dyne.s/cm5 vs. 974.4±230 dyne.s/cm5; p<0.05). In the orthostatic position, at 10', there was repetition of findings, with lower absolute values of SV compared to controls (64.1±14.0 ml vs 65.5±11.3 ml vs 82.8±15.6 ml; p<0.05). TPVR, on the other hand, showed a relative drop in Group II, in comparison to Group I. CONCLUSION: Reduced SV was consistently observed in the groups of patients with orthostatic intolerance in comparison to the control group. Two different responses to tilt test were observed: one group with elevated TPVR and another with a relative drop in TPVR, possibly suggesting a more severe failure of compensation mechanisms.

Reduced Systolic Volume: Main Pathophysiological Mechanism in Patients with Orthostatic Intolerance? / Volume Sistólico Reduzido: Mecanismo Fisiopatológico Principal em Pacientes com Intolerância Ortostática?

Abstract Background: Orthostatic intolerance patients' pathophysiological mechanism is still obscure, contributing to the difficulty in their clinical management. Objective: To investigate hemodynamic changes during tilt test in individuals with orthostatic intolerance symptoms, including syncope or near syncope. Methods: Sixty-one patients who underwent tilt test at - 70° in the phase without vasodilators were divided into two groups. For data analysis, only the first 20 minutes of tilting were considered. Group I was made up of 33 patients who had an increase of total peripheral vascular resistance (TPVR) during orthostatic position; and Group II was made up of 28 patients with a decrease in TPVR (characterizing insufficient peripheral vascular resistance). The control group consisted of 24 healthy asymptomatic individuals. Hemodynamic parameters were obtained by a non-invasive hemodynamic monitor in three different moments (supine position, tilt 10' and tilt 20') adjusted for age. Results: In the supine position, systolic volume (SV) was significantly reduced in both Group II and I in comparison to the control group, respectively (66.4 ±14.9 ml vs. 81.8±14.8 ml vs. 101.5±24.2 ml; p<0.05). TPVR, however, was higher in Group II in comparison to Group I and controls, respectively (1750.5± 442 dyne.s/cm5 vs.1424±404 dyne.s/cm5 vs. 974.4±230 dyne.s/cm5; p<0.05). In the orthostatic position, at 10', there was repetition of findings, with lower absolute values of SV compared to controls (64.1±14.0 ml vs 65.5±11.3 ml vs 82.8±15.6 ml; p<0.05). TPVR, on the other hand, showed a relative drop in Group II, in comparison to Group I. Conclusion: Reduced SV was consistently observed in the groups of patients with orthostatic intolerance in comparison to the control group. Two different responses to tilt test were observed: one group with elevated TPVR and another with a relative drop in TPVR, possibly suggesting a more severe failure of compensation mechanisms.

Resumo Fundamento: O mecanismo fisiopatológico de pacientes com intolerância ortostática ainda é obscuro, contribuindo para a dificuldade no manejo clínicos desses pacientes. Objetivo: Investigar as alterações hemodinâmicas durante teste de inclinação (tilt teste) em indivíduos com sintomas de intolerância ortostática, incluindo síncope ou pré-síncope. Métodos: Sessenta e um pacientes, com tilt teste a 70º negativo na fase livre de vasodilatador, foram divididos em dois grupos. Para análise dos dados foram considerados apenas os primeiros 20 minutos de inclinação. Grupo I (33 pacientes) que tiveram elevação da resistência vascular periférica total (RVPT) durante posição ortostática e Grupo II (28 pacientes) com queda da RVPT (caracterizando insuficiência de resistência vascular periférica). O grupo controle consistia de indivíduos saudáveis e assintomáticos (24 indivíduos). Os parâmetros hemodinâmicos foram obtidos por um monitor hemodinâmico não invasivo em 3 momentos distintos (posição supina, tilt 10' e tilt 20'), ajustados para idade. Resultados: Na posição supina, o volume sistólico (VS) foi significantemente reduzido tanto no Grupo II quanto no I, quando comparado ao do Grupo controle, respectivamente (66,4 ±14,9 ml vs. 81,8±14,8 ml vs. 101,5±24,2 ml; p<0,05.) A RVPT, no entanto, foi mais elevada no Grupo II, quando comparada a do Grupo I e controles, respectivamente (1750,5± 442 dyne.s/cm5 vs.1424±404 dyne.s/cm5 vs. 974,4±230 dyne.s/cm5; p<0,05). Na posição ortostática, aos 10', houve repetição dos achados, com valores absolutos inferiores de VS Comparado aos controles (64,1±14,0 ml vs 65,5±11,3 ml vs 82,8±15,6 ml; p<0,05). A RVPT, todavia, apresentou queda relativa no Grupo II comparado ao I. Conclusão: Volume sistólico reduzido foi consistentemente observado nos grupos de pacientes com intolerância ortostática, quando comparado ao grupo controle. Foram observadas duas respostas distintas ao teste de inclinação: um grupo com elevação de RVPT e outro com queda relativa desta, indicando, possivelmente, falência mais acentuada dos mecanismos de compensação.

Hidroterapia no equilíbrio dinâmico e nas atividades de vida diária de pacientes com neurotoxoplasmose associada à síndrome da imunodeficiência adquirida / Hydrotherapy on dynamic balance and in activities of daily living in patients withneurotoxoplasmosis associated with the acquired immune deficiency syndrome

INTRODUÇÃO: Por comprometer as células de defesa do organismo, o Vírus da Imunodeficiência Humana torna o indivíduo vulnerável ao aparecimento de diversas doenças, entre elas a neurotoxoplasmose. OBJETIVO: Verificar a influência de um protocolo de hidroterapia no equilíbrio dinâmico e nas atividades de vida diária de pacientes com neurotoxoplasmose associada à Síndrome da Imunodeficiência Adquirida (SIDA). MÉTODOS: Participaram 15 voluntários, três (20%) do sexo feminino e 12 (80%) do masculino, com média de idade de 37,44±5,5 anos e diagnóstico de neurotoxoplasmose decorrente da SIDA, cadastrados na Unidade de Referência Especializada em Doenças Infectocontagiosas Parasitárias Especiais. Foram submetidos à avaliação do equilíbrio dinâmico pelo Índice de Marcha Dinâmico e à avaliação das atividades de vida diária pelo Índice de Barthel, pré- e pós-hidroterapia, em piscina à temperatura média de 35°C, três vezes por semana em dias alternados, durante 50 minutos, totalizando oito semanas, ou seja, 24 sessões. Foi utilizado o teste de Shapiro-Wilk para análise de variâncias do Índice de Marcha Dinâmica e do Índice de Barthel, e o teste t de Student para as comparações pré e pós-tratamento e nível de significância de α=0.05. RESULTADOS: O equilíbrio dinâmico, considerando o escore total, apresentou significância estatística (p<0,0001), quando comparado pós-teste (20,3±2,5) em relação ao pré-teste (13,2±3,2). Quanto às atividades de vida diária, foi evidenciado valor estatisticamente significante (p=0,049) no pós-teste (98,8±2.2) quando comparado ao pré-teste (95,6±3.9). CONCLUSÃO: Neste estudo, o protocolo de hidroterapia melhorou o equilíbrio dinâmico e as atividades de vida diária de pacientes com neurotoxoplasmose associada à SIDA.

INTRODUCTION: For compromising the defense cells of the body, the Human Immunodeficiency Virus makes the individual vulnerable to the emergence of various diseases, including the neurotoxoplasmosis. OBJECTIVE: To determine the effect of a hydrotherapy protocol in dynamic balance and the activities ofdaily living of patients with cerebral toxoplasmosis associated with the Acquired Immuno Deficiency Syndrome (AIDS). METHODS: 15 volunteers participated, three (20%) were female and 12 of them (80%) were male; mean age 37.44±5.5 years, diagnosed with cerebral toxoplasmosis resulting from AIDS registered in Specialized Reference Unit on Infectious Diseases Parasitic Infectious Specials. Underwent evaluation of dynamic balance by the Dynamic Gait Index and the activities of daily living by Barthel Index, pre and post hydrotherapy, in the pool at an average temperature of 35°C, 3 times per week on alternate days, lasting 50 minutes, a total of 8 weeksor 24 sessions. We used the Shapiro-Wilk test for analysis of the Dynamic Gait Index and Barthel Index variances, and T Student test for pre and post-treatment comparison and significance level of α=0.05. RESULTS: Total score of dynamic balance presented statistically significance (p<0.0001), comparison post-test (20.3±2.5) compared to pre-test (13.2±3.2). As for the activities of daily living was evidenced statistically significant value (p=0.049),and the post-test (98.8±2.2) compared to pre-test (95.6±3.9). CONCLUSION: In this study, hydrotherapy protocol improved the dynamic balance and the activities of daily living of patients with cerebral toxoplasmosis associated with AIDS.

[Clinical heterogeneity of atypical fractures during prolonged use of bisphosphonates--risk factors and bone turnover markers]. / Heterogeneidade na apresentação clínica de fraturas atípicas após uso prolongado de bisfosfonatos--fatores de risco e marcadores de remodelação óssea.

We describe four cases of atypical femoral fractures treated at the Department of Endocrinology, Hospital de Clínicas, Federal University of Paraná (SEMPR) which, although characteristic of this type of fracture, presented clinical peculiarities that should be considered and serve as a warning in these patients, such as: late diagnosis with maintenance of bisphosphonates; absence of co-morbidities with excellent result; failure of fracture healing; use of anabolic medication after the fracture and the use of bone turnover markers at the follow up.

Composição química e estudo da atividade antibacteriana de Bowdichiavirgilioides Kunth (Sucupira) – Fabaceae – Papilonoidae / Study on the chemical composition and antibacterial activity of Bowdichia virgilioides kunth (Sucupira) - Fabaceae - Papilonoidae

Bowdichia virgilioides (Fabaceae - Papilionoidea), popularly known as Sucupira-preta, is a Brazilian native tree used in the traditional medicine against throat infections. Due this fact and due the interest to validate the traditional use, the objective of this work was evaluates the in vitro antibacterial activity of extracts and fractions of the stem and heartwood of the plant. The phytochemical profile revealed the presence of tannins and flavonoids in the stem and heartwood, and only alkaloids in the stem.The HPLC analysis revealed the presence of flavonoids and phenolic acids, natural products with several biological activities, including the modifying antibiotic activity. All microrganisms were inhibited only with MIC > 1024 microgramo/mL. However, when associated with aminoglycosides, was demonstrated a potentiation of these antibiotics when associated with almost all products assayed and against one bacterium at least.

Bowdichia virgilioides (Fabaceae - Papilionoidea), popularmente conhecida como Sucupira-preta, é uma espécie arbórea nativa do Brasil utilizadas na medicina popular para infecções de garganta. Com base nessas evidências, e com o interesse para justificar o uso popular, este trabalho teve como objetivo verificar a atividade antibacteriana in vitro de extratos brutos e fracionados de cascas e cerne da planta. Observou-se pela conclusão do levantamento fitoquímico a presença de taninos e flavonóides nas cascas e no cerne, e alcalóides apenas encontrados na casca. A análise por HPLC revelou a presença de flavonóides e ácidos fenólicos, produtos naturais, com diversas atividades biológicas, incluindo a atividade modificadora antibiótica. Todos os microorganismos foram inibidos apenas com o CIM > 1024 ug/mL. No entanto, quando associado a antibióticos aminoglicosídeos, foi demonstrada potenciação destes em quase todos os produtos testados e em pelo menos uma bactéria foi observada uma atividade moduladora significativa.

Energy metabolism, leptin, and biochemical parameters are altered in rats subjected to the chronic administration of olanzapine.

OBJECTIVES: Olanzapine, an atypical antipsychotic drug with affinities for dopamine, serotonin, and histamine binding sites appears to be associated with substantial weight gain and metabolic alterations. The aim of this study was to evaluate weight gain and metabolic alterations in rats treated with olanzapine on a hypercaloric diet. METHODS: We used 40 rats divided into 4 groups: Group 1, standard food and water conditions (control); Group 2, standard diet plus olanzapine; Group 3, cafeteria diet (hypercaloric); and Group 4, olanzapine plus cafeteria diet. Olanzapine was administered by gavage at a dose of 3 mg/kg for 9 weeks. RESULTS There were no significant changes in the cholesterol levels in any group. Glucose levels increased in Group 3 by the fourth week. Triglyceride levels were altered in group 2 toward the end of the experiment. Leptin levels decreased in Groups 2 and 4. Complex II activity in the muscles and liver was altered in Group 2 (muscle), and Groups 2, 3, and 4 (liver). Complex IV activity was altered only in the liver in Group 2, without significant alterations within the muscles. CONCLUSION: These results suggest that olanzapine is correlated with weight gain and the risks associated with obesity.

Energy metabolism, leptin, and biochemical parameters are altered in rats subjected to the chronic administration of olanzapine / Metabolismo calórico, leptina e parâmetros bioquímicos se alteram em ratos submetidos à administração crônica de olanzapina

OBJECTIVES: Olanzapine, an atypical antipsychotic drug with affinities for dopamine, serotonin, and histamine binding sites appears to be associated with substantial weight gain and metabolic alterations. The aim of this study was to evaluate weight gain and metabolic alterations in rats treated with olanzapine on a hypercaloric diet. METHODS: We used 40 rats divided into 4 groups: Group 1, standard food and water conditions (control); Group 2, standard diet plus olanzapine; Group 3, cafeteria diet (hypercaloric); and Group 4, olanzapine plus cafeteria diet. Olanzapine was administered by gavage at a dose of 3 mg/kg for 9 weeks. RESULTS There were no significant changes in the cholesterol levels in any group. Glucose levels increased in Group 3 by the fourth week. Triglyceride levels were altered in group 2 toward the end of the experiment. Leptin levels decreased in Groups 2 and 4. Complex II activity in the muscles and liver was altered in Group 2 (muscle), and Groups 2, 3, and 4 (liver). Complex IV activity was altered only in the liver in Group 2, without significant alterations within the muscles. CONCLUSION: These results suggest that olanzapine is correlated with weight gain and the risks associated with obesity.

OBJETIVOS: A olanzapina, uma droga antipsicótica atípica com afinidade por locais de ligação de dopamina, serotonina e histamina, parece se associar a um ganho de peso e a alterações metabólicas consideráveis. O objetivo desse estudo foi avaliar o ganho de peso e as alterações metabólicas em ratos tratados com olanzapina numa dieta hipercalórica. MÉTODOS: Usamos 40 ratos divididos em 4 grupos: Grupo 1, condições padrão de alimento e água (controle); Grupo 2, dieta padrão mais olanzapina; Grupo 3, dieta hipercalórica; e Grupo 4, olanzapina mais dieta hipercalórica. Olanzapina foi administrada por gavagem a uma dose de 3 mg/kg por 9 semanas. RESULTADOS: Não houve alterações significativas nos níveis de colesterol em qualquer um dos grupos. Os níveis de glicose aumentaram no Grupo 3 por volta da quarta semana. Os níveis de triglicerídeos estavam alterados no Grupo 2 ao final do experimento. Os níveis de leptina diminuíram nos Grupos 2 e 4. A atividade do complexo II nos músculos e no fígado se alterou no Grupo 2 (músculos) e nos Grupos 2, 3 e 4 (fígado). A atividade do complexo IV se alterou apenas no fígado no Grupo 2, sem alterações significativas nos músculos. CONCLUSÃO: Esses resultados sugerem que olanzapina se correlaciona ao ganho de peso e aos riscos associados à obesidade.

Effects of pregabalin on behavioral alterations induced by ketamine in rats.

OBJECTIVE: The aim of this study is to investigate the effects of pregabalin on the behavior of rats under the influence of ketamine, an NMDA receptor antagonist that mimics the symptoms of schizophrenia. METHODS: Rats were injected with saline or 25 mg/kg ketamine intraperitoneally. After that, behavior modifications were investigated by the evaluation of stereotypy and hyperlocomotion, after treating rats with pregabalin (at doses of 30 mg/kg or 100 mg/kg) or placebo (saline solution). RESULTS: The administration of pregabalin reduced ketamine-induced hyperlocomotion. However, neither doses of pregabalin had a significant effect on ketamineinduced stereotypy. CONCLUSION: This is the first study to investigate the effects of pregabalin using an animal model of psychosis. Furthermore, our results indicate that behavioral changes induced by ketamine in rats can be reversed with the use of pregabalin, suggesting its potential to treat psychotic symptoms.

My legs are getting old: sinvastatin-induced polyneuropathy.

Axonal degeneration is the most common type of neuropathy induced by medication. The literature describes isolated cases in which polyneuropathy of the lower limb was observed during treatment with statins. The authors present a case of polyneuropathy associated with the use of a statin. An 82-year-old female patient presented with a complaint of weakness and discomfort in her lower limbs after 7 years of therapy with simvastatin. The results of an electromyographic study were compatible with polyneuropathy (sensorimotor axonal neuropathy--moderate to severe). One month after the therapy with simvastatin was discontinued, the symptoms were reduced.