Alzheimer's disease (AD) is a neurodegenerative disorder characterized by synaptic loss and cognitive impairments. The presence of extracellular senile plaques (mainly composed of amyloid-β (Aβ) peptide) is an important molecular hallmark in AD and neuronal damage has been attributed, at least in part, to Aβ-mediated toxicity. Although the molecular mechanisms involved in the pathogenesis of AD are not yet completely understood, several lines of evidence indicate that oxidative stress and cholesterol dyshomeostasis play crucial roles in mediating the synaptic loss and cognitive deficits observed in AD patients. This study evaluated the effects of Probucol, a phenolic lipid-lowering agent with anti-inflammatory and antioxidant properties, on biochemical parameters related to oxidative stress and synaptic function (hippocampal glutathione and synaptophysin levels; glutathione peroxidase, glutathione reductase and acetylcholinesterase activities; lipid peroxidation), as well as on behavioral parameters related to the cognitive function (displaced and new object recognition tasks) in Aβ-exposed mice. Animals were treated with a single intracerebroventricular (i.c.v.) injection of aggregated Aβ(1-40) (400 pmol/site) and, subsequently, received Probucol (10 mg/kg, i.p.) once a day, during the following 2 weeks. At the end of treatments, Aβ(1-40)-exposed animals showed a significant impairment on learning-memory ability, which was paralleled by a significant decrease in hippocampal synaptophysin levels, as well as by an increase in hippocampal acetylcholinesterase activity. Importantly, Probucol treatment blunted the deleterious effects of Aβ(1-40) on learning-memory ability and hippocampal biochemistry. Although Aβ(1-40) treatment did not change hippocampal glutathione levels and glutathione peroxidase (GPx) and glutathione reductase (GR) activities, Aβ(1-40)-exposed animals showed increased hippocampal lipid peroxidation and this event was completely blunted by Probucol treatment. These findings reinforce and extend the notion of the hazardous effects of Aβ(1-40) toward hippocampal synaptic homeostasis and cognitive functions. In addition, the present results indicate that Probucol is able to counteract the cognitive and biochemical impairments induced by i.c.v. Aβ(1-40) administration in mice. The study is the first to report the protective effects of Probucol (a "non-statin cholesterol-lowering drug") against Aβ(1-40)-induced synaptic and behavioral impairments, rendering this compound a promising molecule for further pharmacological studies on the search for therapeutic strategies to treat or prevent AD.

Many health claims have been made about the medicinal benefits of drinking green tea, including neuroprotection. This study mainly focuses on Epigallocatechin 3-gallate (EGCG), a potent antioxidant, which is abundantly found in green tea. Cadmium [Cd(2+)] is a toxic pollutant that leads to neurotoxicity in both animals and humans. Although the entrance of Cd(2+) in the adult central nervous system is limited, developmental neurotoxicity has been evidenced as result of the blood-brain barrier (BBB) immaturity. Moreover, high Cd(2+) levels are known to impair BBB function. Furthermore, the molecular mechanisms related to its neurotoxic properties remain unknown. This study evaluates the potential protective effect of the major green tea polyphenol, EGCG, against Cd(2+)-induced mitotoxicity under in vitro conditions, using mitochondrial-enriched fractions from rat brain. Co-incubation of EGCG with Cd(2+) prevented the Cd(2+)-induced mitochondrial dysfunction (capacity to reduce MTT to formazan). In addition, EGCG completely prevented mitochondrial lipid peroxidation induced by Cd(2+) but did not affect non protein thiols levels. Spectroscopic studies have shown EGCG able to form a chemical complex with Cd(2+), in an equimolar ratio. In this study we demonstrate EGCG effectiveness in protecting against Cd(2+)-induced mitochondrial dysfunction and lipid peroxidation probably due to its antioxidant and chelating effects.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic nigrostriatal neurons. Although the etiology of the majority of human PD cases is unknown, experimental evidence points to oxidative stress as an early and causal event. Probucol is a lipid-lowering phenolic compound with anti-inflammatory and antioxidant properties that has been recently reported as protective in neurotoxicity and neurodegeneration models. This study was designed to investigate the effects of probucol on the vulnerability of striatal dopaminergic neurons to oxidative stress in a PD in vivo model. Swiss mice were treated with probucol during 21 days (11.8 mg/kg; oral route). Two weeks after the beginning of treatment, mice received a single intracerebroventricular (i.c.v.) infusion of 6-hydroxydopamine (6-OHDA). On the 21st day, locomotor performance, striatal oxidative stress-related parameters, and striatal tyrosine hydroxylase and synaptophysin levels, were measured as outcomes of toxicity. 6-OHDA-infused mice showed hyperlocomotion and a significant decrease in striatal tyrosine hydroxylase (TH) and synaptophysin levels. In addition, 6-OHDA-infused mice showed reduced superoxide dismutase activity and increased lipid peroxidation and catalase activity in the striatum. Notably, probucol protected against 6-OHDA-induced hyperlocomotion and striatal lipid peroxidation, catalase upregulation and decrease of TH levels. Overall, the present results show that probucol protects against 6-OHDA-induced toxicity in mice. These findings may render probucol as a promising molecule for further pharmacological studies on the search for disease-modifying treatment in PD.

The organophosphorus (OP) pesticide malathion is a highly neurotoxic compound and its toxicity is primarily caused by the inhibition of acetylcholinesterase (AChE), leading to cholinergic syndrome. Although oximes have been used as potential antidotal treatments in malathion poisoning because of their potential capability to reactivate the inhibited enzyme, the clinical experience with the clinically available oximes (e.g. pralidoxime) is disappointing and their routine use has been questioned. In the present study, we investigated the potency of pralidoxime and K074 in reactivating AChE after acute exposure to malathion, as well as in preventing malathion-induced changes in oxidative-stress related parameters in mice. Malathion (1.25 g/kg, s.c.) induced a significant decrease in cortico-cerebral, hippocampal and blood AChE activities at 24h after exposure. Oxime treatments (1/4 of LD(50), i.m., 6h after malathion poisoning) showed that pralidoxime significantly reversed malathion-induced blood AChE inhibition, although no significant effects were observed after K074 treatment. Interestingly, both oximes tested were unable to reactivate the cortico-cerebral and hippocampal enzymes after intramuscular or intracerebroventricular injection (1/4 of LD(50), 6h after malathion poisoning). Biochemical parameters related to oxidative stress (cerebro-cortical and hippocampal glutathione peroxidase, glutathione reductase and catalase activities, as well as lipid peroxidation) were not affected in animals treated with malathion, oximes or atropine alone. However, pralidoxime and K074, administered intramuscularly 6h after malathion poisoning, were able to increase the endogenous activities of these antioxidant enzymes in the prefrontal cortex and hippocampus. Taken together, the results presented herein showed that pralidoxime (the most common clinically used oxime) and the recently developed oxime K074, administered 6h after malathion poisoning, were unable to reactivate the inhibited AChE in mouse prefrontal cortex and hippocampus. However, only pralidoxime significantly reversed the blood AChE inhibition induced by malathion poisoning. This indicates that peripheral and central AChE activities are not necessarily correlated after the treatment of OP compounds and/or oximes, which should be taken into account in the diagnosis and management of OP-exposed humans. In addition, considering that the available treatments to malathion poisoning appear to be ineffective, the present study reinforce the need to search for potential new AChE reactivators able to efficiently reactivate the brain and blood AChEs after malathion poisoning.

No abstract

No abstract

This study aimed to evaluate the rate of sustained virological response (SVR) and the clinical and treatment characteristics of patients with chronic hepatitis C (CHC). A retrospective uncontrolled cohort study was conducted among patients who received treatment for CHC between 2005 and 2008 attended at the Center for the Application and Monitoring of Injectable Medications, in Florianopolis, SC, Brazil. The inclusion criteria were: patients over 18 years of age, with a confirmed diagnosis of chronic hepatitis C according to Brazilian guidelines, treated with PEG-IFN alfa-2a or 2b associated with RBV. A total of 188 patients were included in the study: 70% men, 59% genotype 1, 27% coinfected with HIV, 31% with cirrhosis. The SVR rate, calculated by probability theory, was determined as 26% (max=57.4% and min=12.8%) and the intention to treat was 12.8%. Associations between Sustained Virological Response (SVR) and the variables sex (p=0.017), age (p=0.003), genotype (p=0.648) and cirrhosis (p=0.275), were determined in the bivariate analysis and only sex and age were significantly associated with SVR. The SVR rate was considered low, which can be partially explained by patients' unfavorable pretreatment characteristics.Uniterms: Hepatitis C. Hepatitis C Chronic. Effectiveness. Interferon alfa-2a. Interferon alfa-2b.O objetivo do estudo foi avaliar a taxa de resposta viral sustentada (RVS) e as características clínicas e do tratamento dos pacientes portadores de hepatite C crônica. Realizou-se uma coorte retrospectiva não controlada com recorte temporal dos anos de 2005 a 2008, dos pacientes atendidos no Polo de Aplicação e Monitoramento de Medicamentos Injetáveis, em Florianópolis, SC. Os critérios de inclusão foram: pacientes maiores de 18 anos, com diagnóstico confirmado de hepatite C crônica de acordo com o protocolo brasileiro, tratados com PEG-IFN alfa-2a ou 2b associado a ribavirina. Total de 188 pacientes foi incluído no estudo, 70% homens, 59% genótipo 1, 27% co-infectados com o HIV e 31% apresentando cirrose. A taxa de RVS calculada através da teoria das probabilidades foi de 26% (max=57,4% and min=12,8%) e por intenção de tratamento de 12,8%. Verificou-se a associação da RVS com as variáveis: sexo (p=0,017), idade (p=0,003), genótipo (p=0,648) e presença de cirrose (p=0,275). Somente sexo e idade foram associados significativamente com a RVS. A taxa de RVS foi considerada baixa e, em parte, pode ser explicada pelas características desfavoráveis dos pacientes para a obtenção de RVS.Unitermos: Hepatite C. Hepatite C Crônica. Efetividade. Interferona alfa-2a. Interferona alfa-2b.

Resumo Com a pandemia da COVID-19 e a importância das políticas públicas de proteção social, questões sanitaristas incluindo as imunizações se tornaram destaque. O estudo tem o objetivo de analisar a dinâmica dos registros sanitários de vacinas no país e as vacinas disponibilizadas por meio do Programa Nacional de Imunização (PNI), com destaque para o calendário vacinal no período entre 2004 e 2018. Realizou-se um estudo descritivo, documental e exploratório dos processos de registro sanitário na Agência Nacional de Vigilância Sanitária (Anvisa) e a incorporação dos produtos no PNI. Como base da pesquisa foram utilizados o banco de dados de registro sanitário disponibilizado pela Anvisa, a análise documental de publicações oficiais/normativas e os dados da literatura. Os dados demonstram a incorporação das vacinas no PNI, assim como um país com potencial industrial para a produção das vacinas, no entanto ainda centrado na transferência de tecnologias, necessitando de investimentos e atenção pública no desenvolvimento de novas tecnologias, garantindo a independência do setor.