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- ItemSomente MetadadadosAntinociceptive effect of purine nucleotides(Assoc Bras Divulg Cientifica, 1996-10-01) Mello, C. F.; Begnini, J.; DeLaVega, D. D.; Lopes, F. P.; Schwartz, C. C.; JimenezBernal, R. E.; Bellot, Rogerio Gentil [UNIFESP]; Frussa-Filho, Roberto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)The antinociceptive effect of purine nucleotides administered systemically (sc) was determined using the formalin and writhing tests in adult male albino mice. The mechanisms underlying nucleotide-induced antinociception were investigated by preinjecting the animals (sc) with specific antagonists for opioid (naloxone, 1 mg/kg), purinergic P-1 (caffeine, 5, 10 or 30 mg/kg); theophylline, 10 mg/kg) or purinergic P-2 receptors (suramin, 100 mg/kg, Coomassie blue, 30-300 mg/kg; quinidine, 10 mg/kg). Adenosine, adenosine monophosphate (AMP), diphosphate (ADP) and triphosphate (ATP) caused a reduction in the number of writhes and in the time of licking the formalin-injected paw. Naloxone had no effect on adenosine- or adenine nucleotide-induced antinociception. Caffeine (30 mg/kg) and theophylline (10 mg/kg) reversed the antinociceptive action of adenosine and adenine nucleotide derivatives in both tests. P-2 antagonists did not reverse adenine nucleotide-induced antinociception. These results suggest that the antinociceptive effect of adenine nucleotides is mediated by adenosine.
- ItemSomente MetadadadosAvaliação do efeito neuroprotetor da cafeína em modelo experimental de doença de parkinson: um estudo comportamental, neuroquímico e imunohistoquímico(Universidade Federal de São Paulo (UNIFESP), 2013-12-20) Machado Filho, Joao Ananias [UNIFESP]; Cavalheiro, Esper Abrao Cavalheiro [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. The occurrence of clinical symptoms is related to the loss of approximately 80% of striatal dopamine and 50% of nigral neurons. Caffeine (CAF) is a methylxanthine with extensive use in medicines and products such as coffee, tea and chocolates, and being assigned neuroprotective activities. This study evaluated neuroprotective effects of caffeine in an animal model of PD induced by 6 - OHDA through behavioral studies, neurochemical and immunohistochemical studies. The animals, male Wistar rats (250-300g) were subjected to three protocols (P1, P2, P3) of striatal lesion by 6-OHDA, with concentration of 24μg/2μL in P1, and 12μg/2μL in P2 and P3. The preventive and curative treatment was done as follows in the these protocols: P1 - CAF treatment (10 and 20mg/kg) for two weeks after the injury (curative); P2 - CAF treatment (10 and 20mg/kg) for two weeks after the injury (curative); another group was treated with CAF (10 mg/kg) and L-Dopa (10mg/kg) after injury (curative); P3 - treated with CAF (5, 10 and 20mg/kg) for two weeks prior to the injury (prophylactic) and continued for two weeks after the injury (curative). The results demonstrate that the 6- OHDA caused an increase in the number of contralateral rotations induced by apomorphine and reduction of striatal dopamine levels with the degree of lesion probably directly related to the dose of 6-OHDA. These effects were reversed by the administration of CAF (10 and 20mg/kg) in P1 and P2, besides being observed increased neuronal viability and immunohystochemical changes that, together, denote neuroprotective activity of CAF in this model. Co-administration of levodopa (10 mg/kg) and CAF (10mg/kg) showed no effect on striatal dopamine concentrations beyond those already observed in the treatment with isolated CAF. CAF (20mg/kg) produced a significant increase in dopamine levels in sham animals and animals lesioned with 6-OHDA. Preventive treatment with caffeine (P3) showed similar results to curative treatment (P2) as observed in the neurochemical and behavioral assessments. Thus, it was demonstrated the neuroprotective effect of caffeine in this experimental study, presenting itself as a potential substance for the prevention and treatment of Parkinson's disease.
- ItemAcesso aberto (Open Access)Cafeína para o tratamento de dor(Sociedade Brasileira de Anestesiologia, 2012-06-01) Tavares, Cristiane [UNIFESP]; Sakata, Rioko Kimiko [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)BACKGROUND AND OBJECTIVES: Caffeine is a widely used substance with effects on several systems, presenting characteristic of pharmacokinetic and pharmacodynamic which cause interactions with several drugs. This study's objective is to review the effects caused by caffeine. CONTENT: This review assesses the caffeine pharmacology, its action mechanisms, indications, contraindications, doses, interactions and adverse effects. CONCLUSIONS: There are insufficient double-blind randomized controlled studies that assess the analgesic effect of caffeine on several painful syndromes. Patients presenting chronic pain need caution when it comes to tolerance development, abstinence and drug interaction from chronic caffeine use.
- ItemSomente MetadadadosCan energy drinks reduce the depressor effect of ethanol? An experimental study in mice(Elsevier B.V., 2004-10-15) Ferreira, S. E.; Quadros, IMH; Trindade, A. A.; Takahashi, S.; Koyama, R. G.; Souza-Formigoni, MLO; Universidade Federal de São Paulo (UNIFESP)Although the popularization of the combined use of alcoholic beverages and energy drinks (ED) containing caffeine, taurine and other substances has increased, there are no controlled experimental studies on the effects of ED alone or combined with ethanol. This work aimed at evaluating the effects of different doses of ED combined or not with ethanol, on the locomotor activity of Swiss mice. the administration of 3.57, 10.71 or 17.86 ml/kg of ED alone increased the locomotor activity of the animals in relation to a control group. Low doses of ethanol (0.5, 1.0 and 1.5 g/kg) alone or in combination with 10.71 ml/kg of ED did not affect their locomotor activity. However, the reduction of activity observed after 2.5 g/kg of ethanol was antagonized by 10.71 ml/kg of ED. Further studies on the mechanisms of this interaction are still needed. (C) 2004 Elsevier Inc. All rights reserved.
- ItemAcesso aberto (Open Access)Desenvolvimento de nanopartículas de papaína complexada com alginato de sódio como promotor de permeação cutânea(Universidade Federal de São Paulo, 2023-11-21) Pimentel, Debora Regina de Oliveira [UNIFESP]; Silva, Vânia Rodrigues Leite e [UNIFESP]; Andréo Filho, Newton [UNIFESP]; http://lattes.cnpq.br/4715398927727906; http://lattes.cnpq.br/0737387413540260; http://lattes.cnpq.br/0705342031342161A via de administração transdérmica é uma das formas de permeação mais antiga da história humana, na qual plantas e outras substâncias naturais eram aplicadas na pele para tratar diversos tipos de afecções. No entanto, as propriedades de barreira da pele fazem dela um obstáculo importante, e um desafio a ser superado. Desta forma, este trabalho propõe a obtenção de nanopartículas poliméricas biodegradáveis de alginato de sódio e papaína (AG-PPN) como possível promotor de permeação cutânea de ativos cosméticos utilizando a cafeína como bioativo modelo. O sistema nanoparticulado AG-PPN foi desenvolvido utilizando o método de coacervação através da neutralização de cargas iônicas das macromoléculas, permitindo a obtenção de PPN ativa e imobilizada. A dispersão obtida foi caracterizada por tamanho e uniformidade através de difração a laser (DL), revelando a formação de 99,93% de nanopartículas abaixo de 500nm e diâmetro médio de 0,19µm. A análise por DLS indicou a formação de um sistema monodisperso, com PdI de 0,332. O valor de potencial zeta foi de -50,4mV demonstrando a prevalência da carga negativa do AG. A dispersão foi caracterizada por diversas técnicas físico-químicas. E a atividade enzimática da PPN na dispersão de AG-PPN em diferentes condições de armazenamento demonstrou que após 10 dias a atividade da amostra armazenada em geladeira se manteve em 96,2%. A adição de crioprotetores à dispersão de AG-PPN demonstrou que a recuperação das nanopartículas com o crioprotetor PVP revelou a formação de 99,80% de partículas com tamanho abaixo ou igual a 500nm, e o crioprotetor PLL 100%, em concentrações de 5 e 4%, respectivamente. No entanto, o crioprotetor lactose, manteve a atividade da PPN em 72,73%. O ensaio de permeação ex vivo demonstrou que nas condições avaliadas, a PPN livre e nanoencapsulada (AG-PPN) não contribuiu para o aumento da permeação da cafeína.
- ItemAcesso aberto (Open Access)Estabilidade de comprimidos de liberação controlada baseados em hidroxietilcelulose(Universidade Federal de São Paulo (UNIFESP), 2016-02-25) Gaiotto, Cristina Aparecida Andrade Raymundo [UNIFESP]; Tada, Dayane Batista [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Cellulose derivatives are polymers commonly used for drug delivery. In this work one of these derivatives, the hydroxiethylcellulose has been applied in the formulation of compressed tablets for controlled release purposes. The tablets were produced by using the same excipients normally used in the commercially available tablets and caffeine was used as model drug. The characterization of raw materials and tablets were performed by using the following techniques: Differential Scanning Calorimetry analysis (DSC), spectroscopic measurements of Raman and UV/VIS, scanning electron microscopy (SEM). The swelling behavior of the polymeric matrix was evaluated by immersion in water and exposition to atmospheric humidity. The drug release profile of the tablets was obtained in ?in vitro? assays in water. The mechanisms of drug release and swelling were characterized by adjusting kinetic data to Higuchi, Korsmeyer and Vergnaud model. Additionally to the establishment of an appropriated formulation for controlled release of caffeine, the present work has identified the effects of compression pressure and storage over the drug release kinetic profile of the tablets. It was observed that the higher compression pressure generates tablets with slower drug release in a anomalous mechanism of release and swelling. The storage under 75/%RH and 30/ºC and 40/ºC increased the rate of drug release in both types of tablets (compressed at higher and at lower pressure). This change has been identified as a consequence of the increased water content of the tablets as well as a result of the relaxation of the polymeric chains due to the increased temperature. Overal, the results obtained, suggested that a criterious planning and combination of raw materials in the design of formulations as well as the set up of the parameters during the production of tablets are critical points to the success of a system for controlled release purposes. Besides, monitoring storage conditions as temperature and humidity is essencial in order to guarantee the controlled release behavior of HEC-based tablets.
- ItemSomente MetadadadosIntracellular calcium mobilization by muscarinic receptors is regulated by micromolar concentrations of external Ca2+(Springer, 2001-06-01) Smaili, Soraya Soubhi [UNIFESP]; Carvalho, Solange Maria Torchia [UNIFESP]; Cavalcanti, Paulo MS [UNIFESP]; Jurkiewicz, Neide H. [UNIFESP]; Garcia, Antonio G.; Jurkiewicz, Aron [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Autonoma MadridCarbachol-induced contractions of rat stomach fundus strips, obtained in a nutrient solution containing 1.8 mM Ca2+, were resistant to Ca2+ withdrawal, even after 1 h of bathing the tissues in a nominal 0 Ca2+ solution. This was not observed when K+ was used to evoke contractions, which were rapidly inhibited after Ca2+ removal (t(1/)2=2 min). the effect of carbachol in 0 Ca2+ solution was reduced by using drugs that reduce intracellular pools of Ca2+, such as caffeine (1-3 mM), ryanodine (30 muM) or thapsigargin (1 muM), corroborating the involvement of intracellular Ca2+ stores. On the other hand, when the 0 Ca2+ solution contained EGTA, a complete decline of carbachol effects was observed within about 8 min, indicating the involvement of extracellular Ca2+. Atomic absorption spectrometry showed that our 0 Ca2+ solution still contained 45 muM Ca2+, which was drastically reduced to 5.9 nM in the presence of EGTA. Taken together, our results indicate that the effects of carbachol are due to the mobilization of caffeine-, ryanodine- and thapsigargin-sensitive intracellular Ca2+ stores, and that these stores are not inactivated or depleted if micromolar concentrations (45 muM), but not nanomolar concentrations (5.9 nM) of Ca2+ are maintained in the extracellular milieu.
- ItemSomente MetadadadosThe plus-maze discriminative avoidance task: a new model to study memory-anxiety interactions. Effects of chlordiazepoxide and caffeine(Elsevier B.V., 2000-10-30) Silva, R. H.; Frussa, R.; Universidade Federal de São Paulo (UNIFESP)The plus-maze discriminative avoidance paradigm is a new animal model of learning/memory that provides simultaneous information about anxiety. Mice are conditioned to choose between the two enclosed arms tin one of which light and noise are presented as aversive stimuli) while avoiding the two open arms of the apparatus. the test has the advantage of measuring, at the same time and in the same animals, learning/memory (by the percent time spent in aversive enclosed arm - PTAV) and anxiety (by the percent time spent in the open arms - PTO). the effects of chlordiazepoxide and caffeine on learning/memory and anxiety of mice tested in this paradigm were investigated. Chlordiazepoxide (5 mg/kg) significantly increased and caffeine (20 mg/kg) significantly decreased PTO during the training session, suggesting an anxiolytic and an anxiogenic effect, respectively. in the test session, chlordiazepoxide- or caffeine-treated mice presented higher PTAV, suggesting amnestic effects. Given together, chlordiazepoxide plus caffeine did not alter PTO, and the amnesic effect produced by each drug was no longer observed. It is concluded that learning/memory depends on an optimum emotional level. the pins-maze discriminative avoidance model appears to be a useful test to investigate this critical relationship between learning/memory and anxiety. (C) 2000 Elsevier Science B.V. All rights reserved.
- ItemSomente MetadadadosRole of state-dependent learning in the cognitive effects of caffeine in mice(Cambridge Univ Press, 2013-08-01) Sanday, Leandro [UNIFESP]; Zanin, Karina Agustini [UNIFESP]; Patti, Camilla de Lima [UNIFESP]; Fernandes-Santos, Luciano [UNIFESP]; Oliveira, Larissa C. [UNIFESP]; Longo, Beatriz Monteiro [UNIFESP]; Andersen, Monica Levy [UNIFESP]; Tufik, Sergio [UNIFESP]; Frussa-Filho, Roberto [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Caffeine is the most widely used psychoactive substance in the world and it is generally believed that it promotes beneficial effects on cognitive performance. However, there is also evidence suggesting that caffeine has inhibitory effects on learning and memory. Considering that caffeine may have anxiogenic effects, thus changing the emotional state of the subjects, state-dependent learning may play a role in caffeine-induced cognitive alterations. Mice were administered 20 mg/kg caffeine before training and/or before testing both in the plus-maze discriminative avoidance task (an animal model that concomitantly evaluates learning, memory, anxiety-like behaviour and general activity) and in the inhibitory avoidance task, a classic paradigm for evaluating memory in rodents. Pre-training caffeine administration did not modify learning, but produced an anxiogenic effect and impaired memory retention. While pre-test administration of caffeine did not modify retrieval on its own, the pre-test administration counteracted the memory deficit induced by the pre-training caffeine injection in both the plus-maze discriminative and inhibitory avoidance tasks. Our data demonstrate that caffeine-induced memory deficits are critically related to state-dependent learning, reinforcing the importance of considering the participation of state-dependency on the interpretation of the cognitive effects of caffeine. the possible participation of caffeine-induced anxiety alterations in state-dependent memory deficits is discussed.
- ItemSomente MetadadadosSmoking-associated factors in myocardial infarction and unstable angina: Do gender differences exist?(Elsevier B.V., 2007-06-01) Perez, Gloria Heloise; Nicolau, Jose Carlos; Romano, Bellkiss Wilma; Laranjeira, Ronaldo; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)The aim of this study was to investigate demographic and psychological characteristics associated with smoking in patients with acute coronary syndrome (myocardial infarction or unstable angina). Interviews were conducted with 348 consecutive hospitalized patients with acute coronary syndrome and included questions about demographic characteristics, coffee consumption, heart disease risk perception, economic status, alcohol consumption, depression, anxiety, and stress. Female group multivariate analysis showed that smoking in females was significantly and negatively associated with age, heart disease risk perception, and positively associated with coffee consumption. Male group multivariate analysis showed that for males, smoking was significantly and negatively associated with age, heart disease risk perception, and positively associated with coffee and alcohol consumption. Unlike studies conducted with non-heart disease patients, our results do not show an association between smoking and depression. Compared with nonsmokers, smokers with acute coronary syndrome are younger, more likely to drink coffee, and less likely to perceive smoking as a heart disease risk. Male smokers are also more likely to drink alcohol, indicating that they use more psycho-stimulants than do nonsmoking men and women who smoke. (c) 2006 Elsevier B.V. All rights reserved.