RESUMO
BACKGROUND AND OBJECTIVE: Periodontal disease has been described as playing a role in the atherosclerosis process, and its relation with intimal thickness and vascular endothelial function (EF) has been investigated. The present study sought to determine whether there are differences in parameters of arterial stiffness and EF between patients with and without severe periodontal disease (SPD). MATERIAL AND METHODS: Patients referred to the School of Dentistry University of Buenos Aires, were assessed. Demographic characteristics, atherogenic risk factors and concomitant pathologies were recorded. Patients with known cardiovascular pathology were excluded. Using carotid Doppler ultrasound an operator assessed arterial stiffness parameters: compliance, elastic modulus (EM), ß stiffness index (ßSI) and vascular EF by brachial artery flow-mediated dilatation. The patients were divided into two groups: with and without SPD. RESULTS: Forty patients were included; 60% were women; 15 were in the SPD group and 25 in the group without SPD. Respective results of the studied variables were: age 56.53 ± 17.58 vs. 51.12 ± 12.97 years (NS); probing depth 2.53 ± 1.30 (95% CI 1.81-3.25) vs. 1.25 ± 0.51 (95% CI 1.31-1.73) p = 0.02; clinical attachment level 4.80 ± 2.00 (95% CI 3.69-5.91) vs. 1.72 ± 0.93 (95% CI 1.33-2.11) p = 0.001; intimal thickness 0.10 ± 0.17 (95% CI 0.095-0.11) vs. 0.82 ± 0.18 (95% CI 0.074-0.98) (NS); EM 48.33 ± 12.53 vs. 38.86 ± 7.69 (p = 0.005); ßSI 4.21 ± 1.03 vs. 3.64 ± 1.02 (p = 0.004); EF 16.13 ± 5.02 vs. 22.76 ± 4.50 (p = 0.0003). Correlation between: EM and clinical attachment level r = 0.58 (p < 0.001), ßSI and clinical attachment level r = 0.66 (p < 0.001), EF and clinical attachment level 0.59 (p < 0.001). CONCLUSIONS: Parameters of arterial stiffness and EF were worse in patients with SPD and correlated moderately with clinical attachment level. Correlation with compliance and EF was negative.
Assuntos
Doenças Periodontais/complicações , Rigidez Vascular , Perda do Osso Alveolar/complicações , Perda do Osso Alveolar/diagnóstico por imagem , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Perda da Inserção Periodontal/complicações , Estudos Prospectivos , Radiografia DentáriaRESUMO
We report a case of cavitary pneumonia caused by N. otitidiscaviarum in a man with diabetes mellitus and thrombocytopenia treated with systemic corticosteroid. Taxonomic identification involved phenotypic testing and molecular identification that was carried out by DNA sequencing of the 16SrRNA gene.
Assuntos
Humanos , Masculino , Adulto , Corticosteroides , Sequência de Bases , Resistência Microbiana a Medicamentos , Pneumopatias , Nocardia/genética , Nocardia/isolamento & purificação , Nocardiose/diagnóstico , Nocardiose/genética , Classificação , Técnicas e Procedimentos Diagnósticos , Métodos , FenótipoRESUMO
We report a case of cavitary pneumonia caused by N. otitidiscaviarum in a man with diabetes mellitus and thrombocytopenia treated with systemic corticosteroid. Taxonomic identification involved phenotypic testing and molecular identification that was carried out by DNA sequencing of the 16SrRNA gene.
RESUMO
We report a case of cavitary pneumonia caused by N. otitidiscaviarum in a man with diabetes mellitus and thrombocytopenia treated with systemic corticosteroid. Taxonomic identification involved phenotypic testing and molecular identification that was carried out by DNA sequencing of the 16SrRNA gene.
RESUMO
This study describes the genetic relationships and antimicrobial resistance determinants found among 99 clinical isolates of enterococci from 15 different hospitals in Cuba. Pulsed-field gel electrophoresis SmaI analysis demonstrated a high degree of genetic diversity. A limited number of multiresistant Enterococcus faecalis clones, showing resistance to three or more families of antimicrobial agents, were detected simultaneously in different institutions, suggesting inter-hospital circulation of selected clones, and/or selection of particular clones following their introduction into the hospital environment. Antimicrobial resistance determinants, including erm(B), aac(6')-aph(2'), aph(3'), ant(6), vanB (E. faecalis) and vanA (Enterococcus faecium) were detected by PCR in various isolates.
Assuntos
Enterococcus/efeitos dos fármacos , Enterococcus/genética , Aminoglicosídeos/metabolismo , Aminoglicosídeos/farmacologia , Farmacorresistência Bacteriana/genética , HumanosRESUMO
Benzodiazepines are anxiolytic, anticonvulsant, sedative and hypnotic compounds usually prescribed on a long-term basis. Chronic treatment with these compounds induces tolerance, which has been extensively attributed to modifications in the GABAergic neurotransmission. However, a compensatory increase in the excitatory response, named as an oppositional response, has also been put forward as a means for explaining such tolerance. Changes in the excitatory neurotransmission have been found in withdrawn rats after a long treatment with benzodiazepines but these modifications have not been conclusively studied during tolerance. In this work we studied several parameters of the glutamatergic neurotransmission in rats made tolerant to the sedative effect of 3 mg/kg (i.p.) of lorazepam (LZ). We found a decrease in the affinity of cortical NMDA receptors for (3)H-glutamate (K(D): 124.4 +/- 13.3 nM in tolerant rats, 71.6 +/- 10.4 nM in controls, P<0.05) together with a decrease in the in vitro 60 mM K(+)-stimulated cortical glutamate release (59+/- 12% vs. 153 +/- 38%, tolerant rats vs. controls, P<0.05). We conclude that tolerance to the sedative effect of LZ correlates with a decreased sensitivity for glutamate that may in turn diminish the cortical response to a chemical stimulus. Our findings constitute an evidence against the oppositional model of pharmacodynamic tolerance in this experimental condition.
Assuntos
Córtex Cerebral/metabolismo , Ácido Glutâmico/metabolismo , Hipnóticos e Sedativos/farmacologia , Lorazepam/farmacologia , Animais , Sítios de Ligação , Córtex Cerebral/efeitos dos fármacos , Relação Dose-Resposta a Droga , Tolerância a Medicamentos/fisiologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
In previous studies we have demonstrated a possible interaction between the gamma-aminobutyric acid (GABA)ergic and opioid systems involved in the antinociceptive effect of the GABAB agonist, baclofen (BAC). In addition, we have demonstrated that BAC was able to prevent the morphine (MOR) withdrawal syndrome in female, as well as male mice. On the other hand, seasonal variations have been observed in some MOR effects. In the present study, we analysed the effects of BAC on naloxone (NAL)-precipitated withdrawal, during two different seasons. The experiments were performed during two seasons: spring-summer (SS) and autumn-winter (AW) for two years, on male Swiss-Webster albino mice (27-33 g). Mice were rendered dependent by intraperitoneal (i.p.) injection of MOR (2mg/kg), twice daily for 9 days. On the tenth day the dependent animals were divided into two groups: one received NAL (6mg/kg, i.p.) 60 min after the last dose of MOR, to develop the NAL-precipitated withdrawal; the other group received BAC (2mg/kg, i.p.) followed by NAL (6mg/kg, i.p.), injected 30 and 60 min after the last dose of MOR, respectively. Behavioural signs were recorded in the open field for 30 min. Although there were seasonal variations in the MOR withdrawal syndrome, we found that BAC prevents MOR withdrawal irrespective of seasonal variation.
Assuntos
Baclofeno/farmacologia , Morfina/efeitos adversos , Estações do Ano , Síndrome de Abstinência a Substâncias/fisiopatologia , Animais , Nível de Alerta/efeitos dos fármacos , Feminino , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologiaRESUMO
The pharmacological response to benzodiazepines has been demonstrated to be different in aged individuals in comparison to adults. We studied the age-dependent changes in some of the in vitro and behavioral effects of diazepam in aged (24 months old) rats, comparing them to adults (3 months old). We evaluated the in vitro gamma-aminobutyric acid (GABA)-induced 36Cl- uptake and the diazepam potentiation of GABA-stimulated 36Cl- uptake in microsacs from cerebral cortex of both groups of animals. We found no differences in the GABA-stimulated 36Cl- uptake between adult and aged animals, and diazepam failed to potentiate GABA-induced 36Cl- flux in the aged cortical microsacs. We also examined the effect of 0.03-10 mg of diazepam on locomotor activity in an open-field test and the anxiolytic-like action of diazepam in doses ranging from 0.03 to 1 in a dark-light transition test. We observed no anxiolytic-like action of the drug in the dark-light transition test in the aged rats, while there was a shift to the left in the diminution of locomotor activity evaluated by the open-field test. We conclude that the pharmacodynamic changes observed in cortical GABA(A) receptors in aged rats could partially explain the lack of anxiolytic-like action but not the oversedation evidenced in this group of animals.
Assuntos
Envelhecimento/efeitos dos fármacos , Ansiolíticos/farmacologia , Cloretos/metabolismo , Diazepam/farmacologia , Atividade Motora/efeitos dos fármacos , Ácido gama-Aminobutírico/farmacologia , Envelhecimento/fisiologia , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Masculino , Atividade Motora/fisiologia , Ratos , Ratos WistarRESUMO
In previous studies we have demonstrated a possible interaction between the GABAergic and opioid systems involved in the antinociceptive effect of the GABA(B) agonist, baclofen (BAC). On the other hand, sex differences have been observed for the antinociceptive effect of morphine (MOR). In the present study, we analyzed sex-related differences in the MOR abstinence syndrome and its prevention with BAC. Prepubertal male and female Swiss-Webster albino mice (27-33 g) were rendered dependent by intraperitoneal (i.p.) injection of MOR (2, 4 and 8 mg/kg), twice daily for 9 days. On the tenth day the dependent animals were divided into two groups: one received naloxone (NAL) (6 mg/kg, i.p.) 60 min after the last dose of MOR, to precipitate the abstinence syndrome; the other group received BAC (2 mg/kg, i.p.) followed by NAL (6 mg/kg, i.p.), injected 30 and 60 min after the last dose of MOR, respectively. Behavioral signs were recorded in the open field for 30 min. Although there were sex differences in the MOR withdrawal syndrome, we found a lack of sex differences in the prevention of the MOR abstinence syndrome by BAC.
Assuntos
Analgésicos Opioides/efeitos adversos , Baclofeno/farmacologia , Agonistas GABAérgicos/farmacologia , Morfina/efeitos adversos , Síndrome de Abstinência a Substâncias/prevenção & controle , Animais , Comportamento Animal/efeitos dos fármacos , Defecação/efeitos dos fármacos , Estro/efeitos dos fármacos , Feminino , Masculino , Camundongos , Dependência de Morfina/psicologia , Reflexo/efeitos dos fármacos , Caracteres Sexuais , Síndrome de Abstinência a Substâncias/psicologiaRESUMO
Previous works have shown that the administration of the racemic beta -adrenoceptor agent clenbuterol produces a desensitization of the relaxant response in rat uterus. The aim of this work was to study the effects of the optical isomers of clenbuterol on the relaxant response in rat uterus. The administration of (L)-clenbuterol (0.25 mg per kg per day) over 1 or 10 consecutive days, produced a reduction of the relaxant response to isoproterenol in uterine rings precontracted with 50 m m KCl from oestrogenic rats. The administration of (D)-clenbuterol (0.25 mg per kg per day) over 1 or 10 days did not affect the relaxant response of isoproterenol. (L)-clenbuterol also produced a concentration-dependent relaxant effect that was not observed with (D)-clenbuterol. These results show that the beta-adrenergic relaxant response and the desensitization of the relaxant effect to isoproterenol is due to the (L)-isomer and that the (D)-isomer is not involved in these effects.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Clembuterol/farmacologia , Relaxamento Muscular/efeitos dos fármacos , Miométrio/efeitos dos fármacos , Agonistas Adrenérgicos beta/química , Animais , Clembuterol/química , Relação Dose-Resposta a Droga , Feminino , Relaxamento Muscular/fisiologia , Miométrio/fisiologia , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Receptores Adrenérgicos beta 2/fisiologia , EstereoisomerismoRESUMO
Prolonged treatment with the beta(2)-adrenergic agonist clenbuterol (0.25 mg kg(-1) s.c. once daily for 10 days) produced a reduction of the relaxant response and cAMP production mediated by stimulation of beta-adrenoceptors in oestrogen-treated rat uterus. Substantial decreases in the relaxant effect of isoproterenol is observed in uterine rings precontracted with 50 mM KCl from clenbuterol-treated rats. The recovery of the relaxant response was also studied and significant differences were seen between acute and prolonged treatment with clenbuterol (P<0.05 vs control). In contrast the relaxant effect of forskolin and 3-isobutyl-1-methylxanthine was similar in untreated or treated rats. Sodium fluoride also showed a relaxant response which was not affected by the treatment with clenbuterol. The radioligand studies showed a reduction in the number of beta-adrenoreceptors after acute and prolonged treatment with clenbuterol in rat uterus. These results suggest that prolonged treatment with clenbuterol caused a desensitization of the relaxant uterine response through beta(2)-adrenoceptors and also showed differences in the recovery of the relaxant response depending on the duration of treatment.
Assuntos
Agonistas Adrenérgicos beta/farmacologia , Clembuterol/farmacologia , Contração Uterina/efeitos dos fármacos , Antagonistas Adrenérgicos beta/metabolismo , Animais , AMP Cíclico/biossíntese , Di-Hidroalprenolol/metabolismo , Feminino , Técnicas In Vitro , Cinética , Proteínas de Membrana/metabolismo , Relaxamento Muscular/efeitos dos fármacos , Ensaio Radioligante , Ratos , Ratos Wistar , Receptores Adrenérgicos beta 2/efeitos dos fármacos , Receptores Adrenérgicos beta 2/metabolismo , Útero/efeitos dos fármacos , Útero/metabolismoRESUMO
The aim of this study was to analyze the population pharmacokinetics of oxcarbazepine (OCBZ) measuring the serum level of its active metabolite, monohydroxylated oxcarbazepine (MHD). We studied a group of patients with symptomatic and cryptogenic epilepsy treated with OCBZ monotherapy orally, at least for 3 weeks. The mean doses, age and weight of the patients were 17.9 +/- 7.8 mg/kg/day, 35.6 +/- 16.4 years and 70.3 +/- 19.2 kg, respectively. Blood samples were taken before the first morning dose of OCBZ and MHD levels were determined by HPLC. A linear relationship was found between OCBZ dose and MHD serum level (r = 0.844, p < 0.001). The MHD serum concentration (mg/l) can be predicted as 0.85 x OCBZ dose (mg/kg). There was a significant correlation between observed and predicted MHD concentrations for each patient. The mean MHD clearance (Cl/F) calculated was 4.05 +/- 1.69 l/h, with a coefficient variation of 41%. It was independent of dose, age and weight and followed a non normal distribution. The half-life of MHD was 10.50 +/- 3.17 hours. The influence of other antiepileptic drugs on MHD pharmacokinetics was analyzed by comparing the Cl/F medians from groups of patients receiving concomitant drugs with OCBZ monotherapy group where no significant differences were found. The results can be used to estimate a priori OCBZ doses, in order to individualize the treatment.
Assuntos
Anticonvulsivantes/farmacocinética , Carbamazepina/farmacocinética , Epilepsia/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticonvulsivantes/administração & dosagem , Carbamazepina/administração & dosagem , Carbamazepina/análogos & derivados , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , OxcarbazepinaRESUMO
The aim of this study was to analyze the population pharmacokinetics of oxcarbazepine (OCBZ) measuring the serum level of its active metabolite, monohydroxylated oxcarbazepine (MHD). We studied a group of patients with symptomatic and cryptogenic epilepsy treated with OCBZ monotherapy orally, at least for 3 weeks. The mean doses, age and weight of the patients were 17.9 +/- 7.8 mg/kg/day, 35.6 +/- 16.4 years and 70.3 +/- 19.2 kg, respectively. Blood samples were taken before the first morning dose of OCBZ and MHD levels were determined by HPLC. A linear relationship was found between OCBZ dose and MHD serum level (r = 0.844, p < 0.001). The MHD serum concentration (mg/l) can be predicted as 0.85 x OCBZ dose (mg/kg). There was a significant correlation between observed and predicted MHD concentrations for each patient. The mean MHD clearance (Cl/F) calculated was 4.05 +/- 1.69 l/h, with a coefficient variation of 41
. It was independent of dose, age and weight and followed a non normal distribution. The half-life of MHD was 10.50 +/- 3.17 hours. The influence of other antiepileptic drugs on MHD pharmacokinetics was analyzed by comparing the Cl/F medians from groups of patients receiving concomitant drugs with OCBZ monotherapy group where no significant differences were found. The results can be used to estimate a priori OCBZ doses, in order to individualize the treatment.
RESUMO
Rat liver slices were employed as experimental model to characterise the system involved in the transport process which participates in liver tyramine uptake. The uptake of 0.4 micromol l-1of [3H]tyramine by rat liver slices was linear from 5 min up to the end of incubation. At 15 min the uptake was 4.58+/-0.18 pmol mg-1protein. The accumulation of [3H]tyramine was sensitive to temperature (69. 3+/-4.0% inhibition at 0 degrees C, P<0.001), to sodium omission replaced by 150 mmol l-1Tris or 110 mmol l-1Tris+40 mmol l-1choline (27.6+/-6.0%, P<0.01, and 24.6+/-3.8% inhibition, P<0.01, respectively), and the inhibition of Na+-K+-adenosine triphosphatase by 150 micromol l-1ouabain (20.4+/-2.6% decrease, P<0.01). Uptake of [3H]tyramine was cocaine- (10 micromol l-1) and desipramine- (1 micromol l-1) dependent (32.2+/-6.4%, P<0.05, and 31.6+/-4.0% inhibition, P<0.05, respectively). Uptake of [3H]tyramine in rat liver slices was not modified by 30 micromol l-1isoprenaline, 30 micromol l-1corticosterone, 30 micromol l-1normetanephrine and noradrenaline up to 4 micrometers at higher noradrenaline concentrations tyramine transport was diminished (P<0.05). Results achieved by incubation with increasing tyramine concentrations indicate that at the micromolar level hepatic uptake occurs by a combined passive diffusion and transport-mediated mechanism, whereas at greater tyramine concentrations passive transport predominates. These results suggest that both simple diffusion and a transport-mediated mechanism are involved in this uptake from hepatocytes, which presents features similar to those described for type 1 non-neuronal uptake systems.
Assuntos
Fígado/metabolismo , Simpatomiméticos/farmacocinética , Tiramina/farmacocinética , Corticosteroides/farmacologia , Inibidores da Captação Adrenérgica , Animais , Sobrevivência Celular/efeitos dos fármacos , Cocaína/farmacologia , Desipramina/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Técnicas In Vitro , Isoproterenol/farmacologia , Fígado/citologia , Fígado/efeitos dos fármacos , Masculino , Norepinefrina/farmacocinética , Normetanefrina/farmacologia , Ratos , Ratos Wistar , Sódio/farmacologia , Temperatura , Fatores de Tempo , TrítioRESUMO
The aim of this study is to compare four statistical methods for outlier identification in Bioequivalence tests. The methods are based in four confidence intervals, 'parametric','non- parametric','robust with the asymptotic distribution of the M-estimator' and 'robust with the bootstrap distribution'. The drug we used was Diltiazen, in a two sequence randomized crossover study design. The pharmacokinetic parameters measured were the area under the plasma concentration curve (AUC), and the peak drug concentration (CMAX). Time to peak drug concentration (TMAX), was not used here in order to separate the efficiency of the methods from the efficiency of the measurements. The methods were applied to simulated and experimental data. We made two simulations, one with normal data and another one with outliers data. When simulating normal data all methods showed similar profiles and high power. On the contrary, when simulating experiments with outliers data, the parametric method showed low power, whereas robust methods showed just a slight decrement in power. When we analyzed experimental data of AUC, if we used the parametric method (recommended by U.S.P), we were not able to conclude Bioequivalence, but with the other methods, this was possible. This disagreement between parametric and robust procedures was a sign of outliers data. We conclude that the robust methods in bioequivalence assays help us in the identification of outliers as observations with weight equal zero.
Assuntos
Diltiazem/farmacocinética , Equivalência Terapêutica , Adulto , Simulação por Computador , Estudos Cross-Over , Humanos , Masculino , Modelos Estatísticos , Modelos Teóricos , Valores de ReferênciaRESUMO
Adult female rats, undernourished at perinatal age, were evaluated for anxiolytic action in the plus-maze test after acute and chronic administration of diazepam (DZP) and pentobarbital (PTB). Deprived (D) rats chronically treated with vehicle showed an increased anxiety as compared with control (C) animals. A single intraperitoneal (i.p.) administration of DZP (1 mg/kg) or PTB (7.5 mg/kg) produced similar anticonflict effect in both C and D rats. Tolerance to the anxiolytic effect of DZP and PBT developed in C rats after a 15-day administration schedule, whereas no tolerance was observed in D animals. Drug disposition was not altered after chronic treatment either in C or in D rats. Gamma-aminobutyric acid (GABA)-mediated chloride uptake in microsacs of cerebral cortex of naive D rats was decreased as compared with naive C rats. After chronic DZP administration (1 mg/kg/day i.p. for 15 days), GABA-mediated 36Cl- influx in brain cortex microsacs of C rats did not change; however, GABA efficacy was increased in microsacs of D animals. In addition, chronic DZP treatment induced GABA-benzodiazepine uncoupling in brain cortex of C rats, but not in D animals, as assessed by chloride uptake in microsacs. Chronic PTB treatment (7.5 or 30 mg/kg/day i.p. for 15 days) did not modify GABA stimulation or GABA-PTB interaction in cortical microsacs of C or D rats.
Assuntos
Animais Recém-Nascidos/fisiologia , Ansiolíticos/administração & dosagem , Diazepam/administração & dosagem , Distúrbios Nutricionais/fisiopatologia , Pentobarbital/administração & dosagem , Fenômenos Fisiológicos da Nutrição Animal , Animais , Ansiolíticos/farmacocinética , Ansiolíticos/farmacologia , Encéfalo/metabolismo , Cloretos/farmacocinética , Diazepam/farmacocinética , Diazepam/farmacologia , Sinergismo Farmacológico , Tolerância a Medicamentos/fisiologia , Feminino , Aprendizagem em Labirinto/efeitos dos fármacos , Pentobarbital/farmacocinética , Pentobarbital/farmacologia , Ratos , Ratos Wistar , Fatores de Tempo , Ácido gama-Aminobutírico/farmacologiaRESUMO
1. The duodenal transfer of baclofen from sacs of mouse intestine was determined. 2. A linear relationship between the steady-state transfer rate of total and the initial mucosal baclofen concentration was observed, suggesting that the clearance is the same at different concentrations. 3. There was no significant difference in the amount of total drug removed between control and everted tissues. 4. The data support the idea that the principal transfer mechanism for baclofen is simple diffusion in mouse intestine.
Assuntos
Baclofeno/farmacocinética , Absorção Intestinal/fisiologia , Relaxantes Musculares Centrais/farmacocinética , Animais , Baclofeno/análise , Fenômenos Químicos , Físico-Química , Cromatografia Líquida de Alta Pressão , Difusão , Duodeno/metabolismo , Técnicas In Vitro , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Relaxantes Musculares Centrais/análise , Espectrofotometria UltravioletaRESUMO
In rat isolated atria spontaneously beating and labelled with [3H]noradrenaline, exposure to the flavonoid apigenin increased the atrial rate in a concentration-dependent manner (0.01-30 microM). This increase was accompanied by a reduction of 60% in the uptake of [3H]noradrenaline as well as by a modification in the pattern of [3H]noradrenaline and metabolites spontaneously released. Sixty minutes after exposure to 30 microM apigenin, the proportion of unmetabolized [3H]noradrenaline increased from 11% to 45% of the total products collected in the organ bath whereas the tritiated O-methylated deaminated metabolites decreased from 33% to 14% of the total efflux. A small but significant decrease in the outflow of [3H]3,4-dihydroxymandelic acid as well as a tendency to a decrease in the efflux of [3H]3,4-dihydroxyphenylglycol was also observed. Furthermore, apigenin inhibited in a concentration-dependent manner the activity of monoamine oxidase in the rat atrial homogenates. The calculated IC50 (7.7 microM) was within the range that produced 50% of the maximal increase in atrial rate. It is concluded that apigenin possesses the property to increase the atrial rate, probably as a result of a reduction in noradrenaline uptake as well as in monoamine oxidase activity.
Assuntos
Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Átrios do Coração/efeitos dos fármacos , Monoaminoxidase/metabolismo , Norepinefrina/metabolismo , Óleos Voláteis/farmacologia , Animais , Função Atrial , Camomila , Feminino , Átrios do Coração/enzimologia , Átrios do Coração/metabolismo , Técnicas In Vitro , Masculino , Plantas Medicinais , Ratos , Ratos Wistar , TrítioRESUMO
1. The in vitro effect of valproic acid (VA) (10(-6) to 10(-3) M) on glutamic acid decarboxylase (GAD) activity in whole brain and cerebral cortex (CC) of neonates and of adult rats was examined. 2. VA did not induce changes on GAD activity either in CC or in the rest of the brain (RB) of adult animals. 3. But at 10(-3) M, VA induced an increase in GAD activity in homogenates of noncortical brain areas of neonates; no increments were found in CC of these animals. This latter increase was detected in the membrane-bound fraction of the enzyme and was not due to physicochemical nonspecific changes related to the potential solvent activity of VA at this high concentration. 4. We may conclude that VA induces changes on GAD activity in neonatal stages of development but not in adult brain. Therefore, although a direct enhancement of GAD activity may play a role in the mechanism of action of VA in pediatric patients, this cannot be verified in the adult population.
Assuntos
Animais Recém-Nascidos/metabolismo , Encéfalo/enzimologia , Inibidores Enzimáticos/farmacologia , Glutamato Descarboxilase/antagonistas & inibidores , Ácido Valproico/farmacologia , Envelhecimento , Animais , Encéfalo/crescimento & desenvolvimento , Técnicas In Vitro , Masculino , Membranas/efeitos dos fármacos , Membranas/enzimologia , Ratos , Ratos WistarRESUMO
The effect of acute and chronic (10 days) administration of 200 mg/kg (i.p.) of valproic acid (VPA) on endogenous levels of aspartate, glutamate, alanine, glycine and taurine in the cerebral frontal cortex and corpus striatum of rats was studied. Quantification of the amino acid levels was performed by HPLC.Valproic acid (VPA) did not either induce changes on these neurotransmitters contents in corpus striatum after acute treatment. After chronic administration we found a decrease on the endogenous levels of glutamic acid (24%, p < 0.05) which was related to an increase (250%, p < 0.02) of the in vitro KCl evoked release of glutamate. We found decrements in taurine endogenous levels (22%, p < 0.05) which was not associated with an increase of its release.In cerebral frontal cortex there was not found any change neither under the acute nor under the chronic condition.Thus, it may be conclude that chronic treatment with VPA produces decreases on the endogenous levels of glutamate and taurine. However the relevance of this effect concerning it therapeutic action remains unclear.