RESUMO
Cellular mitochondrial function can be assessed using high-resolution respirometry that measures the O2 consumption rate (OCR) across a number of cells. However, a direct measurement of cellular mitochondrial function provides valuable information and physiological insight. In the present study, we used a quantitative histochemical technique to measure the activity of succinate dehydrogenase (SDH), a key enzyme located in the inner mitochondrial membrane, which participates in both the tricarboxylic acid (TCA) cycle and electron transport chain (ETC) as Complex II. In this study, we determine the maximum velocity of the SDH reaction (SDHmax) in individual human airway smooth muscle (hASM) cells. To measure SDHmax, hASM cells were exposed to a solution containing 80 mM succinate and 1.5 mM nitroblue tetrazolium (NBT, reaction indicator). As the reaction proceeded, the change in optical density (OD) due to the reduction of NBT to its diformazan (peak absorbance wavelength of 570 nm) was measured using a confocal microscope with the pathlength for light absorbance tightly controlled. SDHmax was determined during the linear period of the SDH reaction and expressed as mmol fumarate/liter of cell/min. We determine that this technique is rigorous and reproducible, and reliable for the measurement of mitochondrial function in individual cells.
Assuntos
Ciclo do Ácido Cítrico , Mitocôndrias , Humanos , Mitocôndrias/metabolismo , Miócitos de Músculo LisoRESUMO
Cricopharyngeal (CP) dysfunction is a frequent cause of dysphagia among patients with inclusion body myositis. Early identification and prompt treatment is necessary because aspiration pneumonia is a leading cause of mortality among these patients. We present a case of a 57-year-old woman with a history of inclusion body myositis who presented with progressive dysphagia and aspiration pneumonia found to have CP dysfunction treated with endoscopic CP myotomy. Postoperatively, patient's dysphagia improved with no further episodes of aspiration at 2-year follow-up.
RESUMO
Hippocampal synaptic plasticity has been related to learning and adaptive processes developed during chronic drug administration, suggesting the existence of a common neurobiological mechanism mediating drug addiction and memory. Moreover, protein kinase M zeta (PKMζ) is critical for the maintenance of hippocampal long-term potentiation (LTP) and spatial conditioned long-term memories. Also, a link between activity-regulated cytoskeleton-associated protein (Arc), PKMζ and LTP has been proposed. Our previous results demonstrated that re-exposure to the withdrawal environment was able to evoke the memory acquired when the anxiety measured as a diazepam (DZ) withdrawal sign was experienced. In the present work we evaluated if the memory associated with DZ withdrawal could be affected by changes in the contextual cues presented during withdrawal and by intrahippocampal administration of a PKMζ inhibitor. We found that the context was relevant for the expression of withdrawal signs as changes in contextual cues prevented the expression of the anxiety-like behavior observed during plus-maze (PM) re-exposure, the associated enhanced synaptic plasticity and the increase in Arc expression. Furthermore, intrahippocampal administration of PKMζ inhibitor previous to re-exposure to the PM test also impaired expression of anxiety-like behavior and the facilitated LTP. These results support the relevance of the hippocampal synaptic plasticity in the maintenance of the memory trace during benzodiazepines withdrawal, adding new evidences for common mechanisms between memory and drug addiction that can be intervened for treatment or prevention of this pathology.
Assuntos
Sinais (Psicologia) , Proteínas do Citoesqueleto/metabolismo , Diazepam/farmacologia , Hipocampo/metabolismo , Potenciação de Longa Duração , Memória de Longo Prazo , Proteínas do Tecido Nervoso/metabolismo , Proteína Quinase C/metabolismo , Síndrome de Abstinência a Substâncias/metabolismo , Animais , Ansiedade/induzido quimicamente , Ansiedade/metabolismo , Proteínas do Citoesqueleto/genética , Diazepam/efeitos adversos , Potenciais Pós-Sinápticos Excitadores , Expressão Gênica , Hipocampo/fisiologia , Masculino , Proteínas do Tecido Nervoso/genética , Proteína Quinase C/antagonistas & inibidores , Ratos , Ratos WistarRESUMO
Leucine accumulates in fluids and tissues of patients affected by maple syrup urine disease, an inherited metabolic disorder, predominantly characterized by neurological dysfunction. Although, a variable degree of cognition/psychomotor delay/mental retardation is found in a considerable number of individuals affected by this deficiency, the mechanisms underlying the neuropathology of these alterations are still not defined. Therefore, the aim of this study was to investigate the effect of acute intra-hippocampal leucine administration in the step-down test in rats. In addition, the leucine effects on the electrophysiological parameter, long-term potentiation generation, and on the activities of the respiratory chain were also investigated. Male Wistar rats were bilaterally administrated with leucine (80 nmol/hippocampus; 160 nmol/rat) or artificial cerebrospinal fluid (controls) into the hippocampus immediately post-training in the behavioral task. Twenty-four hours after training in the step-down test, the latency time was evaluated and afterwards animals were sacrificed for assessing the ex vivo biochemical measurements. Leucine-treated animals showed impairment in memory consolidation and a complete inhibition of long-term potentiation generation at supramaximal stimulation. In addition, a significant increment in complex IV activity was observed in hippocampus from leucine-administered rats. These data strongly indicate that leucine compromise memory consolidation, and that impairment of long-term potentiation generation and unbalance of the respiratory chain may be plausible mechanisms underlying the deleterious leucine effect on cognition.
Assuntos
Hipocampo , Leucina/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Memória/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Eletrofisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Humanos , Potenciação de Longa Duração/fisiologia , Masculino , Memória/fisiologia , Testes Neuropsicológicos , Ratos , Ratos WistarRESUMO
The present study describes the effects of sauroine (1), the main alkaloid obtained from Huperzia saururus, on memory retention and learning. To evaluate this, electrophysiological experiments and behavioral tests (step down) were performed on male Wistar rats. The results showed that 1 improved memory retention in the step-down test, significantly increasing hippocampal plasticity. Thus, 1 seems to be a constituent responsible for the activity claimed in folk medicine for H. saururus in Argentina.
Assuntos
Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Comportamento/efeitos dos fármacos , Huperzia/química , Memória/efeitos dos fármacos , Plantas Medicinais/química , Alcaloides/química , Animais , Argentina , Hipocampo/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
UNLABELLED: Infection by Helicobacter pylori (H. pylori) and its associated complications, such as gastric cancer, constitute a true public health problem due to the high morbidity and mortality rates in Colombia and Latin America, where it is highly prevalent. OBJECTIVE: To characterize the prevalence of H. pylori infection in the medical population ofMedellin, Colombia. METHODS: A transversal-cut observational epidemiological study was done, 342 physicians were included. The presence of H. pylori infection, diagnosed with carbon 13-labelled urea breath test, and its association with personal aspects, history of gastric disease and clinical manifestations was evaluated. RESULTS: The general prevalence of H. pylori infection was found to be 77.2% (CI 95%: 72.4% to 81.5%). Discriminating by gender, it represents a prevalence of 78.4% in men and 72.6% in women, without any significant association (chi-square, p = 0.37). Of the total 342 participants, 183 (53.5%) presented at least one suspected episode of gastric disease, and of these, 141 (77%) were positive and 42 (23%) were negative for H. pylori; of the 264 H. pylori positive participants, 141 (53.4%) had history of gastric disease and 123 (46.6%) were asymptomatic. CONCLUSIONS: Prevalence of H. pylori infection in the medical population in Medellin, Colombia, is 77.2% (CI 95%: 72.4% to 81.5%), in accordance to the epidemiologic profile of the region. Also, 46.6% of individuals infected by H. pylori were asymptomatic and with no history or symptoms suggestive of the presence of the bacteria, which is only possible to determine after appropriate testing of the individuals.
Assuntos
Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Doenças Profissionais/epidemiologia , Médicos/estatística & dados numéricos , Carbono , Colômbia/epidemiologia , Estudos Transversais , Dispepsia/epidemiologia , Dispepsia/microbiologia , Feminino , Helicobacter pylori/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estatísticas não Paramétricas , UreiaRESUMO
Cellular prion protein (PrP(c)) has been associated with some physiological functions in the last few years. In a previous paper, we have demonstrated an increased hippocampal synaptic transmission in adult mice lacking this protein. In the present study, we investigate the impact of aging on the generation and maintenance of hippocampal long-term Potentiation (LTP) in 9-month-old mice devoid of PrP(c) protein (Prnp(0/0)). We observed a lower threshold for inducing LTP in 9-month-old Prnp(0/0) mice compared to wild-type ones at the same age. The maintenance of dentate gyrus LTP was more persistent in hippocampal slices from Prnp(0/0) mice. Furthermore, the expression of mRNA for NR2A and NR2B subunits of the NMDA glutamatergic receptor in hippocampus of aged Prnp(0/0) animals showed an increase compared to the wild type. We propose that increased hippocampal glutamatergic transmission in Prnp(0/0) mice is related to the enhanced plasticity and persistence of the dentate LTP.
Assuntos
Envelhecimento/metabolismo , Regulação da Expressão Gênica/fisiologia , Potenciação de Longa Duração/fisiologia , Proteínas PrPC/fisiologia , Envelhecimento/genética , Animais , Hipocampo/fisiologia , Potenciação de Longa Duração/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas PrPC/deficiência , Proteínas PrPC/genética , Receptores de N-Metil-D-Aspartato/biossíntese , Receptores de N-Metil-D-Aspartato/genéticaRESUMO
We have previously described that perinatally undernourished rats showed increased locus coeruleus activity, a phenomenon reversed by repeated desipramine or fluoxetine administration. Since there is reciprocal modulation between the locus coeruleus and the dorsal raphe nucleus, and because these structures are associated with the pathophysiology of different states of anxiety, we evaluated the activity of serotonergic dorsal raphe neurons from early malnourished animals compared with controls, using in vivo extracellular single-unit recordings. The number of spontaneously active cells/track was significantly higher in protein-deprived animals, although the firing rate and the sensitivity of 5-HT(1A) receptors did not differ from those of controls. Five days of fluoxetine administration (5 mg/kg/day i.p.) was able to reverse the increased number of active serotonergic cells without affecting their firing rate. Furthermore, subsensitivity of 5-HT(1A) autoreceptors developed in the same way after repeated fluoxetine administration in both control and protein-deprived animals. These results suggest that the increased noradrenergic transmission observed in protein-deprived animals may induce an activation of serotonergic neurons in the dorsal raphe nucleus, and that this effect is normalized following fluoxetine treatment, which normalizes locus coeruleus activity.
Assuntos
Fluoxetina/farmacologia , Deficiência de Proteína/metabolismo , Núcleos da Rafe/efeitos dos fármacos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Serotonina/metabolismo , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Potenciais de Ação , Animais , Relação Dose-Resposta a Droga , Feminino , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Gravidez , Núcleos da Rafe/metabolismo , Ratos , Ratos Wistar , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Receptor 5-HT1A de Serotonina/metabolismo , Agonistas do Receptor de SerotoninaRESUMO
The cellular prion protein plays a role in the etiology of transmissible and inherited spongiform encephalopathies. However, the physiological role of the cellular prion protein is still under debate. Results regarding the synaptic transmission using the same strain of animals where the cellular prion protein gene was ablated are controversial, and need further investigation. In this work, we have studied the hippocampal synaptic transmission in mice devoid of normal cellular prion protein, and have shown that these animals present an increased excitability in this area by the lower threshold (20 Hz) to generate long-term potentiation (LTP) in hippocampal dentate gyrus when compared to wild-type animals. The mice devoid of normal cellular prion protein are also more sensitive to the blocking effects of dizocilpine and 2-amino-5-phosphonopentanoic acid on the hippocampal long-term potentiation generation. In situ hydridization experiments demonstrated overexpression of the mRNAs for the N-methyl-D-aspartate (NMDA) receptor NR2A and NR2B subunits in mice devoid of normal cellular prion protein. Therefore, our results indicate that these animals have an increased hippocampal synaptic plasticity which can be explained by a facilitated glutamatergic transmission. The higher expression of specific N-methyl-d-aspartate receptor subunits may account for these effects.
Assuntos
Giro Denteado/fisiologia , Plasticidade Neuronal/fisiologia , Proteínas PrPC/genética , Animais , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Expressão Gênica , Hibridização In Situ , Potenciação de Longa Duração/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores de N-Metil-D-Aspartato/genéticaRESUMO
The present study attempts to determine which mechanisms underlie the retrograde facilitation of memory induced by microinjection hippocampal melanin-concentrating hormone (MCH) on the inhibitory avoidance paradigm. Previous reports using this test on the hippocampus suggest that NMDA receptor-mediated mechanisms are involved in memory processing and are also necessary for the induction of long-term potentiation (LTP) of the hippocampal dentate gyrus. In addition, alterations in expression of synaptic NMDA subunits in the hippocampus have been associated with memory formation of an inhibitory avoidance task. We have studied the effects of the neuropeptide upon the electrophysiological parameters using hippocampal slices from rats injected with the peptide and tested in step-down tests as well as possible changes in the mRNA expression of NMDA receptor subunits. We postulate that the increased facility to induce LTP, and the overexpression of this N-methyl-D-aspartate mRNA receptor subunits induced by MCH, could be behind the retrograde facilitation observed after MCH hippocampal microinjection.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hormônios Hipotalâmicos/farmacologia , Potenciação de Longa Duração/efeitos dos fármacos , Melaninas/farmacologia , N-Metilaspartato/metabolismo , Hormônios Hipofisários/farmacologia , Subunidades Proteicas/genética , Receptores de N-Metil-D-Aspartato/genética , Animais , Eletrofisiologia , Hipocampo/metabolismo , Hibridização In Situ , Injeções , Potenciação de Longa Duração/fisiologia , Masculino , Subunidades Proteicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
The development of tolerance to the hypolocomotor effects of Diazepam (DZ) is thought to be a contingent or learning phenomenon. In previous reports, we demonstrated a positive correlation between the development of tolerance to the sedative effects of DZ and hippocampal synaptic plasticity. Furthermore, previous exposure to the drug administration context blocks both the tolerance to sedative effects of DZ and the increased hippocampal plasticity. The results of the present investigation show that the development of tolerance to hypolocomotor action of DZ (5 mg/kg/day) for 4 days results in a significant increase in the hybridization signals for mRNA for N-methyl-D-aspartate (NMDA) glutamatergic receptor NR1 and NR2B subunits in the hippocampal dentate gyrus. Furthermore, we have observed more benzodiazepine binding sites in the hippocampus of non-tolerant animals. We conclude that the increased hippocampal synaptic efficacy in DZ tolerant rats, may be NMDA receptor dependent due to an increased recombinant NR1-NR2B complex observed in the hippocampal formation of tolerant rats.
Assuntos
Diazepam/farmacologia , Tolerância a Medicamentos , Moduladores GABAérgicos/farmacologia , Hipocampo/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/biossíntese , Animais , Benzodiazepinas/farmacocinética , Sítios de Ligação , Contagem de Células , Expressão Gênica , Hipocampo/anatomia & histologia , Hipocampo/metabolismo , Imuno-Histoquímica , Hibridização In Situ , Masculino , Atividade Motora/efeitos dos fármacos , Sondas de Oligonucleotídeos , RNA Mensageiro/biossíntese , RNA Mensageiro/efeitos dos fármacos , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/genética , Sinaptossomos/efeitos dos fármacosRESUMO
Early results from our laboratory have demonstrated a positive correlation between increased hippocampal synaptic plasticity and development of tolerance to hypolocomotive effect of Diazepam (DZ). We have found recently, that pre-exposure to DZ administration context impairs increase of hippocampal synaptic plasticity in conjunction with tolerance to DZ. These findings have suggested, that the tolerance to DZ is context specific. Furthermore, the hippocampus can be critically involved in the behavioral expression of conditioned tolerance to DZ. The results of the present investigation show that animals chronically treated with DZ for 18 days exhibit withdrawal signs, evaluated as an increased anxiety in an elevated plus maze. These animals also show, a facilitation in the threshold to induce long-term potentiation in the hippocampal formation. These phenomena have a strong dependency on the drug administration context, since both are reversed after the introduction of some changes in the drug administration environment. Furthermore, the alteration of some environmental cues increased the locomotive activity in animals that did not show anxiety as a withdrawal signs. We conclude that a common neural system could underlie the behavioral expression of the conditioned tolerance and dependence on DZ.
Assuntos
Ansiolíticos/efeitos adversos , Diazepam/efeitos adversos , Meio Ambiente , Síndrome de Abstinência a Substâncias/psicologia , Animais , Ansiedade/psicologia , Sinais (Psicologia) , Giro Denteado/fisiologia , Eletrofisiologia , Hipocampo/fisiologia , Técnicas In Vitro , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Atividade Motora/fisiologia , Ratos , Transmissão Sináptica/fisiologiaRESUMO
The chronic diazepam administration in rats has been show from our previous results, to produce an increased synaptic plasticity. Furthermore, this occurs with a concomitant over expression of the mRNA NR1 and NR2B N-methyl-D-aspartate receptor subunits. MK-801, a non-competitive antagonist of N-methyl-D-aspartate receptor, impairs both the development of conditioned tolerance to diazepam and the hippocampal long-term potentiation generation. In the present study, we have further investigated the hippocampal glutamatergic transmission in the development of tolerance to diazepam. Our results demonstrate that the development of tolerance to the hypolocomotive effect of diazepam, along with the increased hippocampal synaptic plasticity and the associated over expression of the mRNA NR1 and NR2B N-methyl-D-aspartate receptor subunits, were blocked by previous MK-801 administration. We suggest that the participation of hippocampal glutamatergic transmission is relevant to increased hippocampal synaptic plasticity, the latter being a neurobiological mechanism behind the development of the conditioned tolerance to diazepam.
Assuntos
Diazepam/administração & dosagem , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Análise de Variância , Animais , Comportamento Animal , Contagem de Células/métodos , Interações Medicamentosas , Tolerância a Medicamentos , Estimulação Elétrica/métodos , Eletrofisiologia/métodos , Potenciais Evocados/efeitos dos fármacos , Potenciais Evocados/efeitos da radiação , Moduladores GABAérgicos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/efeitos da radiação , Hibridização In Situ/métodos , Potenciação de Longa Duração/efeitos dos fármacos , Potenciação de Longa Duração/efeitos da radiação , Masculino , Atividade Motora/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/genéticaRESUMO
We have previously described an increased locus coeruleus activity in perinatally protein-deprived rats. Since locus coeruleus dysfunction has been involved in different types of anxiety disorders and considering the modulating action of serotonergic transmission on locus coeruleus activity, we assessed the effect of fluoxetine, a selective serotonin reuptake inhibitor (SSRI), on locus coeruleus activity as measured by the firing rate and the number of spontaneously active cells/track. Repeated fluoxetine administration reduced locus coeruleus activity in both control and protein-deprived rats, although the reduction was greater in protein-deprived rats. Dose-response curves for the inhibitory effect of clonidine showed subsensitivity of alpha2-adrenergic autoreceptors in protein-deprived rats, a phenomenon reversed by fluoxetine treatment. Dose-response curves for the inhibitory effect of 2,5-dimethoxy-4-iodoamphetamine (DOI) were similar in both groups of rats. Following fluoxetine administration, subsensitivity to this effect developed in control but not in protein-deprived rats. Extracellular noradrenaline level in the prefrontal cortex, as measured by microdialysis procedure, was higher in protein-deprived rats compared to controls, and this difference was reduced after fluoxetine administration. A challenge with yohimbine increased the extracellular noradrenaline level in control but not in protein-deprived rats, suggesting subsensitivity of alpha2-adrenergic autoreceptors in early protein malnourished animals. These results stress the complexity of plastic changes induced by early protein malnutrition and sustain the hypothesis that perinatally protein-deprived rats may represent a useful animal model for screening antipanic agents.
Assuntos
Antidepressivos de Segunda Geração/farmacologia , Fluoxetina/farmacologia , Locus Cerúleo/fisiologia , Desnutrição Proteico-Calórica/fisiopatologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Agonistas alfa-Adrenérgicos/farmacologia , Antagonistas Adrenérgicos alfa/farmacologia , Anfetaminas/farmacologia , Animais , Monoaminas Biogênicas/metabolismo , Clonidina/farmacologia , Relação Dose-Resposta a Droga , Eletrofisiologia , Espaço Extracelular/efeitos dos fármacos , Espaço Extracelular/metabolismo , Feminino , Locus Cerúleo/citologia , Locus Cerúleo/efeitos dos fármacos , Microdiálise , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/fisiologia , Norepinefrina/metabolismo , Norepinefrina/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Gravidez , Ratos , Ratos Wistar , Agonistas do Receptor de Serotonina/farmacologia , Ioimbina/farmacologiaRESUMO
RATIONALE: The medial prefrontal cortex (mPFC), a forebrain region that regulates cognitive function and reward-motivated behaviors, has been implicated in the neuropathological mechanisms of drug addiction and withdrawal. In cocaine-abstinent human addicts, neuronal activity of the mPFC is increased in response to cocaine re-exposure or drug-associated cues. Additionally, repeated cocaine exposure alters the membrane properties and ion channel function of mPFC pyramidal neurons in drug-withdrawn rats, leading to an increased firing in response to excitatory stimuli. Nitric oxide (NO), a diffusible neuromodulator of neuronal excitability, may play a role in initiating and maintaining behavioral effects of psychostimulants. However, the role of NO in the mechanisms by which cocaine affects membrane excitability is not well clarified. OBJECTIVES: In this study, we attempted to determine whether inhibition of neuronal nitric oxide synthase (nNOS) altered the changes induced by repeated cocaine exposure and withdrawal. METHODS: Visualized whole-cell current clamp recordings in brain slices containing the mPFC of rats administered (once per day for 5 days) with either vehicle (10% Cremophor EL in saline 0.9%), cocaine (15 mg/kg, i.p.), or cocaine and the nNOS inhibitor 7-NI (50 mg/kg, i.p.) were employed. RESULTS: We found that nNOS inhibition prevented cocaine sensitization and the increased membrane excitability of pyramidal cells, evidenced by an increased number of evoked spikes and reductions in inward rectification observed after short-term withdrawal from cocaine. CONCLUSIONS: These findings suggest that NO plays an important role in chronic cocaine-induced deregulation of the mPFC activity that may contribute to the development of behavioral sensitization and cocaine withdrawal.
Assuntos
Cocaína/administração & dosagem , Óxido Nítrico Sintase Tipo I/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Animais , Comportamento Animal/efeitos dos fármacos , Transtornos Relacionados ao Uso de Cocaína/enzimologia , Inibidores Enzimáticos/farmacologia , Indazóis/farmacologia , Masculino , Óxido Nítrico Sintase Tipo I/antagonistas & inibidores , Técnicas de Patch-Clamp , Córtex Pré-Frontal/metabolismo , Células Piramidais/metabolismo , Ratos , Ratos Sprague-Dawley , Recompensa , Síndrome de Abstinência a Substâncias/fisiopatologiaRESUMO
Although the hypothalamus has been long considered the main ghrelin (Ghr) target organ mediating orexigenic effects, recently it has been shown that in-vivo Ghr hippocampus administration improves learning and memory in the inhibitory avoidance paradigm. However, the possible mechanisms underlying this memory facilitation effect have not been clarified. Given that the biochemical memory cascade into the hippocampus involves nitric oxide (NO) synthesis via NO synthase (NOS) activation, we investigated 1) if Ghr administration modulated NOS activity in the hippocampus; and 2) if hippocampal NOS inhibition influenced Ghr-induced memory facilitation, using a behavioral paradigm, biochemical determinations and an electrophysiological model. Our results showed that intra-hippocampal Ghr administration increased the NOS activity in a dose dependent manner, and reduced the threshold for LTP generation in dentate gyrus of rat hippocampus. Moreover, pre-administration of NG-nitro-l-arginine (l-NOArg) in the hippocampus partially prevented the Ghr-induced memory improvement, abolished the increase in NOS activity, and prevented the decreased threshold to generate LTP induced by Ghr. These findings suggest that activation of the NOS/NO pathway in hippocampus participates in the effects of Ghr on memory consolidation and is related with plastic properties of the hippocampal three-synaptic loop.
Assuntos
Giro Denteado/enzimologia , Grelina/fisiologia , Potenciação de Longa Duração/fisiologia , Memória/fisiologia , Óxido Nítrico Sintase/metabolismo , Análise de Variância , Animais , Aprendizagem da Esquiva/fisiologia , Giro Denteado/efeitos dos fármacos , Giro Denteado/fisiologia , Relação Dose-Resposta a Droga , Ativação Enzimática , Grelina/administração & dosagem , Técnicas In Vitro , Potenciação de Longa Duração/efeitos dos fármacos , Masculino , Memória/efeitos dos fármacos , Óxido Nítrico Sintase/efeitos dos fármacos , Ratos , Ratos Wistar , Análise de Regressão , Sistemas do Segundo Mensageiro/fisiologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
La infección por Helicobacter pylori (H. pylori) y las omplicaciones asociadas, como el cáncer gástrico, representan un verdadero problema de salud pública porque lideran las tasas de morbilidad y mortalidad en Colombia y Latinoamérica, en donde es altamente prevalente. Objetivo: caracterizar la prevalencia de la infección por H. pylori en la población médica de Medellín, Colombia. Métodos: se realizó un estudio epidemiológico bservacional transversal donde se incluyeron 342 médicos. Se evaluó la presencia de la infección por H. pylori mediante la prueba de aliento con urea marcada con carbono 13 y su asociación con aspectos personales, antecedentes de enfermedad gástrica y manifestaciones clínicas. Resultados: se encontró una prevalencia general de infección por H. pylori de 77.2% (IC 95%: 72.4% a 81.5%), que discriminada por género epresenta una prevalencia de 78.4% en hombres y 72.6% en mujeres, sin asociación significativa (Chi- cuadrado p= 0.37). Del total de los 342 participantes, 183 (53.5%) presentaron al menos un evento sospechoso de enfermedad gástrica y de éstos, 141 (77%) fueron positivos y 42 (23%) negativos para H. pylori; de los 264 participantes H. pylori positivos, 141 (53.4%) presentaban antecedentes de enfermedad gástrica y 123 (46.6%) fueron asintomáticos. Conclusiones: la prevalencia de la infección por H. pylori en lapoblación médica de Medellín, Colombia, es de 77.2% (IC 95%: 72.4% a 81.5%), acorde con el perfil epidemiológico de la región. Además, el 46.6% de los individuos infectados por H. pylori fueron asintomáticos y no hay antecedentes ni síntomas que permitan sospechar la presencia de la bacteria, la cual sólo es posible determinar tras el estudio apropiado de los individuos.
Infection by Helicobacter pylori (H. pylori) and its associated complications, such as gastric cancer, constitute a true public health problem due to the high morbidity and mortality rates in Colombia and Latin America, where it is highly prevalent. Objective: To characterize the prevalence of H. pylori infection in the medical population of Medellín, Colombia. Methods: A transversal-cut observational epidemiological study was done, 342 physicians were included. The presence of H. pylori infection, diagnosed with carbon 13-labelled urea breath test, and its association with personal aspects, history of gastric disease and clinical manifestations was evaluated. Results: The general prevalence of H. pylori infection was found to be 77.2% (CI 95%: 72.4% to 81.5%). Discriminating by gender, it represents a prevalence of 78.4% in men and 72.6% in women, without any significant association (chisquare, p=0.37). Of the total 342 participants, 183 (53.5%) presented at least one suspected episode of gastric disease, and of these, 141 (77%) were positive and 42 (23%) were negative for H. pylori; of the 264 H. pylori positive participants, 141 (53.4%) had history of gastric disease and 123 (46.6%) were asymptomatic. Conclusions: Prevalence of H. pylori infection in the medical population in Medellín, Colombia, is 77.2% (CI 95%: 72.4% to 81.5%), in accordance to the epidemiologic profile of the region. Also, 46.6% of individuals infected by H. pylori were asymptomatic and with no history or symptoms suggestive of the presence of the bacteria, which is only possible to determine after appropriate testing of the individuals.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Infecções por Helicobacter/epidemiologia , Doenças Profissionais/epidemiologia , Médicos/estatística & dados numéricos , Carbono , Colômbia/epidemiologia , Estudos Transversais , Dispepsia/epidemiologia , Dispepsia/microbiologia , Helicobacter pylori/isolamento & purificação , Prevalência , Estatísticas não Paramétricas , UreiaRESUMO
La infección por Helicobacter pylori (H. pylori) y las omplicaciones asociadas, como el cáncer gástrico, representan un verdadero problema de salud pública porque lideran las tasas de morbilidad y mortalidad en Colombia y Latinoamérica, en donde es altamente prevalente. Objetivo: caracterizar la prevalencia de la infección por H. pylori en la población médica de Medellín, Colombia. Métodos: se realizó un estudio epidemiológico bservacional transversal donde se incluyeron 342 médicos. Se evaluó la presencia de la infección por H. pylori mediante la prueba de aliento con urea marcada con carbono 13 y su asociación con aspectos personales, antecedentes de enfermedad gástrica y manifestaciones clínicas. Resultados: se encontró una prevalencia general de infección por H. pylori de 77.2% (IC 95%: 72.4% a 81.5%), que discriminada por género epresenta una prevalencia de 78.4% en hombres y 72.6% en mujeres, sin asociación significativa (Chi- ¹cuadrado p= 0.37). Del total de los 342 participantes, 183 (53.5%) presentaron al menos un evento sospechoso de enfermedad gástrica y de éstos, 141 (77%) fueron positivos y 42 (23%) negativos para H. pylori; de los 264 participantes H. pylori positivos, 141 (53.4%) presentaban antecedentes de enfermedad gástrica y 123 (46.6%) fueron asintomáticos. Conclusiones: la prevalencia de la infección por H. pylori en lapoblación médica de Medellín, Colombia, es de 77.2% (IC 95%: 72.4% a 81.5%), acorde con el perfil epidemiológico de la región. Además, el 46.6% de los individuos infectados por H. pylori fueron asintomáticos y no hay antecedentes ni síntomas que permitan sospechar la presencia de la bacteria, la cual sólo es posible determinar tras el estudio apropiado de los individuos.(AU)
Infection by Helicobacter pylori (H. pylori) and its associated complications, such as gastric cancer, constitute a true public health problem due to the high morbidity and mortality rates in Colombia and Latin America, where it is highly prevalent. Objective: To characterize the prevalence of H. pylori infection in the medical population of Medellín, Colombia. Methods: A transversal-cut observational epidemiological study was done, 342 physicians were included. The presence of H. pylori infection, diagnosed with carbon 13-labelled urea breath test, and its association with personal aspects, history of gastric disease and clinical manifestations was evaluated. Results: The general prevalence of H. pylori infection was found to be 77.2% (CI 95%: 72.4% to 81.5%). Discriminating by gender, it represents a prevalence of 78.4% in men and 72.6% in women, without any significant association (chisquare, p=0.37). Of the total 342 participants, 183 (53.5%) presented at least one suspected episode of gastric disease, and of these, 141 (77%) were positive and 42 (23%) were negative for H. pylori; of the 264 H. pylori positive participants, 141 (53.4%) had history of gastric disease and 123 (46.6%) were asymptomatic. Conclusions: Prevalence of H. pylori infection in the medical population in Medellín, Colombia, is 77.2% (CI 95%: 72.4% to 81.5%), in accordance to the epidemiologic profile of the region. Also, 46.6% of individuals infected by H. pylori were asymptomatic and with no history or symptoms suggestive of the presence of the bacteria, which is only possible to determine after appropriate testing of the individuals.(AU)
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Infecções por Helicobacter/epidemiologia , Doenças Profissionais/epidemiologia , Médicos/estatística & dados numéricos , Carbono/diagnóstico , Colômbia/epidemiologia , Estudos Transversais , Dispepsia/epidemiologia , Dispepsia/microbiologia , Helicobacter pylori/isolamento & purificação , Estatísticas não Paramétricas , Prevalência , Ureia/diagnósticoRESUMO
Con el fin de localizar los sitios del cerebro donde las aferencias serotoninérgicas podrian regular las respuestas lordóticas, se inyectó la neurotoxina 5-7-dihidroxitriptamina en el núcleo ventromediano hipotalámo (VMN) o en la amígdala medial (AM) inducida por administración de estrógeno fue medida mediante el cociente lordótico, siendo significantemente mayor en animales que recibieron la neurotoxina en AM. Por el contrario, el cociente loraótico fue menor en animales inyectados en el VMN. No se encontraron diferencias significantes con los controles cuando los mismos animales fueron tratados con progesterona. Se propone que las aferencias serotoninérgicas actuan en el VMN facilitando las respuestas lordóticas, mientras que dichas aferencias tienen un efecto opuesto en AM. No es necesario que los terminales serotoninérgicos en VMN y AM estén intactos para que la progesterona ejerza su efecto potenciador de la receptividad sexual (AU)
Assuntos
Ratos , Animais , Feminino , Comportamento Sexual Animal/efeitos dos fármacos , Serotonina/farmacologia , Postura , Di-Hidroxitriptaminas/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Cérebro/patologiaRESUMO
Con el fin de localizar los sitios del cerebro donde las aferencias serotoninérgicas podrian regular las respuestas lordóticas, se inyectó la neurotoxina 5-7-dihidroxitriptamina en el núcleo ventromediano hipotalámo (VMN) o en la amígdala medial (AM) inducida por administración de estrógeno fue medida mediante el cociente lordótico, siendo significantemente mayor en animales que recibieron la neurotoxina en AM. Por el contrario, el cociente loraótico fue menor en animales inyectados en el VMN. No se encontraron diferencias significantes con los controles cuando los mismos animales fueron tratados con progesterona. Se propone que las aferencias serotoninérgicas actuan en el VMN facilitando las respuestas lordóticas, mientras que dichas aferencias tienen un efecto opuesto en AM. No es necesario que los terminales serotoninérgicos en VMN y AM estén intactos para que la progesterona ejerza su efecto potenciador de la receptividad sexual