RESUMO
Two experiments using rats in a contextual fear memory preparation compared two approaches to reduce conditioned fear: (1) pharmacological reconsolidation blockade and (2) reactivation-plus-extinction training. In Experiment 1, we explored different combinations of reactivation-plus-extinction parameters to reduce conditioned fear and attenuate reacquisition. In Experiment 2, memory reactivation was followed by extinction training or administration of midazolam (MDZ) (vs. vehicle) to reduce conditioned fear and attenuate spontaneous recovery. We found both treatments to be equally effective in both experiments. This study suggests that parameters leading to memory destabilization during reactivation are critical to observe long-lasting effects of MDZ or reactivation plus extinction.
Assuntos
Medo/efeitos dos fármacos , Medo/fisiologia , Memória/efeitos dos fármacos , Memória/fisiologia , Testes Psicológicos , Animais , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Masculino , Midazolam/farmacologia , Psicotrópicos/farmacologia , Distribuição Aleatória , Ratos WistarRESUMO
El síndrome de SAPHO es una condición relativamente rara, la cual designa varios desordenes que gana su nombre del epónimo por la sinovitis, acné, pustulosis, hiperostosis, osteítis. Relato de caso. Masculino, 15 años de edad, blanco, estudiante que hace dos años se encuentra en tratamiento por acné conglobata, que hace dos meses evoluciona con artralgia en pierna izquierda, tarsitis derecha y lumbalgia inflamatoria. Al examen físico se encuentra, palidez cutánea, pies invertidos y planos, rodillas en valgo, sacroileítis acentuada a la izquierda, tarsitis derecha, dolor en entesis (calcáneos) piel con lesiones cutáneas acneiformes extensas en rostro, dorso y tórax anterior. Exámenes complementarios: anemia normocitica y normo crómica, RX: sacro iliacas con señales de sacroileítis bilateral con psuedo alargamiento en la parte izquierda. USG de los pies normales, fondo de ojo: normal, HLAB27: negativa. Se inició indometacina y fisioterapia. Discusión: cuadro clínico de acné, artropatía inflamatoria característica del síndrome SAPHO, tratamiento conservador.
SAPHO syndrome is a relatively rare condition which designates several disorders that gain its name from the eponymous by synovitis, acne, pustular, hyperostosis, osteitis. Case report. Male, 15 years old, white, student who two years ago is in treatment for acne conglobata, who two months ago evolves with left leg arthralgia, right tarsitis and inflammatory low back pain. Physical examination includes skin paleness, inverted and flat feet, valgus knees, left sore sacroiliitis, right tarsitis, pain in entesis (calcaneus) skin with extensive acneiform skin lesions on face, dorsum and anterior thorax. Complementary examinations: normocytic anemia and normal chromosome, RX: iliac sacrum with signs of bilateral sacroiliitis with psuedo elongation in the left side. USG of normal feet. Fundus of eye: normal, HLAB27: negative. Indomethacin and physiotherapy were started. Discussion: clinical picture of acne, inflammatory arthropathy characteristic of SAPHO syndrome, conservative treatment.
Assuntos
Masculino , Humanos , Adolescente , Síndrome de Hiperostose Adquirida/diagnóstico , Síndrome de Hiperostose Adquirida/terapia , Acne Conglobata/complicações , Avulsões CutâneasRESUMO
It is known that a consolidated memory can return to a labile state and become transiently malleable following reactivation. This instability is followed by a restabilization phase termed reconsolidation. In this work, we explored whether an unrelated appetitive experience (voluntary consumption of diluted sucrose) can affect a contextual fear memory in rats during the reactivation-induced destabilization phase. Our findings show that exposure to an appetitive experience following reactivation can diminish fear retention. This effect persisted after 1 wk. Importantly, it was achieved only under conditions that induced fear memory destabilization. This result could not be explained as a potentiated extinction, because sucrose was unable to promote extinction. Since GluN2B-containing NMDA receptors in the basolateral amygdala complex (BLA) have been implicated in triggering fear memory destabilization, we decided to block pharmacologically these receptors to explore the neurobiological bases of the observed effect. Intra-BLA infusion with ifenprodil, a GluN2B-NMDA antagonist, prevented the fear reduction caused by the appetitive experience. In sum, these results suggest that the expression of a fear memory can be dampened by an unrelated appetitive experience, as long as memory destabilization is achieved during reactivation. Possible mechanisms behind this effect and its clinical implications are discussed.
Assuntos
Comportamento Apetitivo , Complexo Nuclear Basolateral da Amígdala/fisiologia , Medo , Consolidação da Memória/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologia , Retenção Psicológica/fisiologia , Animais , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Masculino , Piperidinas/administração & dosagem , Ratos Wistar , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
The objective of the study was to evaluate prospectively real-life experience on the effect of belimumab on patients with active systemic lupus erythematosus (SLE). Forty-eight patients with active SLE were evaluated after 1 year of continuous treatment. Thirty-eight patients were still on treatment at the end of 1 year, and it was possible to observe significant clinical improvement in the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score with a decrease from 12 ± 3.0 to 2.5 ± 2.5, also a decrease on the daily steroid dose from 30 ± 12.5 to 7.5 ± 5.0 mg and partial improvement on serology. Belimumab treatment is associated with real benefit in the majority of patients that maintain active disease in spite of continuing on standard of care.
Assuntos
Corticosteroides/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Corticosteroides/efeitos adversos , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Brasil , Ensaios Clínicos como Assunto , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto JovemRESUMO
It has been suggested that, unlike pure extinction which typically results in the return of the fear response under a variety of circumstances, memory reactivation followed by extinction can attenuate the reemergence of conditioned fear. The reactivation-extinction procedure has attracted the attention of basic and clinical researchers due to its potential clinical value for the treatment of psychiatric conditions, such as anxiety and drug abuse disorders. However, mixed results have been achieved so far in replicating and understanding this paradigm. It has been proposed that memory destabilization could be critical in this sense. Using contextual fear conditioning in rats and midazolam as an amnesic agent, we first determined what reactivation conditions are necessary to destabilize the mnemonic trace. After establishing the conditions for memory destabilization, a series of experiments was conducted to determine if destabilization is critical for the success of the reactivation-extinction procedure. Data confirmed the importance of memory destabilization prior to extinction inside the reconsolidation window to attenuate spontaneous recovery and retard reacquisition of conditioned fear. The present report offers a candidate explanation of the discrepancy in results obtained with the reactivation-extinction procedure by different laboratories.
Assuntos
Condicionamento Clássico/fisiologia , Extinção Psicológica/fisiologia , Memória/fisiologia , Análise de Variância , Animais , Ansiolíticos/farmacologia , Condicionamento Clássico/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Medo/efeitos dos fármacos , Medo/psicologia , Masculino , Memória/efeitos dos fármacos , Midazolam/farmacologia , Ratos , Ratos Wistar , Fatores de Tempo , Gravação em VídeoRESUMO
JUSTIFICATIVA E OBJETIVOS: A artrite reumatoide (AR) é uma doença crônica, na maioria é insidiosa,de etiologia desconhecida, cuja principal manifestação é a sinovite persistente com acometimento de articulações periféricas de forma simétrica. A lesão na cartilagem e as erosões ósseas com as mudanças subsequentes na integridade articular são as principais marcas da doença. A AR é uma doença sistêmica, em que acomete outros órgãos e sistemas, como pele, coração,pulmões, músculos e, mais raramente, vasos sanguíneos levando a vasculite reumatoide. O objetivo deste estudo foi descrever um caso de AR evoluindo com vasculite reumatoide, uma condição rara e grave.RELATO DO CASO: Paciente do sexo feminino, 61 anos, portadora de AR que iniciou com quadro de edema nos membros inferiores, dor, eritema e calor local, evoluiu com nódulos duros que ulceraram. Na região glútea apresentou eritema em placas, sem prurido, indolor, com nódulos semelhantes aos das pernas que também ulceraram.A dor de intensidade moderada foi controlada com tramadol e paracetamol, por via oral.CONCLUSÃO: A vasculite reumatoide é complicação grave da AR que pode levar a amputação do membro e evolui com dor moderada facilmente controlada com opioides fracos.
BACKGROUND AND OBJECTIVES: Rheumatoid arthritis (RA) is a chronic, mostly insidious disease of unknown etiology, the primary manifestation of which is persistent synovitis symmetrically affecting peripheralj oints. Cartilaginous injuries and bone corrosions with subsequent changes in articular integrity are the primary marks of the disease. RA is a systemic disease affecting other organs and systems such as skin, heart, lungs, muscles and, less commonly, blood vessels leading to rheumatoid vasculitis. This study aimed at describing an RAcase evolving with rheumatoid vasculitis, which is a rareand severe condition.CASE REPORT: Female patient, 61 years old, with RA starting with lower limbs edema, pain, erythema and local heat, and evolving with hard nodules which ulcerated.The gluteus region had erythema in plaques, without pruritus, pain less, with nodules similar to those of the legs, which also ulcerated. Moderate pain was controlled with oral tramadol and paracetamol.CONCLUSION: Rheumatoid vasculitis is a severe RA complication which may lead to limb amputation and evolves with moderate pain easily controlled with weak opioids.
Assuntos
Artrite Reumatoide , Febre Reumática , VasculiteRESUMO
JUSTIFICATIVA E OBJETIVOS: A dermatomiosite é umadoença sistêmica crônica, de etiologia desconhecida, que se caracterizapor acometimento inflamatório da pele e dos músculos.O diagnóstico baseia-se nos achados clínicos e laboratoriais. Os corticoides são a terapia mais utilizada. As causas de óbito maisfrequentes são neoplasia maligna, septicemia e fibrose pulmonar.O objetivo deste estudo foi efetuar uma ampla revisão de literatura com foco no reconhecimento dos principais achados clínicos e no tratamento desta doença.CONTEÚDO: A dermatomiosite é uma doença sistêmica crônica que se caracteriza por acometimento inflamatório da pele e dos músculos. Possui duas formas principais: miopática, maisfrequente, onde se encontram lesões musculares e cutâneas; e amiopática, somente com lesões cutâneas. O sexo feminino é o mais afetado, e a idade média do diagnóstico é 40 anos. Manifestações cutâneas são observadas em todos os pacientes. Das alterações sistêmicas, a manifestação muscular mais frequente é a perda de força proximal, e a manifestação pulmonar mais comum é a pneumopatia intersticial. Podem ser observadas neoplasias durante o seguimento da doença, sendo mais frequentes nos pacientes acima de 60 anos. A desidrogenase lática é a enzima muscular alterada na maioria dos casos. O diagnóstico da dermatomiositepode ser realizado por exame anatomopatológico de biópsia muscular,além de eletroneuromiografia. Os corticoides são os mais utilizados. As causas de óbito mais frequentes são neoplasia maligna,septicemia e fibrose pulmonar. Não há causa conhecida. Odiagnóstico baseia-se nos achados clínicos e laboratoriais.CONCLUSÃO: Através da analise dos dados bibliográficos foi possível concluir que a dermatomiosite é uma doença de diagnóstico predominantemente clínico. Os exames laboratoriais e de imagem constituem importantes confirmadores do quadro, mas nunca são identificadores isolados, sendo sempre a clínica, soberana no diagnóstico desta doença.(...)
BACKGROUND AND OBJECTIVES: The dermatomyosits is a systemic chronic disease, of unknown etiology, which is characterized for inflammatory attack of the skin and muscles. The diagnosis is based on clinical and laboratory finds. The corticosteroids are the most used therapy. The most frequent causes of death are: the malignant neoplasia, the septicemia and the pulmonary fibrosis. A bibliographical revision was carried out, with the objective of attracting attention of the doctors for the recognition of the principal clinical finds of this illness. CONTENTS: The dermatomyositis is a systemic chronic disease that is characterized by the inflammatory attack of the skin and muscles. It has two principal forms: miopatic that is more frequent, and presents muscular and skin injuries; and the amiopatic that presents skin injuries only. The feminine sex is more affected mainly at the middle age of 40s. Skin manifestations are observed in all the patients. Among the systemic alterations,the most frequent muscular demonstration is the loss of strength proximal, and the commonest pulmonary demonstration is interstitial pneumopathy. Neoplasis can be observed during the continuation of the disease, and is more frequent in the patients above 60 years old. The Lactic dehydrogenase means that the muscular enzyme is altered in most of the cases. The diagnosis of the dermatomyositis can be done for the muscular biopsy applyinganatomopatologic exam, besides electroneuromiography examination. The corticosteroids are the most used therapy. The most frequent causes of death are the malignant neoplasis, sepsis, and the pulmonary fibrosis and there is no known cause. The diagnosis is based on the clinical and laboratories finds.CONCLUSION: Through the analyzes of the bibliographical facts it is possible to conclude that dermatomiositis is a disease of predominantly clinical diagnosis.(...)
Assuntos
Humanos , Dermatomiosite/epidemiologia , Dermatomiosite/etiologia , Dermatomiosite/patologia , MiositeRESUMO
Non-competitive NMDA-receptor-antagonist drugs such as dizocilpine (MK801) induce behavioral changes and neurotoxicity that have made an impact in different fields of neuroscience. New approaches in research use transgenic mice to elucidate cellular mechanisms and circuits involved in the effects of these drugs. However, the neurodegeneration induced by these drugs has been extensively studied in rats, but the data in mice is limited. Therefore it is important to characterize if the neurotoxic pattern in mice corresponds to that of rats. A comparative analysis of the neurodegeneration induced by MK801 (10mg/kg) between Wistar rats, and CD-1, CF-1, and C57BL/6-129/Sv mice of both sexes, at different survival times (15, 24, 32, 48, 56 and 72 h) was analysed with the amino-cupric-silver and fluoro-jade B techniques. To compare different administration patterns, groups of mice received subchronic treatments with different doses (final doses of 20 and 40 mg/kg). Results showed that mice treated with MK801 presented different neurotoxic profiles, such as excitotoxic-like cell death in the retrosplenial cortex, terminal degeneration in CA1 and apoptotic-like degeneration in the olfactory bulb. Unlike rats, mice subjected to the same treatment failed to show neurodegeneration in corticolimbic areas such as piriform cortex and dentate gyrus. The amount of degeneration was lower in mice, and the subchronic administration of MK801 did not change the neurotoxic pattern. Additionally, mice lacked the sexually dimorphic response to MK801 toxicity observed in rats. Altogether these results indicate important species dissimilarities. Neurotoxicological studies aimed to explore pathways and mechanisms of MK801 toxicity should consider these differences when using mice as rodent models.
Assuntos
Maleato de Dizocilpina/toxicidade , Antagonistas de Aminoácidos Excitatórios/toxicidade , Doenças Neurodegenerativas/induzido quimicamente , Análise de Variância , Animais , Comportamento Animal , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Doenças Neurodegenerativas/patologia , Doenças Neurodegenerativas/fisiopatologia , Neurônios/patologia , Ratos , Ratos Wistar , Fatores Sexuais , Fatores de TempoRESUMO
MK801, PCP, and ketamine are non-competitive NMDA receptor-antagonists drugs that in humans produce psychomimetic effects and neurocognitive disturbances reminiscent to those of schizophrenia. The administration of these drugs in animals has been used as a pharmacological model to study the NMDA receptor hypofunction-hypothesis of schizophrenia. In animals, the biological effect of MK801 is dose-dependent. Low doses induce behavioral disturbances and higher doses, in addition, promote neurotoxicity in many brain regions, particularly the granular retrosplenial cortex (RSG). The neurotoxic effect of MK801 is sexually dimorphic, being females markedly more sensitive than males; however, the involvement of gonadal hormones is elusive. Here we show that a single intraperitoneal injection of 5 mg/kg of MK801 induced overt neurodegeneration in RSG of female rats, including abundant somatic degeneration in layer 4, and somatodendritic and terminal degeneration in layers 1, 4, and 5. MK801-degeneration in males was scarce and mainly evidenced by the presence of few argirophilic somas in layer 4. Ovariectomized rats were not significantly different than intact females, while orchiectomized rats showed robust MK801-toxicity. Testosterone and dihydrotestosterone (DHT) inhibit MK801-toxicity in orchiectomized rats. In ovariectomized rats only DHT, but not testosterone, prevented MK801-induced degeneration, while in intact females, DHT was only partially protective. Treatment of intact males with estradiol benzoate significantly enhanced MK801-toxicity. Altogether, our experiments indicate that non-aromatizable androgens protect RSG from MK801-toxicity, while estrogens counteract this protection. Thus, the balance of androgens and estrogens delineate the sexual dimorphism of the RSG to the toxic effect of MK801.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Maleato de Dizocilpina/toxicidade , Hormônios Gonadais/farmacologia , Degeneração Neural/prevenção & controle , Neurônios/efeitos dos fármacos , Androgênios/administração & dosagem , Androgênios/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/patologia , Anticoncepcionais/administração & dosagem , Anticoncepcionais/farmacologia , Di-Hidrotestosterona/administração & dosagem , Di-Hidrotestosterona/farmacologia , Maleato de Dizocilpina/administração & dosagem , Estradiol/administração & dosagem , Estradiol/análogos & derivados , Estradiol/farmacologia , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/toxicidade , Feminino , Hormônios Gonadais/administração & dosagem , Injeções Intraperitoneais , Injeções Subcutâneas , Masculino , Degeneração Neural/induzido quimicamente , Neurônios/patologia , Orquiectomia , Ovariectomia , Ratos , Ratos Wistar , Fatores Sexuais , Propionato de Testosterona/administração & dosagem , Propionato de Testosterona/farmacologiaRESUMO
The neurotoxic effect following a single intraperitoneal injection of MK-801 (10 mg/kg) in adult female Wistar rats at different survival times was studied with the 1994 version of de Olmos' Amino-Cupric-Silver (A-Cu-Ag) technique for detection of neural degeneration. In addition to the well documented somatodendritic degeneration observable in cortical olfactory structures, dentate gyrus, retrosplenial and sensory cortices, we detected this type of neuronal degeneration also in the main olfactory bulb, motor and anterior cingulate cortices, thalamus and cerebellum. Terminal degeneration, not reported by previous authors, was detected in cortical olfactory structures, hippocampal formation, sensory, infralimbic, prelimbic, agranular insular, ectorhinal, perirhinal and lateral orbital cortices. These results demonstrate that the A-Cu-Ag procedure is more efficient than other silver methods for detecting the degeneration induced by MK-801. In fact, the use of the A-Cu-Ag method has made it possible to infer the connectional relations between the damaged cell bodies and corresponding terminal degeneration. Our results also indicate that the A-Cu-Ag technique may be a suitable method for the staining of neurons undergoing apoptotic-like degeneration. The probable degenerative mechanism of MK-801 in the main olfactory system is discussed.
Assuntos
Encefalopatias/induzido quimicamente , Encéfalo/patologia , Maleato de Dizocilpina/toxicidade , Antagonistas de Aminoácidos Excitatórios/toxicidade , Degeneração Neural/induzido quimicamente , Animais , Apoptose , Encéfalo/efeitos dos fármacos , Encefalopatias/patologia , Cobre , Feminino , Ratos , Ratos Wistar , Prata , Coloração e Rotulagem/métodos , Fatores de TempoRESUMO
The strain and sex of a species under investigation may influence the animal's physiological response to a variety of stimuli. Strain and sex differences are important considerations when evaluating animal models. In the rodent MK-801 model of schizophrenia, degenerative changes occur widely in the main olfactory system and in a number of cortical brain regions. In the present report, we compare the effects of MK-801 neurotoxicity in two strains of female rats and also two lines within each strain. The magnitude and regional extent of the neurodegeneration detected with the amino-cupric-silver method varied markedly both between the Sprague-Dawley and Wistar rat strains and also between two lines derived from each strain. For example, terminal degeneration occurred in layer VI of somatosensory cortex and the central extended amygdala in Sprague-Dawley but not Wistar rats. Moreover, MK-801 treatment led to somatodendritic degeneration in the dentate gyrus of the dorsal hippocampus and basolateral amygdala in Wistar rats from Charles River Laboratories but not those from Ferreyra Institute. There are thus both strain and intrastrain differences in the magnitude of the neurodegenerative response to MK-801 treatment. The differing neurotoxicity of MK-801 between rat strains and between lines within a strain may reflect genetic variation and/or differences in hepatic biotransformation and thus the bioavailability of the drug between strains and lines within a strain.