Dual-step pharmacological intervention for traumatic-like memories: implications from D-cycloserine and cannabidiol or clonidine in male and female rats.

RATIONALE: Therapeutic approaches to mitigating traumatic memories have often faced resistance. Exploring safe reconsolidation blockers, drugs capable of reducing the emotional valence of the memory upon brief retrieval and reactivation, emerges as a promising pharmacological strategy. Towards this objective, preclinical investigations should focus on aversive memories resulting in maladaptive outcomes and consider sex-related differences to enhance their translatability. OBJECTIVES: After selecting a relatively high training magnitude leading to the formation of a more intense and generalized fear memory in adult female and male rats, we investigated whether two clinically approved drugs disrupting its reconsolidation remain effective. RESULTS: We found resistant reconsolidation impairment by the α2-adrenergic receptor agonist clonidine or cannabidiol, a major non-psychotomimetic Cannabis sativa component. However, pre-retrieval administration of D-cycloserine, a partial agonist at the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor complex, facilitated their impairing effects on reconsolidation. A similar reconsolidation blockade by clonidine or cannabidiol was achieved following exposure to a non-conditioned but generalized context after D-cycloserine administration. This suggests that sufficient memory destabilization can accompany generalized fear expression. Combining clonidine with cannabidiol without potentiating memory destabilization by D-cycloserine was ineffective. CONCLUSIONS: These findings highlight the importance of NMDA receptor signaling in memory destabilization and underscore the efficacy of a dual-step pharmacological intervention in attenuating traumatic-like memories, even in a context different from the original learning environment.

Ayahuasca-enhanced extinction of fear behaviour: Role of infralimbic cortex 5-HT2A and 5-HT1A receptors.

BACKGROUND AND PURPOSE: Ayahuasca (AYA) is a botanical psychedelic with promising results in observational and small clinical trials for depression, trauma and drug use disorders. Its psychoactive effects primarily stem from N,N-dimethyltryptamine (DMT). However, there is a lack of research on how and where AYA acts in the brain. This study addressed these questions by examining the extinction of aversive memories in AYA-treated rats. EXPERIMENTAL APPROACH: We focused on the 5-HT1A and 5-HT2A receptors, as DMT exhibits a high affinity for both of them, along with the infralimbic cortex in which activity and plasticity play crucial roles in regulating the mnemonic process under analysis. KEY RESULTS: A single oral treatment with AYA containing 0.3 mg·kg-1 of DMT increased the within-session extinction of contextual freezing behaviour without affecting its recall. This protocol, when repeated twice on consecutive days, enhanced extinction recall. These effects were consistent for both 1- and 21-day-old memories in males and females. AYA effects on fear extinction were independent of changes in anxiety and general exploratory activity: AYA- and vehicle-treated animals showed no differences when tested in the elevated plus-maze. The 5-HT2A receptor antagonist MDL-11,939 and the 5-HT1A receptor antagonist WAY-100635 infused into the infralimbic cortex respectively blocked within- and between-session fear extinction effects resulting from repeated oral administration of AYA. CONCLUSION AND IMPLICATIONS: Our findings highlight complementary mechanisms by which AYA facilitates the behavioural suppression of aversive memories in the rat infralimbic cortex. These results suggest potential beneficial effects of AYA or DMT in stress-related disorders.

A homeopatia como opção na manutenção da saúde

A Homeopatia nasceu do descontentamento de Hahnemann, médico alemão, com os métodos e medicamentos utilizados pela medicina empregada em sua época e pela busca de uma medicina menos invasiva e eficiente. Seu desejo de uma medicação que promovesse a cura do paciente, não apenas na parte física, embasou-se nos conceitos de Hipócrates e no vitalismo. Dessa maneira, para se obter a cura do paciente é preciso entender sua doença do ponto de vista físico e psicomental. De acordo com a filosofia vitalista, todo ser humano é dotado de uma Força ou Energia Vital capaz de atuar na manutenção e recuperação do equilíbrio, apontado como o responsável pela saúde do paciente. Desta forma, utilizando princípios como o da semelhança, Hahnemann estudou substâncias que seriam capazes de despertar no organismo a doença em proporções mínimas, de modo a favorecer a reação e o trabalho da cura. Suas idéias foram organizadas após extensas pesquisas e vem comprovando, até os dias atuais, a possibilidade do paciente ser tratado em um caminho que culmina em sua saúde novamente. Acolher o ser humano como um todo, dentro da consulta homeopática, faz parte do tratamento, onde a doença não deve ser vista como um evento isolado e restrito ao corpo físico. O trabalho foi realizado a partir de uma revisão bibliográfica em livros tradicionais e meio eletrônico. Ao final, conclui-se que a Homeopatia e sua maneira de entender paciente e processo de doença e saúde podem oferecer ao ser humano uma maneira menos agressiva e um caminho direcionado para o bem estar e a cura. (AU)

Homeopathy is born of discontent Hahnemann, a German physician, with the methods and drugs used in medicine employed in his time and the search for a less invasive and effective medicine. His desire for a medication that promotes the healing of the patient, not just the physical part, he underwrote the concepts of Hippocrates and vitalism. Thus, to obtain the patient's healing is necessary to understand their physical and disease psychomental view. According to the vitalist philosophy, every human being is endowed with a force or vital energy capable of acting in maintaining and restoring balance, appointed as responsible for the health of the patient. Thus, using the similar principles as Hahnemann studied substances which would be capable of awakening the body disease in minor proportions, in order to promote the reaction and the work of healing. His ideas were organized after extensive research and is proving, to the present day, the patient's possibility to be treated in a way that culminates in his health again. To accept the human being as a whole, within the homeopathic consultation is part of the treatment where the disease should not be seen as an isolated and restricted to the physical body event. The study was conducted from a literature review on traditional books and electronic media. Finally, it is concluded that homeopathy and his way to understand patient and disease and health process can offer to man a less aggressive way and a path directed to the well-being and healing. (AU)

Immunomodulatory treatment with thalidomide in experimental leptospirosis in Golden Syrian hamsters (Mesocricetus auratus).

BACKGROUND: The benefit of antibiotics in leptospirosis is limited when treatment is started four days after symptoms appear, and new adjuvant therapeutic options are urgently needed. METHODS: Hamsters (Mesocricetus auratus) were infected by Leptospira interrogans strain L1-130, and groups were assigned based on no treatment (NONE), thalidomide only (TAL), ampicillin only (AMP) or both (AMP-TAL). Treatment was started two days after the onset of symptoms (experiment 1) and immediately after detection of the first death (experiment 2). RESULTS: Experiment 1: all hamsters from the groups AMP and AMP-TAL survived (n=8), while all hamsters from groups NONE (n=6) and TAL (n=8) died. The AMP and the AMP-TAL groups showed no renal or liver pathology and absent or very low leptospiral burden in target organs. Experiment 2: lethal outcome was observed in 6/6 hamsters in the NONE group, 8/8 in the TAL group, and 6/8 in both the AMP and AMP-TAL groups. Thalidomide showed no survival benefit when compared to hamsters treated with ampicillin alone. The TAL, AMP and AMP-TAL groups had very low tissue leptospiral counts. CONCLUSION: Thalidomide had minimal impact on survival in the late treatment of leptospirosis hamster model.

Ionic imbalance and lack of effect of adjuvant treatment with methylene blue in the hamster model of leptospirosis.

Leptospirosis in humans usually involves hypokalaemia and hypomagnesaemia and the putative mechanism underlying such ionic imbalances may be related to nitric oxide (NO) production. We previously demonstrated the correlation between serum levels of NO and the severity of renal disease in patients with severe leptospirosis. Methylene blue inhibits soluble guanylyl cyclase (downstream of the action of any NO synthase isoforms) and was recently reported to have beneficial effects on clinical and experimental sepsis. We investigated the occurrence of serum ionic changes in experimental leptospirosis at various time points (4, 8, 16 and 28 days) in a hamster model. We also determined the effect of methylene blue treatment when administered as an adjuvant therapy, combined with late initiation of standard antibiotic (ampicillin) treatment. Hypokalaemia was not reproduced in this model: all of the groups developed increased levels of serum potassium (K). Furthermore, hypermagnesaemia, rather than magnesium (Mg) depletion, was observed in this hamster model of acute infection. These findings may be associated with an accelerated progression to acute renal failure. Adjuvant treatment with methylene blue had no effect on survival or serum Mg and K levels during acute-phase leptospirosis in hamsters.

Ionic imbalance and lack of effect of adjuvant treatment with methylene blue in the hamster model of leptospirosis

Leptospirosis in humans usually involves hypokalaemia and hypomagnesaemia and the putative mechanism underlying such ionic imbalances may be related to nitric oxide (NO) production. We previously demonstrated the correlation between serum levels of NO and the severity of renal disease in patients with severe leptospirosis. Methylene blue inhibits soluble guanylyl cyclase (downstream of the action of any NO synthase isoforms) and was recently reported to have beneficial effects on clinical and experimental sepsis. We investigated the occurrence of serum ionic changes in experimental leptospirosis at various time points (4, 8, 16 and 28 days) in a hamster model. We also determined the effect of methylene blue treatment when administered as an adjuvant therapy, combined with late initiation of standard antibiotic (ampicillin) treatment. Hypokalaemia was not reproduced in this model: all of the groups developed increased levels of serum potassium (K). Furthermore, hypermagnesaemia, rather than magnesium (Mg) depletion, was observed in this hamster model of acute infection. These findings may be associated with an accelerated progression to acute renal failure. Adjuvant treatment with methylene blue had no effect on survival or serum Mg and K levels during acute-phase leptospirosis in hamsters. .

O uso da talidomida como terapia adjuvante na leptospirose experimental / The use of thalidomide as adjuvant therapy in experimental leptospirosis

A leptospirose é uma zoonose de importância global, causada por leptospiras patogênicas. Seu tratamento é limitado quando iniciado após quatro dias do surgimento de sintomas, portanto, novas terapias adjuvantes são necessárias. Objetivo. Testar a droga imunomoduladora talidomida como terapia adjuvante à ampicilina no modelo de tratamento tardio da leptospirose experimental em hamsters. Métodos. 60 hamsters foram infectados via intraperitoneal por Leptospirainterrogans cepa L1-130, e foram separados em grupos: nenhum tratamento (NONE), talidomida (TAL), ampicilina (AMP) e ambos (AMP-TAL)...

Leptospirosis is a zoonosis of global importance, caused by pathogenic leptospira. His treatment is limited when started after four days of onset of symptoms, increasing the risk of morbidity and mortality, so new adjuvant therapies are needed.Objectives.To test the immunomodulatory drug, thalidomide, as an adjuvant therapy to antibiotics in experimental leptospirosis. Methods. Hamsters were infected by Leptospirainterrogans strain L1-130, and groups were assigned based on no treatment (NONE), thalidomide only (TAL), ampicillin only (AMP) or both (AMP-TAL). Thalidomide was administered via a gastric tube: 50 mg/kg in linseed oil and 2 ml/kg for three days. Ampicillin was administered intramuscularly at the rate of 100 mg/kg/bid for six days. Treatment was started two days after the onset of symptoms (experiment 1) and immediately after detection of the first death (experiment 2). Results. Experiment 1: all hamsters from the groups AMP and AMP-TAL...

Detection and quantification of Leptospira interrogans in hamster and rat kidney samples: immunofluorescent imprints versus real-time PCR.

A major limitation in the clinical management and experimental research of leptospirosis is the poor performance of the available methods for the direct detection of leptospires. In this study, we compared real-time PCR (qPCR), targeting the lipL32 gene, with the immunofluorescent imprint method (IM) for the detection and quantification of leptospires in kidney samples from the rat and hamster experimental models of leptospirosis. Using a virulent strain of Leptospira interrogans serovar Copenhageni, a chronic infection was established in the rat model, which were euthanized 28 days post-infection, while the hamster model simulated an acute infection and the hamsters were euthanized eight days after inoculation. Leptospires in the kidney samples were detected using culture isolation, qPCR and the IM, and quantified using qPCR and the IM. In both the acute and chronic infection models, the correlation between quantification by qPCR and the IM was found to be positive and statistically significant (P<0.05). Therefore, this study demonstrates that the IM is a viable alternative for not only the detection but also the quantification of leptospires, particularly when the use of qPCR is not feasible.

Attenuated nephritis in inducible nitric oxide synthase knockout C57BL/6 mice and pulmonary hemorrhage in CB17 SCID and recombination activating gene 1 knockout C57BL/6 mice infected with Leptospira interrogans.

The aims of this study were to investigate the frequency of pulmonary hemorrhage (PH) in mice unable to produce functional B and T lymphocytes and to explore the effect of an inducible nitric oxide synthase gene (Inos) knockout (KO) on the frequency/severity of interstitial nephritis in vivo. We studied the outcome of infection by the virulent Leptospira interrogans serovar Copenhageni strain Cop. The animals used were Inos KO mice, recombination activating gene 1 (Rag1) KO mice, CB17 severe combined immunodeficiency (SCID) mice, and the respective wild-type (WT) C57BL/6 and BALB/c controls. The Inos KO and WT mice survived with no clinical symptoms of leptospirosis. The frequency and severity of nephritis was significantly lower in the Inos KO mice. All of the Rag1 KO and SCID animals died of acute leptospirosis, whereas all of the WT mice survived. PH was observed in 57 and 94% of Rag1 KO mice and in 83 and 100% of SCID mice, using inoculum doses of 10(7) and 10(6) leptospires, respectively. There was no evidence of PH in the WT controls. In conclusion, the loss of the Inos gene had a negligible effect on the outcome of leptospiral infection, although we observed a reduced susceptibility for interstitial nephritis in this group. Of note, the absence of functional B- and T-cell lymphocytes did not preclude the occurrence of PH. These data provide evidence that PH in leptospirosis may not be related only to autoimmune mechanisms.

ESEF 70 Anos: o processo de federalização sob o olhar discente / ESEF 70 Years: The process of federalization under the student's view / ESEF 70 Años: el proceso de federalización bajo la mirada discente

Este artigo analisa o processo de federalização da Escola de Educação Física da Universidade Federal do Rio Grande do Sul sob o olhar dos discentes que se graduaram em 1970 na primeira turma formada sob o regime federal de ensino. Fundamentada no aporte teórico da História Cultural analisamos aspectos relacionados ao envolvimento político dos alunos nesse processo bem como aspectos relacionados a estrutura e funcionamento da Escola como um todo. Para tanto, recorremos a História Oral entrevistando discentes e docentes do período bem como analisamos fontes de diversa natureza tais como documentos, atas de reuniões, livros, reportagens de jornal, fotografia entre outras. Da análise realizada apreendemos que esta turma vivenciou a federalização de modo muito peculiar: por dentro do processo, mas, em certa medida, muito afastada dele

This paper analyzes the process of federalization of the School of Physical Education of the Federal University of Rio Grande do Sul under the eyes of students who graduated in 1970 in the first group formed under the federal system of education. Based on the theoretical support of Cultural History, we reviewed issues related to political involvement of students in this process and aspects of the structure and functioning of the school as a whole. To this end, we resorted to Oral History, interviewing students and teachers of the period, and analyzed sources of various kinds such as documents, minutes of meetings, books, newspaper reports, photographs, and more. Based on the analysis, we noted that this class has experienced federalization in a very peculiar way: within the process, but to some extent, far away from it

Este artículo analiza el proceso de federalización de la Escuela de Educación Física de la Universidad Federal de Rio Grande do Sul bajo la mirada de los discentes que se graduaron en 1970 en la primera promoción formada bajo el régimen federal de enseñanza. Fundamentada con el aporte teórico de la Historia Cultural analizamos aspectos relacionados al compromiso político de los alumnos en ese proceso así como también aspectos relacionados a la estructura y funcionamiento de la Escuela como un todo. Para esto, recorremos la Historia Oral entrevistando discentes y docentes del periodo así como también analizamos fuentes de diversa naturaleza tales como documentos, actas de reuniones, libros, reportajes de periódicos, fotografías, entre otras. Del análisis realizado aprendemos que esta promoción vivió la federalización de modo muy particular: por dentro del proceso, pero, en cierta medida, muy alejada de é

Características demográficas (sexo e idade) e as atividades básicas e instrumentais de vida diária em adultos e idosos saudáveis / Demographic characteristics (age and sex) and basic and instrumental activities of daily living in adults and elderly healthy

Introdução: A sociedade está envelhecendo, e dentre os comprometimentos advindos do avanço cronológico da idade está a incapacidade funcional. Objetivo: Identificar e analisar as relações entre características demográficas (sexo e idade) e as atividades básicas e instrumentais de Vida Diária em adultos e idosos saudáveis. Métodos: Realizou-se um estudo transversal, em 2008, com 75 indivíduos. Para a avaliação das atividades básicas e instrumentais, foram empregados o Índice de Katz e a Escala de Lawton, respectivamente. Resultados: Houve apenas diferença significativa, quando comparadas as atividades instrumentais com o sexo, observando uma menor capacidade do homem em realizar tarefas como arrumar a casa, preparar as refeições e lavar e passar as roupas. Conclusões: Os resultados sugerem que a idade influencia no processo de envelhecimento, que o sexo está relacionado à execução de atividades domésticas e que o estilo de vida adotado pelo indivíduo interfere diretamente na sua qualidade de vida.

Introduction: The society is aging, and among the compromises that come with advancing chronological age, is the occurrence of disability. Objective: To identify and analyze the relationship between demographic characteristics (age and gender) and the basic activities of daily living for healthy adults and seniors. Methods: We conducted a cross-sectional study, in 2008, with 75 individuals. For the evaluation of basic and instrumental activities were employed the Katz Index and the Lawton Scale, respectively. Results: There were significant differences only when comparing the instrumental activities with the gender, observing a smaller man?s ability to perform tasks like cleaning the house, preparing meals and washing and ironing clothes. Conclusions: The results suggest that age influences the aging process, sex is related to the performance of household activities and the lifestyle adopted by the individual directly influences its quality of life.

Acompanhamento interdisciplinar de idosos fragilizados / Interdisciplinary monitoring of frail elderly

Acompanhamento interdisciplinar de idosos fragilizados da Enfermaria de Geriatria do Hospital São Paulo - Unifesp - EPM, que podem apresentar alterações de deglutição, que, por sua vez, podem levar a um quadro de desnutrição e/ou aspiração. Os sujeitos foram avaliados pela equipe interdisciplinar da Enfermaria de Geriatria do HSP - médico, fisioterapeuta, fonoaudióloga, nutricionista, assistente social, por meio de um protocolo elaborado pela equipe com base nos protocolos de cada profissional utilizados entre o primeiro e meados do segundo semestre de 1996, dos quais foram retirados os aspectos relevantes a serem abordados nas avaliações dos pacientes para posterior discussão do caso e planejamento da intervenção. De meados de abril ao final de outubro de 1996, foram avaliados 53 pacientes, com idade entre 65 e 95 anos. A média de internação foi de 17 dias, ocorrendo 17 óbitos e 36 altas. Dos 36, 14 passaram pelo Ambulatório de Alta e foram atendidos por médico, fonoaudióloga e nutricionista. Dentre os 14, cinco não apresentaram alteração de deglutição e/ou quadro de aspiração; 6 necessitaram de intervenção fonoaudiológica, mantendo-se a dieta via oral - dois desnutridos e quatro eutróficos; e os três restantes, um desnutrido e dois eutróficos, receberam sonda nasoenteral. Não foi encontrada relação direta entre idoso fragilizado e alteração de deglutição, mas quando observada, a intervenção interdisciplinar colaborou para melhoria do paciente (AU)

Acompanhamento interdisciplinar de idosos fragilizados / Interdisciplinary monitoring of frail elderly

Acompanhamento interdisciplinar de idosos fragilizados da Enfermaria de Geriatria do Hospital Säo Paulo - Unifesp - EPM, que podem apresentar alteraçöes de deglutiçäo, que, por sua vez, podem levar a um quadro de desnutriçäo e/ou aspiraçäo. Os sujeitos foram avaliados pela equipe interdisciplinar da Enfermaria de Geriatria do HSP - médico, fisioterapeuta, fonoaudióloga, nutricionista, assistente social, pormeio de um protocolo elaborado pela equipe com base nos protocolos de cada profissional utilizados entre o primeiro e meados do segundo semestre de 1996, dos quais foram retirados os aspectos relevantes a serem abordados nas avaliaçöes dos pacientes para posterior discussäo do caso e planejamento da intervençäo. De meados de abril ao final de outubro de 1996, foram avaliados 53 pacientes, com idade entre 65 e 95 anos. A média de internaçäo foi de 17 dias, ocorrendo 17 óbitos e 36 altas. Dos 36, 14 passaram pelo Ambulatório de Alta e foram atendidos por médico, fonoaudióloga e nutricionista. Dentre os 14, cinco näo apresentaram alteraçäo de deglutiçäo e/ou quadro de aspiraçäo; 6 necessitaram de intervençäo fonoaudiológica, mantendo-se a dieta via oral - dois desnutridos e quatro eutróficos; e os três restantes, um desnutrido e dois eutróficos, receberam sonda nasoenteral. Näo foi encontrada relaçäo direta entre idoso fragilizado e alteraçäo de deglutiçäo, mas quando observada, a intervençäo interdisciplinar colaborou para melhoria do paciente