Abstract This is a nonclinical, controlled, and triple-blind study to investigate the effects of codeine-associated geraniol on the modulation of orofacial nociception and its potential central nervous system depressing effect in an animal model. The orofacial antinociceptive activity of geraniol in combination with codeine was assessed through the following tests: (i) formalin-induced pain, (ii) glutamate-induced pain, and (iii) capsaicin-induced pain. Six animals were equally distributed into six groups and received the following treatments, given intraperitoneally (i.p.) 30 minutes before the experiments: a) geraniol/codeine 50/30 mg/kg; b) geraniol/codeine 50/15 mg/kg; c) geraniol/codeine 50/7.5 mg/kg; d) geraniol 50 mg/kg; e) codeine 30 mg/kg (positive control); or f) 0.9% sodium chloride (negative control). We performed pain behavior analysis after the injection of formalin (20 µL, 20%), glutamate (20 µL, 25 µM), and capsaicin (20 µL, 2.5 µg) into the paranasal region. Rubbing time of the paranasal region by the hind or front paw was used as a parameter. In the neurogenic phase of the formalin test, the geraniol/codeine at 50/7.5 mg/kg was able to promote the maximum antinociceptive effect, reducing nociception by 71.9% (p < 0.0001). In the inflammatory phase of the formalin test, geraniol/codeine at 50/30 mg/kg significantly reduced orofacial nociception (p < 0.005). In the glutamate test, geraniol/codeine at 50/30 mg/kg reduced the rubbing time by 54.2% and reduced nociception in the capsaicin test by 66.7% (p < 0.005). Geraniol alone or in combination does not promote nonspecific depressing effects on the central nervous system. Based on our findings, we suggest the possible synergy between geraniol and codeine in the modulation of orofacial pain. nonclinical controlled tripleblind triple blind codeineassociated associated model tests i (i formalininduced induced ii (ii glutamateinduced iii (iii capsaicininduced treatments i.p. ip p (i.p. 3 experiments geraniolcodeine 5030 50/3 mgkg mg kg b 5015 15 50/1 c 5075 7 5 50/7. d e positive control control) f 09 0 9 0.9 negative control. . 20 (2 µL 20%, 20% , 20%) 2 µM, µM µM) 2. µg parameter 719 71 71.9 0.0001. 00001 0.0001 0001 0.0001) 0.005. 0005 0.005 005 0.005) 542 54 54.2 667 66 66.7 findings i.p (i.p 503 50/ 501 1 507 50/7 0. ( 71. 0000 0.000 000 0.00 00 54. 6 66. 0.0

Abstract Background-Pulmonary arterial hypertension (PAH) increases afterload in the right ventricle (RV), inducing adverse ventricular remodelling. Objective- This study explored the protective effects of thyroid hormones and grape juice on serum biomarkers and proteins related to intermediary metabolism in the RV in a model of PAH. Methods- PAH was induced in Wistar rats via the administration of monocrotaline (60 mg/kg i.p.) and they were subsequently treated with organic grape juice (GJ) and thyroid hormones (TH), administered separately or in combination. Results: The RV systolic diameter significantly increased (20%) in the PAH group compared to the control group (P = 0.002). Total CK, LDH, and ALT levels were reduced (~50%) (P<0.001) in the PAH+TH+GJ group as compared to PAH group. Glucose, albumin, triglyceride, and total cholesterol levels were reduced (~50%) (P<0.001) in the PAH group; however, these parameters returned to baseline in the PAH+GJ group. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) protein expression increased two-fold (P<0.001) and PDH protein levels were reduced (~25%) in the PAH+TH+GJ group compared to the PAH group (P<0.001). Conclusion: The data suggest that serum biomarkers can help in the evaluation of this disease, and that this therapeutic approach can attenuate maladaptive remodelling in the PAH model. BackgroundPulmonary Background Pulmonary (PAH RV, , (RV) Objective Methods 60 (6 mgkg mg kg i.p. ip i p GJ (GJ TH, TH (TH) combination Results 20% 20 (20% P 0.002. 0002 0.002 . 0 002 0.002) CK LDH ~50% 50 (~50% P<0.001 P0001 001 (P<0.001 PAHTHGJ Glucose albumin triglyceride however PAHGJ proliferatoractivated proliferator activated 1alpha alpha 1 PGC1α PGCα PGC 1α α (PGC-1α twofold two fold ~25% 25 (~25% P<0.001. Conclusion disease (RV 6 ( i.p (TH 2 (20 000 0.00 00 ~50 5 (~50 P<0.00 P000 (P<0.00 ~25 (~25 (2 0.0 ~5 (~5 P<0.0 P00 (P<0.0 ~2 (~2 0. ~ (~ P<0. P0 (P<0. P<0 (P<0 P< (P<

RESUMO O uso de agentes inalatórios gasosos para a eutanásia de animais oferece ação rápida devido ao fácil acesso à circulação arterial. A propriedade neuroprotetora para a coleta de tecido cerebral post mortem foi investigada utilizando-se isoflurano e dióxido de carbono (CO2) sobre os bioindicadores séricos de sódio e potássio. Amostras de soro foram coletadas de três grupos de animais (n=8) e doadas para este estudo, previamente aprovado pelo Comitê de Ética no Uso de Animais (CEUA 173/2020). Os grupos de soro analisados foram denominados isoflurano, CO2 e canabidiol (CBD/CO2). Os resultados demonstraram que os três grupos apresentaram níveis elevados de potássio em comparação ao grupo controle (*, P<0,05), indicando hipercalemia, enquanto nenhuma diferença foi observada no sódio sérico. Além disso, os grupos CO2 e CBD/CO2 diferiram significativamente do grupo isoflurano (#, P<0,05), que apresentou o maior nível de hipercalemia. Esses achados contribuem para a compreensão dos efeitos fisiológicos dos diferentes métodos de eutanásia sobre os perfis bioquímicos dos animais. Como conclusão, recomenda-se o uso de CO2 como método de eutanásia para coleta de tecido cerebral devido ao menor impacto sobre os níveis de potássio. arterial utilizandose utilizando se CO (CO2 n=8 n8 n 8 (n=8 estudo CEUA 173/2020. 1732020 173/2020 . 173 2020 173/2020) CBD/CO2. CBDCO2 CBDCO CBD (CBD/CO2) *, (* P<0,05, P005 P P<0,05 , 0 05 P<0,05) hipercalemia sérico disso CBD/CO #, (# conclusão recomendase recomenda (CO n= (n= 173202 173/202 17 202 (CBD/CO2 * ( P00 P<0,0 # (n 17320 173/20 1 20 (CBD/CO P0 P<0, 1732 173/2 2 P<0 173/ P<

ABSTRACT The use of gaseous inhalation agents for animal euthanasia offers rapid action due to easy access to the arterial circulation. The neuroprotective property of postmortem brain tissue collection was investigated using isoflurane and carbon dioxide (CO2) on the serum bioindicators of sodium and potassium. Serum samples were collected from 3 groups of animals (n=8) and donated to this study, previously approved by the Ethics Committee on the Use of Animals (CEUA 173/2020). The serum groups analyzed were named isoflurane, CO2 and cannabidiol (CBD/CO2). The results demonstrated that the three groups had elevated potassium levels compared to the control group (*, p<0.05), indicating hyperkalemia, while no difference was observed in serum sodium. Furthermore, the CO2 and CBD/CO2 groups differed significantly from the isoflurane group (#, p<0.05), which had the highest level of hyperkalemia. These findings contribute to our understanding of the physiological effects of different euthanasia methods on the biochemical profiles of animals. In conclusion, the use of CO2 is recommended as a euthanasia method for collecting brain tissue due to the lowest impact on potassium levels. circulation CO (CO2 n=8 n8 n 8 (n=8 study CEUA 173/2020. 1732020 173/2020 . 173 2020 173/2020) CBD/CO2. CBDCO2 CBDCO CBD (CBD/CO2) *, (* p<0.05, p005 p p<0.05 , 0 05 p<0.05) hyperkalemia Furthermore CBD/CO #, (# conclusion (CO n= (n= 173202 173/202 17 202 (CBD/CO2 * ( p00 p<0.0 # (n 17320 173/20 1 20 (CBD/CO p0 p<0. 1732 173/2 2 p<0 173/ p<

Abstract This article analyses the institutional awareness of children's perceptions within municipal urban planning, based on qualitative methods. Within this framework, 7 interviews have been conducted with political actors and administrative staff which are all connected to urban planning strategies in the municipalities of Almada and Sintra. In course of this, a content analysis of the gathered data has been undertaken, through which the following results have been reached: municipal actors continue to emancipate a vision of children's participation in a dependent paradigm, where playing and actively engaging remain the core rights recognized by the city. This is articulated through the need of effective participation in urban planning as it occurs of relevance within institutional discourses, where the sharing of power and responsibility in decision-making dynamics are not yet implemented. This issue exposes a matter between paradigmatic and pragmatic conceptions: the child as a subject of rights, and the child as an instrument of general political performance (or the maximum of consultation and information).

Resumo Este texto analisou as perceções institucionais sobre a participação das crianças no planeamento urbano municipal. Metodologicamente, a pesquisa adotou uma estratégia qualitativa através da realização de 7 entrevistas com atores políticos e técnicos dos Municípios de Almada e Sintra ligados ao planeamento urbano, as quais foram depois alvo de uma análise de conteúdo. Os resultados evidenciaram que os atores municipais ainda percecionam muito as crianças num paradigma de dependência, em que o brincar e o cuidar são os principais direitos à cidade reconhecidos, não havendo, por via de uma participação efetiva no planeamento urbano, uma articulação com direitos cívicos e políticos. Assim, ao mesmo tempo que a importância de incluir a participação das crianças no planeamento urbano faz já parte do discurso institucional, a partilha de poder e responsabilidade nas decisões não é ainda visível nos projetos existentes, evidenciando uma problemática entre o paradigmático (a criança como um sujeito de direitos) e o pragmático (a criança como instrumento geralmente de performance política ou no máximo de consulta e informação).

Resumo Em Lisboa, a mansarda surge no léxico arquitetónico português no século XVIII, importada de modelos franceses. Os exemplos pioneiros de Carlos Mardel adaptam-na à realidade construtiva do país ao executá-la com os materiais disponíveis, neste caso a telha cerâmica de canudo. Contudo, a mansarda não se sedimentará na cultura arquitetónica da cidade, e o seu uso como forma de definição espacial de cobertura desapareceria, retornando somente nas décadas finais de Oitocentos. Desta vez, o modelo de mansarda ecoa os exemplares feitos durante a reforma de Paris por Georges-Eugène Haussmann, sendo mais uma vez adaptado aos novos materiais disponibilizados pela indústria da construção da época, tais como a chapa metálica, a telha Marselha, os soletos de ardósia e os azulejos. Neste artigo, é analisado o contexto do surgimento destes materiais e das técnicas construtivas a eles associadas, sendo levantadas hipóteses que visam compreender a escolha de cada um deles para a realização deste tipo de artefacto arquitetónico indispensável na caraterização da Baixa Pombalina de Lisboa.

Abstract In Lisbon, the mansard roof appears in the Portuguese architectural lexicon in the 18th century, imported from French models. Carlos Mardel’s pioneering examples replicated the foreign model, however, he adapted it to the country’s constructive reality by executing it with the available materials, in this case, the ceramic tile. However, the mansard would not settle in the city’s architectural culture, and its use as a roofing system disappeared, returning only in the final decades of the 1800s. By this time, the model echoed the ones made during Paris renovation by Georges-Eugène Haussmann, being once again adapted according to the new materials made available by the construction industry at the time, such as metal sheets, Marseille tiles, slate shingles and azulejo tiles. In this article, the context of the emergence of these materials is analyzed, in addition to hypotheses that aim to understand the choice of one over the other for mansards.

RESUMO Este estudo objetivou reavaliar microscopicamente os diagnósticos de lesões melanocíticas estabelecidos pelo setor de Patologia Animal da Universidade Federal de Uberlândia, em um período de 11 anos, e, com base nesse levantamento, realizar uma análise comparativa entre o método histopatológico convencional (HC) e o método de despigmentação de melanócitos (DM) com permanganato de potássio, ácido sulfúrico e ácido oxálico. A DM revelou discordância em 24,32% dos diagnósticos previamente estabelecidos por HC, apresentando baixa concordância (61,0%) e baixo valor de coeficiente Kappa (0,2267). A alteração mais frequente foi o melanoma, com maior ocorrência em cadelas idosas sem raça definida (SRD). A localização mais frequente dos melanomas foi cutânea. A presença ou ausência de disseminação pagetoide nos casos cutâneos, a forma de distribuição da melanina, o padrão de disposição das células, a morfologia celular, o grau de atipia celular e a quantidade de mitoses verificada após a despigmentação foram critérios de elevada importância para firmar o diagnóstico quanto à malignidade ou benignidade da lesão. A despigmentação foi considerada pelos patologistas avaliadores como essencial para o diagnóstico na maioria dos casos, o que leva a concluir que ela constitui um método complementar eficiente no diagnóstico das lesões melanocíticas, mesmo em casos com grau moderado de pigmentação.

ABSTRACT The aim of this study was to microscopically re-evaluate the melanocytic lesions diagnoses established by the Animal Pathology Laboratory of the Federal University of Uberlândia, in the state of Minas Gerais, Brazil, over a period of eleven years; in addition, to perform a comparative analysis between the conventional histopathological (CH) method and the use of the melanin bleaching (MB) technique with potassium permanganate, sulfuric acid, and oxalic acid solutions. The results of the MB method presented a disagreement in 24.32% of the diagnosis previously by CH, with low agreement (61.0%) and low Kappa coefficient (0.2267). Melanoma was the most frequent lesion, more frequent in elderly and non-breed female dogs. The most frequent melanoma location was in the cutaneous tissue. The presence or absence of a pagetoid spread in cutaneous samples, distribution of melanin, pattern of cell layout, cell morphology, degree of cellular atypia, and the number of mitoses verified after MB were the most important criteria to confirm the diagnosis of malignancy or benignity of the lesions. Evaluating pathologists considered MB to be essential for the majority of diagnoses and an efficient complementary method for the diagnosis of melanocytic lesions, even in cases with a moderate degree of pigmentation.

ABSTRACT Clozapine is an antipsychotic that produces serious withdrawal effects in schizophrenic patients. Olfactory deficits are well known as part of negative symptoms, but it is not known whether antipsychotic use and/or withdrawal are implicated. Then, we tested clozapine withdrawal in association with two widely used schizophrenia models: Neonatal immune challenge by Polycitidilic-polyinosinic acid (polyI:C) and ketamine. PolyI:C (or saline) was injected subcutaneously in neonatal period, dose of 5 mg/kg from 2 to 6 Post Natal Days, and ketamine or saline at the dose 25mg/kg intraperitoneally (i.p.), daily for 7 days from 53 to 60 post natal day. Clozapine 10mg/kg (or saline) was administered i.p. from 46 to 60 post natal day. Olfactory discrimination test (sensorial and cognitive deficit) was performed at 61 post natal day, 24h after the last injections. The association of PolyI:C, ketamine and clozapine disrupted Olfactory Discrimination, equating time in familiar and non-familiar compartments. PolyI:C plus ketamine increased crossings between compartments. It was produced, for the first time, an olfactory deficit induced by clozapine withdrawal in Wistar rats subjected to schizophrenia animal models.

Abstract Many medicinal herbs are used in folk medicine without taking into account their toxicity. Hamelia patens Jacq. (Rubiaceae), a Mexican endemic species, is used for the empirical treatment of pain. The aim of this work was to evaluate the toxicity and antinociceptive effects of ethanolic extracts of H. patens leaves. The toxicity of H. patens leaves (500–5000 mg/kg) was evaluated in acute (14 days) and subacute (28 days) assays. In the subacute assay, a blood analysis (both hematology and chemistry) was carried out. The antinociceptive effects of H. patens leaves (50–200 mg/kg) were evaluated using thermal-induced nociception (hot plate) and the chemical-induced nociceptive tests (acid acetic and formalin). In the acute toxicity test, the LD50 estimated for H. patens leaves was 2964 mg/kg i.p. and >5000 mg/kg p.o., whereas in the subacute test HPE did not affect hematological or biochemical parameters. In chemical-induced nociception models, H. patens (100 and 200 mg/kg p.o.) showed antinociceptive effects with similar activity than 100 mg/kg naproxen. In the hot plate test, HPE at 100 mg/kg (17%) and 200 mg/kg (25%) showed moderate antinociceptive effects. HPE could be a good source of antinociceptive agents because of its good activity and low toxicity.

Cisplatina (cisdiaminodicloroplatinum) é um agente quimioterápico usado para o tratamento de várias linhagens de neoplasias, mormente as de cabeça e pescoço. Sua ototoxicidade permanece sendo um dos efeitos colaterais causadores de significativa morbidade e limita sua utilização. OBJETIVO: Avaliar a sensibilidade das emissões otoacústicas evocadas produtos de distorção (EOAPD) e potenciais auditivos evocados de tronco encefálico (PAETE) na detecção da ototoxicidade secundária a diferentes doses e formas de administração de cisplatina em ratos. FORMA DE ESTUDO: Experimental. MATERIAL E MÉTODO: Ratos Wistar machos, administrou-se cisplatina por via intraperitoneal (IP) nas doses de 24 mg/kg, fracionada em três doses diárias ou 16 mg/kg em infusão única. Avaliaram-se os animais através de EOAPD ou PAETE no terceiro (D3) e quarto (D4) dias após o início da infusão das drogas. RESULTADOS: O grupo tratado com 24 mg/kg mostrou diminuição significativa da amplitude das EOAPD e aumento do limiar eletrofisiológico pelo PAETE. A dose de 16 mg/kg não foi capaz de promover redução significativa da amplitude das EOAPD, mas elevou o limiar auditivo dos animais, detectado através de PAETE. CONCLUSÃO: Em ratos, os PAETE foram mais sensíveis que as OEAPD na detecção da ototoxicidade por cisplatina para diferentes doses e formas de administração.

Cisplatin (cis-diamminedicloroplatinum) is an antineoplastic drug used in the treatment of a variety of cancers, especially head-and-neck cancer. Its ototoxicity, however, has been noted as a common side-effect which limits its use and causes significant morbidity. AIM: to assess distortion-product otoacoustic emissions (DPOAE) and brainstem evoked response audiometry (BERA) sensitivity to detect secondary ototoxicity caused by different doses and means of administration of cisplatin in rats. STUDY DESIGN: Experimental. MATERIAL AND METHODS: Male Wistar rats were intraperitoneally (i.p.) injected with 24 mg/kg cisplatin, divided into three equal doses (8mg/kg) or a single i.p. injection of 16 mg/kg. The animals were evaluated by distortion product otoacoustic emission (DPOAE) or brainstem evoked response audiometry (BERA) on the 3rd and 4th days after the cisplatin injection. RESULTS: Treatment with cisplatin 24 mg/kg resulted in significant DPOAE decrease and it raised the BERA electrophysiological threshold. The 16mg/kg dose could not significantly reduce the DPOAE amplitude, but it raised the animals' hearing thresholds - detected by the BERA. CONCLUSION: In rats, BERA was more sensitivity than DPOAE at detecting cisplatin-induced ototoxicity in rats considering different doses and means of administration.

On the basis of previous studies on Trypanosoma lewisi immunosuppression model groups of 5 Wistar rats were infected with. T. gondii and T. lewisi according to the following protocol. One group was inoculated i.p. with 10(6) T. lewisi tripanomastigotes and 4 days later with 10(7) T. gondii tachyzoites. The second and third groups were infected only with T. lewisi or T. gondii respectively. The fourth group was not infected and served as control. Rats were bled before the infection and then every day for seven days. Serum samples were collected and the levels of IFN-g, IL-2 and TNF-a were measured. The results indicates that the level of IFN-g is very high 24 hour after infection in rats inoculated with T. gondii only, while in those animals infected with both parasites (first group), IFN-g was not detected 24 hours after infections with T. gondii. These data give evidence that a reduction of IFN-g levels is one of the reasons for the immunosuppressive effect induced by T. lewisi, increasing T. gondii multiplication in an animal as the rat, which is remarkable resistant to this parasite

De acuerdo con estudios anteriores, en donde se ha demostrado el efecto de inmunosupresión producido por Trypanosoma lewisi sobre infecciones con Toxoplasma gondii, grupos de 5 ratas Wistar fueron inoculadas según el siguiente protocolo. Un grupo fue inoculado i.p. con 10(6) tripomastigotos de T. lewisi y 4 días después con 10(7) taquizoitos de T. gondii. El segundo y el tercer grupo fueron inoculados sólo con T. gondii o con T. lewisi respectivamente. Un cuarto grupo no fue infectado y sirvió como control. Las ratas fueron sangradas antes de la infección y luego cada día durante 7 días. Los sueron fueron colectados para determinar la presencia de IFN-g, IL-2 y TNF-a .El nivel de IFN-g fue muy alto después de 24 h de infección en las ratas inoculadas únicamente con T. gondii, mientras que en los animales infectados con ambos parásitos (el primer grupo) el IFN-g no fue detectado en el mismo período de infección con T. gondii; IL-2 y TNF-a no fueron detectados. Estos datos son una evidencia preliminar de que en este proceso de inmuno-supresión, existe una reducción en los niveles deIFN-g, inducida por T. lewisi, lo cual es probablemente una de las razones por las que la rata se ve disminuida en su resistencia natural al T. gondii

the response to an oral calcium load test was assessed in 17 hypercalciuric nephrolithiasis patients who presented elevated parathyroid hormone (PTH) irrespective of the ionized calcium (sCa2+) levels. Blood samples were collected at baseline (0 min) and at 60 and 180 min after 1 g calcium load for serum PTH, total calcium, sCa2+, and 1.25(OH)2D3 determinations. According to the sCa2+ level at baseline, patients were classified as normocalcemic (N = 9) or hypercalcemic (N = 8). Six healthy subjects were also evaluated as controls. Bone mineral density was reduced in 14/17 patients. In the normocalcemic group, mean PTH levels at 0, 60 and 180 min (95 ± 76, 56 ± 40, 57 ± 45 pg/ml, respectively) did not differ from the hypercalcemic group (130 ± 75, 68 ± 35, 80 ± 33 pg/ml) but were significantly higher compared to healthy subjects despite a similar elevation in sCa2+ after 60 and 180 min vs baseline in all 3 groups. Mean total calcium and 1.25(OH)2D3 were similar in the 3 groups. Additionally, we observed that 5 of 9 normocalcemic patients presented a significantly higher concentration-time curve for serum PTH (AUC0',60',180') than the other 4 patients and the healthy subjects, suggesting a primary parathyroid dysfunction. These data suggest that the individual response to an oral calcium load test may be a valuable dynamic tool to disclose a subtle primary hyperparathyroidism in patients with high PTH and fluctuating sCa2+ levels, avoiding repeated measurements of both parameters.

Resumen Se realizó el presente estudio con el propósito de determinar diferencias fenotípicas en la sensibilidad a la exposición crónica al manganeso. Para ello se utilizaron ratones albinos y ratones negros C57BL/6J, divididos en dos grupos. A un grupo de cada cepa se le administraron inyecciones i.p. diarias de MnCl2 durante 9 semanas. El grupo control de cada cepa fue tratado en forma similar con solución salina. La administración prolongada de Mn no produjo alteraciones en la actividad locomotora en ninguna de las cepas examinadas. Se analizaron varias monoaminas y sus metabolitos mediante Cromatografía Líquida de Alta Presión con detección electroquímica, en la substancia negra (SN), el cuerpo estriado (CE) y el locus coeruleus (LC). El tratamiento crónico con Mn no alteró en forma significativa ninguna de las aminas biogénicas analizadas en las dos cepas de ratones. Sin embargo, los resultados revelaron diferencias importantes en los niveles endógenos de catecolaminas presentes en ambas cepas: las concentraciones de dopamina en SN y en CE de los C57, fueron marcadamente inferiores a las encontradas en ratones albinos. Se encontraron niveles de ácido dihidroxi-fenilacético mayores en el CE de los ratones C57; mientras que no se evidenciaron diferencias en el ácido homovanílico. Los contenidos de adrenalina y serotonina, fueron inferiores en el estriado de los ratones C57, pero no fueron diferentes en SN y el LC. Por otro lado y, contrastando con los hallazgos obtenidos para los otros neurotransmisores, se encontraron niveles de noradrenalina (NA) significativamente mayores en el LC y en el estriado de los ratones negros C57 cuando se compararon con los niveles de NA presentes en los ratones albinos. Se concluye que, a pesar de las diferencias observadas en el contenido endógeno de catecolaminas entre ambas cepas, los ratones C57 no son, aparentemente, más sensibles al efecto del manganeso que los ratones albinos.

Abstract The present study was conducted to further examine the observed phenotypic differences in the sensitivity to chronic manganese exposure. Albino mice (NMRI-IVIC strain) and C57BL/6 black mice were divided into two groups. One group of mice was given daily i.p. injections of manganese during 9 weeks. The control group of each strain was treated with saline. After treatment, we examined their spontaneus motor activity. Manganese administration did not alter the measured locomotor activity in any of the strains. We also determined the concentrations of several monoamines and their metabolites, in the substantia nigra (SN), corpus striatum (CS) and locus coeruleus (LC), by High Pressure Liquid Chromatography with electrochemical detection. In our study, the administration of Mn did not change any of the brain amines analyzed. However, it was evident that there were striking differences in the endogenous levels of monoamines between both strains: dopamine concentrations in SN and CS of C57 mice were markedly lower than those present in albino mice. Dihydroxy phenyl acetic acid levels were higher in CS of C57 mice; whereas there was no difference in the homovanillic acid content. The concentrations of adrenalin and serotonin were lower in the CS of C57 mice, but did not differ in SN and LC. We found higher levels of noradrenaline in the LC and CS of C57 mice. We conclude that in spite of the observed differences in the amine concentrations of the two strains, C57 black mice were not more susceptible to the effects of manganese, than the albino mice strain studied

OBJETIVO: Investigar o papel do óxido nítrico (NO) no influxo celular (IC) e a incapacitação articular (IA) na artrite por zymosan (AZy). MÉTODOS: Ratos Wistar receberam injeção de Zy (1mg) no joelho direito. Grupos-controles receberam salina. A IA foi avaliada pelo Teste de incapacitação articular para ratos. Após sacrifício, o IC e a liberação de PGE2 foram avaliados no lavado articular. Avaliou-se o edema pela diferença peso úmido/peso seco do tecido articular. Grupos foram tratados i.p. com L-NAME - inibidor de sintases de NO (NOS) (LN=30-300mg/kg) ou aminoguanidina (AG= 30-300mg/kg) - inibidor seletivo de iNOS 30 min antes ou 2 h após o Zy. RESULTADOS: O pré-tratamento com L-NAME ou AG inibiu de forma dose-dependente a IA e o IC, mas não o edema ou a liberação de PGE2, sendo máximo para LN ou AG (100mg/kg). L-arginina (1g/kg) co-injetada com LN (100mg/kg) reverteu a inibição da IA e do IC. D-NAME (100mg/kg) não teve efeito. Co-injeção de naloxona (antagonista opióide) reverteu o efeito de LN e AG sobre a IA. A pressão arterial média elevou-se (p<0,01) após LN (100mg/kg), mas não com AG (100mg/kg). LN e AG (100mg/kg) dados 2 h após Zy não tiveram efeito. Azul de metileno (inibidor de GMPc), e não hemoglobina (scavenger de NO), reduziu IA e IC (p<0,01). Nitroprussiato de sódio (doador de NO) dado 2 h após Zy, reduziu a IA, mas não o IC (p<0,01). CONCLUSÕES: A antinocicepção na AZy por inibição da iNOS só ocorre como pré-tratamento, por efeito antiinflamatório via GMPc, independentemente de NO exógeno ou de PGE2, associada à liberação de opióides endógenos. Um doador de NO produz analgesia na AZy. Enfim, o trabalho demonstra efeito analgésico de um doador de NO em um modelo de periartrite, abrindo a perspectiva do uso dessas substâncias em humanos.

OBJECTIVE: To study the role of nitric oxide (NO) in the cell influx (CI) and the articular incapacitation (AI) in the zymosan induced-arthritis (ZyA). METHODS: Wistar rats received 1 mg of zymosan (Zy) into the right knee joint, and controls received saline. The AI was evaluated by the Test for AI in rats. After sacrifice, the CI and the release of prostaglandin E2 (PGE2) were assessed in the joint exudate. The joint edema was measured by the wet/dry weight ratio of the articular tissue. Groups were treated i.p. with L-NAME - NO synthase (NOS) inhibitor (LN = 30-300 mg/kg) or aminoguanidine (AG = 30-300 mg/kg) - selective iNOS inhibitor - 30 minutes before or 2 hours after the Zy. RESULTS: Pretreatment with L-NAME or AG dose-dependently inhibited the AI and the CI, but not altering edema or PGE2 release, being maximal for the 100 mg/kg doses of L-N and AG. Coinjection of L-arginine (1g/kg) and LN (100 mg/kg) reversed the inhibition of the AI and of the CI. D-NAME (100 mg/kg) had no effect. Coinjection of naloxone (opioid antagonist) reversed LN or AG effect on the AI. Mean arterial pressure increased (p<0,01) with LN (100 mg/kg), but not with AG (100 mg/ kg). LN and AG (100 mg/kg) given 2 hours after the Zy had no effect. Methylene blue (GMPc inhibitor), but not hemoglobin (NO scavenger) reversed AI and CI (p<0,01). Sodium nitroprusside (NO donor) given 2 hours after Zy reduced significantly AI, but not CI (p<0,01). CONCLUSIONS: The antinociceptive effect of iNOS inhibition in ZyA happens only with a prophylactic administration, due to an anti-inflammatory effect via GMPc, independently of exogenous NO or PGE2 release, but is associated to endogenous opioid release. The administration of an NO donor produces analgesia in ZyA.

O efeito da desnutrição durante a lactação sobre a agressividade foi investigado em ratos adultos tratados ou não com citalopram, um inibidor seletivo da recaptação de serotonina (ISRS). Os animais foram divididos em dois grupos de acordo com a dieta: grupo nutrido-- ratos que receberam toda a vida dieta controle (23% de proteína); e grupo desnutrido-- ratos que tiveram suas mães submetidas a dieta com 7,8% de proteína na lactação. Aos 120 dias de idade, cada grupo foi sub-dividido conforme o tratamento: agudo -- consistindo de injeção única i.p. de solução salina ou 20mg/Kg de citalopram; crônico - consistindo de injeções únicas (1 por dia durante 14 dias) de salina ou 20mg/Kg de citalopram. O tratamento agudo ou crônico com ISRS reduziu a resposta agressiva nos ratos nutridos, mas não nos desnutridos. Assim, a desnutrição durante o período crítico de desenvolvimento do cérebro parece acarretar alterações duradouras na função da neurotransmissão serotoninérgica.

The effect of the malnutrition during suckling on the aggressiveness was investigated in adult rats treated or not with citalopram, a selective serotonin reuptake inhibitor (SSRI). The animals were divided into two groups according to the diet used: nourished group-- the rats received the control diet with 23% protein during the life; and malnourished group-- the rats had its mothers submitted to diet with 7.8% protein during suckling. At 120 days of age, each group was sub-divided according to the treatment: acute -- consisting a single i.p. injection of saline solution or 20-mg/Kg citalopram; chronic -- consisting the single injections (1 per day during 14 days) of saline or 20 mg/Kg citalopram. The acute or chronic treatment with SSRI reduces aggressive response in nourished rats, but not in malnourished ones. Thus, the malnutrition during the critical period of brain development seems to induce durable alterations in the function of the serotoninergic neurotransmission