No description available.

Un substitut fiable est nécessaire après résection circonférentielle étendue de la trachée. La transplantation trachéale (TT) s’est heurtée à l’impossibilité d’une revascularisation directe et au rejet. Ayant démontré chez l’animal la faisabilité du remplacement trachéal (RT) par allogreffe aortique (AA) sans immunosuppression, nous avons conduit une étude clinique à partir de 2005. Six patients atteints de cancer étaient inclus (27% des cas de la littérature) ; actuellement 3 sont en vie et en rémission (suivi moyen 81 mois). Cependant, contrairement à l’animal, nous n’avons pas observé chez l’homme de régénération trachéale des greffons, probable conséquence de leur ischémie initiale. Pour résoudre ce problème, nous avons conduit 5 séries d’investigations sur modèle lagomorphe : Etude de l’efficacité de l’enveloppement fascial (EF) sur la néo angiogenèse de l’AA. EF appliqué à un greffon composite (AA entourée d’anneaux cartilagineux allogéniques). RT avec ce greffon.Quarante neuf lapins étaient donneurs et 74 étaient receveurs de sexe opposé. Il n’y avait pas d’immunosuppression. Lors des EF, les greffons étaient enveloppés dans un lambeau de fascia latéro-thoracique, puis implantés sous la peau. Lors des RT et TT en 2 temps, la résection de la trachée du receveur était suivie d’une rotation au cou du greffon enveloppé, qui était suturé à la trachée native. Lors des RT en 1 temps, le greffon était directement interposé après résection de la trachée du receveur. Les lapins ont été suivis jusqu’au décès ou sacrifiés. Les études microscopiques, la détection des chromosomes X et Y (FISH) et des cellules en apoptose (APOSTAIN) ont permis d’étudier la revascularisation, la viabilité et le rejet des greffons.L’EF de l’AA (n=19) a permis de construire un nouvel organe tubulé et revascularisé. La FISH a démontré la migration de cellules de l’hôte au sein de l’AA, et la persistance de cellules du donneur, témoignant d’une ischémie minimale après EF. Mais ce greffon n’avait pas la rigidité requise pour un RT.• L’EF du greffon composite (n=9) a permis de construire un substitut trachéal rigide, à la structure cartilagineuse préservée. • Après RT avec greffon composite (n=10) les lapins sont décédés d’obstruction de la voie aérienne. Sept greffons sur 10 avaient une rigidité satisfaisante par calcification des cartilages, mais tous présentaient des lésions ischémiques (résultats insuffisants pour une application clinique).• Après EF, les segments d’ATDC (n=13) étaient viables. L’infiltration inflammatoire était minime, sans lymphocyte. L’apoptose observée évoquait une réaction de rejet à minima.• Après TT par longs segments d’ATDC (n=7), 6 lapins sont décédés de sténose par prolifération endoluminale fibroblastique de J3 à J48. Après TT par segments courts (n=7), 3 lapins sont décédés et 4, sacrifiés de J33 à J220, présentaient une perméabilité et une morphologie normale du greffon. Tous les greffons, présentaient des signes de néo angiogenèse. L’infiltration inflammatoire était variable, sans lymphocyte. Les cartilages se calcifiaient, de 90% à 100% après 30 jours. Enfin, la régénération épithéliale était observée dès J20. [...] / After extended circumferential resection of the trachea, a reliable substitute is needed. Tracheal transplantation (TT) failed because of impossibility for direct revascularization, and rejection. On the other hand, our animal studies have demonstrated the feasibility of tracheal replacement (TR) with aortic allografts (AA). Since 2005, we performed this procedure in 6 cancer patients (accounting for 27% of cases in the available literature), and 3 are alive with no evidence of disease (mean follow-up: 81 months). The graft of patients did not display, however, cartilage regeneration as shown in animal models, possibly due to critical ischemia prior to neoangiogenesis. To solve this issue, investigations were conducted in rabbit models: • Study of the efficacy of the lateral thoracic fascial flap wrap (FW) for neoangiogenesis of AA. FW applied to a composite graft (AA with external cartilage-ring support). Staged TR using the composite graft.FW applied to segments of tracheal allograft, epithelium-denuded and cryopreserved to reduce immunologic reaction. Staged, and then direct TT using these tracheal segments.Forty-nine rabbits were used as donors and 74 sex-mismatched as recipients. No immunosuppressive therapy was given. During FW, grafts were wrapped using a lateral thoracic fascial flap, and then implanted under the skin of the chest wall. During staged TR or TT, tracheal resection was followed by rotation of the flap-wrapped graft to the neck, and anastomosis to the native trachea. During direct TT, the allograft segment was interposed between the stumps of the resected trachea.Rabbits were followed-up to death or sacrifice. Microscopic examination, FISH analysis for detection of both X and Y chromosomes, and detecting apoptotic cells (APOSTAIN), were used to study the morphology, revascularization, viability, and determine rejection. The FW applied to AA (n=19) ensured the construction of a novel well-vascularized tube-shaped organ. FISH analysis showed migration of recipient cells into the AA, and persistence of normal cells from the donor suggestive of minimal ischemia. This construct, however, did not show stiffness sufficient to ensure TR. • The 9 animals in which FW was applied to composite graft showed a rigid tracheal substitute with preserved histological structure of cartilages.• The 10 rabbits undergoing TR with this composite graft died of central airway obstruction. Despite severe ischemic lesions, satisfactory graft stiffness was shown in 7 out of 10 animals, due to cartilage calcifications. The results did not allow, however, the use of the construct in the clinical setting.• The 13 animals in which FW was applied to epithelium-denuded-cryopreserved tracheal segments maintained viability. The inflammatory reaction was minimal, with no lymphocytes. Apoptosis events were suggestive of minimal immunological response.• The results of TT using long segments of epithelium-denuded-cryopreserved allografts were disappointing, since 6 rabbits sustained a graft stenosis because of intraluminal fibroblastic proliferation. Of 7 rabbits undergoing TT with short segments, 4 were euthanized between 33 and 220 days. They showed patency and satisfactory strain abilities of their graft due to cartilage calcification deposits; and microscopically, neoangiogenesis, non-specific inflammatory infiltrate with no lymphocytes and satisfactory epithelial cell ingrowths from day 20 [...]

Type 2 diabetes mellitus (T2DM) is mainly caused by genetic modifications and inappropriate life styles. The complexity of T2DM has brought us challenges for a comprehensive understanding of altered metabolic pathways that contributing to the development of T2DM. Therefore, a comprehensive metabolic analysis is needed. To date, taking regular exercise is a common and effective therapeutic way known to antagonize the metabolic disorders of T2DM. However, the regulatory effects of exercise on T2DM or T2DM induced complications have not been clearly characterized. Here, we present the effect of physical activity on biochemical changes in diabetic db/db mice in plasma, urine, skeletal muscle and kidney samples. Based on liquid chromatography coupled with high resolution Orbitrap mass spectrometry (LC-MS) and gas chromatography coupled with mass spectrometry (GC-MS), two major approaches, untargeted and targeted metabolomics studies, have been developed to delineate metabolic signatures in various kinds of biofluid and tissue samples. Targeted quantification methods on acylcarnitines and acyl-CoA have been developed. Untargeted metabolomics analysis by GC-MS and LC-MS have also been developed to draw a more comprehensive view of the metabolic changes in response to T2DM and exercise on db/db diabetic mice. The transcript expressions of mRNA in pathways of interest have also been measured to confirm the hypothesis. Firstly, a targeted quantification method of acylcarnitines by using high resolution parallel reaction monitoring (PRM) on LC-MS platform has been developed. A total of 117 acylcarnitines were detected from plasma and urine samples. The application of targeted profiling of acylcarnitines in db/m+ control and db/db diabetic mice indicated incomplete amino acid and fatty acid oxidation in diabetic mice. Interestingly, the reduction of medium odd-numbered chain acylcarnitines in urine samples was firstly observed between db/m+ and db/db mice. The high resolution PRM method makes it possible to monitor the widespread metabolic changes of the acylcarnitines in response to stimuli. Besides, the accurate MS and MS/MS spectra data of the 117 acylcarnitines could be used as mass spectrometric resources for the identification of acylcarnitines. In addition to targeted metabolomics analysis, untargeted metabolomics profiling analysis in plasma samples indicated that db/db diabetic mice may be more susceptible to exercise for energy expenditure. Interestingly, all the results from plasma, skeletal muscle and kidney samples may demonstrate that physical activity could mitigate insulin resistance in T2DM mice through improving fatty acid β-oxidation (FAO) and eliminating overloaded intermediate which contribute to insulin resistance. Specifically, the results from kidney samples demonstrated that exercise exhibit beneficial effect in reducing hyperlipidemia, expression levels of inflammatory markers (TNFα, IL-6 and COX2) and fibrosis markers (Collagen 1), and alleviating diabetic nephropathy (DN) induced mesangial expansion in kidneys of diabetic mice. The results of metabolic changes in kidney of db/db mice revealed that the accumulation of acyl-CoA, phospholipids and hydroxylated acylcarnitines were substantially ameliorated by exercise, and the reduction of important enzymes CTP1α and Acadl in FAO were partially reversed. In addition, branched-chain amino acids (BCAA) metabolism which positively related to inflammation (TNFα) was down-regulated in DN mice by exercise. What’s more, the accumulation of uric acid, which contributes to inflammation and tubulointestitial fibrosis in kidney disease, together with its six precursors have also been substantially reduced. The results in kidney samples demonstrated that in addition to beneficial effect in alleviating lipotoxicity through improving FAO efficiency, exercise also ameliorated diabetic induced inflammation and fibrosis via promoting BCAA catabolism and accelerating the elimination of uric acid. Together, the mass spectrometry-based metabolomics study is a powerful tool to investigate the regulatory effect of exercise on complex metabolic diseases. The results may provide informative insights into the underlying the mechanism of exercise on T2DM and T2DM induced complications.

O uso de tetracloreto de carbono (CCl4) em ratos é um modelo experimental de dano ao tecido hepático, desencadeando fibrose e, a longo prazo, cirrose. A cirrose hepática é uma doença crônica progressiva que representa um estado de disfunção hepática irreversível ou lentamente reversível, caracterizado pela formação de nódulos fibróticos. Este estudo possui como objetivo avaliar as alterações hepáticas e pulmonares causadas pelo modelo de cirrose hepática através da utilização de CCl4 intraperitoneal. Foram utilizados 18 ratos Wistar machos divididos em 3 grupos: grupo controle (CO) e outros 2 grupos divididos pelo tempo de indução da cirrose por CCl4. G1 (11 semanas), G2 (16 semanas). Verificamos a elevação significativa no nível das transaminases hepáticas, na lipoperoxidação do tecido hepático e pulmonar (TBARS) e nas enzimas antioxidantes SOD e CAT, além de um aumento da expressão de TNF-M e IL-1N no pulmão dos animais cirróticos. Observamos alteração nas trocas gasosas de ambos os grupos cirróticos. Podemos concluir que nosso modelo reproduziu a cirrose hepática, além de causar alterações no sistema pulmonar, provocando alteração nas trocas gasosas e alterando o tamanho dos vasos pulmonares. / The use of carbon tetrachloride (CCl4) in rats is an experimental model of hepatic tissue damage, which leads to fibrosis, and at the long term, cirrhosis. Cirrhosis is a chronic progressive disease that represents a state of irreversible or slowly reversible hepatic disfunction, characterized by fibrotic nodules formation. The aim of this study is to evaluate the changes caused by cirrhosis in lung and liver, through the experimental model of intraperitoneal CCl4 administration. We used 18 male Wistar rats divided into three groups: control (CO) and two groups divided by the time of cirrhosis induction by CCl4. G1 (11semanas), G2 (16semanas). We found significant increase of transaminase levels and lipid peroxidation (TBARS) in liver and lung tissue. Also, increased antioxidant enzymes SOD and CAT, as well as the expression of TNF-M and IL-1N in the lung of cirrhotic animals. We observed changes in gas exchange in both cirrhotic groups. We can conclude that our model reproduces the liver cirrhosis, that causes alterations in the pulmonary system that leads to changes in gas exchange and size of pulmonary vessels.

Background: The 18 kDa translocator protein (TSPO), expressed at a low level in the healthy human central nervous system (CNS), is upregulated in inflammatory brain diseases by activated microglia and other immune cells. Using positron emission tomography (PET) radioligands targeting TSPO, it is possible to localise this signal and map the course of microglial activation and its effects on disease progression. Here, a newly developed second generation TSPO PET ligand, [18F]GE-180, was evaluated in different models of preclinical and clinical neuroinflammatory disease. Methods: A preclinical model of low-level inflammation with lipopolysaccharide (LPS) was designed. Rats were scanned with the first generation TSPO ligand [11C]- (R)-PK11195 and either [18F]GE-180 or [18F]DPA-714, with dual scanning enabling the direct comparison of second generation tracers with [11C]-(R)-PK11195. An arterial blood sampling system for rodent imaging with [18F]DPA-714 was set up and characterised. The performance of [18F]GE-180 was assessed in a clinical study in nine relapsing-remitting multiple sclerosis patients (RRMS) and ten healthy volunteers (HV). A comparison of kinetic modelling approaches for [18F]GE-180 human brain PET data was performed, as well as a longitudinal analysis with intervention using the disease-modifying treatment, natalizumab to evaluate the potential of [18F]GE-180 as a biomarker for therapy monitoring in MS subjects. Finally, the plasma-protein binding behaviour of [18F]GE-180 was evaluated in vitro using ultrafiltration. Results: In LPS animals, [18F]GE-180 produced a significantly higher ipsi- to contralateral uptake ratio and binding potential () than [11C]-(R)-PK11195 (p = 0.03), but [18F]DPA-714 did not. There was no significant difference between animals scanned with [18F]GE-180 and [18F]DPA-714, suggesting no overall superiority of the former. Characterisation of an arterial sampling system for rodent studies with [18F]DPA-714 allowed correction for dispersion effects. A comparison of reference regions showed that a novel externally derived tissue estimated with lower bias than a contralateral reference region. In human [18F]GE-180 brain PET data, the unconstrained two-tissue compartment model (2TCM) best described tracer behaviour in RRMS and HV subjects. Normal appearing white matter (NAWM) in patients was elevated over that of HVs. Standardised uptake values (SUVs) for the tracer in rodents were 0.28±0.12 and 0.84±0.31 in healthy tissue and LPS lesions respectively, and in humans were 0.36±0.04 (HV) and 0.58 (in a gadolinium- enhancing MS lesion). [18F]GE-180 uptake was also significantly reduced in the brains of RRMS subjects treated with natalizumab, correlating with clinically-identified improvement. [18F]GE-180 has a free fraction of between 1 and 8%.Conclusions: [18F]GE-180 shows good brain uptake in the rodent brain and produces superior signal to [11C]-(R)-PK11195, but not to [18F]DPA-714. The 2TCM fits human [18F]GE-180 PET data well, and the tracer is able to identify an elevated signal in RRMS patients compared to healthy subjects. [18F]GE-180 shows a large fraction of non-displaceable binding in human blood, thus further optimisation of kinetic modelling approaches is suggested.

Text in Afrikaans / Hierdie studie handel oor die ontwerp van 'n post traumatiese terapie deur die opvoedkundige sielkundige waar troeteldiere as fasiliteerder ingespan kan word. Dit fokus op getraumatiseerdes wat na afloop van 'n trauma in 'n post traumatiese situasie verkeer, en nie klinies aan die diagnose van post traumatiese stres versteuring voldoen nie. Die ontwerp van die terapie val in vier fases uiteen wat nie noodwendig streng chronologies in terapie hoef te verloop nie. Eerstens is daar die affektiewe fase wat handel oor die bantering van emosies. Tweedens fokus die kognitiewe fase op kognitiewe herstrukturering by die getraumatiseerde en veral die internalisering daarvan. Die fase van voorraadopname maak voorsiening vir die identifisering van psigologiese gestremdhede en sterker modaliteite van die getraumatiseerde. Die kompensatoriese fase handel oor die ontwerp van 'n aksieplan vir die sinvolle voortsetting van die getraumatiseerde se lewe asook inoefeningsaspekte daarvan. Die terapeutiese ontwerp het beslag gekry na 'n uitgebreide literatuurstudie van verskeie terapeutiese skole se post traumatiese terapiee en tegnieke. Oorhoofs word bogenoemde ontwerp in die relasieterapie ingebed. Hierdie terapie le besondere klem op die kompensatoriese fase met die oog op adekwate aktualisering van die getraumatiseerde in sy toekomstige gesitueerdheid. Alhoewel daar 'n uitgebreide beskrywing van troeteldier gefasiliteerde terapie volg, het die navorser slegs sekere getraumatiseerde kliente ge'identifiseer wat sat baat by troeteldier gefasiliteerde terapie. Daar is tydens die studie aandag gegee aan die ontwerp van 'n vraelys wat as operasionele metingsinstrument dien om die omvang van die trauma ten opsigte van die getraumatiseerde se filnksionering, selfgesprekke, belewenis, betekenisgewing, betrokkenheid, seltkonsep, relasies en selfaktualisering te bepaal. Fasiliteerders van die affektiewe fase sluit onder andere soos reeds genoem hierbo, troeteldiere in. Ondersoek is ingestel na die riglyne vir troeteldier gefasiliteerde terapie, en verskeie aspekte soos determinante by die getraumatiseerde vir troeteldier gefasiliteerde terapie, die aard van mens-dier interaksie, risiko's en menslike voorwaardes verbonde aan troeteldier gefasiliteerde terapie, is beskryf Tydens die empiriese ondersoek is gevind dat alhoewel die ontwerp beperkinge het, daar besliste ruimte vir troeteldier gefasiliteerde post traumatiese terapie op Sielkundige Opvoedkunde terrein bestaan / This study deals with the design of a post traumatic therapy that can be administered by the educational psychologist. Pets were used for the first time as facilitators in such a therapy. This therapy was primarily designed for persons in a post traumatic situation after an experienced trauma, who _do not ~fy foc!h<L~!i_ni~_ctl _ cri!~!"ia gf post traumatic _stress disorder. Four phases can be distinguished in the course of the therapy. This doesn't however imply a hierargical order. First of all the affective phase deals with the emotional side of the traumatised person. Secondly cognitive restructuring is taken up in the cognitive phase as well as internalization thereof The third phase of stock taking makes provision for the identification of psychological handicaps and stronger modalities of the traumatised person. A plan of action is developed in the final compensatory phase and it deals with optimal future actualization of the traumatised person. If necessary, opportunity is provided for excercising the newly required skills. This design was developed after extensive literature studies of post traumatic therapies and techniques, and it is embedded in the overall approach of relationship therapy. Strong emphasis is placed on the compensatory phase in view of the traumatised person's adequate future actualization. Although an extensive description of pet fasilitated therapy is given, only certain traumatised clients were identified who will benefit from this therapy. A questionnaire as operational measuring instrument was developed for the purpose of this study. Information as to the traumatised person's functioning, selftalk, experiences, allocation of meaning, involvement, selfconcept, relationship formation and selfactualization can be ascertained via this instrument. One of the facilitators of the affective phase, already mentioned, includes pets. A thorough study into guidelines for pet facilitated therapy, as well as aspects such as determinants of traumatised people as indication for this kind of therapy, the nature of human-animal interaction, risks and human conditions for pet facilitated therapy, was undertaken. The empirical study proved that in spite of limitations of pet facilitated post traumatic therapy, definite opportunity exists in the field of Psychology of Education for this kind of therapy / D.Ed. (Sielkundige Opvoedkunde)

O uso de tetracloreto de carbono (CCl4) em ratos é um modelo experimental de dano ao tecido hepático, desencadeando fibrose e, a longo prazo, cirrose. A cirrose hepática é uma doença crônica progressiva que representa um estado de disfunção hepática irreversível ou lentamente reversível, caracterizado pela formação de nódulos fibróticos. Este estudo possui como objetivo avaliar as alterações hepáticas e pulmonares causadas pelo modelo de cirrose hepática através da utilização de CCl4 intraperitoneal. Foram utilizados 18 ratos Wistar machos divididos em 3 grupos: grupo controle (CO) e outros 2 grupos divididos pelo tempo de indução da cirrose por CCl4. G1 (11 semanas), G2 (16 semanas). Verificamos a elevação significativa no nível das transaminases hepáticas, na lipoperoxidação do tecido hepático e pulmonar (TBARS) e nas enzimas antioxidantes SOD e CAT, além de um aumento da expressão de TNF-M e IL-1N no pulmão dos animais cirróticos. Observamos alteração nas trocas gasosas de ambos os grupos cirróticos. Podemos concluir que nosso modelo reproduziu a cirrose hepática, além de causar alterações no sistema pulmonar, provocando alteração nas trocas gasosas e alterando o tamanho dos vasos pulmonares. / The use of carbon tetrachloride (CCl4) in rats is an experimental model of hepatic tissue damage, which leads to fibrosis, and at the long term, cirrhosis. Cirrhosis is a chronic progressive disease that represents a state of irreversible or slowly reversible hepatic disfunction, characterized by fibrotic nodules formation. The aim of this study is to evaluate the changes caused by cirrhosis in lung and liver, through the experimental model of intraperitoneal CCl4 administration. We used 18 male Wistar rats divided into three groups: control (CO) and two groups divided by the time of cirrhosis induction by CCl4. G1 (11semanas), G2 (16semanas). We found significant increase of transaminase levels and lipid peroxidation (TBARS) in liver and lung tissue. Also, increased antioxidant enzymes SOD and CAT, as well as the expression of TNF-M and IL-1N in the lung of cirrhotic animals. We observed changes in gas exchange in both cirrhotic groups. We can conclude that our model reproduces the liver cirrhosis, that causes alterations in the pulmonary system that leads to changes in gas exchange and size of pulmonary vessels.

CoordenaÃÃo de AperfeiÃoamento de NÃvel Superior / A depressÃo à uma doenÃa recorrente e incapacitante cujo tratamento clÃnico està relacionado com modulaÃÃes nos sistemas monoaminÃrgicos em diversas Ãreas cerebrais. A riparina II (ripII), alcamida isolada do fruto verde de Aniba riparia, apresentou previamente efeito antidepressivo em modelos comportamentais. Dessa forma, objetivando investigar o potencial antidepressivo da ripII, foram realizados experimentos comportamentais como o teste do nado forÃado, suspensÃo da cauda e campo aberto. Para avaliar o envolvimento do sistema monoaminÃrgico, os animais foram prÃ-tratados com antagonistas especÃficos para receptores 5-HT1A, 5-HT2A/2C e 5-HT3 de serotonina (5-HT), D1 e D2 de dopamina (DA) e a1 e a2 de noradrenalina (NA) no teste do nado forÃado. AlÃm disso, os animais previamente tratados com ripII e submetidos ao teste do nado forÃado tiveram as Ãreas cerebrais hipocampo, corpo estriado e cÃrtex prÃ-frontal retiradas para detecÃÃo dos nÃveis de monoaminas em HPLC eletroquÃmico ou para realizaÃÃo dos experimentos de estresse oxidativo, para o qual foram investigadas a atividade enzimÃtica da superÃxido dismutase, quantificaÃÃo dos nÃveis de glutationa reduzida (GSH) e nitrito/nitrato, alÃm do grau de lipoperoxidaÃÃo. A ripII foi administrada agudamente, por via oral, na dose de 50 mg/kg, em todos os testes realizados. Os resultados mostraram que a ripII apresentou efeito antidepressivo nos modelos de nado forÃado e suspensÃo da cauda sugerindo que este efeito seja especÃfico, uma vez que os animais nÃo apresentaram alteraÃÃes na atividade locomotora no teste do campo aberto. Na avaliaÃÃo dos sistemas monoaminÃrgicos, os resultados mostraram que os antagonistas SCH23390 (D1), sulpirida (D2), prazosina (a1), NAN-190 (5-HT1A) e ondansentron (5-HT3) reverteram o tempo de imobilidade da ripII no nado forÃado sugerindo a participaÃÃo desses receptores para o efeito antidepressivo da substÃncia, enquanto nÃo houve alteraÃÃo deste efeito na presenÃa dos antagonistas ioimbina (a2) e ritanserina (5-HT2A/2C) sugerindo a nÃo participaÃÃo desses receptores no efeito da droga. A administraÃÃo prÃvia de ripII, antes do nado forÃado, reverteu o aumento nos nÃveis de peroxidaÃÃo lipÃdica, mas aumentou os nÃveis de GSH em hipocampo, corpo estriado e cÃrtex prÃ-frontal. Em conclusÃo, o estudo sugere uma aÃÃo moduladora, exercida por ripII, sobre o funcionamento dos sistemas noradrenÃrgico, dopaminÃrgico e serotonÃrgico, em nÃvel central, como mecanismo para o efeito antidepressivo no teste do nado forÃado, bem como a participaÃÃo de propriedades antioxidantes diretas ou indiretas dessa droga, atravÃs da capacidade de modificar a resposta ao estresse oxidativo neuronal. / Depression is a disabling and recurrent disease whose clinical treatment is related to modulations in monoaminergic systems in various brain areas. Riparina II (ripII), alkamide isolated from unripe fruit of Aniba riparia, has shown previously antidepressant-like effects in animal behavioral models. Thus, in order to investigate the potential antidepressant ripII, behavioral experiments were performed as the forced swim, tail suspension and open field tests. To assess the involvement of monoaminergic system, animals were pretreated with specific antagonists to 5-HT1A-, 5-HT2A/2C-, and 5-HT3-serotonin (5-HT) receptors, to D1- and D2-dopamine (DA) receptors and to &#61537;1- and &#61537;2-noradrenaline (NA) receptors in the forced swimming test. Furthermore, animals pretreated with ripII and submitted to the forced swim test had their brain areas such as hippocampus, striatum and prefrontal cortex removed for detection of monoamine levels in HPLC electrochemical or to carry out the experiments of oxidative stress. In the oxidative stress assays we investigated enzymatic activities of superoxide dismutase, measured the levels of reduced glutathione (GSH) and nitrite/nitrate, and lipid peroxidation degree. RipII was acutely administered orally at a dose of 50 mg/kg in all tests. The results showed that ripII presented antidepressant effect on the forced swim and tail suspension tests suggesting that this effect is specific, since the animals showed no changes in locomotor activity in open field test. In the evaluation of monoaminergic systems, the results showed that the antagonists SCH23390 (D1), sulpiride (D2), prazosin (&#61537;1), NAN-190 (5-HT1A) and ondansentron (5-HT3) reversed the immobility time of ripII on the forced swim test suggesting the involvement of these receptors for the antidepressant effect of ripII, while no change of this effect in the presence of the antagonists yohimbine (&#61537;2) and ritanserin (5-HT2A/2C) was observed, suggesting non-participation of these receptors on the drug effect. The prior administration of ripII before the forced swimming, reversed the increased levels of lipid peroxidation and increased levels of GSH in hippocampus, striatum and prefrontal cortex. In conclusion, the study suggests a modulating action exerted by ripII on the functioning of the noradrenergic, dopaminergic and serotonergic levels in the brain, as a mechanism for the antidepressant effect in the forced swimming test, as well as the participation of direct or indirect antioxidant properties of this drug through the ability to modify the neuronal response to oxidative stress.

O uso de tetracloreto de carbono (CCl4) em ratos é um modelo experimental de dano ao tecido hepático, desencadeando fibrose e, a longo prazo, cirrose. A cirrose hepática é uma doença crônica progressiva que representa um estado de disfunção hepática irreversível ou lentamente reversível, caracterizado pela formação de nódulos fibróticos. Este estudo possui como objetivo avaliar as alterações hepáticas e pulmonares causadas pelo modelo de cirrose hepática através da utilização de CCl4 intraperitoneal. Foram utilizados 18 ratos Wistar machos divididos em 3 grupos: grupo controle (CO) e outros 2 grupos divididos pelo tempo de indução da cirrose por CCl4. G1 (11 semanas), G2 (16 semanas). Verificamos a elevação significativa no nível das transaminases hepáticas, na lipoperoxidação do tecido hepático e pulmonar (TBARS) e nas enzimas antioxidantes SOD e CAT, além de um aumento da expressão de TNF-M e IL-1N no pulmão dos animais cirróticos. Observamos alteração nas trocas gasosas de ambos os grupos cirróticos. Podemos concluir que nosso modelo reproduziu a cirrose hepática, além de causar alterações no sistema pulmonar, provocando alteração nas trocas gasosas e alterando o tamanho dos vasos pulmonares. / The use of carbon tetrachloride (CCl4) in rats is an experimental model of hepatic tissue damage, which leads to fibrosis, and at the long term, cirrhosis. Cirrhosis is a chronic progressive disease that represents a state of irreversible or slowly reversible hepatic disfunction, characterized by fibrotic nodules formation. The aim of this study is to evaluate the changes caused by cirrhosis in lung and liver, through the experimental model of intraperitoneal CCl4 administration. We used 18 male Wistar rats divided into three groups: control (CO) and two groups divided by the time of cirrhosis induction by CCl4. G1 (11semanas), G2 (16semanas). We found significant increase of transaminase levels and lipid peroxidation (TBARS) in liver and lung tissue. Also, increased antioxidant enzymes SOD and CAT, as well as the expression of TNF-M and IL-1N in the lung of cirrhotic animals. We observed changes in gas exchange in both cirrhotic groups. We can conclude that our model reproduces the liver cirrhosis, that causes alterations in the pulmonary system that leads to changes in gas exchange and size of pulmonary vessels.

No description available.