Anthropogenic activities are increasing inorganic nitrogen (N) loadings to lakes in the northern hemisphere. In many boreal lakes phytoplankton are N limited, wherefore enhanced N input may affect the productivity of pelagic food webs. Simultaneously, global change causes increased inflows of terrestrial dissolved organic carbon (DOC) to boreal lakes. Between clear and humic lakes, whole lake primary and consumer production naturally differs. However, research is inconclusive as to what controls pelagic production in these lakes. Further, it is unclear how DOC affects the response of the pelagic food web to enhanced inorganic N availability. The overarching goal of this thesis was to study the effects of inorganic N and organic C for pelagic food webs in boreal lakes. In the thesis, I first identified the main drivers of pelagic production during summer in eight non-manipulated Swedish boreal lakes with naturally low or high DOC. Then I investigated how increased N availability affects the pelagic food chain, and how the response differs with DOC. Therefore, whole lake inorganic N fertilization experiments were conducted in six Swedish boreal lakes across a DOC gradient (low, medium, high) divided into three lake pairs (control, N enriched) with one reference and two impact years. In each lake, I also investigated the response of zooplankton growth using in situ mesocosm experiments excluding planktivores. I found that humic boreal lakes had lower phytoplankton production and biomass than clear water lakes. Further, phytoplankton community composition and food quality differed with DOC. However, high DOC did not reduce pelagic energy mobilization or zooplankton biomass, but promoted a higher dominance of cladoceran relative to copepod species. N addition clearly enhanced phytoplankton biomass and production in the experimental lakes. However, this stimulating N effect decreased with DOC as caused by light limitation. Further, the newly available phytoplankton energy derived from N addition was not efficiently transferred to zooplankton, which indicates a mismatch between producer energy supply and consumer energy use. Indeed, the mesocosm experiment revealed that decreased food quality of phytoplankton in response to N addition resulted in reduced food web performance, especially in clearer lakes. In humic lakes, zooplankton production and food web efficiency were clearly more resilient to N addition. In summary, my thesis suggests that any change in the landscape that enhances inorganic N availability will especially affect pelagic food webs in clear water lakes. In contrast, brownification will result in more lakes being resilient to eutrophication caused by enhanced N deposition.

Decision-making is necessary to adapt to the variable environment in everyday life. During this process, our goal is to select the most beneficial course of action in order to obtain the best outcome, to develop efficient choice strategies. That is, estimating the probability to obtain any of the available outcomes as well as their value. Moreover, poor decision-making ability is a common symptom to several psychiatric disorders, such as pathological gambling, depression, schizophrenia and bipolar disorder.The cognitive and emotional mechanisms controlling decision-making processes depend, among others, on the striatum, Basal Ganglia’s main input nucleus. The striatum is divided into the dorsal striatum, responsible for motor and cognitive control that initiate actions (Dorsomedial Striatum, DMS) and generate habits (Dorsolateral Striatum, DLS), and Nucleus Accumbens (NAc) which manages reward and the influence of motivation on motor behavior. A2A-expressing and D1-expressing medium spiny neurons (iMSNs and dMSNs, respectively), accounting for 95% of striatal neurons act in coordination to generate adaptive behavioral responses. It has been shown that imbalanced activity between these two populations leads to abnormal behaviors: overactivation of striatonigral neurons promotes an increased locomotion as well as a higher sensitivity for reward, whereas overactivation of striatopallidal neurons produces the exact opposite effects. However, the specific contributions to decision-making of these two populations in each striatal territory remains unclear. Here, we made use of a chemogenetic (DREADD) tool to manipulate striatal projection neurons’ activity within each specific striatal area and tested their role in a decision-making operant protocol. To do so, we used two different mouse models that allowed us to target specifically iMSNs (A2A-Cre mice) or dMSNs (D1-Cre mice) and induce neuronal-specific expression of the hM3Dq DREADD receptor. CNO-mediated activation of these receptors led to neuronal activation. Then, we tested DREADD-dependent activation of MSNs during the Iowa Gambling Task (IGT), a test used to assess the influence of different rewards on choice and to evaluate the ability of mice to develop advantageous choice strategies. We found an exclusive role of DMS’ dMSNs in controlling choice preference, as DREADD-induced activation of these neurons produced a loss of preference. Manipulations of MSNs in other striatal areas led to altered task performance without affecting choice preference.These results contribute to a better understanding of the role of the striatum on decision-making and moreover, suggest the existence of a high level of functional specialization in this area, a fact that could be explained by the local circuits in which each MSN population is involved. / Doctorat en Sciences biomédicales et pharmaceutiques (Médecine) / info:eu-repo/semantics/nonPublished

Obesity is a growing problem globally. Currently 2.3 billion adults are overweight, and this number is rising. The most common method for weight loss is calorie counting, in which to lose weight a person should be in a calorie deficit. Basal Metabolic Rate accounts for the majority of calories a person burns in a day and it is therefore a major contributor to accurate calorie counting. This paper uses a Dynamic Bayesian Network to estimate Basal Metabolic Rate (BMR) for a sample of 219 individuals from all Body Mass Index (BMI) categories. The data was collected through the Lifesum app. A comparison of the estimated BMR values was made with the commonly used Harris Benedict equation, finding that food journaling is a sufficient method to estimate BMR. Next day weight prediction was also computed based on the estimated BMR. The results stated that the Harris Benedict equation produced more accurate predictions than the metabolic model proposed, therefore more work is necessary to find a model that accurately estimates BMR.

A demanda crescente de alimentos gera problemas ambientais, principalmente devido à remoção das coberturas vegetais nativas para a expansão da agricultura no Brasil. Essas alterações no uso da terra acarretam mudanças na dinâmica da matéria orgânica do solo. O tipo de vegetação também tem influência sobre a biota do solo e, por isso, a sua alteração ocasiona mudanças na biomassa microbiana, como revelam estudos envolvendo desmatamento. Os microorganismos representam a maior diversidade biológica e fisiológica do solo, além de serem responsáveis por mais de 95% dos processos de decomposição e ciclagem de nutrientes. Por este motivo, a demanda por indicadores rápidos e confiáveis para detectar alterações na qualidade do solo, principalmente por aqueles com base nos microrganismos, vem crescendo continuamente. O objetivo geral foi verificar se há diferenciação dos padrões da atividade e da diversidade funcional da biomassa microbiana dos solos sob as diferentes vegetações naturais, pastagens em uso e sistemas agrícolas recém implantados. A área de abrangência desta pesquisa corresponde aos estados de Rondônia (RO) e Mato Grosso (MT), que foi dividida em 11 ecorregiões relativamente homogêneas em termos de solos, vegetação nativa, geologia, clima e relevo. Foi realizada a análise da variável canônica de alguns atributos físicos, químicos e microbiológicos de cada ecorregião e uso da terra, buscando evidenciar padrões e as variáveis que os diferenciam. As áreas nativas apresentaram padrões distintos na dinâmica dos atributos microbiológicos relacionadas principalmente à quantidade de serapilheira em cada bioma estudado. Em relação às áreas antropizadas, observaram-se resultados similares entre pastagens e áreas nativas, significativamente diferentes dos resultados obtidos em áreas agrícolas, que devido à diferença de manejo e diversidade de culturas analisadas apresentou uma grande variabilidade no seu resultado final. Os resultados obtidos reforçam a recomendação da utilização dos atributos microbiológicos como indicadores de mudança de uso da terra, aliados a fatores químicos e físicos. A respiração induzida por substratos (ou diversidade catabólica) mostrou-se eficiente na separação dos usos da terra e ecorregiões. Estes resultados suportam a idéia de que cada forma de uso da terra induz a presença de grupos específicos de microrganismos, independente de tipo de solo, clima ou outras influências externas. / The increasing demand for food creates environmental problems, mainly due to the removal of native vegetation cover for agriculture expansion in Brazil. These changes in land use leads to changes in the soil organic matter dynamics. The vegetation type also affects the soil biota and, therefore, its change causes modifications in the microbial biomass, as shown by studies involving deforestation. Microorganisms represent the most biological and physiological diverse in soil, as well as being responsible for more than 95% of the decomposition and nutrient cycling. For this reason, the demand for fast and reliable indicators to detect changes in soil quality, especially for those based on micro-organisms has been growing continuously. The main objective in this research was to check the differentiation of patterns in activity and functional diversity of soil microbial biomass under natural vegetation, pastures and agricultural systems in use. The area covered by this study corresponds to the states of Rondônia (RO) and Mato Grosso (MT), which was divided into 11 ecoregions relatively homogeneous in terms of soil, vegetation, geology, climate and landscape. A canonical variate analysis was used in some physical, chemical and microbiological factors in each ecoregion and land use, looking for patterns and variables that can differentiate them. The native areas showed distinct patterns in the dynamics of microbiological attributes mainly related to the amount of litter in each biome studied. For the disturbed areas, there were similar results between pastures and native areas, significantly different from the results obtained in agricultural areas, which due to differences in management and kind of cultures analyzed showed a great variability in its final result. The results support the recommendation for use of microbiological attributes as indicators of land use change, combined with chemical and physical factors. The substrate-induced respiration (or catabolic diversity) was efficient in the separation of land uses and ecoregions. These findings support the idea that specific land uses have specific groups of microbial biomass, regardless soil type, climate or other external influences.

INTRODUÇÃO: Os pacientes com asma crônica podem compartilhar similaridades clínicas e fisiológicas com pacientes com doença pulmonar obstrutiva crônica, tal como reversibilidade parcial ao broncodilatador ou pouca obstrução persistente do fluxo expiratório. Entretanto, não existem estudos comparando a patologia destas duas doenças em pacientes com idade similares e mesma gravidade da doença. MÉTODOS: Nós comparamos as dimensões das grandes e pequenas vias aéreas de 12 pacientes adultos (média±erro padrão, 32±3 anos) e 15 pacientes idosos e pré-idosos idosos (65±1 ano) não tabagista que foram a óbito por asma fatal com 14 pacientes tabagistas crônicos que foram a óbito por DPOC grave (71± 1 ano) e 19 pacientes-controle (56±1 ano). Usando a coloração de Movat e H&E, e a técnica de análise de imagens, nós quantificamos a espessura da membrana basal (MB) (valores expressos em ?m) a área de glândula submucosa nas grandes vias aéreas. Nas grandes e pequenas vias aéreas quantificamos a área de camada interna, a área de músculo liso e a área de camada externa. As áreas foram normalizadas pelo perímetro da MB (?m/?m2). RESULTADOS: os pacientes asmáticos adultos apresentaram a MB, área de músculo liso e a área da camada externa nas grandes e pequenas vias aéreas mais espessas, quando comparadas com os controles com idade similar com DPOC grave. Nos pacientes idosos e pré-idosos com asma, houve uma sobreposição na espessura da MB e na área da glândula submucosa, enquanto que nas pequenas e grandes vias aéreas a área de músculo liso foi mais espessa quando comparados com os controles com idade similar com pacientes com DPOC grave. Os pacientes com DPOC apresentaram nas pequenas e grandes vias aéreas as áreas de músculo liso menor quando comparada aos controles com idade similar. Os asmáticos adultos apresentaram a área de músculo liso maior quando comparada aos asmáticos idosos. CONCLUSÃO: Nossos dados fornecem novas informações sobre as mudanças patológicas que podem nos ajudar a entender melhor as similaridades e diferenças patológicas no pacientes adultos e idosos com asma comparados ao DPOC / Background: In some patients with chronic asthma, clinical and physiological similarities with chronic obstructive pulmonary disease may co-exist, such as partial reversibility to bronchodilators despite persistent expiratory airflow obstruction. However, pathologic analyses comparing both diseases in patients of similar age and disease severity are scarce. Methods: We compared the large and small airway dimensions in 12 younger (mean±SD, age 32 yr±3 yr) and 15 older (65 yr±1 yr) non-smoking fatal asthmatics with 14 chronic smokers with severe, fatal COPD (71 yr±1 yr) and 19 control patients (56 yr±1 yr). Using H&E, Movat\'s pentachrome staining and image analysis, we quantified large airway basement membrane (BM) thickness (?m); submucosal gland area; and large and small airway inner wall, smooth muscle and outer wall areas. Areas were normalized by BM perimeter (?m2/?m). Results: Younger adult fatal asthmatics had thicker BM, smooth muscle, and outer wall areas in both small and large airways when compared to agematched controls and fatal COPD patients. In older asthmatics, there was an overlap in BM thickness and submucosal gland area, whereas both large and small airway smooth muscle areas were thicker compared to age-matched controls and fatal COPD patients. COPD patients had thinner large and small airway smooth muscle areas compared to age-matched controls. Younger asthmatics had thicker small airway smooth muscle area compared to older asthmatics. Conclusion: Our data provide novel pathological substrate changes that may help us better understand physiological similarities and differences in younger and older patients with asthma compared to COPD.

Em epidemiologia matemática, muitos modelos de propagação de doenças infecciosas em populações têm sido analisados matematicamente e aplicados para doenças específicas. Neste trabalho um modelo de propagação de dengue é analisado considerando-se diferentes hipóteses sobre o tamanho da população humana. Mais precisamente, estamos interessados em verificar o impacto das variações populacionais a longo prazo no cálculo do parâmetro Ro e no equilíbrio endêmico. Vamos discutir algumas ideias que nortearam o processo de definição do parâmetro Ro a partir da construção do Operador de Próxima Geração. Através de um estudo qualitativo do modelo matemático, obtivemos que o equilíbrio livre de doença é globalmente assintoticamente estável se Ro é menor ou igual a 1 e instável se Ro>1. Para Ro>1, a estabilidade global do equilíbrio endêmico é provada usando um critério geral para estabilidade orbital de órbitas periódicas associadas a sistemas autônomos não lineares de altas ordens e resultados da teoria de sistemas competitivos para equações diferenciais ordinárias. Também foi desenvolvida uma análise de sensibilidade do Ro e do equilíbrio endêmico com relação aos parâmetros do modelo de propagação. Diversos cenários foram simulados a partir dos índices de sensibilidade obtidos nesta análise. Os resultados demonstram que, de forma geral, o parâmetro Ro e o equilíbrio endêmico apresentam considerável sensibilidade a taxa de picadas do vetor e a taxa de mortalidade do vetor. / In mathematical epidemiology many models of spread of infectious diseases in populations have been analyzed mathematically and applied to specific diseases. In this work a dengue propagation model is analyzed considering different assumptions about the size of the human population. More precisely, we are interested to verify the impact of population long-term variations in the calculation of the parameter Ro and endemic equilibrium. We will discuss some ideas that guided the parameter setting process Ro from the construction of the Next Generation Operator. Through a qualitative study of the mathematical model, we found that the disease-free equilibrium is globally asymptotically stable if Ro is less or equal than 1 and unstable if Ro> 1. For Ro> 1 the global stability of the endemic equilibrium is proved using a general criterion for orbital stability of periodic orbits associated with nonlinear autonomous systems of higher orders and results of the theory of competitive systems for ordinary differential equations. Also a sensitivity analysis of the Ro and the endemic equilibrium with respect to the parameters of the propagation model was developed. Several scenarios were simulated from the sensitivity index obtained in this analysis. The results demonstrate that in general the parameter Ro and the endemic equilibrium are the most sensitive to the vector biting rate and the vector mortality rate.

Propósito: Observar obesas pré e pós-dieta hipocalórica moderada, mais treinamento em circuito ou caminhada. quanto a variáveis nutricionais. Métodos: Grupos: treinamento em circuito, CIRC, n = 26, índice de massa corporal (IMC, kg/m2) = 33,2 ± 7,9 (Média±desvio padrão); idade = 32,6 ± 9,7 anos; e treinamento em caminhada, CAM, n = 24, IMC = 29,2±3,4; idade = 38,8 ± 10,5 anos. Avaliações: a composição corporal, coleta de urina e sangue, calorimetria indireta e testes físicos eram obtidos no inicio (M1) e final (M2) do estudo. Treinamento: mês 1 = 1 h x 3 d/semana; e mês 2 = 1 h x 4 d/semana. Dieta: foi adaptada do registro alimentar de uma semana, ajustado ao gasto energético de repouso (GER) e balanceada, com a seguinte proporção: 20% de proteínas; 20% de gorduras; e 60% de carbohidratos. Resultados: Pré-intervenção: 76% tinham algum familiar obeso; havia sintomatologia indicativa de: 60% ansiosas, 12% depressivas, 34% compulsivas e 32% distúrbio do sono, avaliadas por questionário no exame clínico. Foram encontrados níveis alterados de colesterol total (CT, mg/dL), e ou frações em 22% das sujeitas. O peso, IMC, o índice abdômem/quadril (IAQ), a soma de oito pregas cutâneas (SP8) se correlacionaram significativamente a quatro variáveis bioquímicas, e a circunferência do abdômen (CAb), e o percentual de gordura por antropometria (%GAntro) a cinco. Intervenção: O peso, IMC, %GAntro, endomorfia, massa gorda por bioimpedância (MGBia) e percentual de gordura por bioimpedância (%GBia), foram reduzidos significativamente nos dois grupos. O CIRC melhorou significativamente em todos (seis) e o CAM em três testes físicos. O CIRC teve significância para: ¯glicose (Gli), ¯AU, ¯CT, ¯Tg (todos em mg/dL), ­glóbulos vermelhos (GV) (mm3) e ­hematócrito (Ht) (%); e o CAM para: ¯Gli, ¯AU, ¯HDL, ­CT/HDL, ­GV, ­Ht. O GER não teve diferença em ambos os grupos. Conclusões: Pré-intervenção: Os dados antropometricos indicam boa correlação com os fatores bioquímicos de risco, mas não tem uma tendência constante. A taxa CT/HDL apresentou correlação com todas as medidas antropométircas e a Gli com nenhuma. A obesidade destas mulheres parece ter múltiplos fatores e o estilo de vida papel determinante. Intervenção: A atividade física per se foi importante para causar modificações nutricionais e da composição corporal nestas obesas. O CIRC teve melhor associação com o incremento da performance física e dados bioquímicos sanguineos e ambos os grupos preservaram o GER. / Purpose: To observe obese women before and after a low-calorie diet plus circuit training or jogging regarding nutritional parameters. Methods: Groups: circuit training, CIRC, n = 26, body mass index (BMI, kg/m2) = 33.2 ± 7.9 (Mean±SD), age = 32.6 ± 9.7 years; and jogging training, JOGG, n = 24, BMI = 29.2 ± 3.4; age = 38.8 ± 10.5 years. Evaluations: body composition, collection of urine and blood samples, indirect calorimetry and physical tests were performed at the beginning (M1) and at the end (M2) of the study. Training: month one: 1 h x 3 d/week; month two: 1 h x 4 d/week. Diet: was adapted on the basis of a one week feeding record feed and adjusted to the resting metabolic rate (RMR) measured by indirect calorimetry, with the following proportion: 20% protein, 20% fat; and 60% carbohydrate. Results: Pre-intervention: 76% had one or more obese family members; there were symptoms indicating that 60% were anxious, 12% depressive, 34% compulsive, and 32% had sleep disorders, evaluated by a questionnaire during clinical examination. Altered levels of total cholesterol (TC) and/or fractions were found in 22% of the subjects. Weight (W), BMI, waist/hip ratio (WHR), and the sum of eight skin folds (8SF), were significantly correlated with four biochemistry variables, and abdominal circumference (AbC), and anthropometric fat percentage (%FAnthro) were correlated with five. Intervention: Weight, BMI, %FAnthro, endomorphy, body fat mass by bioimpedance (BFMBia) and percent body fat by bioimpedance (%FBia) were reduced in both groups. CIRC significantly increased performance in all (six) tests and the JOGG in three physical tests. CIRC showed significant differences for: ¯glucose (Glu), ¯UA, ¯TC (TC), ¯Tg (all in mg/dL), ­red blood cells (RBC) (mm3) and ­hematocrit (Ht) (%); and JOGG for: ¯Glu, ¯UA, ¯HDL, ­CT/HDL, ­RBC, ­Ht. The RMR was not significantly reduced in both groups. Conclusions: Pre-intervention: Anthropometric data indicated a good correlation with biochemical factors, but did not show a constant tendency. CT/HDL showed correlation with all anthropometric measurements and Glu with none. The obesity of these women appears to have multiple factors, with life style playing a determinant role. Intervention: Physical activities were determined to favor body composition, reduced weight and blood markers. CIRC were better in terms of physical performance and blood markers. Both types of training were sufficient to prevent a fall of RMR.

O Brasil é o maior produtor mundial de citros, com destaque para o estado de São Paulo, maior produtor nacional. Recentes estudos mostram que a área irrigada de citros no estado tem aumentado significativamente nos últimos anos. Porém, a falta de informações sobre o manejo eficiente da irrigação na cultura do citros é uma das principais dificuldades enfrentadas pelos produtores. Com o intuito de atender essa necessidade, este trabalho teve como objetivos determinar a evapotranspiração de uma planta adulta de limeira ácida \'Tahiti\' (Citrus latifolia Tan.) e o coeficiente de cultivo no período seco (outono - inverno) utilizando a técnica de lisimetria de pesagem. O coeficiente de cultivo (Kc = ETc/ETo) foi calculado considerando-se a contribuição independente da evaporação do solo e transpiração da planta, sendo substituído por dois coeficientes: Ke, um coeficiente de evaporação de água do solo e Kcb, um coeficiente basal de transpiração da cultura. Avaliar os aspectos produtivos e de qualidade de fruto, frente a diferentes níveis de irrigação, com o fornecimento crescente de 50 a 125 % da evapotranspiração da cultura. O experimento foi realizado na ESALQ/ USP em Piracicaba - SP, em uma área irrigada por gotejamento, com plantas espaçadas de 7 x 4 m, sendo que cada planta foi atendida por 4 pontos de molhamento no solo distribuídos de forma eqüidistantes entre si. Foi realizado o monitoramento climático utilizando estação meteorológica automatizada e a obtenção da evapotranspiração da cultura por lisímetro de pesagem. Durante o período de estudo, Kc variou entre 0,82 a 1,18, e Kcb variou entre 0,86 a 1,05. Os resultados mostraram que a irrigação calculada pelo método do Kcb+Ke, tem um ajuste muito bom e representa com precisão o consumo de água pela planta. Os maiores consumos foram observados nos meses de maior temperatura média (abril e setembro). A reposição de 100 % da água evapotranspirada resultou em maior produtividade de frutos de limeira acida \'Tahiti\' em condições de campo. Quanto à qualidade de frutos, não houve diferença significativa entre os níveis de irrigação avaliados. / Brazil is the largest world producer of citrus crop, with São Paulo state leading as the largest national producer. Recent studies show that irrigated areas of citrus in the state have been increasing significantly in the last few years. However, lack of information on irrigation management related to this crop is one of the main problems encountered by the farmers. In order to address the above problem, the objective of this work was to determine the evapotranspiration of acid lime adult plant variety \'Tahiti\' (Citrus latifolia Tan.) and the crop coefficient during dry period (autumn - winter) using a weighing lysimeter technique. The crop coefficient (Kc = ETc/ETo) was calculated by considering the independent contribution of the evaporation of the soil and transpiration of the plant, being substituted by two coefficients: Ke, a soil water evaporation coefficient and Kcb, a basal crop coefficient. To evaluate the productive aspects as well as the fruit quality, different irrigation levels were applied in an increasing manner from 50 to 125 % of the crop evapotranspiration. The experiment was carried out at ESALQ / USP in Piracicaba - SP, in a drip irrigated area with plant spacing of 7 x 4 m. Each plant was supplied with four wetting equidistant emitters. The climatic data was obtained by the use of automated meteorological station and the crop evapotraspiration by the use of a weighing lysimeter. During the study period, Kc varied from 0.82 to 1.18, and Kcb varied from 0.86 to 1.05. The results showed that the irrigation amount calculated by the method of Kcb+Ke had a very good water consumption precision by the plant. The highest consumptions were observed in the months of high average temperature (April and September). The reposition of 100 % of the evapotranspirated water resulted in the highest fruit production of acid lime tree variety \'Tahiti\' in field conditions. Irrigation levels had no significant effect at 0.05 level on the quality of the fruits.

OBJETIVOS: Determinar a correlação entre a completa regeneração da membrana basal epitelial (MBE) e o desaparecimento de miofibroblastos do estroma anterior e consequente restauração da transparência corneana após diferentes mecanismos de trauma em coelhos. MÉTODOS: Foram utilizados 32 coelhos que tiveram um de seus olhos incluídos em um dos três grupos de estudo: (1) -9 dioptrias (D) ceratectomia fotorrefrativa (PRK), (2) Incisões corneanas verticais de espessura parcial (350 um), ou (3) Ceratite bacteriana, enquanto os olhos contralaterais compuseram o grupo controle. Os animais foram examinados, sacrificados, e tiveram suas córneas analisadas em diferentes momentos afim de investigar com detalhes o processo de cicatrização corneano usando técnicas de imunohistoquímica (IHQ) e microscopia de transmissão eletrônica (MTE). RESULTADOS: No grupo \"-9D PRK\", as córneas apresentavam opacidade corneana densa e nenhuma evidência de regeneração da MBE 1 mês após a cirurgia. Dois meses após a cirurgia, no entanto, pequenas áreas de córnea transparente começaram a surgir em meio à opacidade difusa, correspondendo a pequenas ilhas de MBE completamente regenerada. Após 4 meses da cirurgia a MBE estava completamente regenerada e a transparência corneana havia sido reestabelecida na região ablada pelo laser. No grupo \"incisões corneanas\", o par de densas opacidades corneanas lineares observadas após 1 mês do procedimento tornou-se progressivamente mais tênue ao longo dos próximos 2 meses. A ultraestrutura da MBE estava completamente regenerada e não houve formação de miofibroblastos no local das incisões 1 mês após o procedimento, inclusive ao redor dos plugs epiteliais que se estendiam até o estroma. No grupo \"ceratite bacteriana\", as córneas que haviam sido infectadas apresentaram opacidade densa, vascularização, miofibroblastos em toda a sua espessura, e nenhuma evidência de regeneração da MBE 1 mês após a infecção. Observou-se ao longo dos próximos 3 meses substancial redução da opacidade, evidências ultraestruturais de regeneração da MBE, e desaparecimento de miofibroblastos das porções mais anteriores do estroma, persistindo apenas nas regiões do estroma mais posterior nas quais o endotélio e a membrana de Descemet encontravam-se lesadas. CONCLUSÃO: No modelo animal apresentado, a resolução espontânea da opacidade corneana tardia mediada por miofibroblastos após a ablação com excimer laser ou ceratites infeciosas graves é desencadeada pela completa regeneração da estrutura e função da MBE. As incisões corneanas de espessura parcial em coelhos, no entanto, cicatrizam sem geração de miofibroblastos devido à completa regeneração da MBE após 1 mês do procedimento. Determinou-se, portanto, a correlação entre a reparação da membrana basal epitelial e a consequente redução da opacidade e restauração da transparência corneana / PURPOSE: To determine the correlation between epithelial basement membrane (EBM) regeneration and the disappearance of myofibroblasts from anterior stroma and consequent restoration of corneal transparency after different types of injury in rabbits. METHODS: Thirty-two rabbits had one of their eyes included in one of the 3 study groups: (1) -9 diopters (D) photorefractive keratectomy (PRK), (2) Two vertical partial-thickness (350 um) corneal incisions, or (3) Bacterial keratitis, whereas the opposite eyes served as unwounded control group. The animals were examined, sacrificed, and had their corneas analysed in different time points in order to investigate the corneal wound healing process using immunohistochemistry and transmission electron microscopy. RESULTS: In the \"-9D PRK\" group, corneas at 1 month after surgery had dense corneal opacity and no evidence of regenerated EBM. However, by 2 months after surgery small areas of stromal clearing began to appear within the confluent opacity, and these corresponded to small islands of normally regenerated EBM. By 4 months after surgery, the EBM was fully regenerated and the corneal transparency was completely restored in the ablated zone. In the \"corneal incisions\" group, the two dense, linear corneal opacities observed at 1 month after the procedure progressively faded during the next 2 months. The EBM ultrastructure was fully regenerated and there were no myofibroblasts at the site of the incisions by 1 month after the procedure, including around the epithelial plugs that extended into the stroma. In the \"bacterial keratitis\" group, all the corneas that have been infected presented dense stromal scarring, vascularization, myofibroblasts in the full stromal thickness and no evidence of EBM regeneration by 1 month after the infection. There was a definite decrease in opacity during the next 3 months, besides ultrastructural evidence of EBM regeneration and disappearance of myofibroblasts in the most anterior part of the stroma, which persisted only in the most posterior stroma where the endothelium and Descemet\'s membrane were damaged. CONCLUSION: In the rabbit model, spontaneous resolution of myofibroblast-mediated corneal opacity (fibrosis) after high correction PRK or infectious keratitis is triggered by regeneration of normal EBM structure and function. Conversely, incisional wounds heal in rabbit corneas without the development of myofibroblasts because the EBM regenerates normally by 1 month after the injury. Therefore, it has been determined the correlation between the EBM regeneration and the restoration of corneal transparency after different types of corneal injury

La maladie de Parkinson (MP) est une maladie neurodégénérative caractérisée par une perte dopaminergique (DA) de la voie nigro-striée. Cette dégénérescence des neurones DA, induit un déséquilibre entre les transmissions dopaminergique, GABAergique et glutamatergique au sein des ganglions de la base qui se traduit par des troubles de l'excitabilité neuronale aboutissant à l'apparition des symptômes moteurs et non-moteurs. Nous avons étudié l'effet de la modulation des canaux SK et Kv4 par des toxines issues de venins d'animaux. Pour ce faire, nous avons utilisé deux modèles lésionnels à la 6-hydroxydopamine (6-OHDA): une lésion bilatérale partielle du striatum mimant la phase précoce de la MP pour tester les déficits cognitifs et émotionnels, et une lésion unilatérale totale au niveau de la substance noire mimant la rigidité et la bradykinésie en phase tardive pour tester les déficits moteurs. Nos résultats montrent que le blocage des canaux SK par l'apamine (injection systémique, 0.1-0.3 mg/kg) améliore partiellement et transitoirement les déficits moteurs dans le test du cylindre et la rotation induite par l'apomorphine dans le modèle tardif de la MP. L'AmmTX3 (injection intrastriatale, 0.2-0.4 g), réduit les déficits moteurs et restaure des comportements cognitifs déficitaires (mémoire sociale et spatiale à court terme) et émotionnels (anxiété), après une dégénérescence DA bilatérale et partielle. L'ensemble de ces données suggère que l'inhibition pharmacologique de l'activité des canaux SK par l'apamine et Kv4 par l'AmmTX3, pourrait représenter une voie thérapeutique innovatrice quant au traitement des déficits moteurs, cognitifs et émotionnels de la MP. / Parkinson's disease (PD) is a neurodegenerative disease associated to a loss of dopaminergic nigrostriatal pathway that innervates the basal ganglia (GB). The DA neuron degeneration in PD induces imbalance between dopaminergic transmission, GABAergic and glutamatergic resulting in impaired neuronal excitability leading to the onset of motor and non-motor symptoms. Potassium channels, Kv4 and SK, are extensively involved in the phenomenon of neuronal excitability. We addressed the question of whether further blockade of SK or Kv4 activity could restore normal GB function in vivo. In this aim, we used a neurotoxin, 6-hydroxydopamine (6-OHDA) to produce two lesional models of Parkinson's disease in rats that mimics the cognitive and emotional deficits of the early phase of PD (partial and bilateral striatal lesions) and the motor deficits observed in the late phase of the disease (total unilateral nigral lesion). Apamin from bee venom (systemic injection, 0.1-0.3 mg/kg) and AmmTX3 from scorpion venom (intrastriatal injection, 0.2-0.4 g) were chosen to block SK and Kv4 channels respectively.In a first study, apamin treatment partially reduced motor deficits in the cylinder test and the rotation induced by apomorphine. In the second study, the AmmTX3 also decreased parkinsonian motor deficits. This late toxin restored cognitive behaviors (short-term social and spatial memory) and emotion (anxiety).Taken together, these results underlie the importance of SK channels as modulators of neuronal excitability of Kv4 channels as players of the homeostatic responses, and more importantly, provide potential targets for adjunctive therapies for Parkinson's disease.