Para avaliar a influência da intoxicação cúprica cumulativa e do seu tratamento com tetratiomolibdato de amônia (TTM) sobre a função renal e sobre o metabolismo oxidativo, foram empregados 10 cordeiros da raça Santa Inês os quais receberam doses crescentes de sulfato de cobre, até o surgimento de hemoglobinúria macroscópica. Neste momento foram distribuídos ao acaso cinco ovinos para cada um dos dois grupos, onde foi o primeiro foi mantido como controle (C) e o grupo subseqüente foram tratados diariamente, no decorrer de quatro dias, com 3,4 mg TTM por kg de peso vivo. Todos os ovinos do grupo C sucumbiram no decorrer de quatro dias, enquanto que tal fato só ocorreu em um animal tratado com TTM. A intoxicação provocou um quadro clínico típico, gerando grandes alterações na função renal como diminuição da taxa de filtração glomerular, a qual provocou oligúria ou anúria, proteinúria e uremia. O quadro tóxico ainda determinou drásticas diminuições na capacidade de reabsorção tubular manifestada por: glicosúria, menor densidade urinária, maiores excreções urinárias de fósforo, sódio, cloro, potássio, cobre e ferro, maior atividade da enzima NAG na urina. Uma acidúria também foi constatada. O tratamento com TTM promoveu melhora na maioria destas variáveis dentro do 2º ou 5º dias após o início do tratamento. No tocante ao metabolismo oxidativo o quadro tóxico provocou uma intensa formação de radicais livres, com concomitante redução no teor de glutationa reduzida eritrocitária, embora tenha aumentado a capacidade anti-oxidante no plasma, em parte por formação de ácido úrico. Quanto maior foi a formação de radicais livres menor foi a taxa de filtração glomerular. O tratamento com TTM reduziu de maneira significativa a formação de radicais livres,aumentando a concentração de glutationa reduzida eritrocitária. / Twelve Santa Inês lambs were used to study the effects of cumulative copper poisoning and the treatment with ammonium tetrathiomolybdate (TTM) on renal function and oxidative metabolism. The lambs were drenched with increasing doses of copper sulfate until the onset of macroscopic hemoglobinuria. So the lambs were randomly distributed in two groups of five sheep each and treated (TTM) or not (C) with tetrathiomolybdate (3.4 mg/kg BW/ per day, for four days). All sheep C succumbed in four days of hemoglobinuria, while only one lamb died in the other group. A typical clinical picture was observed in both groups causing a marked renal insufficiency with decreased glomerular filtration rate, which caused anuria or oliguria, proteinuria and uremia. The poisoning also generated an intense decreased in the tubular reabsorption capacity with higher urinary excretion of glucose, phosphorus, sodium, chloride, potassium, iron and copper, higher urinary NAG activity and lower urinary density. An aciduria was also detected. The treatment with TTM caused a marked improvement in the renal function within 2 to 5 days. As far as the oxidative is concerned, the poisoning caused a higher formation of free radicals and decreased the erythrocyte levels of reduced glutathione, although the plasma anti-oxidant capacity was increased, partially by production of uric acid. The higher the free radical formation, the lower the glomerular filtration rate. The treatment with TTM decreased significantly the amount of free radical formation and increased the levels of erythrocyte reduced glutathione.

Os trabalhos na área de neuroimunomodulação vêm contribuindo de forma marcante para o entendimento da regulação/modulação das respostas adaptativas dos organismos frente ao estresse ou às doenças. A integração de modelos biológicos e psicológicos surge e torna-se cada vez mais importante para a neuroimunologia. Cada animal comunica-se com outros de sua ou de outra espécie através de mecanismos que são característicos dentro de seus respectivos grupos; sabe-se que a comunicação entre os animais pode ser visual, táctil, química e sonora. Procuramos neste trabalho identificar o(s) tipo(s) de comunicação mais relevante(s) entre camundongas saudáveis e conspecíficas doentes. Mais especificamente, avaliamos efeitos neuroimunes decorrentes da convivência por 14 dias com companheiras inoculadas com tumor ascítico de Ehrlich e buscamos caracterizar o tipo de comunicação envolvida com este processo. Os resultados obtidos mostraram que a simples convivência com um portador do tumor de Ehrlich produziu em camundongas: 1) redução do peso e celulariedade do baço; 2) redução na contagem diferencial de blastos, eritrócitos jovens e linfócitos no esplenograma; 3) redução da porcentagem de linfócitos B e T helper e na proporção CD4/CD8 no baço; 4) aumento da atividade citotóxica de células NK; 5) aumento da celulariedade total da medula; 6) aumento na contagem absoluta de blastos e redução de eritrócitos jovens e de linfócitos no mielograma; na contagem relativa observamos um aumento dos blastos; 7) aumento de células na fase G1 e redução na fase G2 do ciclo celular da medula; 8) aumento de células tumorais de Ehrlich na fase G1 e redução destas na fase G2, 9) aumento de permanência na zona animal estranho e redução de tempo na zona companheiro doente em um labirinto em T, 10) aumento de interação social; 11) redução do burst oxidativo basal de neutrófilos provenientes de animais que conviveram com dois doentes, e reversão destas alterações quanto da convivência com dois sadios. Observamos, ainda que: 12) a convivência não modificou os níveis de corticosterona dos animais desafiados ou não por contenção; 13) a ausência de contato físico não foi relevante para reverter as alterações induzidas pela convivência; 14) a falta de contato visual também não foi relevante para reverter as alterações observadas; 15) os estímulos olfativos foram relevantes para as alterações induzidas pela convivência sobre o burst oxidativo e fagocitose de neutrófilos, crescimento tumoral, alterações comportamentais, dosagem plasmática de noradrenalina e de adrenalina e níveis hipotalâmicos de noradrenalina. Em seu conjunto observamos que a convivência por 14 dias com um animal portador de um tumor de Ehrlich produziu relevantes alterações no comportamento, em parâmetros neuroquímicos e de atividade imune inata de camundongas. Nossos resultados sugerem que a percepção do odor da doente esteja diretamente relacionada com as alterações relatadas. / Several papers are showing relevant neuroimmune regulation and/or modulation during stress or diseases. The incorporation of biological and psychological models of humans conditions are of high relevance in neuroscience. Animals exhibit a variety of adaptative behaviors for communicating with conspecifics; communication between animals can be visual, tactile, chemical and sound induced. The present experiment was designed to analyze the effects induced by cohabitation with a sick cage mate and some aspects of communication between sick mice and their companions. Specifically, we analyzed some neuroimmune effects induced by cohabitation with a sick cage-mate for 14 days (mice bearing an ascitic Ehrlich tumor), looking also for the type of communication related to this process. Our results showed that cohabitation with a sick cage-mate induced, in female mice 1) decreased spleen weight and total cellullarity; 2) decreased the number of blast, young erythrocytes and lymphocytes in spleen 3) decreased percentage of B and T helper cells, and decreased proportion of CD4/CD8 cells in the spleen; 4) increased NK cells cytotoxicity; 5) increased bone marrow total celullarity; 6) increased absolute number of blasts, and decreased the number of young erythrocytes and lymphocytes; in the relative count, an increase of blast cells in bone marrow was observed; 7) increased amount of cells on G1 cellular cycle phase, and a decreased population of cells on G2 cellular cycle phase in the bone marrow; 8) increased amount of Ehrlich tumor cells in G0-G1 cellular cycle phases, and decreased population of tumor cells in S/G2/M phases; 9) increased time spent with an strange animal and decreased time spent will sick companion in a T maze and increased locomotion in this apparatus; 10) increased social interaction; 11) decreased neutrophil basal oxidative burst in animals that lived with two sick companions. We also observed that: 12) cohabitation with a sick partner was unable to modify serum corticosterone levels with or without an immobilization stress challenge; 13) physical contact was not relevant for the neuroimune changes induced by cohabitation; 14) visual cues were not relevant for the present contextual immune changes; 15) odor cues were effective mechanisms of communication used by the mice in the present experiment; because it removal abrogated or reversed the neuroimmune changes reported above for cohabitation. The present findings showed that cohabitation with an ascitic Ehrlich tumor bearing mice produced behavioral, neurochemical, and immunological changes. The present results strongly suggest that volatile compounds released by the sick companion are directly relationed to the neuroimmune changes now reported in mice for cohabitation with a sick companion.

Os trabalhos na área de neuroimunomodulação vêm contribuindo de forma marcante para o entendimento da regulação/modulação das respostas adaptativas dos organismos frente ao estresse ou às doenças. A integração de modelos biológicos e psicológicos surge e torna-se cada vez mais importante para a neuroimunologia. Cada animal comunica-se com outros de sua ou de outra espécie através de mecanismos que são característicos dentro de seus respectivos grupos; sabe-se que a comunicação entre os animais pode ser visual, táctil, química e sonora. Procuramos neste trabalho identificar o(s) tipo(s) de comunicação mais relevante(s) entre camundongas saudáveis e conspecíficas doentes. Mais especificamente, avaliamos efeitos neuroimunes decorrentes da convivência por 14 dias com companheiras inoculadas com tumor ascítico de Ehrlich e buscamos caracterizar o tipo de comunicação envolvida com este processo. Os resultados obtidos mostraram que a simples convivência com um portador do tumor de Ehrlich produziu em camundongas: 1) redução do peso e celulariedade do baço; 2) redução na contagem diferencial de blastos, eritrócitos jovens e linfócitos no esplenograma; 3) redução da porcentagem de linfócitos B e T helper e na proporção CD4/CD8 no baço; 4) aumento da atividade citotóxica de células NK; 5) aumento da celulariedade total da medula; 6) aumento na contagem absoluta de blastos e redução de eritrócitos jovens e de linfócitos no mielograma; na contagem relativa observamos um aumento dos blastos; 7) aumento de células na fase G1 e redução na fase G2 do ciclo celular da medula; 8) aumento de células tumorais de Ehrlich na fase G1 e redução destas na fase G2, 9) aumento de permanência na zona animal estranho e redução de tempo na zona companheiro doente em um labirinto em T, 10) aumento de interação social; 11) redução do burst oxidativo basal de neutrófilos provenientes de animais que conviveram com dois doentes, e reversão destas alterações quanto da convivência com dois sadios. Observamos, ainda que: 12) a convivência não modificou os níveis de corticosterona dos animais desafiados ou não por contenção; 13) a ausência de contato físico não foi relevante para reverter as alterações induzidas pela convivência; 14) a falta de contato visual também não foi relevante para reverter as alterações observadas; 15) os estímulos olfativos foram relevantes para as alterações induzidas pela convivência sobre o burst oxidativo e fagocitose de neutrófilos, crescimento tumoral, alterações comportamentais, dosagem plasmática de noradrenalina e de adrenalina e níveis hipotalâmicos de noradrenalina. Em seu conjunto observamos que a convivência por 14 dias com um animal portador de um tumor de Ehrlich produziu relevantes alterações no comportamento, em parâmetros neuroquímicos e de atividade imune inata de camundongas. Nossos resultados sugerem que a percepção do odor da doente esteja diretamente relacionada com as alterações relatadas. / Several papers are showing relevant neuroimmune regulation and/or modulation during stress or diseases. The incorporation of biological and psychological models of humans conditions are of high relevance in neuroscience. Animals exhibit a variety of adaptative behaviors for communicating with conspecifics; communication between animals can be visual, tactile, chemical and sound induced. The present experiment was designed to analyze the effects induced by cohabitation with a sick cage mate and some aspects of communication between sick mice and their companions. Specifically, we analyzed some neuroimmune effects induced by cohabitation with a sick cage-mate for 14 days (mice bearing an ascitic Ehrlich tumor), looking also for the type of communication related to this process. Our results showed that cohabitation with a sick cage-mate induced, in female mice 1) decreased spleen weight and total cellullarity; 2) decreased the number of blast, young erythrocytes and lymphocytes in spleen 3) decreased percentage of B and T helper cells, and decreased proportion of CD4/CD8 cells in the spleen; 4) increased NK cells cytotoxicity; 5) increased bone marrow total celullarity; 6) increased absolute number of blasts, and decreased the number of young erythrocytes and lymphocytes; in the relative count, an increase of blast cells in bone marrow was observed; 7) increased amount of cells on G1 cellular cycle phase, and a decreased population of cells on G2 cellular cycle phase in the bone marrow; 8) increased amount of Ehrlich tumor cells in G0-G1 cellular cycle phases, and decreased population of tumor cells in S/G2/M phases; 9) increased time spent with an strange animal and decreased time spent will sick companion in a T maze and increased locomotion in this apparatus; 10) increased social interaction; 11) decreased neutrophil basal oxidative burst in animals that lived with two sick companions. We also observed that: 12) cohabitation with a sick partner was unable to modify serum corticosterone levels with or without an immobilization stress challenge; 13) physical contact was not relevant for the neuroimune changes induced by cohabitation; 14) visual cues were not relevant for the present contextual immune changes; 15) odor cues were effective mechanisms of communication used by the mice in the present experiment; because it removal abrogated or reversed the neuroimmune changes reported above for cohabitation. The present findings showed that cohabitation with an ascitic Ehrlich tumor bearing mice produced behavioral, neurochemical, and immunological changes. The present results strongly suggest that volatile compounds released by the sick companion are directly relationed to the neuroimmune changes now reported in mice for cohabitation with a sick companion.

Para avaliar a influência da intoxicação cúprica cumulativa e do seu tratamento com tetratiomolibdato de amônia (TTM) sobre a função renal e sobre o metabolismo oxidativo, foram empregados 10 cordeiros da raça Santa Inês os quais receberam doses crescentes de sulfato de cobre, até o surgimento de hemoglobinúria macroscópica. Neste momento foram distribuídos ao acaso cinco ovinos para cada um dos dois grupos, onde foi o primeiro foi mantido como controle (C) e o grupo subseqüente foram tratados diariamente, no decorrer de quatro dias, com 3,4 mg TTM por kg de peso vivo. Todos os ovinos do grupo C sucumbiram no decorrer de quatro dias, enquanto que tal fato só ocorreu em um animal tratado com TTM. A intoxicação provocou um quadro clínico típico, gerando grandes alterações na função renal como diminuição da taxa de filtração glomerular, a qual provocou oligúria ou anúria, proteinúria e uremia. O quadro tóxico ainda determinou drásticas diminuições na capacidade de reabsorção tubular manifestada por: glicosúria, menor densidade urinária, maiores excreções urinárias de fósforo, sódio, cloro, potássio, cobre e ferro, maior atividade da enzima NAG na urina. Uma acidúria também foi constatada. O tratamento com TTM promoveu melhora na maioria destas variáveis dentro do 2º ou 5º dias após o início do tratamento. No tocante ao metabolismo oxidativo o quadro tóxico provocou uma intensa formação de radicais livres, com concomitante redução no teor de glutationa reduzida eritrocitária, embora tenha aumentado a capacidade anti-oxidante no plasma, em parte por formação de ácido úrico. Quanto maior foi a formação de radicais livres menor foi a taxa de filtração glomerular. O tratamento com TTM reduziu de maneira significativa a formação de radicais livres,aumentando a concentração de glutationa reduzida eritrocitária. / Twelve Santa Inês lambs were used to study the effects of cumulative copper poisoning and the treatment with ammonium tetrathiomolybdate (TTM) on renal function and oxidative metabolism. The lambs were drenched with increasing doses of copper sulfate until the onset of macroscopic hemoglobinuria. So the lambs were randomly distributed in two groups of five sheep each and treated (TTM) or not (C) with tetrathiomolybdate (3.4 mg/kg BW/ per day, for four days). All sheep C succumbed in four days of hemoglobinuria, while only one lamb died in the other group. A typical clinical picture was observed in both groups causing a marked renal insufficiency with decreased glomerular filtration rate, which caused anuria or oliguria, proteinuria and uremia. The poisoning also generated an intense decreased in the tubular reabsorption capacity with higher urinary excretion of glucose, phosphorus, sodium, chloride, potassium, iron and copper, higher urinary NAG activity and lower urinary density. An aciduria was also detected. The treatment with TTM caused a marked improvement in the renal function within 2 to 5 days. As far as the oxidative is concerned, the poisoning caused a higher formation of free radicals and decreased the erythrocyte levels of reduced glutathione, although the plasma anti-oxidant capacity was increased, partially by production of uric acid. The higher the free radical formation, the lower the glomerular filtration rate. The treatment with TTM decreased significantly the amount of free radical formation and increased the levels of erythrocyte reduced glutathione.

The current legal framework pertaining to animals does not sufficiently address the welfare of animals. The Animal Protection Act 71 of 1962 does not specifically regulate the welfare of animals contained in research laboratories. Animals utilized for experimental research purposes endure tremendous “unnecessary suffering” due to legislative inaptitude. Experimental animals suffer inherent abuses associated with experimental research because of the methods, procedures and processes relevant to the experiments. The most controversial method of experimental research is vivisection. The method of vivisection is not only invasive but also causes “unnecessary suffering” to animals. The non-inherent abuses animals suffer during confinement in a laboratory solely relates to uncontrolled and unregulated conduct of staff. Continuing the application of the current legislative framework may also be detrimental to the health and well-being of humans. Animals are specifically utilized as objects of science in research laboratories. The data obtained from research experiments conducted on animals are for the benefit of humankind rather than the animals. Scientific research concluded that not only are invasive methods of research conducted on live animals generally regarded as useless but extrapolating data from animals to humans can also be misleading, unnecessary and dangerous. False results and questionable methodologies are some of the other problems that seem to require urgent attention. Ethically, neither human nor animal should be utilized at the expense of the other and therefore it would be reasonable to recommend that legislative reform takes place. The human perception of animals in terms of the relationship we have with them is the reason why legislative inaptitude in terms of animal welfare exists. The current approach followed is the philosophy of Utilitarianism. Utilitarians believe that neither humans nor animals have rights but interests. Utilitarianism focuses on the permissibility of an act (the use of animals) by weighing the benefits of such an act to the costs suffered because of such act. If the benefits outweigh the costs suffered, the act is permissible. The application of Utilitarianism seems to be the crux of our legislative inaptitude. The human perception and view of animals must therefore be re-directed to develop a sufficient legal framework in terms of animal welfare. A solution offered is to apply an alternative interpretation to the concept of “dignity” (capabilities approach) and progressive realisation. In terms of this solution a species capabilities in terms of its value, capabilities and worth are considered. Inherent to its value, capabilities and worth, is its “dignity”. Once the alternative interpretation of “dignity” is acknowledged, the progressive realisation of its interests can be achieved. / Thesis (LLM)--North-West University, Potchefstroom Campus, 2013

The current legal framework pertaining to animals does not sufficiently address the welfare of animals. The Animal Protection Act 71 of 1962 does not specifically regulate the welfare of animals contained in research laboratories. Animals utilized for experimental research purposes endure tremendous “unnecessary suffering” due to legislative inaptitude. Experimental animals suffer inherent abuses associated with experimental research because of the methods, procedures and processes relevant to the experiments. The most controversial method of experimental research is vivisection. The method of vivisection is not only invasive but also causes “unnecessary suffering” to animals. The non-inherent abuses animals suffer during confinement in a laboratory solely relates to uncontrolled and unregulated conduct of staff. Continuing the application of the current legislative framework may also be detrimental to the health and well-being of humans. Animals are specifically utilized as objects of science in research laboratories. The data obtained from research experiments conducted on animals are for the benefit of humankind rather than the animals. Scientific research concluded that not only are invasive methods of research conducted on live animals generally regarded as useless but extrapolating data from animals to humans can also be misleading, unnecessary and dangerous. False results and questionable methodologies are some of the other problems that seem to require urgent attention. Ethically, neither human nor animal should be utilized at the expense of the other and therefore it would be reasonable to recommend that legislative reform takes place. The human perception of animals in terms of the relationship we have with them is the reason why legislative inaptitude in terms of animal welfare exists. The current approach followed is the philosophy of Utilitarianism. Utilitarians believe that neither humans nor animals have rights but interests. Utilitarianism focuses on the permissibility of an act (the use of animals) by weighing the benefits of such an act to the costs suffered because of such act. If the benefits outweigh the costs suffered, the act is permissible. The application of Utilitarianism seems to be the crux of our legislative inaptitude. The human perception and view of animals must therefore be re-directed to develop a sufficient legal framework in terms of animal welfare. A solution offered is to apply an alternative interpretation to the concept of “dignity” (capabilities approach) and progressive realisation. In terms of this solution a species capabilities in terms of its value, capabilities and worth are considered. Inherent to its value, capabilities and worth, is its “dignity”. Once the alternative interpretation of “dignity” is acknowledged, the progressive realisation of its interests can be achieved. / Thesis (LLM)--North-West University, Potchefstroom Campus, 2013