Thesis (doctoral)--Universität Tübingen, 1934.

Thesis (doctoral)--Universität Tübingen, 1934.

The possibility that regions of the medial forebrain bundle-lateral hypothalamic area (MFB-LHA) are concerned with mediating the rewarding effect of electrical stimulation of the brain was examined by making unilateral injections of 2% procaine hydrochloride (2 ul) into this region during bar pressing for electrical stimulation in the septum or preoptic area. When the injection was made into the same side of the brain as the stimulating electrode, there was a strong suppression of self-stimulating rates as compared to the effect of isotonic saline injections, and the effect occurred with injections anywhere along the entire length of the MFH-LHA. The finding that the suppression was significantly less severe when the injections were made into the MFB-LHA on the side of the brain opposite to the electrode suggests that the suppression was not due to general disruptive effects. As a further control for nonspecific disturbances, similar injections were made in animals bar-pressing for food reward; the results showed that these injections suppressed bar-pressing for food but only when the injections were made into those regions of the MFB-LHA which have been shown to be involved in feeding behavior. These results suggest that the entire MFB-LHA is a part of a system mediating the rewarding effect of electrical stimulation of the septum and preoptic area. / Arts, Faculty of / Psychology, Department of / Graduate

Thesis (M.D.)--Boston University

No description available.

Diss. (sammanfattning) Uppsala : Sveriges lantbruksuniv., 2007. / Härtill 5 uppsatser.

A derivatization reaction, based on a copulation reaction of diazonium salt of an analyte with a reagent (1-aminonaphthalene or NEDA) producing colour, spectrophotometrically detectable product, has been used for determination of two analytes (procain hydrochloride, sulfamethoxazole) containing amino group in the molecule. The conditions of batch spectrophotometric determination were studied. It was found, that the batch determination is applicable only for procain hydrochloride analysis, because sulfamethoxazole gives time-unstable colour product. FIA arrangement was proposed and effects of selected parameters were optimized using two levels factorial design. The calibration dependences were measured for both analysis with both reagents, and subsequently were applied on determination of analytes in medical forms. Key words: diazotization, flow injection analysis, procaine, spectrophotometry, sulfamethoxazole

Modelos de Relações Quantitativas entre Estrutura Química e Atividade Biológica (QSAR), previamente gerados no grupo para uma série de brometos de N-benzil-N,N-dimetil-2-(4-X-benzamido)etan-1-amônio substituídos (compostos estruturalmente análogos à procaína), mostraram uma contribuição positiva da lipofilicidade (expressa pelo parâmetro lipofílico, logPapp) para a atividade de bloqueio da transmissão neuromuscular observada para estes. Como os compostos desta série são sais de amônio quaternários, sendo alguns altamente hidrofílicos, as determinações dos seus valores de logPapp pelo método shake-flask acarretam dificuldades experimentais, levando a altas incertezas. Para contornar estas dificuldades, em outro trabalho iniciado no grupo, sugeriu-se, como estratégia metodológica, avaliar a aplicação do conceito do par iônico, usando, para tanto, um contraíon grande e hidrofóbico. Assim, observou-se, para um único composto desta série, o aumento da sua lipofilicidade, por possível formação de par iônico, tornando-o menos hidrofílico. Nesta dissertação, visando ampliar os estudos envolvendo a aplicação desta estratégia metodológica e seus efeitos sobre a lipofilicidade, outros compostos foram selecionados para que uma faixa mais ampla de valores de LogPapp pudesse ser avaliada. Para tanto, os valores de logPapp de cinco compostos desta série foram determinados pelo método shake-flask, usando o sistema n-octanol/água, avaliando-se, ainda, os efeitos da força iônica na partição. Para estes, a faixa de valores de LogPapp determinados variou de -1,73 a 0,99. Para avaliar a aplicação do conceito do par iônico como estratégia, os valores de LogPapp destes compostos foram determinados na presença de diferentes concentrações do contraíon hidrofóbico n-octil sulfato de sódio (OcS). Verificou-se aumento da lipofilicidade com aumento das concentrações de OcS. Obteve-se, também, os correspondentes valores de LogPapp extrapolados para concentração zero de OcS (LogPapp0), que concordaram, dentro do erro experimental, com os valores determinados diretamente na ausência de OcS. Estes resultados indicam que o conceito do par iônico pode ser aplicado como estratégia metodológica, para melhorar as condições experimentais e diminuir as incertezas nas determinações de valores de LogPapp para esta série de brometos de amônio quaternários hidrofílicos. Finalmente, foram realizados experimentos complementares para verificar a formação de par iônico: (i) determinações dos valores de logP da benzamida (composto sem carga permanente) na presença de OcS; (ii) análise por RMN de um dos compostos desta série, na presença de OcS. Ambos indicaram que, somente para os brometos de amônio quaternários estudados, o aumento da lipofilicidade observado ocorre por possível formação de par iônico. E, ainda, foi avaliada a aplicação do conceito do par iônico e seus efeitos sobre a lipofilicidade do QX-222 e do brometo de neostigmina (compostos altamente hidrofílicos), revelando limitações na sua aplicação como estratégia metodológica. / Quantitative Structure-Activity Relationships (QSAR) models previously generated in our group for a set of N-benzyl-N,N-dimethyl-2-(4-X-benzamido)ethan-1-ammonium bromides (procaine structural analogs) showed a positive contribution of the lipophilic term (expressed by the partition coefficient, logPapp) to their neuromuscular blockage activity. However, since some of them are hydrophilic quaternary ammonium bromides, their logPapp measurements were usually associated with experimental shortcomings, leading to low accuracy logPapp values. In order to make these experiments more feasible, the application of the ion-pair concept was evaluated as a methodological strategy in another previous work, initially to one compound of this set. For this purpose, logPapp measurements have been done in the presence of a large and hydrophobic counter ion, leading to an increase of its lipophilicity, due to possible ion-pair formation. In the present work, in order to further investigate this strategy and its effects on the lipophilicity, we include more compounds, allowing the assessment of a wider range of logPapp values. Thus, logPapp values of five compounds were obtained by the shake-flask method, using n-octanol/water, with and without ionic strength adjustment. For them, logPapp range values were determined from -1.73 to 0.99. To evaluate the application of the ion-pair concept as strategy, logPapp values of these compounds were determined in the presence of eleven sodium octyl sulfate (OcS) concentrations. It was observed that the lipophilicity of these compounds, increased with the addition of OcS. Moreover, we obtained the corresponding logPapp values extrapolated to zero OcS concentration (logPapp0), which agreed, within the experimental error, with the corresponding values determined in absence of OcS. These results suggest that the ion-pair concept can be applied as a strategy to improve the experimental conditions, increasing the accuracy of logPapp measurements for this set of hydrophilic quaternary ammonium bromides. Finally, supplementary experiments were done to verify the ion-pair formation: (i) measurement of logP values of benzamide (not a permanent ion) in presence of OcS; (ii) NMR spectroscopy analysis of one compound of this set, also in presence of OcS. Both indicated that only for the studied quaternary ammonium bromides the lipophilicity increase is due to possible ion-pair formation. Additionally, the application of the ion-pair concept and its effects on the lipophilicity was evaluated for QX-222 and for neostigmine bromide (highly hydrophilic compounds), which revealed limitations in its application as a methodological strateg

Modelos de Relações Quantitativas entre Estrutura Química e Atividade Biológica (QSAR), previamente gerados no grupo para uma série de brometos de N-benzil-N,N-dimetil-2-(4-X-benzamido)etan-1-amônio substituídos (compostos estruturalmente análogos à procaína), mostraram uma contribuição positiva da lipofilicidade (expressa pelo parâmetro lipofílico, logPapp) para a atividade de bloqueio da transmissão neuromuscular observada para estes. Como os compostos desta série são sais de amônio quaternários, sendo alguns altamente hidrofílicos, as determinações dos seus valores de logPapp pelo método shake-flask acarretam dificuldades experimentais, levando a altas incertezas. Para contornar estas dificuldades, em outro trabalho iniciado no grupo, sugeriu-se, como estratégia metodológica, avaliar a aplicação do conceito do par iônico, usando, para tanto, um contraíon grande e hidrofóbico. Assim, observou-se, para um único composto desta série, o aumento da sua lipofilicidade, por possível formação de par iônico, tornando-o menos hidrofílico. Nesta dissertação, visando ampliar os estudos envolvendo a aplicação desta estratégia metodológica e seus efeitos sobre a lipofilicidade, outros compostos foram selecionados para que uma faixa mais ampla de valores de LogPapp pudesse ser avaliada. Para tanto, os valores de logPapp de cinco compostos desta série foram determinados pelo método shake-flask, usando o sistema n-octanol/água, avaliando-se, ainda, os efeitos da força iônica na partição. Para estes, a faixa de valores de LogPapp determinados variou de -1,73 a 0,99. Para avaliar a aplicação do conceito do par iônico como estratégia, os valores de LogPapp destes compostos foram determinados na presença de diferentes concentrações do contraíon hidrofóbico n-octil sulfato de sódio (OcS). Verificou-se aumento da lipofilicidade com aumento das concentrações de OcS. Obteve-se, também, os correspondentes valores de LogPapp extrapolados para concentração zero de OcS (LogPapp0), que concordaram, dentro do erro experimental, com os valores determinados diretamente na ausência de OcS. Estes resultados indicam que o conceito do par iônico pode ser aplicado como estratégia metodológica, para melhorar as condições experimentais e diminuir as incertezas nas determinações de valores de LogPapp para esta série de brometos de amônio quaternários hidrofílicos. Finalmente, foram realizados experimentos complementares para verificar a formação de par iônico: (i) determinações dos valores de logP da benzamida (composto sem carga permanente) na presença de OcS; (ii) análise por RMN de um dos compostos desta série, na presença de OcS. Ambos indicaram que, somente para os brometos de amônio quaternários estudados, o aumento da lipofilicidade observado ocorre por possível formação de par iônico. E, ainda, foi avaliada a aplicação do conceito do par iônico e seus efeitos sobre a lipofilicidade do QX-222 e do brometo de neostigmina (compostos altamente hidrofílicos), revelando limitações na sua aplicação como estratégia metodológica. / Quantitative Structure-Activity Relationships (QSAR) models previously generated in our group for a set of N-benzyl-N,N-dimethyl-2-(4-X-benzamido)ethan-1-ammonium bromides (procaine structural analogs) showed a positive contribution of the lipophilic term (expressed by the partition coefficient, logPapp) to their neuromuscular blockage activity. However, since some of them are hydrophilic quaternary ammonium bromides, their logPapp measurements were usually associated with experimental shortcomings, leading to low accuracy logPapp values. In order to make these experiments more feasible, the application of the ion-pair concept was evaluated as a methodological strategy in another previous work, initially to one compound of this set. For this purpose, logPapp measurements have been done in the presence of a large and hydrophobic counter ion, leading to an increase of its lipophilicity, due to possible ion-pair formation. In the present work, in order to further investigate this strategy and its effects on the lipophilicity, we include more compounds, allowing the assessment of a wider range of logPapp values. Thus, logPapp values of five compounds were obtained by the shake-flask method, using n-octanol/water, with and without ionic strength adjustment. For them, logPapp range values were determined from -1.73 to 0.99. To evaluate the application of the ion-pair concept as strategy, logPapp values of these compounds were determined in the presence of eleven sodium octyl sulfate (OcS) concentrations. It was observed that the lipophilicity of these compounds, increased with the addition of OcS. Moreover, we obtained the corresponding logPapp values extrapolated to zero OcS concentration (logPapp0), which agreed, within the experimental error, with the corresponding values determined in absence of OcS. These results suggest that the ion-pair concept can be applied as a strategy to improve the experimental conditions, increasing the accuracy of logPapp measurements for this set of hydrophilic quaternary ammonium bromides. Finally, supplementary experiments were done to verify the ion-pair formation: (i) measurement of logP values of benzamide (not a permanent ion) in presence of OcS; (ii) NMR spectroscopy analysis of one compound of this set, also in presence of OcS. Both indicated that only for the studied quaternary ammonium bromides the lipophilicity increase is due to possible ion-pair formation. Additionally, the application of the ion-pair concept and its effects on the lipophilicity was evaluated for QX-222 and for neostigmine bromide (highly hydrophilic compounds), which revealed limitations in its application as a methodological strateg

This diploma thesis is focused to the determination of procaine using flow injection and sequential injection analysis coupled with spectrophotometric detection. This determination is based on the reaction of procaine with a colouring agent, 1,2-naphthoquinone-4-sulfonic acid. An orange coloured product is formed, which is determined spectrophotometrically at the wavelength 484 nm. The high of the absorption signal of the product is directly proportional to the concentration of procaine. The aim of this work was to optimize the parameters of both methods of flow analysis so that the limit concentration of procaine can be as low as possible and at the same time, high sensibility is achieved. The next step was to apply these methods on the determination of procaine in real samples. It was found that in flow injection analysis, the absorbance of procaine hydrochloride obeys Beer's law for concentrations from 2.5 to 120 µg/ml. The linear regression equation of calibration graph was y = 0.0059x - 0.0051, with a linear regression correlation coefficient 0.9993. Limit of detection was 0.72 µg/ml. Effects of standing time (stopped-flow), flow rate, concentration of colouring agent, pH and the volume of the sample loop have been examined and optimized. It was also found that in sequential injection...