Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

This study was designed to investigate the inhibiting effect that caffeine may have in inducing deeper states of relaxation. The degree of relaxation was assessed by physiological measures, self-ratings, and behavioral observations of relaxation behavior.

Introdução: pesquisas sobre consumo de café têm sido feitas para determinar os componentes da bebida e suas respectivas funções, além de características sensoriais e efeitos associados à saúde humana. A cafeína é uma das substâncias psicoativas mais consumidas no mundo. Durante as últimas cinco décadas, seu consumo mundial per capita dobrou através do consumo de água cafeinada, de bebidas energéticas e, principalmente, do café. Por este motivo, muitos trabalhos têm sido realizados sobre os efeitos fisiológicos desta substância, resultando na impossibilidade de se chegar a um consenso sobre seus efeitos positivos e negativos. Tal dicotomia acarreta um aumento do consumo de café descafeinado, muitas vezes por aconselhamento médico. A descafeinação é realizada nos grãos crus inteiros, antes do processo de torrefação. A maioria dos métodos de descafeinação existentes utiliza solventes para extração da cafeína, como diclorometano, clorofórmio, álcool, acetona, água e outros, sendo o diclorometano mais utilizado no Brasil. Embora existam vários estudos sobre a composição química do café integral, pouco se sabe sobre a composição do café descafeinado. Tais modificações químicas podem acarretar não somente alterações nas características sensoriais da bebida, como também em termos fisiológicos. Objetivo: identificar o grau de aceitação e de preferência da bebida de café preparada com grãos submetidos a diferentes condições de extração da cafeína em consumidores habituais da bebida. Métodos: três amostras de café foram submetidas aos métodos: tradicional (não descafeinado), descafeinado pelo método químico (diclorometano) e descafeinado pelo método natural (água), depois torrados e moídos. Cento e dez consumidores receberam as amostras do café, de forma monádica e aleatória, e o açúcar ou adoçante porcionados. Os testes foram executados pelo teste afetivo de aceitação com escala hedônica (1: desgostei muito a 7: gostei muito) para 4 atributos (cor, aroma, corpo e sabor). O café foi preparado e filtrado na concentração 7%. Os resultados foram coletados e analisados prelo programa Fizz (Byosysteme) - ANOVA e Tukey, p = 0,05). As amostras foram submetidas à análise física para determinar umidade, cinzas, proteínas, lipídios totais, carboidratos e cafeína. Resultados: o café descafeinado tratado pelo método químico apresentou média abaixo dos outros dois cafés nos quatro atributos, mas com diferenças estatisticamente significativa para o sabor e corpo. Entretanto, em relação ao sabor, houve diferença estatística entre os cafés tradicionais e descafeinado com água e o descafeinado com o diclorometano. Foram encontradas diferenças significativas nas análises físico-químicas para proteína e lipídios nos cafés descafeinados em comparação ao tradicional Discussão: a extração de compostos do café pelos métodos físico e químico resultou em diferentes bebidas no que se refere ao sabor. O método químico pôde mudar as características sensoriais da bebida. / Introduction: researches have been made to determine the coffee components and its functions, sensory characteristics and effects related to human health. Caffeine is one of the most consumed psychoactive substances in the world. During the last five decades, the worldwide caffeine consumption almost doubled, mainly trough coffee. For this reason, many studies have been conducted on the effects of this substance, resulting in the inability to reach a consensus on its positive and negative effects. This dichotomy ultimately causes increased consumption of decaffeinated coffee, often for medical advice. The decaffeination and raw whole grains in place before the process of roasting. Several methods of decaffeination use solvents for extraction of caffeine, dichloromethane is the most used in Brazil. During the extraction of caffeine, the loss of other components is expected. Objective: identify the degree of acceptance and preference of coffee prepared with different conditions of extraction of caffeine for habitual consumers of the drink. Methods: three samples of coffee were obtained: traditional (not decaf), decaffeinated by chemical method (dichloromethane) and decaffeinated by the natural method (water) and after roasted and grounded. 110 consumers received the coffee samples, monadic and random, with portionated sugar or sweetener. Tests were performed with affective form of quantitative assessment of (1: I hate very much to 7: I like very much) for 4 attributes (color, aroma, body and flavor). The coffee was filtrated (concentration 7%). The results were collected and analyzed through the Fizz (ANOVA and Tukey, p = 0,05) The samples were submited by a physicochemical analysis to determine moisture, ash, protein, total lipids, carbohydrates and caffeine. Results: the decaffeinated coffee treated by chemical methods presented lower acceptance when compared with the other two coffees on 4 attributes, but with differences to the flavor and body. However, related to flavor, there was statistical difference between the traditional and decaffeinated coffees with water with decaffeinated with the dichloromethane. Significant differences were found in physical-chemical analysis for protein and lipids in decaffeinated coffee compared to the traditional one. Discussion: the extraction of different compounds of coffee by the method of decaffeination showed particular physical and chemical differences of coffee flavor on the extraction with chemical method. This chemical method might change the sensory characteristics of the drink. No differences were perceived through the physicochemical analysis.

Purpose Monoamine oxidase (MAO) consists of two isoforms, namely MAO-A and MAO-B. Both these isoforms are involved in the oxidation of dopamine. In Parkinson’s disease (PD) therapy, the inhibition of the oxidation of dopamine by MAO may elevate the levels of dopamine in the brain and prevent the generation of toxic by-products such as hydrogen peroxide. MAO-B inhibitors have found application as monotherapy in PD and it has been shown that MAO-B inhibitors may also be useful as adjuvants to L-dopa in PD therapy. For example, an earlier study has shown that the combination of L-dopa with (R)-deprenyl (a selective MAO-B inhibitor), may lead to a reduction of the dose of L-dopa required for alleviating the motor symptoms in PD patients. However, older MAO inhibitors may possess adverse side effects such as psychotoxicity, liver toxicity and cardiovascular effects. The irreversible mode of inhibition of the older MAO-B inhibitors, such as (R)-deprenyl, may also be considered as less desirable. After the use of irreversible inhibitors, it may require several weeks for the MAO enzyme to recover activity. In contrast, after administration of a reversible inhibitor, enzyme activity is recovered as soon as the inhibitor is cleared form the tissues. The adverse effects and disadvantages of the older MAO-B inhibitors prompted us to undertake the discovery of safer and reversible inhibitors of MAO-B. Such compounds may find application in the treatment of PD. Rationale It was recently discovered that (E)-8-(3-chlorostyryl)caffeine (CSC) is a potent inhibitor of MAO-B, with an IC50 value of 0.128 µM. CSC has a caffeine moiety, which is thought to be essential for MAO-B inhibition. It was also reported that a related series of 8- (phenoxymethyl)caffeine derivatives are potent and reversible inhibitors of MAO-A and –B. The IC50 values of the 8-(phenoxymethyl)caffeines ranged from 0.148–5.78 µM for the inhibition of MAO-B. For the purpose of this study the phenoxymethyl side-chain was replaced with a phenylsulfanyl moiety at C8. The aim of this study was therefore to synthesize a series of 8-[(phenylsulfanyl)methyl]caffeine analogues and to compare their MAO-B inhibition potencies to the previously synthesised 8-(phenoxymethyl)caffeine derivatives. A series of five 8-[(phenylsulfanyl)ethyl]caffeine analogues was also synthesized in order to determine the effect of carbon chain elongation on the potency of MAO inhibition. O C-8 N N O N N Caffeine Cl O N N (E) O N N CSC O N N O O N N 8-(Phenoxymethyl)caffeine O N N O N N S 8-[(Phenylsulfanyl)methyl]caffeine O N N S O N N 8-[(Phenylsulfanyl)ethyl]caffeine Compound R1 R2 1a H H 1b Cl H 1c Br H 1d F H 1e CH3 H 1f OCH3 H 1g OCH2CH3 H 1h H Cl 1i H Br Compound R1 R2 2a H H 2b Cl H 2c Br H 2d H Cl 2e H Br Methods The C8 substituted caffeine analogues were synthesised by reacting 1,3-dimethyl-5,6-diaminouracil with an appropriately substituted 2-(phenylsulfanyl)acetic acid or 3-(phenylsulfanyl)propanoic acid in the presence of a carbodiimide activating reagent, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC). Ring closure of the intermediary amide was effected by reaction with sodium hydroxide. Resulting theophylline analogues were subsequently methylated in the presence of iodomethane to yield the target compounds. The structures of the C8 substituted caffeine analogues were verified by NMR and MS analysis. The purities thereof were subsequently estimated by HPLC analysis. The 8-[(phenylsulfanyl)methyl]caffeine and 8-[(phenylsulfanyl)ethyl]caffeine analogues were evaluated as MAO-A and –B inhibitors. The recombinant human enzymes were used as enzyme sources. The inhibitory potencies of the caffeine derivatives were expressed as IC50 values (the concentration of a drug that is required for 50% inhibition in vitro). The time- dependency of inhibition of MAO-B by the most potent inhibitor was also evaluated in order to determine the reversibility of inhibition of the test compound. A study was also conducted to determine the inhibition mode of the most potent test compound, by constructing a set of Lineweaver Burk plots. Results The results showed that the 8-[(phenylsulfanyl)methyl]caffeine analogues were inhibitors of MAO-A and –B. The most potent inhibitor in the first series (1a–i) of this study were 8-[(3- bromophenylsulfanyl)methyl]caffeine and 8-[(4-bromophenylsulfanyl)methyl]caffeine with IC50 values of 4.90 and 4.05 µM, respectively. When these results were compared to those of the previously studied 8-(phenoxymethyl)caffeine derivatives it was found that, for these compounds, the bromine substituted homologues were also the most potent MAO-B inhibitors. The bromine substituted 8-(phenoxymethyl)caffeine derivatives exhibited IC50 values of 0.148 and 0.189 µM for those homologues containing bromine on the meta and para positions of the phenoxy side chain, respectively. In general, the 8- [(phenylsulfanyl)methyl]caffeine derivatives were found to be less potent MAO-B inhibitors than the 8-(phenoxymethyl)caffeine derivatives. The 8-[(phenylsulfanyl)methyl]caffeine derivatives also did not show as high a degree of selectivity for MAO-B (compared to MAO- A) as did the 8-(phenoxymethyl)caffeines. Similar to the 8-(phenoxymethyl)caffeines, the 8- [(phenylsulfanyl)methyl]caffeines also proved to be weak MAO-A inhibitors. The most potent inhibitor of MAO-A among the test compounds exhibited an IC50 value of 19.4 µM. The most potent MAO-A inhibitor among the previously studied 8-(phenoxymethyl)caffeines was more potent with an IC50 value of 4.59 µM. From these results it may be concluded that the phenoxy side chain is more suited for the design of caffeine derived MAO inhibitors than the phenylsulfanyl side chain. The results for the second series investigated in this study, the 8-[(phenylsulfanyl)ethyl]caffeines (2a–e), revealed the chlorine substituted derivatives to be the most potent MAO-B inhibitors. The meta and para chlorine substituted derivatives exhibited IC50 values of 5.67 and 7.79 µM, respectively, for the inhibition of MAO-B. Interestingly, the meta substituted derivative exhibited no inhibition toward the MAO-A isoenzyme. However, the 8-[(phenylsulfanyl)ethyl]caffeine derivatives were found to be very weak inhibitors of both MAO-A and –B and may be considered as less potent than the 8-[(phenylsulfanyl)methyl]caffeine derivatives. Since one of the aims of this study was to synthesise reversible MAO inhibitors, a time- dependency study was carried out with the best inhibitor (1i). The aim of this study was to determine the reversibility of inhibition by the 8-[(phenylsulfanyl)methyl]caffeine derivatives. From the results, it was concluded that the inhibition of MAO-B by compound 1i is reversible. To determine the mode of inhibition, a set of Lineweaver-Burk plots was constructed and since the plots were linear and intersected on the y-axis, it was concluded that 1i is a competitive inhibitor of MAO-B. Conclusion This study concludes that the phenoxymethyl side-chain is more suited for the design of caffeine derived MAO-B inhibitors than the (phenylsulfanyl)methyl side-chain. / Thesis (MSc (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2013.

Purpose Monoamine oxidase (MAO) consists of two isoforms, namely MAO-A and MAO-B. Both these isoforms are involved in the oxidation of dopamine. In Parkinson’s disease (PD) therapy, the inhibition of the oxidation of dopamine by MAO may elevate the levels of dopamine in the brain and prevent the generation of toxic by-products such as hydrogen peroxide. MAO-B inhibitors have found application as monotherapy in PD and it has been shown that MAO-B inhibitors may also be useful as adjuvants to L-dopa in PD therapy. For example, an earlier study has shown that the combination of L-dopa with (R)-deprenyl (a selective MAO-B inhibitor), may lead to a reduction of the dose of L-dopa required for alleviating the motor symptoms in PD patients. However, older MAO inhibitors may possess adverse side effects such as psychotoxicity, liver toxicity and cardiovascular effects. The irreversible mode of inhibition of the older MAO-B inhibitors, such as (R)-deprenyl, may also be considered as less desirable. After the use of irreversible inhibitors, it may require several weeks for the MAO enzyme to recover activity. In contrast, after administration of a reversible inhibitor, enzyme activity is recovered as soon as the inhibitor is cleared form the tissues. The adverse effects and disadvantages of the older MAO-B inhibitors prompted us to undertake the discovery of safer and reversible inhibitors of MAO-B. Such compounds may find application in the treatment of PD. Rationale It was recently discovered that (E)-8-(3-chlorostyryl)caffeine (CSC) is a potent inhibitor of MAO-B, with an IC50 value of 0.128 µM. CSC has a caffeine moiety, which is thought to be essential for MAO-B inhibition. It was also reported that a related series of 8- (phenoxymethyl)caffeine derivatives are potent and reversible inhibitors of MAO-A and –B. The IC50 values of the 8-(phenoxymethyl)caffeines ranged from 0.148–5.78 µM for the inhibition of MAO-B. For the purpose of this study the phenoxymethyl side-chain was replaced with a phenylsulfanyl moiety at C8. The aim of this study was therefore to synthesize a series of 8-[(phenylsulfanyl)methyl]caffeine analogues and to compare their MAO-B inhibition potencies to the previously synthesised 8-(phenoxymethyl)caffeine derivatives. A series of five 8-[(phenylsulfanyl)ethyl]caffeine analogues was also synthesized in order to determine the effect of carbon chain elongation on the potency of MAO inhibition. O C-8 N N O N N Caffeine Cl O N N (E) O N N CSC O N N O O N N 8-(Phenoxymethyl)caffeine O N N O N N S 8-[(Phenylsulfanyl)methyl]caffeine O N N S O N N 8-[(Phenylsulfanyl)ethyl]caffeine Compound R1 R2 1a H H 1b Cl H 1c Br H 1d F H 1e CH3 H 1f OCH3 H 1g OCH2CH3 H 1h H Cl 1i H Br Compound R1 R2 2a H H 2b Cl H 2c Br H 2d H Cl 2e H Br Methods The C8 substituted caffeine analogues were synthesised by reacting 1,3-dimethyl-5,6-diaminouracil with an appropriately substituted 2-(phenylsulfanyl)acetic acid or 3-(phenylsulfanyl)propanoic acid in the presence of a carbodiimide activating reagent, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDAC). Ring closure of the intermediary amide was effected by reaction with sodium hydroxide. Resulting theophylline analogues were subsequently methylated in the presence of iodomethane to yield the target compounds. The structures of the C8 substituted caffeine analogues were verified by NMR and MS analysis. The purities thereof were subsequently estimated by HPLC analysis. The 8-[(phenylsulfanyl)methyl]caffeine and 8-[(phenylsulfanyl)ethyl]caffeine analogues were evaluated as MAO-A and –B inhibitors. The recombinant human enzymes were used as enzyme sources. The inhibitory potencies of the caffeine derivatives were expressed as IC50 values (the concentration of a drug that is required for 50% inhibition in vitro). The time- dependency of inhibition of MAO-B by the most potent inhibitor was also evaluated in order to determine the reversibility of inhibition of the test compound. A study was also conducted to determine the inhibition mode of the most potent test compound, by constructing a set of Lineweaver Burk plots. Results The results showed that the 8-[(phenylsulfanyl)methyl]caffeine analogues were inhibitors of MAO-A and –B. The most potent inhibitor in the first series (1a–i) of this study were 8-[(3- bromophenylsulfanyl)methyl]caffeine and 8-[(4-bromophenylsulfanyl)methyl]caffeine with IC50 values of 4.90 and 4.05 µM, respectively. When these results were compared to those of the previously studied 8-(phenoxymethyl)caffeine derivatives it was found that, for these compounds, the bromine substituted homologues were also the most potent MAO-B inhibitors. The bromine substituted 8-(phenoxymethyl)caffeine derivatives exhibited IC50 values of 0.148 and 0.189 µM for those homologues containing bromine on the meta and para positions of the phenoxy side chain, respectively. In general, the 8- [(phenylsulfanyl)methyl]caffeine derivatives were found to be less potent MAO-B inhibitors than the 8-(phenoxymethyl)caffeine derivatives. The 8-[(phenylsulfanyl)methyl]caffeine derivatives also did not show as high a degree of selectivity for MAO-B (compared to MAO- A) as did the 8-(phenoxymethyl)caffeines. Similar to the 8-(phenoxymethyl)caffeines, the 8- [(phenylsulfanyl)methyl]caffeines also proved to be weak MAO-A inhibitors. The most potent inhibitor of MAO-A among the test compounds exhibited an IC50 value of 19.4 µM. The most potent MAO-A inhibitor among the previously studied 8-(phenoxymethyl)caffeines was more potent with an IC50 value of 4.59 µM. From these results it may be concluded that the phenoxy side chain is more suited for the design of caffeine derived MAO inhibitors than the phenylsulfanyl side chain. The results for the second series investigated in this study, the 8-[(phenylsulfanyl)ethyl]caffeines (2a–e), revealed the chlorine substituted derivatives to be the most potent MAO-B inhibitors. The meta and para chlorine substituted derivatives exhibited IC50 values of 5.67 and 7.79 µM, respectively, for the inhibition of MAO-B. Interestingly, the meta substituted derivative exhibited no inhibition toward the MAO-A isoenzyme. However, the 8-[(phenylsulfanyl)ethyl]caffeine derivatives were found to be very weak inhibitors of both MAO-A and –B and may be considered as less potent than the 8-[(phenylsulfanyl)methyl]caffeine derivatives. Since one of the aims of this study was to synthesise reversible MAO inhibitors, a time- dependency study was carried out with the best inhibitor (1i). The aim of this study was to determine the reversibility of inhibition by the 8-[(phenylsulfanyl)methyl]caffeine derivatives. From the results, it was concluded that the inhibition of MAO-B by compound 1i is reversible. To determine the mode of inhibition, a set of Lineweaver-Burk plots was constructed and since the plots were linear and intersected on the y-axis, it was concluded that 1i is a competitive inhibitor of MAO-B. Conclusion This study concludes that the phenoxymethyl side-chain is more suited for the design of caffeine derived MAO-B inhibitors than the (phenylsulfanyl)methyl side-chain. / Thesis (MSc (Pharmaceutical Chemistry))--North-West University, Potchefstroom Campus, 2013.

This study was directed toward investigating effects of menstrual cycle stages and caffein ingestion on various physiological and psychological processes. Subjects maintained a daily log of basal waking temperature (BWT), occurrence of menstruation, and consumption of caffein containing beverages and medications. At each session, visuo-spatial discrimination, depth perception, and time estimation (15 and 30 sec) were assessed. The Menstrual Distress Questionnaire (MDQ), The Measurement of Depression (MOD), and a self-report scale were completed.Multiple linear discriminant analyses were conducted on menstrual cycle and caffein ingestion data. Variables that contributed significantly to the discrimination of level of caffein ingestion were visuo-spatial discrimination; MDQ Water Retention and Control; cervical, lumbar, and saccral temperatures; time required to reach baseline; and total daily consumption of caffein-containing beverages.

Call number: LD2668 .T4 1978 O43 / Master of Science

Call number: LD2668 .T4 1984 H365 / Master of Science

No description available.