|
|
Peptides regulating food intake and their lipidized analogs for possible treatment of obesity and cachexia
Buková, Anna-Marie ; Maletínská, Lenka (advisor) ; Janovská, Petra (referee)
In spite of good living conditions, the number of people in the state where the total food intake or individual nutrients is insufficient, unnecessary or unbalanced has increased in recent years. In case of superfluous food intake, amount of fat tissue increases and overweight and obesity appear, which is associated with an increased risk of type 2 of diabetes, cardiovascular disease or certain types of cancer. Insufficient intake of food may, for example, result in the function of the immune system, resulting in an increased risk of infection or poor wound healing. In addition to primary malnutrition, we can see malnutrition as the secondary manifestation of another illness. The state of weight loss and malnutrition caused by another disease is called cachexia. This is a serious complication of primary therapies. At present, in addition to established approaches to the treatment of these diseases, some studies address treatment options using compounds that influence the regulation of food intake. One group of these compounds is peptides able to reduce food intake (anorexigenic peptides) or increase it (orexigenic peptides). To these natural substances in the organism are also sought analogs with properties more favorable for use in practice. One of the possibilities are lipidized analogs, among...
|
|
|
Impact of stable ghrelin receptor agonists and antagonists on food intake regulation
Holubová, Martina
The thesis is focused on the effect of ghrelin receptor (GHS-R1a) agonists and antagonist on food intake regulation. Ghrelin is the only known periferally produced orexigenic hormone and the only known acylated hormone. GHS-R1a agonists and antagonists could be useful in the treatment of cachexia and obesity, respectively. In the first part of the thesis, newly designed peptidic GHS-R1a agonists were characterized. The agonists were stabilized by replacing octanoylated Ser3 with a fatty acid coupled to diaminopropionic acid by a stable amide bond. Other noncoded amino acids were also incorporated. Ghrelin analogs were modified by replacing the octanoyl group with another fatty acid, incorporation of the second fatty acid or shortening the peptide chain. Most of the tested GHS-R1a agonists were found to possess high affinities for GHS-R1a (Ki = 10-9 - 10-10 nM) and to activate signaling pathways of ghrelin. After subcutaneous (SC) administration to mice, agonists showed significant and prolonged orexigenic effect. In the second part of the thesis, acute and long-term effects of pseudopeptide GHS- R1a agonist JMV1843 were tested in lean C57BL/6 mice. Acute SC administration of JMV1843 to fed mice increased food intake in a dose-dependent manner (ED50 = 1.94 mg/kg). JMV1843 was stable in blood serum...
|
|
|
Impact of stable ghrelin receptor agonists and antagonists on food intake regulation
Holubová, Martina ; Maletínská, Lenka (advisor) ; Kopecký, Jan (referee) ; Sobotka, Luboš (referee)
The thesis is focused on the effect of ghrelin receptor (GHS-R1a) agonists and antagonist on food intake regulation. Ghrelin is the only known periferally produced orexigenic hormone and the only known acylated hormone. GHS-R1a agonists and antagonists could be useful in the treatment of cachexia and obesity, respectively. In the first part of the thesis, newly designed peptidic GHS-R1a agonists were characterized. The agonists were stabilized by replacing octanoylated Ser3 with a fatty acid coupled to diaminopropionic acid by a stable amide bond. Other noncoded amino acids were also incorporated. Ghrelin analogs were modified by replacing the octanoyl group with another fatty acid, incorporation of the second fatty acid or shortening the peptide chain. Most of the tested GHS-R1a agonists were found to possess high affinities for GHS-R1a (Ki = 10-9 - 10-10 nM) and to activate signaling pathways of ghrelin. After subcutaneous (SC) administration to mice, agonists showed significant and prolonged orexigenic effect. In the second part of the thesis, acute and long-term effects of pseudopeptide GHS-R1a agonist JMV1843 were tested in lean C57BL/6 mice. Acute SC administration of JMV1843 to fed mice increased food intake in a dose-dependent manner (ED50 = 1.94 mg/kg). JMV1843 was stable in blood serum in...
|
|
|
Peptides regulating food intake and their lipidized analogs for possible treatment of obesity and cachexia
Buková, Anna-Marie ; Maletínská, Lenka (advisor) ; Janovská, Petra (referee)
In spite of good living conditions, the number of people in the state where the total food intake or individual nutrients is insufficient, unnecessary or unbalanced has increased in recent years. In case of superfluous food intake, amount of fat tissue increases and overweight and obesity appear, which is associated with an increased risk of type 2 of diabetes, cardiovascular disease or certain types of cancer. Insufficient intake of food may, for example, result in the function of the immune system, resulting in an increased risk of infection or poor wound healing. In addition to primary malnutrition, we can see malnutrition as the secondary manifestation of another illness. The state of weight loss and malnutrition caused by another disease is called cachexia. This is a serious complication of primary therapies. At present, in addition to established approaches to the treatment of these diseases, some studies address treatment options using compounds that influence the regulation of food intake. One group of these compounds is peptides able to reduce food intake (anorexigenic peptides) or increase it (orexigenic peptides). To these natural substances in the organism are also sought analogs with properties more favorable for use in practice. One of the possibilities are lipidized analogs, among...
|
|
|
Impact of stable ghrelin receptor agonists and antagonists on food intake regulation
Holubová, Martina
The thesis is focused on the effect of ghrelin receptor (GHS-R1a) agonists and antagonist on food intake regulation. Ghrelin is the only known periferally produced orexigenic hormone and the only known acylated hormone. GHS-R1a agonists and antagonists could be useful in the treatment of cachexia and obesity, respectively. In the first part of the thesis, newly designed peptidic GHS-R1a agonists were characterized. The agonists were stabilized by replacing octanoylated Ser3 with a fatty acid coupled to diaminopropionic acid by a stable amide bond. Other noncoded amino acids were also incorporated. Ghrelin analogs were modified by replacing the octanoyl group with another fatty acid, incorporation of the second fatty acid or shortening the peptide chain. Most of the tested GHS-R1a agonists were found to possess high affinities for GHS-R1a (Ki = 10-9 - 10-10 nM) and to activate signaling pathways of ghrelin. After subcutaneous (SC) administration to mice, agonists showed significant and prolonged orexigenic effect. In the second part of the thesis, acute and long-term effects of pseudopeptide GHS- R1a agonist JMV1843 were tested in lean C57BL/6 mice. Acute SC administration of JMV1843 to fed mice increased food intake in a dose-dependent manner (ED50 = 1.94 mg/kg). JMV1843 was stable in blood serum...
|
|
|
Impact of stable ghrelin receptor agonists and antagonists on food intake regulation
Holubová, Martina ; Maletínská, Lenka (advisor) ; Kopecký, Jan (referee) ; Sobotka, Luboš (referee)
The thesis is focused on the effect of ghrelin receptor (GHS-R1a) agonists and antagonist on food intake regulation. Ghrelin is the only known periferally produced orexigenic hormone and the only known acylated hormone. GHS-R1a agonists and antagonists could be useful in the treatment of cachexia and obesity, respectively. In the first part of the thesis, newly designed peptidic GHS-R1a agonists were characterized. The agonists were stabilized by replacing octanoylated Ser3 with a fatty acid coupled to diaminopropionic acid by a stable amide bond. Other noncoded amino acids were also incorporated. Ghrelin analogs were modified by replacing the octanoyl group with another fatty acid, incorporation of the second fatty acid or shortening the peptide chain. Most of the tested GHS-R1a agonists were found to possess high affinities for GHS-R1a (Ki = 10-9 - 10-10 nM) and to activate signaling pathways of ghrelin. After subcutaneous (SC) administration to mice, agonists showed significant and prolonged orexigenic effect. In the second part of the thesis, acute and long-term effects of pseudopeptide GHS-R1a agonist JMV1843 were tested in lean C57BL/6 mice. Acute SC administration of JMV1843 to fed mice increased food intake in a dose-dependent manner (ED50 = 1.94 mg/kg). JMV1843 was stable in blood serum in...
|
|
|
Specifical nutritional requirements of oncological patients
KRAUSOVÁ, Lada
Nourishment in oncological patients is a very complicated problem. Up to half of the patients experience a lack of appetite that borders to food aversion which is often followed by an almost immediate sense of fullness after first few bites. Furthermore, some of the treatments themselves may lead to nausea, diarrhea and problems with swallowing. Malnutrition, consequently, will often worsen the prognosis for patient with a malignant tumor; lower his susceptibility to oncological treatment and increase the probability of further complications. A complete clinical picture of malnutrition, called cachexia, is characterized by noticeable gauntness, loss of both musculature and subcutaneous fat. Studies show that 30% to 90% of oncological patients suffer from malnutrition. Also, a continuous weight loss considerably lowers the quality of life, and this must not be overlooked for nutrition should not only lead to a prolonged survival, but also to an appropriate life-quality. The aim of this study was to find out how nutritive registry is kept at oncological wards in selected hospitals in the Czech Republic. Further, to find out if nurses are familiar with the causes of malnutrition in oncology patients and have sufficient knowledge of the specific nutritional principals. The hypotheses set were {--} 1) at the selected oncological wards nutritive registry is used, 2) the nurses there do know about causes of malnutrition while 3) nurses in other wards do not have this knowledge. 4) Nurses know about the necessary nutritional principals in oncology patients. Quantitative approach was used for this research. The questioning method was to collect data by distributing questionnaires. The results show that at oncology wards but at other, non-oncological wards as well, nutritive registry is used, and furthermore, a position of nutritional therapist has been appointed and nutritional staff established. The first hypothesis has been proven to be correct. The second and fourth hypotheses are correct as nurses do know the causes of malnutrition in oncology patients and have the knowledge of the necessary nutritional principals. The third hypothesis presumed that nurses from non-oncological wards lack this knowledge and has consequently been proven wrong. These nurses are indeed knowledgeable of the nutritional problems. In practice, a stressed necessity of nurses{\crq} efficient knowledge of the nutritional problem for patients with malnutrition and cachexia at both oncological and non-oncological wards is recommended, together with the introduction and observance of nursing standards concerning the nutritional problems of oncology patients, proper information given to the patients relating their special diet as a consequence of the illness and its subsequent treatment, and finally, a multidisciplinary approach and collaboration (nutritional staff).
|
guest ::
