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Preparation and characterization of nanoliposomal carriers of hydrophobic cytostatics using nanofluidic mixing
Zelníčková, Jaroslava ; Mašek,, Josef (referee) ; Turánek, Jaroslav (advisor)
This diploma thesis is focused on preparation of liposome by relatively new method called nanofluidisation. This method allows the controlled preparation of small unilamellar liposomes in one step. In my thesis I was dealing with optimalization of liposomes preparation which carry hydrophobic cytostatics using this method. Cytotoxic effect of liposomes carrying hydrophobic cytostatics in vitro on cell lines A549 and MCF-7 was determined. In cytotoxicyty test I compared the effect of hydrophobic cytostatics (paclitaxel and derivates of vitamin E specifically alfa-Tos, alfa-TEA) that were incorporated into liposomes prepared via nanofluidisation method and lipid film hydration method. Moreover, a technology of lyophilisation in the presence of cryoprotectants for preparation of liposomes using the method of nanofluidisation was developed.
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The role of nociceptive synaptic transmission modulation at the spinal cord level in different pain states
Adámek, Pavel ; Paleček, Jiří (advisor) ; Vaculín, Šimon (referee) ; Vlachová, Viktorie (referee)
Pain is a common symptom of many clinical syndromes and diseases. In particular, the treatment of neuropathic pain represents a serious public health issue because currently available analgesia is ineffective in many cases or it has adverse effects. Treatment of pain-related suffering requires knowledge of how pain signals are initially generated and subsequently transmitted by the nervous system. A nociceptive system plays a key role in this process of encoding and transmission of pain signals. Modulation of the nociceptive synaptic transmission in the spinal cord dorsal horn represents an important mechanism in the development and maintenance of different pathological pain states. This doctoral thesis has aimed to investigate and clarify some of the mechanisms involved in the modulation of the spinal nociceptive processing in different pain states. The main attention was paid to study the following issues: (I.) Which is the role of Transient Receptor Potential Vanilloid type 1 channels (TRPV1), Toll-Like Receptors 4 (TLR4), and phosphatidylinositol 3-kinase (PI3K) in the development of neuropathic pain induced by paclitaxel (PAC) chemotherapy in acute in vitro, and subchronic in vivo murine model of PAC-induced peripheral neuropathy (PIPN)? (II.) How is affected spinal inhibitory synaptic control...
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Optimization of separation conditions for HPCCC of paclitaxel
Havrlantová, Šárka ; Kučera, Radim (advisor) ; Šatínský, Dalibor (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Šárka Havrlantová Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Name of diploma thesis: Optimization of separation conditions for HPCCC of paclitaxel The aim of this work is a feasibility study of natural substances isolation (in my case it is paclitaxel and its intermediate 10-deacetylbaccatin) using modern technique called High performance countercurrent chromatography (HPCCC) available in Teva in Opava. For this basic research it was necessary to study the literature and test various solvent systems. Chosen solvent systems were then tested together with natural substance in HPCCC, results were processed and discussed. Countercurrent chromatography is considered a modern separation technique based on two immiscible liquids. One of them is called a stationary phase and is held inside the column by centrifugal force, the second liquid is called a mobile phase and is pumped through the column. Then the injected liquid sample is also pumped through the column and depending on distribution coefficients the sample components are either held in the stationary phase or pass through the column and detector into fraction collector. Advantages of this method are e.g. total...
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Modulation of synaptic transmission in the development of painful states
Slepička, Jakub ; Paleček, Jiří (advisor) ; Hejnová, Lucie (referee)
My thesis introduces the topic of nociceptive signalisation and processes involved in the formation and spreading of neuropathic pain. This study focuses on the mechanisms of nociceptive synaptic transmission mechanisms in the level of spinal dorsal horn and its modulation by paclitaxel, a chemotherapeutic drug inducing neuropathic changes. The attention is put especially on the possibility of glial activity participation in paclitaxel side effects. This idea stems from the existing hypothesis of the functional connection between TLR4 and TRPV1 receptor activity. TRPV1 is well known for its participation in chemical, thermal and nociceptive sensory transmission. Minocycline antibiotic is considered as an inhibitor of microglial activation therefore it was used for blocking neuroinflammation. The experimental part is comparing an impact of substances applied to the model of tachyphylaxis used for monitoring of nociceptive transmission changes according to decreasing activity of TRPV1 receptors. Electrophysiological recording of miniature excitatory postsynaptic currents from neurons in the Rexed laminae I. and II. of spinal dorsal horn was used. The results of my measurements show that minocycline is able to suppress acute effects of paclitaxel application in vitro if the spinal slice is incubated...
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The role of nociceptive synaptic transmission modulation at the spinal cord level in different pain states
Adámek, Pavel
Pain is a common symptom of many clinical syndromes and diseases. In particular, the treatment of neuropathic pain represents a serious public health issue because currently available analgesia is ineffective in many cases or it has adverse effects. Treatment of pain-related suffering requires knowledge of how pain signals are initially generated and subsequently transmitted by the nervous system. A nociceptive system plays a key role in this process of encoding and transmission of pain signals. Modulation of the nociceptive synaptic transmission in the spinal cord dorsal horn represents an important mechanism in the development and maintenance of different pathological pain states. This doctoral thesis has aimed to investigate and clarify some of the mechanisms involved in the modulation of the spinal nociceptive processing in different pain states. The main attention was paid to study the following issues: (I.) Which is the role of Transient Receptor Potential Vanilloid type 1 channels (TRPV1), Toll-Like Receptors 4 (TLR4), and phosphatidylinositol 3-kinase (PI3K) in the development of neuropathic pain induced by paclitaxel (PAC) chemotherapy in acute in vitro, and subchronic in vivo murine model of PAC-induced peripheral neuropathy (PIPN)? (II.) How is affected spinal inhibitory synaptic control...
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Relationship of selected indicators of nutritional status and results of oesophageal cancer treatment with chemoradiotherapy and surgery
Zemanová, Milada ; Tvrzická, Eva (advisor) ; Vaňásek, Jaroslav (referee) ; Kazdová, Ludmila (referee)
The impact was assessed of clinical and nutritional factors on prognosis of 107 oesophageal cancer patients treated with neoadjuvant chemoradiotherapy (CHRT) and surgery. Individualised nutritional support, according to grade of dysphagia was carried out in all the patients. Serum leptin, soluble leptin receptors (SLR), TNF, IGF and fatty acid (FA) profiles in plasma phosphatidylcholine (PC) were studied as well. Addition of paclitaxel to carboplatin and continual fluorouracil significantly increased toxicity without influencing efficacy of the treatment. Post-operative node negativity, grade of dysphagia, weight loss and serum albumin were proved to be prognostic factors of survival and time to progression. CHRT led to decrease of SLR, palmitoleic and oleic acid and increase of n-3 polyunsaturated FA in PC. Lower concentrations of SLR were associated with improved survival of the patients. Key words: oesophageal cancer, neoadjuvant chemoradiotherapy, weight loss, paclitaxel, albumin, soluble leptin receptor, fatty acids
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Optimization of separation conditions for HPCCC of paclitaxel
Havrlantová, Šárka ; Kučera, Radim (advisor) ; Šatínský, Dalibor (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Šárka Havrlantová Supervisor: doc. PharmDr. Radim Kučera, Ph.D. Name of diploma thesis: Optimization of separation conditions for HPCCC of paclitaxel The aim of this work is a feasibility study of natural substances isolation (in my case it is paclitaxel and its intermediate 10-deacetylbaccatin) using modern technique called High performance countercurrent chromatography (HPCCC) available in Teva in Opava. For this basic research it was necessary to study the literature and test various solvent systems. Chosen solvent systems were then tested together with natural substance in HPCCC, results were processed and discussed. Countercurrent chromatography is considered a modern separation technique based on two immiscible liquids. One of them is called a stationary phase and is held inside the column by centrifugal force, the second liquid is called a mobile phase and is pumped through the column. Then the injected liquid sample is also pumped through the column and depending on distribution coefficients the sample components are either held in the stationary phase or pass through the column and detector into fraction collector. Advantages of this method are e.g. total...
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The role of nociceptive synaptic transmission modulation at the spinal cord level in different pain states
Adámek, Pavel
Pain is a common symptom of many clinical syndromes and diseases. In particular, the treatment of neuropathic pain represents a serious public health issue because currently available analgesia is ineffective in many cases or it has adverse effects. Treatment of pain-related suffering requires knowledge of how pain signals are initially generated and subsequently transmitted by the nervous system. A nociceptive system plays a key role in this process of encoding and transmission of pain signals. Modulation of the nociceptive synaptic transmission in the spinal cord dorsal horn represents an important mechanism in the development and maintenance of different pathological pain states. This doctoral thesis has aimed to investigate and clarify some of the mechanisms involved in the modulation of the spinal nociceptive processing in different pain states. The main attention was paid to study the following issues: (I.) Which is the role of Transient Receptor Potential Vanilloid type 1 channels (TRPV1), Toll-Like Receptors 4 (TLR4), and phosphatidylinositol 3-kinase (PI3K) in the development of neuropathic pain induced by paclitaxel (PAC) chemotherapy in acute in vitro, and subchronic in vivo murine model of PAC-induced peripheral neuropathy (PIPN)? (II.) How is affected spinal inhibitory synaptic control...
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Modulation of synaptic transmission in the development of painful states
Slepička, Jakub ; Paleček, Jiří (advisor) ; Hejnová, Lucie (referee)
My thesis introduces the topic of nociceptive signalisation and processes involved in the formation and spreading of neuropathic pain. This study focuses on the mechanisms of nociceptive synaptic transmission mechanisms in the level of spinal dorsal horn and its modulation by paclitaxel, a chemotherapeutic drug inducing neuropathic changes. The attention is put especially on the possibility of glial activity participation in paclitaxel side effects. This idea stems from the existing hypothesis of the functional connection between TLR4 and TRPV1 receptor activity. TRPV1 is well known for its participation in chemical, thermal and nociceptive sensory transmission. Minocycline antibiotic is considered as an inhibitor of microglial activation therefore it was used for blocking neuroinflammation. The experimental part is comparing an impact of substances applied to the model of tachyphylaxis used for monitoring of nociceptive transmission changes according to decreasing activity of TRPV1 receptors. Electrophysiological recording of miniature excitatory postsynaptic currents from neurons in the Rexed laminae I. and II. of spinal dorsal horn was used. The results of my measurements show that minocycline is able to suppress acute effects of paclitaxel application in vitro if the spinal slice is incubated...
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The role of nociceptive synaptic transmission modulation at the spinal cord level in different pain states
Adámek, Pavel ; Paleček, Jiří (advisor) ; Vaculín, Šimon (referee) ; Vlachová, Viktorie (referee)
Pain is a common symptom of many clinical syndromes and diseases. In particular, the treatment of neuropathic pain represents a serious public health issue because currently available analgesia is ineffective in many cases or it has adverse effects. Treatment of pain-related suffering requires knowledge of how pain signals are initially generated and subsequently transmitted by the nervous system. A nociceptive system plays a key role in this process of encoding and transmission of pain signals. Modulation of the nociceptive synaptic transmission in the spinal cord dorsal horn represents an important mechanism in the development and maintenance of different pathological pain states. This doctoral thesis has aimed to investigate and clarify some of the mechanisms involved in the modulation of the spinal nociceptive processing in different pain states. The main attention was paid to study the following issues: (I.) Which is the role of Transient Receptor Potential Vanilloid type 1 channels (TRPV1), Toll-Like Receptors 4 (TLR4), and phosphatidylinositol 3-kinase (PI3K) in the development of neuropathic pain induced by paclitaxel (PAC) chemotherapy in acute in vitro, and subchronic in vivo murine model of PAC-induced peripheral neuropathy (PIPN)? (II.) How is affected spinal inhibitory synaptic control...
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