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Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüft Abweichender Titel laut Übersetzung des Verfassers/der Verfasserin Karl-Franzens-Universität Graz, Diplomarbeit, 2019 (VLID)4584316

Background: The use of transcranial laser or light-emitting diode (LED) therapy in the treatment of different neurological diseases is attracting increasing attention. The main goal of this study was to investigate different kinds of scientifically and commercially available laser (yellow, red, and infrared) and LED stimulation systems for the first time using a chick embryo model under a fixed human cadaver (scalp and/or skull) and without this anatomical preparation. Methods: In the present study, the extra-embryonic vasculature of a 1-week-old chick embryo chorioallantoic membrane (CAM) was investigated. For stimulation, four different systems were used (infrared LED and yellow, red, and infrared laser). Four measurement periods were compared: before stimulation, immediately after stimulation onset, immediately after the 10-min stimulation was turned off, and 6 min after stimulation had ended. Special image processing programs developed at the Beijing University of Science and Technology were used for data analysis. Results: The different kinds of laser induced different effects, e.g. the direct stimulation with yellow laser led to initial vasoconstriction (-17%), whereas yellow laser stimulation through a human skull resulted in an increase in blood volume. These effects could only be observed after mathematical processing of the images. Conclusion: After intensive basic research (e.g. CAM model), transcranial laser stimulation may open up new therapies for lifestyle-related diseases such as stroke, dementia, Alzheimer's or possibly Parkinson's disease.

Wahrend uber die Pathophysiologie des Alterungsprozesses gut gesicherte Erkenntnisse vorliegen, dessen molekularbiologische Grundlagen weitgehend entschlusselt sind, gibt es bis dato noch keine abgesicherte interventionelle Masnahme, fur die eine Lebensverlangerung wirklich relevant ware. Wahrend Wachstum und Entwicklung auf genetischen Programmen basieren, stellt der Alterungsprozess lediglich die Anhaufung von zufalligen Schaden und Storungen dar und nicht einen spezifischen Mechanismus. Unter Altern im biologischen Wortsinn wird jene, teils endo-, teils exogen verursachte, irreversible Veranderung auf Zell-, Organ- und Organismusebene verstanden, dem die Individuen aller Arten lebenslang unterliegen, letztlich begrenzt durch wahrscheinlich genetisch programmierte, unterschiedlich lange maximale Lebensspannen.

Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüft Abweichender Titel laut Übersetzung des Verfassers/der Verfasserin Karl-Franzens-Universität Graz, Univ., Diplomarbeit, 2016

Experiences with long-term intraspinal infusion of opioid drugs using the new implantable medication pump VIP 30 in patients with chronic non-malignant pain are reported. During a 19-month period 10 patients with chronic pain - mainly mixed nociceptive-neuropathic pain -underwent implantation of the medication pump for long-term treatment. The mean follow-up period was 9.5 months. Pain relief was classified as very good in 22.2 %, good in 44.4 %, moderate in 22.2% and poor in 11. 1%. In 88.9% of the cases the patients stated they would undergo the same procedure again. Technical problems (catheter dislocation) developed in 1/10 patients could be surgically corrected. One pump including catheter was explanted because of an infected seroma within the pocket area. Long-term intrathecal application of opioids with the VIP 30 pumps is an effective and safe treatment in patients with chronic non-malignant pain.

In order to assess possible renal mechanisms causing the as yet unexplained side-effects of peripheral edema, weight gain and swollen limbs seen during the chronic administration of opioids in patients, a rat study was designed, mimicking a constant infusion (24 h) of morphine (CAS 57-27-2) using subcutaneous drug delivery device systems. Subcutaneous (s.c.) morphine infusions (0, 10, 30 mg/kg body weight/24 h) have been administered using implantable mini-osmotic pumps with a delivery rate of 10 µl/h. In addition, s.c. implantable inulin/PAH clearance depot systems were used in order to measure renal functions such as glomerular filtration rate (GFR = inulin clearance), renal plasma flow (RPF = PAH clearance), creatinine clearance and urea clearance in the conscious rat. Compared to controls, morphine caused an increase in PAH clearance, creatinine clearance (both dose dependent), urea clearance (higher dose), body weight, and urine potassium concentration (both groups). Urine minute volume was reduced in the 10 mg morphine group, a dose dependent highly significant decrease of urine sodium in the 30 mg morphine group compared to controls and a significant decrease compared to the 10 mg group could be found. Serum sodium was highly significant and food uptake was significantly increased in the 30 mg group compared to controls. The histological examination of kidneys revealed no differences among the various groups. These data indicate a role of the kidney in the induction of peripheral edema during permanent morphine administration.

The erythroleukemia cell lines K562 and human erythroleukemia (HEL) are established models to study erythroid and megakaryocytic differentiation in vitro. In this study, we show that the alpha1-adrenergic antagonists, benoxathian and prazosin, inhibit the proliferation and induce apoptosis in K562 and HEL cells. Furthermore, both tested substances induced the expression of the megakaryocytic marker CD41a, whereas the expression of the erythroid marker glycophorin-a was decreased or unchanged. Even though the expression of differentiation markers was similar after benoxathian and prazosin treatment in both cell lines, endomitosis of erythroleukemia cells was observed only after prazosin treatment. So far, benoxathian and prazosin are the first described extracellular ligands, which cause megakaryocytic differentiation in K562 and HEL cells. In summary, these results indicate a possible role of alpha1-adrenergic receptor signaling in the regulation of erythroid and megakaryocytic differentiation, even though the receptor dependence of the observed effects needs further investigation.

Medullary thyroid carcinoma (MTC) is a tumor associated with poor prognosis since it exhibits high resistance against conventional cancer therapy. Recent studies have shown that quinazolines exhibit a pro-apoptotic effect on malignant cells. The aim of the present study was to elucidate whether MTC cells are affected by quinazolines, in particular prazosin.Proliferation, apoptosis and cell morphology of the MTC cell line TT were analyzed by WST-1 assay, caspase 3/7 activation tests and microscopy. Fibroblasts were used as control for non-malignant cells.Prazosin potently inhibited the growth of TT cells, induced apoptosis and caused vacuolization, as well as needle-like filopodia. Fibroblasts were affected by prazosin in the same way as MTC cells.MTC cells are responsive to prazosin treatment similar to other malignancies. The fact that fibroblasts also respond to prazosin further highlights the importance to identify the unknown pro-apoptotic target of quinazolines.

vorgelegt von Thomas Sadjak Graz, Univ., Dipl.-Arb., 2015

Studien zeigten, dass Clonidin — intraartikular ins Kniegelenk verabreicht — eine periphere Analgesie bewirkt. Wir untersuchten, ob es durch eine solche Injektion zur Resorption und zum Aufbau einer messbaren systemischen Konzentration von Clonidin kommt. Randomisiert, placebokontrolliert und doppelblind wurde die Studie an arthroskopischen Eingriffen im Kniegelenk durchgefuhrt. Gruppe I der Patienten erhielt Clonidin 150 μg intraartikular, Gruppe II Clonidin 150 μg i.v. und Gruppe III Placebo. Zur postoperativen Schmerztherapie diente Morphinhydochlorid i.v.. Schmerzscore und Nebenwirkungen wurden uber 24 h aufgezeichnet. Es wurden 69 Patienten in die Studie aufgenommen. Zwischen den 3 Gruppen waren keine Unterschiede bei den demographischen Daten: Dauer von Op. und Anasthesie, Diagnosen und Operationen. Der Schmerzscore in Ruhe war signifikant niedriger in Gruppe I. In den ersten 20 min war die systemisch gemessene Konzentration von Clonidin i.v. signifikant hoher als bei intraartikularer Clonidin-Verabreichung. Clonidin intraartikular bewirkt nach arthroskopischen Eingriffen eine postoperative Analgesie, die auf eine periphere Wirkung zuruckzufuhren ist.

Stricter emission regulations, the threat of global warming, and the dependence of our society on fossil fuels have lead to activities around the world to find solutions for a sustainable future for our mobile and energy-dependent society. At the forefront of such activities and seen as a pioneer in this field is the California Fuel Cell Partnership (CaFCP) (www.cafcp.org).This article will examine the activities of the CaFCP, with an emphasis on the role played by one of its members, DaimlerChrysler.

Patients with moderate to severe pain were treated with buprenorphine patches in one of 3 concentrations: 35 micrograms/h, 52.5 micrograms/h and 70 micrograms/h (= 0.8 mg/d, 1.2 mg/d and 1.6 mg/d respectively). The aim of this review was to assess the efficacy and tolerability of this transdermal system (TDS) in patients with chronic pain. A total of 445 patients were included in 3 double-blinded studies. The dosage titration with buprenorphine patches followed pretreatment with buprenorphine sublingual tablets, higher doses of weak opioids (level 2 substances), low dose morphine (level 3) or other analgesics. Patients with chronic tumour or non-tumour pain were recruited for these studies and treated with buprenorphine patches or placebo for 6 to 15 days. All patients were offered, in addition, buprenorphine sublingual tablets to be taken as required for supplementary pain relief. Pain intensity, analgesia, consumption of buprenorphine sublingual tablets and sleep duration were all assessed. All patients in the double-blinded studies were between the ages of 22 and 88. 249 patients suffered from tumour pain and 196 patients suffered from non-tumour pain. To examine long-term efficacy and tolerability of the transdermal system, treatment was expanded, if the patients were interested in participating in an open-label-study. In all 3 studies, the number of patients with moderate, severe and very severe pain increased in the placebo-patch treated group, while the patients in the buprenorphine transdermal system treated group had a greater incidence of mild or no pain. A further benefit in the buprenorphine transdermal system treated group was evidenced by a great number of patients with a daily sleep duration of more than 6 hours compared to the placebo group--an indicator of greater well-being. The systemic side-effects were typically opioid in nature and rare and usually only mild. Of particular note was the very low incidence of constipation in only 5.3% of cases. Dermatological reactions to the patches were only rarely encountered. The dermatological reactions consisted mainly of erythema and pruritus with a mild to moderate extent. Half the cases of erythema and more than on third of the cases of pruritus were spontaneously reversible. More than half the patients (53.7%) in the double blind studies wished to continued treatment with buprenorphine transdermal system. These results demonstrate that buprenorphine patches achieved a very good analgesic effect in all 3 studies and that in particular with respect to the quality of life of the patient these patches offer an exceptional alternative to other conventional therapies.

Fragestellung. Lornoxicam ist ein Nichtopioidanalgetikum und gehort zu der Gruppe der Oxicame.Das Ziel der Studie war es festzustellen, ob Lornoxicam einen analgetischen praemptiven Effekt aufweist. Methodik. Die Untersuchung erfolgte doppelblind randomisiert bei 66 Patienten mit gynakologischen Operationen in 3 Gruppen. Gruppe I erhielt 8mg Lornoxicam praoperativ i.v. und dann alle 8 h Bolus von Lornoxicam 8mg,Gesamtdosis 24 mg in den ersten 24 h.Gruppe II erhielt vor Operationsende 8 mg Lornoxicam als Bolus und dann 8mg Lornoxicam alle 8 h,Gesamtdosis 24 mg Lornoxicam in den ersten 24 h.Gruppe III erhielt Placebo vor und nach der Operation und uber 24 h. Die Wirksamkeit wurde postoperativ anhand einer visuellen Analogskala (Ruhe,Belastung), anhand des gesamten Analgetikaverbrauches Morphinhydrochlorid innerhalb der ersten 24 h postoperativ gemessen.Vitalparameter und Nebenwirkungen wurden dokumentiert. Ergebnisse. Gruppe I und Gruppe II zeigen zu gewissen Zeitpunkten signifikant geringere Schmerzscores als Gruppe III.Gruppe I zeigt auch einen schwach signifikant geringeren postoperativen Analgetikaverbrauch von Morphinhydrochlorid verglichen mit den Gruppen II und III. Schlussfolgerung. Lornoxicam praemptiv verabreicht scheint zu einer verbesserten Analgesiequalitat postoperativ und zu einer Verringerung des postoperativen Analgetikaverbrauches zu fuhren.

Clonidine ((2-[2,6-dichlorophenyl]amino)-2-imidazoline) preferentially stimulates central alpha(2)-adrenoceptors, which leads to inhibition of sympathetic tone, resulting in a lowering of arterial pressure and of heart rate. Additionally, many other desirable and undesirable effects are described, including analgesia, sedation and withdrawal reactions, which consist of a sudden rise in arterial pressure, nervousness, agitation and increased heart rate. The present study has the goal to develop a simple and effective method for the analysis of trace amounts of clonidine in human blood serum. Special emphasis is necessary to make application of electron impact ionization and separation of the analyte fragments in a quadruple mass analyzer suitable. The procedure comprises solid phase extraction followed by formation of the pentafluorobenzyl derivative. Further purification is achieved by phase transfer extraction into an acidic aqueous solution succeeded by re-extraction into dichloromethane. After solvent exchange, an aliquot is injected into the gas chromatograph equipped with a DB5 MS capillary column and a mass spectrometric detector. Chromatograms are recorded in single ion monitoring mode. Quantification is accomplished by internal standardization with moxonidine [4-chloro-5-(2-imidazolin-2-yl-amino)-6-methoxy-2-methylpyridine].

Medullary thyroid carcinoma (MTC) originates from the C‑cells of the thyroid and is not sensitive to radiation or chemotherapy. Therefore, surgical removal of the tumor tissue in its entirety is the only curative treatment for MTC. The present study aimed to examine the potential mechanisms of action of extracts of Trailliaedoxa gracilis (TG; WW Smith & Forrest), a plant from the province of Sichuan, China, and of ursolic acid (UA), a pentacyclic triterpen present in TG, on the MTC‑SK MTC cell line. A total of 13 TG fractions and UA were examined in vitro for their effects on cell morphology, cell number, proliferation and rates of apoptosis. Reverse transcription‑quantitative polymerase chain reaction of nuclear factor‑κB essential modifier (NEMO) was performed to delineate the role of the apoptotic pathway following treatment with UA. TG and UA were examined in vivo in xenotransplanted MTC‑bearing severe combined immunodeficient mice. The TG fractions exhibited antiproliferative effects, with inhibition of mitochondrial activity in the tumor cells at concentrations, which caused no impairment of the normal control cells. The apoptotic rates of the MTC‑SK cells treated with the TG fractions and UA were determined, in which no marked tumor inhibition was observed in the treated MTC‑mice, and no change in the expression of NEMO was detected in the treated MTC‑SK cells. The observation of early‑onset activation of caspase 8 suggested that the responsible factor was linked to NEMO, an anti‑apoptotic protein. However, no differences in the mRNA transcription levels of NEMO were detected in MTC‑SK cells treated with UA, suggesting that this protein was not associated with the signal transducer and activator of transcription 3 pathway.

Background It has previously been found that in cardiac risk patients undergoing non-cardiac surgery post-operative cardiac complications are correlated with high post-operative serum levels of troponin T (TNT) and troponin I (TNI). We investigated whether perioperative changes in the release of free (fCAs) and conjugated catecholamines (cCAs) correlate with the increased serum level of TN (TN upward arrow). Materials and methods Plasma levels of CAs were determined in 28 patients at risk for or with definite coronary artery disease. Blood sampling was performed in the morning on the day before surgery, on the day of surgery before induction of anaesthesia and until the fifth post-operative day for measurement of CAs by high-performance liquid chromatography. Results The plasma concentrations of free and conjugated noradrenaline (fNA and cNA) as well as of free and conjugated adrenaline (fA and cA) were increased significantly in TN upward arrow patients post-operatively. The plasma levels of free as well as of conjugated NA and A in TN upward arrow patients were significantly higher than in TN0 patients over the whole post-operative period. Conclusion This study demonstrates that increased post-operative release of fNA and fA as well as of cNA and cA correlates with high post-operative serum levels of troponins in cardiac risk patients undergoing non-cardiac surgery.

Fragestellung: Aufgrund des zentralen analgetischen Wirkmechanismus von Ketoprofen durch die Kynurensaure erwarteten wir, einen analgetischen praemptiven Effekt nach dem Design von Breivik/Stubhaug zu finden. Methoden: Die Untersuchung erfolgte doppelblind randomisiert bei 81 Patientinnen mit gynakologischen Operationen in drei Gruppen: Gruppe I erhielt 100 mg Ketoprofen praoperativ intravenos und dann 12 mg/h kontinuierlich wahrend der Operation und uber 48 h postoperativ. Gruppe II erhielt vor Operationsende 100 mg Ketoprofen als Bolus und dann kontinuierlich Ketoprofen mit 12 mg/h uber 48 h postoperativ. Gruppe III erhielt Plazebo wahrend und nach der Operation uber 48 h. Die Wirksamkeit wurde postoperativ anhand einer visuellen Analogskala (Ruhe, Belastung) und anhand des gesamten Analgetikaverbrauchs (PCA-Piritramid) innerhalb der ersten 48 h postoperativ gemessen. Weiters wurde der Zeitpunkt der ersten Analgetikaanforderung aufgezeichnet. Vitalparameter und Nebenwirkungen wurden dokumentiert. Ergebnisse: Der Zeitpunkt der ersten Analgetikanforderung in Gruppe I war signifikant spater als in Gruppe II und III. Der postoperative Analgetikaverbrauch kumulativ in den ersten 24 h war signifikant niedriger in Gruppe I als in Gruppe III. Die Kombination eines Opioids mit einem Nichtopioid erzielte einen geringeren Schmerzscore (VAS in Ruhe und Belastung) in Gruppe I und II als in Gruppe III (Plazebo). Schlusfolgerung: Wir konnten mit unserer Studie einen praemptiven Effekt mit Ketoprofen nach dem Design von Breivik/Stubhaug zeigen.

Neuroendocrine tumors are relatively insensitive to radiation therapy, as well as chemotherapy. Thus, new approaches for alternative therapies are needed. We found that glutamate receptor antagonists are capable of suppressing tumor growth and cell activity of different peripheral malignancies. In the present article we review scientific literature in this field of science. Subtype-specific, non-competitive, metabotropic glutamate receptor-1 antagonists differently suppressed the growth and metabolic cell activity of one human medullary thyroid carcinoma cell line, as well as of four different human midgut neuroendocrine tumor cell lines. Furthermore, PCR analyses revealed that this subtype of glutamate receptor is expressed in these cell lines. These first results indicate that specific metabotropic glutamate receptor antagonists suppress the proliferation and cell activity of neuroendocrine tumor cells, which makes them possible targets in cancer therapy.

Neuroendocrine tumors respond poorly to radiation and conventional chemotherapy, hence surgical removal of the neoplastic tissue is still the most effective way of treatment. In an attempt to find new therapeutic plant extracts of Christia vespertilionis (CV) their antitumor potential in human medullary thyroid carcinoma (MTC) and human small intestinal neuroendocrine tumor (SI-NET) cell lines were tested. Proliferation and viability were analyzed using cell counting and WST-1 assay. Apoptosis was determined by microscopy, luminescence assays for caspases 3/7, and expression studies of apoptosis-related genes. CV extracts showed antiproliferative and proapoptotic effects in all MTC and SI-NET cell lines, whereby high growth inhibition was observed by treatment with the ethylacetate-extracts (CV-45) in tumor cell lines but not in normal human fibroblasts. Furthermore CV-45 treatment resulted in alterations of gene expression of PDCD5, MTDH and TNFRSF10b in MTC as well as in SI-NET cells. The results indicate that Christia vespertilionis could serve as an anticancer therapeutic for treatment of neuroendocrine tumors.

MSCs (mesenchymal stem cells) are planned foruse in regenerative medicine to offset age-dependent alterations. However, MSCs are affected by replicative senescence associated with decreasing proliferation potential, telomere shortening and DNA damage during in vitro propagation. To monitor in vitro senescence, we have assessed the integrity of DNA by the alkaline comet assay. For optimization of the comet assay we have enhanced the stability of comet slides in liquid and minimized the background noise of the method by improving adhesion of agarose gels on the comet slides and concentrating cells on a defined small area on the slides. The modifications of the slide preparation increase the overall efficiency and reproducibility of the comet assay and minimize the image capture and storage. DNA damage of human MSCs during in vitro cultivation increased with time, as assessed by the comet assay, which therefore offers a fast and easy screening tool in future efforts to minimize replicative senescence of MSCs in vitro.

The major excitatory neurotransmitter glutamate is also found in the periphery in an increasing number of nonexcitable cells. In line with this it became apparent that glutamate can regulate a broad array of peripheral biological responses, as well. Of particular interest is the discovery that glutamate receptor reactive reagents can influence tumor biology. However, the knowledge of glutamate signaling in peripheral tissues is still incomplete and, in the case of head and neck areas, is almost lacking. The roles of glutamate signaling pathways in these regions are manifold and include orofacial pain, periodontal bone production, skin and airway inflammation, as well as salivation. Furthermore, the interrelations between glutamate and cancers in the oral cavity, thyroid gland, and other regions are discussed. In summary, this review shall strengthen the view that glutamate receptor reagents may also be promising targets for novel therapeutic concepts suitable for a number of diseases in peripheral tissues. The contents of this review cover the following sections: Introduction; The "Glutamate System"; The Taste of Glutamate; Glutamate Signaling in Dental Regions; Glutamate Signaling in Head and Neck Areas; Glutamate Signaling in Head and Neck Cancer; A Brief Overview of Glutamate Signaling in Other Cancers; and Conclusion.

Preliminary data showed that α1-adrenergic antagonists induce apoptosis and a switch towards megakaryocytic differentiation in human erythroleukemia cells. To test the hypothesis whether survival and differentiation of erythroleukemia cells are under control of α1-adrenergic signalling, we examined α1-adrenoceptor expression of erythroleukemia cells and compared the in vitro effects of α-adrenergic antagonists with those of agonists. We discovered that α1-adrenergic agonists suppress both erythroid differentiation and growth of erythroleukemia cells concomitant with lipofuscin accumulation, autophagy and necrotic cell death. α1-adrenergic agonists also inhibit the in vitro growth of physiologic hematopoietic progenitors obtained from umbilical cord blood with high selectivity for the erythroid lineage. Interestingly, the observed effects could not be related to α1-adrenoceptors, even though agonists and antagonists displayed opposing effects regarding cellular growth and differentiation of erythroleukemia cells. Our data suggest that the effects of α1-adrenergic drugs are related to a non-adrenoceptor binding site, controlling the fate of erythroid progenitor cells towards differentiation and cell death. Since the observed effects are not mediated through adrenoceptors, the physiologic relevance of our data remains unclear, so far. Nevertheless, the identification of the still unknown binding site(s) might disclose new insights into regulation of erythroid differentiation and cell death.