Global ETD Search

41	Der Einfluss von Clozapin, N-Desmethylclozapin und Chlorpromazin auf die in-vitro-Produktion von Thromboxan Schmidt, Renate Luise 07 July 2014 (has links) Die Hypothese, dass das AP Clozapin, ebenso wie dessen Metabolit NDMC die Produktion von TxA2 beeinfluss könnten, stellten wir nach ausführlicher Literaturrecherche auf. Letztere zeigte, dass bereits beim ersten AP CPZ eine reduzierende Wirkung auf die TxA2-Produktion nachgewiesen werden konnte. TxA2 und die Aktivierung seines Rezeptors modulieren Vasokonstriktion und Thrombozytenaggregation. Weiterhin nehmen sie Einfluss auf dopaminerge und serotonerge Signalwege. In der Pathophysiologie der Schizophrenie spielen eben diese eine bedeutende Rolle und stellen somit Zielstrukturen für APs dar. Um die Konzentration von TxB2, dem Metaboliten des instabilen Moleküls TxA2 in stimulierten und unstimulierten Blutproben 10 gesunder Probandinnen zu messen, verwendeten wir ein Vollblutverfahren. Um signifikante Ergebnisse zu erhalten, stimulierten wir die Proben mit TSST-1 oder dem monoklonalen Antikörper OKT3 (Muromonab-CD3), der gegen das Oberflächenantigen CD3 gerichtet ist, kombiniert mit dem monoklonalen Antikörper 5C3, der mit dem Protein CD40 interagiert und es stimuliert. Weiterhin versetzten wir das Blut mit den APs CPZ, Clozapin oder NDMC in einer von vier verschiedenen Konzentrationen. Außerdem wurden die Thromboxanspiegel im Blut ohne Zusatz von APs unter verschiedenen Stimulationskonditionen gemessen. Durch den Zusatz von Clozapin in den verschiedenen Konzentrationen kam es zu einer signifikanten (p<0.05) Verringerung der TxB2-Produktion in den mit TSST-1 und ebenso in den mit OKT3/5C3 versetzen Proben, was wir im Rahmen unserer Studie feststellen konnten. Weiterhin konnten wir zeigen, dass CPZ in sehr niedriger Konzentration die TxB2-Spiegel im unstimulierten und im mit TSST-1 stimulierten Blut reduziert. Daraus lässt sich schlussfolgern, dass Clozapin, NDMC und CPZ auch über eine Modulation der TxA2- und TxB2-Produktion das Neurotransmittersystem beeinflussen könnten. Auch typische Nebenwirkungen der AP, wie zum Beispiel die orthostatische Hypotension, könnten aus den Veränderungen der TxA2- und TxB2-Konzentrationen resultieren. info:eu-repo/classification/ddc/610 ddc:610
42	Microstructural elucidation of self-emulsifying system: effect of chemical structure Patil, S.S., Venugopal, E., Bhat, S., Mahadik, K.R., Paradkar, Anant R January 2012 (has links) No / PURPOSE: Self-emulsifying systems (SES) emulsify spontaneously to produce fine oil-in-water emulsion when introduced into aqueous phase. The self-emulsification process plays an important role during formation of emulsion. The objective of current work was to understand and explore the inner structuration of SES through controlled hydration and further to study the influence of additive on the same which ultimately governs performance of final formulation in terms of droplet size. METHODS: Droplet size of final formulations containing structural analogues of ibuprofen was determined. Microstructural properties of intermediate hydrated regimes of SES were investigated using techniques such as small angle X-ray scattering, differential scanning calorimetry and rheology. RESULTS: The current work established inverse relationship between droplet size of the formulations containing structural analogues of ibuprofen and their Log P values. Microstructural analysis of intermediate hydrated regimes of the prepared samples showed formation of local lamellar structure. Structural analogues of ibuprofen significantly altered microstructure of lamellae which was well correlated with the droplet size of final formulations. In vitro drug release study showed increase in dissolution rate of lipophillic drugs when formulated as SES. CONCLUSION: The current work emphasizes the fact that tailor-made formulations can be prepared by controlling the properties of intermediate regimes. Analgesics Calorimetry Diffusion Emulsions Ibuprofen Oils Particle size Pharmaceutical vehicles Rheology Scattering Solubility Surface-active agents Water X-Ray diffraction REF 2014 Non-Narcotic Administration & dosage Chemistry Differential scanning Flurbiprofen Analogs & derivatives Ketoprofen Lamellar structure Small angle
43	The prostamide-related glaucoma therapy, bimatoprost, offers a novel approach for treating scalp alopecias Khidhir, K. G., Woodward, D. F., Farjo, N. P., Farjo, B. K., Tang, E. S., Wang, J. W., Picksley, S. M., Randall, V. A. January 2013 (has links) Balding causes widespread psychological distress but is poorly controlled. The commonest treatment, minoxidil, was originally an antihypertensive drug that promoted unwanted hair. We hypothesized that another serendipitous discovery, increased eyelash growth side-effects of prostamide F(2alpha)-related eyedrops for glaucoma, may be relevant for scalp alopecias. Eyelash hairs and follicles are highly specialized and remain unaffected by androgens that inhibit scalp follicles and stimulate many others. Therefore, we investigated whether non-eyelash follicles could respond to bimatoprost, a prostamide F(2alpha) analog recently licensed for eyelash hypotrichosis. Bimatoprost, at pharmacologically selective concentrations, increased hair synthesis in scalp follicle organ culture and advanced mouse pelage hair regrowth in vivo compared to vehicle alone. A prostamide receptor antagonist blocked isolated follicle growth, confirming a direct, receptor-mediated mechanism within follicles; RT-PCR analysis identified 3 relevant receptor genes in scalp follicles in vivo. Receptors were located in the key follicle regulator, the dermal papilla, by analyzing individual follicular structures and immunohistochemistry. Thus, bimatoprost stimulates human scalp follicles in culture and rodent pelage follicles in vivo, mirroring eyelash behavior, and scalp follicles contain bimatoprost-sensitive prostamide receptors in vivo. This highlights a new follicular signaling system and confirms that bimatoprost offers a novel, low-risk therapeutic approach for scalp alopecias. Administration, Topical Adult Animals Base Sequence Female Glaucoma/drug therapy Humans Immunohistochemistry Male Mice Middle Aged Organ Culture Techniques RNA, Messenger/genetics/metabolism effects/genetics/metabolism Scalp/drug effects/metabolism Young Adult REF 2014
44	Enhanced DNA binding capacity on up-regulated epidermal wild-type p53 in vitiligo by H2O2-mediated oxidation: a possible repair mechanism for DNA damage Salem, Mohamed M.A., Shalbaf, Mohammad, Gibbons, Nick C., Chavan, Bhavan, Thornton, M. Julie, Schallreuter, Karin U. January 2009 (has links) No / Vitiligo is characterized by a patchy loss of inherited skin color affecting approximately 0.5% of individuals of all races. Despite the absence of the protecting pigment and the overwhelming evidence for hydrogen peroxide (H(2)O(2))-induced oxidative stress in the entire epidermis of these patients, there is neither increased photodamage/skin aging nor a higher incidence for sun-induced nonmelanoma skin cancer. Here we demonstrate for the first time increased DNA damage via 8-oxoguanine in the skin and plasma in association with epidermal up-regulated phosphorylated/acetylated p53 and high levels of the p53 antagonist p76(MDM2). Short-patch base-excision repair via hOgg1, APE1, and polymerasebeta DNA repair is up-regulated. Overexpression of Bcl-2 and low caspase 3 and cytochrome c levels argue against increased apoptosis in this disease. Moreover, we show the presence of high epidermal peroxynitrite (ONOO(-)) levels via nitrotyrosine together with high nitrated p53 levels. We demonstrate by EMSA that nitration of p53 by ONOO(-) (300 x 10(-6) M) abrogates DNA binding, while H(2)O(2)-oxidized p53 (10(-3) M) enhances DNA binding capacity and prevents ONOO(-)-induced abrogation of DNA binding. Taken together, we add a novel reactive oxygen species to the list of oxidative stress inducers in vitiligo. Moreover, we propose up-regulated wild-type p53 together with p76(MDM2) as major players in the control of DNA damage/repair and prevention of photodamage and nonmelanoma skin cancer in vitiligo. Adult Apoptosis Physiology Ataxia Telangiectasia Mutated Proteins Caspase 3 Biosynthesis Cell cycle proteins Metabolism Cytochromes c DNA DNA damage Drug effects DNA repair DNA-binding proteins Electrophoretic mobility shift assay Epidermis Guanosine Analogs & derivatives Humans Hydrogen peroxide Pharmacology Middle aged Oxidation-reduction Oxidative stress Peroxynitrous acid Protein-Serine-Threonine Kinases Proto-Oncogene Proteins c-bcl-2 Proto-Oncogene Proteins c-mdm2 Tumor Suppressor Protein p53 Tumor Suppressor Proteins Up-Regulation Vitiligo p300-CBP Transcription Factors REF 2014

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