@article{EnigkWagnerSamapatietal.2014,
  author    = {Enigk, Fabian and Wagner, Antje and Samapati, Rudi and Rittner, Heike and Brack, Alexander and Mousa, Shaaban A. and Sch{\"a}fer, Michael and Habazettl, Helmut and Sch{\"a}per, J{\"o}rn},
  title     = {Thoracic epidural anesthesia decreases endotoxin-induced endothelial injury},
  series = {BMC Anesthesiology},
  volume    = {14},
  journal   = {BMC Anesthesiology},
  number    = {23},
  doi       = {10.1186/1471-2253-14-23},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-116787},
  year      = {2014},
  abstract  = {Background: The sympathetic nervous system is considered to modulate the endotoxin-induced activation of immune cells. Here we investigate whether thoracic epidural anesthesia with its regional symapathetic blocking effect alters endotoxin-induced leukocyte-endothelium activation and interaction with subsequent endothelial injury. Methods: Sprague Dawley rats were anesthetized, cannulated and hemodynamically monitored. E. coli lipopolysaccharide (Serotype 0127: B8, 1.5 mg x kg(-1) x h(-1)) or isotonic saline (controls) was infused for 300 minutes. An epidural catheter was inserted for continuous application of lidocaine or normal saline in endotoxemic animals and saline in controls. After 300 minutes we measured catecholamine and cytokine plasma concentrations, adhesion molecule expression, leukocyte adhesion, and intestinal tissue edema. Results: In endotoxemic animals with epidural saline, LPS significantly increased the interleukin-1 beta plasma concentration (48\%), the expression of endothelial adhesion molecules E-selectin (34\%) and ICAM-1 (42\%), and the number of adherent leukocytes (40\%) with an increase in intestinal myeloperoxidase activity (26\%) and tissue edema (75\%) when compared to healthy controls. In endotoxemic animals with epidural infusion of lidocaine the values were similar to those in control animals, while epinephrine plasma concentration was 32\% lower compared to endotoxemic animals with epidural saline. Conclusions: Thoracic epidural anesthesia attenuated the endotoxin-induced increase of IL-1 beta concentration, adhesion molecule expression and leukocyte-adhesion with subsequent endothelial injury. A potential mechanism is the reduction in the plasma concentration of epinephrine.},
  language  = {en}
}
@phdthesis{Sitaru2002,
  author    = {Sitaru, Cassian},
  title     = {Pathogenicity of autoantibodies to type VII collagen from patients with epidermolysis bullosa acquisita},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-3982},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2002},
  abstract  = {Die Epidermolysis bullosa acquisita (EBA) ist eine subepidermal blasenbildende Autoimmundermatose, die mit Autoantik{\"o}rpern gegen Typ VII Kollagen, den Hauptbestandteil der Verankerungsfibrillen der dermo-epidermalen Junktionszone (DEJ), assoziert ist. Bislang war jedoch unklar, ob diese Autoantik{\"o}rper tats{\"a}chlich eine Blasenbildung verursachen. In der vorliegenden Arbeit gingen wir dieser Frage unter Verwendung eines Gefrierschnitt-Modells nach. Nach Koinkubation mit Leukozyten gesunder Spender induzierten 14 von 16 EBA-Seren eine subepidermale Spaltbildung, nicht jedoch die Seren von gesunden Freiwilligen. Die Spaltbildung erfolgte im Bereich der Lamina lucida der DEJ und war von der Rekrutierung und Aktivierung neutrophiler Granulozyten, nicht jedoch von der Pr{\"a}senz mononuklearer Zellen abh{\"a}ngig. Autoantik{\"o}rper von Patienten, die gegen eine rekombinante Form der NC1-Dom{\"a}ne des Typ VII Kollagens affinit{\"a}tsaufgereinigt wurden, und der gegen die NC-1-Dom{\"a}ne gerichtete monoklonale Antik{\"o}rper LH7.2 induzierten ebenfalls eine subepidermale Spaltildung. Dagegen f{\"u}hrte die Pr{\"a}adsorption der EBA-Seren mit rekombinantem Typ VII Kollagen zum Verlust des blaseninduzierenden Potentials. Diese F{\"a}higkeit verloren auch durch Pepsinverdau hergestellte F(ab')2-Fragmente der Patienten-Autoantik{\"o}rper gegen Typ VII Kollagen. Die Ergebnisse dieser Arbeit zeigen, dass Autoantik{\"o}rper gegen Typ VII Kollagen eine Fcg-abh{\"a}ngige Entz{\"u}ndung und subepidermale Spaltbildung in Gefrierschnitten humaner Haut hervorrufen.},
  language  = {en}
}
@article{PritchardFalkLarssonetal.2016,
  author    = {Pritchard, Rory A. and Falk, Lovissa and Larsson, Mathilda and Leinders, Mathias and Sorkin, Linda S.},
  title     = {Different phosphoinositide 3-kinase isoforms mediate carrageenan nociception and inflammation},
  series = {Pain},
  volume    = {157},
  journal   = {Pain},
  number    = {1},
  doi       = {10.1097/j.pain.0000000000000341},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150248},
  pages     = {137-146},
  year      = {2016},
  abstract  = {Phosphoinositide 3-kinases (PI3Ks) participate in signal transduction cascades that can directly activate and sensitize nociceptors and enhance pain transmission. They also play essential roles in chemotaxis and immune cell infiltration leading to inflammation. We wished to determine which PI3K isoforms were involved in each of these processes. Lightly anesthetized rats (isoflurane) were injected subcutaneously with carrageenan in their hind paws. This was preceded by a local injection of 1\% DMSO vehicle or an isoform-specific antagonist to PI3K-α (compound 15-e), -β (TGX221), -δ (Cal-101), or -γ (AS252424). We measured changes in the mechanical pain threshold and spinal c-Fos expression (4 hours after injection) as indices of nociception. Paw volume, plasma extravasation (Evans blue, 0.3 hours after injection), and neutrophil (myeloperoxidase; 1 hour after injection) and macrophage (CD11b+; 4 hour after injection) infiltration into paw tissue were the measured inflammation endpoints. Only PI3K-γ antagonist before treatment reduced the carrageenan-induced pain behavior and spinal expression of c-Fos (P ≤ 0.01). In contrast, pretreatment with PI3K-α, -δ, and-γ antagonists reduced early indices of inflammation. Plasma extravasation PI3K-α (P ≤ 0.05), -δ (P ≤ 0.05), and -γ (P ≤ 0.01), early (0-2 hour) edema -α (P ≤ 0.05), -δ (P ≤ 0.001), and -γ (P ≤ 0.05), and neutrophil infiltration (all P ≤ 0.001) were all reduced compared to vehicle pretreatment. Later (2-4 hour), edema and macrophage infiltration (P ≤ 0.05) were reduced by only the PI3K-δ and -γ isoform antagonists, with the PI3K-δ antagonist having a greater effect on edema. PI3K-β antagonism was ineffective in all paradigms. These data indicate that pain and clinical inflammation are pharmacologically separable and may help to explain clinical conditions in which inflammation naturally wanes or goes into remission, but pain continues unabated.},
  language  = {en}
}
@phdthesis{Heydarian2021,
  author    = {Heydarian, Motaharehsadat},
  title     = {Development of human 3D tissue models for studying \(Neisseria\) \(gonorrhoeae\) infection},
  doi       = {10.25972/OPUS-20496},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204967},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2021},
  abstract  = {Gonorrhea is the second most common sexually transmitted infection worldwide and is caused by Gram-negative, human-specific diplococcus Neisseria gonorrhoeae. It colonizes the mucosal surface of the female reproductive tract and the male urethra. A rapid increase in antibiotic resistance makes gonorrhea a serious threat to public health worldwide. Since N. gonorrhoeae is a human-specific pathogen, animal infection models are not able to recapitulate all the features of infection. Therefore, a realistic in vitro cell culture model is urgently required for studying the gonorrhea infection. In this study, we established and characterized three independent 3D tissue models based on the porcine small intestinal submucosa (SIS) scaffold by co-culturing human dermal fibroblasts with human colorectal carcinoma, endometrial epithelial, and male uroepithelial cells. The histological, immunohistochemical, and ultra-structural analysis showed that the 3D SIS scaffold-based models closely mimic the main characteristics of the site of gonococcal infection in the human host including the formation of epithelial monolayer, underlying connective tissue, mucus production, tight junction (TJ), and microvilli. In addition, functional analysis such as transepithelial electrical resistance (TEER) and barrier permeability indicated high barrier integrity of the cell layer. We infected the established 3D tissue models with different N. gonorrhoeae strains and derivatives presenting various phenotypes regarding adhesion and invasion. The results showed disruption of TJs and growing the interleukins production in response to the infection, which depends on the type of strain and cell. In addition, the 3D tissue models supported bacterial survival, which provided an appropriate in vitro model for long-term infection study. This could be mainly because of the high resilience of the 3D tissue models based on the SIS scaffold to the infection in terms of alteration in permeability, cell destruction, and bacterial transmigration. During gonorrhea infection, a high level of neutrophils migrates to the site of infection. The studies also showed that N. gonorrhoeae can survive or even replicate inside the neutrophils. Therefore, studying the interaction between neutrophils and N. gonorrhoeae is substantially under scrutiny. For this purpose, we generated a 3D tissue model by triple co-culturing of human primary fibroblast cells, human colorectal carcinoma cells, and human umbilical vein endothelial cells. The tissue model was subsequently infected by N. gonorrhoeae. A perfusion-based bioreactor system was employed to recreate blood flow in the side of endothelial cells and consequently study human neutrophils transmigration to the site of infection. We observed neutrophils activation upon the infection. Furthermore, we demonstrated the uptake of N. gonorrhoeae by human neutrophils and reverse transmigration of neutrophils to the basal side carrying N. gonorrhoeae. In summary, the introduced 3D tissue models in this research represent a promising tool to investigate N. gonorrhoeae infections under close-to-natural conditions.},
  subject      = {3D-Gewebemodell},
  language  = {en}
}