@article{EvdokimovFrankKlitschetal.2019,
  author    = {Evdokimov, Dimitar and Frank, Johanna and Klitsch, Alexander and Unterecker, Stefan and Warrings, Bodo and Serra, Jordi and Papagianni, Aikaterini and Saffer, Nadine and Meyer zu Altenschildesche, Caren and Kampik, Daniel and Malik, Rayaz A. and Sommer, Claudia and {\"U}ceyler, Nurcan},
  title     = {Reduction of skin innervation is associated with a severe fibromyalgia phenotype},
  series = {Annals of Neurology},
  volume    = {86},
  journal   = {Annals of Neurology},
  number    = {4},
  doi       = {10.1002/ana.25565},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206168},
  pages     = {504-516},
  year      = {2019},
  abstract  = {Objective: To assess patterns and impact of small nerve fiber dysfunction and pathology in patients with fibromyalgia syndrome (FMS). Methods: One hundred seventeen women with FMS underwent neurological examination, questionnaire assessment, neurophysiology assessment, and small fiber tests: skin punch biopsy, corneal confocal microscopy, microneurography, quantitative sensory testing including C-tactile afferents, and pain-related evoked potentials. Data were compared with those of women with major depressive disorder and chronic widespread pain (MD-P) and healthy women. Results: Intraepidermal nerve fiber density (IENFD) was reduced at different biopsy sites in 63\% of FMS patients (MDP: 10\%, controls: 18\%; p < 0.001 for each). We found 4 patterns of skin innervation in FMS: normal, distally reduced, proximally reduced, and both distally and proximally reduced (p < 0.01 for each compared to controls). Microneurography revealed initial activity-dependent acceleration of conduction velocity upon low frequencies of stimulation in 1A fibers, besides 1B fiber spontaneous activity and mechanical sensitization in FMS patients. FMS patients had elevated warm detection thresholds (p < 0.01), impaired C-tactile afferents (p < 0.05), and reduced amplitudes (p < 0.001) of pain-related evoked potentials compared to controls. Compared to FMS patients with normal skin innervation, those with generalized IENFD reduction had higher pain intensity and impairment due to pain, higher disease burden, more stabbing pain and paresthesias, and more anxiety (p < 0.05 for each). FMS patients with generalized IENFD reduction also had lower corneal nerve fiber density (p < 0.01) and length (p < 0.05). Interpretation: The extent of small fiber pathology is related to symptom severity in FMS. This knowledge may have implications for the diagnostic classification and treatment of patients with FMS.},
  language  = {en}
}
@article{OderUeceylerLiuetal.2016,
  author    = {Oder, Daniel and {\"U}ceyler, Nurcan and Liu, Dan and Hu, Kai and Petritsch, Bernhard and Sommer, Claudia and Ertl, Georg and Wanner, Christoph and Nordbeck, Peter},
  title     = {Organ manifestations and long-term outcome of Fabry disease in patients with the GLA haplotype D313Y},
  series = {BMJ Open},
  volume    = {6},
  journal   = {BMJ Open},
  doi       = {10.1136/bmjopen-2015-010422},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161210},
  pages     = {e010422},
  year      = {2016},
  abstract  = {Objectives: The severity of Fabry disease is dependent on the type of mutation in the α-galactosidase A (AgalA) encoding gene (GLA). This study focused on the impact of the GLA haplotype D313Y on long-term organ involvement and function. Setting and participants: In this monocentric study, all participants presenting with the D313Y haplotype between 2001 and 2015 were comprehensively clinically investigated at baseline and during a 4-year follow-up if available. Five females and one male were included. Primary and secondary outcome measures: Cardiac, nephrological, neurological, laboratory and quality of life data. Results: AgalA enzyme activity in leucocytes (0.3±0.9 nmol/min/mg protein (mean±SD)) and serum lyso-Gb3 (0.6±0.3 ng/mL at baseline) were in normal range in all patients. Cardiac morphology and function were normal (left-ventricular (LV) ejection fraction 66±8\%; interventricular septum 7.7±1.4 mm; LV posterior wall 7.5±1.4 mm; normalised LV mass in MRI 52±9 g/m2; LV global longitudinal strain -21.6±1.9\%) and there were no signs of myocardial fibrosis in cardiac MRI. Cardiospecific biomarkers were also in normal range. Renal function was not impaired (estimated glomerular filtration rate MDRD 103±15 mL/min; serum-creatinine 0.75±0.07 mg/dL; cystatin-c 0.71±0.12 mg/L). One female patient (also carrying a Factor V Leiden mutation) had a transitory ischaemic attack. One patient showed white matter lesions in brain MRI, but none had Fabry-associated pain attacks, pain crises, evoked pain or permanent pain. Health-related quality of life analysis revealed a reduction in individual well-being. At long-term follow-up after 4 years, no significant change was seen in any parameter. Conclusions: The results of the current study suggest that the D313Y genotype does not lead to severe organ manifestations as seen in genotypes known to be causal for classical FD."},
  language  = {en}
}
@article{PoliteiBouhassiraGermainetal.2016,
  author    = {Politei, Juan M. and Bouhassira, Didier and Germain, Dominique P. and Goizet, Cyril and Guerrero-Sola, Antonio and Hilz, Max J. and Hutton, Elspeth J. and Karaa, Amel and Liuori, Rocco and {\"U}ceyler, Nurcan and Zeltzer, Lonnie K. and Burlina, Alessandro},
  title     = {Pain in fabry disease: practical recommendations for diagnosis and treatment},
  series = {CNS Neuroscience \& Therapeutics},
  volume    = {22},
  journal   = {CNS Neuroscience \& Therapeutics},
  number    = {7},
  doi       = {10.1111/cns.12542},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188127},
  pages     = {568-576},
  year      = {2016},
  abstract  = {Aims: Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed. Methods: In 2014, experts met to discuss recent advances on this topic and update clinical guidance. Results: Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Wurzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs. Conclusion: To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications.},
  language  = {en}
}
@article{UeceylerHaeuserSommer2011,
  author    = {{\"U}ceyler, Nurcan and H{\"a}user, Winfried and Sommer, Claudia},
  title     = {Systematic review with meta-analysis: Cytokines in fibromyalgia syndrome},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69189},
  year      = {2011},
  abstract  = {Background: To perform a systematic review and meta-analysis on cytokine levels in patients with fibromyalgia syndrome (FMS). Methods: Through December 2010 we systematically reviewed the databases PubMed, MEDLINE, and PsycINFO and screened the reference lists of 22 review articles for suitable original articles. Original articles investigating cytokines in patients with FMS were included. Data were extracted by two independent authors. Differences of the cytokine levels of FMS patients and controls were summarized by standardized mean differences (SMD) using a random effects model. Study quality was assessed applying methodological scores: modified Center of Evidence Based Medicine, Newcastle-Ottawa-Scale, and W{\"u}rzburg Methodological Quality Score. Results: Twenty-five articles were included investigating 1255 FMS patients and 800 healthy controls. Data of 13/25 studies entered meta-analysis. The overall methodological quality of studies was low. The results of the majority of studies were not comparable because methods, investigated material, and investigated target cytokines differed. Systematic review of the selected 25 articles revealed that FMS patients had higher serum levels of interleukin (IL)-1 receptor antagonist, IL-6, and IL-8, and higher plasma levels of IL-8. Meta-analysis of eligible studies showed that FMS patients had higher plasma IL-6 levels compared to controls (SMD = -0.34 [-0.64, -0.03] 95\% CI; p = 0.03). The majority of investigated cytokines were not different between patients and controls. Conclusions: The pathophysiological role of cytokines in FMS is still unclear. Studies of higher quality and with higher numbers of subjects are needed.},
  subject      = {Fibromyalgie},
  language  = {en}
}
@phdthesis{Ueceyler2003,
  author    = {{\"U}ceyler, Nurcan},
  title     = {Charakterisierung genomischer Polymorphismen und somatischer Mutationen, sowie der Expression der gastrointestinalen Glutathionperoxidase im Rahmen der kolorektalen Karzinogenese},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-5815},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {Das kolorektale Karzinom ist in der westlichen Welt die zweith{\"a}ufigste Todesursache bei M{\"a}nner und Frauen. Wichtige Pathomechanismen der kolorektalen Karzinome konnten in den letzten Jahren aufgedeckt werden. Die Anh{\"a}ufung von genetischen Alterationen spielen sowohl bei sporadischen, als auch bei den heredit{\"a}ren Formen eine wichtige Rolle. Zwei molekulargenetische Hauptwege sind bei der kolorektalen Karzinogenese identifiziert worden: erstens der Tumorsuppressor-Pathway, bei dem es zu Alterationen in Tumorsuppresor- und Onkogenen kommt und zweitens der Mutatior-Pathway, der auf genetischen Alterationen in DNA-mismatch-Reparatur-Genen beruht, die zu einer genetischen Instabilit{\"a}t f{\"u}hren mit einer hohen Mutationsrate in repetitiven DNA-Sequenzen (sog. Mikrosatelliten). Es konnte gezeigt werden, dass oxidativer Stress, der durch die Bildung von H2O2 und anderen reaktiven Sauerstoffspezies (ROS) hervorgerufen wird, zur Entstehung von zellul{\"a}ren und DNA-Sch{\"a}den wie z.B. oxidative Basensch{\"a}den, die ihrerseits u.a. die Entstehung von fixen Punktmutationen, Fragmentation der Desoxiribose und DNA-Strangbr{\"u}che initiieren, f{\"u}hren kann. Diese Ver{\"a}nderungen und auch die Mismatch-Reparatur-Defizienz beg{\"u}nstigen die Tumorprogression im Kolon. Es wird gesch{\"a}tzt, dass durch ROS t{\"a}glich ca.20 000 hits pro Zelle verursacht werden. Es existieren sowohl extrazellul{\"a}re, als auch zellul{\"a}re antioxidative Abwhrsysteme, die Biomolek{\"u}le wie u.a. die DNA vor dem oxidativen Stress sch{\"u}tzen. Unter diesen protektiven Enzymen gibt es neben der Superoxidismutase und der Katalase auch zahlreiche Selenoproteine, die Selenocystein in ihrem aktiven Zentrum tragen. Zu diesen Enzymen, die antioxidative Funktionen wahrnehmen geh{\"o}ren u.a. die Glutathionperoxidase, die Thioredoxinreduktase und das Selenoprotein P. Die Glutathionperoxidase-Familie besteht aus der cytosolischen Glutathioperoxidase (cGPx), der plasmatischen Glutathionperoxidase (pGPx), der gastrointestinalen Glutathionperoxidase (GI-GPx) und der Phospholipid-Hydroperoxid-Glutathionperoxidase (PH-GPx). Diese Enzymfamilie ist an der Reduktion von Hydroperoxiden beteiligt, wobei sie Glutathion als Cofaktor benutzt. Die Thioredoxinreduktase-Familie (TrxR-alpha und Trxr-beta) regeneriert oxidiertes Thioresoxin, das in die DNA-Synthese involviert ist und auch in zellul{\"a}re Redox-Regulationssysteme eingreift und Transkriptionsfaktoren beeinflusst. Das Selenoprotein P, das bis zu 10 Seleocysteinreste pro Molek{\"u}l enth{\"a}lt, baut Peroxinitrit ab, das seinerseits ein starkes Agens bei der Nitrosylation von Biomolek{\"u}len ist. Zus{\"a}tzlich reduziert Selenoprotein P auch Phospholipid-Hydroperoxide, wenn auch weniger effektiv als PH-GPx. Es konnte in Vorarbeiten gezeigt werden, dass Selenoproteine im Gastrointestinaltrakt eine differentielle Expression aufweisen. K{\"u}rzlich konnte in unserer Arbeitsgruppe die inverse mRNA-Expression selnocysteinhaltigen Proteine GI-GPx und Selenoprotein P in kolorektalen Adenomen im Vergleich zur Normalmukosa charakterisiert werden. Dabei zeigte sich eine dramatische Abnahme der Selenoprotein P-Expression, w{\"a}hrend die Expression der GI-GPx signifikant erh{\"o}ht war. Im Rahmen der vorliegenden Arbeit untersuchten wir die Expression der GI-GPx in kolorektalen Karzinomen und Kolonkarzinom-Zelllinien, um auf Ebene der Selenoprotein-kodierenden Gene nach Alterationen zu suchen, die die ver{\"a}nderte Expression mit verursachen k{\"o}nnten.},
  language  = {de}
}