Volume 39, Issue 3

Aggressive periodontitis (AgP) is a multifactorial disease with unknown association to the development and function of peripheral lymphocytes. The aim of this study was to elucidate a connection between the periodontal condition in 10 patients with AgP and their potential state of immunodeficiency. Based on full periodontal examination and radiographs, 10 females (ages 29.8±8.62 years) with established diagnosis of aggressive periodontitis were included in this study. Flow cytometric analysis revealed substantial reduction of switched memory B cells (IgM – , IgD – , CD27 + ) in 9 of 10 patients, whereas numbers of naïve, IgM + memory, transitional, and activated B cells were normal. Serum levels of IgM, IgG, IgA, and subclasses were normal. In vitro differentiation of B cells showed normal amounts of secreted IgG and IgA at day 5 of culture. Our results indicate that lowered numbers of switched memory B cells – typically referred to the state of common variable immunodeficiency type I (Freiburg classification) – are unlikely to influence immunoglobulin serum levels or clinical anamnesis of our patients with AgP. Lipopolysaccharide-induced elevated levels of IL-1β and IL-8 and lowering of IL-4 are more likely to trigger a pro-inflammatory circle that attracts lymphocytes to local pockets of aggressive periodontitis.

Zusammenfassung Klinische und experimentelle Untersuchungen haben gezeigt, dass enge Wechselwirkungen zwischen dem essentiellen Spurenelement Zink und dem Immunsystem existieren. Zink beeinflusst die zellulären und humoralen Komponenten sowohl des angeborenen als auch des erworbenen Immunsystems. Zinkmangelzustände beim Menschen sind häufig mit einer gestörten Immunfunktion, also einem sekundären Immundefekt vergesellschaftet. Je nach zugrundeliegender Ursache des Zinkmangels führt eine kontrollierte Zinksubstitution zu einer Normalisierung des Serumzinks, der Zinkhomöostase des Körpers und zu einer Verbesserung der Immunfunktion. In vitro wirken geringe Zinkkonzentrationen stimulierend auf funktionelle Parameter von Immunzellen, höhere Zinkkonzentrationen sind supprimierend oder zytotoxisch für diese Zellen. Arbeiten der letzten Jahre belegen die immunsuppressive Wirkung von Zink in T-Zell-vermittelten autoimmunen Tiermodellen, wie der Experimentellen Autoimmunen Enzephalomyelitis (EAE). Zudem wurde bei einer Reihe von Autoimmunerkrankungen eine Abnahme der Serum-/Plasma-Zinkkonzentrationen nachgewiesen. In zukünftigen klinischen Studien sollte bei diesen Erkrankungen der mögliche Einsatz einer kontrollierten immunsuppressiven Zinktherapie geprüft werden.

Zusammenfassung 2014 wurden in Zusammenarbeit von zwei großen internationalen Expertengruppen Empfehlungen zur Bestimmung von Autoantikörpern gegen zelluläre Antigene, herkömmlich als antinukleäre Antikörper bezeichnet, herausgegeben. Die Empfehlungen wurden in einer 25 Punkte umfassenden Tabelle zusammengefasst und in einer weiteren Tabelle jene Muster beschrieben, die von einem Autoimmunlabor erkannt werden sollten. Internationale Empfehlungen haben für zertifizierte Labore Gültigkeit und erfordern ein Überdenken des analytischen Vorgehens. Die österreichische Arbeitsgruppe für Autoimmundiagnostik (http://www.easi-network.com) hat sich auf einen Konsens geeinigt, wie im deutschen Sprachraum diese 2014 veröffentlichten Empfehlungen umgesetzt werden könnten.

Telaprevir (TVR) was approved by the FDA in May 2011 for the treatment of hepatitis C. This protease inhibitor converts into two diastereomers with significant difference in antiviral activity. Clinical efficacy has been correlated with serum concentrations. Therefore, a sensitive and selective high-performance liquid chromatographic method for the simultaneous determination of both clinically relevant diastereomers of TVR was developed. Linearity ranged from 20 to 10,000 ng/mL. The coefficients of variation were <7.3%, and accuracy was between −4.0 and 5.4%. In 105 clinical samples, both diastereomers of TVR had a high degree of correlation to each other, but concentrations showed a broad range and an increase during therapy.

Background: A commercially available in vitro diagnostics (IVD)-approved mass spectrometric assay for the quantification of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in urine (RECIPE Chemicals+Instruments GmbH, Munich, Germany) was verified for monitoring of recent alcohol intake after transplantation. Methods: For sample preparation, 50 μL of urine sample was mixed with an isotope-labeled internal standard solution. After centrifugation, 5 μL of the supernatant was analyzed by LC-MS/MS in a total run time of 3 min. An API 6500 tandem mass spectrometer (AB SCIEX, Toronto, Canada) combined with a Shimadzu UFLC system (Duisburg, Germany) was applied. Results: The limits of quantification for the commercial assay were 0.07 mg/L for EtG and 0.03 mg/L for EtS in urine. The coefficient of variation for both analytes was lower than 7% (within-day) and 15% (between-days). Accuracy ranged between 101 and 144% for samples from an external quality assurance program. The comparison of the commercial test kit and an established LC-MS/MS method showed a very good agreement for EtG (r=0.96) and EtS (r=0.97) over a broad urine concentration range. Conclusions: The commercial IVD-certified LC-MS/MS assay is suitable for the analysis of EtG and EtS in human urine[0] to assess recent alcohol intake in transplant monitoring.

Background: Epidemiological studies suggested that caffeine/coffee could be an effective therapeutic agent against Alzheimer disease (AD). The mechanism has not been well established; however, molecular genetic analyses suggest that many genes influence it. Methods: Using developing zebrafish ( Danio rerio ), we studied the regulatory effect of caffeine on AD molecular factors, APP, Psen1, Psen2, ApoE, and Sorl1, and on receptor expression of two cell communication systems involved in the disease, adenosine (AR) and dopamine receptors (DR). Results: All genes are already expressed at early developmental stages. No morphological changes were found at tested concentrations and control. Caffeine significantly down-regulated the expression of all AD tested genes at 24 h post-fertilization (hpf) and APP, Sorl1, and Psen1 at 96 and 168 hpf. A 2aa and A 2ab receptors have higher affinity for caffeine than A 2b . Significant down-regulation occurred in A 2b at 168 hpf in both concentrations. Caffeine blocked the expression of drd 2a and drd 2c at 24 hpf but significantly stimulated the expression at 96 and 168 hpf. Conclusions: Zebrafish is a promising organism in studying AD at the molecular level because all tested factors are already expressed at early developmental stages. Caffeine has a regulatory effect on all tested genes and may protect against the disease via amyloid pathway as well as AR and DR.

Background: Vitamin D deficiency is associated with acute coronary syndrome (ACS). We aimed to evaluate calcidiol status and its relationship with coronary angiography findings in two selected groups of ACS patients. Methods: We investigated two groups of patients with ACS: 75 patients with ST-segment-elevation myocardial infarction (STEMI) and 68 patients with unstable angina pectoris (USAP). The ACS diagnosis was confirmed by coronary angiography findings. Biochemical parameters were studied at the first visit of the patients with automated instruments and ready-to-use kits. Results: Calcidiol levels were significantly lower in the STEMI group compared to the USAP group (p<0.001), while the prevalence of calcidiol deficiency in the STEMI group was significantly higher (p<0.001). Serious calcidiol deficiency (<4 ng/mL) was present in 17% of the STEMI group and in 7% of the USAP group. We did not observe any significant relationship between calcidiol status and coronary angiography findings. Conclusions: Our results support the previously described associations between ACS and calcidiol deficiency. Besides, we report a more severe calcidiol deficiency and an extraordinarily high prevalence of vitamin D deficiency or insufficiency in these patients.