Mikropartikel als neuer Risikofaktor bei Frauen mit rezidivierenden Spontanaborten

RSA liegt ein multifaktorielles Geschehen zugrunde. Ziel dieser Arbeit war es, unter Fokussierung auf Aspekte innerhalb möglicher Veränderungen des Gerinnungssystems bei Frauen mit RSA durch Beleuchtung eines neuen, möglichen Risikofaktors einen weiteren Erklärungsansatz für RSA zu liefern. In unseren Untersuchungen von RSA-Patientinnen konnten wir keine signifikanten Unterschiede in Bezug auf zirkulierende MP-Konzentrationen im Vergleich zu Frauen der Kontrollgruppe nachweisen. Lediglich in einer Subgruppe der RSA-Patientinnen zeigten sich erhöhte Konzentrationen von Annexin V+ MP. Das prokoagulatorische Potential dieser MP in Bezug auf die Thrombinbildung in vivo und in vitro zeigte ebenso keine signifikanten Unterschiede innerhalb der Studiengruppen. Entscheidend in diesem Zusammenhang ist, dass sich die Bedeutung von MP nicht allein auf Veränderungen hinsichtlich einer vermehrten Gerinnbarkeit beschränken. Vielmehr scheinen MP auf vielfältige andere Prozessabläufe bezüglich Endothelfunktionen, Angiogenese, Entzündungsprozesse sowie interzellulärem Transport und Austausch Einfluss zu nehmen

Two sub-states of the red2 state of methyl-coenzyme M reductase revealed by high-field EPR spectroscopy

Methyl-coenzyme M reductase (MCR) catalyzes the formation of methane from methyl-coenzyme M and coenzyme B in methanogenic archaea. The enzyme has two structurally interlinked active sites embedded in an α2β2γ2 subunit structure. Each active site has the nickel porphyrinoid F430 as a prosthetic group. In the active state, F430 contains the transition metal in the Ni(I) oxidation state. The active enzyme exhibits an axial Ni(I)-based continuous wave (CW) electron paramagnetic resonance (EPR) signal, called red1a in the absence of substrates or red1c in the presence of coenzyme M. Addition of coenzyme B to the MCR-red1 state can partially and reversibly convert it into the MCR-red2 form, which shows a rhombic Ni(I)-based EPR signal (at X-band microwave frequencies of approximately 9.4GHz). In this report we present evidence from high-field/high-frequency CW EPR spectroscopy (W-band, microwave frequency of approximately 94GHz) that the red2 state consists of two substates that could not be resolved by EPR spectroscopy at X-band frequencies. At W-band it becomes apparent that upon addition of coenzyme B to MCR in the red1c state, two red2 EPR signals are induced, not one as was previously believed. The first signal is the well-characterized (ortho)rhombic EPR signal, thus far called red2, while the second previously unidentified signal is axial. We have named the two substates MCR-red2r and MCR-red2a after their rhombic and axial signals, respectivel

Systemic changes in haemostatic balance are not associated with increased levels of circulating microparticles in women with recurrent spontaneous abortion

PROBLEM: Placental fibrin deposits in patients wih recurrent spontaneous abortion (RSA) indicate an exaggerated haemostatic response. This 'hypercoagulability' may involve pro-coagulant factors such as circulating microparticles (MPs). We investigated the relationship between circulating pro-coagulant MPs and systemic coagulation in RSA patients. METHOD OF STUDY: Platelet- and endothelial cell-derived microparticles (PMPs, EMPs) were evaluated by flow cytometry in RSA patients (n = 51) and compared to controls (n = 24) using annexin V (total numbers of MP), and antibodies against CD61, CD63 and CD62P (PMP), as well as CD144 and CD62E (EMP). Prothrombin fragment 1 + 2 (F(1+2)) and thrombin generation were determined to assess the pro-coagulant potential of MP. RESULTS: Numbers of annexin V-binding MP were nearly similar in RSA patients and controls. However, a subgroup of ten RSA patients (10/51; 20%) presented with MP concentrations >10,000 x 10(6)/L, compared to only one women out of the control group (1/24; 4%; P = 0.038). Neither PMP and EMP nor F(1+2) and thrombin generation differed significantly within the study population. CONCLUSION: The present study shows that circulating MPs are not directly associated with the extent of systemic coagulation activation in RSA patients. We hypothesize that increased numbers of circulating MPs either are only indirectly associated with coagulation during pregnancy of RSA patients, or affect abortion via mechanisms independently from hypercoagulatio

Single mandibular implant study (SMIS) - masticatory performance - results from a randomized clinical trial using two different loading protocols

OBJECTIVES This multi-centre randomized controlled trial was conducted to investigate, whether the masticatory performance of elderly edentulous patients is improved by placement of a single implant in the midline of the edentulous mandible, and whether improvements differ with respect to the loading protocol, i.e., implant is loaded either directly or three months later after second stage surgery. METHODS Edentulous seniors aged 60-89 years were screened according to inclusion and exclusion criteria and 163 underwent implant placement. Of those, 158 were randomly assigned either to the direct loading group A (n=81) or the conventional loading group B (n=77). Chewing efficacy was obtained before treatment, one month after implant placement during the submerged healing phase (only group B) and 1 and 4 months after implant loading. RESULTS The masticatory performance increased over time in both groups. Four months after loading, a significant increase was observed for both groups compared to the baseline data without implant (p≤0.05). However, between the two groups, chewing efficiency did not differ significantly at any point in time (p>0.05). CONCLUSIONS A single midline implant in the edentulous mandible increases masticatory performance significantly, independently from the loading protocol. CLINICAL SIGNIFICANCE A single midline implant in the edentulous mandible increases masticatory performance. The loading protocol has no influence

Therapy of uncomplicated falciparum malaria in Europe: MALTHER - a prospective observational multicentre study

Background: Malaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe. Methods: A prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine. Results: Between December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p = 0.005) and adverse events (p = 0.001), parasite and fever clearance times (p <0.001), and hospitalization rates (p = 0.0066) and durations (p = 0.001). Four recrudescences and two progressions to severe disease were observed. Compared to other regimens, quinine alone was associated with more frequent switches to second line treatment, more adverse events and longer inpatient stays. Parasite and fever clearance times were shortest with artemether-mefloquine combination treatment. Vomiting was the most frequent cause of treatment change, occurring in 5.5% of all patients but 9% of the atovaquone-proguanil group. Conclusions: This study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malari

Two sub-states of the red2 state of methyl-coenzyme M reductase revealed by high-field EPR spectroscopy

Methyl-coenzyme M reductase (MCR) catalyzes the formation of methane from methyl-coenzyme M and coenzyme B in methanogenic archaea. The enzyme has two structurally interlinked active sites embedded in an alpha(2)beta(2)gamma(2) subunit structure. Each active site has the nickel porphyrinoid F(430) as a prosthetic group. In the active state, F(430) contains the transition metal in the Ni(I) oxidation state. The active enzyme exhibits an axial Ni(I)-based continuous wave (CW) electron paramagnetic resonance (EPR) signal, called red1a in the absence of substrates or red1c in the presence of coenzyme M. Addition of coenzyme B to the MCR-red1 state can partially and reversibly convert it into the MCR-red2 form, which shows a rhombic Ni(I)-based EPR signal (at X-band microwave frequencies of approximately 9.4 GHz). In this report we present evidence from high-field/high-frequency CW EPR spectroscopy (W-band, microwave frequency of approximately 94 GHz) that the red2 state consists of two substates that could not be resolved by EPR spectroscopy at X-band frequencies. At W-band it becomes apparent that upon addition of coenzyme B to MCR in the red1c state, two red2 EPR signals are induced, not one as was previously believed. The first signal is the well-characterized (ortho)rhombic EPR signal, thus far called red2, while the second previously unidentified signal is axial. We have named the two substates MCR-red2r and MCR-red2a after their rhombic and axial signals, respectively

Clustering of motor and nonmotor traits in leucine-rich repeat kinase 2 G2019S Parkinson's disease nonparkinsonian relatives: A multicenter family study

Objectives: The objective of this study was to determine phenotypic features that differentiate nonparkinsonian first-degree relatives of PD leucine-rich repeat kinase 2 (LRRK2) G2019S multiplex families, regardless of carrier status, from healthy controls because nonparkinsonian individuals in multiplex families seem to share a propensity to present neurological features. Methods: We included nonparkinsonian first-degree relatives of LRRK2 G2019S familial PD cases and unrelated healthy controls participating in established multiplex family LRRK2 cohorts. Study participants underwent neurologic assessment including cognitive screening, olfaction testing, and questionnaires for daytime sleepiness, depression, and anxiety. We used a multiple logistic regression model with backward variable selection, validated with bootstrap resampling, to establish the best combination of motor and nonmotor features that differentiates nonparkinsonian first-degree relatives of LRRK2 G2019S familial PD cases from unrelated healthy controls. Results: We included 142 nonparkinsonian family members and 172 unrelated healthy controls. The combination of past or current symptoms of anxiety (adjusted odds ratio, 4.16; 95% confidence interval, 2.01-8.63), less daytime sleepiness (adjusted odds ratio [1 unit], 0.90; 95% confidence interval, 0.83-0.97], and worse motor UPDRS score (adjusted odds ratio [1 unit], 1.4; 95% confidence interval, 1.20-1.67) distinguished nonparkinsonian family members, regardless of LRRK2 G2019S mutation status, from unrelated healthy controls. The model accuracy was good (area under the curve = 79.3%). Conclusions: A set of motor and nonmotor features distinguishes first-degree relatives of LRRK2 G2019S probands, regardless of mutation status, from unrelated healthy controls. Environmental or non-LRRK2 genetic factors in LRRK2-associated PD may influence penetrance of the LRRK2 G2019S mutation. The relationship of these features to actual PD risk requires longitudinal observation of LRRK2 familial PD cohorts. © 2018 International Parkinson and Movement Disorder Society