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A mild one-pot methodology has been developed to deracemise rac-2-phenyl-1-propanol by combining the use of non-selective laccase/TEMPO-mediated oxidation with enantioselective bioreduction of the racemic aldehyde intermediate under dynamic conditions. The process was easily scalable and stereocontrollable by selecting the suitable biocatalyst.

The combination of two cofactor self-sufficient biocatalytic cascade modules allowed the successful transformation of cyclohexanol into the nylon-6 monomer 6-aminohexanoic acid at the expense of only oxygen and ammonia. A hitherto unprecedented carboxylic acid capping strategy was introduced to minimize the formation of the dead-end intermediate 6-hydroxyhexanoic acid. For this purpose, the precursor e-caprolactone was converted in aqueous medium in the presence of methanol into the corresponding methyl ester instead of the acid. Hence, it was shown for the first time that esterases--specifically horse liver esterase--can perform the selective ring-opening of e-caprolactone with a clear preference for methanol over water as the nucleophile.

Background Previous studies have demonstrated typical findings in the ultrasound of salivary glands (USG) in patients with primary Sjogren syndrome (pSS) compared with healthy controls. However, it is unknown, if these findings are only seen in patients with pSS but also in patients with secondary Sjogren syndrome (sSS) or other connective tissue diseases with positive Ro-SSA/La-SSB antibodies. Methods We used an ultrasound score developed by Zhang [1] to investigate salivary glands with a score ranging from 0–48. We compared the score from patients with pSS according the criteria of the American-European Consensus Group (group 1) with patients who fulfilled the clinical criteria (1–4), but were Ro-SSA/La-SSB negative (group 2), with patients who had another rheumatic disease, but had sicca symptoms and were Ro-SSA and/or La-SSB positive (sSS) (group 3), with patients with other rheumatic disease without Ro-SSA or La-SSB antibodies (group 4), with patients with other rheumatic disease with Ro-SSA antibodies but no sicca symptoms (group 5) and with patients with no rheumatic disease (group 6), respectively. We investigated the parotid and the submandibular salivary glands bilaterally. The USG was assessed with a score from 0–48 points with a maximum of 12 points for 4 items each (hyoechoic areas, hyperechoic reflexes, inhomogeneity and distinct organ border). If available the score was correlated with the scintigraphically measured function of the salivary glands. Results We included USG of 92 patients in our study. Group 1 (n=33) had a score of 16.6±11.6; group 2 (n=7) 2.4±3.5; group 3 (n=16) 8.6±9.5; group 4 (n=16) 5.3±7.8; group 5 (n=11) 4.5±6.7 and group 6 (n=9) 1.5±2.3, respectively. The score between group 1 and all other groups was significantly different (p Conclusions USG showed significantly higher scores in patients with pSS, than in patients with sSS or other rheumatic disease. USG as a non invasive investigation might be similarly helpful for the diagnosis of pSS like salivary gland functional tests. USG findings can reliable distinguish between pSS and sSS associated with other rheumatic disease, also if they are positive for Ro-SSA/La-SSB. References Zhang X, Zhang S, He J, Hu F, Liu H, Li J, Zhu J, Li Z. Ultrasonographic evaluation of major salivary glands in primary Sjogren9s syndrome: comparison of two scoring systems. Rheumatology (Oxford). 2015 Sep;54(9):1680–7. Disclosure of Interest None declared

Deracemisierung, also die Umwandlung eines Racemats in ein enantiomerenreines Produkt mit theoretisch 100 % Ausbeute und 100 % ee, stellt eine attraktive, aber auch anspruchsvolle Option fur die asymmetrische Synthese dar. Hier beschreiben wir ein neuartiges Konzept einer chemo-enzymatischen Deracemisierung mittels einer Kaskadenreaktion. Die Reaktionsfolge beinhaltet zwei enantioselektive Oxidationsschritte und einen nicht stereoselektiven Reduktionsschritt, durch welche zur gleichen Zeit eine Stereoinversion und eine kinetische Racematspaltung realisiert werden. Dieses Konzept wird anhand der Umwandlung von rac-Benzylisochinolinen in optisch reine (S)-Berbine vorgestellt. Die racemischen Substrate wurden in enantiomerenreine Produkte (ee>97 %) umgewandelt, wobei Umsatze von bis zu 98 % und Ausbeuten von bis zu 88 % erreicht wurden.

Various enantiocomplementary ω-transaminases (ωTAs) were investigated in kinetic resolution and asymmetric reductive amination reactions to prepare silodosin amine. Whilst the enzymatic kinetic resolution gave moderate to good results with respect to the yield and enantioselectivity, the asymmetric reductive amination proved to be superior. The best results were obtained with the ωTA originating from (R)-Arthrobacter sp. which afforded the desired bioactive (R)-enantiomer in enantiomerically pure form (ee >97%) at excellent conversion (conv. >97%) under mild and benign reaction conditions.

Chemo-enzymatic deracemisation was applied to obtain the (S)-enantiomer of 1-benzylisoquinolines from the racemate in high isolated yield (up to 85%) and excellent optical purity (ee > 97%). The one-pot deracemisation protocol encompassed enantioselective oxidation by a monoamine oxidase (MAO-N) and concomitant reduction of the resulting iminium species by ammonia-borane. The challenge was the oxidation at the sterically demanding chiral centre. Recently developed variants of MAO-N, featuring an enlarged active-site pocket, turned out to be suitable biocatalysts for these substrates. In contrast to previous MAO-N variants, which preferentially converted the (S)-enantiomer, the MAO-N variant D11 used in the present study was found to oxidise all tested benzylisoquinoline substrates with (R)-enantiopreference. The structural determinants of enantioselectivity were investigated by means of protein–ligand docking simulations. The applicability of the deracemisation system was demonstrated on preparative scale (150 mg) for three benzylisoquinoline alkaloids (natural as well as non-natural), including the hypotensive and antispasmodic agent (S)-reticuline.

Various (S)-selective and (R)-selective ω-transaminases were investigated for the amination of 1- and 2-tetralone and derivatives as well as of 3- and 4-chromanone. All ketones tested were aminated to give the corresponding enantiopure amines (ee > 99%) employing at least one of the enzymes investigated. In most of the cases the (S)- as well as the (R)-enantiomer was obtained in optically pure form. The amination of 3-chromanone was performed on a 100 mg scale leading to optically pure (R)-3-aminochromane (ee > 99%) with complete conversion and 78% isolated yield.

Various artificial network designs that involve biocatalysts were tested for the asymmetric amination of sec-alcohols to the corresponding α-chiral primary amines. The artificial systems tested involved three to five redox enzymes and were exemplary of a range of different sec-alcohol substrates. Alcohols were oxidised to the corresponding ketone by an alcohol dehydrogenase. The ketones were subsequently aminated by employing a ω-transaminase. Of special interest were redox-neutral designs in which the hydride abstracted in the oxidation step was reused in the amination step of the cascade. Under optimised conditions up to 91 % conversion of an alcohol to the amine was achieved.

Introduction: The number of publications concerning mesenteric Doppler sonography (mesDS) is immense and does not correlate with the frequency of its use in clinical practice. This is astonishing since it provides real time blood flow (perfusion) information without side effects. Despite uncontrollable parameters like the technical limitations in some situations the optimization of (possibly) controllable parameters like standardization, production of normal values and reduction of the investigator variability by evaluating stable parameters could change the situation. Patients and methods: 10 investigators experienced in abdominal sonography (“DEGUM-Seminarleiter”) performed mesenteric Doppler sonography in 5 healthy subjects with 5 different machines. Results: The portal vein at the confluence and the common hepatic artery provide a significant portion of investigations with intromission angles of more than 60°. Values of diameter, resistance index and pulsatility index of the celiac trunc could be obtained with inter-observer variability values below 25 %. The proper and the common hepatic artery show no differences in inter-observer variability values, whereas the intrahepatic measure point of the portal vein showed a higher reproducibility. Discussion: We define frame conditions for future mesenteric Doppler studies: the portal vein should be investigated at the intrahepatic measure point. Pathophysiological studies should refrain from velocity parameters except in the case of larger vessels running in a straight course towards the probe.

PurposeTo determine the sensitivity to change of the US7 score among RA patients under various therapies and to analyze the effect of each therapeutic option over 1 year. To estimate predictors for development of destructive bone changes.MethodsMusculoskeletal ultrasound (US7 score), DAS28, CRP and ESR were performed in 432 RA patients at baseline and after 3, 6 and 12 months. The cohort was divided into four sub-groups: first-line DMARDs (Group 1; 27.3%), therapy switch: DMARDs to second DMARDs (Group 2; 25.0%), first-line biologic after DMARDs therapy (Group 3; 35.4%) and therapy change from biologic to second biologic (Group 4; 12.3%).ResultsThe US7 synovitis and tenosynovitis sum scores in grey-scale (GSUS) and power Doppler ultrasound (PDUS) as well as ESR, CRP decreased significantly (pConclusionsThe comparable developments of the US7 score with clinical and laboratory data illustrates its potential to reflect therapeutic response. Therefore, the novel US7 score is sensitive to change. Patients who switched from one biologic to another exhibited a significant decline in erosions after 12 months, while the erosions scores in the other groups were stable.

(S)-Rivastigmine [(S)-1] was obtained via a four-step synthesis using an asymmetric enzymatic transamination protocol as the key step. An early introduction of the carbamate pharmacophore side chain avoided the use of protective group strategies and hence led to a considerable shortcut. This strategy required a novel ω-transaminase from Paracoccus denitrificans, which could transform the highly polar key substrate 3-acetylphenyl ethyl(methyl)carbamate (4) to the corresponding amine (S)-5 in 99% ee and >80% conversion.

Objective To introduce and evaluate a new standardized ultrasound (US) score developed for large joints in patients with rheumatoid arthritis (RA). Methods A US score was designed to determine the degree of inflammation in the shoulder, the elbow, the hip, and the knee joint in patients with RA (Sonography of Large Joints in Rheumatology [SOLAR] score). Synovitis and synovial vascularity were scored semiquantitatively (grade 0–3) by gray-scale US (GSUS) and power Doppler US (PDUS). Patients with RA were examined at baseline and 3, 6, and 12 months after initiation of local or systemic therapy (disease-modifying antirheumatic drugs [DMARDs]/biologic agents). Erythrocyte sedimentation rate, anti–cyclic citrullinated peptide antibodies, and the clinical Disease Activity Score in 28 joints (DAS28) were determined. Results A cohort of 199 patients were analyzed and followed up over 12 months. At baseline, before modification of the therapy, patients received either DMARDs (n = 131), DMARDs plus biologic agents (n = 46), biologic monotherapy (n = 8), or no DMARD therapy (n = 14). At baseline, the mean DAS28 score was 4.6 and decreased to 3.2 after 1 year of therapy (P < 0.001). All US scores demonstrated a statistically significant improvement except for the PDUS scores for the shoulder and the hip. In detail, the mean synovitis GSUS score for the knee decreased from 5.2 at baseline to 2.2 after 12 months of followup. The mean GSUS score for the shoulder fell from 2.6 to 1.6, for the elbow fell from 5.2 to 2.6, and for the hip fell from 2.2 to 0.4 (P < 0.05 for each). Conclusion The SOLAR score is a feasible tool for the qualitative and quantitative evaluation of large joint involvement in patients with RA using US.

Die Sonografie ermoglicht sehr gut, allgemeine Arthritiszeichen zu erfassen. Sie hat aber ihre Grenze in der Differenzialdiagnose. Der folgende Beitrag versucht, die Moglichenkeiten und Grenzen der Sonografie bei entzundlich-rheumatischen Erkrankungen aufzuzeigen. Die endgultige Diagnose ist immer im Kontext von Laborergebnissen, klinischer Untersuchung und Bildgebung zu stellen.

A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C-C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates rac-1 required for the biotransformation were prepared in 4-8 linear steps using either a Bischler-Napieralski cyclization or a C1-Cα alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and gave overall yields of up to 20% over 5-9 linear steps.

The combination of an oxidation and a reduction in a cascade allows performing transformations in a very economic and efficient fashion. The challenge is how to combine an oxidation with a reduction in one pot, either by running the two reactions simultaneously or in a stepwise fashion without isolation of intermediates. The broader availability of various redox enzymes nowadays has triggered the recent investigation of various oxidation–reduction cascades.

Four (R)-ω-transaminases originating from Hyphomonas neptunium (HN-ωTA), Aspergillus terreus (AT-ωTA) and Arthrobacter sp. (ArR-ωTA), as well as an evolved transaminase (ArRmut11-ωTA) were successfully employed for the amination of prochiral ketones leading to optically pure (R)-amines. The first three transaminases displayed perfect stereoselectivity for the amination of all substrates tested (ee >99%). Furthermore, the transaminase AT-ωTA led in most cases to better conversion than ArR-ωTA and HN-ωTA using D-alanine as amine donor. α-Tetralone, which was the only substrate not accepted by HN-ωTA, ArR-ωTA, and AT-ωTA, was successfully transformed with perfect enantioselectivity (ee >99%) into the corresponding optically pure amine employing the variant ArRmut11-ωTA.

Objective To introduce a new standardized ultrasound score based on 7 joints of the clinically dominant hand and foot (German US7 score) implemented in daily rheumatologic practice. Methods The ultrasound score included the following joints of the clinically dominant hand and foot: wrist, second and third metacarpophalangeal and proximal interphalangeal, and second and fifth metatarsophalangeal joints. Synovitis and synovial/tenosynovial vascularity were scored semiquantitatively (grade 0–3) by gray-scale (GS) and power Doppler (PD) ultrasound. Tenosynovitis and erosions were scored for presence. The scoring range was 0–27 for GS synovitis, 0–39 for PD synovitis, 0–7 for GS tenosynovitis, 0–21 for PD tenosynovitis, and 0–14 for erosions. Patients with arthritis were examined at baseline and after the start or change of disease-modifying antirheumatic drug (DMARD) and/or tumor necrosis factor α (TNFα) inhibitor therapy 3 and 6 months later. C-reactive protein level, erythrocyte sedimentation rate, rheumatoid factor, anti–cyclic citrullinated peptide, Disease Activity Score in 28 joints (DAS28), and radiographs of the hands and feet were performed. Results One hundred twenty patients (76% women) with rheumatoid arthritis (91%) and psoriatic arthritis (9%) were enrolled. In 52 cases (43%), erosions were seen in radiography at baseline. Patients received DMARDs (41%), DMARDs plus TNFα inhibitors (41%), or TNFα inhibitor monotherapy (18%). At baseline, the mean DAS28 was 5.0 and the synovitis scores were 8.1 in GS ultrasound and 3.3 in PD ultrasound. After 6 months of therapy, the DAS28 significantly decreased to 3.6 (Δ = 1.4), and the GS and PD ultrasound scores significantly decreased to 5.5 (−32%) and 2.0 (−39%), respectively. Conclusion The German US7 score is a viable tool for examining patients with arthritis in daily rheumatologic practice because it significantly reflects therapeutic response.

BACKGROUND: The early manifestation of the rheumatoid arthritis consists of a soft tissue affection of the joints. GOAL: Purpose of the study was the production of an arthrosonographic staging for the description of the soft tissue and cartilage/bone changes with rheumatoid arthritis of the hand and finger joints. Correlations of the arthrosonographic examination to the established DAS 28 as well as to parameters of the clinical examination were undertaken. PATIENTS AND METHODS: Clinical and arthrosonographic examinations as well as raising the established DAS 28 of 35 patients (with confirmed rheumatoid arthritis) and 10 control persons were carried out. The results werecompared and correlated to each other. RESULTS: A detailed staging can be made which exhibits a very high positive correlation to DAS 28 as well as to parameters of the clinical investigation. More than a quarter of the arthrosonographically determined joint changes correspond to the stage 1 (purely soft tissue changes) and would thus not be detectable radiologically. CONCLUSIONS: On account of the outstanding results of the arthrosonographic examination it is meaningful to establish anduse this imaging method as a standardized staging in the routine diagnostics of the rheumatoid arthritis.

BACKGROUND: Manisfestations of rheumatoid arthritis in the musculoskeletal system affect above all the small joints of the hand and here initially the soft-tissue parts. Destruction of bone is assessed by means of established radiological classifications (e. g., “Larsen stages”). AIM: In this study a new sonographic system to assess the status of the hand and finger joints in a collective of rheumatoid arthritis patients is presented, validated and compared with conventional X-ray diagnostics. MATERIALS AND METHODS: The hand and finger joints of 20 patients with a confirmed diagnosis of rheumatoid arthritis were examined by means of ultrasonography and conventional X-ray methods. The results were compared and correlated. The DAS 28 score was used as the criterion to assess disease activity. RESULTS: In total, on sonography 20 % more joints showed pathological sot-tissue affections (synovialitis/effusions) than on X-ray diagnosis. The correlation of the sonographic assessment system with the DAS 28 score was higher than that with the X-ray findings. In the initial studies, even with low DAS 28 scores, joint affections, e. g., also erosions, could be detected. CONCLUSIONS: The high sensitivity (in totals, 20 % more joint affections were detected) and specificity (Spearman’s correlation coefficient between sonographic score and DAS 28 score = + 0.4) of the sonographic method justify its routine use in diagnosis and follow-up, especially in early rheumatoid arthritis as well. This method makes possible the early and secure detection of joint changes due to inflammation.

Die Sonographie der Bewegungsorgane ist ein wichtiges bildgebendes Verfahren in der Diagnostik der rheumatoiden Arthritis und Bestandteil der Weiterbildung zum Rheumatologen in Deutschland. Daruber hinaus werden zahlreiche Kurse angeboten, um spezielle Kenntnisse und praktische Fahigkeiten zu erwerben. Die internationale Bedeutung der Sonographie in der Rheumatologie hat in den letzten funf Jahren erheblich zugenommen. Die Sonographie kann in der Praxis und am Krankenbett als Fortsetzung des klinischen Status durchgefuhrt werden. Sie ist fur den Patienten nicht belastend und kann jederzeit und beliebig oft wiederholt werden. Der Einfluss auf therapeutische Entscheidungen ist erheblich. Voraussetzung ist ein Ultraschallgerat mit einem Linearschallkopf mit ≥5 MHz. Am haufigsten werden Schallkopfe mit ca.7,5 MHz verwendet. Moderne, hoherfrequente, hochauflosende Schallkopfe (>7,5 MHz) erlauben zusatzliche diagnostische Aussagen. Die Sonographie ist dem konventionellen Rontgen beim Nachweis von Erosionen uberlegen soweit die knochernen Lasionen der sonographischen Untersuchung zuganglich sind. Sie ist sensitiver als die klinische Untersuchung, was den Nachweis von Synovitiden, Tenosynovitiden, Tendinitiden und Bursitiden sowie deren Differenzierung voneinander betrifft. Die Farbdoppler-Sonographie ermoglicht daruber hinaus die Einschatzung der Entzundungsaktivitat und hilft bei der Differenzierung intraartikularer Strukturen. Carpal- und Ulnartunnelsyndrom konnen bei der rheumatoiden Arthritis auftreten. Sie sind haufig mit einer sonographisch nachweisbaren charakteristischen Schwellung der Nerven verbunden. Punktionen und Injektionen konnen sonographie-gestutzt oder sonographie-gesteuert durchgefuhrt werden.

Der Einsatz der Arthrosonographie an der Hand gewinnt insbesondere in der Fruharthritisdiagnostik eine zunehmende Bedeutung. Sehr sensitiv gelingt der Nachweis kleinster Flussigkeitsansammlungen in den Gelenken und Sehnenscheiden sowie das Aufdecken kleinster erosiver Knochenlasionen mitunter eher als mit der konventionellen Rontgendiagnostik. Die Arthrosonographie ist ebenfalls hilfreich bei der morphologischen Analyse der Veranderungen des Nervus medianus beim Karpaltunnel-Syndrom. Folgende Standardschnittebenen werden fur die sonographische Untersuchung am Handgelenk empfohlen: 1. dorsaler Longitudinalschnittuber dem Radiokarpal- und 2. Ulnokarpalgelenk mit der Frage nach Gelenkerguss und Synovialisproliferation, Ganglien, Sehnenscheidenentzundungen, Unregelmasigkeiten der knochernen Oberflache wie bei knochernen Appositionen sowie bei Erosionen und 3. dorsaler Transversalschnitt uber dem Handgelenk zur Darstellung der Strukturen in einer weiteren Ebene, 4. volarer Longitudinalschnitt uber dem Radiocarpal- und 5. Ulnokarpalgelenk und 6. volarer Transversalschnittuber dem Handgelenk mit gleicher Fragestellung wie in den vorgenannten Ebenen sowie zur Beurteilung des Nervus medianus im Rahmen der Abklarung eines Karpaltunnel-Syndroms, optional 7. ulnarer Longitudinal- und 8. Transversalschnitt uber dem ulnaren Gelenkspalt und dem M. extensor carpi ulnaris zur Erfassung einer Tenosynovitis in diesem Bereich sowie des Caput ulnae Syndroms, 9. radialer Longitudinal- und 10. Transversalschnitt mit gleicher Fragestellung wie in den vorgenannten Ebenen. An den Fingergelenken werden folgende Standardschnittebenen fur die sonographische Untersuchung empfohlen: 1.volarer Longitudinal- und 2.volarer Transversalschnitt in Extension uber dem Daumensattelgelenk (DSG), MCP-, PIP- und DIP-Gelenken mit der Frage nach Gelenkerguss und Synovialisproliferation, Sehnenscheidenentzundungen, Unregelmasigkeiten der knochernen Oberflache wie bei knochernen Appositionen (Osteophyten) sowie bei Erosionen, 3. dorsaler Longitudinal und 4.dorsaler Transversalschnittin Extension und Flexion von ca. 70° uber den MCP-, PIP- und DIP-Gelenken sowie dem DSG in Extension mit der Frage nach Gelenkerguss und Synovialisproliferation, Sehnenscheidenentzundungen bzw. Tendinitis, Unregelmasigkeiten der knochernen Oberflache wie bei Arthrose sowie bei Erosionen, optional 5. Medialer Longitudinalschnitt in Hohe der MCP-Gelenke I, II, sowie der PIP- und DIP-Gelenke und 6. lateraler Longitudinalschnitt in Hohe des MCP-Gelenkes V sowie der PIP- und DIP-Gelenke zur Erfassung von Erosionen und Instabilitaten. Verwendet werden sollten Linearschallsonden mit einer Frequenz von etwa 7,5–12 MHz. Ein Erguss oder eine Synovialitis im Handgelenk gelten als wahrscheinlich bei einem ventralen Knochen-Gelenkkapsel-Abstand von ≥3 mm und als sicher bei ≥4 mm. Er ist wahrscheinlich bei einer Seitendifferenz von ≥1mm und sicher bei ≥2 mm. Bei einer Querschnittsflache des Nervus medianus von ≥12 mm2 ist ein Karpaltunnel-Syndrom wahrscheinlich.

Die Arthrosonographie im Bereich der Huftregion hat eine grose Bedeutung als leicht einzusetzende, kostengunstige und patientenfreundliche Untersuchungsmethode, da die klinische Untersuchung bei rheumatischen Fragestellungen oft unzureichend ist. Folgende Standardebenen werden empfohlen: 1. ventraler Longitudinalschnitt mit der Frage nach Gelenkerguss, Bursitis iliopectinea, Unregelmasigkeiten der knochernen Oberflache bei Arthrose, Morbus Perthes sowie bei Erosionen, 2. ventraler Transversalschnitt zur Darstellung der Strukturen in einer weiteren Ebene, 3. lateraler Longitudinalschnitt am Huftgelenk mit gleicher Fragestellung wie in den vorgenannten Ebenen sowie 4. lateraler Longitudinalschnitt und 5. lateraler Transversalschnitt am Trochanter major zur Beurteilung einer Bursitis trochanterica und knochernen Unregelmasigkeiten bei Enthesiopathien und 6. optional ein dorsaler Schragschnitt. Dabei konnen seltenere, ausschlieslich dorsal lokalisierte Huftgelenkergusse und Pannus nachgewiesen werden. Eine rotierende Gelenkbewegung ist unerlasslich, um kleine Ergusse zu erfassen. Verwendet werden sollten Schallkopfe mit 5 bis 7,5MHz. Bei adiposen oder muskularen Patienten muss gelegentlich wegen der notwendigen Eindringtiefe auf einen 3,5MHz Schallkopf ausgewichen werden. Ein Huftgelenkerguss oder eine Synovialitis gelten als wahrscheinlich bei einem ventralen Knochen-Gelenkkapsel-Abstand von ≥7mm und als sicher bei ≥8mm. Er ist wahrscheinlich bei einer Seitendifferenz von ≥2mm und sicher bei ≥3mm.

An efficient route for the synthesis of all four diastereomers of PMP-protected α-amino-γ-butyrolacton to access γ-hydroxynorvaline was established. The asymmetric key steps comprise an organocatalytic Mannich reaction and an enzymatic ketone reduction. Three reaction steps could be integrated in a one-pot process, using 2-PrOH both as solvent and as reducing agent. The sequential construction of stereogenic centres gave access to each of the four stereoisomers in high yield and with excellent stereocontrol.

Lactobacillus brevis ADH (LBADH) is an alcohol dehydrogenase that is commonly employed to reduce alkyl or aryl ketones usually bearing a methyl, an ethyl or a chloromethyl as a small ketone substituent to the corresponding (R)-alcohols. Herein we have tested a series of 24 acetophenone derivatives differing in their size and electronic properties for their reduction employing LBADH. After plotting the relative activity against the measured substrate volumes we observed that apart from the substrate size other effects must be responsible for the activity obtained. Compared to acetophenone (100% relative activity), other small substrates such as propiophenone, α,α,α-trifluoroacetophenone, α-hydroxyacetophenone, and benzoylacetonitrile had relative activities lower than 30%, while medium-sized ketones such as α-bromo-, α,α-dichloro-, and α,α-dibromoacetophenone presented relative activities between 70% and 550%. Moreover, the comparison between the enzymatic activity and the obtained final conversions using an excess or just 2.5 equiv. of the hydrogen donor 2-propanol, denoted again deviations between them. These data supported that these hydrogen transfer (HT) transformations are mainly thermodynamically controlled. For instance, bulky α-halogenated derivatives could be quantitatively reduced by LBADH even employing 2.5 equiv. of 2-propanol independently of their kinetic values. Finally, we found good correlations between the IR absorption band of the carbonyl groups and the degrees of conversion obtained in these HT processes, making this simple method a convenient tool to predict the success of these transformations.

Background To evaluate the utility of the recently introduced SOLAR score (sonography of large joints in Rheumatology), which has been validated in RA patients, in a cohort of patients with Psoriatic Arthritis (PsA) and Ankylosing Spondylitis (AS) presenting with involvement of large peripheral joints. Methods The recently established SOLAR score has been designed to determine the degree of inflammation in the shoulder, the elbow, the hip and the knee joint in patients suffering from RA. Since large joints are frequently involved in PsA and AS, synovitis and synovial vascularity were scored semiquantitatively (grade 0–3) by grey scale (GSUS) and power Doppler ultrasound (PDUS) utilizing the validated scoring system. Each joint was scanned from different angles, the knee joint for example was divided into four areas to score for synovitis: the suprapatellar longitudinal, the medial longitudinal, the lateral longitudinal, and the posterior region. Each area was scored from 0–3, so a maximum score of 12 could be achieved. PsA and AS patients presenting with peripheral joint disease involving large joints were examined at baseline, 3 and 6 months after initiation of local or systemic therapy (DMARDs/Biologics). For evaluation of the inflammatory status, the erythrocyte sedimentation rate (ESR) was determined. Results A cohort of 126 patients were enclosed, and 83 of these were followed for 6 months. At baseline before modification of the therapy, patients received DMARDs (n = 83), DMARDs plus biologics (n = 30), or biologic monotherapy (n = 29). Following intervention, all US scores demonstrated a marked improvement. The GSUS and the PDUS scores for all joint areas, except the PDUS score of the hip, exhibited a significant improvement (p Conclusion The SOLAR score, which has been recently introduced for RA patients, is a very suitable instrument for the qualitative and quantitative evaluation of large joint involvement in PsA and AS patients and allows for treatment monitoring.

This account focuses on the application of ω-transaminases, lyases, and oxidases for the preparation of amines considering mainly work from our own lab. Examples are given to access α-chiral primary amines from the corresponding ketones as well as terminal amines from primary alcohols via a two-step biocascade. 2,6-Disubstituted piperidines, as examples for secondary amines, are prepared by biocatalytical regioselective asymmetric monoamination of designated diketones followed by spontaneous ring closure and a subsequent diastereoselective reduction step. Optically pure tert-amines such as berbines and N-methyl benzylisoquinolines are obtained by kinetic resolution via an enantioselective aerobic oxidative C–C bond formation.

Background Novel treatment options together with a treat-to-target strategy present new challenges to imaging procedures in terms of therapy monitoring. Objectives To evaluate the functional outcome measured by Health Assessment Questionnaire (HAQ) as the primary outcome in patients with early rheumatoid arthritis (RA) who were treated by standard clinical care (clinical cohort) in comparison to patients in whom treatment decisions were additionally based on musculoskeletal ultrasound (US) using the US7 score (US-cohort) in a nationwide investigator initiated study in Germany. Methods Functional (HAQ), clinical (DAS28, patient9s Visual Analogue Scale [VAS] for disease activity) and laboratory parameters (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) were analyzed at seven different time points for a total of 18 months and compared between the two study cohorts. Treatment decision was made according to local standard of care (SOC) with a treatment goal of DAS28 Results Data of 313 patients (US-cohort [n=166], clinical cohort [n=147]) demonstrated a reduction of HAQ, DAS28, VAS and laboratory activity (ESR, CRP) to a low disease activity status 18 months after the beginning/change of antirheumatic therapy according to SOC (table 1). The results of functional and clinical outcome in both cohorts did not show significant differences. However, subgroup analysis of the US-cohort with imaging remission resulted in a significantly lower HAQ, DAS28 and VAS compared to patients not fulfilling these US remission criteria (table 1). Conclusions Treatment strategies by a treat to target approach in early RA patients reduced disease activity and improved functional outcome of HAQ irrespective of imaging guidance. However, patients with imaging remission by US exhibited a significantly better functional outcome and lower disease activity status. Accordingly, an additional ultrasound examination aiming at imaging remission should be strongly considered in clinical practice. Disclosure of Interest None declared

Es gibt fruhe unspezifische und spate spezifische Zeichen einer Omarthritis. Je mehr spezifische Zeichen zusammengetragen werden konnen, desto sicherer ist die Diagnose, die Verlaufsbeobachtungen erfordert. Besonders wichtige Schnitte sind axillare Quer- und Langsschnitte, um die perikapitale Synovialitis und fruhe unspezifische Ergusse im axillaren Recessus zu sehen. Destruktionen wie Usuren sind hochspezifisch.