Structural Studies of Transition Metal Complexes with 4,5-Bis(2-pyridylmethylsulfanyl)-4‘,5‘-ethylenedithiotetrathiafulvalene: Probing Their Potential for the Construction of Multifunctional Molecular Assemblies

Three divalent transition metal complexes of 4,5-bis(2-pyridylmethylsulfanyl)-4‘,5‘-ethylenedithiotetrathiafulvalene have been prepared and crystallographically characterized. The isostructural Co(II) and the Ni(II) complexes show octahedral geometries around the metal ions with the coordination sites occupied by the pyridyl nitrogen atoms and the thioether sulfur atoms of the ligand and cis coordination of the halide ions. Cyclic voltammetry reveals that the complexation leads to a small anodic shift in the first oxidation potential of the TTF system.

1,2-Bis(2-benzimidazolyl)-1,2-ethanediol, a chiral, tridentate, facially coordinating ligand

The ligand 1,2-bis(1H-benzimidazol-2-yl)-1,2-ethanediol, 1, and its methylated derivative 2 are readily synthesized from tartaric acid, and act as chiral, facially coordinating tridentate ligands, forming complexes of composition ML2 with octahedral transition metals. The copper(II) complexes show distorted 4 + 2 coordination with benzimidazoles occupying the equatorial sites and alcohol functions weakly binding in the axial sites. Nickel(II) complexes in three different states of protonation show regular octahedral geometry with the alcohols mutually cis. Deprotonation of the coordinated alcohol produces little structural change but the monodeprotonated complex forms a hydrogen bonded dimer. Magnetic measurements show the hydrogen bonded bridge to offer a pathway for weak antiferromagnetic coupling. UV-Visible spectroscopy shows the ligand to have a field intermediate between water and pyridine. The diastereoselectivity of complexation depends on the geometry: nickel(II) shows a weak preference for the homochiral complex, whereas copper(II) forms almost exclusively homochiral complexes.

Lead discovery, chemistry optimization, and biological evaluation studies of novel biamide derivatives as CB2 receptor inverse agonists and osteoclast inhibitors

N,N'-((4-(Dimethylamino)phenyl)methylene)bis(2-phenylacetamide) was discovered by using 3D pharmacophore database searches and was biologically confirmed as a new class of CB(2) inverse agonists. Subsequently, 52 derivatives were designed and synthesized through lead chemistry optimization by modifying the rings A-C and the core structure in further SAR studies. Five compounds were developed and also confirmed as CB(2) inverse agonists with the highest CB(2) binding affinity (CB(2)K(i) of 22-85 nM, EC(50) of 4-28 nM) and best selectivity (CB(1)/CB(2) of 235- to 909-fold). Furthermore, osteoclastogenesis bioassay indicated that PAM compounds showed great inhibition of osteoclast formation. Especially, compound 26 showed 72% inhibition activity even at the low concentration of 0.1 μM. The cytotoxicity assay suggested that the inhibition of PAM compounds on osteoclastogenesis did not result from its cytotoxicity. Therefore, these PAM derivatives could be used as potential leads for the development of a new type of antiosteoporosis agent.

Fructose-1,6-bisphosphate preserves intracellular glutathione and protects cortical neurons against oxidative stress

Fructose-1,6-bisphosphate (FBP), an endogenous intermediate of glycolysis, protects the brain against ischemia-reperfusion injury. The mechanisms of FBP protection after cerebral ischemia are not well understood. The current study was undertaken to determine whether FBP protects primary neurons against hypoxia and oxidative stress by preserving reduced glutathione (GSH). Cultures of pure cortical neurons were subjected to oxygen deprivation, a donor of nitric oxide and superoxide radicals (3-morpholinosydnonimine), an inhibitor of glutathione synthesis (L-buthionine-sulfoximine) or glutathione reductase (1,3-bis(2-chloroethyl)-1-nitrosourea) in the presence or absence of FBP (3.5 mM). Neuronal viability was determined using an 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay. FBP protected neurons against hypoxia-reoxygenation and oxidative stress under conditions of compromised GSH metabolism. The efficacy of FBP depended on duration of hypoxia and was associated with higher intracellular GSH concentration, an effect partly mediated via increased glutathione reductase activity.

Differenzialdiagnose der infektiösen posterioren Uveitis

Infektiöse Ursachen bilden die größte ätiologische Gruppe posteriorer Uveitiden. Als Einzeldiagnosen stehen die Toxoplasmose als infektiöse Erkrankung und der Morbus Behçet als nicht infektiöse Erkrankung an erster Stelle. Bei akuten Entzündungsprozessen immunkompetenter Patienten ist eine exakte Diagnose häufig infolge einer recht dichten Glaskörperinfiltration schwierig zu stellen. In diesen Fällen trägt die Beurteilung des Krankheitsverlaufs zur Differenzialdiagnose wesentlich bei. Virale Netzhautnekrosen verschlechtern sich typischerweise hochakut, Sehstörungen und klinische Symptome bei Morbus Behçet und Toxoplasmose nehmen innerhalb weniger Tage bis 2 Wochen zu, während andere Erkrankungen einen eher schleichenden Verlauf zeigen. Die Dauer der Erkrankung und systemische Grunderkrankungen sind bei der ersten okulären Manifestation häufig nicht bekannt. Grundsätzlich ist die Sehfunktion bedroht, wenn die Makula in den entzündlichen Prozess einbezogen ist, wenn häufige Rezidive zu einer Beteiligung der Makula führen, aber auch wenn sich Sekundärkomplikationen wie ein Makulaödem entwickeln. Bei Kindern muss außerdem an die Gefahr einer Amblyopie infolge entzündlicher Medientrübungen gedacht werden, insbesondere bei Glaskörpertrübungen. Deshalb ist eine rasche interdisziplinäre diagnostische Abklärung und darauf basierende Therapiestrategie erforderlich. Diese muss einerseits ätiologisch abgestützt sein, andererseits sollte sie rechtzeitig steroidsparende Immunsuppresiva und eventuell chirurgische Maßnahmen beinhalten.

A Pt(II) complex with both a phenanthroline and a tetrathiafulvalene-extended dithiolate ligand: Synthesis, crystal structure, electrochemical and spectroscopic properties

The reaction of 4,5-bis(2'-cyanoethylsulfanyl)-4',5'-dipropylthiotetrathiafulvalene with Pt(phen)Cl-2 (phen = 1,10-phenanthroline) with CsOH as base in CH3OH-THE affords the target complex I in 44% yield. This complex crystallizes in the monoclinic space group P2(1)/c, M = 790.01, a = 12.1732(12), b = 15.851(2), c = 14.5371(16) angstrom, beta = 107.693(12)degrees, V = 2672.4(5) angstrom(3) and Z = 4. It undergoes two reversible single-electron oxidation and two irreversible reduction processes. An intense electronic absorption band at 15200 cm(-1) (658 nm) in CH2Cl2 is assigned to the intramolecular mixed metal/ligand-to-ligand charge transfer (LLCT) from a tetrathiafulvalene-extended dithiolate-based HOMO to a phenanthroline-based LUMO. This band shifts hypsochromically with increasing solvent polarity. Systematic changes in the optical spectra upon oxidation allow precise tuning of the oxidation states of 1 and reversible control over its optical properties. Irradiation of 1 at 15625 cm(-1) (640 nm) in glassy solution below 150K results in emission from the (LLCT)-L-3 excited state. GRAPHICS (C) 2013 Elsevier Ltd. All rights reserved.

German Total Ankle Replacement Register of the German Foot and Ankle Society (D. A. F.) - presentation of design and reliability of the data as well as first results

INTRODUCTION Even though arthroplasty of the ankle joint is considered to be an established procedure, only about 1,300 endoprostheses are implanted in Germany annually. Arthrodeses of the ankle joint are performed almost three times more often. This may be due to the availability of the procedure - more than twice as many providers perform arthrodesis - as well as the postulated high frequency of revision procedures of arthroplasties in the literature. In those publications, however, there is often no clear differentiation between revision surgery with exchange of components, subsequent interventions due to complications and subsequent surgery not associated with complications. The German Orthopaedic Foot and Ankle Association's (D. A. F.) registry for total ankle replacement collects data pertaining to perioperative complications as well as cause, nature and extent of the subsequent interventions, and postoperative patient satisfaction. MATERIAL AND METHODS The D. A. F.'s total ankle replacement register is a nation-wide, voluntary registry. After giving written informed consent, the patients can be added to the database by participating providers. Data are collected during hospital stay for surgical treatment, during routine follow-up inspections and in the context of revision surgery. The information can be submitted in paper-based or online formats. The survey instruments are available as minimum data sets or scientific questionnaires which include patient-reported outcome measures (PROMs). The pseudonymous clinical data are collected and evaluated at the Institute for Evaluative Research in Medicine, University of Bern/Switzerland (IEFM). The patient-related data remain on the register's module server in North Rhine-Westphalia, Germany. The registry's methodology as well as the results of the revisions and patient satisfaction for 115 patients with a two year follow-up period are presented. Statistical analyses are performed with SAS™ (Version 9.4, SAS Institute, Inc., Cary, NC, USA). RESULTS About 2½ years after the register was launched there are 621 datasets on primary implantations, 1,427 on follow-ups and 121 records on re-operation available. 49 % of the patients received their implants due to post-traumatic osteoarthritis, 27 % because of a primary osteoarthritis and 15 % of patients suffered from a rheumatic disease. More than 90 % of the primary interventions proceeded without complications. Subsequent interventions were recorded for 84 patients, which corresponds to a rate of 13.5 % with respect to the primary implantations. It should be noted that these secondary procedures also include two-stage procedures not due to a complication. "True revisions" are interventions with exchange of components due to mechanical complications and/or infection and were present in 7.6 % of patients. 415 of the patients commented on their satisfaction with the operative result during the last follow-up: 89.9 % of patients evaluate their outcome as excellent or good, 9.4 % as moderate and only 0.7 % (3 patients) as poor. In these three cases a component loosening or symptomatic USG osteoarthritis was present. Two-year follow-up data using the American Orthopedic Foot and Ankle Society Ankle and Hindfoot Scale (AOFAS-AHS) are already available for 115 patients. The median AOFAS-AHS score increased from 33 points preoperatively to more than 80 points three to six months postoperatively. This increase remained nearly constant over the entire two-year follow-up period. CONCLUSION Covering less than 10 % of the approximately 240 providers in Germany and approximately 12 % of the annually implanted total ankle-replacements, the D. A. F.-register is still far from being seen as a national registry. Nevertheless, geographical coverage and inclusion of "high-" (more than 100 total ankle replacements a year) and "low-volume surgeons" (less than 5 total ankle replacements a year) make the register representative for Germany. The registry data show that the number of subsequent interventions and in particular the "true revision" procedures are markedly lower than the 20 % often postulated in the literature. In addition, a high level of patient satisfaction over the short and medium term is recorded. From the perspective of the authors, these results indicate that total ankle arthroplasty - given a correct indication and appropriate selection of patients - is not inferior to an ankle arthrodesis concerning patients' satisfaction and function. First valid survival rates can be expected about 10 years after the register's start.