New catalysts for the oxidative polymerization of 2,6-dimethylphenol, 2. Copper complexes containing the dicyanoethenedithiolatocuprate structure as the ligand

It was found that the reaction of 1,2-dicyano-1,2-ethenedithiolate, resp. of bis(1,2-dicyano-1,2-ethenedithiolato)cuprate(2-), with Cu²⁺ does not lead to copper bis(1,2-dicyano-1,2-ethenedithiolato)cuprate(2-) dihydrate ( 1a ) as described in the literature but to a reaction product which has a complex structure containing mainly Cu⁺. This compound as well as complexes with the same ligand, but with Cu⁺, Cu²⁺ or Cu³⁺ as the central atom, were synthesized and tested with and without added cuprous chloride as catalysts for the oxidative polymerization of 2,6-dimethylphenol. Included in this investigation were some copper complexes with the isomeric ligand 2,2-dicyano-1,1-ethenedithiolate.     

Amphotere ionenaustauscher, 5

Amphoteric ion exchangers with uniform structure were obtained by copolymerization of aziridinyl monomers followed by alkaline saponification of the ester groups of the polymers. The following compounds were copolymerized: Diethyl 2,4-di(1-aziridinyl)glutarate ( 1 ) with either diethyl (1-aziridinyl)succinate ( 4 ), diethyl (1-aziridinyl)fumarate ( 5 ) or dimethyl (1-aziridinylmethyl)succinate ( 6 ); diethyl ester of 3,3′-(1,4-phenylene) and 3,3′-(1,3-phenylene)di[3-(1-aziridinyl)propionic acid] ( 2a ) and ( 2b ), respectively, with either methyl (1-aziridinyl) acetate ( 7 ) or methyl (1-aziridinyl)propionate ( 8 ); dimethyl 3,6-di(1-aziridinyl)cyclohexane-1,2-dicarboxylate ( 3 ) with dimethyl 6-(1-aziridinyl)cyclo-2-hexene-1,2-dicarboxylate ( 9 ). Further the dioctylester of 3,3′-(1,4-phenylene)di[3-(1-aziridinyl)propionic acid] ( 10 ) was homopolymerized. The properties of the amphoteric resins were investigated. In particular the binding ability for Cu^2⊕, Ni^2⊕, Zn^2⊕, and Mg^2⊕ ions and the swelling ability were studied as function of the pH of the solution. The uptake of CU²⁺ ions was determined as a function of time. An average capacity for Cu²⁺ ions of 2,5 to 3,75 mmol/g of dry resin was found at pH 5,5–6.     

Clonogenicity of normal and malignant hematopoietic progenitor cells after exposure to synthetic alkyl-lymphospholipids

Summary Alkyl-lysophospholipids (ALP) are synthetic analogues of natural lysophosphatidylcholine and represent a new class of anti-tumor agents. They are cytotoxic in vitro with a high selectivity for neoplastic cells which, in contrast to normal cells, lack an alkyl-cleavage enzyme to degrade the adsorbed ALP molecules. As ALP accumulates, it interferes with normal membrane phospholipid turnover and eventually causes disruption of membrane integrity. To evaluate the potential value of ALP in eliminating leukemic cells from remission marrows prior to autologous transplantation, we tested the effect of various ALPs on the clongenicity of normal human marrow cells and on promyelocytic leukemia HL-60. A remarkable difference in the dose response to ALP of normal marrow cells an HL-60 was observed. After an incubation period of 24 h, the same inhibition of clonogenicity in HL-60 occurred at ALP concentrations 4 times lower than in normal marrow cells. Reducing the exposure time to 6 h enhanced the selectivity further: whereas HL-60 colonies were nearly completely inhibited at 16 g ALP/ml, more than 50% of normal CFU-c and BFU-E were recovered after incubation with 48 g/ml. No further increase in selectivity was achieved by changing the incubation temperature. Both thioether- and alkyl-analogues were active and no difference was observed between methoxy- and acylamino-substituted ALPs. We conclude that this selective cytotoxicity makes ALP compounds worth further study as purging agents in autologous bone marrow transplantation programs.Supported by the Deutsche Forschungsgemeinschaft An 111/3     

Ornithine decarboxylase in motoneurons during regeneration

The activity of ornithine decarboxylase, the rate-limiting enzyme in polyamine synthesis, was assayed in the isolated facial nucleus of the rat at various times after axotomy of the facial nerve. In addition, it was measured 24 h after the second of a series of two lesions (conditioning lesion design) with various times between the first and second operations. Ornithine decarboxylase activity was found to increase 8 h after nerve transection and was maximum after 24 h (300% of control). Thereafter the activity declined to subnormal levels where it remained for several weeks. Ornithine decarboxylase activity did not increase again when a second axotomy was made 2 weeks after the first lesion. However, ornithine decarboxylase did respond to the second axotomy if it was carried out 3 weeks after the first lesion. Histochemical localization of ornithine decarboxylase demonstrated that the increase in enzyme activity was mainly confined to the perikarya of the motoneurons. These data suggest that this enzyme is somehow involved in triggering the "regeneration program" and clearly indicate that at least some aspects of the neuronal response to axotomy are not further stimulated by a conditioning lesion.     

Polymyxin B,a selective inhibitor of protein kinase C,diminishes the release of noradrenaline and the enhancement of release caused by phorbol 12,13-dibutyrate

Summary Slices of the rabbit hippocampus were labelled with ³H-noradrenaline, superfused continuously with a modified Krebs-Henseleit medium containing the uptake inhibitor cocaine and stimulated electrically (2 ms, 3 Hz, 24 mA, 5 V/cm). Phorbol 12,13-dibutyrate (PDB), a potent activator of protein kinase C (PKC), strongly enhanced the electrically-evoked overflow of tritium. In contrast, polymyxin B, a relatively selective inhibitor of PKC, diminished the evoked tritium overflow in a time-and concentration-dependent manner. The enhancement of the evoked overflow of tritium caused by PDB was strongly reduced in the presence of polymyxin B (100 mol/l). These results suggest 1. that PKC may be involved in the physiological mechanism of action-potential-induced noradrenaline release from noradrenergic nerve terminals and 2. that the PDB-induced enhancement of noradrenaline release may be due to a direct activation of PKC.Abbreviations PKC protein kinase C - PDB phorbol 12,13-dibutyrate - TPA 12-O-tetradecanoyl 13-acetate     

Traumatic aneurysms of the descending thoracic aorta

From July 1979 to December 1985 we observed 51 patients with traumatic lesions of the descending thoracic aorta. Twenty-nine had acute ruptures, mostly accompanied by multiple injuries, and 27 had to be operated upon immediately. Twenty-two patients (19 males, 3 females) had chronic traumatic aneurysms of the descending thoracic aorta (more than six weeks after trauma). Mean age at the time of trauma was 24 years. Mean age at time of surgery was 36.5 years. Twelve patients were symptomatic. All were treated surgically. At surgery, complete aortic disruption was found in 15 patients and partial rupture in seven. We did not use aortic shunting of any kind, only aortic cross-clamping. Hypertension was controlled by intravenous drug infusion. The ruptured aortic segment was replaced in all cases by prosthetic Dacron graft. There were no operative deaths. One patient (age 77) died 11 weeks after surgery from multiple organ failure. One case of postoperative paraplegia was observed. This patient recovered almost completely from his neurological deficit.     

High-Protein,Low-Glycaemic Meal Replacement Decreases Fasting Insulin and Inflammation Markers—A 12-Month Subanalysis of the ACOORH Trial

Lifestyle interventions, including meal replacement, are effective in the prevention and treatment of type-2-diabetes and obesity. Since insulin is the key weight regulator, we hypothesised that the addition of meal replacement to a lifestyle intervention reduces insulin levels more effectively than lifestyle intervention alone. In the international multicentre randomised controlled ACOORH (Almased Concept against Overweight and Obesity and Related Health Risk) trial, overweight or obese persons who meet the criteria for metabolic syndrome (n = 463) were randomised into two groups. Both groups received nutritional advice focusing on carbohydrate restriction and the use of telemonitoring devices. The intervention group substituted all three main meals per day in week 1, two meals per day in weeks 2–4, and one meal per day in weeks 5–26 with a protein-rich, low-glycaemic meal replacement. Data were collected at baseline and after 1, 3, 6 and 12 months. All datasets providing insulin data (n = 446) were included in this predefined subanalysis. Significantly higher reductions in insulin (−3.3 ± 8.7 µU/mL vs. −1.6 ± 9.8 µU/mL), weight (−6.1 ± 5.2 kg vs. −3.2 ± 4.6 kg), and inflammation markers were observed in the intervention group. Insulin reduction correlated with weight reduction and the highest amount of weight loss (−7.6 ± 4.9 kg) was observed in those participants with an insulin decrease > 2 µU/mL. These results underline the potential for meal replacement-based lifestyle interventions in diabetes prevention, and measurement of insulin levels may serve as an indicator for adherence to carbohydrate restriction.     

Inflammation and the Association of Vitamin D and Depressive Symptomatology

Depression and vitamin D deficiency are major public health problems. The existing literature indicates the complex relationship between depression and vitamin D. The purpose of this study was to examine whether this relationship is moderated or mediated by inflammation. A community sample (n = 7162) from the LIFE-Adult-Study was investigated, for whom depressive symptoms were assessed via the German version of CES-D scale and serum 25-hydroxyvitamin D (25(OH)D) levels and inflammatory markers (IL-6 and CRP levels, WBC count) were quantified. Mediation analyses were performed using Hayes’ PROCESS macro and regression analyses were conducted to test moderation effects. There was a significant negative correlation between CES-D and 25(OH)D, and positive associations between inflammatory markers and CES-D scores. Only WBC partially mediated the association between 25(OH)D levels and depressive symptoms both in a simple mediation model (ab: −0.0042) and a model including covariates (ab: −0.0011). None of the inflammatory markers showed a moderation effect on the association between 25(OH)D levels and depressive symptoms. This present work highlighted the complex relationship between vitamin D, depressive symptoms and inflammation. Future studies are needed to examine the effect of vitamin D supplementation on inflammation and depressive symptomatology for causality assessment.     

In vitro evidence for participation of DEC-205 expressed by thymic cortical epithelial cells in clearance of apoptotic thymocytes

Binding of apoptotic cells was compared after incubation of thymocytes with two clones of murine thymic stromal cells to which CD4(+)/CD8(+) thymocytes attach. With the BA/10, but not the BA/2, clone, thymocytes with apoptotic morphology were bound irreversibly. These tightly bound thymocytes were further identified as apoptotic in terms of active caspase-3 and DNA fragmentation assayed in situ. FACS analysis indicated that the apoptotic thymocytes are at an early double-positive stage and results with mice mutant for the Fas gene showed that the Fas-Fas ligand system is not involved. Comparison of BA/10 and BA/2 cells showed that the former, but not the latter, can be induced to express CDR-1 antigen which is characteristic of cortical epithelial thymic stroma and constitutively express DEC-205, a surface protein common to cortical thymic epithelium and dendritic cells. Antibody NLDC-145 that is specific for the DEC-205 protein strongly reduced the number of stromal cells with bound apoptotic thymocytes. Preincubation of thymocytes in dexamethasone dramatically increased the number of bound apoptotic cells, indicating that the thymic cortical epithelial cells can participate in clearance of apoptotic thymocytes through involvement of DEC-205.