Woodinine and its Stereomers - Absolute Configuration

The synthesis of all the four stereomers of the alkaloid woodinine ( 12a )¹⁾ is described and the stereochemical conclusions of Païs³⁾ and Still⁶⁾ are discussed. The absol. configurations of woodinine ( 12a ) and its diastereomer 8b are unequivocally deduced from the pertinent piperazinediones 16 and 17 .     

The foundation of experimental ophthalmology by Theodor Leber

Theodor Leber grew up in Heidelberg as the son of a professor of Romance languages. Initially he planned to study natural sciences. Bunsen's advice led him to medicine. During his studies he succeeded in solving a competition problem posed by Helmholtz in the medical department. A short period of practical work in the eye hospital of Knapp was unsatisfactory. In Vienna with the physiologist Carl Ludwig, he was able in 1863/64, at the age of only 24 years, to demonstrate the blood circulation of the eye by color injections into the arteries and veins. Since that time the schematic drawings of his results can be found in every textbook of ophthalmology. On the occasion of the congress of the German Ophthalmological Society in Heidelberg in 1864, Theodor Leber reported on these findings and met with immense approval. In 1864–67 he followed an invitation as coworker of Liebreich to Paris; in 1867 he became A.v. Graefe's coworker in Berlin; in 1871 he moved to Göttingen, which became the first eye clinic with a laboratory for experimental investigations.The second epoch-making discovery accomplished by Leber was the detection of the fluid exchange in the eye. These results have also been confirmed by modern methods. Therefore, Theodor Leber can be called the father of experimental ophthalmology.     

Rheo-optical fourier transform infrared spectroscopy of polyurethanes and their blends with polyolefins

Rheo-optical Fourier transform infrared spectroscopy was used to analyze the orientational behavior of hard and soft segments of thermoplastic poly(ether urethane)s (TPU-Et) and poly(ester urethane)s (TPU-Es) and their blends with a 20 mass-% contribution of either polyethylene (PE) or polypropylene with an amorphous rubber phase (PP). The blends show a reduced stress level, lower elongation-to-break and a lower degree of orientation of the segments — especially for the TPU-Es blends — compared to those of pure TPU's when uniaxially elongated. Blends of TPU-Et with PP show reduced stress but increased strain compared to pure films of TPU-Et. This is caused by an improved adhesion of the rubber phase in the polypropylene and the polyether phase of TPU-Et. Optical micrographs visualize deformed polyolefin particles in elongated films of TPU-Et/PP blends. In the TPU-Et/PP blend we could achieve equivalent orientation for the polyolefin phase and the segments of TPU-Et caused by this higher phase adhesion compared to the other blends. Orientation functions (OF's) of absorption bands which specifically represent hard or soft polyurethane segments or which are characteristic of the polyolefin phase have been calculated to monitor the molecular alignment due to the mechanical treatment.     

18F-FDG PET for detecting myocardial viability: validation of 3D data acquisition.

(18)F-FDG PET is an important diagnostic tool for detecting myocardial viability in patients with coronary artery disease. In combination with perfusion scanning, (18)F-FDG PET allows differentiation between reversibly and irreversibly damaged myocardium and selection of patients likely to benefit from revascularization. Viability PET is usually performed in two-dimensional (2D) mode. Taking into account the rising number of three-dimensional (3D)-only scanners, a validation of 3D acquisition is required. METHODS: Twenty-one patients with coronary artery disease referred for (18)F-FDG PET underwent an imaging protocol of nongated 2D (2D-NG) and gated 2D (2D-G) acquisitions for 15 min each, followed by 3D gated acquisitions for 10 min (3D-10) and 5 min (3D-5), using an ECAT Exact HR+ scanner. Results were analyzed using a 20-segment polar map in terms of activity concentration (Bq/mL), viability (50% uptake threshold), regional activity distribution, visual assessment of viability based on a 3-point rating scale, and left ventricular ejection fraction. RESULTS: Activity concentration measured in each segment with 2D-G, 3D-10, and 3D-5 showed a good linear correlation with 2D-NG. Quantitative viability assessment with 3D-5 gave a sensitivity of 84% and a specificity of 98%, compared with 2D-NG. No differences in regional activity distribution and visual viability assessment were found between the various protocols. Left ventricular ejection fractions obtained with 3D-10 and 3D-5 showed a good linear correlation with those measured with 2D-G. CONCLUSION: An ECG-gated 3D imaging protocol gave results comparable to those of 2D acquisition with regard to absolute and regional myocardial activity distribution, left ventricular function, and visual viability assessment. Sensitivity for viability assessment with a 50% uptake threshold was significantly less with 3D, but specificity was maintained. This protocol delivers a clinical performance nearly equivalent to that of 2D acquisition.     

Expression profiling identifies the CRH/CRH-R1 system as a modulator of neurovascular gene activity.

Corticotropin-releasing hormone receptor type 1 (CRH-R1)-deficient mice display reduced anxiety-like behavior, a chronic corticosterone deficit, and an impaired neuroendocrine stress response caused by disruption of the hypothalamic-pituitary-adrenocortical (HPA) axis. The molecular substrates and pathways of CRH/CRH-R1-dependent signaling mechanisms underlying the behavioral phenotype as well as the consequences of lifelong glucocorticoid deficit remain largely obscure. To dissect involved neuronal circuitries, we performed comparative expression profiling of brains of CRH-R1 mutant and wild-type mice using our custom made MPIP (Max Planck Institute of Psychiatry) 17k cDNA microarray. Microarray analysis yielded 107 genes showing altered expression levels when comparing CRH-R1 knockout mice with wild-type littermates. A significant proportion of differentially expressed genes was related to control of HPA and hypothalamic-pituitary-thyroid (HPT) axes reflecting not only the disturbance of the HPA axis in CRH-R1 mutant mice but also the interplay of both neuroendocrine systems. The spatial analysis of regulated genes revealed a prevalence for genes expressed in the cerebral microvasculature. This phenotype was confirmed by the successful cross-validation of regulated genes in CRH overexpressing mice. Analysis of the cerebral vasculature of CRH-R1 mutant and CRH overexpressing mice revealed alterations of functional rather than structural properties. A direct role of the CRH/CRH-R1 system was supported by demonstrating Crhr1 expression in the adult murine cerebral vasculature. In conclusion, these data suggest a novel, previously unknown role of the CRH/CRH-R1 system in modulating neurovascular gene expression and function.