Anellierte Thiopyrone, 3. Mitt. Sulfone aus Thiopyrano[3,2-b]indol-4(5H)-on- und Thiopyrano[2,3-b]indol-4(9H)-on-2-carbonsäuremethylestern

Fused Thiopyrones, III: Sulfones from Methyl 4,5-Dihydro-4-oxothiopyrano[3,2-b]indole-2-carboxylate and Methyl 4,9-Dihydro-4-oxothiopyrano[2,3-b]indole-2-carboxylate On treatment with m-chloroperbenzoic acid (mCPBA) the thiopyrones 1 and 4 are oxidized to the sulfones 2 and 5 , which add ethanol to yield the thiopyranosulfones 3 and 6 as mixtures of diastereomers. In one case a 3-hydroxy compound ( 7 ) could be isolated.     

3-Alkoxy-1.2.3-oxathiazolidin-4-on-2-oxide und 1-Alkoxy-indolin-2-one aus N-Alkoxyglykolamiden und Thionylchlorid oder 1.1′-Thionyldiimidazol

3-Alkoxy-1.2.3-oxathiazolidin-4-one-2-oxides and 1-Alkoxyindolin-2-ones from N-Alkoxyglycolamides and Thionyl Chloride or 1.1′-Thionyldiimidazole The reaction of N-alkoxyglycolamides 1 with thionyl chloride or 1.1′-thionyldiimidazole is shown to produce, dependending on the substituents at C-2 in 1 , either 3-alkoxy-1.2.3-oxathiazolidin-4-one-2-oxides 4 or 1-alkoxy-3-arylindolin-2-ones 6 .     

Lack of correlation after reperfusion between ventricular function and infarct size estimated by thallium single-photon emission computed tomography

In 32 patients with acute myocardial infarction, who had undergone successful intracoronary thrombolysis, the results of regional wall motion measured from contrast cineangiograms 10 to 21 days after thrombolysis were related to the results of thallium single-photon emission computed tomography (SPECT) after intravenous dipyridamole. Wall motion was measured by means of the centerline method, and thallium defect size was estimated by comparing the patient's circumferential profile with that of 20 normals. No correlation was found between ejection fraction or regional wall motion and thallium defect size. The time from symptom onset to thrombolysis was inversely correlated with the degree of hypokinesis (r=–0.51) but not with thallium defect size. In patients treated within 3 hours, hypokinesis was significantly less than in patients treated later (–1.1±0.6 SD vs –2.2±0.8 SD, p<0.01) whereas thallium defect size was not significantly different in both groups. It is concluded that, in patients after thrombolysis, thallium defect size determined by SPECT does not reflect the degree of left ventricular dysfunction.     

New x-ray tube performance in computed tomography by introducing the rotating envelope tube technology

The future demands of computed tomography imaging regarding the x-ray source can be summarized with higher scan power, shorter rotation times, shorter cool down times and smaller focal spots. We report on a new tube technology satisfying all these demands by making use of a novel cooling principle on one hand and of a novel beam control system on the other hand. Nowadays tubes use a rotating anode disk mainly cooled via radiation. The Straton x-ray tube is the first tube available for clinical routine utilizing convective cooling exclusively. It is demonstrated that this cooling principle makes large heat storage capacities of the anode disk obsolete. The unprecedented cooling rate of 4.8 MHU/min eliminates the need for waiting times due to anode cooling in clinical workflow. Moreover, an electronic beam deflection system for focal spot position and size control opens the door to advanced applications. The physical backgrounds are discussed and the technical realization is presented. From this discussion the superior suitability of this tube to withstand g-forces well above 20 g created by fast rotating gantries will become evident. Experience from a large clinical trial is reported and possible ways for future developments are discussed.     

Equalization of asymmetries of tonus in the optomotor system of rabbits

Summary Turning a rabbit on a turn-table for a few degrees induces compensatory eye-movements and results in an asymmetry of tonus in the optomotor system. If the visual input is discontinued (darkness), this asymmetry decays and the eyes drift back to the mid-position within 12–18 sec. The equalization of such asymmetries of tonus under normal conditions and under curare is described. Tonus asymmetries induced by tilting the animals about the longitudinal axis are neither compensated under visual, nor under non-visual, conditions. Recordings were taken from oculomotor neurons, and changes of their firing frequencies were used as a measure for eye movements.A preliminary report was given at the spring meeting of the German Physiological Society 1973.Supported by the Deutsche Forschungsgemeinschaft, SFB 33.     

Chondroitin sulfate A released from platelets blocks RANTES presentation on cell surfaces and RANTES-dependent firm adhesion of leukocytes

The sequestration of chemokines on the surface of microvascular endothelium is an early event in the selective recruitment of leukocytes. The sequestration and presentation of chemokines must be tightly controlled to confine the extravasation of leukocytes and to prevent uncontrolled inflammation. We investigated whether soluble molecules released under physiological conditions could control chemokine immobilization on cell surfaces and function as regulatory chemokine binding molecules. We determined that human serum contains a molecule that suppresses RANTES (CCL5) binding to endothelial cells, PBMC and CHO cells. Using platelet-rich and platelet-free plasma, serum from patients with thrombocytopenia, and purified platelets, we identified platelets as the source of the chemokine-binding molecule and further identified it as chondroitin sulfate A. In contrast to platelet-derived fully-sulfated chondroitin sulfate A, low-sulfated chondroitin sulfate A present in plasma was almost inactive. Under physiological flow conditions chondroitin sulfate A was found to block RANTES-mediated firm adhesion of monocytes to endothelial cells. It also prevented RANTES-mediated influx of calcium in CCR5-transfected CHO cells while internalization of CCR5 was only marginally reduced. Taken together, chondroitin sulfate A released from platelets appears to act as an important regulatory molecule for cellular responses to chemokines.     

Organotypic culture of embryonic electromotor system tissues from Torpedo marmorata

An explant culture system has been used to study the electric organ and electric lobe tissues of Torpedo marmorata at different stages during the development of the electromotor system.The myotubes in tissue expiants, taken from the electric organ primordia of 33–38 mm body-length embryos prior to electrocyte differentiation, contract spontaneously on explantation and have electrogenic membranes. The myotubes subsequently lose these properties in vitro and can differentiate in the absence of neural tissue into immature electrocytes which have morphologically characteristic postsynaptic membranes.Isolated expiants of differentiated electric organ tissue from 60–100 mm body-length embryos can be maintained for 3 to 4 weeks in vitro but cellular outgrowth is minimal. In contrast, a rapid, dense outgrowth of cells and a subsequent regeneration of myotubes occurs when differentiated electric organ explants are co-cultured with electric lobe tissue from embryos of the same stage. Cellular outgrowth from differentiated electric-organ tissue expiants can be stimulated by spinal cord, medulla, cerebellum and heart tissues but a subsequent regeneration of myotubes has not been observed. Myotube regeneration in the presence of electric lobe tissue is maximal with tissue from 60–80 mm body-length embryos. The myotubes that regenerate from differentiated electric organ expiants have not been observed to differentiate into electrocytes.Neuritic outgrowth in vitro occurs with electric lobe tissue taken at two different embryonic stages. The first stage corresponds to a period when most of the neuroepithelial cells in the lobe anlagen are withdrawing from the mitotic cycle and projecting axons into the branchial arches. The second, later stage is when the electromotorneurones are normally generating axon collaterals that are invading the interelectrocyte space of electrocyte columns. Maximum neuritic outgrowth at this second, later stage is obtained with tissue from 60–80 mm body-length embryos. Although neuritic invasion of electrocyte column expiants can be obtained in electric organ—electric lobe co-cultures at this later stage, synapses similar to those observed during the early stages of synaptogenesis in the electric organs in vivo have not been observed in vitro.     

Transgenic rat model of Huntington's disease

Huntington's disease (HD) is a late manifesting neurodegenerative disorder in humans caused by an expansion of a CAG trinucleotide repeat of more than 39 units in a gene of unknown function. Several mouse models have been reported which show rapid progression of a phenotype leading to death within 3-5 months (transgenic models) resembling the rare juvenile course of HD (Westphal variant) or which do not present with any symptoms (knock-in mice). Owing to the small size of the brain, mice are not suitable for repetitive in vivo imaging studies. Also, rapid progression of the disease in the transgenic models limits their usefulness for neurotransplantation. We therefore generated a rat model transgenic of HD, which carries a truncated huntingtin cDNA fragment with 51 CAG repeats under control of the native rat huntingtin promoter. This is the first transgenic rat model of a neurodegenerative disorder of the brain. These rats exhibit adult-onset neurological phenotypes with reduced anxiety, cognitive impairments, and slowly progressive motor dysfunction as well as typical histopathological alterations in the form of neuronal nuclear inclusions in the brain. As in HD patients, in vivo imaging demonstrates striatal shrinkage in magnetic resonance images and a reduced brain glucose metabolism in high-resolution fluor-deoxy-glucose positron emission tomography studies. This model allows longitudinal in vivo imaging studies and is therefore ideally suited for the evaluation of novel therapeutic approaches such as neurotransplantation.