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.     

Heart rate analysis in 24 patients treated with 150 mg amitriptyline per day

Twenty-four patients treated with 150 mg amitriptyline per day for an episode of major depression underwent a standardized heart rate analysis (HRA) before therapy and after 14 days. The battery of cardiovascular reflex tests included the determination of the coefficient of variation (CV) while resting and during deep respiration, a spectral analysis of heart rate, the heart rate response to standing, and the Valsalva manoeuvre. The results of the initial HRA did not differ from a group of 24 normal control subjects matched for age and sex. On day 14 of treatment the patients showed significantly reduced values of heart rate variability in all tests (P<0.0001), probably due to the anticholinergic side effects of amitriptyline. Heart rate increased form 78.1 to 93.6 bpm on average (P<0.0001). Abnormal CV at rest was registered in 96% of the patients; during deep respiration 29% showed abnormal CV results. An abnormal spectral analysis was found in 100% of the cases (low frequency peak: 42%, mid-frequency peak: 100%, high frequency peak: 79%). The heart rate response to standing was abnormal in 75% and the Valsalva test in 33% of the cases. Eighty-eight percent of the patients fulfilled the criteria of a cardiovascular autonomic neuropathy under the conditions of amitriptyline therapy. As yet, the consequences of these changes for the patients have not been sufficiently elucidated.     

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 .     

Quantification of oxidative DNA modifications in mitochondria

Specific repair endonucleases were used to quantify oxidativemodifications in mitochondrial DNA (mtDNA) from rat liver andfrom porcine liver and kidney by means of a relaxation assay.In rat liver mitochondria the number of modifications sensitiveto formamidopyrimidine-DNA glycosylase (FPG protein), whichinclude 8-hydroxyguanine (8-oxo-7, 8-dihydro-guanine) residues,was only 0.8±0.2 per 10⁵ base pairs (bp). Even lowervalues were observed in porcine kidney (0.5±0.3 per 10⁵bp) and liver (0.4±0.2 per 10⁵ bp). The numbers of sitesof base loss (AP sites) sensitive to T4 endonuclease V and of5,6-dihydropyrimidines sensitive to endonuclease III were lessthan 0.2 per 10⁵ bp in all cases. The data provide evidencethat the steady-state levels of oxidative mtDNA modificationsare low under physiological conditions, either because reactiveoxygen species generated in the mitochondria are instantly inactivatedor because of efficient DNA repair processes inside mitochondria.     

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.