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Biomedical subjects

N Deutschländer

Publications and source records attributed to N Deutschländer.

17 recordsLinked to original sources

Amyloid beta-(1-40) stimulates cyclic GMP production via release of kinins in primary cultured endothelial cells.

Increased beta-amyloid production is believed to play a central role in the pathogenesis of Alzheimer's disease. Amyloid is deposited not only in the brain of Alzheimer patients as senile plaques but also in the cerebral vessel wall leading to cerebral amyloid angiopathy. Freshly solubilised amyloid beta-(1-40) was previously reported to exert a vasoconstrictor effect. We investigated whether amyloid beta-(1-40) affects the nitric oxide (NO)/cyclic GMP pathway in primary cultured endothelial cells from bovine aorta and rat coronary microvessels. Surprisingly, a significant increase in cyclic GMP production after incubation with freshly dissolved amyloid beta-(1-40) was found. The stimulation of cyclic GMP production could be inhibited by the bradykinin B(2) receptor antagonist icatibant, the NO synthase inhibitor N-omega-nitro-L-arginine, the serine protease inhibitor 3, 4-dichloroisocoumarin and the selective plasma kallikrein inhibitor Pefabloc PK, suggesting activation of the plasma kallikrein-kinin system. This is supported by a three- to four-fold increase in kinins in the supernatant of both types of endothelial cells after incubation with amyloid beta-(1-40) at concentrations of 10(-7) and 10(-6) mol/l.

Amyloid beta-Peptides↗

Clinical evaluation of hypothermic ventricular fibrillation, multi-dose blood cardioplegia, and single-dose Bretschneider cardioplegia in coronary surgery.

37 patients undergoing coronary revascularization were randomly assigned to three protocols for intraoperative myocardial protection: hypothermic ventricular fibrillation (HF) (n = 13), multi-dose blood cardioplegia (BCP) (n = 12) and single-dose Bretschneider's crystalloid cardioplegia (CCP) (n = 12). As intraoperative markers of ischemic damage myocardial ultrastructure, ATP, and CP contents were determined in left ventricular biopsy specimens taken before and after cardiac arrest. Release of serum enzymes (CK, CK-MB, LDH, SGOT) was determined pre- and postoperatively. Hemodynamic data were assessed before, during, and after operation. The incidence of low cardiac output, positive inotropic support, intraaortic balloon counterpulsation, peri-operative myocardial infarction, rhythm disturbances, and the rate of spontaneous defibrillation was compared between groups. The results show a better preservation of high energy phosphates in the BCP group as compared to the HF and CCP groups. Myocardial ultrastructure showed moderate ischemic damage in the hypothermic fibrillation group; in contrast, only slightly deteriorated cells were seen after cardiac arrest, when cardioplegia was used. The incidence of rhythm disturbances was 25% for HF and 42% for CCP. In contrast, only 17% of new rhythm disturbances were seen in the BCP group. Functional recovery (i.e. CI and SWI) of hearts protected with BCP was generally greater as compared to HF and CCP. Release of MB-creatine-kinase isoenzyme was higher in the HF group as compared to cardioplegia. Clinical outcome in terms of incidence of peri-operative infarction, positive inotropic support and low cardiac output was superior in the BCP group but not significantly different between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardioplegic Solutions↗

Perfluorochemical perfusion of the isolated guinea pig heart.

We studied the influence of a perfluorochemical (PFC) emulsion on the ultrastructure and function of the isolated perfused guinea pig heart compared to a Krebs-Henseleit solution. The PFC perfusion enhanced the force of contraction and reduced the coronary flow rate, but had no influence on the frequency and the oxygen consumption. The positive inotropic action of K-strophanthin and isoproterenol was slightly strengthened, whereas the beta-adrenergic antagonism by propranolol and the vasodilatation by glycerol trinitrate remained unchanged. The positive chronotropic action of isoproterenol was reduced during PFC perfusion. No histological differences depending on the perfusion medium were observed. It is concluded that PFC perfusion improves the functional state of the Langendorff preparation.

Animals↗

[Swine dysentery].

The microbiological and serological properties of Treponema hyodysenteriae, its mediators of pathogenicity and the morphological changes in infected animals were presented. From these changes and from the disturbances of the intestinal function, the clinical symptoms could be derived. Finally problems of epidemiology, therapy and prophylaxis of swine dysentery were discussed.

Agglutination Tests↗

Histopathology of experimental Chagas disease in NMRI-mice. A long term study following paw infection.

NMRI-mice were infected subcutaneously with T. cruzi Brazil and the pathohistological findings in 17 organs at different times after infection are described. The paw was chosen as injection site, for, due to the great variety of tissues found in a single histological section, the first reactions between host and parasite are best studied here. For this purpose the complete paw was embedded in plastic and sectioned longitudinally. After infection with 5 X 10(4) parasites a shift of parasitism from the initial host cells (macrophages) to the neighbouring muscle cells was observed. This occurred on the 9th day after infection. On the 18th day a generalized parasitism of organs containing muscle had developed, especially of myocardium and alimentary tract. Destruction and inflammation of heart muscle was the most important consequence with respect to mortality. The autonomous nervous system of heart and alimentary tract was involved, although not selectively. Liver and spleen played no role as host tissues. After infection with 10(2) or 10(3) parasites specific alterations in the animals surviving the acute phase were not observed from the 60th to 201st day. A perivenous encephalitis without cerebral parasitism was found in about one half of the experimental animals. It does not correspond to the known 'Chagas encephalitis' and is for the present defined as parainfectious.

Animals↗

Studies of reperfusion injury in skeletal muscle: preserved cellular viability after extended periods of warm ischemia.

Four hours of complete normothermic ischemia in the rat hindlimb has been thought to produce extensive and irreversible damage and no possibility of salvage by reperfusion. This study tests the hypothesis that, in contrast to conventional wisdom, the cellular integrity is preserved after 4 hours of complete warm ischemia and control of the initial reperfusion can restore immediate contractility in these limbs. Ninety-two rat hindlimbs were isolated and 26 of the 92 did not undergo ischemia or reperfusion and served as controls. Sixty-six limbs were subjected to 4 hours of complete warm ischemia; of those 34 were assessed after the ischemic period without reperfusion and 32 were reperfused after the ischemic period. Nineteen hindlimbs were reperfused with Krebs-Henseleit buffer at a pressure of 100 mmHg to simulate embolectomy (uncontrolled reperfusion). In 13 legs a modified reperfusate at a pressure of 60 mmHg was used during the initial 30 minutes followed by an additional 30 minutes of reperfusion with 100 mmHg using Krebs-Henseleit buffer (controlled reperfusion). At the end of each experimental protocol, limbs were assessed by the following methods: muscle contraction, water content, volume, high energy phosphate content, muscle pH, effluent pH, mitochondrial function, ultrastructure, flow, and creatinkinase activity in the effluent. Data are expressed as mean +/- SEM. Significant differences were defined as probabilities for each test of p less than 0.05. Four hours of complete warm ischemia resulted in a severe reduction of adenosine triphosphate (4.0 +/- 0.8 vs 27.1 +/- 6.7 mumol/gm protein, p less than 0.001) and no contractions could be stimulated (0.0 +/- 0.0% CC). Muscle pH fell to 6.3 +/- 0.1 (p less than 0.001), and ultrastructural damage occurred (score 3.3 +/- 0.4 vs 0.8 +/- 0.1, p less than 0.002). However, there was only a slight increase in water content of the soleus muscle (78.7 +/- 0.2% vs 74.8 +/- 1.1%, p less than 0.05) without increase in limb volume (103.6 +/- 0.6% CV). In addition mitochondrial function was preserved well: mitochondrial oxidative phosphorylation capacity remained at 94% of control levels, ST3 at 93%, and ADP/O at 100% of control. Most importantly, controlled reperfusion restored immediate contractility in all limbs and was superior in all parameters investigated compared to uncontrolled reperfusion. These data support our inference that necrosis of skeletal muscle does not invariably occur after four hours of complete warm ischemia and suggest that muscle salvage by controlled reperfusion is possible after at least 4 hours of warm ischemia.

Adenosine Triphosphate↗