Distinct effects of acute and chronic nicotine application on microvascular thrombus formation and endothelial function in male and female mice

Background and aims Cigarette smoking is linked to thromboembolic events; however, a relationship between nicotine exposition and thrombosis has not been established. Thus, we intended to study the effect of acute and chronic nicotine application in an in vivo mouse model. Materials and methods In microvessels of the dorsal skin fold chamber, light-dye-induced thrombus formation was analyzed using intravital fluorescence microscopy. Male and female C57BL/6J mice received nicotine chronically via the drinking water (100 μg/ml) for 8 weeks. An additional series of experiments was performed with acute iv nicotine treatment (3 mg/kg body weight). Results No significant differences in microvascular thrombus formation were detected after chronic nicotine application in male and female animals when compared with controls. Accordingly, flow cytometric analysis did not show significant effects on platelet activity. Chronic nicotine treatment resulted in a significantly reduced endothelial activation in male, but not in female mice. In contrast, acute iv application of nicotine revealed significantly shorter thrombosis times in arterioles of female mice and a significantly increased endothelial P-selectin expression in mice of both genders. Conclusion Chronic nicotine application does not promote microvascular thrombus formation in mice of either gender, whereas acute high-dose iv administration caused a significant increase of arteriolar thrombosis in female animals probably via a synergistic effect of increased endothelial P-selectin expression and female hormone levels. A gender-dependency of acute nicotine action can be presumed. Best abstracts — Surgical Forum 2007     

Chirurgische Aspekte der Carotisinsuffizienz

Zusammenfassung In den Jahren 1970–1978 wurden 403 Carotis-Rekonstruktionen an 330 Patienten vorgenommen. Operationsmorbidität und-letalität zeigten eine deutliche Abhängigkeit von der Schwere des neurologischen Defizits zum Zeitpunkt der Operation: Stadiuml (137 Operationen): 1,5 % bzw. 0,7 %, Stadium II (134 Operationen): 2,2 % bzw. 3,7 %, Stadium III (29 Operationen): 3,4% bzw. 10,3%, Stadium IV (103 Operationen): 3,9 % bzw. 7,8 %. Nach der Life-table-Analyse (durchschnittliche Nachbeobachtungszeit : 40 Monate) sind 94 % der im Stadium I, 85 % der im Stadium II, 84 % der im Stadium III und 70 % der im Stadium IV operierten Patienten geheilt oder gebessert.

---

Reconstructive surgery of the internal carotid artery

Summary Between 1970 and 1978 we performed 403 endarterectomies of the internal carotid artery on 330 patients. Operative morbidity (and mortality) depended on the severity of the ischemic cerebral damage at the time of the operation: stage I (137 operations): 1.5 % (0.7 %); stage II (134 operations): 2.2 % (3.7 %); stage III (29 operations): 3.4 % (10.3 %) ; stage IV (103 operations): 3.9 % (7.8 %). According to the life-table analysis (average follow-up: 40 months) the rate of cured or improved patients amounts to 94 % (operated at stage I), 85 % (stage II), 84 % (stage III) and 70 % (stage IV).

Vortrag gehalten auf der 96. Tagung der Deutschen Gesellschaft für Chirurgie     

Small numbers in mutagenicity tests

Experimental control material for statistical analysis of the results of the micronuclei test in the mouse (NMRI strain) and the Chinese hamster and for the host-mediated assay in the mouse (NMRI strain) using auxotrophic bacterial strains are presented. The binomial distribution of the micronuclei makes it possible to analyse the sample size according to the formula of Cochran and Cox (1957).For the host-mediated assay, the experimental principles are given which make it possible to evaluate the results obtained even with a weakly mutagenic, unknown substance.Critical points in comparative tests are not only the methodological questions, but also pharmacokinetic problems of the substance being tested which can only be clarified in the species used for the mutagenicity test. If this is ignored then even experimentally based findings can only be recorded as speculations.Presented at the 3rd Meeting of the Gesellschaft für Umwelt-Mutationsforschung e. V., Neuherberg, July 1–2, 1976     

Die Coarctatio aortae abdominalis

Ohne Zusammenfassung Mit 5 Textabbildungen in 9 Einzeldarstellungen     

Rapamycin induces regression of endometriotic lesions by inhibiting neovascularization and cell proliferation

BACKGROUND AND PURPOSE: Rapamycin is a widely used drug with antifungal, immunosuppressant and antiangiogenic effects. Herein, we studied whether immunosuppressive doses of rapamycin are capable of influencing endometriotic lesions. EXPERIMENTAL APPROACH: We tested in vitro the potential of rapamycin to inhibit endothelial cell sprouting using the aortic ring assay and we further studied its effect on the expression of proliferating cell nuclear antigen (PCNA), apoptotic cell death-associated activated caspase-3 and vascular endothelial growth factor (VEGF) in cultured endometrial tissue fragments. In addition, we analyzed the drug in vivo after induction of endometriotic lesions by transplanting isolated endometrial fragments into the dorsal skinfold chamber of Syrian golden hamsters. Using intravital fluorescence microscopy, we repetitively analyzed angiogenesis, neovascularization and microcirculatory parameters over a time period of 14 days in rapamycin-treated animals and DMSO-treated controls. KEY RESULTS: Administration of rapamycin significantly reduced the size of the endometriotic lesions. This was associated by inhibition of VEGF-mediated angiogenesis as indicated by a suppression of endothelial cell sprouting in vitro and a reduction of microvessel density in endometriotic lesions in vivo. Moreover, rapamycin directly inhibited cell proliferation within endometrial tissue, while manifestation of apoptotic cell death remained unaffected. CONCLUSIONS AND IMPLICATIONS: Our data indicate that administration of rapamycin may represent a novel therapeutic approach for an antiangiogenic treatment of endometriosis.