Distribution of phenolic compounds in Middleeuropean taxa of the Achillea millefolium L. aggregate

Achillea millefolium L. s.l. is a cytogenetically, morphologically, and chemically polymorphic aggregate. Besides the sesquiterpenes that possess chemotaxonomic relevance and mediate the antiphlogistic activity, the plant contains phenolic compounds such as dicaffeoylquinic acids and flavonoids causing choleretic and spasmolytic effects. To evaluate their contribution to the chemotaxonomy of European taxa of the A. millefolium group, we developed a SPE-HPLC/UV method that allows quantification of the phenolic constituents in the different taxa. The investigated species displayed differences in the quantitative and qualitative composition of phenolic acids and flavonoids. Hence, they seem to be of chemotaxonomic significance, especially for the distinction of the diploid taxa. Combining the obtained results with the data of the sesquiterpene analyses gives a comprehensive insight into the distribution of those pharmacologically relevant plant constituents in the A. millefolium group.     

Vaccination-induced syphilis and the Hübner malpractice litigation

This article examines smallpox vaccination in the 19th century as background for a notorious medical malpractice case that occupied Bavarian courts from April 1853 until May 1854. Dr. Georg Hübner, the defendant, was accused of having initiated a small epidemic of syphilis by using the lymph of a syphilitic infant to vaccinate 13 infants. The litigation and its published contemporaneous discussion demonstrate conflicts in the understanding of syphilis, the hazards of having to make a purely clinical diagnosis, the effect of obsolete legal wording in medical litigation, and the attitude of leading physicians to a guilty colleague. This case ultimately led to efforts to make arm-to-arm smallpox vaccination safer, and by 1898 to abandon the technique in favor of bovine sources that were sterilized and stabilized by various methods.     

Impaired endothelium-mediated relaxation in isolated cerebral arteries from insulin-resistant rats

Insulin resistance (IR) impairs vascular responses in peripheral arteries. However, the effects of IR on cerebrovascular control mechanisms are completely unexplored. We examined the vascular function of isolated middle cerebral arteries (MCAs) from fructose-fed IR and control rats. Endothelium-dependent vasodilation elicited by bradykinin (BK) was reduced in IR compared with control MCAs. Maximal dilation to BK (10(-6) M) was 38 +/- 3% (n = 13) in control and 19 +/- 3% (n = 10) in IR arteries (P < 0.01). N(omega)-nitro-L-arginine methyl ester (L-NAME; 10 microM) decreased responses to BK in control arteries by approximately 65% and inhibited the already reduced responses completely in IR MCAs. Indomethacin (10 microM) reduced relaxation to BK in control MCAs by approximately 40% but was largely ineffective in IR arteries. Combined L-NAME and indomethacin treatments eliminated the BK-induced dilation in both groups. Similarly to BK, endothelium-mediated and mainly cyclooxygenase (COX)-dependent dilation to calcium ionophore A23187 was reduced in IR arteries compared with controls. In contrast, vascular relaxation to sodium nitroprusside was similar between the IR and control groups. These findings demonstrate that endothelium-dependent dilation in cerebral arteries is impaired in IR primarily because of a defect of the COX-mediated pathways. In contrast, nitric oxide-mediated dilation remains intact in IR arteries.     

An isobolographic analysis of the hypnotic effects of combinations of dexmedetomidine with fentanyl or diazepam in rats.

The effects of the combinations of dexmedetomidine-fentanyl and dexmedetomidine-diazepam on the righting reflex were studied in rats. The doses that block the righting reflex for the agents given alone and for their combinations were determined with a probit procedure and compared with an isobolographic analysis. The interactions between dexmedetomidine and fentanyl or diazepam were found to be synergistic. In the dexmedetomidine-diazepam combination studies, less than one-fourth of the single drug dose (for each of two agents) was needed to produce the required effect. These data confirm synergistic interactions between dexmedetomidine and fentanyl or diazepam in producing hypnotic-anesthetic action.     

Vasoconstrictor mechanisms in the cerebral circulation are unaffected by insulin resistance

Insulin-resistance (IR) impairs agonist-induced relaxation in cerebral arteries, but little is known about its effect on constrictor mechanisms. We examined the vascular responses of the basilar artery (BA) and its side branches in anesthetized Zucker lean (ZL) and IR Zucker obese (ZO) rats using a cranial window technique. Endothelin-1 (ET-1) constricted the BAs in both the ZL and ZO rats, but there was no significant difference between the two groups (ZL: 36 +/- 8%; ZO: 33 +/- 3% at 10(-8) M). Inhibition of the ET(A) receptors by BQ-123 slightly increased the diameters of the BAs, with no difference shown between the ZL (6 +/- 1%) and ZO (5 +/- 3%) rats. Expressions of the ET(A) receptors and ET-1 mRNA examined by immunoblot analysis and RT-PCR, respectively, were also similar in the ZL and ZO groups. Phorbol 12,13-dibutyrate (PDBu), an activator of protein kinase C (PKC), and the thromboxane A(2) (TxA(2)) mimetic U-46619 constricted the BAs, but similarly to ET-1, there was no significant difference between the ZL and ZO groups (10(-6) M PDBu: ZL: 33 +/- 2%; ZO: 32 +/- 4%; and 10(-7) M U-46619: ZL: 23 +/- 1%; ZO: 19 +/- 2%). Inhibition of Rho-kinase with Y-27632 induced dilation of the BAs, and these responses were also comparable in the ZL and ZO rats (ZL: 39 +/- 4%; ZO: 38 +/- 2% at 10(-5) M). In contrast, nitric oxide-dependent relaxation to bradykinin was significantly reduced in the ZO rats (10(-6) M: 10 +/- 3%) compared with ZLs (29 +/- 7%, P < 0.01). These findings indicate that vasoconstrictor responses of the BA mediated by ET-1, TxA(2), PKC, and Rho-kinase are not affected by IR.     

On anixiopsis stercoraria (hansen) hansen, 1897 and its imperfect stage: Keratinomyces ajelloi vanbreuseghem, 1952

Summary It is herein reported on the discovery of the imperfect stage of an ascomycete,Anixiopsis stercoraria (Hansen)Hansen, 1897, which is also the imperfect stage of another ascomycete,Arthroderma uncinatum,Dawson &Gentles, 1961:Keratinomyces ajelloi Vanbreuseghem, 1952. Thus, the same imperfect form belongs to two different perfect forms.The discovery was made onMicrosporon sp. infected hairs in a case of typical tinea microsporina. The present investigation encompasses 16 strains, all cultured from tinea microsporina. There were both single and double infections.Nine of the cases yieldedAnixiopsis stercoraria along with its imperfect form:Keratinomyces ajelloi Vanbreuseghem, 1952.Four cases revealed a double infection,Keratinomyces ajelloi on one hand and,Arthroderma uncinatum as well asAnixiopsis stercoraria, on the other.The three final cases yieldedM. audouinii andKeratinomyces ajelloi with its perfect form,Anixiopsis stercoraria. K. ajelloi produces only macroconidia, never microconidia. What was mistakenly construed as the microconidia ofK. ajelloi, belongs as microconidia toAnixiopsis stercoraria. Out of these microconidia the development of true macroconidia was observed.Both the relationship of the perfect and imperfect forms ofAnixiopsis stercoraria and cultural characteristics of the perfect form and its pathogenicity are discussed.

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Zusammenfassung Es wird über die Entdeckung der Konidialform eines Ascomyceten berichtet,Anixiopsis stercoraria (Hansen)Hansen, 1897, die zugleich die Konidialform eines anderen Ascomyceten ist,Arthroderma uncinatum,Dawson undGentles, 1961:Keratinomyces ajelloi Vanbreuseghem, 1952. Demzufogle gehört dieselbe Konidialform zwei verschiedenen Ascomyceten an.Die Entdeckung erfolgte an durchMikrosporon infizierten Haaren eines Falles einer klassischen Tinea microsporina. Die gegenwärtige Untersuchung umfasst 16 Fälle, alle von Tinea microsporina der behaarten Kopfhaut herstammend. Die Tinea microsporina war durch einfache und doppelte Infektion verursacht.Neunmal lieferte die KulturAnixiopsis stercoraria zusammen mit der Konidialform:Keratinomyces ajelloi.Viermal lag eine Doppelinfektion vor:Keratinomyces ajelloi, einerseits, undArthroderma uncinatum sowieAnixiopsis stercoraria, andererseits.Endlich lieferten die Kulturen in drei FällenM. audouinii undK. ajelloi zusammen mitAnixiopsis stercoraria. K. ajelloi entwickelt nur Makrokonidia und niemals Mikrokonidia. Was irrtümlicherweise als Mikrokonidia vonK. ajelloi aufgefasst wurde, gehört als MikrokonidiaAnixiopsis stercoraria an. Die Entwicklung von Makrokonidien aus diesen Mikrokonidien wurde beobachtet.Die Wechselbeziehung der Konidial- und Perithecialformen vonAnixiopsis stercoraria, ihr kultureller Charakter und ihre Pathogenität sind einer Diskussion unterzogen.

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Résumé On s'y rapporte à la découverte de la forme conidiale d'un ascomycète,Anixiopsis stercoraria (Hansen)Hansen, 1897, laquelle est, en même temps, la forme conidiale d'un autre ascomycète,Arthroderma uncinatum,Dawson etGentles, 1961:Keratinomyces ajelloi Vanbreuseghem, 1952. Conséquemment, la même forme conidiale appartient aux deux ascomycètes différents.La découverte a été effectuée sur des poils infectés parMicrosporon sp. dans un cas d'une teigne microsporique typique. La présente investigation embrasse 16 cas, provenant tous des cas des teignes microsporiques du cuir chevelu. Des teignes microsporiques ont été causées ou par une simple ou par une double infection.Neuf fois on a obtenu des cultures deAnixiopsis stercoraria avec sa forme conidiale:Keratinomyces ajelloi.Quatre fois il y avait d'infection double:Keratinomyces ajelloi, d'une part, etArthroderma uncinatum etAnixiopsis stercoraria, d'autre part.En fin, les cultures ont démontré en trois cas,M. audouinii etK. ajelloi avecAnixiopsis stercoraria. K. ajelloi ne developpe que des macroconidies et jam ais des micronidies. Ce qu' on avait conçu par erreur comme microconidies deK. ajelloi, appartient comme microconidies à l'Anixiopsis stercoraria. Le développement des macroconidies à partir de ces microconidies a été observé.La relation des formes conidiale et périthéciale del'Anixiopsis stercoraria, son charactère culturel et sa pathogénie ont été discutés.