The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

Reproduktionsmedizin

Since the introduction of in vitro fertilization in 1978, reproductive medicine and its associated scientific fields have developed rapidly. In Germany, progress in this field is impeded by the German Embryo Protection Act. Exemplary are the prohibition of embryo selection and the ban on genetic testing of the pre-implantation embryo. Nevertheless, infertility treatment outcome has to be optimized within the framework of this law, with the aim of making treatment more efficient, lowering the incidence of multiple gestations, making ovarian hyperstimulation safer, as well as reducing the financial costs for the couple.     

Der Einsatz des Prophy-Jet®-Gerätes zur Schmelzpolitur nach der Bracketentfernung

Zusammenfassung In einer In-vitro-Studie wurde die Einsatzfähigkeit des Prophy-Jet-^®-Gerätes für die Schmelzpolitur nach Bracketentfernung untersucht. In die Studie wurden drei verschieden stark gefüllte orthodontische Kleber einbezogen: Concise^®, Genie^® und Mono Lok^®. Alle Proben wurden rasterelektronenoptisch untersucht und fotografisch dokumentiert in Vergrößerungen zwischen 20- und 10 000fach. Die Oberflächenanalyse ergab, daß das Prophy-Jet^®-Gerät allein zur Schmelzpolitur nach Bracketentfernung nicht ausreicht, um unter klinisch vertretbarem Zeitaufwand (1 Minute/Zahn) eine kunststofffreie Schmelzoberfläche zu erzielen. Nach konventioneller makroskopischer Vorreinigung mit Scalern oder rotierenden Hartmetallfinierern zeigten sich nach fünfsekündiger Prophy-Jet^®-Bestrahlung noch geringe Kleberreste. Nach zehnsekündiger Expositionsdauer waren beim Mono Lok^®-Adhäsiv keine Kleberreste mehr nachweisbar, beim Concise^®-bzw. Genie^®-Adhäsiv fanden sich noch vereinzelte geringe Kleberinseln. Das Prophy-Jet^®-Gerät erscheint zur Unterstützung der Schmelzpolitur nach Bracketentfernung sinnvoll; eine sorgfältige Vorreinigung mit Hand- oder rotierenden Instrumenten ist jedoch erforderlich, um eine weitgehende Adhäsivreduktion zu erreichen. Die konventionelle Gummi- und Bimssteinpolitur kann nach 20sekündiger Prophy-Jet^®-Bestrahlung entfallen.

---

Summary The purpose of this in vitro investigation was to ascertain the effects of the Prophy-Jet^® air-powder abrasive system for enamel polishing after debonding. Three adhesives differing in filler content were included in this study: Concise^®, Genie^®, and Mono Lok^®. All specimens were examined by scanning electron microscopy and documented photographically at magnifications from 20 to 10 000. Surface analysis showed that using the Prophy-Jet^® exclusively is not sufficient to produce a clean and smooth enamel surface without residual adhesive after debonding and after one minute of exposure time, as might be justifiable in a clinical situation. After macroscopic conventional clean-up with scalers or rotary finishing instruments and five seconds of exposure time to the Prophy-Jet^® some occasional adhesive remnants could be located. After ten seconds of Prophy-Jet^® treatment all Mono Lok^®-adhesive was removed from the enamel surface; in the Concise^® and Genie^®-group few isolated adhesive remnants could be detected. The Prophy-Jet^® air-powder abrasive system was found to be efficient in supporting enamel polishing after debonding; but an accurate pretreatment with scalers or rotary finishing instruments is essential to achieve an extensive reduction of adhesive. Final polishing of the enamel surface with rubber wheels or prophy cup and pumice can be omitted after treatment with the Prophy-Jet^® for 20 seconds.

---

Résumé Le but de ce travail était d'éxaminer à l'aide d'une étude in vitro, l'emploi du Prophy Jet^® pour le polissage de l'émail après l'arrachage des brackets. Dans l'étude on a analysé trois substances adhésives différentes: Concise^®, Genie^® et Mono Lok^®. Après avoir examiné les spécimens par le microscope électronique à balayage, on les a documentés à l'aide de photos d'un grossissement de 20 à 10 000. L'analyse de la surface montre que la seule application du Prophy Jet^® (après l'arrachage des brackets) ne suffit pas pour obtenir une surface d'émail sans substance adhésive en un temps clinique d'une minute par dent. Après prétraitement macroscopique selon la méthode conventionnelle (scaler ou instruments montés sur tour) il demeurait encore de petits restes de la substance adhésive après l'application du Prophy Jet^® pendant cinq secondes. Après une durée d'application de dix secondes, on ne pouvait pas déceler de restes de Mono Lok^®, tandis qu'il y avait sporadiquement des restes de Concise^® et Genie^®. Ces résultats indiquent, que le Prophy Jet^® est efficace pour le polissage de l'émail après l'arrachage des brackets, mais on a tout de même besoin d'un nettoyage précédent minutieux avec des instruments convenables (scaler ou instruments montés sur le tour) pour obtenir une réduction considérable de la substance adhésive. On peut renoncer au polissage conventionnel à l'aide de caoutchouc ou de la pierre ponce après l'application du Prophy Jet^® pendant 20 secondes.

---

---

Vortrag auf der wissenschaftlichen Jahrestagung der Deutschen Gesellschaft für Kieferorthopädie 1985.     

A Chinese adolescent girl with Fechtner-like syndrome

We describe a 15-y-old girl with Fechtner-like syndrome, who is the first Chinese reported to have this rare syndrome. She presented with left homonymous hemianopia and neuroimaging revealed haemorrhage in both parietal and occipital lobes. Peripheral blood smear showed macrothrombocytopenia and intracytoplasmic inclusion bodies inside leucocytes. Thrombocytopenia and proteinuria responded to intravenous immunoglobulin and pulsed methylprednisolone. This case illustrates that life-threatening haemorrhage can occur in patients with Fechtner syndrome. Although there was no effective treatment reported in the literature, high dose steroid and immunoglobulin seemed to be useful in our patient. Our patient also had nephritic-nephrotic syndrome with renal insufficiency, which is unusual in adolescent female patients.     

Orthodontic fine adjustment after vertical callus distraction of an ankylosed incisor using the floating bone concept.

The outcome of vertical callus distraction of a segment of tooth-supporting alveolar process might be functionally and esthetically unsatisfactory because of the unidirectional impact of intraoral distraction devices. In this case report, we describe how, with a shortened consolidation phase and application of the floating bone effect, the tooth-supporting osteotomy segment can be successfully aligned 3 dimensionally. We applied orthodontic force systems that went beyond the unidirectional vector preset by the mechanical properties of the distraction device.     

Solid and papillary epithelial neoplasms of the pancreas: CT findings

Five female patients and one male patient with solid and papillary epithelial neoplasms of the pancreas were examined with computed tomography (CT). The mean age of the patients was 27 years (range, 13-46 years). All cases showed well-encapsulated, round or lobulated masses consisting of both cystic and solid areas. Cystic portions showed CT numbers that suggested hemorrhagic necrosis. There were no internal septations within the masses. In three tumors located in the head of the pancreas, dilatation of the biliary tree was absent or minimal, although the masses were large. Two tumors contained calcifications. One tumor demonstrated metastatic deposits in liver and lymph nodes. Metastatic masses appeared similar to the primary pancreatic mass. Solid and papillary neoplasm of the pancreas should be the primary diagnostic consideration when characteristic CT findings are detected in a young female patient.     

EndocrinologyHormonal profile during the follicular phase in cycles stimulated with a combination of human menopausal gonadotrophin and gonadotrophin-releasing hormone antagonist (Cetrorelix)

A third-generation gonadotrophin-releasing hormone antagonist(Cetrorelix) was used during ovarian stimulation in 32 patientsundergoing assisted reproduction, in order to prevent the prematureluteinizing hormone (LH) surge. In all patients, ovarian stimulationwas carried out with two or three ampoules of human menopausalgonadotrophin (HMG), starting on day 2 of the menstrual cycle.In addition, 0.5 mg of Cetrorelix was administered daily fromday 6 of HMG treatment until the day of ovulation inductionby human chorionic gonadotrophin (HCG). A significant drop inplasma LH concentration was observed within a few hours of thefirst administration of Cetrorelix (P<0.005). Moreover, noLH surge was detected at any point in the treatment period inany of the 32 patients. A mean oestradiol concentration of 2122±935ng/1 was observed on the day of the HCG administration, indicatingnormal folliculogenesis. Like LH, progesterone concentrationalso dropped within a few hours of the first administrationof Cetrorelix (P< 0.005). A 0.5 mg daily dose of Cetrorelixprevented a premature LH surge in all the 32 patients treated.