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.     

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.     

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.     

CO2 laser surgery of oral premalignant lesions

Experiences gained in the CO2 laser treatment of patients with oral dysplastic precancerous lesions are presented. Besides 7 lichens planus, 50 leukoplakias of all grades of dysplasia, and carcinoma in situ and one lentigo maligna were removed superficially with a defocused laser. Within the average follow-up period of 37 months, 22% local recurrences were observed. In comparison with conservative drug therapy, conventional surgical procedures, and cryosurgical therapy, the CO2 laser treatment of multicentric premalignant diseases of the oral mucosa can be recommended as an alternative therapy.     

246. Moderne Prinzipien der operativen Behandlung von zentralen und zentrolateralen Mittelgesichtsfrakturen

Zusammenfassung Heute betreffen ca. 40 bis 45% aller Gesichtsschädelfrakturen das Mittelgesicht, wobei als häufigste Ursachen Verkehrsunfälle und Rohheitsdelikte zu nennen sind. Die Klassifikation der Mittelgesichtsfrakturen erfolgt in zentrale Mittelgesichtsfrakturen (Le Fort I und II), zentrolaterale Frakturen (Le Fort III) und laterale Mittelgesichtsfrakturen (Jochbein-Jochbogenfrakturen). Das Behandlungsprinzip besteht darin, nach Reposition der Knochenfragmente 1. die korrekte Occlusion und die Kontinuität der Mittelgesichtspfeiler zu erhalten oder wiederherzustellen und 2. die reponierten Fragmente an den cranial angrenzenden und intakten Knochenstrukturen zu fixieren. Die Fixation erfolgt durch intraorale Schienenverbände, fronto-maxilläre oder zygomaticomaxilläre Aufhängung sowie Miniplattenosteosynthesen. Bei Beachtung dieser Prinzipien können in der überwiegenden Anzahl der Fälle funktionell und ästhetisch zufriedenstellende Ergebnisse erreicht werden.     

Long-term biocompatibility of implanted polymer-based intrafascicular electrodes

Polymer-based longitudinal intrafascicular electrodes (polyLIFEs) were chronically implanted into the sciatic nerve of white New Zealand rabbits (n=8) for a period of 6 months (hereafter referred to as the long-term group). The impact of the implantation procedure, as observed 6 months post surgery, was evaluated in a sham-treated control group (n=9). The contralateral sciatic nerve served as the control for each animal. Nerve-fiber counts, fiber diameters, and myelin thickness were estimated at the level of the implant site, 1.5 cm proximally, and 1.5 cm distally for both nerves in sham-treated and long-term groups. Implantation of polyLIFEs had no significant effect on fiber counts, nerve-fiber diameter, or myelin thickness. A slight increase in connective tissue in the vicinity of the implant site was evident in the long-term group, including a thin but dense capsule immediately surrounding the implanted electrode.