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.     

Energy spectra of poly(arylenevinylene)s containing different aromatic units

The energy gaps of poly(p-arylenevinylene)s with phenylene, naphthylene and anthrylene subunits are determined by extrapolating the UV/VIS spectroscopic data of the oligomers. The band structure of the three polymers was theoretically investigated. The topology-, geometry- and correlation-factors were determined upon which the energy spectra of this class of one-dimensional π-electron systems depend.     

Pregnancy after successful therapy of HBV-associated hepatocellular cancer--a case report]

Malignant tumors are a difficult problem in obstetrics, both in pregnancy but also after an successful therapy, especially, if the patient wishes to be pregnant. However, there are borderline cases of medical and ethical regions. In the present paper the case of a young women (21 years old) with HCC is described. In the age of 16 years a solid hepatocellular carcinoma was found and treated by partial resection of the right lobus hepaticus. Anamnestically a blood exchange transfusion caused by a neonatal Rh-incompatibility and a hepatitis B in the age of 11 months are known. 3 and 6 years after the treatment, she was successfully pregnant and is today mother of 2 children.     

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.     

Pharmacokinetics of methylmethacrylate monomer during total hip replacement in man

Summary The concentration of methylmethacrylate monomer (MMA) in the blood stream after implantation of the components of 15 total hip prostheses using bone cement was determined in the pulmonary artery, the radial artery, and the superior vena cava after cement application, and correlated with the observed drop in blood pressure and the increase in the pulmonary arterial pressure. In all samples MMA was found. The values ranged from 0.02 g/ml to 59 gg/ml. The mean maximum value after implantation of the stem was measured to be 7.8g/ml in the pulmonary artery, 4.6 g/ml in the radial artery, and 1.75 g/ml in the superior vena cava. After implantation of the cup the values were clearly lower. The simultaneously recorded blood pressure decreased slightly during the first 3 min and then returned to previous values. The pulmonary arterial mean pressure increased from 18 to 20mmHg during the first 10 min. Although in some patients a drop in blood pressure started at the same time as MMA reached maximum values, high concentrations did not result in a greater effect on the circulatory parameters. Statistical analysis by the Spearman test revealed no correlation between MMA concentrations and the decrease in blood pressure or the increase in the pulmonary arterial pressure.

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Zusammenfassung Während der Implantation von fünfzehn Totalendoprothesen mit Knochenzement wurden die Konzentrationen von Methylmethacrylatmonomer (MMA) in der Arteria pulmonalis, der Arteria radialis and der Vena cava superior bestimmt und mit dem beobachteten Blutdruckabfall and dem Anstieg des pulmonalarteriellen Druckes korreliert. In den Proben konnten MMA-Konzentrationen zwischen 0,02 g/ml and 59 g/ml nachgewiesen werden. Die mittlere Maximalkonzentration betrug nach Implantation des Schaftes 7,8 g/ml in der Pulmonal-, 4,6 g/ml in der Radialarterie und 1,75 g/ml in der Vena cava superior. Die Konzentrationen nach Implantation der Pfanne waren deutlich geringer. Der gleichzeitig aufgezeichnete Blutdruck fiel geringgradig während der ersten drei Minuten and kehrte dann auf Ausgangswerte zuriick. Der pulmonalarterielle Mitteldruck stieg von 18 auf 20 mm Hg während der ersten zehn Minuten. Obwohl bei einigen Patienten der Blutdruckabfall mit dem Auftreten maximaler MMA-Konzentrationen zusammenfiel, hatten höhere MMA-Konzentrationen keinen größeren Effekt auf die zirkulatorischen Parameter. Bei der statistischen Analyse mit dem Spearman Test bestand keine statistische Korrelation zwischen den MMA-Konzentrationen und dem Abfall des Blutdruckes bzw. dem Anstieg des pulmonalarteriellen Druckes.

     

Epidemiological and clinical features of travel-associated cryptosporidiosis

Data concerning the clinical and epidemiological features of travel-associated cryptosporidiosis are lacking. In order to investigate the impact of this disease on travellers' health, a retrospective study was conducted at the Institute of Tropical Medicine, Berlin. In total, 57 cryptosporidial infections were identified between 2000 and 2004, resulting in a prevalence of 2.9% in patients with travel-associated diarrhoea. Travel to south-central Asia, especially India, was associated with a higher prevalence of infection than was travel to other destinations. Clinically, the disease resembled giardiasis, but fever and arthralgias seemed to occur more frequently.     

High throughput parallel analysis of hundreds of patient samples for more than 100 mutations in multiple disease genes

As more mutations are identified in genes of known sequence, there is a crucial need in the areas of medical genetics and genome analysis for rapid, accurate and cost-effective methods of mutation detection. We have developed a multiplex allele-specific diagnostic assay (MASDA) for analysis of large numbers of samples (> 500) simultaneously for a large number of known mutations (> 100) in a single assay. MASDA utilizes oligonucleotide hybridization to interrogate DNA sequences. Multiplex DNA samples are immobilized on a solid support and a single hybridization is performed with a pool of allele-specific oligonucleotide (ASO) probes. Any probes complementary to specific mutations present in a given sample are in effect affinity purified from the pool by the target DNA. Sequence-specific band patterns (fingerprints), generated by chemical or enzymatic sequencing of the bound ASO(s), easily identify the specific mutation(s). Using this design, in a single diagnostic assay, we tested samples for 66 cystic fibrosis (CF) mutations, 14 beta-thalassemia mutations, two sickle cell anemia (SCA) mutations, three Tay-Sachs mutations, eight Gaucher mutations, four mutations in Canavan disease, four mutations in Fanconi anemia, and five mutations in BRCA1. Each mutation was correctly identified. Finally, in a blinded study of 106 of these mutations in > 500 patients, all mutations were properly identified. There were no false positives or false negatives. The MASDA assay is capable of detecting point mutations as well as small insertion or deletion mutations. This technology is amenable to automation and is suitable for immediate utilization for high-throughput genetic diagnostics in clinical and research laboratories.