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.     

Versuche über die Ausscheidung von gasförmigem Stickstoff aus den im Körper umgesetzten Eiweissstoffen

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Thromboembolic and inflammatory complications of knee joint alloplasty with cemented endoprostheses]

In the presented paper the authors evaluate the long-term results of treatment for inflammatory and thromboembolic complications in knee joint alloplasty with cemented endoprostheses. The clinical material spanning the years 1998-2003 are 15 patients with analysed complications, it determine 9% of all operated. They have evaluated achieved results using the HSS knee rating scale in their own modification. As far as the authors are concerned, venographic examination is a prerequisite for appropriate care of the patients following knee joint alloplasty who might have deep venous thrombosis. It is necessary to provide similar treatment when developing infections are suspected in the perioperative period and in cases of late infections. Consequently, antibiotic therapy and a possible quick bacteriological checkup for healing a postoperative wound is a prerequisite for successful treatment. Achieved results induce statement, that thromboembolic and inflammatory complications caused at most operated chronic vein insufficiency, deficit of range of motion at operated joint and gait insufficiency. Thromboembolic complications was always related with inflammation of knee joint alloplasty in our own material.     

Loss of breast cancer metastasis suppressor 1 protein expression predicts reduced disease-free survival in subsets of breast cancer patients.

PURPOSE: This study aims to determine the effect of loss of breast cancer metastasis suppressor 1 (BRMS1) protein expression on disease-free survival in breast cancer patients stratified by estrogen receptor (ER), progesterone receptor (PR), or HER2 status, and to determine whether loss of BRMS1 protein expression correlated with genomic copy number changes. EXPERIMENTAL DESIGN: A tissue microarray immunohistochemical analysis was done on tumors of 238 newly diagnosed breast cancer patients who underwent surgery at the Cleveland Clinic between January 1, 1995 and December 31, 1996, and a comparison was made with 5-year clinical follow-up data. Genomic copy number changes were determined by array-based comparative genomic hybridization in 47 breast cancer cases from this population and compared with BRMS1 staining. RESULTS: BRMS1 protein expression was lost in nearly 25% of cases. Patients with tumors that were PR negative (P=0.006) or HER2 positive (P=0.039) and <50 years old at diagnosis (P=0.02) were more likely to be BRMS1 negative. No overall correlation between BRMS1 staining and disease-free survival was observed. A significant correlation, however, was seen between loss of BRMS1 protein expression and reduced disease-free survival when stratified by either loss of ER (P=0.008) or PR (P=0.029) or HER2 overexpression (P=0.026). Overall, there was poor correlation between BRMS1 protein staining and copy number status. CONCLUSIONS: These data suggest a mechanistic relationship between BRMS1 expression, hormone receptor status, and HER2 growth factor. BRMS1 staining could potentially be used in patient stratification in conjunction with other prognostic markers. Further, mechanisms other than genomic deletion account for loss of BRMS1 gene expression in breast tumors.     

Prehospital care of acute myocardial infarction: a review.

Each year more than 1 million people in the United States suffer from acute myocardial infarction (MI) with most of the deaths occurring within hours of symptom onset. Over the last 25 years, different prehospital systems have evolved throughout the world which allow early cardiac monitoring and treatment of acute MI patients. Thrombolytic therapy in acute MI has been shown to decrease mortality and preserve left ventricular function when administered early after onset of symptoms. The potential role of Emergency Medical Services or Mobile Coronary Care Units in achieving early thrombolysis is under investigation. Several studies of prehospital interventions to achieve early thrombolysis are reviewed. The use of thrombolytics by prehospital personnel has been found to be feasible, safe, and effective in reducing time delays. However, whether this translates into clinical benefit remains to be seen.