Trends in radiation dose for low grade gliomas across the United States

Journal of Neuro-Oncology - Adjuvant radiation is often used in patients with low grade gliomas with high-risk characteristics with a recommended dose of 45–54 Gy. We used the...     

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.     

Effects of mycophenolic acid on IL-6 expression of human renal proximal and distal tubular cells in vitro.

BACKGROUND: Interleukin-6 (IL-6) is a multifunctional cytokine which regulates immune responses and host defence mechanisms. IL-6 has been found to be increased in certain inflammatory conditions of the kidney, in which tubular epithelial cells play a pivotal role. Human renal tubular cells express IL-6. Until now no data about the effect of the immunosuppressant drug mycophenolic acid (MPA) on IL-6 expression were available. METHODS: Proximal and distal tubular epithelial cells (PTC/DTC) have been isolated immunomagnetically. Confluent monolayers were stimulated with interleukin-1beta (IL-1beta; 25 U/ml), IL-1beta+ MPA (0.25-50 micro M) or MPA alone for 48 h. Release of IL-6 protein into the supernatant was evaluated with an enzyme immunoassay, IL-6 mRNA expression was evaluated using the Quantikine mRNA kit. RESULTS: After IL-1beta stimulation, a highly significant 2.6- (PTC) and 3.8-fold (DTC) upregulation of IL-6 expression was detectable. IL-6 mRNA was upregulated by IL-1beta [1.57- (PTC) and 2.03-fold (DTC)]. MPA inhibited this cytokine-induced IL-6 expression in a dose-dependent manner. Incubation with the lowest MPA concentration had no effect on the stimulated upregulation, whereas all higher doses significantly decreased IL-6 expression. Dexamethasone significantly inhibited the cytokine-induced IL-6 protein release in PTC, but not in DTC. CONCLUSIONS: In this study we demonstrated for the first time an inhibitory effect of MPA on the stimulated IL-6 expression of renal tubular epithelial cells. In contrast to older data, which showed a synergistic upregulation of the expression of a CC-chemokine by a combination of cytokines and MPA, in the present study we could demonstrate an immunosuppressive effect of MPA on the expression of an important cytokine.     

Der Einfluss des Phosphors auf den Organismus

Ohne ZusammenfassungNach einem am 8. und 15. Novbr. 1871 unter Demonstration der Originalpräparate in der Berliner med. Gesellschaft gehaltenen Vortrage. Hierzu Taf. I–III.     

Structural analysis of poly(3-alkylthiophene)s

Poly(3-hexylthiophene) (PT6), poly(3-octylthiophene) (PT8), poly(3-decylthiophene) (PT10) and poly(3-dodecylthiophene) (PT12) were synthesized by electrochemical and chemical polymerization. Investigation of these polymers by means of gel permeation chromatography indicates that the polymers prepared from the different monomers under similar conditions do not differ substantially considering molecular weight and molecular weight distribution. Bimodal distributions were found for electropolymerized polymers, and with increasing polymerization time, the high-molecular-weight and probably highly branched fraction increased relatively to the low-molecular-weight fraction. The microstructure of the polymers was investigated by nuclear magnetic resonance, and it has been found that the polymers exhibit more types of structural units than expected from a simple coupling of adjacent thiophene moieties in 2,5′-positions. Chemical oxidation with iron trichloride in chloroform gave soluble, high-molecular-weight poly(3-alkyl-thiophene)s with a rather low amount of irregular couplings, and these more regular polymers exhibited a higher degree of crytallinity. Room temperature conductivities of the oxidized polymers were between 0,1 and 30 S/cm depending on the polymerization conditions, but these values were rather independent of the length of the alkyl substituent.     

LIPOPROTEIN(α) IN HEALTH AND DISEASE

SUMMARY Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)-related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a).     

Ultrasound for diagnosis of apophyseal injuries

Avulsion injuries of the apophysis is a problem in young athletes. A correct diagnosis is necessary for establishing the appropriate treatment and the rehabilitation program. However, it is often difficult to distinguish between a simple muscle strain and an avulsion fracture. The X-ray examination is helpful only when an ossification center of the apophysis exists. Ultrasonography is considered the suitable diagnostic tool for these cases. From June 1988 to June 1993, 243 young athletes were seen with an anamnestic and clinically suspected apophyseal injury of the lower extremity. In all cases X-ray examination and ultrasound examination were performed. In 80 cases the diagnosis was confirmed by X-ray examination and in 97 by ultrasonography. Four criteria were defined for the sonographic examination: (a) a hypoechogenic zone, (b) increased distance to the apophysis, (c) dislocation of the apophysis, and (d) mobility of the apophysis on dynamic examination. These criteria are correlated to (a) edema, (b) lysis, (c) avulsion, and (d) unstable avulsion of the apophysis. Ultrasonography is a proven technique for the detection of apophyseal injuries. In comparison to X-ray examination, it has the advantages of no radiation exposure, early detection even without ossification center, and dynamic examination.