Low molecular weight analogs of trolox with potent antioxidant activity in vitro and in vivo

Alpha-tocopherol and its water-soluble derivative, Trolox, are capable of terminating free radical chain reactions and limiting reperfusion-induced cell damage. In the present study, we have quantitated the effects of two relatively potent analogs of alpha-tocopherol/Trolox, WIN 62079 and U-78517F, which attenuated exogenously generated free radical damage in cultured cells and reperfusion injury in vivo. In a cultured rat renal tubular epithelial cell line (NRK-52E), millimolar concentrations of ascorbate or the combination of Trolox plus ascorbate reduced cellular damage (quantitated as lactate dehydrogenase [LDH] release) induced by radicals generated by hypoxanthine/xanthine oxidase. In contrast, WIN 62079 and U-78517F attenuated damage at micromolar concentrations. Similarly, intravenous administration of WIN 62079 (three hourly doses of 3 mg/kg) and U-78517F (10 mg/kg infused over 5 min) reduced reperfusion-induced myocardial damage in rabbit coronary-occulded hearts: Trolox (three hourly doses of 100 mg/kg) was less potent and required ascorbate (three hourly doses of 150 mg/kg) as a cofactor. These data demonstrate that is feasible to design potent, water-soluble analogs of Trolox which are efficacious against free radical-mediated cell death and which do not require ascorbate as a cofactor. Moreover, since U-78517F and WIN 62079 are two to three orders of magnitude more potent than Trolox, and since they contain different amino side chains, these data further support the concept that side chain modifications of the chromane ring nucleus of alpha-tocopherol derivatives significantly affect activity, possibly by providing additional activity or by enhancing availability to the cellular site of action. © 1992 Wiley-Liss, Inc.     

Hepatic metastasis detection: comparison of three CT contrast enhancement methods

A prospective, blinded comparison of three methods of hepatic contrast enhancement in computed tomography (CT) was conducted in 15 patients with colorectal carcinoma metastatic to the liver. Arterial portography (AP-CT) was performed with injection of contrast material into the superior mesenteric artery during CT. Delayed scanning (DS-CT) was performed 4 hours after intravascular administration of contrast material (mean dose, 280 mL). CT with an ethiodized oil emulsion (EOE-CT) was performed 1 hour after slow intravenous infusion of the emulsion. All patients underwent laparotomy following imaging studies. A lesion-by-lesion analysis of 56 metastases showed no significant differences in sensitivity (AP-CT, 77%; DS-CT, 83%; EOE-CT, 82%), but the false-positive rate for AP-CT was significantly higher than that for DS-CT (P less than .001) or EOE-CT (P less than .01). False-positive rates for EOE-CT and DS-CT were not significantly different. The predictive value of a positive test was 63% for AP-CT, 90% for DS-CT, and 81% for EOE-CT. AP-CT does not appear to be clinically useful for detection of hepatic metastases because of the high false-positive rate. No difference could be demonstrated between DS-CT and EOE-CT. DS-CT is a valuable method for hepatic contrast enhancement.     

Amebic liver abscess: diagnosis and treatment evaluation with MR imaging

Magnetic resonance images were obtained before and after treatment in 17 patients with 29 amebic liver abscesses. Pretreatment T1-weighted images showed a sharply circumscribed, heterogeneous, low-signal-intensity mass, devoid of normal hepatic tissue and corresponding to the abscess cavity as measured sonographically. T2-weighted images showed the abscess cavity as a hyperintense region and also showed a larger region of hyperintensity extending from the cavity margins to the liver surface, corresponding to edematous but morphologically normal liver tissue. After treatment, the abscess cavity became homogeneously hypointense on T1-weighted images, corresponding to liquefaction of the abscess center. With successful treatment, concentric rings corresponding to (a) an inner margin of inflamed granulation tissue, (b) bands of type I collagen, and (c) the outer margin of atrophic and/or mildly inflamed liver tissue became prominent on T1- and T2-weighted images. T2-weighted images showed rapid resolution of the perifocal hepatic edema.     

Shedding of the guinea pig peritoneal macrophage Fc gamma receptor. Effect on apparent association constant and on the number of IgG-binding sites on the cells

During our studies on the structure and properties of guinea pig peritoneal macrophage Fc gamma receptor we observed that these cells spontaneously release an IgG-binding material into supernatant. Although the shedding was accompanied by a decrease in IgG-binding ability of macrophages, the number of IgG-binding sites/cell before and after shedding was similar. However, macrophages after the shedding interacted with IgG with a lower apparent association constant, Ka. Therefore, we assume that the decrease of IgG-binding ability of cells was an effect of decrease in value of Ka. Experiments with protein synthesis inhibitors showed that the shed receptor is replaced by "de novo" synthesized receptor molecules.     

Work in progress: hybrid temporal-energy subtraction in digital fluoroscopy

Initial clinical results using a digital fluoroscopic implementation of the combined time-energy ("hybrid") subtraction technique are described, with emphasis on carotid and renal imaging. Where patient motion artifacts are due to soft-tissue motion alone, hybrid subtraction can remove them. Due to the need for a finite separation time between high- and low-energy pairs, however, the present implementation of the hybrid technique is not completely immune to soft-tissue motion. The intrinsic signal-to-noise ratio of hybrid imaging is less than that of conventional temporal subtraction. However, since the low-energy temporal subtraction images are included in the hybrid data set, the diagnostic quality of the examination is not compromised.     

Effectiveness of prolonged use of continuous passive motion (CPM), as an adjunct to physiotherapy,after total knee arthroplasty

Background  

Adequate and intensive rehabilitation is an important requirement for successful total knee arthroplasty.     

Role of calcium ions in vertebrate phototransduction.

In the recent years several new regulatory calcium-binding proteins were identified in vertebrate photoreceptor cells. Calcium ions can regulate different stages of visual transduction acting through calcium-binding proteins. It is also accepted that Ca(2+)-mediated feedback pathways underlie the light adaptation mechanisms in photoreceptor cells. This article describes the role of calcium ions in the cascade of enzymatic reactions contributing to the vertebrate rod cell phototransduction and to light adaptation.