As to their clinical relevance, a remarkable difference become evident between antibodies to human hsp60 and antibodies against bacterial hsp in the extent of association with CHD. On the basis of these findings and some pertinent literature data, an alternative explanation for the association between high level of anti-hsp antibodies and atherosclerotic vascular diseases is raised.
Human liver biopsy samples, collected from 52 individuals, were analysed by inductively coupled plasma-mass spectrometry (ICP-MS) and total reflection X-ray fluorescence (TXRF) spectrometry in a retrospective study (i.e. patient selection and liver biopsy were not for the purpose of element analysis). The freeze-dried samples (typically 0.5-2 mg dry weight) were digested in a laboratory microwave digestion system and solutions with a final volume of 1 mL were prepared. The concentrations of Cr, Mn, Fe, Ni, Cu, Zn, Rb, and Pb were determined by use of a Thermo Elemental X7 ICP-MS spectrometer. TXRF measurements were performed with an Atomika Extra IIA spectrometer. Yttrium was employed as an internal standard, prepared by dissolution of 5N-purity yttria (Y(2)O(3)) in our laboratory. The accuracy was tested by analysis of NIST 1577a Bovine Liver certified reference material. The concentrations of Fe, Cu, Zn, and Rb determined in human liver biopsy samples were in good agreement with data published by other authors. The distribution of nickel in the samples was surprisingly uneven-nickel concentrations ranged from 0.7 to 12 microg g(-1) (dry weight) in 38 samples and in several samples were extremely high, 36-693 microg g(-1). Analysis of replicate procedural blanks and control measurements were performed to prevent misinterpretation of the data. For patients with steatosis (n=14) Ni concentrations were consistently high except for two who had levels close to those measured for the normal group. As far as we are aware no previous literature data are available on the association of steatosis with high concentration of nickel in human liver biopsies taken from living patients.
A new, simple, and accurate ultrasonic method is elaborated for thyroid volume determination with commercially available high-resolution real-time equipment. The method takes into account the special and variable shape of the thyroid. The measurements were taken in three perpendicular sections. Volume calculations were done by applying the corrected ellipsoid model and computer-aided numerical integration, as well as by the conventional simple ellipsoid model. The accuracy of the method was tested by comparing direct measurements of a silicone rubber phantom with ultrasonography of a tissue-equivalent thyroid phantom. Both phantoms were modeled as casts of the same thyroid, which was obtained at autopsy. From the phantom measurements the deviation between the volume calculated by numerical integration or the corrected ellipsoid method and the real volume determined directly with the silicone rubber phantom was less than 5% on average, while volume calculations using the conventional ellipsoid model involved about +20% systematic error. In vivo studies in 40 subjects gave similar results: the ratios of the volumes calculated by simple and corrected ellipsoid method and by numerical integration [V(E), V(CE), and V(NI), respectively] were [V(E)/V(CE)] = 1.19 +/- 0.11 and [V(NI)/V(CE)] = 1.02 +/- 0.11. In conclusion corrected ellipsoid method is suggested for the clinical practice.
In spite of its widespread clinical application, there is little information on the cellular cardiac effects of the antidiabetic drug rosiglitazone in larger experimental animals. In the present study therefore concentration-dependent effects of rosiglitazone on action potential morphology and the underlying ion currents were studied in dog hearts.
EXPERIMENTAL APPROACHStandard microelectrode techniques, conventional whole cell patch clamp and action potential voltage clamp techniques were applied in enzymatically dispersed ventricular cells from dog hearts.
KEY RESULTSAt concentrations Ն10 mM rosiglitazone decreased the amplitude of phase-1 repolarization, reduced the maximum velocity of depolarization and caused depression of the plateau potential. These effects developed rapidly and were readily reversible upon washout. Rosiglitazone suppressed several transmembrane ion currents, concentration-dependently, under conventional voltage clamp conditions and altered their kinetic properties. The EC50 value for this inhibition was 25.2 Ϯ 2.7 mM for the transient outward K + current (Ito), 72.3 Ϯ 9.3 mM for the rapid delayed rectifier K + current (IKr) and 82.5 Ϯ 9.4 mM for the L-type Ca 2+ current (ICa) with Hill coefficients close to unity. The inward rectifier K + current (IK1) was not affected by rosiglitazone up to concentrations of 100 mM. Suppression of Ito, IKr, and ICa was confirmed also under action potential voltage clamp conditions.
CONCLUSIONS AND IMPLICATIONSAlterations in the densities and kinetic properties of ion currents may carry serious pro-arrhythmic risk in case of overdose with rosiglitazone, especially in patients having multiple cardiovascular risk factors, like elderly diabetic patients.
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In livers with a normal echopattern, none or minimal pathological changes were seen. In DI-type bright liver, connective tissue dominance exists, in DII-type bright liver lipid deposition dominance. On this basis it is proved that the diagnosis of a fatty liver can be established without biopsy, if no other indication for biopsy exists.
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