A new method to evaluate ischemic heart disease: combined use of rest thallium-201 myocardial SPECT and Tc-99m exercise tetrofosmin first pass and myocardial SPECT.

We developed a new diagnostic method for simultaneously evaluating myocardial ischemia, myocardial viability and ventricular function in less than 90 minutes by combined use of rest thallium-201 (Tl) SPECT and exercise Tc-99m tetrofosmin (TF) first pass and SPECT. The subjects were 9 healthy controls, 19 angina pectoris patients, and 19 old myocardial infarction patients, in all of whom coronary angiography had been performed. Rest Tl myocardial SPECT was performed first, and was followed by exercise TF myocardial SPECT. We also performed first pass radionuclide angiography by TF during maximum exercise on a bicycle ergometer to assess the left ventricular ejection fraction (LVEF). The total examination time was less than 90 minutes. SPECT diagnosis was performed by semi-quantitative analysis. LVEF below 55% was regarded as abnormal. In the patients with angina pectoris, analysis according to the coronary artery showed that the diagnostic accuracy of SPECT was 85.0% for ischemia in the region of the left anterior descending branch (LAD), 87.5% for the left circumflex branch (LCX) and 77.8% for the right coronary artery (RCA). The accuracy of diagnosis for angina pectoris was 82.1%, as determined by SPECT alone, and rose to 89.3% when the LVEF levels were also taken into consideration. In the patients with old myocardial infarction, the diagnostic accuracy of SPECT was 84.2% for the LAD, 92.3% for the LCX and 85.0% for the RCA. Analysis by patients showed that the accuracy of diagnosis for myocardial infarction was 85.7%, as determined by SPECT alone. The diagnostic accuracy, however, rose to 89.3% when the LVEF levels also were taken into consideration. In conclusion, it was demonstrated that this combined diagnostic method was highly reliable for evaluating ischemic heart disease within a short time.

Synthesis and biological activities of ferulic acid derivatives.

Three types of ferulic acid derivatives (feruloylaminoacid benzyl or methyl esters, feruloylaminoacids, and 4-0-[N-(carbobenzyloxy)-aminoacyl] ferulic acid) were synthesized by introduction of amino acids at different sites and their platelet aggregation (PA)-inhibitory, tyrosinase-inhibitory, angiotensin converting enzyme (ACE)-inhibitory, and superoxide dismutase (SOD)-like activities were evaluated. PA, one of the mechanisms involved in repair of blood vessel injury, is related to diseases such as thrombosis. Developing a compound capable of inhibiting PA may thus provide a therapeutic tool. From the results of study, particularly in the case of 4-0-[N-(carbobenzyloxy) aminoacyl] ferulic acid (amino acid components: isoleucine, proline), inhibition of collagen-induced aggregation was maintained of the same level as with ferulic acid, but stronger dissociation of ADP-induced aggregation was detected. In other words, these compounds may not only prevent thrombosis but also dissolve thrombi. Further, the compounds with stronger tyrosinase-inhibitory activity were found to scavenge superoxide as effectively as ferulic acid. Since they are also more hydrophobic, they may be particularly efficacious as cosmetic ingredients. Finally, feruloyl-Phe-Ala-Pro-OH had strong ACE inhibitory activity (IC50 = 1.5 microM) lacking in the case of ferulic acid itself.

Detection of impaired fatty acid metabolism in right ventricular hypertrophy: assessment by I-123 beta-methyl iodophenyl pentadecanoic acid (BMIPP) myocardial single-photon emission computed tomography.

Fatty acid metabolism has been reported to be impaired earlier than myocardial blood flow in left ventricular hypertrophic myocardium, e.g., in hypertrophic cardiomyopathy or hypertensive heart disease. The purpose of this study was to determine whether impaired fatty acid metabolism also occurs in right ventricular (RV) hypertrophy. The subjects consisted of 6 patients with chronic obstructive pulmonary disease, 4 with primary pulmonary hypertension, 2 each with refractory pulmonary tuberculosis, tricuspid insufficiency, pulmonary embolism, 1 each with atrial septal defect, ventricular septal defect (Eisenmenger complex), Ebstein anomaly, and endocardial defect, and 7 healthy controls. SPECT imaging with Tl-201 (Tl) and I-123 beta-methyliodophenyl pentadecanoic acid (BMIPP), and Tc-99m RBC first pass and gated blood pool scintigraphy were performed. Based on Tl planar images, the subjects were classified into 3 groups: 7 patients with no RV visualization (Group A), 11 with moderate RV visualization (Group B) and 9 with marked RV visualization (Group C). As a semi-quantitative evaluation by Tl myocardial SPECT, 3 regions in 3 representative short axial images were divided into 9 segments, each of which was graded from 0 to +3, and their sum was calculated as the RV score. The right ventricular ejection fraction (RVEF) and the left ventricular ejection fraction were obtained by Tc-99m RBC cardiac scintigraphy. The groups with marked visualization of the right ventricle had lower RVEF (p < 0.01), and there was a good correlation between the RVEF and the RV score with both Tl and BMIPP (Tl: r = -0.79, BMIPP: r = -0.70). Although a good correlation was demonstrated between the RV score with Tl and BMIPP in Groups A and B (r = 0.86, p < 0.001), in Group C, in which there was marked RV T1 visualization, the RV score with BMIPP was significantly smaller than with Tl (BMIPP vs. Tl: 11.5 +/- 3.7 vs. 16.4 +/- 3.8, p < 0.01). These findings suggest that impaired fatty acid metabolism may exist in severely hypertrophic right ventricle due to RV overload.

Therapeutic effect of co-enzyme Q10 on idiopathic dilated cardiomyopathy: assessment by iodine-123 labelled 15-(p-iodophenyl)-3(R,S)-methylpentadecanoic acid myocardial single-photon emission tomography.

It has been reported that myocardial mitochondrial function can be improved by the administration of co-enzyme Q10 (CoQ10). Recently, iodine-123 labelled 15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was developed for metabolic imaging using single-photon emission tomography (SPET). This study was conducted to determine whether the therapeutic effects of CoQ10 on idiopathic dilated cardiomyopathy can be evaluated by BMIPP myocardial SPET. Fifteen patients, comprising 14 men and one woman (mean age: 64+/-12 years), were examined. CoQ10 was administered at 30 mg/day for a period of 35.7+/-12.4 days. BMIPP myocardial SPET was carried out before and after CoQ10 treatment. The count ratio of the heart (H) to the upper mediastinum (M) (H/M ratio) was calculated using a region of interest method with anterior planar imaging. Representative short-axis tomograms were divided into 27 segments (three slicesxnine segments). Each segmental score was analysed semiquantitatively using a four-point scoring system (normal=0, mild low uptake=1, severe low uptake=2, defect=3). The H/M ratio showed a significant improvement, from 2.39+/-0.39 to 2.54+/-0.47, after treatment (P<0.05). The BMIPP total defect score after CoQ10 treatment was significantly decreased to 10.1+/-4.3, compared to 13. 9+/-4.5 without CoQ10 treatment (P<0.001). However, the percent fractional shortening measured using echocardiography was not significantly different before and after CoQ treatment (19.2+/-8.1 vs 19.7+/-7.1). BMIPP myocardial SPET was confirmed to be sensitive in evaluating the therapeutic effects of CoQ10 in patients with idiopathic dilated cardiomyopathy. This method is unique, since the therapeutic effects can be estimated from the perspective of metabolic SPET imaging.

Comparison of two active HeT-A retroposons of Drosophila melanogaster.

HeT-A elements are Drosophila melanogaster LINE-like retroposons that transpose to broken chromosome ends by attaching themselves with an oligo(A) tail. Since this family of elements is believed to be involved in the vital function of telomere elongation in Drosophila, it is important to understand their transposition mechanism and the molecular aspects of activity. By comparison of several elements we have defined here the unit length of HeT-A elements to be approximately 6 kb. Also, we studied an active HeT-A element that had transposed very recently to the end of a terminally deleted X chromosome. The 12 kb of newly transposed DNA consisted of a tandem array of three different HeT-A elements joined by oligo(A) tails to each other and to the chromosome end broken in the yellow gene. Such an array may have transposed as a single unit or resulted from rapid successive transpositions of individual HeT-A elements. By sequence comparison with another recently transposed HeT-A element, conserved domains in the single open reading frame (ORF), encoding a gag-like polypeptide, of these elements were defined. We conclude that for transposition an intact ORF is required in cis, while the reverse transcriptase is not encoded on the HeT-A element but is provided in trans. This would make HeT-A elements dependent on an external reverse transcriptase for transposition and establish control of the genome over the activity of HeT-A elements. This distinguishes the Drosophila HeT-A element, which has been implicated in Drosophila telomere elongation, from the other, 'selfish' LINE-like elements.