A preliminary feasibility study of simultaneous dual-isotope imaging with a solid-state dedicated cardiac camera for evaluating myocardial perfusion and fatty acid metabolism

Simultaneous dual-isotope SPECT imaging with 201Tl and ¹²³I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) is used to study the perfusion–metabolism mismatch. It predicts post-ischemic functional recovery by detecting stunned myocardium. On the other hand, ^99mTc-MIBI is another radioisotope widely used in myocardial perfusion imaging because of its better image quality and lower radiation exposure than 201Tl. However, since the photopeak energies of ^99mTc and ¹²³I are very similar, crosstalk hampers the simultaneous use of these two radioisotopes. To overcome this problem, we conducted simultaneous dual-isotope imaging study using the D-SPECT scanner (Spectrum-Dynamics, Israel) which has a novel detector design and excellent energy resolution. We first conducted a basic experiment using cardiac phantom to simulate the condition of normal perfusion and impaired fatty acid metabolism. Subsequently, we prospectively recruited 30 consecutive patients who underwent successful percutaneous coronary intervention for acute myocardial infarction, and performed ^99mTc-MIBI/¹²³I-BMIPP dual-isotope imaging within 5 days after reperfusion. Images were interpreted by two experienced cardiovascular radiologists to identify the infarcted and stunned areas based on the coronary artery territories. As a result, cardiac phantom experiment revealed no significant crosstalk between ^99mTc and ¹²³I. In the subsequent clinical study, ^99mTc-MIBI/¹²³I-BMIPP dual-isotope imaging in all participant yielded excellent image quality and detected infarcted and stunned areas correctly when compared with coronary angiographic findings. Furthermore, we were able to reduce radiation exposure to significantly approximately one-eighth. In conclusion, we successfully demonstrated the practical application of simultaneous assessment of myocardial perfusion and fatty acid metabolism by ^99mTc-MIBI and ¹²³I-BMIPP using a D-SPECT cardiac scanner. Compared with conventional ²⁰¹TlCl/¹²³I-BMIPP dual-isotope imaging, the use of ^99mTc-MIBI instead of ²⁰¹TlCl improves image quality as well as lowers radiation exposure.     

Different hypersensitivities against homologous proteins of MGL_1304 in patients with atopic dermatitis

Background

Atopic dermatitis (AD) is exacerbated by sweating, and the skin of most patients with AD are resided by Malassezia (M.) fungi. Recently, MGL_1304 produced by Malassezia globosa was identified as the major histamine releasing antigen in human sweat.

Radical Polymerization and Copolymerization of 12‐[(N‐Methacryloyl)carbamoyloxy]octadecanoic Acid

Radical polymerization of 12‐[(N‐methacryloyl)carbamoyloxy] octadecanoic acid ( 1 ) was kinetically and ESR spectroscopically investigated in acetone, using dimethyl 2,2′‐azobisisobutyrate ( 2 ) as initiator. The polymerization rate (R_p) is given by R_p = k [2]^0.7[1]^1.4 at 50°C. Propagating poly( 1 ) radical was observed as a 13‐lines spectrum by ESR under the actual polymerization conditions. The ESR‐determined k_p values (1.8–7.9 L/mol·s) are much lower than those of usual methacrylate monomers. The rate constant (k_t) of termination was determined to be k_t = 1.0–2.7·10⁴ L/mol·s from decay curve of the propagating radical. The Arrhenius plots of k_p and k_t gave the activation energies of propagation (63 kJ/mol) and termination (24 kJ/mol). A significant solvent effect was observed on the radical polymerization of 1 . The copolymerizations of 1 with styrene(St) and acrylonitrile were examined at 50°C. Copolymerization parameters obtained for the 1  (M₁)/St (M₂) system are as follows; r₁ = 0.73, r₂ = 0.57, Q₁ = 0.83, and e₁ = 0.13.     

Pathological examination of the placenta in small for gestational age (SGA) children with or without postnatal catch-up growth

Background/objective: Approximately 10% of small for gestational age (SGA) infants fail to catch up. The relationship between postnatal growth and placental pathology in SGA infants remains unclear. Our aim was to assess the involvement of placental pathology in postnatal growth of SGA infants.

Methods: We retrospectively evaluated placental pathology and postnatal growth in single-pregnancy infants born after 37 gestational weeks in our institution, with both birth weight and length below ?2 standard deviation scores (SDS) of the normal weight and length. “Catch-up” was defined as height reaching ?2 SDS before the second birthday. Pathology of the placenta was classified into: abnormality due to maternal factors or fatal factors, villitis of unknown etiology (VUE), other abnormalities and no abnormality.

Results: Of the 33?084 infants, 142 met our criteria and 49 of them had analyzable data. The overall catch-up rate was 84%. Catch-up growth took place in all infants with no placental abnormality and only 57% of infants with abnormality due to fatal factors. There was no significant relationship between catch-up rate and other factors.

Conclusion: Placental pathology is associated with postnatal growth in SGA children born at term. Placental abnormality due to fetal factors is related to poor catch-up rate.     

Pivotal function for cytoplasmic protein FROUNT in CCR2-mediated monocyte chemotaxis

Ligation of the chemokine receptor CCR2 on monocytes and macrophages with its ligand CCL2 results in activation of the cascade consisting of phosphatidylinositol-3-OH kinase (PI(3)K), the small G protein Rac and lamellipodium protrusion. We show here that a unique clathrin heavy-chain repeat homology protein, FROUNT, directly bound activated CCR2 and formed clusters at the cell front during chemotaxis. Overexpression of FROUNT amplified the chemokine-elicited PI(3)K-Rac-lamellipodium protrusion cascade and subsequent chemotaxis. Blocking FROUNT function by using a truncated mutant or antisense strategy substantially diminished signaling via CCR2. In a mouse peritonitis model, suppression of endogenous FROUNT markedly prevented macrophage infiltration. Thus, FROUNT links activated CCR2 to the PI(3)K-Rac-lamellipodium protrusion cascade and could be a therapeutic target in chronic inflammatory immune diseases associated with macrophage infiltration.     

Local overexpression of HB-EGF exacerbates remodeling following myocardial infarction by activating noncardiomyocytes

Insulin-like growth factor (IGF), hepatocyte growth factor (HGF), and heparin-binding epidermal growth factor-like growth factor (HB-EGF) are cardiogenic and cardiohypertrophic growth factors. Although the therapeutic effects of IGF and HGF have been well demonstrated in injured hearts, it is uncertain whether natural upregulation of HB-EGF after myocardial infarction (MI) plays a beneficial or pathological role in the process of remodeling. To answer this question, we conducted adenoviral HB-EGF gene transduction in in vitro and in vivo injured heart models, allowing us to highlight and explore the HB-EGF-induced phenotypes. Overexpressed HB-EGF had no cytoprotective or additive death-inducible effect on Fas-induced apoptosis or oxidative stress injury in primary cultured mouse cardiomyocytes, although it significantly induced hypertrophy of cardiomyocytes and proliferation of cardiac fibroblasts. Locally overexpressed HB-EGF in the MI border area in rabbit hearts did not improve cardiac function or exhibit an angiogenic effect, and instead exacerbated remodeling at the subacute and chronic stages post-MI. Namely, it elevated the levels of apoptosis, fibrosis, and the accumulation of myofibroblasts and macrophages in the MI area, in addition to inducing left ventricular hypertrophy. Thus, upregulated HB-EGF plays a pathophysiological role in injured hearts in contrast to the therapeutic roles of IGF and HGF. These results imply that regulation of HB-EGF may be a therapeutic target for treating cardiac hypertrophy and fibrosis.