Detection of Atherosclerotic Plaques in the Rabbit Aorta Using Ultrasound Microbubbles Conjugated to Interleukin-18 Antibodies.

BACKGROUND The purpose of the study was to investigate the ability of microbubbles (MBs) targeting interleukin-18 (IL-18) to detect plaques in a rabbit atherosclerotic plaque model. MATERIAL AND METHODS A rabbit atherosclerotic plaque model was established. The locations of the atherosclerotic plaques were verified by two-dimensional scanning and color Doppler flow imaging. An IL-18 antibody was conjugated to naked MBs (MBc) using the biotin-streptavidin conjugation method, resulting in the formation of MBIL-18. MBc and MBIL-18 were then used for contrast-enhanced ultrasound (CEUS) studies. The locations of CD34 and IL-18 within the plaques were determined by immunohistochemistry, and IL-18 expression levels in the plaques were determined by Western blot analysis. The relationships between IL-18 expression and the contrast intensity of the 2 MBs were analyzed. RESULTS MBc and MBIL-18 were both uniformly dispersed. Fluorescence microscopy and flow cytometry revealed that IL-18 was successfully conjugated to MBs. CEUS images showed that the intensity of the MBIL-18 signal was substantially enhanced and prolonged compared with that of the MBc signal. Immunohistochemistry showed that CD34 expression was significantly increased in the plaques and that IL-18 was mainly located in the inner parts and base of the atherosclerotic plaques. Western blot analysis revealed that IL-18 expression was higher in the plaque regions. Correlation analysis showed that IL-18 expression was correlated with the contrast intensity of MBIL-18 (r=0.903, P<0.05) but not with MBc (r=0.540, P>0.05). CONCLUSIONS MBs targeting IL-18 may be a novel, noninvasive method of diagnosing atherosclerotic plaques.

Attenuation of hepatic fibrosis through ultrasound-microbubble-mediated HGF gene transfer in rats.

OBJECTIVE: The objective was to explore the feasibility of ultrasound-microbubble-mediated hepatocyte growth factor (HGF) gene transfer for treating rat hepatic fibrosis induced by CCl(4). METHODS: Forty-eight male SD rats were divided into ultrasound-microbubble-HGF group (U-M-HGF group), ultrasound-HGF group (U-HGF group), microbubble-HGF group (M-HGF group), HGF group (HGF group), CCl(4) group (control group), and normal group. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), total protein, albumin (ALB), and globulin (GLB) and the ratio of ALB/GLB were determined after treatment. The degree of hepatic fibrosis was evaluated by histopathological numerical scores. The protein expressions of HGF, collagen I, collagen III, and α-smooth muscle antibody (α-SMA) were detected by immunohistochemistry. RESULTS: Ultrasound-microbubble-mediated HGF therapy significantly reduced the serum level of ALT and AST to 59.88% and 49.18% of the control group, respectively. Ultrasound-microbubble-mediated HGF therapy prevented liver fibrosis, with an obvious decrease in fibrosis areas and extracellular matrix production of collagen I, collagen III, and α-SMA. The gene therapy could induce HGF delivery into the fibrotic liver effectively. CONCLUSIONS: Ultrasound-microbubble-mediated HGF gene therapy can reduce liver fibrosis, which provides a novel strategy for gene therapy of chronic liver disease.

Polymorphisms of androgen receptor gene in childhood and adolescent males with first-onset major depressive disorder and association with related symptomatology.

This study was designed to explore the association between CAG repeats in AR gene and major depressive disorder (MDD) in male children and adolescents. The results showed that there were differences between adolescent depressive patients and adolescent controls in CAG repeats' length and alleles' distributions, and the severity of depression and anxiety was negatively correlated with the length of CAG repeats in adolescent patients. This suggested that AR gene might be involved in the depressive upset in adolescents, and the age- and sex-related prevalent differences might also be associated to CAG repeats.

Comparison of the polymorphisms of androgen receptor gene and estrogen alpha and beta gene between adolescent females with first-onset major depressive disorder and controls.

This study was to elucidate the role of genetic variation in androgen receptor (AR) gene, estrogen receptor alpha (ER alpha) and ER beta gene on first-onset major depressive disorder (MDD) in female adolescents. Results showed that AR gene in MDD group have shorter microsatellites' length, and ER beta gene have shorter microsatellites' length and higher rates of S alleles, SS, genotype, and lower rate of LL genotype than control group. The results suggest that shorter length of AR and ER beta gene microsatellites might influence the onset of MDD in female adolescents, a further elucidation of the mechanisms is warranted.