First Evaluation of Radioiodinated Flavonoids as Necrosis-Avid Agents and Application in Early Assessment of Tumor Necrosis.

A rapid and accurate identification of necrotic tissues is of great importance to define disease severity, predict prognosis, and monitor responses to therapies. To seek necrosis-avid agents with clinically translational potential, we first evaluated the necrosis avidity of flavonoids in rodent models of muscular, myocardial, and tumoral necrosis. In this study, the necrosis avidity of eight radioiodinated 5,7-dihydroxyflavones was tested by ex vivo gamma counting, histochemical staining, and autoradiography in mouse models of ethanol-induced muscular necrosis. The necrosis avidity of a lead tracer, 131I-5, was further assessed in rat models of myocardial infarction and reperfusion. Therapy response was evaluated by 131I-5 single photon emission computed tomography/computed tomography imaging 24 h after combretastatin A-4 disodium phosphate (CA4P) therapy on rats bearing W256 breast carcinomas. The necrosis avidity mechanism for the tracers was studied by in vitro DNA binding experiments of 12 5,7-dihydroxyflavones and in vivo blocking experiments of 131I-5. In the results, all 131I-5,7-dihydroxyflavones showed intense uptake to necrotic muscles, and 131I-5 emerged as the most potential tracer among them. 131I-5 obtained a necrotic-viable myocardium ratio of 5.0 ± 0.9 in post-mortem biodistribution on reperfused myocardial infarction models and achieved necrosis imaging on CA4P-treated W256 tumors 4 h after tracer injection. DNA binding studies suggested that necrosis avidity was related to DNA binding to a certain extent. The uptake of 131I-5 in necrotic muscle was markedly blocked by excessive ethidium bromide and cold 5 with a 51.95% and 64.29% decline at 1 h after coinjection, respectively. In conclusion, flavonoids are necrosis-avid agents. Furthermore, 131I-5 can serve as a promising necrosis-avid diagnostic tracer for the rapid imaging of necrotic tissues, supporting the further molecular design of radiotracer based on 5.

5-epi-ent-Kaurane diterpenoids from the aerial parts of Isodon eriocalyx and their anti-atherosclerotic potential.

The phytochemical investigation of the EtOAc extract from the aerial parts of Isodon eriocalyx afforded seventeen diterpenoids, including eight undescribed compounds. Eriocalyxins H-L have unique structural characteristics featuring a 5-epi-ent-kaurane diterpenoid scaffold with eriocalyxins H-K also possess an unusual 6,11-epoxyspiro-lactone ring while eriocalyxin L, a 1,7:3,20-diepoxy-ent kaurene, features an 1,7-oxygen linkage. The structures of these compounds were elucidated by spectroscopic data interpretation, and the absolute configurations of eriocalyxins H, I, L, and M were confirmed by single-crystal X-ray diffraction. The isolates were screened for their inhibitory activities against VCAM-1 and ICAM-1 at 5 µM. While eriocalyxin O, coetsoidin A and laxiflorin P were found to significantly inhibit both VCAM-1 and ICAM-1, 8 (17),13-ent-labdadien-15 â†’ 16-lactone-19-oic acid displayed evidently inhibitory effect against ICAM-1.

Adiponectin gene polymorphism rs2241766 T/G is associated with response to pioglitazone treatment in type 2 diabetic patients from southern China.

INTRODUCTION: Insulin sensitizing drugs such as pioglitazone are not uniformly treatment effective among individual type 2 diabetic patients. Here, the relationship of pioglitazone efficacy to single nucleotide polymorphisms (SNP) of the adiponectin gene, a critical gene directly regulated by the drug, was examined in a cohort of Chinese Han type 2 diabetic patients. METHODS: Eighty type 2 diabetic patients were treated with pioglitazone (15 mg/day) for 12 weeks without interruption of their current therapeutic regimen. Fasting plasma glucose, fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and glycated hemoglobin (HbA1c%) were collected both prior to and following pioglitazone treatment. Response to pioglitazone was defined as a decrease of at least 15% in HbA1c% levels. Three regions of the adiponectin gene containing SNPs (promoter, intron 2 and exon 2, and exon 3) were amplified and sequenced to determine genotype. RESULTS: Serum adiponectin levels were significantly increased (p<0.001) whereas fasting plasma glucose, fasting insulin, HOMA-IR, and HbA1c% values were significantly decreased relative to baseline measurements (p<0.001). Response of patients with TG and TT genotypes at rs2241766 (exon2; 52.9% vs. 12.7%, respectively p = 0.001) was statistically significant relative to all other patients. Amongst rs2241766 TG and TT patients, the mean decrease in HbA1c% levels was greater where the genotype was TG (1.15±0.80 vs. 0.52±0.64, p = 0.001). CONCLUSIONS: The adiponectin gene polymorphism rs2241766 T/G is associated with pioglitazone efficacy in type 2 diabetic patients, and status of the polymorphism may be an important clinical factor to consider prior to pioglitazone treatment.

Screening strategies for thyroid disorders in the first and second trimester of pregnancy in China.

BACKGROUND: Thyroid dysfunction during pregnancy is associated with multiple adverse outcomes, but whether all women should be screened for thyroid disorders during pregnancy remains controversial. OBJECTIVE: To evaluate the effectiveness of the targeted high risk case-finding approach for identifying women with thyroid dysfunction during the first and second trimesters of pregnancy. METHODS: Levels of thyroid stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase antibodies (TPOAb) were measured in 3882 Chinese women during the first and second trimester of pregnancy. All tested women were divided into the high risk or non-high risk groups, based on their history, findings from physical examination, or other clinical features suggestive of a thyroid disorder. Diagnosis of thyroid disorders was made according to the standard trimester-specific reference intervals. The prevalence of thyroid disorders in each group was determined, and the feasibility of a screening approach focusing exclusively on high risk women was evaluated to estimate the ability of finding women with thyroid dysfunction. RESULTS: The prevalence of overt hypothyroidism or hyperthyroidism in the high risk group was higher than in the non-high risk group during the first trimester (0.8% vs 0, χ2 = 7.10, p = 0.008; 1.6% vs 0.2%, χ2 = 7.02, p = 0.008, respectively). The prevalence of hypothyroxinemia or TPOAb positivity was significantly higher in the high risk group than in the non-high risk group during the second trimester (1.3% vs 0.5%, χ2 = 4.49, p = 0.034; 11.6% vs 8.4%, χ2 = 6.396, p = 0.011, respectively). The total prevalence of hypothyroidism or hyperthyroidism and the prevalence of subclinical hypothyroidism or hyperthyroidism were not statistically different between the high risk and non-high risk groups, for either the first or second trimester. CONCLUSION: The high risk screening strategy failed to detect the majority of pregnant women with thyroid disorders. Therefore, we recommend universal screening of sTSH, FT4, and TPOAb during the first trimester and second trimester of pregnancy.