Acoustic droplet vaporization, cavitation, and therapeutic properties of copolymer-stabilized perfluorocarbon nanoemulsions

Journal ArticleAcoustic and therapeutic properties of Doxorubicin (DOX) and paclitaxel (PTX)-loaded perfluorocarbon nanoemulsions have been investigated in a mouse model of ovarian cancer. The nanoemulsions were stabilized by two biodegradable amphiphilic block copolymers that differed in the structure of the hydrophobic block. Acoustic droplet vaporization (ADV) and cavitation parameters were measured as a function of ultrasound frequency, pressure, duty cycles, and temperature. The optimal parameters that induced ADV and inertial cavitation of the formed microbubbles were used in vivo in the experiments on the ultrasound-mediated chemotherapy of ovarian cancer. A combination tumor treatment by intravenous injections of drug-loaded perfluoropentane nanoemulsions and tumor-directed 1-MHz ultrasound resulted in a dramatic decrease of ovarian or breast carcinoma tumor volume and sometimes complete tumor resolution. However, tumors often recurred three to six weeks after the treatment indicating that some cancer cells survived the treatment. The recurrent tumors proved more aggressive and resistant to the repeated therapy than initial tumors suggesting selection for the resistant cells during the first treatment

Effect Modification of Kidney Function on the Non-linear Association Between Serum Calcium Levels and Cardiovascular Mortality in Korean Adults

Objectives This study aimed to evaluate the potential interaction between kidney function and the non-linear association between serum calcium levels and cardiovascular disease (CVD) mortality. Methods This study included 8927 participants enrolled in the Dong-gu Study. Albumin-corrected calcium levels were used and categorized into 6 percentile categories: 97.5th. Restricted cubic spline analysis was used to examine the non-linear association between calcium levels and CVD mortality. Cox proportional hazard regression was used to estimate hazard ratios (HRs) for CVD mortality according to serum calcium categories. All survival analyses were stratified by the estimated glomerular filtration rate. Results Over a follow-up period of 11.9±2.8 years, 1757 participants died, of whom 219 died from CVD. A U-shaped association between serum calcium and CVD mortality was found, and the association was more evident in the low kidney function group. Compared to the 25.0-50.0th percentile group for serum calcium levels, both low and high serum calcium tended to be associated with CVD mortality (97.5th: HR, 2.56; 95% CI, 0.76 to 8.66) in the low kidney function group. In the normal kidney function group, a similar association was found between serum calcium levels and CVD mortality (97.5th: HR, 1.65; 95% CI, 0.70 to 3.93). Conclusions We found a non-linear association between serum calcium levels and CVD mortality, suggesting that calcium dyshomeostasis may contribute to CVD mortality, and kidney function may modify the association

Alpha-Adducin Gly460Trp Polymorphism and Essential Hypertension in Korea

Previous studies have suggested that the Gly460Trp polymorphism of the alpha-adducin gene (ADD-1) is associated with salt sensitivity and primary hypertension. The results of linkage or association studies of ADD-1 of different populations are controversial. This study investigated the relationship between the Gly460Trp polymorphism of ADD-1 and essential hypertension in a Korean population. The subjects (n=903) were participants in a population-based study in Jangseong County, Korea. The Gly460Trp polymorphism of ADD-1 was determined using a polymerase chain reaction method. The frequency of the 460Trp allele was 59.4% in normotensives and 61.1% in hypertensives (p=0.523). The frequencies of the genotypes did not differ significantly between the hypertensive and normotensive groups (16.3% Gly/Gly, 45.8% Gly/Trp, and 38.0% Trp/Trp in normotensives; 16.2% Gly/Gly, 45.8% Gly/Trp, and 38.0% Trp/Trp in hypertensives; p=0.928). After adjusting for other risk factors, Gly/Trp and Trp/Trp were not associated with hypertension (OR 1.00, 95% CI 0.65-1.53, Gly/Trp vs. Gly/Gly; OR 1.22, 95% CI 0.79-1.90, Trp/Trp vs. Gly/Gly). These findings suggest that the Gly460Trp polymorphism of ADD-1 is not associated with hypertension

The Effect of Apolipoprotein E Polymorphism on Lipid Levels in Korean Adults

The aim of this study was to determine the effects of polymorphisms in the apolipoprotein E gene (APOE) on lipid levels in Korean adults and to investigate the interactions between these polymorphisms and environmental factors in determining lipid levels. We performed a cross-sectional study of 1,900 subjects (668 men and 1,232 women; 45-74 yr old) in Namwon, Korea, in 2004. APOE polymorphisms were determined by polymerase chain reaction and restriction enzyme analysis. Carriers of the APOE*E2 (E2) allele had significantly lower total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations than did carriers of the APOE*E3 (E3) or APOE*E4 (E4) alleles, regardless of gender. The APOE allele type had significant effect on high-density lipoprotein cholesterol (HDL-C) and triglyceride levels in women, but not in men. The effect of APOE allele type on HDL-C levels was modified by age in women. In addition, in men, the effect of APOE allele type on triglyceride levels was modified by smoking. These findings highlight the important effect of gene-environment interactions on lipid levels

Distribution of the Ankle-Brachial Index and Associated Cardiovascular Risk Factors in a Population of Middle-Aged and Elderly Koreans

The Doppler ankle-brachial pressure index (ABI) is an objective and efficient tool that can be used to determine the presence and severity of peripheral arterial disease in the lower extremities. The ABI value is inversely associated with other cardiovascular risk factors. To date, there have been no studies of the distribution of ABI in Korea. We performed a cross-sectional study of 1,943 subjects (681 men and 1,262 women; 45-74 yr old) in Namwon, Korea. The prevalence of a low ABI (<0.90) was 2.2% in men and 1.8% in women, and a high ABI (≥1.30) was prevalent in 3.1% of men and 0.8% of women. Age, smoking habits, waist circumference, hypertension, and blood pressure were associated with ABI values in both sexes. The presence of carotid plaques was associated with ABI values only in men, whereas pulse pressure was associated with ABI values only in women (p<0.05). Although the prevalence of a low ABI in the present study was lower than those reported previously for Western populations and Japanese men, our results suggest that the ABI might be used as an indicator of cardiovascular risk factors in adult Koreans

The Effect of Passive Smoking on Asthma Symptoms, Atopy, and Airway Hyperresponsiveness in Schoolchildren

Passive smoking is a major cause of respiratory morbidity, and is associated with increased bronchial responsiveness in children. To evaluate the effect of smoking by a parent on asthma symptoms, atopy, and airway hyperresponsiveness (AHR), we conducted a cross-sectional survey of 503 schoolchildren that involved questionnaires, spirometry, allergy testing, and a bronchial challenge test. If the PC20 methacholine was less than 16 mg/mL, the subject was considered to have AHR. The prevalence of a parent who smoked was 68.7%. The prevalence of AHR was 45.0%. The sensitization rate to common inhalant allergens was 32.6%. Nasal symptoms such as rhinorrhea, sneezing, nasal itching, and nasal obstruction were present in 42.7%. Asthma symptoms such as cough and wheezing were present in 55.4%. The asthma symptoms were significantly more prevalent in children who had a parent who smoked than in those whose parents did not. The nasal symptoms, atopy, and AHR did not differ according to whether a parent smoked. In a multiple logistic regression model, the asthma symptoms and atopy were independently associated with AHR, when adjusted for confounding variables. Passive smoking contributed to asthma symptoms in schoolchildren and was not an independent risk factor of airway hyperresponsiveness in an epidemiological survey