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81.
Hirsh AJ Zhang J Zamurs A Fleegle J Thelin WR Caldwell RA Sabater JR Abraham WM Donowitz M Cha B Johnson KB St George JA Johnson MR Boucher RC 《The Journal of pharmacology and experimental therapeutics》2008,325(1):77-88
Amiloride improves mucociliary clearance (MC) by blocking airway epithelial sodium channels (ENaC) and expanding airway surface liquid (ASL). However, the low potency and rapid absorption of amiloride by airway epithelia translated into a short duration of efficacy as an aerosolized therapy for cystic fibrosis (CF) patients. To improve ENaC blocker CF pharmacotherapy, a more potent and durable ENaC blocker tailored for aerosol delivery was synthesized. Parion compound N-(3,5-diamino-6-chloropyrazine-2-carbonyl)-N'-4-[4-(2,3-dihydroxypropoxy)phenyl]butyl-guanidine methanesulfonate (552-02) was tested for potency and reversibility of ENaC block, epithelial absorption and biotransformation, selectivity, durability of ASL expansion under isotonic and hypertonic conditions in canine and human CF bronchial epithelial cells, and drug dissociation on ENaC in Xenopus oocytes. Short-circuit current assessed compound potency and reversibility, patch-clamp recordings of ENaC current assessed drug off-rate (k(off)), a gravimetric method and confocal microscopy measured mucosal water retention and ASL height, and drug absorption and biotransformation were assessed using liquid chromatography-mass spectrometry. Amiloride and 552-02 were tested in vivo for MC activity in sheep immediately and 4 to 6 h after aerosol dosing. Compared with amiloride, compound 552-02 was 60 to 100-fold more potent, it was 2 to 5-fold less reversible, it was slower at crossing the epithelium, and it exhibited a 170-fold slower k(off) value. 552-02 exhibited greater ASL expansion over 8 h in vitro, and it was more effective than amiloride at increasing MC immediately and 4 to 6 h after dosing. When combining hypertonic saline and 552-02, a synergistic effect on ASL expansion was measured in canine or CF bronchial epithelia. In summary, the preclinical data support the clinical use of 552-02 +/- hypertonic saline for CF lung disease. 相似文献
82.
Jae-Sun Uhm MD PhD Kyu-Yong Ko MD Chi Young Shim MD PhD Je-Wook Park MD Minkwan Kim MD PhD SungA Bae MD PhD In Hyun Jung MD PhD In-Soo Kim MD Jong Youn Kim MD PhD Eui-Young Choi MD PhD Won Jeong Son MS Yun Ho Roh PhD Hee Tae Yu MD PhD Tae-Hoon Kim MD PhD Geu-Ru Hong MD PhD Boyoung Joung MD PhD Hui-Nam Pak MD PhD Moon-Hyoung Lee MD PhD 《Journal of cardiovascular electrophysiology》2023,34(1):189-196
83.
Yoon Ki Joung Hyun Il Kim Sung Soo Kim Kwang Hoe Chung Yang Soo Jang Ki Dong Park 《Journal of controlled release》2003,92(1-2):83-91
For the prevention of coronary restenosis, estrogen was coupled onto a metallic stent and in vitro release of estrogen was investigated. Estrogen was introduced to the metal surface using a hydrolysable covalent bond for local sustained delivery of drug as follows: (i) the stainless steel (SS) surface was activated with silane by plasma polymerization, (ii) the activated surface (SS-Si surface) was treated with acrylic acid by plasma polymerization (SS-Si-AAc surface), and (iii) 17beta-estradiol (E2) was covalently linked to the carboxyl group on that surface (SS-Si-AAc-E2 surface). The modified surfaces were characterized by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared (FT-IR) spectroscopy, and water contact angle measurement. The amount of E2 was measured by UV-visible spectrophotometry and high performance liquid chromatography (HPLC). The in vitro release profile of E2 demonstrated sustained release of E2 in aqueous buffer. In summary, a novel method of immobilizing estrogen onto a metallic stent surface using plasma polymerization has been developed. The obtained results attest to the usefulness of the estrogen-releasing stent for preventing restenosis. 相似文献
84.
Paik KH Lee MK Jin DK Kang HW Lee KH Kim AH Kim C Lee JE Oh YJ Kim S Han SJ Kwon EK Choe YH 《Journal of Korean medical science》2007,22(2):177-182
The plasma ghrelin has been reported to be elevated in Prader-Willi syndrome (PWS) and modulated by insulin. It was hypothesized that insulin might have a more pronounced effect on reducing plasma ghrelin in PWS patients, which would influence appetite. This study investigated the degree of ghrelin suppression using an euglycemic hyperinsulinemic clamp in children with PWS (n=6) and normal children (n=6). After a 90-min infusion of insulin, the plasma ghrelin level decreased from a basal value of 0.86+/-0.15 to 0.58+/-0.12 ng/mL in the controls, and from 2.38+/-0.76 to 1.12+/-0.29 ng/mL in children with PWS (p=0.011). The area under the curve below the baseline level over the 90 min insulin infusion was larger in children with PWS than in controls (-92.82+/-44.4 vs. -10.41+/-2.87 ng/mL/90 min) (p=0.011). The insulin sensitivity measured as the glucose infusion rate at steady state was similar in the two groups (p=0.088). The decrease in the ghrelin levels in response to insulin was more pronounced in the children with PWS than in the controls. However, the level of ghrelin was always higher in the children with PWS during the clamp study. This suggests that even though insulin sensitivity to ghrelin is well maintained, an increase in the baseline ghrelin levels is characteristic of PWS. 相似文献
85.
Jung JH Joo KR Chae MJ Jang JY Lee SG Dong SH Kim HJ Kim BH Chang YW Lee JI Chang R Kim YH Lee SM 《Journal of Korean medical science》2007,22(3):549-552
Benign schwannomas arise in neural crest-derived Schwann cells. They can occur almost anywhere in the body, but their most common locations are the central nervous system, extremities, neck, mediastinum, and retroperitoneum. Schwannomas occurring in the biliary tract are extremely rare and mostly present with obstructive jaundice. We recently experienced a case of extrahepatic biliary schwannomas in a 64-yr-old female patient who presented with intra- and extrahepatic bile duct and gallbladder stones during a screening program. To the best of our knowledge, extrahepatic biliary schwannomas associated with bile duct stones have not been reported previously in the literature. 相似文献
86.
Paik KH Jin DK Lee KH Armstrong L Lee JE Oh YJ Kim S Kwon EK Choe YH 《Journal of Korean medical science》2007,22(3):436-441
Prader-Willi syndrome (PWS) is a contiguous gene syndrome characterized by uncontrollable eating or hyperphagia. Several studies have confirmed that plasma ghrelin levels are markedly elevated in PWS adults and children. The study of anorexigenic hormones is of interest because of their regulation of appetite by negative signals. To study the pattern and response of the anorexigenic hormones such as cholecystokinin (CCK) and peptide YY (PYY) to a meal in PWS, we measured the plasma CCK, PYY, ghrelin and serum insulin levels in PWS patients (n=4) and in controls (n=4) hourly for a day, and analyzed hormone levels and hormonal responses to meals. Repeated measures of ANOVA of hormone levels demonstrated that only insulin levels decreased (p=0.013) and CCK (p=0.005) and ghrelin (p=0.0007) increased in PWS over 24 hr. However, no significant group x time interactions (ghrelin: p=0.89, CCK: p=0.93, PYY: p=0.68 and insulin: p=0.85) were observed; in addition, there were no differences in an assessment of a three-hour area under the curve after breakfast. These results suggest that the response pattern of hormones to meals in PWS patients parallels that of normal controls. In addition, the decrease of insulin levels over 24 hr, in spite of obesity and elevated ghrelin levels, suggests that the baseline insulin level, not the insulin response to meals, may be abnormal in patients with PWS. 相似文献
87.
Background & aims
The association of low-carbohydrate diet with weight loss and the risk of cardiovascular diseases has recently been the focus of increasing research attention. However, studies on low-carbohydrate diet in the Asian population are limited. The present study was aimed to examine the association between low-carbohydrate diet and metabolic syndrome among Korean adults.Methods and results
A total of 16,349 participants aged 30 years or older who participated in a 24-h dietary recall survey of the fifth and sixth Korea National Health and Nutrition Examination Survey were included in this study. Low-carbohydrate diet was evaluated using the low-carbohydrate-diet score, which was calculated based on the percentage of energy from carbohydrate, protein, and fat by sex. The association between the low-carbohydrate-diet score and metabolic syndrome was analyzed using multiple logistic regression analysis. A low-carbohydrate diet was not associated with metabolic syndrome and its components such as waist circumference, blood pressure, and triglyceride levels. However, women in the highest decile of the animal- or plant-based low-carbohydrate-diet score showed a decreased risk of reduced high-density lipoprotein (HDL)-cholesterol levels, and men in the highest decile of the animal-based low-carbohydrate-diet score showed a decreased risk of reduced HDL-cholesterol levels than those in the lowest decile of the low-carbohydrate-diet score.Conclusion
These findings indicate that, in Korea, a low-carbohydrate diet did not increase the risk of metabolic syndrome among adults who typically consume a high-carbohydrate low-fat diet. However, it may moderately decrease the risk of reduced HDL-cholesterol levels. 相似文献88.
Sang-Eun Lee Jae-Sun Uhm Jong-Youn Kim Hui-Nam Pak Moon-Hyoung Lee Boyoung Joung 《Yonsei medical journal》2015,56(4):887-894
Purpose
Acute coronary lesions commonly trigger out-of-hospital cardiac arrest (OHCA). However, the prevalence of coronary artery disease (CAD) in Asian patients with OHCA and whether electrocardiogram (ECG) and other findings might predict acute myocardial infarction (AMI) have not been fully elucidated.Materials and Methods
Of 284 consecutive resuscitated OHCA patients seen between January 2006 and July 2013, we enrolled 135 patients who had undergone coronary evaluation. ECGs, echocardiography, and biomarkers were compared between patients with or without CAD.Results
We included 135 consecutive patients aged 54 years (interquartile range 45-65) with sustained return of spontaneous circulation after OHCA between 2006 and 2012. Sixty six (45%) patients had CAD. The initial rhythm was shockable and non-shockable in 110 (81%) and 25 (19%) patients, respectively. ST-segment elevation predicted CAD with 42% sensitivity, 87% specificity, and 65% accuracy. ST elevation and/or regional wall motion abnormality (RWMA) showed 68% sensitivity, 52% specificity, and 70% accuracy in the prediction of CAD. Finally, a combination of ST elevation and/or RWMA and/or troponin T elevation predicted CAD with 94% sensitivity, 17% specificity, and 55% accuracy.Conclusion
In patients with OHCA without obvious non-cardiac causes, selection for coronary angiogram based on the combined criterion could detect 94% of CADs. However, compared with ECG only criteria, the combined criterion failed to improve diagnostic accuracy with a lower specificity. 相似文献89.
To compare the prevalence of hepatitis B virus (HBV) infection over a 10-year period in terms of population-level trends, we established hypothetical birth cohorts that represented each 10-year interval age group.We used data from the Korean National Health and Nutrition Examination Surveys conducted between 1998 to 2001 and 2008 to 2011. Trends in the HBV infection were calculated using data from individuals aged 20 to 59 years in 1998 to 2001 and those aged 30 to 69 years in 2008 to 2011.In 2008 to 2011, the prevalence of HBV infection, as measured using serum HBV surface antigen (HBsAg) seroprevalence, among participants aged 30 to 69 years was 4.2% (95% CI = 3.7–4.7%), which represents a 1.3% absolute change and 20% change in prevalence ratio, which was significant compared with the prevalence among those aged 20 to 59 years in 1998 to 2001 (5.5%, 95% CI = 4.7–6.3%). The prevalence of HBV infection decreased most in the lowest income group, with marginal significance in males (P = 0.06) and significance in females (P = 0.03). In terms of education, females with at least a high school education showed a significant decrease (P = 0.03).Using a birth cohort approach, the prognosis for HBV infection in terms of death or hospitalization, or resolution upon antiviral treatment of their HBV infections, identified by a decrease in the HBsAg seroprevalence was worse in the lower income group and in females with higher education. We postulate that these socioeconomic inequalities were caused by alcohol consumption, disparities in liver cancer surveillance, and access to antiviral treatment because of cost and reimbursement guidelines. 相似文献
90.
Tae Kyong Kim Youn Joung Cho Jeong Jin Min John M. Murkin Jae-Hyon Bahk Deok Man Hong Yunseok Jeon 《Critical care (London, England)》2015,19(1)
IntroductionMicrovascular reactivity is decreased in patients with septic shock; this is associated with worse clinical outcomes. The objectives of the present study were to investigate microvascular reactivity in cardiac surgery patients and to assess any association with clinical outcomes.MethodsWe retrospectively analyzed a prospectively collected registry. In total, 254 consecutive adult patients undergoing cardiac and thoracic aortic surgeries from January 2013 through May 2014 were analyzed. We performed a vascular occlusion test (VOT) by using near-infrared spectroscopy to measure microvascular reactivity. VOT was performed three times per patient: prior to the induction of anesthesia, at the end of surgery, and on postoperative day 1. The primary endpoint was a composite of major adverse complications, including death, myocardial infarction, acute kidney injury, acute respiratory distress syndrome, and persistent cardiogenic shock.ResultsVOT recovery slope decreased during the surgery. VOT recovery slope on postoperative day 1 was significantly lower in patients with composite complications than those without (3.1 ± 1.6 versus 4.0 ± 1.5 %/s, P = 0.001), although conventional hemodynamic values, such as cardiac output and blood pressure, did not differ between the groups. On multivariable regression and linear analyses, low VOT recovery slope on postoperative day 1 was associated with increases of composite complications (odds ratio 0.742; 95 % confidence interval (CI) 0.584 to 0.943; P = 0.015) and hospital length of stay (regression coefficient (B) −1.276; 95 % CI −2.440 to −0.112; P = 0.032).ConclusionMicrovascular reactivity largely recovered on postoperative day 1 in the patients without composite complications, but this restoration was attenuated in patients with composite complications.