The health benefits of garlic (Allium sativum L.) are derived from a wide variety of components and from the different ways it is administered. The known health benefits of garlic include cardiovascular protective effects, stimulation of immune function, reduction of blood glucose level, protection against microbial, viral and fungal infections, as well as anticancer effects. In the present study, it was examined the effects of water extract of A. sativum (WEAS) on the growth of cultured human tumor cells in order to investigate its anti-proliferative mechanism. Treatment of WEAS to tumor cells resulted in the growth inhibition, especially in leukemia cells, which was associated with induction of G2/M arrest of the cell cycle and apoptosis. In order to further explore the critical events leading to apoptosis in WEAS-treated U937 human leukemia cells, the following effects of WEAS on components of the mitochondrial apoptotic pathway were examined: generation of reactive oxygen species (ROS), alteration of the mitochondrial membrane potential (MMP), and the expression changes of Bcl-2 and IAP family proteins. The cytotoxic effect of WEAS was mediated by its induction of apoptosis as characterized by the occurrence of DNA ladders, apoptotic bodies and chromosome condensation in U937 cells. The WEAS-induced apoptosis in U937 cells was correlated with the generation of intracellular ROS, collapse of MMP, activation of caspase-3 and down-regulation of anti-apoptotic proteins. The quenching of ROS generation with antioxidant N-acetyl-L-cysteine conferred significant protection against WEAS-elicited ROS generation, caspase-3 activation, G2/M arrest and apoptosis. In conclusion, the present study reveals that the cellular ROS generation plays a pivotal role in the initiation of WEAS-triggered apoptotic death in U937 cells.
Journal of the Korea Academia-Industrial cooperation Society
/
v.20
no.8
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pp.331-343
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2019
The purpose of this study is to observe the trends of heart age of Koreans by using the predictor of heart age of the Framingham Heart Study. The subjects were 20,012 adults aged 30~74 years who were enrolled in the Korean National Health and Nutrition Examination Survey from 2005~2013. They filled in the determinants data and they had no history of cardiovascular disease (CVD). The heart age was calculated using a non-laboratory based model of prediction. The difference of heart age and chronological age, and the rate of excessive heart age over 10 years were calculated. The annual trend, the difference according to gender, the age bracket and geographic region, the heart age were all evaluated. Data analysis performed using the SAS program (version 9.3). Complex designed analysis was done. The heart age showed differences according to gender, age bracket and geographic region. The heart age is a useful comprehensive indicator for predicting the CVD events in the near future. So, it could be used for the purposes of exercising caution and guidance on CVD for administering medical care. It is strongly recommended to use heart age as an indicator for customized medical management to focus efforts on relatively vulnerable subjects and their factors for CVD. Further study on Koreans' customized heart age is needed.
Jinhee Kim;Yoo Jin Hong;Kyunghwa Han;Jin Young Kim;Hye-Jeong Lee;Jin Hur;Young Jin Kim;Byoung Wook Choi
Korean Journal of Radiology
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v.24
no.9
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pp.838-848
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2023
Objective: To quantitatively analyze the cardiac magnetic resonance imaging (CMR) characteristics of chemotherapy-related cardiac dysfunction (CTRCD) and explore their prognostic value for major adverse cardiovascular events (MACE). Materials and Methods: A total of 145 patients (male:female = 76:69, mean age = 63.0 years) with cancer and heart failure who underwent CMR between January 2015 and January 2021 were included. CMR was performed using a 3T scanner (Siemens). Biventricular functions, native T1 T2, extracellular volume fraction (ECV) values, and late gadolinium enhancement (LGE) of the left ventricle (LV) were compared between those with and without CTRCD. These were compared between patients with mild-to-moderate CTRCD and those with severe CTRCD. Cox proportional hazard regression analysis was used to evaluate the association between the CMR parameters and MACE occurrence during follow-up in the CTRCD patients. Results: Among 145 patients, 61 had CTRCD and 84 did not have CTRCD. Native T1, ECV, and T2 were significantly higher in the CTRCD group (1336.9 ms, 32.5%, and 44.7 ms, respectively) than those in the non-CTRCD group (1303.4 ms, 30.5%, and 42.0 ms, respectively; P = 0.013, 0.010, and < 0.001, respectively). They were not significantly different between patients with mild-to-moderate and severe CTRCD. Indexed LV mass was significantly smaller in the CTRCD group (65.0 g/m2 vs. 78.9 g/mm2; P < 0.001). According to the multivariable Cox regression analysis, T2 (hazard ratio [HR]: 1.14, 95% confidence interval [CI]: 1.01-1.27; P = 0.028) and quantified LGE (HR: 1.07, 95% CI: 1.01-1.13; P = 0.021) were independently associated with MACE in the CTRCD patients. Conclusion: Quantitative parameters from CMR have the potential to evaluate myocardial changes in CTRCD. Increased T2 with reduced LV mass was demonstrated in CTRCD patients even before the development of severe cardiac dysfunction. T2 and quantified LGE may be independent prognostic factors for MACE in patients with CTRCD.
Since the first implanted in September 1997, the use of On-X prosthetic heart valve has been increasing around in the world. This study was designed to assess the feasibility, safety, and the postoperative hemodynamics with this new valve in clinical setting. Material and Method: The current study was carried out on 52 patients undergoing aortic valve replacement with this prosthesis between April 1999 to August 2002 at Chonnam National University Hospital to evaluate the surgical results. 52% of the patients were male and the average age at implant was 50$\pm$13 years. The study followed the guidelines of the AATS/STS. Preoperatively, 32(61.5%) patients were in NYHA functional class III or IV and 2 patients had previous aortic valve surgery. Concomitant cardiac surgery was performed in 71.1%. The implanted valve sizes were 19 mm in 13 patients, 21 mm in 26, 23 mm in 10 and 25 mm in 3, respectively. Mean follow-up was 16.6$\pm$10.5 months (1∼39 months). Echocardiographic assessment was performed pre- and immediate postoperatively, as well as 3, 6, 12 months after surgery, evaluating pressure loss and regression of left ventricular hypertrophy. Result: Mean cardiopulmonary bypass time was 191$\pm$94.7 minutes with an aortic cross-clamp time of 142$\pm$51.7 minutes. There was no early and late mortality, Freedom from adverse events at 1 year in the study were as follows: thromboembolism, 95.6$\pm$6%; bleeding events, 90.2$\pm$4%; paravalvular leakage 92.3$\pm$4%; and overall valve-related morbidity at 1 year was 76.6$\pm$3%. There were no cases of valve thrombosis, prosthetic valve endocarditis and structural or non-structural failure. Left ventricular function at 12 months after surgery (EF=62.7$\pm$9.8%) revealed a statistically significant improvement compared to preoperative investigation (EF=55.8$\pm$15.9%, p=0.006). Left ventricular mass index was 247.3$\pm$122.3 g/$m^2$ on preoperative echocardiographic study, but regressed to 155.5$\pm$58.2 g/$m^2$ at postoperative 1 year (p=0.002). Over the follow-up period a further decrease of peak transvalvular gradients was observed in all patients: 62.5$\pm$38.0 mmHg on preoperative assessment, 18.2$\pm$6.8 mmHg at immediate postoperative period (p < 0.0001), 7.6$\pm$5.09 mmHg (p<0.0001) at 6 month, 18.0$\pm$10.8 mmHg (p<0.0001) at 1 year. Conclusion: The On-X prosthetic heart valve performs satisfactorily in the first 1 year period. Clinical outcome by examining NYHA functional classification revealed especially good results. Effective regression of left ventricular hypertrophy and statistically significant decrease of transvalvular gradient were observed over the first year, but longer-term follow-up of this patient group is needed to establish the expected rates for late valve-related events as well as the long-term clinical efficacy of this valve.
Background: The existing data indicate that obstructive sleep apnea syndrome contributes to the development of cardiovascular dysfunction such as systemic hypertension and cardiac arrhythmias, and the cardiovascular dysfunction has a major effect on high long-term mortality rate in obstructive sleep apnea syndrome patients. To a large extent the various studies have helped to clarify the pathophysiology of obstructive sleep apnea, but many basic questions still remain unanswered. Methods: In this study, the influence of obstructive sleep apnea on systemic blood pressure, cardiac rhythm and urinary catecholamines concentration was evaluated. Over-night polysomnography, 24-hour ambulatory blood pressure and ECG monitoring, and measurement of urinary catecholamines, norepinephrine (UNE) and epinephrine (UEP), during waking and sleep were undertaken in obstructive sleep apnea syndrome patients group (OSAS, n=29) and control group (Control, n=25). Results: 1) In OSAS and Control, UNE and UEP concentrations during sleep were significantly lower than during waking (P<0.01). In UNE concentrations during sleep, OSAS showed higher levels compare to Control (P<0.05). 2) In OSAS, there was a increasing tendency of the number of non-dipper of nocturnal blood pressure compare to Control (P=0.089). 3) In both group (n=54), mean systolic blood pressure during waking and sleep showed significant correlation with polysomnographic data including apnea index (AI), apnea-hypopnea index (AHI), arterial oxygen saturation nadir ($SaO_2$ nadir) and degree of oxygen desaturation (DOD). And UNE concentrations during sleep were correlated with AI, AHI, $SaO_2$ nadir, DOD and mean diastolic blood pressure during sleep. 4) In OSAS with AI>20 (n==14), there was a significant difference of heart rates before, during and after apneic events (P<0.01), and these changes of heart rates were correlated with the duration of apnea (P<0.01). The difference of heart rates between apneic and postapneic period (${\Delta}HR$) was significantly correlated with the difference of arterial oxygen saturation between before and after apneic event (${\Delta}SaO_2$) (r=0.223, P<0.001). 5) There was no significant difference in the incidence of cardiac arrhythmias between OSAS and Control In Control, the incidence of ventricular ectopy during sleep was significantly lower than during waking. But in OSAS, there was no difference between during waking and sleep. Conclusion : These results suggested that recurrent hypoxia and arousals from sleep in patients with obstructive sleep apnea syndrome may increase sympathetic nervous system activity, and recurrent hypoxia and increased sympathetic nervous system activity could contribute to the development of cardiovascular dysfunction including the changes of systemic blood pressure and cardiac function.
The aim of this study was to evaluate the early and midterm results of off-pump total arterial revascularization using the skeletonized right gastroepiploic artery (RGEA) as a third arterial conduit. Material and Method: We prospectively analyzed 103 patients who underwent off-pump total arterial revascularization using bilateral internal thoracic arteries (ITAS) and RGEA. The RGEA was used as in situ graft in 88 patients, composite graft in 10 patients, and free graft in 5 patients. Postoperative coronary angiographies were performed before discharge in 100 patients, and at postoperative one year in 88 patients. Result: The RGEA showed a significantly higher free flow (130$\pm$95 ml/min) than that of right ITA(113$\pm$57 ml/min) or left ITA (107$\pm$55 ml/min), which was measured before anastomosis (p < 0.05). The total number of distal anastomoses was 3.8$\pm$0.7. The number of distal anastomoses per bilateral ITAs was 2.8$\pm$0.7 and the number of distal anastomosis per RGEA was 1.0. There were two morialities including one operative mortality. The late mortality was not related to cardiac events. Early postoperative morbidities were atrial fibrillation in 15 patients, bleeding reoperation in 4 patients, mediastinitis in 1 patients, perioperative myocardial infarction in 2 patient, and transient ARF in 3 patients. Postoperative coronary angiographies showed the early patency rate of 98.6% (272/276) for ITAs and 97.0% (97/100) for RGEA, respectively (p=ns), and the one-year patency rate of 95.9% (234/244) for ITAs and 88.6% (78/88) for RGEA, respectively (p=0.07). Flow competition between the RGEA and NCA (native coronary artery) was seen in 5 of the 100 patients (5.0%) immediate postoperatively and 7 of the 88 patients (8.0%) 1 year after surgery. Since July, 2000, we measured transit time flow intraoperatively and could reduce flow competition significantly Conclusion: The skeletonized RGEA demonstrated excellent early and midterm patency rates and could be used as a third arterial graft following the bilateral ITAs.
Background: In clinical trials with no upper age limit, the proportion of older patients is usually small, probably reflecting the more conservative approach adopted by clinicians when treating the elderly. An exploratory analysis of elderly patients in the RECORD-1 Trial showed that patients ${\geq}$ 65 y.o. had superior median PFS than overall RECORD-1 population (5.4 months and 4.9 months, respectively). We investigated the efficacy, relative benefit and safety of Everolimus (EVE) as sequential therapy after failure of VEGFr-TKI therapy for older patients with metastatic renal cell cancer (mRCC), in daily practice. Materials and Methods: 172 consecutive IRB approved patients with mRCC (median age 65, M:F 135/37, 78% clear cell) who received salvage EVE at 39 tertiary institutions between October 2009 and August 2011 were included in this analysis. Some 31% had progressed on sunitinib, 22% on sorafenib, 1% on axitinib, 41% on sequential therapy, and 5% had received other therapy. Patients with brain metastases were not included and 95% of the patients had a ECOG (Eastern Cooperative Oncology Group) performance status (PS) of 0 or 1. Previous radiotherapy was an exclusion criterion, but prior chemotherapy was permitted. Adequate organ function and hematologic parameters were mandatory. EVE administration was approved by the institutional review board at each participating institution and signed informed consent was obtained from all patients. Results: Median time of the whole cohort to last follow-up was 3.5 months (range 0.4-15.2 months). Forty four percent were continuing to take EVE at last followup. There were 86 (50%) patients ${\geq}$ 65 y.o. and 86 (50%) <65 y.o. The percentage of patients who showed PR/SD was higher in the older group than in the younger one (5.9%/61.2% vs 1.2%/46.5%, respectively). Median survival of older patients was also significantly longer (3.5 +/- 0.31 vs 3.1 +/- 0.34, hazard ratio=0.45, CI; 0.255-0.802). Analysis using Cox regression model adjusted for gender, PS, number of metastases, site of metastases, histology, smoking history and age detected an association between age and PFS (p=0.011). The frequency of adverse events in elderly patients treated with EVE was no greater than that in younger patients, although such toxicity may have had a greater impact on their quality of life. Conclusions: Older patients should not generally be excluded from accepted therapies (mTOR inhibitors after failure of VEGFr-TKI therapy) for mRCC.
Background : Lung carcinogenesis is a multistage process involving alterations in multiple genes and diverse pathway. Mutational activation of oncogenes and inactivation of tumor suppressor genes, and subsequent increased genetic instability are the major genetic events. The p53 gene and FHIT gene as tumor suppressor genes contribute to the pathogenesis of lung cancer, evidenced by mutation, microsatellite instability(MI) and loss of heterozygosity(LOH). Methods : We analysed genetic mutations of p53 and FHIT gene in 29 surgical specimens of nonsmall cell lung cancer using PCR-single strand conformation polymorphism, DNA sequencing and RT-PCR. MI and LOH were analyzed in loci of D3S1285, D9S171, and TP53. Results : In 2 cases, point mutation of p53 gene was observed on exon 5. MI of 3 times and LOH of 14 times were observed in at least one locus. In terms of the location of microsatellite, D3S1285 as a marker of FH1T was observed in 5 cases out of 26 specimens; D9S171 as a marker of p16 in 5 out of 17; and TP53 as a marker of p53 in 7 out of 27. In view of histologic type, squamous cell carcinoma presented higher frequency of microsatellite alteration, compared to others. Mutation of FHIT gene was observed in 11 cases and 6 cases of those were point mutation as a silent substitution on exon 8. FHIT mRNA expression exhibited deletion on exon 6 to 9 in 4 cases among 15 specimens, presenting beta-actin normally. Conclusion : Our results show comparable frequency of genetic alteration in nonsmall cell lung cancer to previous studies of Western countries. Microsatellite analysis might have a role as a tumor marker especially in squamous cell carcinoma. Understanding molecular abnormalities involved in the pathogenesis could potentially lead to prevention, earlier diagnosis and the development of novel investigational approaches to the treatment of lung cancer.
Hwang, Hui Seung;Lee, Na Young;Han, Seung Beom;Kwak, Ga Young;Lee, Soo Young;Chung, Seung Yun;Kang, Jin Han;Jeong, Dae Chul
Clinical and Experimental Pediatrics
/
v.51
no.11
/
pp.1158-1164
/
2008
Purpose : To investigate the discriminative ability of pediatric index of mortality 2 (PIM2) and pediatric risk of mortality III (PRISM III) in predicting mortality in children admitted into the intensive care unit (ICU). Methods : We retrospectively analyzed variables of PIM2 and PRISM III based on medical records with children cared for in a single hospital ICU from January 2003 to December 2007. Exclusions were children who died within 2 h of admission into ICU or hopeless discharge. We used Students t test and ANOVA for general characteristics and for correlation between survivors and non-survivors for variables of PIM2 and PRISM III. In addition, we performed multiple logistic regression analysis for Hosmer-Lemeshow goodness-of-fit, receiver operating characteristic curve (ROC) for discrimination, and calculated standardized mortality ratio (SMR) for estimation of prediction. Results : We collected 193 medical records but analyzed 190 events because three children died within 2 h of ICU admission. The variables of PIM2 correlated with survival, except for the presence of post-procedure and low risk. In PRISM III, there was a significant correlation for cardiovascular/neurologic signs, arterial blood gas analysis but not for biochemical and hematologic data. Discriminatory performance by ROC showed an area under the curve 0.858 (95% confidence interval; 0.779-0.938) for PIM2, 0.798 (95% CI; 0.686-0.891) for PRISM III, respectively. Further, SMR was calculated approximately as 1 for the 2 systems, and multiple logistic regression analysis showed ${\chi}^2(13)=14.986$, P=0.308 for PIM2, ${\chi}^2(13)=12.899$, P=0.456 for PRISM III in Hosmer-Lemeshow goodness-of-fit. However, PIM2 was significant for PRISM III in the likelihood ratio test (${\chi}^2(4)=55.3$, P<0.01). Conclusion : We identified two acceptable scoring systems (PRISM III, PIM2) for the prediction of mortality in children admitted into the ICU. PIM2 was more accurate and had a better fit than PRISM III on the model tested.
Rheumatic valvulitis produces at least three distinct pathologic changes, the degree varying widely among the patients: fusion of the valve leaflets at the commissures; fusion and shortening of chordae tendinae: and fibrosis of the leaflets with subsequent stiffening, contraction and calcification. The most extensive changes usually are seen in patients with recurrent attacks of rheumatic fever. We studied on outcome of the surgical treatments of rheumatic valvular diseases that have been experienced for 12 years since 1982 at Pusan National University Hospital. The diagnoses were made by rheumatic fever history, echocardiographic findings, gross operative findings and microscopic findings. Total 502 patients were performed surgery for valvular heart diseases and 440 patients of rheumatic origin have bene analysed. There were more female than male patients as 1.3:1, and the mean age was 37.8 years old. 96.3% of them affected to the mitral valve, 19.8% to aortic valve, 16.3% affected to the tricuspid valve. Most of them underwent valve replacement, and valve repair was done in 3.9% of patients. There were 36 hospital deaths(8.2%) mainly from low cardiac output syndrome, and 15 late deaths equally due to embolism and hemorrhage. Follow up was 90.1% completed(2890 patient- year). Linealized rates of late complication events are follows : thromboembolism 1.3% per patient year; anticoagulant related hemorrhage 0.8% per patient year. Overall actuarial survival including hospital mortality was 92.7+/-2.9% in 1 year, 88.0+/-4.5% in 5 year, 82.3+/-7.7% in 10 year. We conclude that the rheumatic disease is still the most frequent and the most important cause of heart valve disease. So more intensive study is needed in spite of the abrupt decreasing rate of rheumatic fever in U.S.A. and other industrial country.
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