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LATAR BELAKANG : Saat ini, berbagai tanaman asli Indonesia dikembangkan sebagai bahan perawatan luka untuk hasil penyembuhan yang lebih baik. Salah satunya, yaitu Moringa oleifera L., yang merupakan tanaman asli Indonesia serta berpotensi dapat membantu penyembuhan luka melalui regulasi jalur sitokin inflamasi, interleukin (IL)-1 dan IL-10. TUJUAN : Untuk mengetahui pengaruh pemberian ekstrak Moringa oleifera L. terhadap IL-1, IL-10, dan rasio IL-1: IL-10 di jaringan kulit, pada tikus dengan luka insisi. METODE : Penelitian ini menggunakan desain post test only controlled group dengan sampel berupa 15 tikus Wistar yang dilakukan luka insisi. Sampel dibagi menjadi 3 kelompok perlakuan: perawatan luka dengan framycetin sulphate (KP), krim ekstrak Moringa oleifera L. 15% (M), dan krim plasebo (KN). Pengukuran kadar IL-1, IL-10, dan rasio IL-1: IL-10 dilakukan pada hari ke-10 perlakuan melalui pengambilan jaringan. HASIL : Kadar IL-1 pada kelompok perlakuan (M) tidak berbeda bermakna dibanding KN dan KP (33,56±4,68 vs 40,92±27,32 vs 30,23±3,92 pg/mL, p=0,543). Kelompok KP memiliki IL-10 lebih tinggi dibandingkan kelompok M dan KN (113,95±9,38; 91,75±5,65 dan 94,93±2,39 pg/mL, p

Background: High-fat diet (HFD) and cigarette smoke exposure (CSE) have been used to induce atherosclerosis in wild-type (WT) rats however, their effectivity remains unclear.Objective: To confirm and compare the effectivity of HFD and CSE on both the histopathology of aorta and the level of malondialdehyde (MDA) in WT rats.Methods: Thirty-six WT Wistar rats were divided into four main groups (K0, K1, K2, and K3) and four subgroups (K3A, K3B, K3C, and K3D). The negative control group (K0) was fed with regular diet. Group K1 was treated with an intravenous adrenaline followed by high-fat diet (HFD), K2 was fed with regular diet and given CSE, while K3 was treated with a combination of CSE and HFD. The serum and cardiac MDA levels were measured using ELISA. Hematoxylin eosin and oil red O staining of aorta were done for measuring of the intima-media thickness (IMT) ratio and for counting of foam cells, respectively. Results: Both serum and cardiac tissue MDA levels in either K1, K2, or K3 were significant higher (p

Organizational structures that are more complex and innovative are starting to develop, especially in large companies but bring new challenges in their implementation. This study examines the implications of organizational structure changes on employee career opportunities and organizational citizenship behavior. This research was conducted at PT. XYZ is in the department of Human Resource Development (HRD) with a total population of 97 people, while the sample used is saturated. The method used is PLS-SEM using the SmartPLS software tool. As a result, organizational structure changes negatively affect organizational citizenship behavior but positively affect career opportunities. While career opportunities have a positive and significant effect on organizational citizenship behavior, on the other hand, career opportunities can indirectly affect organizational structure changes and organizational citizenship behavior in a positive and significant way.

The purpose of the study was to determine the effect of pricing on consumer purchasing decisions, to determine the effect of packaging on consumer purchasing decisions and to jointly determine the effect of pricing and packaging on consumer purchasing decisions. B in Serang City. This study uses quantitative research methods, data collection using research instruments, quantitative/statistical data analysis with the aim of testing the established hypothesis. The population in this study are consumers or visitors to Mr. Shop. B in Serang City who had made a purchase at Mr. Shop. B in Serang City. Based on the results of testing hypothesis 1, it shows that pricing has a significant effect on consumer purchasing decisions. B in Serang City, in this case, if the price fixing increases, the consumer's purchasing decisions will increase. The results of testing hypothesis 2 show that packaging has a significant effect on consumer purchasing decisions. B in Serang City, in this case, if the packaging increases, the consumer's purchasing decisions will increase. The results of the submission of hypothesis 3 show that pricing and packaging have a significant effect on consumer purchasing decisions. B in Serang City, this is if the pricing and packaging increase, the consumer's purchasing decisions will increase. Keywords: Pricing, Packaging and Consumer, Purchase Decisions

Isolated systolic hypertension (ISH) reflects atherosclerosis. Studies reported hypertension prevalence among diabetes mellitus (DM); however, limited studies provided community prevalence. Present study aimed to explore ISH prevalence among DM in Indonesia. This study obtained data from the 2018 Indonesian basic health survey. The DM category was determined by fasting plasma glucose (PG) level ≥126 mg/dL or 2-hours postprandial and random PG level ≥200 mg/dL or previously diagnosed by a doctor. ISH is categorized if systolic blood pressure is≥140 mmHg and diastolic blood pressure is 90 mmHg. This study also explored the subject's determinants, i.e., compliance, demography, and lipid profile. A Chi-square and Binary logistic regression were used to determine the association. The study included 3,911 DM individuals and disclosed the prevalence of ISH 17.5%. ≥65 years old (OR=13.61 95%CI: 3.297-19.365) and 45-64 years old OR=4.59 95%CI: 3.297-6.383)), high HDL-cholesterol (OR=0.77; 95%CI: 0.626-0.936), and longer DM duration (OR=2.89; 95%CI: 2.405-3.474), all together were related to the ISH. Subjects with the oldest age category, i.e., ≥65 years old, had the highest OR. Older DM individuals with low HDL-C and longer DM duration were related to the ISH, suggesting lipid profile treatments, mainly the HDL-C, is a pivotal effort to delay ISH.

Background: Double coronary culprit lesions in ST-segment elevation myocardial infarction (STEMI) is uncommon. Despite successful primary percutaneous coronary intervention (PPCI) in all culprit lesions, the clinical outcome remains unfavorable and the possible factors for the outcome are not fully understood.Cases Presentation: We reported four cases of double culprit lesions STEMI underwent PPCI. Patient A, a 62 y.o. male with extensive anterior-inferior STEMI, had total occlusion (TO) at both proximal left anterior descending (LAD) and mid right coronary artery (RCA). Patient B, a 42 y.o. male with extensive anterior-inferior STEMI, had subtotal occlusion (STO) at proximal RCA and TO at proximal LAD. Both of them had RBBB ECG pattern. Patient C, a 67 y.o. male with inferior STEMI had 90% thrombus occlusion at proximal–mid LAD and TO at proximal RCA. Patient D, a 65 y.o. male with anteroseptal STEMI, had STO at proximal LAD and 80% thrombus occlusion at mid left circumflex. The cardiomyocyte infarction biomarkers increased in all patients. Although all of them underwent successful PPCI in all of culprit lesions, they suffered from acute heart failure and two of them experienced recurrent ventricular arrhythmia episodes. One of them (patient A) died two days post PPCI. He was only patient who suffering from total occlusion in LAD and RCA with TIMI thrombus 5 and experienced a total atrioventricular block post-PPCI.Conclusion: STEMI with coronary double culprits have severe clinical outcome, regardless of the successful PCI. The degree of coronary occlusions might be linked to the patient clinical outcome.

Background: Atherosclerosis is related to hypercholesterolaemia and inflammation. Edamame is one of the soybeans with high levels of genistein which protects the formation of atherosclerosis. Purpose: This research aimed to evaluate the effects of genistein-rich edamame on LDL, hs-CRP, Neutrophil-Lymphocyte Ratio (NLR) and Monocyte-Lymphocyte Ratio (MLR) on atherosclerosis-induced mice. Method: This research is a true experimental study with posttest only-controlled group design. Thirty male rats were divided randomly into five groups: negative control group without any intervention, positive control group with atherosclerosis induction, first intervention group with edamame extract supplementation, second intervention group with genistein-rich edamame extract supplementation, and third intervention group treated with atorvastatin. After 28 days, serum LDL, hs-CRP, LDL and MLR were measured. Results: There were significant differences (p

Latar Belakang: Jumlah CD4 merupakan parameter penting pada penderita HIV dan berhubungan dengan peningkatan risiko disfungsi sistolik. Hingga saat ini, korelasi antara jumlah CD4 dengan parameter global longitudinal strain (GLS) sebagai indikator fungsi sistolik subklinis masih belum jelas. Metode: Penelitian ini merupakan studi observasional dengan metode belah lintang. GLS ventrikel kiri diperiksa menggunakan ekokardiografi dua dimensi. Jumlah CD4 baseline dan nadir diperoleh dari rekam medis sedangkan jumlah CD4 aktual dan CD4 percentage (CD4%) diperiksa menggunakan metode flow cytometry. Hasil: Total 37 pasien HIV asimptomatik mengikuti penelitian dengan rerata umur 31,95± 7,54 tahun dan median durasi penggunaan ARV adalah 34 bulan. Median CD4 baseline dan CD4 nadir adalah 272 sel/uL dan 223 sel/uL, sedangkan rerata CD4 aktual dan CD4% adalah 516,08±252,03 sel/uL dan 19,66±7,97 %. Semua subyek penelitian memiliki fungsi sistolik normal. Rerata GLS ventrikel kiri adalah 17,02±0,71. GLS ventrikel kiri berkorelasi positif dengan CD4 aktual (r=0,43; p=0,008) dan CD4% (r=0,349; p=0,034). Penderita HIV dengan jumlah CD4 aktual ?400 sel/uL memiliki GLS ventrikel kiri yang lebih baik dibandingkan dengan yang

Background: Central obesity stands for the corner-stone of cardio-metabolic health, while nitric oxide (NO) is a major regulator of cardiovascular function. To day, the correlation between serum NO metabolites nitrate/nitrite and the obesity components in young adults remains elusive. Thus, this current study was conducted to know the correlation between serum NO metabolites levels and body fat percentage, waist circumference (WC) as well as body mass index (BMI) in young adults with central obesity.Materials and Methods: A cross-sectional study was conducted in Riau, Indonesia, involving 79 young adults aged 18-25 years, composing of 39 and 40 subjects with and without central obesity, respectively. Anthropometric measurements were performed to assess WC and BMI. Body fat percentage was measured using bioelectrical impedance analysis and serum NO metabolites levels were assessed using Griess methods.Results: Levels of serum NO metabolites were significant higher in the subjects with central obesity (168.41±12.64 μmol/L) than that of normal subjects (70.57±44.99 μmol/L, p

Serum uric acid (UA) is taken up by endothelial cells and reduces the level of nitric oxide (NO) by inhibiting its production and accelerating its degradation. Cytosolic and plasma xanthine oxidase (XO) generates superoxide and also decreases the NO level. Thus, hyperuricemia is associated with impaired endothelial function. Hyperuricemia is often associated with vascular diseases such as chronic kidney disease (CKD) and cardiovascular disease (CVD). It has long been debated whether hyperuricemia is causally related to the development of these diseases. The 2020 American College of Rheumatology Guideline for the Management of Gout (ACR2020) does not recommend pharmacological treatment of hyperuricemia in patients with CKD/CVD. In contrast, the Japanese Guideline on Management of Hyperuricemia and Gout (JGMHG), 3rdedition, recommends pharmacological treatment of hyperuricemia in patients with CKD. In a FREED study on Japanese hyperuricemic patients with CVD, an XO inhibitor, febuxostat, improved the primary composite endpoint of cerebro-cardio-renovascular events, providing a rationale for the use of urate-lowering agents (ULAs). Since a CARES study on American gout patients with CVD treated with febuxostat revealed increased mortality, ACR2020 recommends switching to different ULAs. However, there was no difference in the mortality of Japanese patients between the febuxostat-treated group and the placebo or allopurinol-treated groups in either the FEATHER or FREED studies.

Serum uric acid level above 7 mg/dl is defined as hyperuricemia, which gives rise to the monosodium urate (MSU), causing gout and urolithiasis. Hyperuricemia is an independent risk factor as well as a marker for hypertension, heart failure, atherosclerosis, atrial fibrillation, and chronic kidney disease. MSU crystals, soluble uric acid (UA), or oxidative stress derived from xanthine oxidoreductase (XOR) might be plausible explanations for the association of cardio-renovascular diseases with hyperuricemia. In macrophages, MSU activates the Nod-like receptor family, pyrin domain containing 3(NLRP3) inflammasome, and proteolytic processing mediated by caspase-1 with enhanced interleukin (IL)-1β and IL-18 secretion. Soluble UA accumulates intracellularly through UA transporters (UAT) in vascular and atrial myocytes, causing endothelial dysfunction ad atrial electrical remodeling. XOR generates reactive oxygen species (ROS) that lead to cardiovascular diseases. Since it remains unclear whether asymptomatic hyperuricemia could be a risk factor for cardiovascular and kidney diseases, European and American guidelines do not recommend pharmacological treatment for asymptomatic patients with cardio-renovascular diseases. The Japanese guideline, on the contrary, recommends pharmacological treatment for hyperuricemia with CKD to protect renal function, and it attaches importance of the cardio-renal interaction for the treatment of asymptomatic hyperuricemia patients with hypertension and heart failure.

Background: Iron overload can cause DNA oxidation which increase TGF β1, type 1 fibrilarprotein and myocardium fibrosis. Myocardium fibrosis is the main cause of death on the state of iron overload. The iron influx towards the cell during iron overload is still unknown, some research suggested LTCC acts as iron influx. This research aims to investigate the role of azelnidipine as type L calcium channel blocker, lowering TGF β1, collagen and myocardium fibrosis. Method: The research subjects consisted of 25 male Balb-C mice(8 weeks, 30-40mg) divided into 5 groups. Group 1 (NaCl+S) 0,3 cc Na Cl 0,9% (I.P) and drug solvent (Aquabidest, CMC and Nipagin) orally. Group 2Fe+S) 0.3 cc 1,5 mg Fe+sucrose (Venofer®) (I.P) and drug solvent (Aquabidest, CMC and Nipagin) orally. Group 3 (Fe+Dfx) 1,5 mg Fe+sucrose (Venofer®) (I.P) and deferasirox 20 mg/kg body weight/day orally, group 4 (Fe+Azl) 1,5 mg Fe+sucrose (Venofer®) (I.P) and azelnidipine 14 mg/day orally and group 5 (Fe+Dfx-Azl) 1,5 mg Fe+sucrose (Venofer®) (I.P) and mixture of deferasirox 20 mg/kg body weight/day and azelnidipine 14 mg/day orally. Fe-sucorse was diluted with NaCl 0.9 %. Intraperitoneal injection were administered intermittently for 60 days of treatment. Result: The highest Expression of TGF β, collagen I and fibrosis area fractions are in group Fe+S. The result of Post Hoc test between 2 treatment groups indicated that there were no difference in TGF β expression between groups NaCl+S with Fe+Dfx (P>0.05) , Fe+Dzl (P>0.05). There are no significant in collagen expression between groups NaCl+S with Fe+Dfx (P > 0.05) ,Fe+Dzl (P>0.05). Conclusion: Azelnidipine, LTCC have roles on the influx of iron into the myocardium, lowering TGF β, collagen Iexpressionsand myocardium fibrosis. Bangladesh Journal of Medical Science Vol.19(2) 2020 p.223-228

The mechanism of cardiac-troponin elevation after exercise remains unclear. Studies have reported that leucocyte ratios are related to coronary artery disease. The present study explored the relationship between leucocyte ratios, exercise intensity, and post-exercise cardiac-troponin I (cTnI) levels. Ninety-two participants in a long-distance cycling tour were included in this study. Baseline and post-exercise blood samples were collected to determine cTnI concentrations. Biochemical parameters and leucocyte ratios were measured at baseline. Exercise intensity was examined by recording the heart rate (HR). Exercise intensity was determined as the percentage of peak HR to maximal predicted HR. Based on clinical cutoff points of the cTnI assay, cTnI levels were defined as

Background: Coronary collateral circulation (CCC) is linked to myocardial remodeling severity in patients with chronic ischaemic heart disease (IHD). However its effect on left ventricular reverse remodeling (LVRR) in patients with chronic IHD underwent coronary artery bypass surgery (CABG) has never been reported. Purpose of this study was to investigate the effect of CCC grade on the LVRR event in patients with chronic IHD underwent CABG. Methods: This prospective cohort study was performed in patients with chronic IHD underwent CABG. The CCC was classified using Rentrop collateral score, i.e low CCC grade (Rentrop score 0 and 1) and high CCC grade (Rentrop score 2 and 3). LVRR event was defined as a reduction in left ventricular end systolic volume (LVESV) of 10% or more, measured by a 3D echocardiography at 1.5 months post CABG compared to the baseline before CABG. Results: A total of 22 patients (81.8% male) with mean of age 58.6 years old were enrolled. LVRR occurred in 50% patients. LVRR event was significantly higher in the patients with high CCC grade than the low CCC grade patients (p=0.009). The high CCC grade increased LVRR event independently (odds ratio=26.67; relative risk=6.93). Conclusions: High coronary collateral circulation may increase left ventricular reverse remodeling event in patients with chronic ischemic heart disease underwent coronary artery bypass surgery. Keywords: coronary collateral circulation; left ventricular reverse remodeling; chronic ischaemic heart disease; coronary artery bypass surgery; 3D echocardiography.

Background: To date, the mechanisms of post-exercise cardiac troponin elevation are debatable. Previous studies have reported that oxidative stress happens after extended exercise. Objectives: This study purposed to establish the association between the elevation of malondialdehyde (MDA), which is a marker of oxidative stress, and cardiac troponin-I (cTn-I) after prolonged cycling. Methods: Ninety-two males in Indonesian cycling tours participated in the present study. Baseline and post-exercise blood specimens were obtained to define MDA and cTn-I levels. The elevations of MDA and cTn-I were determined as positive differences of post-cycling MDA and cTn-I levels to the baseline, respectively. Results: Eighty-eight participants (age, mean = 45.3 years old, [SD]:11.47; body mass index (BMI), mean=24.2 kg/m2, [SD]: 3.03) finished the cycling tours. Subjects’ characteristics were comparable based on the touring category, except for the family history of coronary artery disease, high-density lipoprotein cholesterol level, neutrophil count, resting heart rate, exercise intensity, and cTn-I elevation. MDA significantly escalated at the level of 210.90 µmol/mL at post-exercise, from 190.18 µmol/mL at baseline. cTn-I also increased at the level of 13.65 ng/dL from 5.16 ng/dL. The elevation of MDA was related to the elevation of cTn-I. Elevation of cTn-I after prolonged cycling was contributed by elevation of MDA and exercise intensity. Conclusions: The present findings support existing confirmation that cTn-I elevation after prolonged exercise is related to oxidative stress and exercise intensity.

The present study aimed to explore the prevalence of isolated systolic hypertension (ISH) and its risk factors among diabetes mellitus (DM) subjects in the community setting study in Indonesia. This cross-sectional study extracted secondary data from basic health survey (Riset Kesehatan Dasar; RISKESDAS) conducted in 2018. DM subjects were defined based on fasting blood glucose level ≥ 126 mg/dL or 2 hours postprandial and random blood glucose level ≥ 200 mg/dL or previously had been diagnosed by a doctor; while ISH was determined based on systolic blood pressure ≥ 140 mmHg and diastolic blood pressure < 90 mmHg. We also observed the subject’s characteristics, such as demography, lipid profile, and subject’s compliance. Data were then analyzed using Chi-square and Binary logistic regression. Study involved 3,911 DM subjects, revealed the overall prevalence of ISH 17.5%. Age category of 35-44 years old (POR= 10.80; 95%CI: 2.595-44.957), 45-54 years old (POR=22.81; 95%CI: 5.616-92.677), 55-64 years old (POR=46.12; 95% CI: 11.393-186.720); 65-74 years old (POR= 81.82; 95% CI: 20.110-332.868); ≥75 years old (POR=109.64; 95% CI: 26.373-455.789), low HDL cholesterol (POR= 0,80; 95% CI: 0.653-0.972); duration of DM (POR= 1.73; 95% CI: 1.257-2.389) were associated with the ISH. The prevalence of ISH among DM subjects was 17.5%. Older DM subjects, low HDL cholesterol, and duration of DM were associated with the ISH, suggesting that modification lipid profile, especially the HDL cholesterol level, is an important measure to delay ISH in elderly and long-duration DM subjects.

BackgroundPrevious studies reported recurrent SARS-CoV-2 RNA positivity in individuals who had recovered from COVID-19 infections. However, little is known regarding the systematic review of recurrent SARS-CoV-2 RNA positivity. The current study conducted a systematic review and meta-analysis, aimed to estimate the incidence of recurrent SARS-CoV-2 RNA positivity after recovery from COVID-19 and to determine the factors associated with recurrent positivity.MethodsWe searched the PubMed, MedRxiv, BioRxiv, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry for studies published to June 12, 2020. Studies were reviewed to determine the risk of bias. A random-effects model was used to pool results. Heterogeneity was assessed using I2.ResultsFourteen studies of 2,568 individuals were included. The incidence of recurrent SARS-CoV-2 positivity was 14.81% (95% confidence interval [CI]: 11.44–18.19%). The pooled estimate of the interval from disease onset to recurrence was 35.44 days (95% CI: 32.65–38.24 days), and from the last negative to recurrent positive result was 9.76 days (95% CI: 7.31–12.22 days). Patients with younger age (mean difference [MD]=-2.27, 95% CI: -2.95 to -1.80) and a longer initial illness (MD=8.24 days; 95% CI: 7.54 – 8.95; I2=98.9%) were more likely to experience recurrent SARS-CoV-2 positivity, while patients with diabetes (RR=0.52; 95% CI: 0.30-0.90; I2=53%), severe disease (RR=0.54; 95% CI: 0.35-0.84; I2=70%), and a low lymphocyte count (RR=0.58; 95% CI: 0.39 – 0.86; I2=48%) were less likely to experience recurrent SARS-CoV-2 positivity.ConclusionsThe incidence of recurrent SARS-CoV-2 positivity was 14.81%. The estimated interval from disease onset to repeat positivity was 35.44 days, and the estimated interval from the last negative result to recurrent positive result duration was 9.76 days.

The establishment of subcritical fluid application for zingiberene extraction was studied by employing water as a green solvent. The zingiberene content was observed by using Liquid Chromatography-Mass Spectrofotometry and regarding to the independent variable of temperature, extraction time, ginger-solvent ratio and aging time. By applying subcritical water, the critical value of zingiberene content obtained was 0.036%. This value was approached by the surface modeling of alpha for rotatability design which performed at 125  C, 20 min of extraction time, 0.08 of ginger to solvent ratio and 9 min of aging time of extraction parameters. The surface modeling was validated by plotting the observed and predicted value of zingiberene content and evidenced by the value of R-square at 0.76.

Latar Belakang: Gagal jantung merupakansalah satu masalah kesehatan masyarakat global dengan jumlah penderita yang diperkirakan terus mengalami peningkatan. Meskipun terdapat kemajuan dalam tata kelolanya, gagal jantung masih memiliki prognosis yang buruk. Vitamin D merupakan mikronutrien yang berpengaruh terhadap prognosis pasien gagal jantung kronik. Saat ini belum ada data mengenai kadar vitamin D serum pada pasien gagal jantung kronik yang dirawat pada populasi Indonesia. Tujuan penelitian ini adalah untuk mengetahui kadar vitamin D serum pada pasien gagal jantung kronik yang menjalani rawat inap.Metode: Penelitian observasional pada pasien gagal jantung kronik yang dirawat di RSUP. Dr. Kariadi Semarang mulaibulan November 2017 sampaiJanuar1 2018. Pemeriksaan kadar vitamin D serum [25(OH)D] dilakukan dengan metode chemiluminescence immunoassay (CLIA).Hasil: Sebanyak 102 pasien (median usia 55 (22–65) tahun) yang terlibat, terdapat 69 sampel yang memenuhi kriteria seleksi. Median fraksi ejeksi ventrikel kiri adalah 35 (10-76)%. Median kadar vitamin D serum adalah 47.25 (14.25–143.02) nmol/L.Yang menarik, 88,4% pasien menunjukkan kadar vitamin D lebih rendah dari yang direkomendasikan. Dibandingkan dengan pasien dengan kadar vitamin D normal, pasien dengan kadar rendah tersebut lebih sering disertai denganhipertensi atau diabetes, berjenis kelamin perempuan, dan memiliki riwayat rawat inap ulang yang lebih sering.Kesimpulan: Defisiensi vitamin D serum dialami olehsebagian besar pasien gagal jantung kronik yang dirawat. Data ini menunjukkan perlunya pengukuran kadar vitamin D pada pasien gagal jantung kronik dengan hipertensi, diabetes, jenis kelamin wanita dan rawat inap ulang.Kata Kunci : Gagal jantung, defisiensi vitamin D, rawat inap

Total-Cholesterol(TC) to HDL-Cholesterol(HDL-C) ratio in athletes is well-known better than sedentary people. However, there is lack of information about comparison of TC/HDL-C in different groups of cyclists based on cycling touring characteristics and anthropometry parameters. This study was to compare TC/HDL-C ratio among groups based on type of tour participated in cyclists population.Eighty-eight participants were recruited in this cross-sectional study. Mean differences of parameters between groups analyzed by One-Way Anova test and independent t-test, while multivariate analyses was done by binary logistic-regression. P value

Local anesthetics (LAs) inhibit endoplasmic reticulum-associated protein degradation, however the mechanisms remain elusive. Here, we show that the clinically used LAs pilsicainide and lidocaine bind directly to the 20S proteasome and inhibit its activity. Molecular dynamic calculation indicated that these LAs were bound to the β5 subunit of the 20S proteasome, and not to the other active subunits, β1 and β2. Consistently, pilsicainide inhibited only chymotrypsin-like activity, whereas it did not inhibit the caspase-like and trypsin-like activities. In addition, we confirmed that the aromatic ring of these LAs was critical for inhibiting the proteasome. These LAs stabilized p53 and suppressed proliferation of p53-positive but not of p53-negative cancer cells.

BACKGROUND AND PURPOSE The expression of voltage-dependent K+ channels (Kv) 1.5 is regulated by members of the heat shock protein (Hsp) family. We examined whether the heat shock transcription factor 1 (HSF-1) and its inducer geranylgeranylacetone (GGA) could affect the expression of Kv1.5 channels and its anchoring protein, synapse associated protein 97 (SAP97).

Denaturing high-performance liquid chromatography (DHPLC), which has recently been developed as an automated method to detect mutations, is at least ten times less expensive than the direct sequencing method; however, its sensitivity and specificity for cardiac myosin-binding protein C (MYBPC3) gene mutations in hypertrophic cardiomyopathy have not been reported yet. A mutation analysis of exons 1 to 35 of MYBPC3 gene from 20 Japanese patients with hypertrophic cardiomyopathy was performed using DHPLC and direct sequencing. Compared to direct sequencing, the sensitivity and specificity of DHPLC were 87.5% and 97.42%, respectively. Its positive and negative predictive values were 41.18% and 99.74%. The positive and negative likelihood ratios were 33.95 and 0.13, and the prevalence was 2.02%. DHPLC showed high sensitivity and specificity for detecting MYBPC3 gene mutations in hypertrophic cardiomyopathy. The use of this complementary sequencing method should reduce the cost of detection of MYBPC3 gene mutations, and could be used to screen patients with hypertrophic cardiomyopathy.

We investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the stability of Kv1.5 channel protein. The expression and function of Kv1.5 (Kv1.5-FLAG) in transfected African green monkey kidney fibroblast cells as well as rat atrium were estimated by immunoblotting, immunoprecipitation, immunofluorescence and patch-clamp techniques. Both EPA and DHA immediately blocked Kv1.5 channel current in a dose-dependent manner, accompanied by reduction of their phosphorylation. Chronic treatment (for 12 h) with EPA at lower concentrations (0.3-10 muM) increased the level of Kv1.5-FLAG protein as well as Kv1.5 channel current without changes in its gating kinetics, prolonging its half-life; in contrast, both EPA and DHA at higher concentrations (30-100 muM) decreased the expression of Kv1.5-FLAG. EPA at the higher concentrations also decreased mRNA of Kv1.5 and synapse-associated protein 97 expression. EPA at the lower concentrations increased Kv1.5 expression in the endoplasmic reticulum, Golgi apparatus and cell membrane. EPA-induced increase of Kv1.5 channel expression and current was abolished by pretreatment with the protein transport inhibitor brefeldin A or colchicines, and by the Kv1.5 channel blocker 4-aminopyridine. Oral administration of EPA (30 mg/kg) increased the level of endogenous Kv1.5 in rat atria. These results indicate that chronic treatment with EPA at lower concentrations stabilizes Kv1.5 channel protein in the endoplasmic reticulum and Golgi apparatus thereby enhancing the Kv1.5 channel current on the cell membrane.

The ubiquitin-proteasome system is responsible for the disappearance of truncated cardiac myosin-binding protein C, and the suppression of its activity contributes to cardiac dysfunction. This study investigated whether missense cardiac myosin-binding protein C gene (MYBPC3) mutation in hypertrophic cardiomyopathy (HCM) leads to destabilization of its protein, causes UPS impairment, and is associated with cardiac dysfunction. Mutations were identified in Japanese HCM patients using denaturing HPLC and sequencing. Heterologous expression was investigated in COS-7 cells as well as neonatal rat cardiac myocytes to examine protein stability and proteasome activity. The cardiac function was measured using echocardiography. Five novel MYBPC3 mutations -- E344K, DeltaK814, Delta2864-2865GC, Q998E, and T1046M -- were identified in this study. Compared with the wild type and other mutations, the E334K protein level was significantly lower, it was degraded faster, it had a higher level of polyubiquination, and increased in cells pretreated with the proteasome inhibitor MG132 (50 microM, 6 h). The electrical charge of its amino acid at position 334 influenced its stability, but E334K did not affect its phosphorylation. The E334K protein reduced cellular 20 S proteasome activity, increased the proapoptotic/antiapoptotic protein ratio, and enhanced apoptosis in transfected Cos-7 cells and neonatal rat cardiac myocytes. Patients carrying the E334K mutation presented significant left ventricular dysfunction and dilation. The conclusion is the missense MYBPC3 mutation E334K destabilizes its protein through UPS and may contribute to cardiac dysfunction in HCM through impairment of the ubiquitin-proteasome system.

The aim of this study was to elucidate the mechanisms for regulations of cardiac Kv1.5 channel expression. We particularly focused on the role of heat shock proteins (Hsps). We tested the effects of Hsps on the stability of Kv1.5 channels using biochemical and electrophysiological techniques: co-expression of Kv1.5 and Hsp family proteins in mammalian cell lines, followed by Western blotting, immunoprecipitation, pulse-chase analysis, immunofluorescence and whole-cell patch clamp. Hsp70 and heat shock factor 1 increased the expression of Kv1.5 protein in HeLa and COS7 cells, whereas either Hsp40, 27 or 90 did not. Hsp70 prolonged the half-life of Kv1.5 protein. Hsp70 was co-immunoprecipitated and co-localized with Kv1.5-FLAG. Hsp70 significantly increased the immunoreactivity of Kv1.5 in the endoplasmic reticulum, Golgi apparatus and on the cell membrane. Hsp70 enhanced Kv1.5 current of transfected cells, which was abolished by pretreatment with brefeldin A or colchicine. Thus, Hsp70, but not other Hsps, stabilizes functional Kv1.5 protein.

BACKGROUND The prion protein (PrP) has been reported to serve as a surface maker for isolation of cardiomyogenic progenitors from murine embryonic stem (ES) cells. Although PrP-positive cells exhibited automaticity, their electrophysiological characteristics remain unresolved. The aim of the present study was therefore to investigate the electrophysiological properties of PrP-positive cells in comparison with those of HCN4p-or Nkx2.5-positive cells. METHODS AND RESULTS Differentiation of AB1, HCN5p-EGFP and hcgp7 ES cells into cardiac progenitors was induced by embryoid body (EB) formation. EBs were dissociated and cells expressing PrP, HCN4-EGFP and/or Nkx2.5-GFP were collected via flow cytometry. Sorted cells were subjected to reverse transcriptase-polymerase chain reaction, immunostaining and patch-clamp experiments. PrP-positive cells expressed mRNA of undifferentiation markers, first and second heart field markers, and cardiac-specific genes and ion channels, indicating their commitment to cardiomyogenic progenitors. PrP-positive cells with automaticity showed positive and negative chronotropic responses to isoproterenol and carbamylcholine, respectively. Hyperpolarization-activated cation current (I(f)) was barely detectable, whereas Na(+) and L-type Ca(2+) channel currents were frequently observed. Their spontaneous activity was slowed by inhibition of sarcoplasmic reticulum Ca(2+) uptake and release but not by blocking I(f). The maximum diastolic potential of their spontaneous firings was more depolarized than that of Nkx2.5-GFP-positive cells. CONCLUSIONS PrP-positive cells contained cardiac progenitors that separated from the lineage of sinoatrial node cells. PrP can be used as a marker to enrich nascent cardiac progenitors.

Changes in the expression of hyperpolarization-activated cyclic nucleotide (HCN)-gated channels and I(f) currents during the differentiation of embryonic stem cells into cardiac cells remain unknown. We examined changes of HCN genes in expression and function during the differentiation of Nkx2.5-positive cardiac precursor cells derived from mouse ES cells using cell sorting, RTPCR, immunofluorescence and whole cell patch-clamp techniques. Cs(+)-induced inhibition of automaticity and transcription of HCN genes increased during differentiation. Expressions of Nkx2.5, a marker of cardiac progenitor cell, and Flk1, a marker of hemangioblast, were mutually exclusive. Messenger RNA and proteins encoded by HCN1 and 4 genes were predominantly observed in Nkx2.5-positive cells on day 15, although Flk1-positive cells did not express genes of the HCN family on that day. Cs(+)-induced prolongation of the cycle of spontaneous action potentials and I(f) currents were predominantly observed on day 15. These results suggested that a fraction of Nkx2.5-positive cardiac precursor cells was committed to pacemaking cells expressing I(f) channels predominantly encoded by HCN 1 and 4 genes.

Proteasomes are the multicatalytic protein complexes with huge molecular weight. It is well known that the ubiquitin proteasome system plays an important role in regulated proteolysis. The 26S proteasome is composed of two 19S regulating components and a 20S proteasome. The 20S proteasome forms barrel shape and is composed of four rings, α- and β-rings; each ring contains highly homological seven α-subunits (1~7) and seven β-subunits (1~7), N-terminal tails of α-ring subunit form a gate to facilitate substrate entry. Each of 1, 2 and 5 β–subunit has different enzyme activity; 1 is caspase-, 2 tryptic- and 5 chymotryptic- like activity, respectively. We found a new protease inhibitor compound-A, which interacts weakly against proteasome. In order to elucidate the binding mode of the compound-A to proteasome, structure determination of the 20S proteosme complexed with compound-A was carried out. Isolated and concentrated 20S proteasome was co-crystallized with compound-A. Sitting drop vapor diffusion method was applied using 0.1M MES-NaOH (pH 6.5), 35% MPD, 50 mM magnesium acetate as a reservoir solution and 10 mg/ml proteasome and 20 mM compound-A as a sample solution. Crystals are isomorphous with the previous report [1]. Diffraction images were recorded at 100 K by using ADSC Quantum 210r CCD detector at NW12A of Photon Factory, Tsukuba, Japan. Initial phases were determined by molecular replacement method using the structure of the yeast 20S proteasome [1RYP] as a starting model and the structure model with a ligand was refined by using Refmac5 in CCP4 program package with an R value of 16.5% at 2.85 Å. The electron densities have been observed at the active site as mentioned above in the β-ring. Binding site of compound-A is closed to Tyr170 and Thr1 of the β5 subunit. The compound-A binds weakly to their residues by hydrogen bondings. It is quite different from the binding mode of the known potent proteasome inhibitor bortezomib [2].

Congenital Adrenal Hyperplasia (CAH) is an adrenal disorders due to impaired activity of one of the enzymes required for cortisol and aldosterone biosynthesis. One of the subtypes of CAH is the salt-wasting (SW) form which there is a renal salt loss due to aldosterone deficiency. Plasma Renin Activity (PRA) is the main index used to evaluate the mineralocorticoid control in CAH. PRA testing is almost very rare done for the CAH patients due to high cost, sophisticated laboratory is not available in all region and no compulsary health insurance in Indonesia. The objective of this research was to describe PRA level in patient with Congenital Adrenal Hyperplasia. This study is a part of CAH cohort study in Center for Biomedical Research (CEBIOR), Semarang, Indonesia. Eighteen patients diagnosed as CAH were drawned blood samples for hormonal test, including 17 OHP, Plasma Renin Activity, Cortisol, and Electrolytes. Clinical history and physical examination was performed to each patients. All 18 patients (17 female and 1 male) have high 17-OHP level and normal electrolites levels, but only 14 patients have PRA data. Four patients did not show their PRA level due to fail in too much blood collection. Out of 14 patient, four patients which had history of SW have very high PRA level, while six patients have PRA level more than normal without history of salt wasting. The mean of PRA level in patients with history of SW (47.72 (SD 18.63)) are higher than the patient without history of SW (13.97 (SD 13.3)). This study suggest that PRA level might be useful for evaluating mineralocorticoid level in CAH. It is proposed to the government to subsidize and provide PRA and other hormonal testing for CAH in many regions with affordable cost.