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1.  Improvement of diabetes and hypertension after gastrectomy: A nationwide cohort study 
AIM: To evaluate the effect of gastrectomy on diabetes mellitus (DM) and hypertension (HTN) in non-obese gastric cancer patients.
METHODS: A total of 100000 patients, diagnosed with either type 2 DM or HTN, were randomly selected from the 2004 Korean National Health Insurance System claims. Among them, 360 diabetes and 351 hypertensive patients with gastric cancer who had been regularly treated without chemotherapy from January 2005 to December 2010 were selected. They were divided into three groups according to their treatment methods: total gastrectomy (TG), subtotal gastrectomy (STG) and endoscopic resection (ER).
RESULTS: The drug discontinuation rate of anti-diabetic and anti-hypertensive agents after gastric cancer treatment was 9.7% and 11.1% respectively. DM appeared to be improved more frequently (22.8%) and earlier (mean ± SE 28.6 ± 1.8 mo) in TG group than in the two other groups [improved in 9.5% of ER group (37.4 ± 1.1 mo) and 6.4% of STG group (47.0 ± 0.8 mo)]. The proportion of patients treated with multiple drugs decreased more notably in TG group compared to others (P = 0.001 in DM, and P = 0.035 in HTN). In TG group, adjusted hazard ratio for the improvement of DM was 2.87 (95%CI: 1.15-7.17) in a multi-variate analysis and better control of DM was observed with survival analysis (P < 0.001).
CONCLUSION: TG was found to decrease the need for anti-diabetic medications which can be reflective of improved glycemic control, to a greater extent than either ER or STG in non-obese diabetic patients.
PMCID: PMC4306161  PMID: 25632190
Diabetes; Hypertension; Gastrectomy; Gastric cancer; National cohort
2.  Monitoring HIV-infected Patients with Diabetes: Hemoglobin A1c, Fructosamine, or Glucose? 
Published studies report inappropriately low hemoglobin A1C (HbA1c) values that underestimate glycemia in HIV patients.
We reviewed the charts of all HIV patients with diabetes mellitus (DM) at our clinic. Fifty-nine patients had HbA1c data, of whom 26 patients also had fructosamine data. We compared the most recent HbA1c to finger-stick (FS) glucose averaged over three months, and fructosamine to FS averaged over six weeks. Predicted average glucose (pAG) was calculated as reported by Nathan et al: pAG (mg/dL) = 28.7 × A1C% − 46.7. Data were analyzed using the Statistical Analysis System (SAS) and Kruskal–Wallis test.
HbA1c values underestimated (UE) actual average glucose (aAG) in 19% of these patients and overestimated (OE) aAG in 27%. HbA1c estimated aAG within the established range in only 54% of the patients. There were no statistical differences in the types of HIV medication used in patients with UE, OE, or accurately estimated (AE) glycemia. A Spearman correlation coefficient between HbA1c and aAG was r = 0.53 (P < 0.0001). Correlation between fructosamine and aAG was r = 0.47 (P = 0.016).
The correlations between HbA1c and aAG and between fructosamine and aAG were weaker than expected, and fructosamine was not more accurate than HbA1c.
PMCID: PMC4259549  PMID: 25520565
glucose; A1C; fructosamine; HIV; diabetes
3.  Total adiponectin, but not inflammatory markers C-reactive protein, tumor necrosis factor-α, interluekin-6 and monocyte chemoattractant protein-1, correlates with increasing glucose intolerance in pregnant Chinese–Americans 
Journal of Diabetes  2014;6(4):360-368.
Elevated insulin, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 levels and decreased high molecular weight adiponectin (HMW-APN) levels have been reported in Caucasians with gestational diabetes mellitus (GDM). No similar studies have been performed in Chinese women.
Serum samples were obtained 1 h after a 50-g glucose challenge test (1HGCT) from Chinese–American women at 24–28 gestational weeks and total adiponectin (T-APN), HMW-APN, CRP, TNF-α, IL-6, and MCP-1 concentrations were measured. Correlation coefficients for glucose (1HGCT), HbA1c, insulin, and body mass index (BMI) were calculated against T-APN, HMW-APN, CRP, TNF-α, IL-6, and MCP-1. Significant P-values were determined using Bonferroni adjustments.
Women with GDM had higher insulin and 1HGCT and lower T-APN. In addition, T-APN was lower in non-GDM subjects who had 1HGCT ≥135 mg/dL with no abnormal or one abnormal glucose value on the 3-h oral glucose tolerance test. There were no significant differences in HMW-APN and inflammatory marker levels between non-GDM and GDM groups. There were negative correlations between T-APN and 1HGCT, insulin, BMI, and HbA1c, as well as between HMW-APN and 1HGCT, insulin, and BMI. No significant correlations were observed between 1HGCT, HbA1c, insulin, or BMI and CRP, TNF-α, IL-6, or MCP-1.
T-APN is reduced in Chinese women with GDM and those without GDM but with evidence of glucose intolerance. Unlike results reported for Caucasians, Chinese–American women with GDM do not exhibit elevated levels of CRP, TNF-α, IL-6, or MCP-1, possibly because Chinese women are relatively leaner compared with Caucasians.
PMCID: PMC4235426  PMID: 24330072
Chinese pregnant women; gestational diabetes; glucose intolerance; HMW-adiponectin; inflammatory markers; T-adiponectin
4.  RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer 
The Journal of Clinical Investigation  2013;123(6):2551-2563.
The PI3K signaling pathway regulates diverse cellular processes, including proliferation, survival, and metabolism, and is aberrantly activated in human cancer. As such, numerous compounds targeting the PI3K pathway are currently being clinically evaluated for the treatment of cancer, and several have shown some early indications of efficacy in breast cancer. However, resistance against these agents, both de novo and acquired, may ultimately limit the efficacy of these compounds. Here, we have taken a systematic functional approach to uncovering potential mechanisms of resistance to PI3K inhibitors and have identified several genes whose expression promotes survival under conditions of PI3K/mammalian target of rapamycin (PI3K/mTOR) blockade, including the ribosomal S6 kinases RPS6KA2 (RSK3) and RPS6KA6 (RSK4). We demonstrate that overexpression of RSK3 or RSK4 supports proliferation upon PI3K inhibition both in vitro and in vivo, in part through the attenuation of the apoptotic response and upregulation of protein translation. Notably, the addition of MEK- or RSK-specific inhibitors can overcome these resistance phenotypes, both in breast cancer cell lines and patient-derived xenograft models with elevated levels of RSK activity. These observations provide a strong rationale for the combined use of RSK and PI3K pathway inhibitors to elicit favorable responses in breast cancer patients with activated RSK.
PMCID: PMC3668839  PMID: 23635776
6.  Systematic interrogation of 3q26 identifies TLOC1 and SKIL as cancer drivers 
Cancer discovery  2013;3(9):1044-1057.
3q26 is frequently amplified in several cancer types with a common amplified region containing 20 genes. To identify cancer driver genes in this region, we interrogated the function of each of these genes by loss- and gain-of-function genetic screens. Specifically, we found that TLOC1 (SEC62) was selectively required for the proliferation of cell lines with 3q26 amplification. Increased TLOC1 expression induced anchorage independent growth and a second 3q26 gene, SKIL (SNON), facilitated cell invasion in immortalized human mammary epithelial cells. Expression of both TLOC1 and SKIL induced subcutaneous tumor growth. Proteomic studies demonstrated that TLOC1 binds to DDX3X, which is essential for TLOC1-induced transformation and affected protein translation. SKIL induced invasion through up-regulation of SLUG (SNAI2) expression. Together, these studies identify TLOC1 and SKIL as driver genes at 3q26 and more broadly suggest that cooperating genes may be co-amplified in other regions with somatic copy number gain.
PMCID: PMC3770815  PMID: 23764425
Copy number alteration; TLOC1; SEC62; SKIL; 3q26; protein translation; cancer
7.  Effect of Steaming, Blanching, and High Temperature/High Pressure Processing on the Amino Acid Contents of Commonly Consumed Korean Vegetables and Pulses 
In the present report, the effects of blanching, steaming, and high temperature/high pressure processing (HTHP) on the amino acid contents of commonly consumed Korean root vegetables, leaf vegetables, and pulses were evaluated using an Automatic Amino Acid Analyzer. The total amino acid content of the samples tested was between 3.38 g/100 g dry weight (DW) and 21.32 g/100 g DW in raw vegetables and between 29.36 g/100 g DW and 30.55 g/100 g DW in raw pulses. With HTHP, we observed significant decreases in the lysine and arginine contents of vegetables and the lysine, arginine, and cysteine contents of pulses. Moreover, the amino acid contents of blanched vegetables and steamed pulses were more similar than the amino acid contents of the HTHP vegetables and HTHP pulses. Interestingly, lysine, arginine, and cysteine were more sensitive to HTHP than the other amino acids. Partial Least Squares-Discriminate Analyses were also performed to discriminate the clusters and patterns of amino acids.
PMCID: PMC4195628  PMID: 25320720
amino acids; vegetables; pulses; Automatic Amino Acid Analyzer; partial least squares-discriminate analysis (PLS-DA)
8.  Functional genomics approach for the identification of human host factors supporting dengue viral propagation 
Dengue virus (DENV) is endemic throughout tropical regions around the world and there are no approved treatments or anti-transmission agents currently available. Consequently, there exists an enormous unmet need to treat the human diseases caused by DENV and block viral transmission by the mosquito vector. RNAi screening represents an efficient method to expand the pool of known host factors that could become viable targets for treatments or provide rationale to consider available drugs as anti-DENV treatments. We developed a high throughput siRNA-based screening protocol that can identify human DENV host factors. The protocol herein describes the materials and the procedures necessary to screen a human cell line in order to identify genes which are either necessary for or restrict DENV propagation at any stage in the viral life cycle.
PMCID: PMC4075997  PMID: 24696344
RNA interference (RNAi); dengue virus; yellow fever virus; whole genome RNAi screening; whole genome siRNA screening; dengue virus host factors; flavivirus
9.  Congenital Ocular Anomaly in an Infant with Trisomy 14 Mosaicism 
Trisomy 14 mosaicism is a rare chromosomal abnormality with distinct and recognizable clinical features. We report a patient with presumed retinal dystrophy having diffuse retinal pigment epithelial abnormalities, which has not been previously reported in association with trisomy 14. This case expands the clinical spectrum of this rare entity.
PMCID: PMC3408541  PMID: 22870035
Retinal dystrophies; Trisomy 14; Trisomy 14 mosaicism
10.  Discordance between Perceived and Actual Cancer Stage among Cancer Patients in Korea: A Nationwide Survey 
PLoS ONE  2014;9(5):e90483.
We assessed the accuracy of communication between doctors and patients by evaluating the consistency between patient perception of cancer stage and the medical records, and analyzed the most influential factors of incongruence among cancer patients at 10 cancer centers across Korea.
Information was gathered from cancer patients at the National Cancer Center and nine regional cancer centers located in every province of Korea between 1 July 2008 and 31 August 2008. Data were analyzed using Pearson's χ2 test and multivariate logistic regression analysis.
The stages of cancer reported by the 1,854 patients showed a low degree of congruence with the stages given in medical records (k = 0.35, P<0.001). Only 57.1% of the patients had accurate knowledge of their cancer stage. In total, 18.5% underestimated their stage of disease, and the more advanced the cancer stage, the more likely they were to underestimate it, in order of local (14.2%), regional (23.7%), and distant (51.6%). Logistic regression analysis showed that congruence was lower in patients with cervical cancer (odds ratio [OR] = 0.51, 95% confidence interval [CI] = 0.30–0.87), recurrence (OR = 0.64, 95% CI = 0.50–0.83), and treatment at the National Cancer Center (OR = 0.53, 95% CI = 0.39–0.72).
There are knowledge gaps between patients' perceived and actual stage of cancer. Patients with cervical cancer, recurrence, and who received treatment at a regional cancer center showed less understanding of their cancer stage.
PMCID: PMC4015901  PMID: 24817193
12.  Retinal Hemorrhage Associated with Perinatal Distress in Newborns 
To describe the ophthalmoscopic features and natural history in a case series of eyes that developed intraocular hemorrhages associated with perinatal distress and to evaluate their clinical courses.
A retrospective chart review of 289 neonates with a medical history of perinatal distress was conducted. Among these 289 patients (578 eyes), 29 eyes of 17 neonates were found to have had retinal hemorrhages or vitreous hemorrhages (VH). A comprehensive chart review, including details of fundoscopic findings and perinatal history, was conducted.
Intraocular hemorrhage was present in 5.5% of the patients. Most hemorrhages (82.7%) were intraretinal. In our population, 17% (n = 5) of hemorrhages resolved within two weeks, but 31% (n = 9) did not resolve even after four weeks. Most hemorrhages spontaneously resolved without any specific sequelae; however, one infant's dense unilateral VH persisted up to three months after birth. When the patient was seen again at 3.5 years of age, she had developed axial myopia and severe amblyopia of the involved eye.
In asphyxiated newborns, the possibility of intraocular hemorrhages should be considered. Long-standing, dense hemorrhages obscuring the macula may lead to severe vision deprivation amblyopia. Therefore, ophthalmic examination should be considered in neonates with perinatal distress, and close observation is necessary for hemorrhages that do not resolve in this amblyogenic age group.
PMCID: PMC3178764  PMID: 21976937
Newborn infant; Perinatal distress; Retinal hemorrhage; Vitreous hemorrhage
13.  Siberian Sturgeon Oocyte Extract Induces Epigenetic Modifications of Porcine Somatic Cells and Improves Developmental Competence of SCNT Embryos 
Somatic cell nuclear transfer (SCNT) has generally demonstrated that a differentiated cell can convert into a undifferentiated or pluripotent state. In the SCNT experiment, nuclear reprogramming is induced by exposure of introduced donor nuclei to the recipient cytoplasm of matured oocytes. However, because the efficiency of SCNT still remains low, a combination of SCNT technique with the ex-ovo method may improve the normal development of SCNT embryos. Here we hypothesized that treatment of somatic cells with extracts prepared from the germinal vesicle (GV) stage Siberian sturgeon oocytes prior to their use as nuclear donor for SCNT would improve in vitro development. A reversible permeability protocol with 4 μg/mL of digitonin for 2 min at 4°C in order to deliver Siberian sturgeon oocyte extract (SOE) to porcine fetal fibroblasts (PFFs) was carried out. As results, the intensity of H3K9ac staining in PFFs following treatment of SOE for 7 h at 18°C was significantly increased but the intensity of H3K9me3 staining in PFFs was significantly decreased as compared with the control (p<0.05). Additionally, the level of histone acetylation in SCNT embryos at the zygote stage was significantly increased when reconstructed using SOE-treated cells (p<0.05), similar to that of IVF embryos at the zygote stage. The number of apoptotic cells was significantly decreased and pluripotency markers (Nanog, Oct4 and Sox2) were highly expressed in the blastocyst stage of SCNT embryos reconstructed using SOE-treated cells as nuclear donor (p<0.05). And there was observed a better development to the blastocyst stage in the SOE-treated group (p<0.05). Our results suggested that pre-treatment of cells with SOE could improve epigenetic reprogramming and the quality of porcine SCNT embryos.
PMCID: PMC4093206  PMID: 25049951
Epigenetic Modifications; Somatic Cell Nuclear Transfer; Siberian Sturgeon Oocyte Extract
14.  Comparison of Nutrient Intake and Diet Quality Between Hyperuricemia Subjects and Controls in Korea 
Clinical Nutrition Research  2014;3(1):56-63.
Hyperuricemia is associated with metabolic syndrome as well as gout, and the prevalence of hyperuricemia is increasing in Korea. This study aimed to compare the nutrient intake and diet quality between hyperuricemia subjects and controls. Of the 28,589 people who participated in a health examination between 2008 and 2011, 9,010 subjects were selected whose 3-day food records were available. Clinical and laboratory data were collected from electronic medical records. Diet quality was evaluated using the food habit score (FHS), nutrient adequacy ratio (NAR), and mean adequacy ratio (MAR). The prevalence of hyperuricemia was 13.8% (27.1%, men; 5.2%, women). Body mass index, waist circumference, triglycerides, total cholesterol, and low-density lipoprotein cholesterol were significantly higher (p < 0.0001), while high-density cholesterol (p < 0.001) was significantly lower in the hyperuricemia subjects than in the controls. The hyperuricemia subjects had a lower intake of vitamin A (p < 0.004), vitamin C, folate, fiber, and calcium than the controls (p < 0.0001). Intake of vegetables and dairy products was significantly lower, whereas alcohol intake was significantly higher in the hyperuricemia subjects than in the controls ( p < 0.0001). The FHS (p < 0.0001), MAR (p < 0.0001), and NARs for vitamin A (p = 0.01), vitamin B2, vitamin C, folate, and calcium (p < 0.0001) were significantly lower in the hyperuricemia subjects than in the controls. In conclusion, the hyperuricemia subjects reported poorer diet quality than the controls, including higher alcohol intake and lower vegetable and dairy product intake.
PMCID: PMC3921296  PMID: 24527421
Hyperuricemia; Uric acid; Diet records; Nutritive Value; Food Habits
15.  Outcomes of Primary Ligation of Patent Ductus Arteriosus Compared With Secondary Ligation After Pharmacologic Failure in Very-Low-Birth-Weight Infants 
Pediatric Cardiology  2013;35(5):793-797.
This study aimed to determine whether primary surgical closure of patent ductus arteriosus (PDA) is a risk factor for morbidity and mortality compared with secondary surgical ligation. The study enrolled 178 very-low-birth-weight infants. The surgical group included 34 patients who did not respond to pharmacologic intervention and eventually required ligation of their PDA as well as 35 patients who underwent direct ligation because of contraindications to the use of oral ibuprofen. The overall outcomes for the primary and secondary ligation groups were compared. The outcome during hospitalization showed no statistically significant difference in terms of morbidity and mortality between the two groups. The group that had primary ligation for PDA experienced more complications associated with premature birth such as lower gestational age and birth weight. The two groups did not differ significantly in terms of overall outcomes.
PMCID: PMC4015055  PMID: 24370764
Surgical ligation; Morbidity; Hemodynamically significant ductus arteriosus
16.  Highly specific and sensitive method for measuring nucleotide excision repair kinetics of ultraviolet photoproducts in human cells 
Nucleic Acids Research  2013;42(4):e29.
The nucleotide excision repair pathway removes ultraviolet (UV) photoproducts from the human genome in the form of short oligonucleotides ∼30 nt in length. Because there are limitations to many of the currently available methods for investigating UV photoproduct repair in vivo, we developed a convenient non-radioisotopic method to directly detect DNA excision repair events in human cells. The approach involves extraction of oligonucleotides from UV-irradiated cells, DNA end-labeling with biotin and streptavidin-mediated chemiluminescent detection of the excised UV photoproduct-containing oligonucleotides that are released from the genome during excision repair. Our novel approach is robust, with essentially no signal in the absence of UV or a functional excision repair system. Furthermore, our non-radioisotopic methodology allows for the sensitive detection of excision products within minutes following UV irradiation and does not require additional enrichment steps such as immunoprecipitation. Finally, this technique allows for quantitative measurements of excision repair in human cells. We suggest that the new techniques presented here will be a useful and powerful approach for studying the mechanism of human nucleotide excision repair in vivo.
PMCID: PMC3936724  PMID: 24271390
17.  An Outbreak of Food Borne Illness Due to Methomyl Pesticide Intoxication in Korea 
Journal of Korean Medical Science  2013;28(11):1677-1681.
On February 21, 2013, 6 elderly people collapsed abruptly after eating bean sprout bibimbab (boiled rice mixed with bean sprouts and seasoned with soybean sauce) at a countryside restaurant in the Chungbuk Province, Korea. Minutes after eating the meal, all of the patients lapsed into a state of stupor. Respiratory arrest developed in 2 patients; and one of two patients died of cardiac arrest. The autopsy identified methomyl and methanol in the deceased patient's gastric contents and in the remaining soybeanbean sauce seasoning. Five of the 6 patients ingested one spoonful of the soybeanbean sauce seasoning and survived, while one patient who died of cardiac arrest, ingested approximately two spoons. Symptoms of toxicity presented quickly in the subjects and progressed rapidly, including chest tightness, an unusual sensation in the pit of the stomach, dizziness, ataxia, and finally, collapse. Three patients who drank ethanol with the meal experienced only mild toxic symptoms. Our analysis of the clinical observations in these cases suggests that ingestion of methomyl pesticide and the additive toxicity of methanol may have been responsible for the intoxication.
PMCID: PMC3835514  PMID: 24265535
Poisoning; Methomyl; Methanol; Mixture Toxicity
18.  Glufosinate Herbicide Intoxication Causing Unconsciousness, Convulsion, and 6th Cranial Nerve Palsy 
Journal of Korean Medical Science  2013;28(11):1687-1689.
Although glufosinate ammonium herbicides are considered safe when used properly, ingestion of the undiluted form can cause grave outcomes. Recently, we treated a 34-yr-old man who ingested glufosinate ammonium herbicide. In the course of treatment, the patient developed apnea, mental deterioration, and sixth cranial nerve palsy; he has since been discharged with full recovery after intensive care. This case report describes the clinical features of glufosinate intoxication with a focus on sixth cranial nerve palsy. Our observation suggests that neurologic manifestations after ingestion of a "low-grade toxicity herbicide" are variable and more complex than that was previously considered.
PMCID: PMC3835516  PMID: 24265537
Glufosinate Ammonium; Neurologic Manifestations; Abducens Nerve Disease
19.  High-dose stereotactic body radiotherapy correlates increased local control and overall survival in patients with inoperable hepatocellular carcinoma 
Recent studies using stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC) have reported high tumor response and local control. However, the optimal SBRT dose remains unknown, and it is still not clear whether a dose response relationship for local control (LC) and overall survival (OS) exist or not. We performed this study to determine whether a dose response relationship for LC and OS is observed in SBRT for inoperable HCC.
Between 2003 and 2011, 108 patients with HCC were treated with SBRT. All patients were unsuitable for surgery or local ablation and had incomplete response to transarterial chemoembolization. Eighty-two patients with a longest tumor diameter (LD) less than or equal to 7.0 cm who were treated with 3-fraction SBRT and were analyzed. This cohort comprised 74 Child-Turcotte-Pugh (CTP) class A patients and 8 CTP class B7 patients. The median LD was 3.0 cm (range, 1.0–7.0 cm), and the median dose was 51 Gy (range, 33–60 Gy).
LC and OS rates at 2 years after SBRT were 87% and 63%, respectively, with a median follow-up duration of 30 months for all patients. The 2-year LC/OS rates for patients treated with doses of > 54, 45–54, and < 45 Gy were 100/71, 78/64, and 64%/30%, respectively (p = .009/p < .001). Multivariate analysis revealed that the SBRT dose (p = .005) and Barcelona Clinic Liver Cancer stage (p = .015) were significant prognostic factors for OS. Correlation analysis revealed a positive linear relationship between the SBRT dose and LC (p = .006, R = .899)/OS (p = .002, R = .940) at 2 years. Based on the tumor-control probability model, a dose of 54.8 Gy provides 2-year LC with a 90% probability. Five patients experienced grade 3 or higher gastrointestinal toxicity, and 6 had deteriorating of CTP score by greater than or equal to 2 within 3 months of SBRT.
This study demonstrated a dose response relationship for LC and OS with SBRT for HCC. Higher LC rates resulting from an increased dose may translate into survival benefits for patients with HCC.
PMCID: PMC4231524  PMID: 24160944
Hepatocellular carcinoma; Radiotherapy; Stereotactic body radiotherapy; Dose–response relationship; Dose-survival relationship
20.  Simultaneous determination of 30 ginsenosides in Panax ginseng preparations using ultra performance liquid chromatography 
Journal of Ginseng Research  2013;37(4):457-467.
A quick and simple method for simultaneous determination of the 30 ginsenosides (ginsenoside Ro, Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, 20(S)-Rg2, 20(R)-Rg2, 20(S)-Rg3, 20(R)-Rg3, 20(S)-Rh1, 20(S)-Rh2, 20(R)-Rh2, F1, F2, F4, Ra1, Rg6, Rh4, Rk3, Rg5, Rk1, Rb3, Rk2, Rh3, compound Y, compound K, and notoginsenoside R1) in Panax ginseng preparations was developed and validated by an ultra performance liquid chromatography photo diode array detector. The separation of the 30 ginsenosides was efficiently undertaken on the Acquity BEH C-18 column with gradient elution with phosphoric acids. Especially the chromatogram of the ginsenoside Ro was dramatically enhanced by adding phosphoric acid. Under optimized conditions, the detection limits were 0.4 to 1.7 mg/L and the calibration curves of the peak areas for the 30 ginsenosides were linear over three orders of magnitude with a correlation coefficients greater than 0.999. The accuracy of the method was tested by a recovery measurement of the spiked samples which yielded good results of 89% to 118%. From these overall results, the proposed method may be helpful in the development and quality of P. ginseng preparations because of its wide range of applications due to the simultaneous analysis of many kinds of ginsenosides.
PMCID: PMC3825861  PMID: 24235860
Panax ginseng; Panax ginseng preparations; Ginsenosides; UPLC-PDA; Simultaneous analysis
21.  Metastatic Esophageal Squamous Cell Carcinoma to the Orbit and Periorbit Masquerading as Periorbital Abscess 
A 61-year-old man with no history of malignancy presented with a rapidly expanding left periorbital mass, first noticed one month prior to presentation. The mass was firm, and a pus-like discharge drained spontaneously from the center of the lesion. A biopsy was performed, and histopathology confirmed squamous cell carcinoma. Systemic evaluation revealed that the patient had a primary esophageal squamous cell carcinoma with multiple metastases. The prognosis of orbital metastasis is generally poor, and this patient expired after one month of conservative treatment.
PMCID: PMC2851000  PMID: 20379463
Abscess; Orbital neoplasms; Squamous cell carcinoma
22.  Metabolism of R- and S-Warfarin by CYP2C19 into Four Hydroxywarfarins 
Drug metabolism letters  2012;6(3):157-164.
Coumadin (R/S-warfarin) is a highly efficacious and widely used anticoagulant; however, its highly variable metabolism remains an important contributor to uncertainties in therapeutic responses. Pharmacogenetic studies report conflicting findings on the clinical relevance of CYP2C19. A resolution to this controversy is impeded by a lack of detail on the potential role of CYP2C19 in warfarin metabolism. Consequently, we assessed the efficiency of CYP2C19 metabolism of R- and S-warfarin and explored possible contributions in the liver using in vitro methods. Recombinant CYP2C19 metabolized R- and S-warfarin mainly to 6-, 7-, and 8-hydroxywarfarin, while 4′-hydroxywarfarin was a minor metabolite. Overall R-warfarin metabolism was slightly more efficient than that for S-warfarin. Metabolic pathways that produce R-6-, 7-, and 8-hydroxywarfarin in human liver microsomal reactions correlated strongly with CYP2C19 S-mephenytoin hydroxylase activity. Similarly, CYP1A2 activity toward phenacetin correlated with formation of R-6 and 7-hydroxywarfarin such that R-8-hydroxywarfarin seems unique to CYP2C19 and possibly a biomarker. In following, CYP2C19 likely impacts R-warfarin metabolism and patient response to therapy. Intriguingly, CYP2C19 may contribute to S-warfarin metabolism in patients, especially when CYP2C9 activity is compromised due to drug interactions or genetic polymorphisms.
PMCID: PMC3713490  PMID: 23331088
Warfarin; CYP2C19; Cytochrome P450; metabolism; biomarker
24.  Changes in Dietary Intake, Body Weight, Nutritional Status, and Metabolic Rate in a Pancreatic Cancer Patient 
Clinical Nutrition Research  2013;2(2):154-158.
Pancreatic cancer patients often have a poor prognosis and suffer from nutritional problems. Malnutrition is characterized by weight loss and decreased dietary intake, and is common among pancreatic cancer patients. The objective of this report was to describe the changes in dietary intake, body weight, nutritional status, and metabolic rate on a continuum from the time of diagnosis until the end of life in a patient with pancreatic cancer. In summary, the patient's nutritional status gradually declined, accompanied by extreme weight loss and decreased dietary intake. Conversely, resting energy expenditure, measured by indirect calorimetry, increased from 24 kcal/kg/day to 35 kcal/kg/day. Nutritional management during cancer treatment is important but may be challenging in pancreatic cancer patients.
PMCID: PMC3728466  PMID: 23908983
Pancreatic cancer; Diet records; Nutritional status; Basal metabolism
25.  Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease: a randomized, double-blind trial 
European Heart Journal  2013;34(31):2453-2463.
Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD).
Methods and results
This randomized, controlled, phase II trial consisted of two parts. In part A, the safety and tolerability of oral BAY 94-8862 [2.5, 5, or 10 mg once daily (q.d.)] was assessed in 65 patients with HFrEF and mild CKD. In part B, BAY 94-8862 (2.5, 5, or 10 mg q.d., or 5 mg twice daily) was compared with placebo and open-label spironolactone (25 or 50 mg/day) in 392 patients with HFrEF and moderate CKD. BAY 94-8862 was associated with significantly smaller mean increases in serum potassium concentration than spironolactone (0.04–0.30 and 0.45 mmol/L, respectively, P < 0.0001–0.0107) and lower incidences of hyperkalaemia (5.3 and 12.7%, respectively, P = 0.048) and WRF. BAY 94-8862 decreased the levels of B-type natriuretic peptide (BNP), amino-terminal proBNP, and albuminuria at least as much as spironolactone. Adverse events related to BAY 94-8862 were infrequent and mostly mild.
In patients with HFrEF and moderate CKD, BAY 94-8862 5–10 mg/day was at least as effective as spironolactone 25 or 50 mg/day in decreasing biomarkers of haemodynamic stress, but it was associated with lower incidences of hyperkalaemia and WRF.
PMCID: PMC3743070  PMID: 23713082
Aldosterone; Antagonist; Chronic kidney disease; Heart failure; Mineralocorticoid receptor

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