• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.265-270
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• 1995

The pharmacokinetics of norfloxacin (100 mg/kg, oral) in renal failure rabbits was studied. Renal failure rabbits were induced by the i.v. injection of folate (50,100 and 150 mg/kg). These produced significant increases of serum creatinine concentration $(S_{cr})$ and blood urea nitrogen (BUN). Plasma concentration and AUC of norfloxacin significantly increased. Elimination rate constant $(K_{el})$ of norfloxacin significantly decreased, and half-life $(t_{1/2})$ of norfloxacin significantly increased. Correlation between serum creatinine concentration $(S_{cr})$ and half-life $(t_{1/2})$ of norfloxacin, and correlation between BUN and AUC of norfloxacin have linear relationship respectively. These results suggest that adjustment or the dosage regimen of norfloxacin is desirable, and serum creatinine concentration $(S_{cr})$ as well as BUN can be used an index for adjusting the dosage regimen of norfloxacin in renal failure.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.4 no.1
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• pp.3-10
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• 2018

The folate receptor (FR) is a promising cell membrane-associated target for nuclear imaging of various cancers (via imaging $FR-{\alpha}$) and potentially also inflammatory diseases (via imaging $FR-{\beta}$), through the use of folic acid-based radioconjugates. However, there have been several drawbacks of previously reported radioconjugates, such as a short half-life of the radiolabel ($^{68}Ga\;t_{1/2}$ 68 min), a complex and time-consuming multistep radiosynthesis, and a high renal uptake of radiolabeled folate derivatives. The goal of this study was to develop an imaging probe by directly labeling folate with radioactive iodine without using an extra prosthetic group. The radiolabeling of folate was optimized using various labeling conditions and the labeled tracers were isolated by high-performance liquid chromatography. The in vitro stability of labeled folate was checked in phosphate-buffered saline and serum. The tumor-targeting efficacy of the probe was also evaluated by biodistribution studies using a murine 4T1 tumor model.

• Korean Journal of Biological Psychiatry
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• v.22 no.4
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• pp.223-232
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• 2015

Objectives In this study, the authors evaluated the correlation between levels of serum lipid, homocysteine, and folate with volumes of hippocampus, amygdala, corpus callosum, and in patients with amnestic mild cognitive impairment (aMCI) or Alzheimer's disease (AD) type. Methods The study recruited patients who visited the dementia clinic of Haeundae Paik Hospital in Korea between March 2010 and June 2014. Among those, patients who had taken the neurocognitive test, brain magnetic resonance imaing, tests for serum lipid, homocysteine, folate, and apolipoprotein E (APOE) genotyping and diagnosed with aMCI or AD were included for analysis. Bilateral hippocampus, entorhinal cortex, amygdala and corpus callosum were selected for region of interest (ROI). The cross-sectional relationships between serum lipid, homocysteine, folate and ROI were assessed by partial correlation analysis and multiple linear regression analysis. Results In patients with aMCI, old age (> 80) and APOE ${\varepsilon}4$ carrier were associated with AD [odds ration (OR) : 12.80 ; 95% confidence interval (CI) : 2.25-72.98 and OR : 4.48 ; 95% CI : 1.58-12.67, respectively]. In patients with aMCI or AD, volumes and thickness of ROI were inversely correlated with levels of serum lipid and homocysteine. In multiple linear regression analyses, higher total cholesterol level was related to lower left, right hippocampus volume and left amygdala volume ; higher low-density lipoprotein cholesterol was related to lower right entorhinal cortex thickness ; higher homocysteine level was related to lower corpus callosum volume. Conclusions Higher serum lipid and homocysteine levels are associated with decreased volume of hippocampus, amygdala, corpus callosum and entorhinal cortex thickness in patients with aMCI or AD. These findings suggest that serum lipid and homocysteine levels are associated with AD as a modifiable risk factor.

• Nutrition Research and Practice
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• v.10 no.1
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• pp.74-80
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• 2016

BACKGROUND/OBJECTIVES: Cardiovascular diseases is a major cause of death and is responsible for 23.8% of deaths in Korea. Clinical symptoms manifest in adulthood, but susceptibility begins in utero. Elevated homocysteine levels and adiposity might be linked to a greater risk in children as well as adults. We hypothesized that those who have simultaneous risk for folate and adiposity would be affected with elevated homocysteine levels at 3 years of age. SUBJECTS/METHODS: From the ongoing birth cohort at Ewha Womans University Mok-Dong Hospital, we compared adiposity parameters, serum homocysteine, and folate levels in 238 children (118 boys and 120 girls) at three years of age. The relationship between birth outcome, current weight and body mass index (BMI), postnatal growth, and homocysteine level were assessed using correlation and general linear model. Additionally, we assessed the combined effect between blood folate status and adiposity on current homocysteine levels. RESULTS: Birth characteristics were not correlated with homocysteine. Current weight, BMI, upper-arm circumference, skinfold thickness, waist circumference, and hip circumference were positively correlated with homocysteine at three years of age (P < 0.05). Folate level was negatively correlated with homocysteine at three years of age (P < 0.0001). A relative high anthropometric measure which is compatible with adiposity and low folate level was associated with high homocysteine levels. CONCLUSION: We found a combined effect of adiposity and folate levels with homocysteine levels at three years of age. This implicates the beneficial role of folate supplementation in the high-risk population at an early age.

• Journal of Nutrition and Health
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• v.38 no.3
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• pp.211-218
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• 2005

Elevated homocysteine concentration is known to be related to placental abruption, spontaneous abortion, and many adverse pregnancy outcomes. The purpose of this study was to investigate the effects of folic acid supplementation ($1000{\cal}ug$ per day) and 5, 10 methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism genotype on serum homocysteine and B vitamin levels in 50 infertile women ($31.2{\pm}3.2\;years$). Blood sampling was performed at baseline and at the end of folic acid supplementation period. In infertile women, serum folate and vitamin $B_{12}$ concentrations were significantly higher in post-supplementation than those in pre-supplementation. Serum homocysteine concentration was significantly lower in post-supplementation than that in pre-supplementation. However, serum homocysteine levels were still higher in the T/T genotype than those in the C/C or C/T even after folic acid supplementation. Serum homo-cysteine was inversely related to serum folate in T/T homozygotes at baseline and at the end of folic acid supplementation. These results suggest that folic acid supplementation is needed for infertile women to improve their vitamin status and also to reduce the risk of hyperhomocysteinemia. These effects were different according to their MTHFR C677T genotypes. Therefore, further studies are necessary to determine the optimal level of supplementation of folic acid by MTHFR genotypes.

• Nutrition Research and Practice
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• v.9 no.5
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• pp.503-510
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• 2015

BACKGROUND/OBJECTIVES: Increased serum homocysteine (Hcy) levels have been reported to be related to the occurrence of cardio- and cerebrovascular diseases. High serum Hcy levels are also related to the development of secondary stroke and all-cause mortality. The purpose of this study was to investigate the prevalence of high serum homocysteine level and relating factors, and the change over the 10 month period post-stroke. SUBJECTS/METHODS: Consecutive stroke patients who were admitted to the Asan Medical Center were enrolled. Ten months after the onset of stroke, an interview with a structured questionnaire was performed and blood samples were obtained for the biochemical parameters. Nutritional status was determined using the mini nutritional assessment (MNA) score and dietary nutrient intakes were also obtained using a 24 hour recall method. RESULTS: Out of 203 patients, 84% were malnourished or at risk of malnutrition, and 26% had high homocysteine levels at 10 months post-stroke. Using logistic regression, the factors related with high homocysteine levels at 10 months post-stroke included heavy alcohol consumption (P = 0.020), low MNA scores (P = 0.026), low serum vitamin $B_{12}$ (P = 0.021) and low serum folate levels (P = 0.003). Of the 156 patients who had normal homocysteine levels at admission, 36 patients developed hyperhomocysteinemia 10 months post-stroke, which was related to heavy alcohol consumption (P = 0.013). Persistent hyperhomocysteinemia, observed in 22 patients (11%), was related to male sex (P = 0.031), old age (P = 0.042), low vitamin $B_6$ intake (P = 0.029), and heavy alcohol consumption (P = 0.013). CONCLUSION: Hyperhomocysteinemia is common in post-stroke, and is related to malnutrition, heavy alcohol drinking and low serum level of folate and vitamin $B_{12}$. Strategies to prevent or manage high homocysteine levels should consider these factors.

• Korean Journal of Community Nutrition
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• v.13 no.2
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• pp.263-275
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• 2008

Impaired fasting glucose (IFG) is one of significant risk factors of developing diabetes. The persons with IFG are, thus, an important target group for primary prevention of diabetes. It is well known that plasma homocysteine concentration may be increased in poor folate nutritional status. Elevated level of plasma homocysteine is considered as a marker of enhanced oxidative stress. In addition, the protective effect against oxidative stress may be diminished in poor antioxidative nutrient status as vitamin C. It is, therefore, important to maintain adequate nutritional status of folate and vitamin C in the patients with type 2 diabetes or IFG. This study was performed to determine the effects of supplementation of folic acid or vitamin C on plasma concentrations of homocysteine, oxidized LDL, and lipids and on the activity of plasma anti-oxidative enzyme in patients with IFG. A total of 97 patients with IFG were participated voluntarily with written consents. They were divided into one of the four experimental groups; Control (C), Folatesupplemented (F), Ascorbate-supplemented (A), and Folate plus ascorbate-supplemented (FA). The subjects in C were taken placebo, those in F were supplemented 1 mg of folate, those in A were received 1,000 mg of vitamin C, and those in FA were given 1 mg of folate plus 1,000 mg of vitamin C daily for 4 weeks. No change in plasma concentrations of vitamin C, lipids, and oxidized LDL and the activity of GSH-Px were observed in vitamin C-supplemented group (A + FA) and folate-supplemented group (F + FA) compared to the placebo group (C + A). Only the folate-supplemented group (F + FA) had significantly increased average serum folate concentration and lowered plasma homocysteine concentration compared to the placebo group (C + A). Thus, it should be recommended the patients with IFG to increase folate intake through diets and, if it is not sufficient, to take folic acid supplements to prevent the development of complications induced by hyperhomocysteinemia as well as oxidative stress.

• Journal of Pharmaceutical Investigation
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• v.31 no.3
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• pp.161-165
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• 2001

Acebutolol (ABT) is almost absorbed after oral administration, but its bioavailability is reduced because of considerable first-pass metabolism in the gastrointestine and liver. The purpose of this study was to report the pharmacokinetic changes of ABT and its metabolite, diacetolol (DAT) after oral administration of acebutolol to control rabbits and rabbits with mild and severe folate-induced renal failure (FIRRs). Both of the area under the plasma concentration-time curve $(AUC^0_{\infty})$ of ABT and DAT were significantly increased in mild (p<0.05) and severe FIRRs (p<0.01), but the $AUC^0_{\infty}$ of DAT was more influenced than that of ABT in severe rabbits. There was a good correlation between serum creatinine and both of $AUC^0_{\infty}$ of ABT and DAT. The elimination half-life of ABT and DAT was significantly prolonged in mild (p<0.05) and severe (p<0.01) FIRRs, but the half-life of DAT was more influenced than that of ABT in severe FIRRs. The results suggest that the dosage of acebutolol should be adjusted according to the degree of renal disorder on the base of the serum creatinine concentration.

• Journal of Nutrition and Health
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• v.35 no.1
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• pp.37-44
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• 2002

The purpose of this study was to provide a reference range for plasma homocysteine and to explore the relation between plasma homocysteine and nutritional indexes in a Korean college women. Thirty women were selected from college students in Seoul area With mean age of 22.4y. Dietary intakes of Vitamins B$_{6}$, B$_{12}$, folate were estimated from a 3 day food diary method and plasma homocysteine concentration was mearsured as well as the levels of blood vitamins. The results obtained are as follows. Mean daily intake of energy, vitamin B$_{6}$, B$_{12}$, and folate were 1731.9kcal, 0.9mg, 2.2mg and 139.8$\mu\textrm{g}$ respectively. Mean plasma homocysteine concentration was 12.4$\mu$mol/l with a range between 6.7 and 17.8$\mu$mol/l and the mean concentrations of plasma vitamin B$_{6}$(PLP), serum vitamin $_{12}$, Serum folate and RBC folate were 77.5nmol/l, 267.4pmol/l, 17.1 nmol/l and 736.5nmol/l arid 736.5nmol/l respectively. we found a negative correlation between plasma homocysteine concentration and dietary vitamins, and blood levels of vitamin although it was not significant.

• Journal of Korean Society of Occupational and Environmental Hygiene
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• v.16 no.3
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• pp.245-253
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• 2006

We evaluated the relations among exposure and urinary levels of Cr, folate, vitamin $B_{12}$ and Hcy levels in the workers chronically exposure to Cr. Subjects were 104 male employees, 65 workers exposed to Cr in 9 electroplating plants and 39 office workers who had never been occupationally exposed to hazardous substances including Cr. The geometric mean(GM) of Cr in workplace was $0.069{\pm}0.101mg/m^3$ and urinary Cr was $0.483{\pm}0.394mg/g$ creatinine and airborne Cr concentration was significantly correlated to the urinary concentration of Cr(r=0.900, p=0.000). The geometric mean concentration of urinary Cr in control group was $0.301{\pm}0.255mg/g$ creatinine. In comparing the workers exposed to Cr with controls, significantly higher mean plasma levels were found of Hcy($11.3{\pm}4.9$ vs $9.4{\pm}4.7{\mu}mol/{\ell}$, p=0.05), but vitamin $B_{12}$ levels ($181.8{\pm}68.7$ vs $216.0{\pm}64.3nmol/{\ell}$, p=0.01) was significantly decreased. Hcy concentrations correlated positively with airborne Cr concentrations(r=0.287, p=0.004) and urinary Cr concentrations(r=0.244, p=0.015) but folate concentrations correlated negatively with airborne(r=-0.234, p=0.020) and urinary Cr concentrations(r=-0.640, p=0.090), respectively. No correlations were observed between vitamin $B_{12}$, airborne and urinary Cr concentrations. Also, Hcy concentrations correlated positively with vitamin $B_{12}$(r=0.295, p=0.0020 and negatively with folate concentrations(r=-0.196, p=0.046). The various biological(i.e. age and serum indicates) or lifestyle factors(i.e. medication, smoking, alcohol and coffee intake), also taken into account as potential confounders, did not influence the correlations found. Thus, this study found evidence that Cr might be associated with elevated plasma levels of Hcy. Furthermore, elevated plasma levels of Hcy were significantly associated with folate and vitamin $B_{12}$ concentration.