• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.7-20
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• 1995

Taurine, a ${\beta}-amino$ acid, plays an important role as a neuromodulator and is necessary for the normal development of the brain. Since de novo synthesis of taurine in the brain is minimal and in vivo studies suggest that taurine dose not cross the blood-brain barrier, we examined whether the choroid plexus, the blood-cerebrospinal fluid (CSF) barrier, plays a role in taurine transport in the central nervous system. The uptake of $[^3H]-taurine$ into ATP depleted choroid plexus from rabbit was substantially greater in the presence of an inwardly directed $Na^+$ gradient taurine accumulation was negligible. A transient in side-negative potential gradient enhanced the $Na^+-driven$ uptake of taurine into the tissue slices, suggesting that the transport process is electrogenic, $Na^+-driven$ taurine uptake was saturable with an estimated $V_{max}$ of $111\;{\pm}\;20.2\;nmole/g/15\;min$ and a $K_M\;of\;99.8{\pm}29.9\;{\mu}M$. The estimated coupling ratio of $Na^+$ and taurine was $1.80\;{\pm}\;0.122.$ $Na^+-dependent$ taurine uptake was significantly inhibited by ${\beta}-amino$ acids, but not by ${\alpha}-amino$ acids, indicating that the transporter is selective for ${\beta}-amino$ acids. Since it is known that the physiological concentration of taurine in the CSF is lower than that in the plasma, the active transport system we characterized may face the brush border (i.e., CSF facing) side of the choroid plexus and actively transport taurine out of the CSF. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to determine whether elimination kinetics of taurine from the CSF is consistent with the in vitro study. Using a stereotaxic device, cannulaes were placed into the lateral ventricle and the cisterna magna of the rat. Radio-labelled taurine and inulin (a marker of CSF flow) were injected into the lateral ventricle, and the concentrations of the labelled compounds in the CSF were monitored for upto 3 hrs in the cisterna magna. The apparent clearance of taurine from CSF was greater than the estimated CSF flow (p<0.005) indicating that there is a clearance process in addition to the CSF flow. Taurine distribution into the choroid plexus was at least 10 fold higher than that found in other brain areas (e. g., cerebellum, olfactory bulb and cortex). When unlabelled taurine was co-administered with radio-labelled taurine, the apparent clearance of taurine was reduced (p<0.0l), suggesting a saturable disposition of taurine from CSF. Distribution of taurine into the choroid plexus, cerebellum, olfactory bulb and cortex was similarly diminished, indicating that the saturable uptake of taurine into these tissues is responsible for the non-linear disposition. A pharmacokinetic model involving first order elimination and saturable distribution described these data adequately. The Michaelis-Menten rate constant estimated from in vivo elimination study is similar to that obtained in the in vitro uptake experiment. Collectively, our results demonstrate that taurine is transported in the choroid plexus via a $Na^+-dependent,saturable$ and apparently ${\beta}-amino$ acid selective mechanism. This process may be functionally relevant to taurine homeostasis in the brain.

• Microbiology and Biotechnology Letters
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• v.44 no.1
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• pp.48-54
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• 2016

In this study, biosugar production by the red-algae Eucheuma cottonii was investigated using dilute sulfuric acid-catalyzed hydrolysis and data analysis by response surface methodology. This approach yielded 25.8 g/l total reducing sugar under the conditions of $160.1^{\circ}C$, 1% (v/v) sulfuric acid, and 13.1 min. The sugar concentration showed a linear inverse correlation with the combined severity factor (CSF) of the reaction conditions. CSF was calculated as $log(t{\cdot}e{xp}[(T_H-T_R)/14.75])-pH$, where t is the coupling reaction time, $T_H$ is the target temperature, and $T_R$ is the reference temperature ($100^{\circ}C$). In addition, levulinic acid production showed a linear positive correlation with CSF. E. cottonii may represent a useful feedstock for sugar production in the field of bioenergy.

• Korean Journal of Medicinal Crop Science
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• v.20 no.1
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• pp.8-15
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• 2012

The present study investigated an ethanol extract of Chaenomeles sinensis fruit (CSF) for possible neuroprotective effects on neurotoxicity induced by amyloid ${\beta}$ protein ($A{\beta}$) (25-35) in cultured rat cortical neurons and also for antidementia activity in mice. Exposure of cultured cortical neurons to $10{\mu}M\;A{\beta}$ (25-35) for 36 h induced neuronal apoptotic death. At $0.1-10{\mu}g/m{\ell}$, CSF inhibited neuronal death, elevation of intracellular calcium concentration ($[Ca^{2+}]_i$), and generation of reactive oxygen species (ROS) induced by $A{\beta}$ (25-35) in primary cultures of rat cortical neurons. Memory loss induced by intracerebroventricular injection of mice with 15 nmol $A{\beta}$ (25-35) was inhibited by chronic treatment with CSF (10, 25 and 50 mg/kg, p.o. for 7 days) as measured by a passive avoidance test. CSF (50 mg/kg) inhibited the increase of cholinesterase activity in $A{\beta}$ (25-35)-injected mice brain. From these results, we suggest that the antidementia effect of CSF is due to its neuroprotective effect against $A{\beta}$ (25-35)-induced neurotoxicity and that CSF may have a therapeutic role for preventing the progression of Alzheimer's disease.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.3
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• pp.356-362
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• 2010

When pine (Pinus densiflora) needles were fractionated into cold water (PD-CW), hot water (PD-HW) and methanol extract (PD-M), PD-M showed potent simulating activity (1.19-fold of the saline control) for proliferation of bone marrow cells mediated by Peyer's patch cells in vitro. MeOH extracts were prepared by homogenization, stirring or reflux to identify the method of methanol extraction, and MeOH extract by reflux method showed significantly highest intestinal immune system modulating activity (1.30-fold) in vitro. The intestinal immune system modulating effect of orally administered PD-M fractionated from pine needles also were studied in mice. Analyzing intestinal immune system modulating activity mediated Peyer's patch cells from C3H/He mice which had been fed with PD-M at different doses for 7 days, 1.0 g/kg of BW/day indicated that the bone marrow cells had proliferated (3.65-fold of 3% EtOH administered group). In addition, the amounts of IL-6 in the culture supernatant of Peyer's patch cells at 1.0 g/kg of BW/day were increased (1.13-fold) whereas the production of GM-CSF was not dose dependent. These results indicate that oral administration of PD-M enhances the secretion of hematopoietic growth factors such as GM-CSF and IL-6 from Peyer's patch cells, and these cytokines also act on modulator of bone marrow cell proliferation.

• Journal of Microbiology and Biotechnology
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• v.13 no.2
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• pp.196-201
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• 2003

The mixture (PM) of Saccharomyces cerevisiae and fermented rice bran on the activation of macrophage and bone marrow cell proliferation was studied in mice. PM stimulated not only the activation of macrophage (1.8-fold of saline) but also IL-6 production from macrophage (1.5-fold) at 2.0 g/㎏/day during 7 days of oral administration. By the culture supernatant of Peyer's patch cells from C3H/HeJ mice fed PM at 2.0 g/㎏/day for 7 days, the bone marrow cells significantly proliferated compared with that of mice receiving only saline (1.7-fold). In addition, the contents of GM-CSF and IL-6 in the culture supernatant of Peyer's patch cells from mice fed PM at 2.0 g/㎏/day were increased in comparison with those from the control (1.8 and 1.4-fold, respectively). These results revealed that oral administration of PM may modulate IL-6 production to induce the activation of macrophage, and also enhance secretion of hematopoietic growth factors such as GM-CSF and IL-6 from Peyer's patch cells.

• Journal of Radiation Protection and Research
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• v.38 no.4
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• pp.179-184
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• 2013

The biological effects of radiation are dependent on the dose rate and dose of radiation. In this study, effects of dose and dose rate using whole body radiation on plasma cytokines and blood count from male BALB/c mice were evaluated. We examined the blood and cytokine changes in mice exposed to a low (3.49m Gy $h^{-1}$) and high (2.6 Gy $min^{-1}$) dose rate of radiation at a total dose of 0.5 and 2 Gy, respectively. Blood from mice exposed to radiation were evaluated using cytokine assays and complete blood count. Peripheral lymphocytes and neutrophils decreased in a dose dependent manner following high dose rate radiation. The peripheral lymphocytes population remained unchanged following low dose rate radiation; however, the neutrophils population increased after radiation. The sera from these mice exhibited elevated levels of flt3 ligand and granulocyte-colony-stimulating factor (G-CSF), after high/low dose rate radiation. These results suggest that low-dose-rate radiation does not induce blood damage, which was unlike high-dose-rate radiation treatment; low-dose-rate radiation exposure activated the hematopoiesis through the increase of flt3 ligand and G-CSF.

• Biomolecules & Therapeutics
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• v.6 no.4
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• pp.400-405
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• 1998

The pharmacokinetics of CJ-50001 (recombinant human granulocyte-colony stimulating factor, developed by R&D center of Cheil Jedang Corp.) were investigated in rats and dogs. The serum concentrations of CJ-50001 were measured by a sandwich enzyme immunoassay. After single intravenous (iv) administration of Cf-50001 to rats at a dose of 5 $\mu$g/kg, the mean terminal half-life and area under the concentration-time curve (AUC) were 0.96 h and 124.497g . h/ml, respectively. After single subcutaneous (sc) administration at the same dose, maximum serum concentration was observed at about 2 hours after administration, and the mean terminal half-life, AUC and the bioavailability were 1.11 h,63.58$\mu$g . h/ml and 51.07%, respectively. In repeated dosing studies, CJ-50001 was administered iv and sc to rats at a daily dose of 5$\mu$g/kg for 7 days. The pharmacokinetic parameters, such as mean AUC and terminal half-life, were no significantly different from those of single administration. Following single iv and sc administration of CJ-50001 to dogs at a dose of 5 $\mu$g/kg, mean AUCs were much higher than those of rats, due to the decreased clearence (CL). After sc administration to dogs, maximum serum concentration was observed at 2~4 hours after administration and the bioavailability was 54.60%.

• Journal of Fisheries and Marine Sciences Education
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• v.27 no.5
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• pp.1470-1478
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• 2015

Adjuvant is an immune enhancer commonly used during vaccination to enhance the host immune response. In the present study, we produced the several recombinant protein from immune related gene of olive flounder (Paralichthys olivaceus). Especially, to produce the soluble type of recombinant protein, we constructed the MBP (Maltose binding protein) fusion G-CSF (Granulocyte colony stimulating factor) recombinant protein among the flounder immune related genes. To verify the immune stimulatory effect and safety of this recombinant protein (rPoGCSF), expression changes of several immune genes were tested using quantitative real-time PCR method with gene specific primer from flounder head kidney leukocytes. As a result, we confirmed that the rPoGCSF has an ability of immune stimulatory effect, also it has broad range of pH and temperature.

• Toxicological Research
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• v.31 no.4
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• pp.371-392
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• 2015

TS-DP2 is a recombinant human granulocyte colony stimulating factor (rhG-CSF) manufactured by TS Corporation. We conducted a four-week study of TS-DP2 (test article) in repeated intravenous doses in male and female Sprague-Dawley (SD) rats. Lenograstim was used as a reference article and was administered intravenously at a dose of $1000{\mu}g/kg/day$. Rats received TS-DP2 intravenously at doses of 250, 500, and $1000{\mu}g/kg/day$ once daily for 4 weeks, and evaluated following a 2-week recovery period. Edema in the hind limbs and loss of mean body weight and body weight gain were observed in both the highest dose group of TS-DP2 and the lenograstim group in male rats. Fibro-osseous lesions were observed in the lenograstim group in both sexes, and at all groups of TS-DP2 in males, and at doses of TS-DP2 $500{\mu}g/kg/day$ and higher in females. The lesion was considered a toxicological change. Therefore, bone is the primary toxicological target of TS-DP2. The lowest observed adverse effect level (LOAEL) in males was $250{\mu}g/kg/day$, and no observed adverse effect level (NOAEL) in females was $250{\mu}g/kg/day$ in this study. In the toxicokinetic study, the serum concentrations of G-CSF were maintained until 8 hr after administration. The systemic exposures ($AUC_{0-24h}$ and $C_0$) were not markedly different between male and female rats, between the administration periods, or between TS-DP2 and lenograstim. In conclusion, TS-DP2 shows toxicological similarity to lenograstim over 4-weeks of repeated doses in rats.

• The Korea Journal of Herbology
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• v.23 no.1
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• pp.85-92
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• 2008

Objectives : This study was performed to efficiently make Black Panax Ginseng (BPG) and evaluate its antitumor activity. Methods : Panax ginseng was steamed at $95^{\circ}C$ for 3 h, dried and steamed again at $115^{\circ}C$ for 6 h. The main ginsenosides of BPG were $Rg_{3}$, $Rk_{1}$ and $Rg_{5}$. Results : Among the saponins in BPG, the amount of ginsenoside $Rg_{3}$ was determined by HPLC method. The 11.48 mg of ginsenoside $Rg_{3}$ was obtained from lg of dried BPG. The crude saponin fraction (CSF) of BPG was tested in vitro for its cytotoxic activities against various human cancer cell lines, such as ACHN, NCI-H23, HCT-15 and PC-3. The CSF of BPG exhibited stronger cytotoxic activity than that of red Panax ginsneng. CSF of BPG exhibited good cytotoxic activities against ACFIN, HCT-15, and PC-3 cell lines with $IC_{50}$ values of 60.3-90.8 ${\mu}g$/ml. However, CSF of BPG did not show any cytotoxic activity against NCI-H23 cell line. Conclusions : BPG produced by new manufacturing is more effective than BPG produced by existing processing in anticancer activity. And new BPG has a possibility of investigation because of high contents of Rg3, Rk1 and Rg5 that have various phisological activities.