• The Korean Journal of Physiology and Pharmacology
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• v.23 no.4
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• pp.231-236
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• 2019

In drug discovery or preclinical stages of development, potency parameters such as $IC_{50}$, $K_i$, or $K_d$ in vitro have been routinely used to predict the parameters of efficacious exposure (AUC, $C_{min}$, etc.) in humans. However, to our knowledge, the fundamental assumption that the potency in vitro is correlated with the efficacious concentration in vivo in humans has not been investigated extensively. Thus, the present review examined this assumption by comparing a wide range of published pharmacokinetic (PK) and potency data. If the drug potency in vitro and its in vivo effectiveness in humans are well correlated, the steady-state average unbound concentrations in humans [$C_{u_-ss.avg}=f_u{\cdot}F{\cdot}Dose/(CL{\cdot}{\tau})=f_u{\cdot}AUCss/{\tau}$] after treatment with approved dosage regimens should be higher than, or at least comparable to, the potency parameters assessed in vitro. We reviewed the ratios of $C_{u_-ss.avg}$/potency in vitro for a total of 54 drug entities (13 major therapeutic classes) using the dosage, PK, and in vitro potency reported in the published literature. For 54 drugs, the $C_{u_-ss.avg}$/in vitro potency ratios were < 1 for 38 (69%) and < 0.1 for 22 (34%) drugs. When the ratios were plotted against $f_u$ (unbound fraction), "ratio < 1" was predominant for drugs with high protein binding (90% of drugs with $f_u{\leq}5%$; i.e., 28 of 31 drugs). Thus, predicting the in vivo efficacious unbound concentrations in humans using only in vitro potency data and $f_u$ should be avoided, especially for molecules with high protein binding.

• Journal of Animal Science and Technology
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• v.63 no.5
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• pp.1018-1033
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• 2021

In this study, we aimed to assess the effect of flaking on the nutrient digestibility of corn grain in ruminants. In this regard, in vitro rumen fermentation, in situ rumen degradability, and in vivo metabolic experiments were performed. The automated gas production technique was used for the in vitro fermentation experiments. Six types of corn flakes with various degrees of gelatinization (32%, 41%, 48%, 66%, 86%, and 89%) were ground and incubated in rumen fluid to measure rumen fermentation characteristics and digestion rate. The in situ degradability of ground corn, whole corn, and corn flakes with 62% and 66% gelatinization was measured by incubation in the rumen of two cannulated Holstein cows. In vivo metabolic experiments were performed using 12 crossbred goats (29.8 ± 4.37 kg) using a 3 × 3 Latin square design. The dietary treatments consisted of ground corn and flaked corn with 48% or 62% gelatinization. In vitro experiments showed that as the degree of gelatinization increased, the digestion rate increased linearly, while the discrete lag time decreased linearly (p < 0.05). The effective rumen dry matter degradability, determined by in situ fermentation, was 37%p lower in corn flakes than ground corn, assuming a passage rate of 6%/h (p < 0.01), and there was no difference between the two flakes. In the in vivo experiment, there was no difference in dry matter intake, average daily gain, feed efficiency, and nitrogen utilization among the treatment groups (p > 0.05); however, the crude fat digestibility was lower for corn flakes than for ground corn (p < 0.05). To summarize, the rate of fermentation of corn flakes increased as the degree of gelatinization increased. However, non-ground corn flakes had lower rumen digestibility and did not improve in vivo apparent nutrient digestibility, compared with ground corn. In contrast to the assumption that flaked corn provides more energy to ruminant animals than ground corn, we conclude that the digestibility and energy value of corn flakes are lower than those of ground corn if mastication does not sufficiently reduce the particle size of corn flakes.

• Reproductive and Developmental Biology
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• v.32 no.3
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• pp.183-191
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• 2008

This study was conducted to investigate the development and gene expression in miniature pig nuclear transfer (mNT) embryos produced under different osmolarity culture conditions. Control group of mNT embryos was cultured in PZM-3 for 6 days. Treatment group of mNT embryos was cultured in modified PZM-3 with NaCl (mPZM-3, 320 mOsmol) for 2 days, and then cultured in PZM-3 (270 mOsmol) for 4 days. Blastocyst formation rate of the treatment group was significantly higher than the control and the apoptosis rate was significantly lower in treatment group. Bax-$\alpha$ and caspase-3 mRNA expression were significantly higher in the control than the treatment group. Also, the majority of imprinting genes were expressed aberrantly in in vitro produced mNT blastocysts compared to in vivo derived blastocyst H19 and Xist mRNA expression were significantly lower in the control than the treatment group or in vivo. IGF2 mRNA expression was significantly higher in the control than the treatment group or in vivo. IGF2r mRNA expression was significantly lower in the control. Methylation profiles of individual DNA strands in H19 upstream T-DMR sequences showed a similar methylation status between treatment group and in vivo. These results indicate that the modification of osmolarity in culture medium at early culture stage could provide more beneficial culture environments for mNT embryos.

• Advances in Traditional Medicine
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• v.7 no.1
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• pp.51-64
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• 2007

Mucus is an aqueous gel complex with a constitution of about 95% water, high molecular weight glycoprotein (mucin), lipid, salts etc. Mucus appears to represent a significant barrier to the absorption of some compounds. Natural mucoadhesive agent was isolated and purified from the aqueous extract of the seeds of prosopis pallida (PP). Formulated tablet with the isolated material by wet granulation method. Some natural edible substances are in consideration for candidates as mucoadhesive agents to claim more effective controlled drug delivery as an alternative to the currently used synthetic mucoadhesive polymers. Subjected the materials obtained from natural source i.e. PP and standard synthetic substance, sodium carboxymethyl cellulose for evaluation of mucoadhesive property by various in vitro and in vivo methods. Through standard dissolution test and a model developed with rabbit, evaluated in vitro controlled release and bioadhesive property of theophylline formulation. Mucoadhesive agent obtained from PP showed good mucoadhesive potential in the demonstrated in vitro and in viνo models. The results suggest that the mucoadhesive agent showed controlled release properties by their application, substantially. In order to assess the gastrointestinal transit time in vivo, a radio opaque X-ray study performed in healthy rabbit testing the same controlled release formulation with and without bioadhesive polymer. Plasma levels of theophylline determined by the HPLC method and those allowed correlations to the in vitro mucoadhesive study results. Better correlation found between the results in different models. PP may acts as a better natural mucoadhesive agent in the extended drug delivery system.

• Nutrition Research and Practice
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• v.8 no.5
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• pp.487-493
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• 2014

BACKGROUND/OBJECTIVES: D. candidum is a traditional Chinese food or medicine widely used in Asia. There has been little research into the anticancer effects of D. candidum, particularly the effects in colon cancer cells. The aim of this study was to investigate the anticancer effects of D. candidum in vitro and in vivo. MATERIALS/METHODS: The in vitro anti-cancer effects on HCT-116 colon cancer cells and in vivo anti-metastatic effects of DCME (Dendrobium canidum methanolic extract) were examined using the experimental methods of MTT assay, DAPI staining, flow cytometry analysis, RT-PCR, and Western blot analysis. RESULTS: At a concentration of 1.0 mg/mL, DCME inhibited the growth of HCT-116 cells by 84%, which was higher than at concentrations of 0.5 and 0.25 mg/mL. Chromatin condensation and formation of apoptotic bodies were observed in cancer cells cultured with DCME as well. In addition, DCME induced significant apoptosis in cancer cells by upregulation of Bax, caspase 9, and caspase 3, and downregulation of Bcl-2. Expression of genes commonly associated with inflammation, NF-${\kappa}B$, iNOS, and COX-2, was significantly downregulated by DCME. DCME also exerted an anti-metastasis effect on cancer cells as demonstrated by decreased expression of MMP genes and increased expression of TIMPs, which was confirmed by the inhibition of induced tumor metastasis in colon 26-M3.1 cells in BALB/c mice. CONCLUSIONS: Our results demonstrated that D. candidum had a potent in vitro anti-cancer effect, induced apoptosis, exhibited anti-inflammatory activities, and exerted in vivo anti-metastatic effects.

• The Journal of Pediatrics of Korean Medicine
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• v.18 no.1
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• pp.221-246
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• 2004

Objective: The purpose of this study was to investigate the effects of Kamikwiryongtang (KKT) on the immune response and growth in a young mouse (3 weeks mice). Methods The viability of thymocytes and splenocytes in vivo and in vitro system, the population of helper T (Th) cells and cytotoxic T (Tc) cells in thymocytes and increased the population of T-lymphocytes and the population of Th cells in splenocytes, the production of ${\gamma}$ -interferon, interleukin-2 and interleukin-4 in splenocytes was investigated. KKT (500mg/kg) was administerd p.o. once a day for 7 days. Results: KKT increased the viability of thymocytes and splenocytes in vivo, but did not affect the viability of thymocytes and enhanced the viability of splenocytes in vitro system. In addition, KKT did not affect the population of helper T (Th) cells and cytotoxic T (Tc) cells in thymocytes and increased the population of T -lymphocytes and the population of Th cells in splenocytes. Also, KKT increased the production of ${\gamma}$-interferon, interleukin-2 and interleukin-4 in splenocytes. Furthermore, KKT increased the production of nitric oxide in vivo, but did not affect the production of nitric oxide in vitro system. KKT enhanced the phagocytic activity of peritoneal macrophages in vivo, but decreased the phagocytic activity in vitro system: KKT increased the body weight of a young mouse. Conclusions: KKT stimulates the specific immune response via increase of, the viability of thymocytes and splenocytes and the non-specific immune response via increase of phagocytic activity of peritoneal macrophages and stimulates the growth of a young mouse.

• Fisheries and Aquatic Sciences
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• v.6 no.2
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• pp.74-80
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• 2003

Two cellular biomarker parameters of the farmed Pacific oyster Crassostrea gigas were studied in vivo and in vitro after exposure to concentrations of polychlorinated biphenyls in terms of neural red uptake (NRU) and lysozyme activity. The oysters exposed in vivo to the xenobiotic concentrations, 0, 30, 90, and 180 ng/g for 14 days, enhanced hemocyte NRU with occasional significant differences (P<0.05), depending on the chemical concentration and duration. An adverse tendency was manifest in the lysozyme activities both in the hemocyte and serum of the oyster treated with the chemical in a same manner, rendering these two cellular parameters as biomarker candidates against the chemical. The oysters exposed in vitro to the chemical concentrations, 0, 1, 5, 10, 100, 1,000, and 10,000 ng/g for 24 hrs at $10^{\circ}C$ showed a similar tendancy as those exposed in vivo to the chemical. Unlike in vivo response, however, the in vitro NRU was first influenced by very low concentration of the chemical. In in vitro results, marked but not significant increase of hemocyte NRU was noticed at the chemical concentration of 5 ng/g, where the value was almost as high as those exposed to higher chemical concentrations, up to 10,000 ng/g. An unusual result was observed in the in vitro lysozyme activity of hemocyte in which significant decrease was first noticed at the chemical concentration of 100 ng/g.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.53 no.3
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• pp.423-431
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• 2020

This study was conducted to investigate in vivo and in vitro digestibility in juvenile Atlantic Bluefin tuna Thunnus thynnus. In vivo digestibility was compared between four experimental diets to determine the optimum dietary inclusion level of an enzyme-treated sardine fish meal (EFM) and sardine fish meal (FM). The experimental diets were as follows; EFM75 (75% EFM), EFM60 (60% EFM and 15% FM), FM75 (75% FM) and SL (frozen sand lance) as a raw fish feed. Feces of Bluefin tuna (90.3 g) were collected both by siphoning from a 700 L cage and by dissection in 69 ton concrete rearing tanks. For the siphoning method, protein digestibility was higher in the tuna fed SL diet than that of other groups. The lowest protein digestibility was observed in FM75. For the dissection method, protein digestibility was higher in tuna fed EFM75 diet than that of other groups. The lowest protein digestibility was observed in the EFM60 group. In vitro digestibility was compared in six protein sources to find an alternative source of EFM for the tuna feed. The highest in vitro digestibility was observed in EFM (92%) followed by low temperature FM (72%), meat meal (65%), feather meal (60%), sardine fish meal (57%) and poultry by-product meal (55%).

• Proceedings of the Korean Society of Applied Pharmacology
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• 1996.11a
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• pp.99-113
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• 1996

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 does not cross the blood-brain barrier, the blood-cerebrospinal fluid (CSF) barrier is likely to play a role in taurine transport between the central nervous system and the systemic circulation. Therefore, we examined in vivo elimination of taurine from the CSF in the rat to characterize in vivo kinetics of elimination for 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 up to 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 the labeled taurine was reduced (p<0.01), 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 taurine is cleared from the CSF via a saturable process. This process may be functionally relevant to taurine homeostasis in the brain.

• Food Science of Animal Resources
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• v.34 no.3
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• pp.325-332
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• 2014

The antioxidant capacity of porcine splenic hydrolysate (PSH) was studied in vitro and in vivo. Peptide hydrolysates were prepared, using the proteolytic enzyme $Alcalase^{(R)}$. The molecular weights of PSH were 37,666, 10,673, 6,029, and 2,918 g/mol. Rats were fed a 5% (w/v) PSH diet, instead of a casein diet, for 4 wk. The food intake, body weight gain, and liver weight of rats in the PSH group were similar to those in the control (CONT) group. There were no differences in the serum total cholesterol, triglyceride, total protein, or albumin levels between PSH and CONT groups. However, the level of in vivo hepatic lipid peroxidation in PSH group was significantly lower than that in CONT. In vivo hepatic catalase and glutathione peroxidase activities in the PSH group were significantly higher than those in the control group. The in vitro protein digestibility of PSH was lower than that of casein. The in vitro trolox equivalent antioxidant capacity of PSH was significantly higher than that of the peptide hydrolysate from casein. The in vitro radical scavenging activities of PSH were significantly higher than those of the peptide hydrolysate from casein. The present findings suggest that porcine splenic peptides improve the antioxidant status in rats by enhancing hepatic catalase and GSH-Px activities, and indicate a potential mechanism of radical scavenging activity during gastrointestinal passage.