• YAKHAK HOEJI
• /
• v.45 no.6
• /
• pp.739-745
• /
• 2001

Of all pesticides, carbamates are known to be most common, since alternatives such as organophosphates have long lifetime and are extremely toxic to produce a delayed neurotoxic effect. Although a number of studies about toxicity of carbofuran, a most widely used carbamate, have been reported, its cardiovascular toxicity has not yet been studied. In the present study, we investigated its cardiovascular toxic effect in anesthetized rat in vivo and in isolated Langendorff rat heart, In anesthetized rat model, carbofuran (10 mg/kg) significantly reduced heart rate, and transiently increased blood pressure. In isolated rat heart, carbofuran (10${\mu}{\textrm}{m}$) caused a significant depression in the left ventricular developed pressure (LVDP), indicating contractile dysfunction by carbofuran. Carbofuran (10${\mu}{\textrm}{m}$) also decreased coronary flow rate (CFR) in isolated heart, indicating carbofuran-induced coronary dysfunction. These results suggest that carbofuran can cause cardiac dysfunction in rat in vivo and vitro.

• Biomolecules & Therapeutics
• /
• v.1 no.2
• /
• pp.220-225
• /
• 1993

Effect of BR-900317 on the angiotensin I-induced pressor response in pithed rats and the effects of its single oral administration on plasma angiotensin converting enzyme (ACE) activities in normotensive rats and on the cardiovascular system in hypertensive model rats (SHR, RHR), were compared with those of captopril. BR-900317 attenuated the angiotensin I-induced pressor effects in pithed rats. In a single oral dose administration study, BR-900317 inhibited the plasma ACE activities in a dose-dependent fashion. Duration of the action of BR-900317 was similar to that of captopril. BR-900317 produced antihypertensive effect in spontaneously hypertensive rats and dose-dependent antihypertensive effect in 2-kidney Goldblatt hypertensive rats without affecting heart rate. These results suggest that the main mechanism of the antihypertensive effect of BR-900317 is the suppression of angiotensin II production due to the inhibition of the ACE.

• Journal of Animal Science and Technology
• /
• v.64 no.5
• /
• pp.911-921
• /
• 2022

Maximum residue limits (MRL) for pesticides in feed have been set to protect public health and produce safe livestock products. In vivo experiments to establish MRL are essential, as livestock are commonly used to obtain reliable in vivo quantitative information. Here, we aimed to evaluate whether small laboratory animals can replace or reduce monogastric livestock in experiments to quantify pesticide residues in vivo after oral consumption through feed. First, 24 pigs and rats were randomly assigned to four groups and fed 0, 3, 9, or 30 mg/kg of sulfoxaflor. After four weeks, serum, muscle, fat, liver, kidney, and small intestine samples were collected, and sulfoxaflor residues were analyzed using liquid chromatography - tandem mass spectrometry. Sulfoxaflor residues in pig tissues were significantly correlated with those in rat tissues. Model equations were formulated based on the residual sulfoxaflor amount in pig and rat tissues. The calculated and measured sulfoxaflor residues in pigs and rats showed more than 90% similarity. Sulfoxaflor did not affect body weight gain, feed intake, or the feed conversion ratio. Therefore, we concluded that pesticide residue quantification in vivo to establish MRL could be performed using small laboratory animals instead of livestock animals. This would contribute to obtaining in vivo pesticide residue information and reducing large-scale livestock animal experiments.

• Proceedings of the KSAR Conference
• /
• 2002.06a
• /
• pp.19-19
• /
• 2002

This study was to examine whether the in vitro differentiated neural cells derived from human embryonic stem (hES, MB03) cells can be survived and expressed tyrosin hydroxylase(TH) in grafted normal or PD rat brain. To differentiate in vitro into neural cells, embryoid bodies (EB: for 5 days, without mitogen) were formed from hES cells, neural progenitor cells(neurosphere, for 7-10 days, 20 ng/㎖ of bFGF added N2 medium) were produced from EB, and then finally neurospheres were differentiated into mature neuron cells in N2 medium(without bFGF) for 2 weeks. In normal rat brain, neural progenitor cells or mature neuron cells (1×10/sup 7/ cells/㎖) were grafted to the striatum of normal rats. After 2 weeks, when the survival of grafted hES cells was examined by immunohistochemical analysis, the neural progenitor cell group indicated higher BrdU, NeuN＋, MAP2＋ and GFAP＋ than mature neuron cell group in grafted sites of normal rats. This result demonstrated that the in vivo differentiation of grafted hES cells be increased simultaneously in both of neuronal and glial cell type. Also, neural progenitor cell grafted normal rats expressed more TH pattern than mature neuron cells. Based on this data, as a preliminary test, when the neural progenitor cells were grafted into the striatum of 6-hydroxydopamine lesioned PD rats, we confirmed the cell survival (by double staining of Nissl and NeuN) and TH expression. This result suggested that in vitro differentiated neural progenitor cells derived from hES cells are more usable than mature neuron cells for the neural cell grafting in animal model and those grafted cells were survived and expressed TH in normal or PD rat brain.

• The Korean Journal of Zoology
• /
• v.35 no.3
• /
• pp.295-307
• /
• 1992

In order to study the differentiation of the epithelial cells during the development of fetal rat lung tissue, histological changeB in organotypic culture and in vivo were examined. Light microscopy and scanning electron microscopy were used to analvre the histological change in rat lung from the 15th nary of gestation to the 111th nary after birth. In organotypic culture system, the pulmonary epithelial cell differentiation was studied by scanning electron microscopy. The results obtained from this study were as follows. 1. During deveiopment of lung, the glandular stage lasted from the Isth day to the lsth naut of gestation; the canalicular stage from the 17th nay to the 19th naut of gestation; the saccuiar stage from 20th nary to the birth. Alveolar stage was observed at the 3rd nary of postnatal rat lung. 2. In organotvpic culture of fetal rat lung cells organized alveolar-like structures resembling those of in uiuo state were observed on the gelatin matrix. In contrast with in vivo state, fetal lung cells formed group of type ll pneumocytes predominently along the contours of the matrix. These cells have large apical surface, short microvilli and secreted materials which may be sunactant. These results suggested that an orsanotypic culture retaining epithelial- -mesenchvmal relationships is appropriate culture model to study the pulmonary epithelial cell (especially type ll pneumocvte) differentation.

• Journal of the Korean Society of Radiology
• /
• v.8 no.7
• /
• pp.389-395
• /
• 2014

The research was carried out to develop a animal model of malignant brain tumor for the researches in glioblastoma multiform (GBM) diagnosis and therapy. C6 cells were transplanted into the right striatum of SD rat using stereotactic instrument for the development. The developed animal model was verified by MRI and H&E stain assay of anatomicohistological examination. The MRI observations showed that the tumor developed at the injection site at the 7 days after glioblastoma inoculation. At 14 days post inoculation, the tumor grew to a large volume occupying almost a half of the right cerebral hemisphere. It was confirmed that the expression of excessive mitosis and pleomorphism in anatomicohistological examination. The developed animal model must be necessary and useful tool for the in vivo level research in the development of the new modality for the diagnosis and therapy of brain cancer.

• Biomedical Science Letters
• /
• v.13 no.3
• /
• pp.207-212
• /
• 2007

The purpose of this preliminary study is to improve the efficiency of gene transfer of nonviral plasmid DNA by in vivo electroporation in ischemic hindlimb muscle, tibialis anterior. Hindlimb ischemic model was aseptically made by excision of left femoral artery. Each $50\;{\mu}g$ of pEGFP-C1 and pGL3-control in $100\;{\mu}l$ 0.9% NaCl was injected in tibialis anterior muscle. In vivo electroporation was applied on the same site with 10 mm-distance 2 needle array electrodes and ECM830. In 3 groups of normal rat with different electric field strength 0, 200 and 800 V/cm, the expression of pEGFP-C1 was comparatively evaluated. In 8 groups of normal rats, the expression of pGL3-control was evaluated in 0, 40, 50, 80, 100, 150, 200 and 300 V/cm of electric field strength. In 5 groups of ischemic models, the expression of pGL3-control was analyzed on 0, 4, 7, 10 and 14 days elapsed after making ischemic models. In 9 groups of ischemic rats, the expression of pGL3-control was analyzed in the electric field strength 0, 60, 70, 80, 100, 150, 200, 250 and 300 V/cm. GFP expressions in normal tibialis anterior were high in the extent and degree in order of electric field strength of 200, 800 and 0 V/cm. Luciferase value was highest in $50{\sim}100\;V/cm$ electric field strength. In the case of ischemic models, luciferase expression was significantly increasing in the order elapsed time after making the model. The degree of luciferase expression was higher in cases of application of in vivo electroporation than in that of non-application and was highest in $100{\sim}150\;V/cm$. In conclusion, in vivo electroporation is effective in transfer and expression of plasmid DNA in normal and ischemic tibialis anterior of rat.

• Journal of Pharmaceutical Investigation
• /
• v.28 no.4
• /
• pp.275-282
• /
• 1998

In order to develop a desirable in vitro release which correlates well with in vivo bioavailability, hollow type suppository containing Propranolol HCl(PPH) powder in the cavity and conventional type suppository with dispersed PPH in the base were prepared. Polyvinyl alcohol (PVA) hydrogel as a base and PPH as a model drug were used for the preparation of suppository. The rates of drug release from the suppositories were studied by Paddle method, Muranish method, Dialysis tubing method and Rotating dialysis cell method. The release profiles from suppositories using the four different release tests were compared. After a rectal administration in rat, the mean $C_{max}$ of hollow type suppository was significantly lower than that of conventional type, but $T_{max}$, $AUC_{0{\to}12}$ and MRT of hollow type were significantly higher 1.6 times, 1.2 times and 1.9 times than those of conventional type, respectively. The computer program was used to simulate plasma concentration from in vitro released amounts of drug and in vivo pharmacokinetic parameters. Based on comparison of the simulated bioavailability from computer program with experimental bioavailability in rat we have found out in vitro release test which correlates well with in vivo bioavailability. Our results have shown the best correlation between in vitro release and in vivo bioavailability in PPH-PVA hydrogel hollow type suppository for the paddle method and conventional type suppository for the rotating dialysis cell method. In this work we propose that PPH-PVA hydrogel suppository shows in vitro-in vivo correlation. This data should help to optimize the formulation of the drug and provide a basis for quality control procedures.

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

• Journal of the Korean Magnetic Resonance Society
• /
• v.10 no.2
• /
• pp.126-140
• /
• 2006

Purpose: Contrary to the human study, it has rarely investigated metabolic alterations in the dorsolateral prefrontal cortex (DLPFC) of depressed rats versus age and sex-matched controls using proton magnetic resonance spectroscopy (MRS). Thus, the purpose of this research was to verify the feasibility of metabolic differences between the normal rat and the depression model rat. Materials and Methods: A homogeneous group of 20 SD male rats was used for MRI and in vivo 1H MRS. To induce a depressed status in SD rats, we performed the forced swimming test (FST). Using image-guide, water suppressed in vivo 1H MRS with 4.7 T MRI/MRS system, NAA/Cr and Cho/Cr ratios were mainly measured between depressed rats and normal subjects. Results: In depressed rats, increased Cho/Cr ratio was measured versus control subjects. However, no significant group effect for NAA/Cr was observed between case-control pairs. Discussion and Conclusions: The present 1H MRS study shows significant brain metabolic alterations of dorsolateral prefrontal cortex with experimental depressed status of SD rat induced by FST compared to normal subjects. This result provides new evidence that in vivo 1 H MRS may be a useful modality for detecting localized functional neurochemical markers alterations in left DLPFC in SD rats.