• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.108-108
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• 1997

The effects of nalbuphine.HCI on the spontaneous locomotor activity and primary humoral immune response were investigated in ICR mice. Nalbuphine was intraperitoneally administered with the dose of 130, 260, 360 mg/kg in mice. The locomotor activity such as distance traveled was observed for 90min at 10min intervals. Nalbuphine showed the biphasic dose-response relationship on the spontaneous locomotor activity. IgM plaque forming cells(PFC) in splenocytes and IgM level in antiserum were significantly decreased depending on the dose of nalbuphine when nalbuphine was administered after the immunization, but slightly increased only at the low dose in the case of nabuphine administration after the immunization(SRBC).

• Archives of Pharmacal Research
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• v.21 no.4
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• pp.370-373
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• 1998

Ten substituted phenacyl derivatives of 4-hydroxypiperidine were synthesized and studied for their effects on the mean arterial blood pressure (MABP) in normotensive anaesthetized rats and smooth muscles contractions of isolated rabbit jejunum. Two derivatives caused fall in blood pressure at the dose of 10-20 mg/kg and one rise in blood pressure at the dose of 20 mg/kg. Two compounds exhibited biphasic response (hypotensive followed by hypertensive) and one gave triphasic response at 10 mg/kg dose. Rest of four derivatives were found devoid of any effect on mean arterial blood pressure up to the dose of 30 mg/kg. All the derivatives except two caused relaxant effect on the spontaneous contraction of rabbit jejunum at the dose range of 0.1 -2 mg/kg.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.114-119
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• 1994

[$^3$H]Ouabain binding parameters ( $K_{D}$ and $B_{max}$) to control rat ventricular strips and Langendorff preparations which were not previously exposed to ouabain were compared with those to both preparations that had been first exposed to a complete ouabain dose range of dose-response curve (10$^{-8}$ to 10$^{4}$M). In rat ventricular strips and Langendorff perfused heart preparations, cumulative dose-response curves of ouabain revealed biphasic positive inotropic effects, a "low-dose" effect and a "high-dose" effect with E $d_{50}$ values of 0.5 $\mu$M and 35 $\mu$M ouabain, respectively. The "low-dose" effect in ventricular strip disappeared or was diminished significantly when the ouabain dose-response curve was repeated after the washout of the effects of the first dose-response curve, whereas there were no significant differences in the maximal "high-dose"effect in both exposures to oubain. However, both of the control and ouabain-preexposed Langendorff perfused hearts revealed the same low-dose effects. The $K_{D}$ value for [$^3$H] ouabain binding and the ouabain binding site concentration ( $B_{max}$) estimated by [$^3$H]ouabain displacement assay in control preparations were 230 nM and 2 pmol/mg protein, respectively. [$^3$H]Ouabain binding parameters were not changed by repeated exposure to high concentrations of ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site ($\alpha$$_2$isoform).).).).).

• Korean Journal of Weed Science
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• v.32 no.3
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• pp.159-169
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• 2012

Hormesis is a dose-response phenomenon that is characterized by low-dose stimulation and high-dose inhibition. This biphasic dose-responses have had a long and extensive history in the fields of chemical toxicology, radiation biology and pharmacology. Hormesis has been found from bacteria, fungi, plants and animals, but hormesis in plants has received relatively little attention. Thus principles, occurrence, factors affecting the expression of hormetic responses, and their mechanisms in plants induced by herbicides are reviewed to provide the potentials for crop enhancement. Bromacil, bromoxynil, chloramben, propachlor, terbacil, EPTC, MSMA, and glyphosate at low doses showed stimulatory response in growth. Subtoxic dose of glyphosate increased sucrose content in sugarcane that is used worldwide in sugarcane production. Low dose of protoporphyrinogen-inhibiting herbicides induced increased pathogen defence, and low dose of triazine herbicides improved nitrogen metabolism and increased protein content in some crops. Further researches on potential benefits and risks of hormesis and its mechanism are needed for application of crop enhancement in agriculture.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.301-301
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• 1994

〔$^3$H〕Ouabain binding parameters(K$\_$D/ and B$\_$max/,) in homogenates prepared fpom control rat ventricular strip and Langendorff preparations which were not previously exposed to ouabain were compared to those in homogenates from ventricular strip and Langendorff preparations that had been first exposed to a complete ouabain dose-response curve(10$\^$-7/M to 10$\^$-4/ M). In rat ventricular strips and Langendorff perfused rat heart preparations, cumulative dose-response cruves of ouabain revealed biphasic positive inotropic effects, a "low-dose" and a "high-dose" effect with ED$\_$50/ values of 0.5${\mu}$M and 35${\mu}$M ouabain, respectively- The "low-dose" effect in rat ventricular strips disappeared or was diminished significantly when the ouabain dose-response curve wag repeated after the washout of the effects of the first curve, whereas the maximal "high-dose" effect was identical in both exposures to oubain. However, there was no change in the "low-dose" effects in both sets of the Langendorff perfused hearts. The contractile activity of the pre-exposed strips did not indicate the presence of residual ouabain since their basal contractile force was decreased 10% compared to initial control. 〔$^3$H〕Ouabain binding parameters, K$\_$D/ and B$\_$max/, were not changed comparing homogenate of control ventricular strips with that of strips pre-exposed to ouabain. These results suggest that digitalis receptor desensitization in the rat ventricular strip may due to the change of post-receptor events induced by ouabain binding to a high affinity site(${\alpha}$$_2$ isoform).

• Environmental Analysis Health and Toxicology
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• v.31
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• pp.1.1-1.13
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• 2016

Objectives To investigate the accuracy and scientific validity of the current very low risk factor for hereditary diseases in humans following exposures to ionizing radiation adopted by the United Nations Scientific Committee on the Effects of Atomic Radiation and the International Commission on Radiological Protection. The value is based on experiments on mice due to reportedly absent effects in the Japanese atomic bomb (A-bomb) survivors. Methods To review the published evidence for heritable effects after ionising radiation exposures particularly, but not restricted to, populations exposed to contamination from the Chernobyl accident and from atmospheric nuclear test fallout. To make a compilation of findings about early deaths, congenital malformations, Down's syndrome, cancer and other genetic effects observed in humans after the exposure of the parents. To also examine more closely the evidence from the Japanese A-bomb epidemiology and discuss its scientific validity. Results Nearly all types of hereditary defects were found at doses as low as one to 10 mSv. We discuss the clash between the current risk model and these observations on the basis of biological mechanism and assumptions about linear relationships between dose and effect in neonatal and foetal epidemiology. The evidence supports a dose response relationship which is non-linear and is either biphasic or supralinear (hogs-back) and largely either saturates or falls above 10 mSv. Conclusions We conclude that the current risk model for heritable effects of radiation is unsafe. The dose response relationship is non-linear with the greatest effects at the lowest doses. Using Chernobyl data we derive an excess relative risk for all malformations of 1.0 per 10 mSv cumulative dose. The safety of the Japanese A-bomb epidemiology is argued to be both scientifically and philosophically questionable owing to errors in the choice of control groups, omission of internal exposure effects and assumptions about linear dose response.

• Korean Journal of Veterinary Research
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• v.34 no.3
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• pp.447-456
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• 1994

In order to elucidate the characterization of receptors involved in inestinal motility of Israeli carp, spontaneously contracting Israeli carp intestinal preperations were prepared and mounted in the organ chambers for contraction traicings using a polygraph. Various contractile agonists were treated and their dose-response curves were constructed. $EC_{50}$ values$(pD_2)$ of each agonist on specific receptors, $pA_2$ values of competitive antagonists against some agonists, and $K_1$, values of noncompetitive antagonists against some agonists were analyzed for characterization of receptors related with the intestinal contraction. Results obtained through the experiments were summarized as follows: 1. Acetylcholine(ACh) exhibited biphasic dose-response curves: initial ACh-induced dose dependent contractions were observed in pM levels but followed by decreased response in in-between concentration levels. Dose dependent contractions reappeared in ${\mu}M$ level. The peaks in pM and ${\mu}M$ levels appeared in $10^{-13}M$ and $3{\times}10^{-5}M$, respectvely. 2. Carbachol(CaCh) exhibited dose dependent contractions from $10^{-9}M$ to $10^{-5}M$, and its $pD_2$ values were higher than those of ACh($5.60{\pm}0.11$). ACh and CaCh exhibited equiactive contractions. Nicotine had no effects on contractile responses of Israeli carp intestine. 3. ACh-induced responses were inhibited by atropine($K_1:7{\times}10^{-8}M$), a muscarinic antagonist, in a non-competitive manner. But CaCh-induced responses were inhibited by both antimuscarinic atropine($pA_2:9.52{\pm}0.14$) and selective $M_2$ antagonistic 4-DAMP($pA_2:8.16{\pm}0.09$), in competitive manners. Nicotine receptor antagonistic decamethonium and hexamethonium had no effects on ACh-and CaCh-induced contractions. Therefore, the cholinergic receptor related to intestinal motility of Israeli carp was assumed as $M_2$ type. 4. In Israeli carp intestine, 5-HT (serotonin) exhibited dose dependent contractions in concentration range from $10^{-8}M$ to $10^{-5}M$. The maximal responses, however, were corresponded to about 50% of those of ACh or CaCh. 5-HT induced contractions were inhibited by $5-HT_2$ antagonistic ketanserin ($K_1: 7.8{\times}10^{-4}M$) in a non-competitive manner, but not by both of anti $5-HT_1$, spiperone and anti $5-HT_3$, MDL-72222. Hence, $5-HT_2$ receptors are suggested to be existed in Isreli carp intestine.

• Archives of Pharmacal Research
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• v.19 no.5
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• pp.381-385
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• 1996

Rat ventricles respond with a biphasic positive inotropic effect to ouabain, low-dose and high-dose effects but rat atria with only a monophasic high dose effect. In an effect to understand the difference in response to ouabain of two tissues between rat atria and ventricles the levels of the $a_{2}$ -isoform of the $Na^{+}$, $K^{+}$-ATPase which has higher affinity for ouabain than the $a_{1}$-iso-form were determined by a $[^{3}H]$ouabain binding assay. The yield of protein per gram wet weight was about 47 mg for atria and 100 mg for ventricles. The $K_{d}$ values of ouabain for the high-affinity ouabain binding site $(a_{2} -isoform)$ were nearly the same (230 nM) in the atria and ventricles. However, the numbers of the $a_{2}$-isoform $(B_{max})$ per mg protein were approximately half in the atria. When the binding data were expressed in unit per gram tissue wet weight, the numbers of $a_{2}$ -isoform in the atria was about 25% of that in the ventricles. THese results demonstrate that the $a_{2}$ -isoform of the $Na^{+}$, $K^{+}$-ATPase in the rat atria could be detected by $[^{3}H]$ouabain binding assay and the levels of this isoform are too low to show the low-dose effect of ouabain.

• Proceedings of the Korea Electromagnetic Engineering Society Conference
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• 1999.07a
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• pp.117-129
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• 1999

Acute effects of locally applied of static magnetic field (SMF) and extremely low frequency electromagnetic field(ELF-EMF) to the cutaneous tissue within a rabbit ear chamber (REC)were evaluated under conscious conditions. Rabbits with the REC were subjected to intravital microscopical investigation by use of microphotoelectric plethysmography(MPPG). There was no dose-response relationship between the extent of vasomotion changes and frequencies(0,20,50, 100Hz)or power levels (1, 5, 10, 25, 50, 100, 200 mT). Under low vascular tone the both fields induce vasodilatation. The effects of SMF (1 mT) on the cutaneous microcirculatory system induced the vasodilatation with enhanced vasomotion under nor-adrenaline-induced high vascular tone as well as the vasoconstriction with reduced vasomotion under acetylcholine-induced low vascular tone. This suggests that the SMF can modulate vascular tone due to the modification of vasomotion biphasically in the cutaneous tissue.

• Development and Reproduction
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• v.18 no.4
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• pp.225-231
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• 2014

Autophagy is a homeostatic degradation process that is involved in tumor development and normal development. Autophagy is induced in cancer cells in response to chemotherapeutic agents, and inhibition of autophagy results in enhanced cancer cell death or survival. Chloroquine (CQ), an anti-malarial drug, is a lysosomotropic agent and is currently used as a potential anticancer agent as well as an autophagy inhibitor. Here, we evaluate the characteristics of these dual activities of CQ using human colorectal cancer cell line HCT15. The results show that CQ inhibited cell viability in dose- and time-dependent manner in the range between 20 to 80 uM, while CQ did not show any antiproliferative activity at 5 and 10 uM. Cotreatment of CQ with antitumor agent NVP-BEZ235, a dual inhibitor of PI3K/mTOR, rescued the cell viability at low concentrations meaning that CQ acted as an autophagy inhibitor, but CQ induced the lethal effect at high concentrations. Acridine orange staining revealed that CQ at high doses induced lysosomal membrane permeabilization (LMP). High doses of CQ produced cellular reactive oxygen species (ROS) and cotreatment of antioxidants, such as NAC and trolox, with high doses of CQ rescued the cell viability. These results suggest that CQ may exert its dual activities, as autophagy inhibitor or LMP inducer, in concentration-dependent manner.