• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5697-5701
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• 2015

Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of antioxidative properties. Punica granatum (PG) (pomegranate) is a well known fruit in this context, but its cytotoxicity in cancer cells has not been extensively studied. Here, we investigated the antiproliferative properties of a peel extract of PG from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate peel (PPE) was prepared. Total phenolic content(TPC) and total flavonoid conetnt (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. The cytotoxicity of different doses of PPE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) was evaluated by MTT assays with A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison with negative controls at all tested doses (5-$1000{\mu}g/ml$). In all studied cancer cells, PPE reduced the cell viability to values below 40%, even at the lowest doses. In all cases, IC50 was determined at doses below $5{\mu}g/ml$. In this regard, MCF-7 breast adenocarcinoma cells were the most responsive cells to antiprolifreative effects of PPE with a maximum mean growth inhibition of 81.0% vs. 69.4%, 79.3% and 77.5% in SKOV3, PC-3 and A549 cells, respectively. Conclusions: Low doses of PPE exert potent anti-proliferative effects in different human cancer cells and it seems that MCF-7 breast adenocarcinoma cells are the most cells and SKOV3 ovarian cancer cells the least responsive in this regard. However, the mechanisms of action need to be addressed.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.198-210
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• 1997

To examine the double-faced thymoleptic(antidepressant and antimanic) effects of risperidone in mood disorders, this article reviews the psychotropic-induced mania, thymoleptic effects of antipsychotics, therapeutic effects of risperidone and risperidone(RIS)-induced mania(RIM) in mood disorders, risk factors of RIM, possible neurochemical mechanism of these thymoleptic effects, pathophysiological and clinical significance of thymoleptic effects, and suggestive clinical guideline of RIS in mood disorders. RIS appeared effective for bipolar disorder at a lower dose than that recommended for schizophrenia, especially in the cases of maintenance of mood stabilizers, and gradual titration from low doses. Manic induction/exacerbation can occur by chance during RIS treatment in mood disorders, schizoaffective disorders, and schizophrenias. The possible risk factors for RIM are refractory mood disorder, especially in bipolar I disorder with poor initial response ; refractory schizoaffective disorders, especially in bipolar type with poor initial response ; refractory chronic schizophrenias, especially with initial responses ; psychotic features ; higher initial doses ; rapid titration ; combined therapy with antidepressants in refractory depression ; and RIS monotherapy in mania/hypomania. RIS is a drug that preferentially block 5-HT2 receptors. The effects of low dose are due mainly to the blockade of 5-HT2 receptors. There are more gradual increase in D2 blockade with increasing dose and this D2 blocking properties become apparent at higher doses. This may be related to a modulation of dopaminergic transmission by 5-HT2 antagonism at lower doses with the direct action of RIS on DA receptors coming into play at higher dose. The serotonergic antagonistic effect may be important for its effects on depressive symptoms. This, together with adequate blo-ckade of D2 receptors, may not necessarily lead to destabilization of mood disorder, but rather to more therapeutic effects. Therefore, this dose-receptor affinity relationship with both antidepressant and antimanic effects according to treatment duration can explain a continuum of antidepressant effect, antimanic effect, behavioral stimulation, and manic/hypomanic induction/exacerbation. It was the recognition of a useful psychiatric side effects by a thoughtful observer with fertile minds that led to their ultimate utilization as psychotropic drugs, i.e., phenothiazine, MAOI, TCA, and lithium. And, in vivo pharmacological challenge by novel psychotropics, as a neurochemical probe, with more specific actions is a useful tool to select pharmacologically homogeneous subgroup of the same phenotypical(clinical) condition, to further study the unknown underlying pathogenesis of various mental illnesses. Finally, RIS may be a useful alternative or adjunctive drug for patients with mood disorders without psychotic features or refractory to treatment with standard antipsychotic drugs. The more conservative doses(tirated slowly from 1-3 mg/d) of RIS, and maintenance of mood stabilizer in the cases with risk factors of RIM are recommended in mood disorder.

• Food Science of Animal Resources
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• v.28 no.3
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• pp.289-294
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• 2008

The influence of gamma irradiation with low doses (0.5, 1.0, and 1.5 kGy) on the meat quality of chicken breast was determined for 6 days of storage at $4^{\circ}C$. The pH of irradiated chicken was lower than that of the control at day 1 (p<0.05), while no difference was found among irradiation at different doses. Drip loss was higher in irradiated chicken with doses of 0.5 and 1.0 kGy compared to the control at day 1 and day 3 (p<0.05). Lightness (L) at day 1 and day 6 was increased due to irradiation (p<0.05). Redness (a) increased with irradiation doses of 1.0 and 1.5 kGy at day 1 and day 3 (p<0.05). However, no significant differences were found in yellowness (b). The number of aerobic plate count of irradiated chicken during storage was significantly lower than the control (p<0.05). E. coli and coliforms were not detected after irradiation at any dose. Also, irradiation doses of 1.0 and 1.5 kGy significantly reduced volatile basic nitrogen (VBN) and 2-thiobarbituric acid reactive substances (TBARS) values compared to the control during storage (p<0.05). These results suggest that low dose gamma irradiation can be useful to extend the shelf life of chicken breast during cold storage.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.142-148
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• 2001

We studied adaptive response in CHL cells by benzidine dihydrochloride, a derivative of benzidine, which was a major mutagenic agent in dye industry. Chromosome aberration analysis was used for the identification of adaptive response to this mutagen. Adaptive and reactive doses were confirmed by cell proliferation rate curve. Cell proliferation rate curve was obtained from the mitotic indices of cells treated with various concentrations of benzidine dihydrochloride for 24 hours. Marked adaptive responses to benzidine dihydrochloride in the induction of chromosome aberration were observed in CHL cells by pre-treatment with low concentrations of benzidine dihydrochloride (0.0047 mg/$m\ell$ or 0.0094 mg/$m\ell$) for 24 hours following post-treatment with high concentrations (0.0187, 0.0375, 0.075, 0.15 mg/$m\ell$) for 24 hours. These adaptive responses were found mostly in the type of chromatid breaks and chromatid exchanges. There is no difference in these results between two adaptive doses, 0.0047 mg/$m\ell$ and 0.0094 mg/$m\ell$. The amount of adaptive response, however, was dependent on post-treatment doses.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.390-401
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• 1997

In order to investigate the pharmacological properties of New Woohwangchungsimwon Liquid (NCL), effects of Woohwangchungsimwon Liquid (CL) and NCL were compared. In isolated rat aorta, NCL and CL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) without regard to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxation of NCL and CL. NCL and CL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NCL and CL significantly decreased heart rate. NCL and CL, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NCL and CL had no effects on parameters of action potential at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NCL and CL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between two preparations.

• 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.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.66-78
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• 1999

In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD$_{90}$ and V$_{max}$ at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.s.

• Korean Journal of Psychosomatic Medicine
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• v.5 no.2
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• pp.195-204
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• 1997

Objectives : The behavioral and physiological effects following low doses and high doses of melatonin have not been fully explored. In this study the authors investigated the nature and extent of the hypnotic effects, oral temperature, blood pressure effects, performance effects and subjective feelings following the acute administration of low pharmacological oral doses of melatonin at mid-day. Methods : Thirty-five healthy young medical students were randomly assigned to receive 6mg of oral melatonin(N=11), 12mg of oral melatonin(N=12) or a placebo(N=12) in a double-blind, placebo controlled trial. Measures of the behavioral and physiological effects used in the study were Stanford Sleepiness Scale, Digit Symbol Substitution Test, Trail test and visual analogue scale for subjective feelings. Oral temperature and blood pressure were measured. The subjects were studied between 10:00 and 16:00 hours. Data were analyzed by using repeated-measures analyses of variance(ANOVA). Results: Melatonin produced statistically significant effects on oral temperature, but there were no significant effects on time and the $dose{\times}time$ interaction. There was a significant difference on oral temperature between the 12mg oral melatonin group and the placebo group at 12:00 and 16:00 hours, but no significant difference between the 12mg and the 6mg oral melatonin groups. Melatonin produced a dose-related increase in subjective sleepiness and had significant effects on time, the $dose{\times}time$ interaction. There was a significant difference on subjective sleepiness among the placebo, 6mg, 12mg oral melatonin groups at 13:00-16:00 hours. Melatonin did not produce statistically significant dose-related effects on subjective fatigue but produced significant effects on time and the $dose{\times}time$ interaction. There was a significant difference on subjective fatigue between the 12mg, the 6mg oral melatonin groups and the placebo group at 13:00 hour. Conclusions : These data indicated that acute administration of melatonin at mid-day increased subjective sleepiness and fatigue but decreased oral temperatures. These effects were shown especially in 12mg oral melatonin group.

• Journal of the Korean Physical Society
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• v.73 no.9
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• pp.1377-1384
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• 2018

Accurate measurement of the absorbed dose and the effective dose is required in dental panoramic radiography involving relatively low energy with a rotational X-ray tube system using long exposures. To determine the effectiveness of measuring the irradiation by using passive dosimetry, we compared the entrance skin doses by using a radiophotoluminescent glass dosimeter (RPL) and an optically stimulated luminescence detector (OSL) in a phantom model consisting of nine and 31 transverse sections. The parameters of the panoramic device were set to 80 kV, 4 mA, and 12 s in the standard program mode. The X-ray spectrum was applied in the same manner as the panoramic dose by using the SpekCalc Software. The results indicated a mass attenuation coefficient of $0.008226cm^2/g$, and an effective energy of 34 keV. The equivalent dose between the RPL and the OSL was calculated based on a product of the absorbed doses. The density of the aluminum attenuators was $2.699g/cm^3$. During the panoramic examination, tissue absorption doses with regard to the RPL were a surface dose of $75.33{\mu}Gy$ and a depth dose of $71.77{\mu}Gy$, those with regard to the OSL were surface dose of $9.2{\mu}Gy$ a depth dose of $70.39{\mu}Gy$ and a mean dose of $74.79{\mu}Gy$. The effective dose based on the International Commission on Radiological Protection Publication 103 tissue weighting factor for the RPL were $0.742{\mu}Sv$, $8.9{\mu}Sv$, $2.96{\mu}Sv$ and those for the OSL were $0.754{\mu}Sv$, $9.05{\mu}Sv$, and $3.018{\mu}Sv$ in the parotid and sublingual glands, orbit, and thyroid gland, respectively. The RPL was more effective than the OSL for measuring the absorbed radiation dose in low-energy systems with a rotational X-ray tube.

• Journal of Microbiology and Biotechnology
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• v.11 no.3
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• pp.524-528
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• 2001

The measurement of radiation response using simple and informative techniques would be of great value in studying the genetic risk following occupational, therapeutic, or accidental exposure to radiation. When patients receive radiation therapy, many suffer from side effects. Since each patient receives a different dose due to different physical conditions, it is important to measure the exact dose of radiation received by each patient to lessen the side effects. Even though several biological dosimetric systems have already been developed, there is no ideal system that can satisfy all the criteria for an idean dosimetric system, especially for low-dose radiation as used in radiation therapy. In this study, an SOS Chromotest of E. coli PQ37 was evaluated as a novel dosimeter for low-dose gamma-rays. E. coli PQ37 was originally developed to screen chemical mutagens using the SOS Chromotest-a colorimtric assay, based on the induction of ${\beta}$-galactosidase ue to DNA damage. The survival fraction of E. coli PQ37 decreased dose-dependently with an increasing dose of cobalt-60 gamma-rays. Also, a good linear correlation was found between the biological damage revealed by the ${\beta}$-galactosidase expression and the doses of gamma-rays. The expression of ${\beta}$-galactosidase activity that responded to low-dose radiation under 1 Gy was $Y=0.404+(0.089{\pm}0.3)D+(-0.018{\pm}0.16)D^2$ (Y, absorbance at 420 nm; D, Dose of irradiation) as calculated using Graph Pad In Plot and Excel. When a rabbit was fed with capsules containing an agar block embdded with E. coli PQ37 showed a linear response to the radiation doses. Accordingly, the results confirm that E. coli PQ37 can be used as a sensitive biological dosimeter fro cobalt-60 gamma-rays. To the best of our knowledge, this is the first time that a bacterium has been used as a biological dosimeter, especially for low-dose radiation.