The safety of the sweetening component of stevia was studied by administrating it to the rats. The $LD_{50}$ determined by intraperitoneal injection was 3,400 mg/Kg as the stevia extract containing 50 % stevioside, i.e. $LD_{50}$ of stevioside was more than 1,700 mg/Kg. Oral administration of large quantities of the stevia extract for 56 days resulted in no effect on the growth of rats. The analyses of total blood (RBC, WBC, Hb and Hct), 17 blood serum components including total protein, glucose, cholesterol, GOT, and 11 items of findings on the liver tissues including nuclear deterioration of liver cells, proliferation of Kupffer cells, fibrosis of portal area showed no significant differences between control and treatments except lactate dehydrogenase activity after 56 day-oral administration of the extract. From the results obtained, it was supposed that the stevia extract/stevioside revealed no acute or sub-acute toxic effects on rats.
Baek, Kwang-Soo;Ahn, Shinbyoung;Lee, Jaehwi;Kim, Ji Hye;Kim, Han Gyung;Kim, Eunji;Kim, Jun Ho;Sung, Nak Yoon;Yang, Sungjae;Kim, Mi Seon;Hong, Sungyoul;Kim, Jong-Hoon;Cho, Jae Youl
The Korean Journal of Physiology and Pharmacology
/
v.19
no.4
/
pp.365-372
/
2015
Aripiprazole (ARI) is a commonly prescribed medication used to treat schizophrenia and bipolar disorder. To date, there have been no studies regarding the molecular pathological and immunotoxicological profiling of aripiprazole. Thus, in the present study, we prepared two different formulas of aripiprazole [Free base crystal of aripiprazole (ARPGCB) and cocrystal of aripiprazole (GCB3004)], and explored their effects on the patterns of survival and apoptosis-regulatory proteins under acute toxicity and cytotoxicity test conditions. Furthermore, we also evaluated the modulatory activity of the different formulations on the immunological responses in macrophages primed by various stimulators such as lipopolysaccharide (LPS), pam3CSK, and poly(I:C) via toll-like receptor 4 (TLR4), TLR2, and TLR3 pathways, respectively. In liver, both ARPGCB and GCB3004 produced similar toxicity profiles. In particular, these two formulas exhibited similar phospho-protein profiling of p65/nuclear factor $(NF)-{\kappa}B$, c-Jun/activator protein (AP)-1, ERK, JNK, p38, caspase 3, and bcl-2 in brain. In contrast, the patterns of these phospho-proteins were variable in other tissues. Moreover, these two formulas did not exhibit any cytotoxicity in C6 glioma cells. Finally, the two formulations at available in vivo concentrations did not block nitric oxide (NO) production from activated macrophage-like RAW264.7 cells stimulated with LPS, pam3CSK, or poly(I:C), nor did they alter the morphological changes of the activated macrophages. Taken together, our present work, as a comparative study of two different formulas of aripiprazole, suggests that these two formulas can be used to achieve similar functional activation of brain proteins related to cell survival and apoptosis and immunotoxicological activities of macrophages.
BACKGROUND/OBJECTIVES: Sargassum horneri is an edible brown alga that grows in the subtidal zone as an annual species along the coasts of South Korea, China, and Japan. Recently, an extreme amount of S. horneri moved into the coasts of Jeju Island from the east coast of China, which made huge economic and environmental loss to the Jeju Island. Thus, utilization of this biomass becomes a big issue with the local authorities. Therefore, the present study was performed to evaluate the anti-inflammatory potential of crude polysaccharides (CPs) extracted from S. horneri China strain in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. MATERIALS/METHODS: CPs were precipitated from S. horneri digests prepared by enzyme assistant extraction using four food-grade enzymes (AMG, Celluclast, Viscozyme, and Alcalase). The production levels of nitric oxide (NO) and pro-inflammatory cytokines, including tumor necrosis factor (TNF)-${\alpha}$ and interleukin (IL)-$1{\beta}$ were measured by Griess assay and enzyme-linked immunosorbent assay, respectively. The levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nuclear factor (NF)-${\kappa}B$, and mitogen-activated protein kinases (MAPKs) were measured by using western blot. The IR spectrums of the CPs were recorded using a fourier transform infrared spectroscopy (FT-IR) spectrometer. RESULTS: The polysaccharides from the Celluclast enzyme digest (CCP) showed the highest inhibition of NO production in LPS-stimulated RAW 264.7 cells ($IC_{50}$ value: $95.7{\mu}g/mL$). Also, CCP dose-dependently down-regulated the protein expression levels of iNOS and COX-2 as well as the production of inflammatory cytokines, including TNF-${\alpha}$ and IL-$1{\beta}$, compared to the only LPS-treated cells. In addition, CCP inhibited the activation of NF-${\kappa}B$ p50 and p65 and the phosphorylation of MAPKs, including p38 and extracellular signal-regulated kinase, in LPS-stimulated RAW 264.7 cells. Furthermore, FT-IR analysis showed that the FT-IR spectrum of CCP is similar to that of commercial fucoidan. CONCLUSIONS: Our results suggest that CCP has anti-inflammatory activities and is a potential candidate for the formulation of a functional food ingredient or/and drug to treat inflammatory diseases.
For the examination of nuclear medicine, myocardial scan is a good method to evaluate a hemodynamic importance of coronary heart disease. but, the automatized qualitative measurement is additionally necessary to improve the decoding efficiency. we suggests the creation of cardiac three-dimensional model and model of three-dimensional cardiac thickness as a new measurement. For the experiment, cardiac reduced cross section was obtained from SPECT. Next, the pre-process was performed and image segmentation was fulfilled by level set. for the modeling of left cardiac thickness, it was realized by applying difference equation of two-dimensional laplace equation. As the result of experiment, it was successful to measure internal wall and external wall and three-dimensional modeling was realized by coordinate. and, with laplace formula, it was successful to develop the thickness of cardiac wall. through the three-dimensional model, defects were observed easily and position of lesion was grasped rapidly by the revolution of model. The model which was developed as the support index of decoding will provide decoding information to doctor additionally and reduce the rate of false diagnosis as well as play a great role for diagnosing IHD early.
The study is to produced a brain phantom simulating corpus striatum, which can evaluate the progression of parkinson's disease, to investigate possibility of reducing the brain exposure dose to CT while maintaining optimal image quality during PET-CT examinations. CT scans were performed by varying tube voltage (100, 120 kVp) and tube current (80, 140, 200 mAs) with $^{18}F$ FP-CIT injected into the phantom's hot sphere and background (radioactivity ratio 3:1)(reference condition; 120 kVp, 140 mAs). Estimated effective dose was calculated by using conversion factor according to each condition, and image quality was evaluated by setting SNR and CRChot image evaluation factors. Experimental results showed that the predicted effective dose below the CT imaging reference condition was reduced by at least 10% and by up to 60%, and the predicted effective dose beyond the reference condition was increased by 40%. In addition, there was no significant difference between SNR and CRChot of PET images, and it was confirmed that brain dose decreased with decrease of tube voltage and tube current. At the same time, there was no significant change in the quality of the image in terms of SNR and CRChot despite the change in scan conditions. This fact suggests that the quality of the images acquired under the existing dose conditions can be obtained even at low dose conditions and it is expected that it will be possible to use the brain PET-CT scan as a basic data for the research on reduction of dose and improvement of image quality.
The objective of this study was to compare the resolution and density appropriate to diagnosis in chest PA radiography. In comparing the resolution, we radiographed with conventional radiography, computed radiography(CR) and digital radiography(DR) using the linear resolution phantom(Nuclear Associates-Carle Place. N.Y.). 2 radiologists and 3 radiological technologists read the resolution value by the blind test. DR, conventional radiography and CR measured 3.95, 3.58, 3.48 resolution value respectively. In analysing the density, we chose the fifty normal chest CR and DR and conventional film. We estimated the density using by densitometer(X-rite company-Model 301) in seven regions(lung field, lung field margine, mediastinum I, mediastinum II, heart shadow I, heart shadow II, diaphragm) of chest film. We adapted to analysis the Japanese chest X-ray evaluating method and table. It was scored 0(farthest density value) to 2(nearest density value). DR scored 2 at mediastinum I, mediastinum II, heart shadow I, heart shadow II and diaphragm. On the contrary with, CR scored 2 at lung field and lung field margine. Consequently, DR superior than CR and conventional radiography film compairing density and resolution. It was due to small pixel size and post processing algorithm with digital radiography.
In order to understand the action mechanism of polyhexamethylene biguanide (PHMB) to the cyst of Accnthcnloebc on the morphological basis, the cysts of four corneal isolates of Acanthanoebc were treated with minimal cysticidal concentration (MCC) of PHMB and their ultrastructural changes were examined by transmission electron microscopy. The most striking change of cysts treated with PHMB compared with normal cysts was the shrinkage of intracystic amoebae, which resulted in the separation of the plasma membrane of intracystic amoeba from endocystic wall. Subplasmalemmal lipid droplets became irregularly shaped . In severely damaged cysts, cytoplasm was aggregated and organelles were severely deformed. Cytoplasmic materials were leaked out through the damaged plasma membrane. Most cysts showed aggregation of nuclear chromatin material. Number of mitochondrial cristae was also reduced. Ecto- and endo-cystic walls were relatively well tolerated. Findings in the present study revealed that PHMB affected mainly on plasma membrane, but lesser on organellar membrane of intracystic amoeba. It seemed likely that PHMB might kill cystic forms of Accnthamoebc by similar mechanism in which this environmental biocide can damage the cell wall of Escherichia coli by binding with acidic phospholipids.
In the course of a developing screening method for resistant radish to Fusarium oxysporum f. sp. raphani, we found that the fungus produces phytotoxic compound against Raphanus sativus. The culture filtrate of F. oxysporum f. sp. raphani KR1 represented the strongest phytotoxicity when the fungus was incubated in the malt extract broth with 150 rpm at $25^{\circ}C$ for 14 days. Under bioassay-guided purification, we isolated a substance from liquid culture of F. oxysporum f. sp. raphani KR1, with phytotoxic effect against R. sativus. The compound was identified as fusaric acid by mass and nuclear magnetic resonance spectral analyses. Phytotoxicity of the compound against cruciferous vegetable crops, including radish, cabbage, and broccoli, was investigated. Fusaric acid represented phytotoxicity on radish seedlings by concentration dependant manner. And the phytotoxin demonstrated strong phytotoxicity on the resistant cultivars as well as susceptible cultivars of radish to F. oxysporum f. sp. raphani. In addition, fusaric acid isolated from the fungus also showed a potent phytotoxic efficacy against non-host Brassicaceae crops of the fungus such as cabbage and broccoli. The results demonstrate that fusaric acid produced by F. oxysporum f. sp. raphani is non-host-specific toxin and for screening of resistant radish to the fungal pathogen, spore suspension of the fungus without the phytotoxin has to be used.
Average life expectancy is getting longer due to medical developments and improvements in living standards. So much so that the elderly have an increased risk of developing osteoporosis. Therefore, it is important to prevent, diagnose, and treat the senile disease at an early stage through a bone density test. Bone density is measured by dual energy X-ray absorption (DXA). In this study, while using DXA, in cases when the measurements for both the lumbar and the femur could not be taken simultaneously, the correlation between both measurements were known, and the measurement of one area was used to make a clinical inference for the value of the other. Measurements were taken using Lunar Prodigy Advance (GE) for 43 participant with clinically significant fractures. Statistical calculations were produced and analysed regarding bone density. In case of T-score, lumbar spine produced a statistical result of $-2.112{\pm}1.836$ and femur neck was $-1.716{\pm}1.565$. In case of Z-score lumbar spine produced a statistical result of $-0.151{\pm}1.513$, and femur neck $-0.026{\pm}1.283$. It is indicated that the pearson correlation coefficient of T-score between lumbar spine and femur neck is high at 0.699, and the pearson correlation coefficient of Z-score is considered relatively high at 0.503. The correlation of bone density between lumbar spine and femur neck is shown to be statistically meaningful in T-score's p-value at 0.000 and Z-score's p-value at 0.001. In conclusion, it seems to have clinical usefulness that we can infer the result of one measurement through that of the other part tested, based on the knowledge of the correlation coefficients between lumbar spine and femur neck.
The cytidine analog decitabine (DEC) acts as a nucleic acid synthesis inhibitor, whereas ammonium pyrrolidine dithiocarbamate (PDTC) is an inhibitor of nuclear factor-${\kappa}B$. The aim of this study was to investigate the possible synergistic inhibitory effect of these two inhibitors on proliferation of human gastric cancer AGS cells. The inhibitory effect of PDTC on AGS cell proliferation was significantly increased by DEC in a concentration-dependent manner, and this inhibition was associated with cell cycle arrest at the G2/M phase and the induction of apoptosis. This induction of apoptosis by the co-treatment with PDTC and DEC was related to the induction of DNA damage, as assessed by H2AX phosphorylation. Further studies demonstrated that co-treatment with PDTC and DEC induced the disruption of mitochondrial membrane potential, increased the generation of intracellular reactive oxygen species (ROS) and the expression of pro-apoptotic Bax, and down-regulated the expression of anti-apoptotic Bcl-2, ultimately resulting in the release of cytochrome c from the mitochondria into the cytoplasm. Co-treatment with PDTC and DEC also activated caspase-8 and caspase-9, which are representative caspases of the extrinsic and intrinsic apoptosis pathways. Co-treatment also activated caspase-3, which was accompanied by proteolytic degradation of poly (ADP-ribose) polymerase. Taken together, these data clearly indicated that co-treatment with PDTC and DEC suppressed the proliferation of AGS cells by increasing DNA damage and activating the ROS-mediated extrinsic and intrinsic apoptosis pathways.
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