• Title/Summary/Keyword: Biochemical changes

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Development of a simplified malnutrition screening tool for hospitalized patients and evaluation of its inter-methods reliability (입원환자의 초기영양평가를 위한 단순영양검색도구 개발 및 도구 간 신뢰도 검증)

  • Yun, Oak Hee;Lee, Gyuhwi;Park, Yoon Jung
    • Journal of Nutrition and Health
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    • v.47 no.2
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    • pp.124-133
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    • 2014
  • Purpose: The current study was designed for development of a simplified malnutrition screening tool (SMST) for hospitalized patients using readily available laboratory and patient information and for evaluation of its reliability compared to well-established tools, such as PGSGA and NRS-2002. Methods: Anthropometric and biochemical measurements, as well as a few subjective assessments, of 903 patients who were preclassified by their nutritional status according to PGSGA were analyzed. Among them, a combination of factors, including age, BMI, albumin, cholesterol, total protein, hematocrit, and changes in body weight and food intake, were statistically selected as variables for SMST. Results: According to SMST, 620 patients (68.7%) were classified as the normal group and 283 patients (31.3%) were classified as the malnutrition group. Significant differences in age, albumin, TLC, BMI, hemoglobin, hematocrit, total protein, cholesterol, and length of stay were observed between the two groups. For inter-methods reliability, the screening results by SMST were compared with those by PGSGA and NRS-2002. The comparison with PGSGA and NRS-2002 showed 'Substantial agreement' (sensitivity 94.4%, specificity 88.4%, ${\kappa}$ = 0.747) and 'Moderate agreement' (sensitivity 96.1%, specificity 79.5%, ${\kappa}$ = 0.505), respectively, indicating that SMST held high inter-methods reliability. Conclusion: In conclusion, SMST, based on readily available laboratory and patient information and simple subjective assessments on changes in food intake and body weight, may be a useful alternative tool with a simple but reliable risk index, especially in resource-limited domestic hospitals.

Studies on effect and Safety of various Aqua-acupunctures from Scutellariae Radix (다양(多樣)한 황금약침제제(黃芩藥鍼製劑)의 안전성(安定性) 및 효능(效能)에 관한 연구(硏究))

  • Kim, Ho-Kyoung;Ma, Jin-Yeul;Cheon, Won-Kyung;Yun, Su-Young;Kang, Eun-Jung;Joo, Hye-Jeong;Ko, Byoung-Seob
    • Korean Journal of Oriental Medicine
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    • v.3 no.1
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    • pp.183-197
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    • 1997
  • In order to detect the safety and effect of various aqua-acupunctures from Scutellariae Radix, the modifications of boiling, filtration and dilution were employed for the manufacture of aqua-acupunctures. We injected 0.2cc of aqua-acupunctures into Joksamri (足三里) of rat, repeatedly. We compared subacute toxicity of them with saline group, distilled water(D.W.) group, acupuncture group and control group. The results were summarized as follows: 1. The groups were all healthy and alive, and there was no special abnormality in physical condition and autopsy. And there were not any toxic symptoms in repeating application of aqua-acupunctures to the rat, including changes of body weight, organ weight, haematological examination and serum biochemical test. 2. There was slight change of body weight in acupuncture group : We could see significance after 3 days(p<0.05) and after 7 days(p<0.001) in body weight loss. After 9 days, all tested groups were suppressed in body weight increment. 3. Result of organ weight : In Palkang aqua-acupuncture(D-2 group), saline group and acupuncture group there were some statistical significance. Especially, acupuncture group revealed significant result in liver and spleen than aqua-acupunctures. From this result, we could suggest that the efficacy of acupuncture was preceded herbal medicine. 4. In serum biochemical test, we examined glucose(GLU), triglyceride(TG) and cholesterol(CHOL). In comparison with control group, the diluted 10 times of Hwanggum aqua-aqupuncture$({\times}10\;group)$ was recognized significant decrease of glucose, but the diluted 100 times of Hwanggum aqua-acupuncture$({\times}100\;group)$, D-2 group, saline group were confirmed significant increment. There was not any meaningful change of CHOL in all of tested group, excepting the acupuncture group was exhibited statistically significant decrease(p<0.05). In TG level all tested group except complex injection of standard compound(CPA group) and HG, there were significant value iii statistically. The diluted solution was more significant decrease than Hwanggum aqua-acupuncture(HG). The mutual relationship of components of aqua-acupunture tended to decrease level of TG, regardless of its concentration. In acupunture guoup, we gained some interesting result In meaningful decrease in 7G. 5. Haematological examination showed significant increment of granulocytes(GR) in all tested groups except Hwanggum aqua-acupuncture. And the diluted solutions of HG expressed very high increment of them(p<0.001). The GR and Mean Corpuscular Volume(MCV) of acupuncture group showed statistical significance.

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Development and Research into Functional Foods from Hydrolyzed Whey Protein Powder with Sialic Acid as Its Index Component - I. Repeated 90-day Oral Administration Toxicity Test using Rats Administered Hydrolyzed Whey Protein Powder containing Normal Concentration of Sialic Acid (7%) with Enzyme Separation Method - (Sialic Acid를 지표성분으로 하는 유청가수분해단백분말의 기능성식품 개발연구 - I. 효소분리로 7% Siailc Acid가 표준적으로 함유된 유청가수분해단백분말(7%)의 랫드를 이용한 90일 반복경구투여 독성시험 평가 연구 -)

  • Noh, Hye-Ji;Cho, Hyang-Hyun;Kim, Hee-Kyong
    • Journal of Dairy Science and Biotechnology
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    • v.34 no.2
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    • pp.99-116
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    • 2016
  • We herein performed animal safety assessment in accordance with Good Laboratory Practice (GLP) regulations with the aim of developing sialic acid from glycomacropeptide (hereafter referred to as "GMP") as an index ingredient and functional component in functional foods. GMP is a type of whey protein derived from milk and a safe food, with multiple functions, such as antiviral activity. A test substance was produced containing 7% (w/w) sialic acid and mostly-hydrolyzed whey protein (hereafter referred to as "7%-GNANA") by enzymatic treatment of substrate GMP. The maximum intake test dose level was selected based on 5,000 mg/kg/day dose set for male NOEL (no-observed-effect-level) and female NOAEL (no-observed-adverse-effect-level) determined by a dose-range finding (DRF) test (GLP Center of Catholic University of Daegu, Report No. 15-NREO-001) that was previously conducted with the same test substance. To evaluate the toxicity of a repeated oral dose of the test substance in connection with the previous DRF study, 1,250, 2,500, and 5,000 mg/kg of the substance were administered by a probe into the stomachs of 6-week-old SPF Sprague-Dawley male and female rats for 90 d. Each test group consisted of 10 male and 10 female rats. To determine the toxicity index, all parameters, such as observation of common signs; measurements of body weight and food consumption; ophthalmic examination; urinalysis, electrolyte, hematological, and serum biochemical examination; measurement of organ weights during autopsy; and visual and histopathological examinations were conducted according to GLP standards. After evaluating the results based on the test toxicity assessment criteria, it was determined that NOAEL of the test substance, 7%-GNANA, was 5,000 mg/kg/day, for both male and female rats. No animal death was noted in any of the test groups, including the control group, during the study period, and there was no significant difference associated with test substance, as compared with the control group, with respect to general symptoms, body weight changes, food consumption, ophthalmic examination, urinalysis, hematological and serum biochemical examination, and electrolyte and blood coagulation tests during the administration period (P<0.05). As assessed by the effects of the test substance on organ weights, food consumption, autopsy, and histopathological safety, change in kidney weight as an indicator of male NOAEL revealed up to 20% kidney weight increase in the high-dose group (5,000 mg/kg/day) compared with the change in the control group. However, it was concluded that this effect of the test substance was minor. In the case of female rats, reduction of food consumption, increase of kidney weight, and decrease of thymus weight were observed in the high-dose group. The kidney weight increased by 10.2% (left) and 8.9% (right) in the high-dose group, with a slight dose-dependency compared with that of the control group. It was observed that the thymus weight decreased by 25.3% in the high-dose group, but it was a minor test substance-associated effect. During the autopsy, botryoid tumor was detected on the ribs of one subject in the high-dose group, but we concluded that the tumor has been caused by a naturally occurring (non-test) substance. Histopathological examination revealed lesions on the kidney, liver, spleen, and other organs in the low-dose test group. Since these lesions were considered a separate phenomenon, or naturally occurring and associated with aging, it was checked whether any target organ showed clear symptoms caused by the test substance. In conclusion, different concentrations of the test substance were fed to rats and, consequently, it was verified that only a minor effect was associated with the test substance in the high-dose (5,000 mg/kg/day) group of both male and female rats, without any other significant effects associated with the test substance. Therefore, it was concluded that NOAEL of 7%-GNANA (product name: Helicobactrol) with male and female rats as test animals was 5,000 mg/kg/day, and it thus was determined that the substance is safe for the ultimate use as an ingredient of health functional foods.

Changes in Distribution and Morphology of Rat Alveolar Macrophage Subpopulations in Acute Hyperoxic Lung Injury Model (고농도 산소로 유발한 흰쥐의 급성폐손상모델에서 폐포대식세포 아형군의 분포와 형태 변화)

  • Shin, Yoon;Lee, Sang-Haak;Yoon, Hyoung-Kyu;Lee, Sook-Young;Kim, Seok-Chan;Kwon, Soon-Seog;Kim, Young-Kyoon;Kim, Kwan-Hyung;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.4
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    • pp.478-486
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    • 2000
  • Background : In acute lung injury, alveolar macrophages play a pivotal role in the inflammatory process during the initiation phase and in the reconstruction and fibrosis process during the later phase. Recently, it has been proven that alveolar macrophages are constituted by morphologically, biochemically and immunologically heterogenous cell subpopulations. The possibility of alterations to these characteristics of the alveolar macrophage population during lung disease has been raised. To investigate such a possibility a hyperoxic rat lung model was made to check the distributional and morphological changes of rat alveolar macrophage subpopulation in acute hyperoxic lung injury. Method : Alveolar macrophage were lavaged from normal and hyperoxic lung injury rats and separated by discontinuous gradients of percoll. After cell counts of each density fraction were accessed, the morphomeric analysis of alveolar macrophages was performed on cytocentrifuged preparations by transmission electron micrograph. Result : 1. The total alveolar macrophage cell count significantly increased up to 24 hours after hyperoxic challenge (normal control group $171.6{\pm}24.1{\times}10^5$, 12 hour group $194.8{\pm}17.9{\times}10^5$, 24 hour group $207.6{\pm}27.1{\times}10^5$, p<0.05). oHoHH However the 48 hour group ($200.0{\pm}77.8{\times}10^5$) did not show a significant difference. 2. Alveolar septal thickness significantly increased up to 24 hours after hyperoxic challenge(normal control group $0.7{\pm}0.2{\mu}m$, 12 hour group $1.5{\pm}0.4{\mu}m$, 24 hour group $2.3{\pm}0.4{\mu}m$, p<0.05). However the 48 hour group did not show further change ($2.5{\pm}0.4{\mu}m$). Number of interstitial macrophage markedly increased at 24 hour group. 3. Hypodense fraction(fraction 1 and fraction 2) of alveolar macrophage showed a significant increase following hyperoxic challenge ($\beta=0.379$.$\beta=0.694$. p<0.05) ; however, fraction 3 was rather decreased following the hyperoxic challenge($\beta=0.815$. p<0.05), and fraction 4 showed an irregular pattern. 4. Electron microscopic observation of alveolar macrophage from each fraction revealed considerable morphologic heterogeneity. Cells of the most dense subfraction(fraction 4) were small, round, and typically highly ruffled with small membrane pseudopods. Cells of the least dense fraction (fraction 1) were large and showed irregular eccentric nucleus and high number of heterogenous inclusions. Conclusion : In conclusion, these results suggest that specific hypodense alveolar macrophage subpopulation may play a an important role in an acute hyperoxic lung injury model But further study, including biochemical and immunological function of these subpopulations, is needed.

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Study on the Human Influence according to RF Pulse Intensity by use Dental Implant on BRAIN MRI: Using the XFDTD Program (Brain MRI 검사 시 치아 임플란트 시술유무와 RF Pulse 세기에 따른 인체 영향에 관한 연구: XFDTD 프로그램을 이용)

  • Choe, Dea-yeon;Kim, Dong-Hyun
    • Journal of the Korean Society of Radiology
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    • v.11 no.5
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    • pp.361-370
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    • 2017
  • In the Brain MRI, RF Pulse is irradiated on the human body in order to acquire an image. At this time, a considerable part of the irradiated RF Pulse energy is absorbed as it is in our body. This will raise the temperature of the human body, but depending on the extent of exposure, it will affect the human body. The change of the SAR and the temperature of the head according to the change of the magnetic field strength is examined. And to investigate the difference in results depending on the use of dental implant. In the human head model, 64 MHz RF Pulse frequency generated from 1.5 T, 128 MHz RF Pulse frequency generated from 3.0 T, and 298 MHz RF Pulse frequency generated from 7.0 T send a frequency and experiment was performed using dental implant using the XFDTD program, we measured the SAR and body temperature changes around the head. The SAR value showed up to about 5800 times the difference at the RF Pulse frequency of 256 MHz, when with dental implant than without dental implant and as the frequency increased, the use of the dental implant increased difference in the SAR value. The change of the temperature of the head showed a temperature rise nearly 2 to 4 times when with dental implant than without dental implant. As the RF Pulse frequency increase, the SAR value increase, but the change of the temperature of the head decrease. Because of as the frequency increase, wavelength is smaller and the more the amount absorbed by the surface of the human. Physiological and biochemical studies of the human body ar necessary through studies of the presence of dental implant and the cause of reaction caused by change in the RF Pulse frequency.

High fructose and high fat diet increased bone volume of trabecular and cortical bone in growing female rats (고과당 및 고지방 식이의 섭취가 성장기 동물모델의 골성장과 골성숙에 미치는 영향)

  • Ahn, Hyejin;Yoo, SooYeon;Park, Yoo-Kyoung
    • Journal of Nutrition and Health
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    • v.48 no.5
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    • pp.381-389
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    • 2015
  • Purpose: The objective of this study was to investigate the effects of a high fructose and fat diet on bone growth and maturation in growing female rats. Methods: Three-week-old female SD rats were randomly assigned to four experimental groups; the control group (CON: fed control diet based on AIN-93G, n = 8); the high-fructose diet group (HFrc: fed control diet with 30% fructose, n = 8); the high-fat diet group (Hfat: fed control diet with 45 kcal% fat, n = 8); and the high-fat diet plus high fructose group (HFrc + HFat: fed diets 45 kcal% fat with 30% fructose, n = 8). Each group was assigned their respective diets for the remaining eight weeks. Bone-related parameters (bone mineral density (BMD) and structural parameters, osteocalcin (OC), deoxypyridinoline (DPD)) and morphologic changes of kidney were analyzed at the end of the experiment. Results: Final body weights and weight gain were higher in the HFat and HFrc + HFat groups and showed higher tendency in the HFrc group compared with those of the CON group (p < 0.05); however, no significant difference in caloric intake was observed among the four experimental groups. The serum OC levels of the HFrc and HFrc + HFat groups were lower than those of the CON and HFat groups (p < 0.05). Urinary levels of DPD did not differ among the experimental groups. BV/TV and Tb.N of trabecular bone were higher in the HFrc + HFat group and showed a higher tendency in the HFrc group than those of the CON and HFat groups (p < 0.05). Tb.Pf of trabecular bone were lower in the HFrc + HFat group than those in the CON and HFat groups (p < 0.05). However, no difference in trabecular BMD was observed among the experimental groups. Cortical bone volume was higher in the HFat and HFrc + HFat groups than in the CON and HFrc groups (p < 0.05). No morphology change in kidney was observed among the experimental groups. Conclusion: Our study suggests that 8 weeks of high-fructose and high fat intake could improve the bone quality (Structural parameters) of trabecular and cortical bone of tibia in growing female rats.

Characterization of Dissolved Organic Matter in Stream and Industrial Waste Waters of Lake Sihwa Watershed by Fluorescence 3D-EEMs Analysis (형광 3D-EEMs를 이용한 시화호유역 하천 및 공단폐수의 유기물 특성 분석)

  • Lee, Mi-Kyung;Choi, Kwang-Soon;Kim, Sea-Won;Kim, Dong-Sup
    • Journal of Korean Society of Environmental Engineers
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    • v.31 no.9
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    • pp.803-810
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    • 2009
  • This study is conducted to examine spatial variations of Dissolved Organic Matter (DOM) in stream and waste waters of the different watershed areas (agricultural, residential, and industrial complex area) by using fluorescence 3D-EEMs (3 Dimensional Excitation Emission Matrix Spectroscopy). Furthermore, the research investigates the changes of DOM characterization by synchronous and 3D-EEMs during a rainfall event. The characterizations of DOM obtained by 3D-EEMs show two noticeable peaks at humic and protein-like regions. Humic-like substances (HLS) are found in rural and urban areas, and humic and protein-like substances (PLS) are shown in industrial area. According to the fluorescence peak $T_1:C_1$ ratios, it is observed that high amount of HLS was discharged from Banweol Industrial Complex (3TG). Additionally, linear relationships (Regression rate, $r^2$=0.65, $r^2$=0.66) have been shown between PLS (peak $T_1,\;B_1$) and biochemical oxygen demand (BOD), which indicates the impact of sewage. For the rainfall event (30 mm), no remarkable difference of DOM was found at rural area except increment of fluorescence intensity comparing dry period. In contrast, HLS at urban area is highly discharged within 30 minutes from the beginning of rainfall. Also, there are high influences of HLS and PLS within 20 minutes at industrial complex (4TG). Fluorescence 3D-EEMs has not only verifies a watershed of DOM origination but also monitors diffuse and point source impacts.

Effects of Radiofrequency Induced Local Hyperthermia on Normal Canine Liver (라디오 파를 이용한 국소 온열치료 : 정상 개의 간에 미치는 영향)

  • Suh Chang Ok;Loh. John J.K.;Shin Hyun Soo;Lee Hyung Sik;Moon Sun Rock;Seong Jin Sil;Chu Sung Sil;Kim Gwi Eon;Han Eun Kyung;Park Chan Il
    • Radiation Oncology Journal
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    • v.9 no.1
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    • pp.37-45
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    • 1991
  • In order to assess the effects of radiofrequency-induced local hyperthermia on the normal liver, histopathologic findings and biochemical changes after localized hyperthermia in canine liver were studied. Hyperthermia was externally adminsitered using the Thermotron RF-8 (Yamamoto Vinyter Co., Japan; Capacitive type heating machine) with parallel opposed electrodes. Thirteen dogs were used and allocated into one control group (N=3) and two treatment groups according to the treatment temperature. Group I (N=5) was heated with $42.5\pm0.5^{\circ}C$ 30 minutes, and Group II (N=5) was heated with $45\pm0.5^{\circ}C$ for 15-30 minutes. Samples of liver tissue were obtained through a needle biopsy immediately after hyperthermia and T,14, and 28 days after treatment. Blood samples were obtained before treatment and W, 3,5, 7,14 and 28 days after treatment and examined for SGOT, SGPT and alkaline phosphatase. Although SGOT and SGPT were elevated after hyperthermia in both groups (three of five in each group), there was no liver cell necrosis or hyperthermia related mortality in Group 1. A hydropic swelling of hepatocytes was prominent histologic finding. Hyperthermia with $45^{\circ}C$ for 30 minutes was fatal and showed extensive liver cell necrosis. In conclusion, liverdamage dy heat of $42.5\pm0.5^{\circ}C$ for 30 minutes is reversible, and liver damage by heat of $45\pm0.5^{\circ}C$ for 30 minutes can be fatal or irreversible. However, these results cannot be applied directly to human trial. Therefore, in erder to apply hyperthermic treatment on human liver tumor safely, close obsewation of temperature with proper thermometry is mandatory. Hyperthermic treatment should be confined to the tumor area while sparing a normal liver as much as possible.

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Manganese and Iron Interaction: a Mechanism of Manganese-Induced Parkinsonism

  • Zheng, Wei
    • Proceedings of the Korea Environmental Mutagen Society Conference
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    • 2003.10a
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    • pp.34-63
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    • 2003
  • Occupational and environmental exposure to manganese continue to represent a realistic public health problem in both developed and developing countries. Increased utility of MMT as a replacement for lead in gasoline creates a new source of environmental exposure to manganese. It is, therefore, imperative that further attention be directed at molecular neurotoxicology of manganese. A Need for a more complete understanding of manganese functions both in health and disease, and for a better defined role of manganese in iron metabolism is well substantiated. The in-depth studies in this area should provide novel information on the potential public health risk associated with manganese exposure. It will also explore novel mechanism(s) of manganese-induced neurotoxicity from the angle of Mn-Fe interaction at both systemic and cellular levels. More importantly, the result of these studies will offer clues to the etiology of IPD and its associated abnormal iron and energy metabolism. To achieve these goals, however, a number of outstanding questions remain to be resolved. First, one must understand what species of manganese in the biological matrices plays critical role in the induction of neurotoxicity, Mn(II) or Mn(III)? In our own studies with aconitase, Cpx-I, and Cpx-II, manganese was added to the buffers as the divalent salt, i.e., $MnCl_2$. While it is quite reasonable to suggest that the effect on aconitase and/or Cpx-I activites was associated with the divalent species of manganese, the experimental design does not preclude the possibility that a manganese species of higher oxidation state, such as Mn(III), is required for the induction of these effects. The ionic radius of Mn(III) is 65 ppm, which is similar to the ionic size to Fe(III) (65 ppm at the high spin state) in aconitase (Nieboer and Fletcher, 1996; Sneed et al., 1953). Thus it is plausible that the higher oxidation state of manganese optimally fits into the geometric space of aconitase, serving as the active species in this enzymatic reaction. In the current literature, most of the studies on manganese toxicity have used Mn(II) as $MnCl_2$ rather than Mn(III). The obvious advantage of Mn(II) is its good water solubility, which allows effortless preparation in either in vivo or in vitro investigation, whereas almost all of the Mn(III) salt products on the comparison between two valent manganese species nearly infeasible. Thus a more intimate collaboration with physiochemists to develop a better way to study Mn(III) species in biological matrices is pressingly needed. Second, In spite of the special affinity of manganese for mitochondria and its similar chemical properties to iron, there is a sound reason to postulate that manganese may act as an iron surrogate in certain iron-requiring enzymes. It is, therefore, imperative to design the physiochemical studies to determine whether manganese can indeed exchange with iron in proteins, and to understand how manganese interacts with tertiary structure of proteins. The studies on binding properties (such as affinity constant, dissociation parameter, etc.) of manganese and iron to key enzymes associated with iron and energy regulation would add additional information to our knowledge of Mn-Fe neurotoxicity. Third, manganese exposure, either in vivo or in vitro, promotes cellular overload of iron. It is still unclear, however, how exactly manganese interacts with cellular iron regulatory processes and what is the mechanism underlying this cellular iron overload. As discussed above, the binding of IRP-I to TfR mRNA leads to the expression of TfR, thereby increasing cellular iron uptake. The sequence encoding TfR mRNA, in particular IRE fragments, has been well-documented in literature. It is therefore possible to use molecular technique to elaborate whether manganese cytotoxicity influences the mRNA expression of iron regulatory proteins and how manganese exposure alters the binding activity of IPRs to TfR mRNA. Finally, the current manganese investigation has largely focused on the issues ranging from disposition/toxicity study to the characterization of clinical symptoms. Much less has been done regarding the risk assessment of environmenta/occupational exposure. One of the unsolved, pressing puzzles is the lack of reliable biomarker(s) for manganese-induced neurologic lesions in long-term, low-level exposure situation. Lack of such a diagnostic means renders it impossible to assess the human health risk and long-term social impact associated with potentially elevated manganese in environment. The biochemical interaction between manganese and iron, particularly the ensuing subtle changes of certain relevant proteins, provides the opportunity to identify and develop such a specific biomarker for manganese-induced neuronal damage. By learning the molecular mechanism of cytotoxicity, one will be able to find a better way for prediction and treatment of manganese-initiated neurodegenerative diseases.

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Single- and Repeated-Dose Oral Toxicity in Rats and Bacterial Reverse Mutation Test of Morus alba L. Extracts (상지추출물의 단회/반복투여 독성 및 복귀돌연변이능 평가)

  • Han, Taewon;Um, Min Young;Lim, Young Hee;Kim, Jeong-Keun;Kim, In-Ho
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.10
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    • pp.1406-1413
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    • 2016
  • This study was carried out to evaluate the toxicity of ethanolic extracts of Morus alba L. branch (ME). In the reverse mutation test, Salmonella Typhimurium TA98, TA100, TA1535, TA1357, and Escherichia coli WP2uvrA were used to estimate the mutagenic potential of ME. Sprague-Dawley rats were orally administered ME at levels of 1,250, 2,500, and 5,000 mg/kg for the single-dose toxicity test and 500, 1,000, and 2,000 mg/kg/d for the repeated-dose toxicity test for 28 consecutive days. As expected, reverse mutation was not detected at any concentration of ME, regardless of application of the metabolic activation system with or without S9 mix. In the single-dose toxicity test, ME caused neither significant visible signs of toxicity nor mortality in rats, and $LD_{50}$ was estimated to be over 5,000 mg/kg. In the repeated-dose toxicity test, ME administration at 500, 1,000, and 2,000 mg/kg for 28 days to male or female rats did not result in mortality. Similarly, no toxicologically significant treatment-related changes in body weight, food intake, or organ weights were noted. Several hematological and biochemical parameters in both genders showed significant differences, but these were within normal ranges. These results support the safe use of ME.