The present study was carried out to examine the toxicity and target organs of oral cholera vaccine (OCV) after repeated oral administration in Sprague-Dawley rats for 6 weeks (3 administrations, once every 2 weeks). OCV is an inactivated oral cholera vaccine that contains Vibrio cholerae and confers protection against cholera caused by V. cholera serogroups O1 (Inaba and Ogawa serotypes) and O139 (strain 4260B). The animals were orally administered either OCV placebo (negative control) or OCV at a dose equivalent to 240 times the anticipated human dose. Throughout the administration period, no significant change was detected in clinical signs, body weight, food or water consumption, urinalysis results, hematological and clinical biochemistry test results, organ weights, necropsy, or histopathological examination results. Minor changes were found in hematological and clinical biochemistry tests; however, these changes were within normal ranges. The above results suggest that oral administration of OCV in rats did not induce any toxicologically meaningful changes, and the target organs could not be determined. This study was conducted in accordance with the guidelines established by Good Laboratory Practice (2009-183, KFDA, December 22, 2009) and the OECD Principles of Good Laboratory Practice (1997).
Woo, Sang Ha;Lee, Jung Hee;Lee, Cho-in;Lee, Yun Kyu;Lee, Hyun-Jong;Kim, Jae Soo
Journal of Acupuncture Research
/
v.38
no.1
/
pp.47-59
/
2021
Background: This study aimed to assess the toxicity of Aconitum sinomontanum Nakai (ASN) pharmacopuncture. Methods: To investigate the toxicity of ASN pharmacopuncture, single and 4-week repeated dose toxicity experiments were conducted on BALB/c mice. In the single-dose toxicity experiment, mice were assigned 1 of 4 groups (5 males, 5 females per group). Then, 31.25, 62.5, and 125 mg/kg of ASN pharmacopuncture were administered to the mice in the experimental groups at acupoint ST36, while 0.2 mL of normal saline was administered to the control group at ST36. After a 4-week repeated dose regimen, the mice were assigned into 4 groups (5 males, 5 females per group). Then, 15.625, 31.25, and 62.5 mg/kg of ASN pharmacopuncture at ST36 were administered to the mice in the experimental groups, while 0.2 mL of normal saline was administered to the control group at ST36. Mortality, morbidity, general body and organ weight changes (after 4 weeks repeated dose), serum hematological and biochemical values, and histopathological changes in the liver and kidney were observed. Results: In both single and 4-week repeated dose toxicity experiments, no deaths or symptoms occurred in any of the groups. There were no significant differences between groups in terms of body and organ weights, serum hematological and biochemical values, and specific organ histopathological changes. Conclusion: ASN pharmacopuncture injection did not demonstrate significant toxicity in BALB/c mice compared with the control group, with a no-observed-adverse-effect level for a single dose of >125 mg/kg, and for 4 weeks repeated dose it was more than 62.5 mg/kg/day.
Jung, Young Pil;Yim, Nam-Hui;Kim, Aeyung;Hwang, Youn-Hwan;Park, Hwayong;Ma, Jin Yeul
The Korea Journal of Herbology
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v.28
no.2
/
pp.61-65
/
2013
Objectives : Samchulgeonbi-tang (shenzhujianpi-tang) has been prescribed as one of traditional herbal medicine for treatment of stomach diseases since ancient time in Korea. Samchulgeonbi-tang extract was fermented by Lactobacillus spp. for improving the effect. However, the toxicity and safety of fermented Samchulgeonbi-tang (FS) extract were not confirmed. Therefore, this study was performed to evaluate the acute toxicity and safety of FS extract. Methods : To evaluate the acute toxicity and safety of FS extract, several doses of FS extract, 0, 500, 1000 and 2000 mg/kg, were orally administered to 20 male and 20 female ICR mice, respectively. After treatment with FS extract, we observed mortality, general toxicity, behavior and change of body weight for the 14 days. After 14 days of oral administration, all mice were sacrificed and hematological parameters were analyzed from blood serum. Results : In present study, the toxic signs such as mortality or abnormal behaviors by FS extract were not observed. There are no significant differences between FS-treated group and control group in body weight, organ weights, and hematological parameters. Conclusions : The remarkable adverse effects by FS extract were not observed in ICR mice. Also, any death was not occurred at all treated FS doses, 500, 1000 and 2000 mg/kg. Therefore, the approximate lethal dose (ALD) of FS extract may be more than 2000 mg/kg.
Objective: The aim of the present study was to evaluate the associations between hematologic parameters related to systemic inflammation and insulin resistance-associated metabolic parameters in women with polycystic ovary syndrome (PCOS). Methods: Eighty-two women between the ages of 18 and 35 years who were diagnosed with PCOS were included in this study. A 2-hour 75-g oral glucose tolerance test (OGTT) was administered to all study participants; fasting and postprandial glucose and insulin levels were measured simultaneously during the 2-hour OGTT. Hematologic parameters were derived from a standard complete blood count and a differential count of fasting-state blood samples. The correlations between hematologic parameters and insulin resistance-associated clinical and metabolic parameters were evaluated using the Spearman rank correlation and partial correlation coefficients. Hematologic parameters related to systemic inflammation were compared between the two groups, categorized by the presence or absence of insulin resistance. Results: Significant differences in the absolute neutrophil count, absolute monocyte count, platelet count, and neutrophil-lymphocyte ratio were found between the insulin-resistant group and insulin-nonresistant group. Correlation analysis found that all hematological parameters, except for the platelet-lymphocyte ratio, were associated with at least one insulin resistance-associated metabolic parameter. However, these significant correlations between hematological and metabolic parameters were attenuated after controlling for the effects of other covariates using partial correlation analysis. Conclusion: The association between hematologic parameters indicative of systemic inflammation and insulin resistance-associated metabolic parameters seems to be strongly influenced by other anthropometric covariates in women with PCOS.
Kim, Eun-Joo;Jeong, Sang-Hee;Ku, Hyun-Ok;Kang, Hwan-Goo;Cho, Joon-Hyoung
Toxicological Research
/
v.23
no.4
/
pp.353-362
/
2007
Deoxynivalenol (DON) is a common food borne mycotoxin and occurs predominantly in grains such as wheat, barley, oats, etc. DON induces systemic health problems such as loss of appetite, emesis and diarrhea in both human and farm animals. Reliable diagnostic parameters for DON intoxication are needed to prevent deep health impact. In order to establish useful diagnostic parameters, we investigated clinical signs, hematological values, serum biochemical values, gross-, histo- and toxico-pathological findings in B6C3F1 male mice after oral administration of DON (0.83, 2.5 and 7.5 mg/kg) for 8 days. Body weight gain was significantly decreased at the highest dose of DON. Anorexia, ataxia, for crudness and lack of vigor were observed at the highest dose DON group. In hematological values, the numbers of WBC and platelets and hemoglobin content were reduced with decreased neutrophil and monocytes by 7.5 mg/kg DON. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were prolonged in a dose-dependent manner and the content of fibrinogen was elevated at high dose of DON. Of serum biochemical values, total protein, globulin, BUN, cholesterol and test-osterone were reduced but total bilirubin and albumin/globulin ratio increased. The enzyme activity of alkaline phosphatase was decreased while that of alanine aminotransferase was elevated. Relative organ weights of thymus, seminal vesicle/prostate and testes were dose-dependently reduced but those of liver and left adrenal gland increased with dose dependency. As for pathological findings, atrophy of thymus, seminal vesicle/prostate and testes and submucosal edema and ulceration in stomach and depletion of lymphocytes in thymus cortex were observed. In conclusion, these clinical, hematological, blood biochemical and patholgical parameters obtained in the present studies can be used for diagnosis of DON-mycotoxicosis, especially, low WBC, platelets, protein, BUN and testosterone and delayed prothrombin time can be available as for reliable diagnostic parameters.
Blood test is a useful tool in establishing medical treatment for livestock. It provides information such as disease diagnosis, treatment effects, prognostic judgment, and health status. This study compared the value of erythrocytes and leukocytes among conventional, transgenic miniature, and transgenic conventional pigs aged six months to 24 months. Further, it analyzed the aspects of hematological value changes according to the pigs' ages. As a result, the number of red blood cells (RBC), which include hemoglobin, and hematocrit, and the number of white blood cells (WBC), which include neutrophils, and lymphocyte, were high among transgenic miniature pigs, compared with the conventional and transgenic conventional pigs. Conventional pigs showed similar values of RBC and WBC regardless of transgenesis. In comparing their age, the RBC decreased as the age increased compared with the pigs among all the three groups aged of 6~12 months. On the other hand, WBC and neutrophils showed no significant difference regardless of different ages among all the three groups. However, various counts in RBC and WBC were mostly found to be higher in each age in transgenic miniature pigs than in conventional and transgenic conventional pigs. The results of this study show that the values of RBC and WBC were generally higher in transgenic miniature pigs than in conventional and transgenic conventional pigs. Based on this research, hematological values can be widely used in diagnosing diseases or checking the health status of transgenic pigs that are used as disease models, organ transplant source and alike.
The purpose of this study was to evaluate the clinical significance of ultrasonographic classification of fatty liver in three grades. From June 2018 to April 2019, 1047 patients (818 males and 229 females) diagnosed as fatty liver among 3607 patients who underwent abdominal ultrasonography at Busan screening center. Ultrasonography was classified into three grades: Grade I (mild fatty liver), Grade II (moderate fatty liver), and Grade III (severe fatty liver) according to the degree of parenchyma texture, acoustic attenuation, Obesity index, hematological test, and metabolic syndrome. The average age of men in each sex increased with the increase of the fatty liver. Body mass index (BMI) and waist circumference were significantly increased in both men and women (p=.000). hematological analysis showed that AST, ALT, ${\gamma}-GTP$, TG, fasting blood sugar, and glycated hemoglobin were significantly different from each other (p<.05). In women, ALT, ${\gamma}-GTP$ and TG showed a significant difference with increasing fatty liver (p<.05). The prevalence of metabolic syndrome was significantly increased in both sexes as the grade of fatty liver increased (p=.000). Based on the results of this study, it is suggested that the use of ultrasound - guided fatty liver according to severity may be useful for the treatment and follow - up of fatty liver if the liver grade is divided in consideration of hematological variables and metabolic syndrome.
Objectives: This study examined the effects of nutrition education and exercise therapies on the hematological status and diabetes knowledge of diabetic patients. For this purpose, a 12-week intensive management program was provided to diabetic patients participating in an exercise program in S health subcenter in Kwangju city and the effects were analyzed. Methods: The subjects were 26 diabetic patients, who provided written informed consent. As a preliminary survey, this study examined the general characteristics, physical status, obesity, blood pressure, hematological status, daily activity level, diabetes knowledge, diet performance, and barriers to diet therapy. After the 12-week intensive management program was completed, a post-test was conducted in the same way as the preliminary test. The data were analyzed with using SPSS 18.0. The data from this study are presented as the mean${\pm}$standard deviation. A paired t-test was conducted to compare differences in the means before and after the program. Statistical significance was set to p<0.05. Results: The results of the program are presented as follows. The HDL-cholesterol levels changed from $39.8{\pm}10.5mg/dL$ to $48.3{\pm}13.1mg/dL$, showing a significant increase (p<0.001). The blood sugar 2 hours after a meal changed from $175.2{\pm}67.1mg/dL$ to $140.5{\pm}42.5mg/dL$, showing a significant decrease (p=0.014). The glycosylated hemoglobin levels decreased significantly from $6.7{\pm}1.1%$ to $6.3{\pm}1.0%$ (p=0.010). The total scores of the daily activity levels increased significantly from $3.8{\pm}2.4$ to $4.8{\pm}2.5$ (p=0.040). The scores of knowledge on diabetes increased from $11.5{\pm}3.6$ to $14.0{\pm}3.8$ (p=0.001). The scores of knowledge on diet therapy changed from $6.7{\pm}2.2$ to $7.9{\pm}1.7$, showing a significant increase (p=0.027). Conclusions: The 12-week intensive management program intervened by nutrition education and exercise therapies induced positive changes to the HDL-cholesterol, blood sugar 2 hours after a meal, glycosylated hemoglobin, daily activity levels, and knowledge on diabetes.
Objectives: Water-soluble carthami flos (WCF) is a new mixture of Carthami flos (CF) pharmacopuncture. We conducted a 4-week toxicity test of repeated intramuscular injections of WCF in Sprague-Dawley rats. Methods: Forty male and 40 female rats were divided into 4 groups of 10 male and 10 female SD rats: The control group received 0.5 mL/animal/day of normal saline whereas the three experimental groups received WCF at doses of 0.125, 0.25, and 0.5 mL/animal/day, respectively. For 4 weeks, the solutions were injected into the femoral muscle of the rats alternating from side to side. Clinical signs, body weights, and food consumption were observed; opthalmological examinations and urinalyses were performed. On day 29, blood samples were taken for hematological and clinical chemistry analyses. Then, necropsy was conducted in all animals to observe weights and external and histopathological changes in the bodily organs. All data were tested using a statistical analysis system (SAS). Results: No deaths were observed. Temporary irregular respiration was observed in male rats of the experimental group for the first 10 days. Body weights, food consumptions, opthalmological examinations, urinalyses, clinical chemistry analyses, organ weights and necropsy produced no findings with toxicological meaning. In the hematological analysis, delay of prothrombin time (PT) was observed in male rats of the 0.25- and the 0.5-mL/animal/day groups. In the histopathological test, a dose-dependent inflammatory cell infiltration into the fascia and panniculitis in perimuscular tissues was observed in all animals of the experimental groups. However, those symptoms were limited to local injection points. No toxicological meanings, except localized changes, were noted. Conclusion: WCF solution has no significant toxicological meaning, but does produce localized symptoms. No observed adverse effect level (NOAEL) of WCF in male and female rats is expected for doses over 0.5 mL/animal/day.
To provide information on the safety of crude antifungal compounds produced by Bacillus subtilus SN7 isolated from Meju, we carried out an acute (single) oral dose toxicity test and 4 week repeated oral dose determination test on crude antifungal compounds in male and female Sprague Dawley rats. In the acute toxicity test, rats were treated with crude antifungal compounds produced by Bacillus subtilus SN7 orally at increasing dose levels (500, 1,000, and 2,000 mg/kg) and observed for 2 weeks. In the repeated-dose 28-day oral dose determination study, rats were orally administered doses of 500, 1,000, and 2,000 mg/kg daily for 4 weeks. There were no test article-related deaths or abnormal clinical signs in the two studies. In the 4 week repeated oral dose determination test, there were also no significant differences in clinical signs, body and organ weight changes, or any other hematological and biochemical parameters between the control and treated groups. The results suggest that the crude antifungal compounds produced by Bacillus subtilus SN7 up to a dosage level of 2,000 mg/kg are not toxic in male and female rats.
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