The Subacute and Subchronic Oral Toxicity of 1,3-Dichloropropane in the Rat

1991 ◽  
Vol 10 (4) ◽  
pp. 421-430 ◽  
Author(s):  
James B. Terrill ◽  
Merrel Robinson ◽  
Gary W. Wolfe ◽  
Leonard H. Billups
Keyword(s):  
Body Weight ◽  
Food Consumption ◽  
Total Protein ◽  
Dose Group ◽  
Low Dose ◽  
Clinical Chemistry ◽  
High Dose Group ◽  
Blood Levels ◽  
High Dose ◽  
Dose Levels

1,3-Dichloropropane (DCP) was administered by gavage for 14 and 90 days to male and female Sprague-Dawley-derived rats (10/sex/group). In the 14-day study using dose levels of 200, 600, and 1800 mg/kg/day, all high-dose group animals died, and none died in the other two treatment groups. Other signs associated with treatment in high-dose animals included languid behavior, salivation (also seen in middose group animals), dyspnea, and prostration. No differences were found between animals in the low-dose or middose groups compared to the control animals for body weight, food consumption, hematology, and gross postmortem and histopathology data. Total protein and albumin blood levels were increased for low-dose and middose females, and middose females, respectively. The clinical chemistry findings appeared to be treatment-related, since they were accompanied by significantly increased liver weights (absolute and relative; both sexes of middose animals) and kidney weights (absolute and relative; middose males). The dose levels used in the 90-day study, chosen on the results of the 14-day study, were 50, 200, and 800 mg/kg/day. All animals survived to termination. Males in the high-dose group exhibited a significant decrease in body weight, whereas females in this group exhibited urine-stained fur. No treatment-related effects were found in food consumption or hematology data. Alkaline phosphatase, alanine aminotransferase (males only), albumin, and total protein for high-dose group animals were increased. These findings were accompanied by increases in liver weight for low-dose (females only), middose, and high-dose animals and kidney weights for middose and high-dose group animals. Microscopic evaluations revealed centrilobular hepatocellular hypertrophy for the high-dose group animals and an exacerbation of chronic progressive nephropathy for middose (males only) and high-dose animals.

scholarly journals The Effect of Ethanolic Extract of Cannabis sativa Leaves from Nigeria on the Antioxidants Markers in Albino Wistar Rats

2020 ◽  
pp. 58-65
Author(s):  
E. B. Umoren ◽  
I. Wopara ◽  
O. G. Adebayo ◽  
U. A. Ezike ◽  
A. O. Obembe
Keyword(s):  
Body Weight ◽  
Wistar Rats ◽  
Dose Group ◽  
Low Dose ◽  
Cannabis Sativa ◽  
Ethanolic Extract ◽  
High Dose Group ◽  
High Dose ◽  
Control Groups ◽  
And Control

Background: Cannabis sativa is an annual herbaceous plant in the Cannabis genus. The cannabis plant is widely regarded as a potent psychoactive, medicinal plant. Reportedly used for recreation and as intoxicant. The medical uses of the plant include effective control and management of chronic health problems such as HIV/AIDs, cancer, cachexia, nausea and vomiting, asthma and hypertension. C. sativa is known to possess antioxidative properties. This study therefore investigated the effects of C. sativa on antioxidant concentrations in albino Wistar rats. Materials and Methods: Thirty (30) rats used for this study were divided into three groups of 10 rats each. Group 1 received distilled water and served as control. Group 2 received C. sativa extract (100 ml/Kg body weight) by gavage and served as low dose group. Group 3 received C. sativa (250 ml/Kg body weight) by gavage and served as high dose group once daily for 28 days. Results: Catalase (CAT) concentration was significantly lower (P<0.05) in the low dose group as compared with control. In the high dose group, CAT concentration was significantly lower (P<0.05) when compared with the low and control groups respectively. Glutathione peroxidase (GPx) and Superoxide dismutase (SOD) concentrations were significantly higher (P<0.05) in the low dose group as compared with their respective control. GPx and SOD concentrations were significantly higher (P<0.05) in the high dose groups as compared to low dose and control groups respectively. Conclusion: CAT concentration decreased dose-dependently, while GPx and SOD concentrations increased dose-dependently among treated groups. Treatment with C. sativa revealed a paradoxical effect on CAT concentration with respect to GPx and SOD concentrations. Therefore, oral ingestion of ethanolic extract of C. sativa may not have significant effect on the body’s antioxidant stores due to the balance created for CAT deficiency by increased GPx and SOD concentrations.

scholarly journals Antiviral Efficacy and Pharmacokinetics of Oral Adefovir Dipivoxil in Chronically Woodchuck Hepatitis Virus-Infected Woodchucks

2001 ◽  
Vol 45 (10) ◽  
pp. 2740-2745 ◽  
Author(s):  
John M. Cullen ◽  
Daniel H. Li ◽  
Cynthia Brown ◽  
Eugene J. Eisenberg ◽  
Kenneth C. Cundy ◽  
...  
Keyword(s):  
Body Weight ◽  
Oral Bioavailability ◽  
Adefovir Dipivoxil ◽  
Dose Group ◽  
Low Dose ◽  
Hepatitis Virus ◽  
High Dose Group ◽  
Woodchuck Hepatitis Virus ◽  
High Dose ◽  
Antiviral Efficacy

ABSTRACT The antiviral efficacy of orally administered adefovir dipivoxil was evaluated in an 18-week study (12 weeks of treatment and 6 weeks of recovery) conducted with woodchucks chronically infected with woodchuck hepatitis virus (WHV). Adefovir dipivoxil is a prodrug of adefovir designed to enhance its oral bioavailability. Following administration of 15 mg of adefovir dipivoxil per kg of body weight in four WHV-infected animals, the mean maximum concentration of adefovir in serum was 0.462 μg/ml, with an elimination half-life of 10.2 h, and the oral bioavailability of adefovir was estimated to be 22.9% (±11.2%). To study antiviral efficacy, the animals were divided into three groups. There were six animals each in a high-dose group (15 mg/kg/day) and a low-dose group (5 mg/kg/day). A vehicle control group consisted of five animals because WHV DNA was detectable only by PCR at the time of the study in one of the original six animals. Efficacy was evaluated by determining the levels of WHV DNA in serum. The geometric mean WHV DNA level for the high-dose group diminished by >40-fold (>1.6 log10) after 2 weeks of treatment and >300-fold (>2.5 log10) at 12 weeks. There was a >10-fold reduction in five of six low-dose animals by 2 weeks, but levels were unchanged in one animal. By 12 weeks of treatment there was a >45-fold (>1.6 log10) reduction of WHV DNA levels, and serum WHV DNA levels were below the limit of quantification in three of six animals. Viral DNA levels returned to pretreatment levels during the 6-week recovery period. There were no clinically significant changes in body weight, hematology, or serum chemistry values, including bicarbonate or lactate, in any of the treated animals. No histologic evidence of liver injury was apparent in the biopsies. Under the conditions of this study, adefovir dipivoxil was an effective antihepadnaviral agent.

scholarly journals Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

2020 ◽  
Vol 22 (1) ◽  
pp. 176
Author(s):  
Toshiaki Iba ◽  
Jerrold H. Levy ◽  
Koichiro Aihara ◽  
Katsuhiko Kadota ◽  
Hiroshi Tanaka ◽  
...  
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Leukocyte Adhesion ◽  
Endothelial Glycocalyx ◽  
High Dose Group ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Circulating Levels

(1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group (n = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both p < 0.05). Circulating levels of syndecan-1 (p < 0.01, high-dose group) and hyaluronan (p < 0.05, low-dose group; p < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group (p < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group (p < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.

scholarly journals Recombinant Human Thyrotropin-Stimulated Radioiodine Therapy in Patients with Multinodular Goiters: A Meta-Analysis of Randomized Controlled Trials

2020 ◽  
Vol 52 (12) ◽  
pp. 841-849
Author(s):  
Chunmei Xu ◽  
Ping Wang ◽  
Huikai Miao ◽  
Tianyue Xie ◽  
Xiaojun Zhou ◽  
...  
Keyword(s):  
Fixed Effects ◽  
Dose Group ◽  
Low Dose ◽  
Radioiodine Therapy ◽  
Meta Analysis ◽  
High Dose Group ◽  
High Dose ◽  
Fixed Effects Model ◽  
Recombinant Human Thyrotropin

AbstractA potential reduction of goiter volume (GV) of recombinant human thyrotropin (rhTSH) on multinodular goiters (MNG) was previously reported but controversial. Hence we conducted a meta-analysis to estimate the effect of rhTSH-stimulated radioiodine therapy in patients with MNG. PubMed, Cochrane, CNKI, VIP, and Wanfang databases were searched. Mean difference (MD) and odds ratios with 95% confidence intervals (95% CI) were derived by using an inverse variance random-effects model and fixed-effects model, respectively. Six studies (n=237) were involved in the analysis. For 12 months follow up, high dose (>0.1 mg) of rhTSH significantly reduced GV (MD=17.61; 95% CI=12.17 to 23.04; p<0.00001) compared with placebo. No effective pooled results of low dose of rhTSH (<0.1 mg) were applicable for only one study included. For 6 months follow up, the source of heterogeneity was determined by subgroup and sensitivity analysis. High dose group showed vast improvement in GV reduction (MD=16.62; 95% CI=1.34 to 31.90; p=0.03). The reduction of low dose group compared with placebo was inferior to high dose group. No available data were obtained to assess the influence of rhTSH after 36 months follow up for the only included study. Hypothyroidism incidence was higher for rhTSH group. No publication bias was seen. High dose of rhTSH treatment-stimulated radioactive 131I therapy after 6 months and 12 months follow up had a better effect in reducing GV, but with higher incidence of hypothyroidism. Owing to the limited methodological quality, more clinical researches are warranted in the future.

Effects of piperonyl butoxide on spontaneous behavior in F1-generation mice

2009 ◽  
Vol 25 (7) ◽  
pp. 489-497 ◽  
Author(s):  
Toyohito Tanaka ◽  
Osamu Takahashi ◽  
Shinshi Oishi ◽  
Akio Ogata
Keyword(s):  
Dose Group ◽  
Female Offspring ◽  
Piperonyl Butoxide ◽  
High Dose Group ◽  
High Dose ◽  
Adult Females ◽  
Developmental Parameters ◽  
Spontaneous Behavior ◽  
Dose Levels ◽  
F1 Generation

Piperonyl butoxide was given in the diet to provide levels of 0 (control), 0.02%, 0.06%, and 0.18% from 5 weeks of age of the F0 generation to 12 weeks of age of the F1 generation in mice. Select reproductive and neurobehavioral parameters were then measured. In exploratory behavior in the F0 generation, vertical time of adult females increased significantly in a dose-related manner. In behavioral developmental parameters, cliff avoidance was delayed significantly in the high-dose group in male offspring, and this effect was significantly dose-related. In female offspring, surface righting was significantly delayed in the high-dose group, and this effect was significantly dose-related. In spontaneous behavior in the F1 generation, females showed more activities in some variables in the high-dose group. Dose levels of piperonyl butoxide used in the present study produced several adverse effects in neurobehavioral parameters in mice.

Effect of Different Doses of Propofol and Nerve block Combined with General Anesthesia on The Intraoperative Anesthesia and Postoperative Awakening and Cognitive Function in Elderly Patients with Knee Osteoarthritis

2021 ◽  
Vol 7 (4) ◽  
pp. 697-705
Author(s):  
Jianhui Ma ◽  
Meimei Pang ◽  
Xin Ding ◽  
Shirong Fang ◽  
Lichao Chu
Keyword(s):  
Cognitive Function ◽  
Elderly Patients ◽  
General Anesthesia ◽  
Nerve Block ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
Knee Oa ◽  
Different Doses

Objective. To explore the effect of different doses of propofol and nerve block combined with general anesthesia on the intraoperative anesthesia and postoperative awakening and cognitive function in elder patients with knee osteoarthritis (OA). Methods. According to the inclusion criteria for research object, we selected 98 elderly patients with knee OA who needed surgery and were admitted to our hospital from January 2019 to January 2021 for the study. Patients were divided into the low dose group (given 2 mg/kg propofol by pumping under constant speed during surgery) and the high dose group (given 4 mg/kg propofol by pumping during surgery) by the number table method to compare their indicators including the intraoperative anesthesia effect, with 49 cases in each group. Results. No between-group difference was shown in the anesthesia time and postoperative VAS scores, but the awakening time of the low dose group was significantly shorter than that of the high dose group (P<0.05); the differences in heart rate (HR) values at various time points between the two groups were not obvious, but the high dose group obtained significantly higher HR values at T4 than the low dose group; the mean arterial pressure (MAP) values of both groups were significantly reduced at Ti and then returned to the level before anesthesia (P>0.05); the bispectral index scores (BIS) of both groups experienced a marked drop at Ti and then recovered gradually, but failed to return to the level at T0 till the end, and a between-group difference in BIS indexes presented at Ti; the plasma corticosterone (CORT) concentration at Ti of both groups were significantly lowered and then returned to the level at T0, with no between-group difference; and compared with the low dose group, the high dose group achieved slightly lower mini-mental state examination (MMSE) scores at 24-72 h after surgery, with no significant difference between them (P>0.05). Conclusion. The therapy of different doses of propofol and nerve block combined with general anesthesia has no significant effect on the cognitive function in elderly knee OA patients after surgery. With the nerve block improving the analgesic effect, a low dose of propofol is good for the postoperative awakening of patients. Different doses of propofol inhibited the stress response to a different degree and produced good anesthesia outcomes in elderly patients, but comparatively speaking, a low-dose propofol ensures more smooth indexes and less effect on the intraoperative hemodynamics.

scholarly journals Comparison of the in-vivo Effect of Two Tranexamic Acid Doses on Fibrinolysis Parameters in Adults Undergoing Valvular Cardiac Surgery with Cardiopulmonary Bypass - A Pilot Investigation

2020 ◽  
Author(s):  
Zhen-feng ZHOU ◽  
Wen Zhai ◽  
Li-na YU ◽  
Kai SUN ◽  
Li-hong SUN ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Placebo Group ◽  
Cardiopulmonary Bypass ◽  
Plasminogen Activator ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
Pai 1

Abstract Background: The blood saving efficacy of TXA in cardiac surgery has been proved in several studies, but TXA dosing regimens were varied in those studies. Therefore, we performed this study to investigate if there is a dose dependent in-vivo effect of TXA on fibrinolysis parameters by measurement of fibrinolysis markers in adults undergoing cardiac surgery with CPB, which has not been systematically elucidated.Methods: A double-blind, randomized, controlled prospective trial was conducted from February 11, 2017 to May 05, 2017. Thirty patients undergoing cardiac valve surgery were identified and randomly divided into a placebo group, low-dose group and high-dose group by 1: 1: 1. Fibrinolysis parameters were measured by plasma levels of D-Dimers, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), plasmin-antiplasmin complex (PAP), tissue plasminogen activator (tPA) and thrombomodulin (TM). Those proteins were measured at five different sample times: preoperatively before the TXA injection (T1), 5 min after the TXA bolus (T2), 5 min after the initiation of CPB (T3), 5 min before the end of CPB (T4) and 5 min after the protamine administration (T5). A Thrombelastography (TEG) and standard coagulation test were also performed.Results: Compared with the control group, the level of the D-Dimers decreased in the low-dose and high-dose groups when the patients arrived at the ICU and on the first postoperative morning. Over time, the concentrations of PAI-1, TAFI, and TM, but not PAP and tPA, showed significant differences between the three groups (p <0.05). Compared with the placebo group, the plasma concentrations of PAI-1 and TAFI decreased significantly at the T3 and T4 (p <0.05); TAFI concentrations also decreased at the T5 in low-dose group (p <0.05). Compared with the low-dose group, the concentration of TM increased significantly at the T4 in high-dose group. No significant differences were observed in the levels of the coagulation proteins at any points between the groups.Conclusions: The vivo effect of low dose TXA is equivalent to high dose TXA on fibrinolysis parameters in adults undergoing valvular cardiac surgery with cardiopulmonary bypass, and we recommend a low dose TXA regimen for those patients.Clinical trial number and registry URL: ChiCTR-IPR-17010303; http://www.chictr.org.cn, Principal investigator: Zhen-feng ZHOU, Date of registration: January 1, 2017.

scholarly journals Effect of Natural Chinese Herbal Supplements (TCMF4) on Lactation Performance and Serum Biomarkers in Peripartal Dairy Cows

2022 ◽  
Vol 8 ◽  
Author(s):  
Yizhe Cui ◽  
Zhuorui Shan ◽  
Lintong Hou ◽  
Qiuju Wang ◽  
Juan J. Loor ◽  
...  
Keyword(s):  
Dairy Cows ◽  
Milk Production ◽  
Total Protein ◽  
Dose Group ◽  
Production Performance ◽  
High Dose Group ◽  
Holstein Cows ◽  
Control Group ◽  
High Dose ◽  
Lactation Performance

This study examined the effect of mixed medicinal herbs from China in the ground form on milk yield and various blood metabolites before and after parturition in Holstein cows. Crushed Agastache rugosus, Scutellaria barbata, Pericarpium citri reticulate, and Radix glycyrrhizae were used to develop TCMF4. Thirty-two Chinese Holstein cows were randomly divided into a control group or groups receiving 0.1, 0.3, or 0.5 kg TCMF4/cow/d from −7 through 21 d relative to parturition. Blood samples for serum isolation were collected at −7, −1, 1, 7, 14, and 21 d relative to parturition and used to measure glucose, β-hydroxybutyric acid (BHBA), total protein, albumin, globulin, and alkaline phosphatase. Milk production was recorded daily for the first 21 d postpartum, and composition was analyzed at 7, 14, and 21 d. Data were analyzed using a one-way analysis of variance (ANOVA) for multiple comparisons. The average milk production during the first 21-d postpartum was 28.7 ± 6.9, 27.2 ± 7.1, 31.2 ± 6.8, and 38.5 ± 6.1 kg/d for control group and groups receiving 0.1, 0.3, or 0.5 kg TCMF4. Thus, average daily milk production increased between 9 to 34% by supplementation with TCMF4 compared with the control group. Compared with the control group, in the middle dose group, milk concentrations of lactose and total protein decreased by 21 and 19%, respectively, at d 7 around parturition, while total solids increased by 23% at d 21 in the high-dose group. Furthermore, compared with the control group, serum BHBA decreased by 50 and 20% at d −1 and 21 around parturition in the high-dose group. Overall, TCMF4 supplementation improved dry matter intake (DMI) and milk production of dairy cows during the periparturient period without adverse effects on liver function, and plasma BHBA concentrations of dairy cows tended to decrease when dietary TCMF4 increased, which suggested that TCMF4 might be used as potential additives in dairy cows to improve production performance.

scholarly journals Research on the Effects of the Extract of Polygala fallax Hemsl on Sex Hormones and ?-EP in Perimenopausal Rat Models

2020 ◽  
Vol 4 (3) ◽  
Author(s):  
Siyuan Yang ◽  
Zhiyong Cao ◽  
Jiabao Chen ◽  
Gang Fang
Keyword(s):  
Menstrual Cycle ◽  
Sex Hormones ◽  
Dose Group ◽  
Low Dose ◽  
Normal Group ◽  
Dose Effect ◽  
High Dose Group ◽  
High Dose ◽  
Model Group ◽  
Rat Models

Objective: To study the effects of the ethnic medicine Polygala fallax Hemsl with Guangxi characteristics on the sex hormones and ?-EP in research objective perimenopausal rat models. Methods: 40 female SPF rats were randomly divided into 4 groups, including the normal, model, high-dose and low-dose groups. Rats of three groups except for the normal one were treated with perimenopausal modelling through the method of subcutaneous injection of compound 4-VCD for 15 consecutive days. Rats of the normal and model group were normally fed without any treatment. Rats of the high-dose and low-dose groups were administered by high- and low-dose intragastric administration of the extract of Polygala fallax Hemsl. According to the menstrual cycle of the vaginal smear of the rat, each menstrual cycle is a course of treatment and 6 consecutive courses of treatment would be given. The indexes of serum sex hormones (E2, FSH, LH) and ?-EP of rats in each group were observed after treatment. Results: After the treatment of 6 cycles, for the levels of ?-EP and E2, the model group was lowest (P<0.05), the normal group was highest (P<0.05); and the high-dose group was higher than the low-dose group; For the levels of FSH and LH, the normal group was lowest (P<0.05), the model group was highest (P<0.05), and the high-dose group was lower than the low-dose group. Conclusion: Guangxi characteristic national medicine Polygala fallax Hemsl can effectively improve the levels of serum sex hormones and ?-EP in perimenopausal rat models and relieve the related symptoms with a certain dose-effect relationship.

Carcinogenesis Bioassay of Propyl Gallate in F344 Rats and B6C3FJ Mice

1983 ◽  
Vol 2 (6) ◽  
pp. 425-433 ◽  
Author(s):  
K. M. Abdo ◽  
J. E. Huff ◽  
J. K. Haseman ◽  
M. P. Dieter ◽  
G. A. Boorman ◽  
...  
Keyword(s):  
Propyl Gallate ◽  
Dose Group ◽  
Low Dose ◽  
Female Rats ◽  
Male Rats ◽  
High Dose Group ◽  
High Dose ◽  
Preputial Gland ◽  
Rats And Mice ◽  
F344 Rats

Chronic toxicity studies were conducted by maintaining groups of 50 F344 rats and 50 B6C3F1 mice of each sex on nutritionally complete diets containing 0%, 0.6%, or 1.2% propyl gallate for 103 weeks. Survival of rats and mice of both sexes was not significantly affected by the administration of this compound. Dosed rats and mice showed growth retardation and reduced feed utilization efficiency. Increased incidence of hepatic cytoplasmic vacuolization and suppurative inflammation of the prostate gland were observed in dosed male rats and were considered to be related to propyl gallate administration. Tumors of the preputial gland, islet ceil tumors of the pancreas, and pheochromocytoma of the adrenal gland were observed with significantly (p < 0.05) higher incidence in the low-dose male rats; however, there was little evidence of a dose response or of an effect in the high-dose group. Rare tumors (an astrocytoma and a glioma) were found in the brains of two low-dose female rats but none was found in the high-dose group. Malignant lymphoma occurred with a significant (p < 0.05) positive trend in male mice and the incidence in the high-dose group was significantly (p < 0.05) higher than that of the concurrent controls. However, the high-dose incidence was not significantly different from the historical control rate for the laboratory that conducted the bioassay. Under the conditions of the bioassay, propyl gallate was not considered to be clearly carcinogenic for F344 rats, although the increased incidence of preputial gland tumors, islet-cell tumors of the pancreas, and pheochromocytoma of the adrenal glands in low-dose male rats may have been related to compound administration. Thus, the evidence for carcinogenicity in male rats is regarded as being equivocal, while there was no indication of a carcinogenic response in female rats. Propyl gallate was not considered to be carcinogenic for B6C3F1 mice, although the increased incidence of malignant lymphoma in dosed male mice may have been related to administration of the test compound.

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