• Journal of Animal Science and Technology
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• v.63 no.5
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• pp.1194-1203
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• 2021

Preparation of recipient stallions is critical step to produce donor spermatogonial stem cell (SSC) derived sperm using transplantation technique. This study was conducted to evaluate the effects of intravenous busulfan infusion on germ cell depletion, semen production, and libido in stallions. Six Thoroughbred stallions were separated into two treatment groups: 1) a multiple low-dose (2.5 mg/kg bw for the first 4 weeks and 5 mg/kg bw for the 5th week); and 2) control group treated with PBS. Testicular samples were obtained at 11 weeks and classified into three different patterns of spermatogenesis, such as normal, Sertoli cell only, and destroyed. Semen collection and libido experiments were performed 1 week before treatment, and 4 and 8 weeks after treatment. For the sperm analysis, total spermatozoa and motility were measured using a light microscope with a motility analyzing system. In the multiple low-dose group, the numbers of tubules categorized as Sertoli cell only were significantly higher than those in the control as well as the total population and total/progressive motility of sperm were significantly decreased 8 weeks after the start of the treatment. The sperm production and motility in the multiple low-dose group appears to be reduced, while libido was maintained. In conclusion, multiple administration of 2.5 mg/kg bw busulfan depletes endogenous germ cells in the stallion recipients for SSC transplantation.

• Korean Journal of Head & Neck Oncology
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• v.17 no.2
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• pp.174-178
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• 2001

Background and Objective: Percutaneous ethanol injection therapy has been used in the treatment of the benign thyroid diseases. Although the reported side-effects of the therapy was mild and transient, some side-effects including local or radiating pain are troublesome to the patients. Radioactive iodine-131($Ra-^{131}I$) also has been effectively and safely used for management of the benign thyroid diseases. So we developed the percutaneous intranodular injection therapy of $Ra-^{131}I$ as an alternative of percutaneous ethanol injection therapy. Materials and Methods: From December 1998 to October 1999, we treated 29 outpatients (25 women and 4 men, mean age: $47{\pm}12$ years). Inclusion criteria were follows; age >30 years, cytologically benign, with normal thyroid function, cold nodule on thyroid scintigram, solid or mixed natured nodules in sonographical evaluation. Nodular volume was estimated by sonography according to the ellipsoid formula. $Ra-^{131}I$(0.1mCi/ml) was administered in a single dose injection. Follow-up studies every 3 months consisted of full history, thyroid function test, and sonography. We determined the therapeutic response is effective if the volume reduction of the nodule occurred above 30%. Results: After at least 3 months follow-up, 11 patients showed effective response, 12 patients showed minimal or unchanged response and 6 patients showed progression. Although side-effects such as injection pain, febrile reaction, and hormonal changes were absent, an infectious complication in injection site was developed from 1 case. Conclusion: Although we need a more prolonged follow-up to evaluate the delayed sequelae, we can suggest that percutaneous intranodular injection therapy of $Ra-^{131}I$ may be an attractive non-surgical treatment in selected cases of benign thyroid nodules.

• Journal of the Korean Society of Food Science and Nutrition
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• v.26 no.4
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• pp.689-696
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• 1997

The effects of Aralia canescens and Phellodendron amurense(AP) extracts on the experimental diabetes in ICR mice were investigated. 96male ICR mice were induced diabetes mellitus by intrape-ritoneal streptozotocin injection(75mg/kg B.W.) and divided into two injection groups which are 5 day injection and 10 day injection group. Then, each injection group was subdivided into 8 groups of 6 animals repspectively. CIC served as control and CI1, CI2 and CI3 were treated with 50, 150, 250mg/kg B.W. of AP extracts powder in 0.9% NaCl solution. Animals of groups DIC, DI1, DI2 and DI3 were strepto-zotocin-induced diabetes. DIC served as diabetic control and the rest groups received 50, 150, 250mg/kg B.W of AP extracts powder in saline solution respectively. The body weight, liver and kiney weight changes and blood levels of glucose, cholesterol and triglyceride were measured. Thiobarbituric acid reactive substance(TBARS), and glutathione reductase(GR) and glutathione peroxidase(GPx) activities were also measured for determining antioxidant effects. AP extracts increased the body weight in diabetic groups. The liver and kidney weight/100g B.W. in DIC group were greater than those of normal ICR group but after AP extracts injection, liver and kidney weight were decreased significantly. These effects were more efficient at 10 days injection group. The total, LDL, VLDL cholesterol and triglyceride levels were significantly higher in DIC group and the extent of decrement responded to AP injection dose. The contents of TBARS and antioxidant enzyme activities were relatively decreased after AP extracts injection. These results suggest that the intraperitoneally administered AP extracts may have not only hypoglycemic effect but act as antioxidants by reducing lipid peroxidation.

• Biomolecules & Therapeutics
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• v.2 no.2
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• pp.190-205
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• 1994

This study was conducted to investigate the repeated dose toxicity of DA-125, a new anthracycline antitumor antibiotic, in rats. Before the 13-week main study, a 4-week dose-range finding (DRF) study was carried out. The administration of DA-125 intravenously at dosage levels of 0, 0.125, 0.5, 2.0, and 8.0 mg/kg/day to rats for 4 weeks resulted in premature deaths of all animals in the 8.0 mg/kg/day group and in the deaths of 4 males and 4 females at 2.0 mg/kg/day. Body weights were markedly reduced in the 8.0 mg/kg/day group and showed dose-related decreases in all treatment groups when compared with the control group. Reductions in weight gain were slight and not significantly different at 0.125 mg/kg/day but animals receiving 0.5 mg/kg/day showed more marked decreases in gain in a clear dose-related manner Based On the results of the above DRF study, a 13-week repeated dose intravenous toxicity study in rats with DA-125 was performed at a dose level of 0, 0.012, 0.08 and 0.3 mg/kg/day. No treatment related effects were noted in behavior or body weight in all treatment groups. One male at the highest dose level died on study day 26, but the death could not be related to test article toxicity. Swelling and scabbing of the ears was present in all of the groups, including the control group. There were no treatment related changes in the hematological, biochemical or urinalysis values in all treatment groups. Thymus weights were significantly reduced ill males receiving 0.3 mg/kg/day and they were sligltly, and not significantly, reduced in females of the same group. While there were no associated histological changes. Treatment related necrosis was found in the tail vein (injection site) at 0.08 and 0.3 mg/kg/day. On the basis of these results, the no observed effect level (NOEL) was 0.012 mg/kg/day and the maximum tolerated dose (MTD) was estimated to be more than 0.3 mg/kg/day under the conditions tested.

• Radiation Oncology Journal
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• v.26 no.2
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• pp.104-112
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• 2008

Purpose: To assess the toxicity and tumor response induced by $DCVac/IR^{(R)}$ dendritic cell(DC) immunotherapy combined with irradiation for refractory colorectal cancer patients with multiple liver metastases. Materials and Methods: Between May 2004 and November 2006, applicants from a pool of refractory colorectal cancer patients with multiple liver metastases were enrolled. The patients were registered after having signed the informed consent form, which had been approved by the Institutional Review Board from the Dong-A University and Busan National University Hospital. DCs were obtained from peripheral blood of each patient, and then cultured in vitro. A total of $6{\times}10^6$ DCs were packed into a vial($DCVac/IR^{(R)}$, 0.5 ml) at the convenience of each patient's schedule. On the day before and on the day of each vaccination, each patient received a 4 Gy radiation dose to the target tumor. On the day of vaccination, the indicated dose of autologous DCs was injected into the irradiated tumor using ultrasound-guided needle injection procedures. A total of four vaccinations were scheduled at three 2-week intervals and one 4 week interval at the Dong-A University and Busan National University Hospital. If the tumor status was deemed to be stable or responding to therapy, an additional vaccination dose or two was approved at 4 week intervals beyond the fourth immunization. A tolerance test for DCs was conducted by injecting a range of doses($3{\times}10^6\;to\;12{\times}10^6$ DCs) after the 3rd injection. Moreover, the maximal tolerable dose was applied to additional patients. Treatment safety was evaluated in all patients who had at least one injection. Treatment feasibility was evaluated by the 10th week by assessing the response of patients having at least 4 injections. For systemic toxicities, the evaluation was performed using the National Cancer Institute Common Toxicity Criteria, whereas adverse effects were recorded using common WHO toxicity criteria. Results: Of the 24 registered patients, 22 received the DCs injections. Moreover, of the 14 patients that applied for the tolerance test, only 11 patients completed it because 3 patients withdrew their testing agreement. A grade 3 or more side effect, which was possibly related to the DC injection, did not occur in additional patients. The $12{\times}10^6$ DC injection was identified as the maximum tolerable dose, and was then injected in an additional 8 patients. Patients tolerated the injection fairly well, with no fatal side effects. In order to assess the feasibility of DC immunotherapy, the response was evaluated in other hepatic lesions outside of the targeted hepatic lesion. The response evaluation was performed in 15 of the 17 patients who received at least 4 injections. Stable and progressive disease was found in 4 and 11 patients, respectively. Conclusion: The DC-based immunotherapy and radiotherapy is theoretically synergistic for the local control and systemic control. The $DCVac/IR^{(R)}$ immunotherapy combined with irradiation was tolerable and safe in the evaluated cases of refractory colorectal cancer with multiple liver metastases. Future work should include well designed a phase II clinical trials.

• Clinical and Experimental Reproductive Medicine
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• v.44 no.4
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• pp.232-238
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• 2017

Objective: To determine whether reducing the cetrorelix dose in the antagonist protocol to 0.125 mg had any deleterious effects on follicular development, the number and quality of retrieved oocytes, or the number of embryos, and to characterize its effects on the affordability of assisted reproductive technology. Methods: This randomized controlled study was conducted at the Fertility Unit of Tanta Educational Hospital of Tanta University, the Egyptian Consultants' Fertility Center, and the Qurrat Aien Fertility Center, from January 1 to June 30, 2017. Patients' demographic data, stimulation protocol, costs, pregnancy rate, and complications were recorded. Patients were randomly allocated into two groups: group I (n = 61) received 0.125 mg of cetrorelix (the study group), and group II (n = 62) received 0.25 mg of cetrorelix (the control group). Results: The demographic data were comparable regarding age, parity, duration of infertility, and body mass index. The dose of recombinant follicle-stimulating hormone units required was $2,350.43{\pm}150.76$ IU in group I and $2,366.25{\pm}140.34$ IU in group II, which was not a significant difference (p= 0.548). The duration of stimulation, number of retrieved oocytes, and number of developed embryos were not significantly different between the groups. The clinical and ongoing pregnancy rates likewise did not significantly differ. The cost of intracytoplasmic sperm injection per cycle was significantly lower in group I than in group II (US $ $494.66{\pm}4.079$ vs. US $ $649.677{\pm}43.637$). Conclusion: Reduction of the cetrorelix dose in the antagonist protocol was not associated with any significant difference either in the number of oocytes retrieved or in the pregnancy rate. Moreover, it was more economically feasible for patients in a low-resource country.

• Journal of Acupuncture Research
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• v.37 no.2
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• pp.110-117
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• 2020

Background: The aim of this pilot study was to assess the safety and dosing of scolopendrid pharmacopuncture (SPP). Methods: A total of 40 healthy Sprague-Dawley rats (males and 20 females 20) were selected following a 7-day inspection and acclimation period. SPP was administered via intramuscular injection, over a 2-week period using 3 doses including a high-dose [0.84 mg of scolopendrid per kg of body weight (BW)], a med-dose (0.42 mg/kg BW), and a low-dose (0.21 mg/kg BW). The control group was injected with sterile water into the muscles. Unusual changes caused by administration of the test substance were observed. Weight, feed intake, organ weight, and hematological examinations were compared among the groups. Using the SPSS statistical program, Levene's test was performed to evaluate the homogeneity of variances, and a one-way ANOVA test was subsequently performed to assess the significance between each test group. Results: During the experiment no animals died. Weight change, food consumption, organ weight, hematological test, and blood biochemical tests showed no significant differences in the treatment groups compared to controls. Conclusion: No toxicological changes related to the administration of test substances were observed. Therefore, the LD₅₀ (lethal-dose that kills 50%) of scolopendrid pharmacoupuncture in rats was greater than 0.84 mg/kg.

• Herbal Formula Science
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• v.21 no.1
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• pp.154-160
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• 2013

Objectives : To investigate the therapeutic effect and underlying mechanisms of rhein on renal fibrosis in diabetic rats. Methods : Diabetic nephropathy (DN) was induced in adult Wistar rats via introperitoneal injection of streptozotocin (STZ) (20 mg/kg/d) for three consecutive days. Two days after the last dose of STZ, rhein was administered to the diabetic rats at a dose of 25 mg/kg or 50 mg/kg, twice a day by gavage, respectively. Following 28 days treatment with rhein, the plasma glucose and creatinine levels were measured, the renal levels of TGF-${\beta}1$ protein and mRNA were examined, and the fibronectin mRNA levels were also determined. Results : Rhein significantly inhibited the increased plasma glucose and creatinine levels of diabetic rats in a dose- and a time-dependent way. Immunohistochemical analysis showed both doses of rhein markedly attenuated elevated induction of renal TGF-${\beta}1$ protein expressions in diabetic rats. Additionally, the high dose of rhein improved both TGF-${\beta}1$ and fibronectin mRNA expressions, while the low dose of rhein only alleviated fibronectin mRNA expressions. Conclusions : Rhein can improve renal fibrosis in diabetic nephropathy rats, and which may be mediated through inhibition of the renal mRNA expressions of TGF-${\beta}1$ and fibronectin.

• Biomolecules & Therapeutics
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• v.1 no.1
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• pp.9-19
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• 1993

DA-125, a new anthracycline antibiotic, showed antitumor activity against animal tumors and human tumors. Therefore we studied the cardiotoxic potential of DA-125 in hamsters and rats as a part of safety research, and compared it with that of doxorubicin(DXR). In acute cardiotoxicity test model used hamsters DA-125 was administered intravenously at a dose of 6, 9, 12 mg/kg, and DXR at 3 mg/kg was given. The electrocardiogram(ECG) of hamsters was recorded for 30 minutes after administration. The DA-125 caused slight ECG alterations at a dose of 6 mg/kg. At a dose of 12 mg/kg DA-125 induced moderate to remarkable changes in ECG like decrease of heart rate, widening of PR interval and 07 interval, and A-V block in 3 out of 5 animals. The severity of ECG alteration at 12 mg/kg of DA-125 was similar to that at 3mg/kg of DXR and these changes caused by DA-125 and DXR recovered within 10 minutes after injection. In chronic cardiotoxicity test model used rats, DA-125 was administered intravenously once a week for three weeks at a dose of 6, 9mg/kg and DXR was given at a dose of 6mg/kg. Electrocardiogram was recorded every week from the start of administration to 2 weeks after the last administration and the animals were sacrificed for histological heart examination at 1 week or 2 weeks after the last administration. DA-125 did not cause any abnormal changes in ECG and in histological heart examination due to administration, but DXR caused widening of ST segment, QRS complex, and QT interval from 1 week after administration and these changes were continued to necropsy. These alterations in ECG were accompanied by cardiac histological lesions such as vacuolation in myocardiac cells, interstitial edema and necrosis of myocytes. These results suggest that DA-125 is less cardiotoxic than DXR.

• Journal of Ginseng Research
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• v.29 no.4
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• pp.176-181
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• 2005

Our previous reports demonstrated that ip. administration of Korean red ginseng acidic polysaccharide (RGAP) exerts antitumor activity In mice. The present study was carried out to compare the effects of ip. and p.o. routes of administration of RGAP on either normal or tumor-bearing BALB/c mice. RGAP was administered either ip. or p.o. at doses of 100, 300, 500, 1000 mg/kg for 1 or 5 weeks. Peritoneal macrophages from mice treated with RGAP p.o. at a dose of 300 mg/kg either for 1 or 5 weeks did not exhibit growth inhibition activity toward WEHI-I64 tumor cells. However, administration of RGAP at a dose of 600 mg/kg for both 1 and 5 weeks increased the antitumor activity of macrophages. Oral administration of RGAP (600 mg/kg) for 5 weeks and ip. administration of RGAP (300 mg/kg) for 1 week resulted in antitumor activities of $40\%$ and $45\%$, respectively, indicating that the effect of i.p. injection is more potent 2 and 5 times than that of p.o. one in terms of dose and duration, respectively. Tumor inhibition rates of RGAP at doses of 300, 500, 1000 mg/kg in mice transplanted with B16-F10 melanoma were 4.4, 12.0, and $45.4\%$, respectively, meaning that p.o. dose higher than 500 mg/kg possess marked antitumor activity. The results above suggests that p.o. administration of RGAP also show antitumor activity in vivo depending on the dose.