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Utility of Micro CT in a Murine Model of Bleomycin-Induced Lung Fibrosis (Bleomycin 유도 폐 섬유화 쥐 모델에서 미세 전산화단층촬영의 유용성)

  • Lee, Jae A;Jin, Gong Yong;Bok, Se Mi;Han, Young Min;Park, Seoung Ju;Lee, Yong Chul;Chung, Myung Ja;Youn, Gun Ha
    • Tuberculosis and Respiratory Diseases
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    • v.67 no.5
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    • pp.436-444
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    • 2009
  • Background: Micro computed tomography (CT) is rapidly developing as an imaging tool, especially for mice, which have become the experimental animal of choice for many pulmonary disease studies. We evaluated the usefulness of micro CT for evaluating lung fibrosis in the murine model of bleomycin-induced lung inflammation and fibrosis. Methods: The control mice (n=10) were treated with saline. The murine model of lung fibrosis (n=60) was established by administering bleomycin intra-tracheally. Among the 70 mice, only 20 mice had successful imaging analyses. We analyzed the micro CT and pathological findings and examined the correlation between imaging scoring in micro CT and histological scoring of pulmonary inflammation or fibrosis. Results: The control group showed normal findings on micro CT. The abnormal findings on micro CT performed at 3 weeks after the administration of bleomycin were ground-glass opacity (GGO) and consolidation. At 6 weeks after bleomycin administration, micro CT showed various patterns such as GGO, consolidation, bronchiectasis, small nodules, and reticular opacity. GGO (r=0.84) and consolidation (r=0.69) on micro CT were significantly correlated with histological scoring that reflected pulmonary inflammation (p<0.05). In addition, bronchiectasis (r=0.63) and reticular opacity (r=0.83) on micro CT shown at 6 weeks after bleomycin administration correlated with histological scoring that reflected lung fibrosis (p<0.05). Conclusion: These results suggest that micro CT findings from a murine model of bleomycin-induced lung fibrosis reflect pathologic findings, and micro CT may be useful for predicting bleomycin-induced lung inflammation and fibrosis in mice.

Function of Environmental Flows for Sustainable Water Resources Management (지속가능한 물 관리를 위한 환경유량의 기능정립에 관한 연구)

  • Choi, Ji-Yong
    • Journal of Environmental Policy
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    • v.6 no.2
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    • pp.47-70
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    • 2007
  • In recent days, people's requests about water resources have been developed from managing quality and quantity of water resources to forming a river environment by restoring normal function of river. To meet these requests, it is necessary to establish the concept of environmental flows. In Korea, the environmental flows was introduced as a concept of river maintenance flows in a sense of river management. The function of river maintenance flows has been changed according to what the major issue is in that age such as navigation, water quality, and prevention of saline water intrusion. As the assesment of river maintenance flows in Korea focused mainly on the function of water usage oriented in human, it could not be defined and emphasized in a sense of ecosystem as a pure meaning of environmental flows. And while the existing river maintenance flows are included the assesment of flows, there is not a practical procedure to supply them and the efficient management in a sense of environment is not performed. The environmental flows should be further developed from the river maintenance flows and changed to a new concept focused on maintaining the health of ecosystem. In other words, the environmental flows should be defined as a necessary flows for maintaining the function of river and its original value, and be considered on the same or higher value of flows for maintenance of economic activity, recreation, and power generation.

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Toxicity of Eun-bi San Pharmacopuncture Injection inthe Muscle of Rats

  • Lee, Jongcheol;Jeong, Hohyun;Cha, Eunhye;Park, Manyong;Choi, Sungyoul;Yook, Taehan;Song, InJa;Kim, Sungchul
    • Journal of Pharmacopuncture
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    • v.18 no.1
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    • pp.63-71
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    • 2015
  • Objectives: This study was carried out to analyze the single-dose toxicity of Eun-Bi San pharmacopuncture injected into the muscle of Sprague-Dawley (SD) rats. Methods: All experiments were performed at Biotoxtech, an institution certified to conduct non-clinical studies under the Good Laboratory Practice (GLP) regulations. Six week old SD rats reared by ORIENTBIO were chosen for this pilot study. The reason SD rats were chosen is that they have been widely used in safety tests in the field of medicine, so the results can be easily compared with many other databases. The Eun-Bi San pharmacopuncture was made in a clean room at the Korean Pharmacopuncture Institute (KPI, K-GMP). The constituents of the Eun-Bi San pharmacopuncture are Angelicae gigantis radix, Strychni semen and Glycyrrhizae radix. These were extracted at low temperature and low pressure in an aseptic room at the KPI. Doses of Eun-Bi San pharmacopuncture, 0.25, 0.5 and 1.0 mL, were administered to the experimental groups, and a dose of normal saline solution, 1.0 mL, was administered to the control group. This study was performed under the approval of the Institutional Animal Ethics Committee of Biotoxtech Co., Ltd. Results: No deaths or abnormalities occurred in any of the four groups. No significant changes in weight, hematological parameters or clinical chemistry between the control group and the experimental groups were observed. To determine if abnormalities existed in any organs and tissues, we used microscopy to examine representative histological sections of each specified organ; the results showed no significant differences in any of the organs or tissues. Conclusion: The results of this study suggest that treatment with Eun-Bi San pharmacopuncture is relatively safe and that its clinical use may be beneficial. Further evaluations and studies on this subject will be needed to provide more concrete evidence in support of these conclusions.

Single-dose Intramuscular Injection Toxicology of Danggui Pharmacopuncture (DGP) in Sprague-Dawley Rats

  • Sun, SeungHo;Jeong, JongJin;Park, Sunju;Lee, KwangHo;Yu, JunSang;Seo, Hyung-Sik;Kwon, KiRok
    • Journal of Pharmacopuncture
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    • v.18 no.1
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    • pp.56-62
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    • 2015
  • Objectives: The purpose of the study is to assess both the approximate lethal dose and the single dose intramuscular injection toxicity of Danggui (Angelica gigantis radix) pharmacopuncture (DGP) in Sprague-Dawley (SD) rats. Methods: The experiments were conducted at the good laboratory practice (GLP) laboratory, Biotoxtech Co., which is a laboratory approved by the ministry of food and drug safety (MFDS). The study was performed according to the GLP regulation and the toxicity test guidelines of the MFDS (2009) after approval of the institutional animal care and use committee of Biotoxtech. Single doses of DGP were injected intramuscularly into the rats in three test groups of 6 week old SD rats (5 male and 5 female rats per groups) in the amounts of 0.1, 0.5, and 1.0 mL/animal for groups 2, 3, and 4, respectively, and normal saline solution in the amount of 1.0 mL/animal was injected intramuscularly into the rats (5 male and 5 female rats) in the control group. Observations of the general symptoms and weight measurements were performed during the 14 day observation period after the injection. Hematologic and serum biochemical examination, necropsy, and a local tolerance test at the injection site were done after the observation period. Results: No death was observed in three test groups (0.1, 0.5 and 1.0 mL/animal group). In addition, the injection of DGP had no effect on general symptoms, weights, hematologic and serum biochemical examination, and necropsy. The results from the local tolerance tests at injection site showed no treatment related effects in the SD rats. Conclusion: The results of single dose intramuscular injection of DGP suggest that the approximate lethal dose is above 1.0 mL/animal for both male and female SD rats and that intramuscular injection of DGP may be safe.

Repeated Intramuscular-dose Toxicity Test of Water-soluble Carthami Flos (WCF) Pharmacopuncture in Sprague-Dawley Rats

  • Choi, Yoo-Min;Jung, Da-Jung;Kim, Seok-Hee;Kim, Jong-Uk;Yook, Tae-Han
    • Journal of Pharmacopuncture
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    • v.18 no.1
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    • pp.36-43
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    • 2015
  • 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.

Effects of Eucommiae Cortex (杜冲) on the Bone Histomorphometry and Metabolism in Ovariectomized Rats (두충(杜冲)이 난소적출(卵巢摘出) 흰쥐의 골조직(骨組織) 형태(形態)와 골대사(骨代謝)에 미치는 영향(影響))

  • Yang, Sung-Woo;Cho, Jung-Hoon;Jang, Jun-Bock;Lee, Kyung-Sub
    • The Journal of Korean Obstetrics and Gynecology
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    • v.18 no.1
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    • pp.128-141
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    • 2005
  • Objective : This study was undertaken to investigate the effects of Eucommiae Cortex on the osteoporosis in ovariectomized rats. Materials and Methods : We used Sprague-Dawley female rats in 8-week-old. They were divided into three groups. Sample group was ovariectomized and administered with 10 mg/100 g/day Eucommiae Cortex extract solution for 10 weeks. Control group was ovariectomized and sham group was conducted by sham's operation. And control group and sham group were administered with normal saline as the same way. We measured rats's body and uterus weight and also measured the serum levels of Ca, phosphorus and ALP. We stained the specimens of rat's tibial bones with Goldner's modified Masson's Trichrome and then examined bone histomorphometry with Bioquant computer program of image analysis system. We measured the thickness of osteoid and callus as static parameters and measured bone volume and mineral apposition rate as dynamic parameters. We observed the expressions of RANKL and OPG mRNA of the tibial bone by RT-PCR. Results : The body weight was significantly (p<0.05) increased in control and sample groups compared with sham group, respectively. The uterus weight was significantly (p<0.05) decreased in control and sample group compared with sham group. In the change of Ca, phosphorus and ALP there were no significant changes among three groups. There were no significant changes of trabecula cortical and osteoid bones' thickness and volume. But trabecula mineral apposition rate (MAR) was significantly (p<0.05) increased in sham and sample group compared with control group. In the expression of RANKL mRNA, sample group was decreased compared with control group, and in that of OPG mRNA, sample group was increased compared with control group. Conclusion : This study shows that Eucommiae Cortex has the beneficial effects on bone histomorphometry and metabolism in the ovariectomized rats. We suggest that Eucommiae Cortex be useful for the treatment of osteoporosis.

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The Effects of Simvastatin on Bone Healing in Mandible Fractured Rats. (백서의 하악골 골절 치유에서 Simvastatin이 미치는 영향)

  • Jeong, Jae-Oo;Kwon, Yong-Seok;Kim, Seok-Kwun;Lee, Keun-Cheol
    • Archives of Plastic Surgery
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    • v.36 no.5
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    • pp.525-530
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    • 2009
  • Purpose: The hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are widely used in the treatment of dyslipidemia for the lowering of cholesterol. And studies about simvastatins have been shown to enhance bone formation in vitro and in vivo in rodents. But some other researchers have reported that there was no anabolic effect abouts simvastatins on bone. The peripheral distribution beyond the liver represents a small fraction of an orally administered dose. We hypothesize that this poor peripheral distribution is the likely reason that simvastatins, yield ambiguous results as anabolic agents. We therefore investigated whether the effects of simvastatins on bone may be enhanced by subcutaneous administration, providing better peripheral delivery of these drugs. Methods: 36 rat unilaterally mandible fractured models were prepared and divided into two groups. The simvastatin treated group where 1 mg/kg of simvastatin was daily injected subcutaneously. The same dose of normal saline was injected on the control group. And 3 rats in each group were sacrificed and taken bone samples in each week. Bone sample was evaluated with tensile strength and histological morphology after 1, 2, 3, 4, 5 and 6 weeks. Results: In simvastatin treated group, the fracture healing process, chondrocyte aggregation, collagen formation and trabecular bone formation was rapidly proceeded than the control group in histologically. The tensile strength of the simvastatin treated group was 1.02, 2.25, 3.95, 4.42, 5.49 and $6.00N/mm^2$ by weeks. The control group data was 0.60, 1.05, 2.17, 3.75, 4.15 and $5.17N/mm^2$ by weeks. The average tensile strength was higher by $1.04N/mm^2$ in simvastatin treated group. Conclusion: The currently available data on the effects of simvastatin on bone has done to confirm the finding that simvastatin helps fracture healing. And the potential for simvastatin to be used as anabolic agents for bone when delivered by the subcutaneous route.

Effect of Bone Marrow Aspirate with Autogenous Bone graft for Alveolar Cleft in a new Rabbit Model (가토의 치조열 모델에서 골수 흡인물이 자가뼈 이식술에 미치는 효과)

  • Bae, Sung Gun;Chung, Ho Yun;Lee, Sang Yun;Cho, Byoung Chae;Yang, Jung Dug;Park, Mee Young
    • Archives of Plastic Surgery
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    • v.36 no.5
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    • pp.531-537
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    • 2009
  • Purpose: Alveolar bone grafting has become an essential process in the treatmemt of alveolar cleft patient for stabilization of the maxillary arch, elimination of oronasal fistula, the reconstruction of the soft tissue nasal base support, and creation of bony support for tooth eruption for implant. The use of Autologous iliac cancellous bone is preferable because of the adequate quantity and high osteoinductive potential. However, even with iliac bone, insufficient osteoregeneration and absorption occur due to several factors such as the patient's age, cleft width, functional stress, and others. In order to increase osteoregeneration where the iliac bone is placed, the present study is associated with bone marrow aspirate (BMA). The experimental study evaluated the efficacy of osteoregeneration in normal cleft rabbits when alveolar bone grafting was performed with autologous iliac corticocancellous bone. Methods: Twenty - four New Zealand White rabbits were divided randomly into 2 groups (BMA, control). All animals underwent harvesting of corticocancellous bone graft from the right posterior iliac crest via standard surgical technique. $1m{\ell}$ of BMA were obtained by scraping the needle and aspirate with $10m{\ell}$ syringe from the contralateral iliac bone wall. The muco - periosteal flap on the palate was elevated. A mixture of Equal bone's volumes with BMA and saline as its control was inserted into the cleft. Animals were sacrificed at 2, 4, and 8 weeks and maxilla was harvested for dental peri - apical X-ray, bone matrix density (BMD),and histologic analysis. Result: BMD of regenerated bone to the cleft in the rabbits was higher than that of the control rabbits. X-ray, histologic analysis showed that increased osteoregeneration and low absorption rate were observed in the BMA group. Conclusion: Our experimental study showed BMA enhanced the osteoregeneration and survival rate of alveolar bone grafting. BMA is easy to extract & cost - time effective. So it can be an effective enhancers for bone grafting mixtures.

Adaptation of Feedlot Cattle to a High-energy Ration by Intraruminal Transplantation of Adapted Ruminal Fluid (제1위내용액 이식에 의한 비육우의 농후사료 적응법에 관한 연구)

  • 이현범;탁연빈;성은주;김기석;이영주;정재석;장종식;권오덕
    • Journal of Veterinary Clinics
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    • v.15 no.1
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    • pp.62-74
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    • 1998
  • In feedlot cattle the abrupt change of diet from roughage to a large quantity of grain for the purpose to improve production often results in increased occurrence of rumen acidosis or acute carbohydrate encouragement enterotoxemia, bloats diarrhea liver abscess and laminitis or robot disease. The common management practice to control these problem is to increase the amount of concentrates in the diet in a stepwise manner until the animals are adapted to a high-grain ration. However this practice requires at least about 3 weeks adaptation period and specially prepared adaptation rations which contain various amount of concentrates. Present experiment was undertaken in order to findout the more simple and rapid adaptation method of cattle to a high grain ration. Nineteen Korean calves aging from four to six month were fed artifical hay (Youngchoun Chuk-Hyup, Korea) which contains 10% of concentrates or alfalfa and rye grass hays for two months and randomly alloted to three experimental groups and two control groups. The experimental group-1 was inoculated by stomach tube for two days with li500 ml/day of ruminal fluid fished from Korean beef cattle that had been previously adapted to a high-energy ration. The experimental group-2 was inoculated by trocalization for two days with the same ruminal fluid. The experimental group-3 was inoculated by trocalization with 1,500 ml/day of bacterial culture which contained 2$\times $10$^{9}$/m1 of Gram-negative bacteria derived from adapted luminal fluid. The two control groups were treated with normal saline solution by the same methods. All animals were fed high-energy ration that contained 80% of grain ad libitum for 30-74 days beginning on the third of the treatment. The effect of the inoculation on the adaptation was observed clinicopathologically with the following results; All of the experimental calves inoculated with the ruminal fluid or Gram-negative bacterial culture derived from adapted cattle did not show any signs of rumen acidosis or other related diseases, while most of the control calves did show diarrhea and bloat and a calf laminitis. The average daily weight gain and feed efficiency of experimental calves were slightly improved compared with control calves. Following the feeding of high-grain rational the pH of the ruminal fluid was lowered in both the experimental and control groups. However severe acidosis with the pH of below 5.0 was observed in only a control group-2. The protozoal number in ruminal fluid was markedly decreased during the high-grain feeding in both the experimental and control calves. However the decrease was mere severe in control calves compared with the experimental calves. The activation of the protozoa were completely disappeared within nine hours at the refrigerator temperature (4"C). No significant differences in heamatological and blood chemical values between the experimental and control calves were recognized. However in one control calf which showed clinically laminitis marked elevations of serum glutamic oxaloacetate transaminase and lactic dehydrogenase activities and a decrease of serum glucose level were observed. From these results it would be concluded the intraruminal transplantation of unadapted calves with the adapted ruminal fluid from cattle previously adapted to a high-energy ration prevents disease problem associated with high-grain feeding and improve weight gain and feed efficiency.ency.

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Antagonistic Effects of Doxapram and Yohimbine on Tiletamine-Zolazepam Anesthesia in Dogs (개에서 Tiletamine-Zolazepam 마취에 대한 Doxapram과 Yohimbine의 길항효과)

  • Park Myeong-ho;Kim Myung-cheol
    • Journal of Veterinary Clinics
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    • v.12 no.1
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    • pp.799-818
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    • 1995
  • This study was performed to examine the general anesthetic efficacy of tiletamine-zolazepam, a mixture of phencyclidine-derived tiletamine and benzodiazepine-related zolazepam. The antagonistic activities of doxapram and yohimbine to the anesthetic effects of tiletamine-zolazepam were also studied. Thirty healthy mongrel dogs were divided into three groups (each of 10) twenty minutes after being anesthetized with tiletamine-zolazepam : T-Z-S group(tiletamine-zolazepam-saline), T-Z-D group (tiletamine -zolazepam-doxapram), T-Z-Y group (tiletamine-zolaz.pam-yohim bine). Various parameters wert evaluated in terms of the onset and recovery time of analgesia, respiration rates, hear rates, body temperature, electrocardiogram, blood chemistry, and lymphocyte blastogenesis. The results obtained through these experiment could be summarized as follows: 1. he anesthetic efficacy of tiletamine-zolazepam was considered desirable, with the onset time of anesthesia being as short as 0.23-0.24 minutes. 2. Both of the antagonistic effects of yohimbine and doxapram on the anesthesia induced by liletamine-zolazepan were evaluated statistically significant(p<0.05) as the recovery time was shortened from 39.3$\pm$4.9 min(T-Z-S group) to 25.3$\pm$2.9 nin(T-Z-Y group) and 29.9$\pm$8.8min(T-Z-D group), respectively. 3. Respiration rates were not changed by the treatments of both doxapram and yohimbine, with the only transient increase in the T-Z-D group. The changes in the respiration rate were not observed during the whole time course of the experiment. 4. Yohimbine(T-Z-Y group) increased the heart rate significantly from 30 minutes after the adminstration compared to the T-Z-S group and T-Z-D group (p<0.05). 5. The decreases in th, body temporature were observed from 30 minutes in the T-Z-S group(p<0.05) and 40 minutes in th, T-Z-D group(p<0.05), after the adminstration. On the other hand, there was no hypothermia in the T-Z-Y group. 6. In the all experimental groups of the T-Z-S, T-Z-D and T-Z-Y, there were no specific findings on the electrocardiograph incept slight shift to the tachycardia in all cases. 1. We could not find any differences in the blood chemistry between all experimental groups (T-Z-S, T-Z-D and T-Z-Y). 8. the inhibition of the lymphocyte blastogenesis shown in the T-Z-S with 3 hours decreasing and thereafter restoring to the normal values up to the point 5 hours were not occurred in the T-Z-D and T-Z-Y groups. With the above results, we could conclude that both doxapram and yohimbine can be clinically used as recovery agents towards anesthesia by tiletamine- zolazepam fi:on the efficacy point of view, but yohimbine is more recommendable in this case if considering the recovery time and lymphocyte blastogenesis.

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