• 한국임상수의학회지
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• 제18권4호
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• pp.350-353
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• 2001

The purpose of this study is to construct fundamental information about the ultrasonographic diagnosis for extrinsic and intrinsic abdominal disease. Normal ultrasonography of liver, gall bladder, spleen, kidney, urinary bladder, stomach, pylorus, duodenum, and heart of 4 cynomolgus monkey(Macaca fascicularis) were determined by use of ultrasonography. One cynomolgus monkey was autopsied at the time of euthanasia which is performed 24 hours after ultrasonography, and above mentioned organs were measured actually. In ultrasonography of cynomolgus monkey, the gall bladder was 17.5 cm long, and 6.6 cm wide. The width of spleen was 8.8 mm. The right kidney was 35.5 mm long, 23.7 mm wide, and 15.2 mm deep. The ultrasonographic measurements of the left kidney in calves was similar. The urinary bladder was 27.7 mm long, and 20.5 mm wide.

• 한국임상수의학회지
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• 제26권5호
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• pp.508-510
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• 2009

Primary renal cell tumors were described in four nonhuman primates (Erythrocebus patas, Macaca cyclopis, Mandrillus sphinx, and Macaca fascicularis) that have been kept for exhibition at Seoul Zoo. Histologically, all of them were renal adenoma. Each one was clear cell type and tubular type, respectively. The rest two were papillary type adenoma. Clear cell type adenoma was bilaterally affected.

• Toxicological Research
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• 제21권3호
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• pp.227-234
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• 2005

• 한국임상수의학회지
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• 제25권4호
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• pp.314-316
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• 2008

급성 위확장은 실험시설에서 사육되고 있는 Macaca 원숭이에서 가장 흔하게 발생하는 응급상황 중에 하나이다. 이 보고서는 사육 원숭이에서 발생한 몇몇 증례를 소개하고자 한다. 급성 위확장증을 보인 원숭이들에는 실험을 위해 원숭이 보정의자에 앉힌 경우나 마취를 한 경우, 그리고 아무런 처치도 하지 않은 경우 등이 있었다. 이환된 동물들은 심한 복부팽만, 탈수, 청색증과 호흡곤란 등을 동반한 혼수 상태를 보였다. 한 증례는 전신장애로 인해 상태가 악화되고 폐사하여 부검을 실시하였다. 나머지 두 증례는 위관과 수액요법으로 응급처치를 한 결과 병증에서 회복되었다. 부검결과, 위의 대부분은 위내 가스와 물 그리고 섭취물로 채워져 있었다. 이 보고서는 영장류에서 급성위확장증의 발생과 관리에 대한 특별한 강조와 더불어 본 질환이 비 특이적인 원인에 의해 발생할 수 도 있음을 시사한다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2003년도 추계학술대회
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• pp.148-148
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• 2003

The cynomolgus monkey(Macaca fascicularis) is used widely in efficacy and safety assessment of new drugs. The ranges of physiological variables are important end points in the toxicological study. Both the basic physiological variables such as body weight, body temperature, blood pressure, urine pH and blood variables such as biochemical and hematological variables were determined in nineteen male and sixteen female monkey prior to treatment.(omitted)

• Toxicological Research
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• 제21권3호
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• pp.209-218
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• 2005

We investigated effects of recombinant human erythropoietin (rHuEPO) on profiles of mRNA transcripts in 6 male cynomolgus (M. fascicularis) monkey's spleen for 4 weeks. Six monkeys, composed of control and treatment group (Control : M1, M2, M3: Treatment : M4, M5, M6) were intravenously administered 3 times per week without or with a dose of rHuEPO 2730 IU/0.1 ml/kg. After 4 weeks rHuEPO treatment, spleen was removed for RNA isolation. Splenic gene expression was assessed using Affymetrix U133A 2.0 arrays containing 18,400 transcripts and variants, including 14,500 well-characterized human genes. Gene expression pattern was very different between individuals even in same treatment. In rHuEPO treated groups showed number of genes were up- or down-regulated (M4: 79: M5: 48; M6: 73 genes). Six genes (epidermal growth factor receptor, calgranulin A, estrogen receptor binding site associated antigen, matrix metalloproteinase 19, zinc finger and BTB domain containing 16, progestin and adipoQ receptor) were commonly expressed in rHuEPO treated group. The different individual response could be major considering factor in monkey experiment. Further study is needed to clarify the different individual response to rHuEPO in molecular level. This study will be valuable in the fundamental understanding and validation of molecular toxicology for bio-generic drugs including rHuEPO in cynomolgus monkey.

• Toxicological Research
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• 제23권2호
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• pp.159-164
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• 2007

Toxicity screening of a newly developed oral heparin derivative were carried out in 6 male cynomolgus monkeys (Macaca fascicularis), composed of a treatment group and vehicle control group. A newly orally active heparin derivative, developed by Seoul National University, was once given to treatment group at dose of 500 mg/kg. A treatment group did not show any change in body weights, hematological parameters including platelet-related varivables (platelet, PDW, PCT, MPV) and serum biochemical parameters (e.g., AST, ALT, BUN, etc.) for 2 weeks compared with those of vehicle control group. We also confirmed the maximum plasma concentration (Cmax, 1.73 IU/ml) and the time (Tmax, 1 hr) to reach Cmax. The present study will be valuable in the proper interpretation for nonclinical study using cynomolgus monkeys in the development of new drug of heparin derivative.

• Toxicological Research
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• 제24권4호
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• pp.289-295
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• 2008

Toxicology screening following treatment with astemizole, a histamine receptor antagonist, at oral doses of 0, 10, 30 and 60 mg/kg was carried out in male cynomolgus monkeys (Macaca fascicularis). No dose-related changes in mortality, clinical signs, body weight changes, food consumption, or urine analysis occurred in any animal compared to the vehicle control. However, the high-dose group showed a decrease in BUN and ALP compared to vehicle control group. In addition, the levels of TG, AST, ALP and CK increased. Although astemizole did not produce significant toxicological changes at any dose tested, we predict that it can cause toxicological changes of the liver and heart based on the changes in the serum parameters related to the heart and liver. The Action Potential Duration (APD) was prolonged in the heart of 60 mg/kg treatment group compared to the control group. The APD increase in 60 mg/kg treatment group along the other related changes in toxicological parameters imply that astemizole has major cardiotoxic effects in the cynomolgus monkey. This study is a valuable assessment for predicting the general toxicity and cardiotoxic effects of antihistamine drugs using nonhuman primates.

• Toxicological Research
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• 제24권3호
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• pp.219-225
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• 2008

A screening study of the acute toxicity of organic arsenics such as arsenobetaine and arsenocholine, a product of arsenic methylation metabolite, and inorganic arsenic was carried out to examine hematological and serum biochemical parameters in cynomolgus monkeys(Macaca fascicularis). We found soft and liquid feces, and vomiting in all treated groups with inorganic and organic arsenics. The monkeys in inorganic arsenic-treated group showed a significant increase in vomiting frequency compared with those in three organic arsenics-treated groups. These results suggest that inorganic arsenic might be more toxic than three other organic arsenics tested. The monkeys in inorganic arsenic-treated group showed a decrease in platelet and an increase in monocyte on day 4 and the monkeys in arsenocholine-treated group showed an increase in reticulocyte percentage on day 8. The monkeys in inorganic-treated group also showed decreases in AST and ALT values and the monkeys in arsenobetaine-treated group showed a decrease in AST value and an increase in T-CHO value. However, these hematological and biochemical changes were within the physiological ranges, showing that the single dose of inorganic and organic arsenics did not affect at least hematological and serum biochemical parameters. The present study of toxicity with single dose of arsenics provides valuable indicators for longer term study of toxicity of repeated doses of arsenics in primates.

• Molecular & Cellular Toxicology
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• 제3권2호
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• pp.137-144
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• 2007

The mechanism of cytotoxicity of doxifluridine, a prodrug fluorouracil (5-FU), has been ascribed to the misincorporation of fluoropyrimidine into RNA and DNA and to the inhibition of the nucleotide synthetic enzyme thymidylate synthase. Increased understanding of the mechanism of 5-FU has led to the development of strategies that increases its anticancer activity or predicts its sensitivity to patients. Using GeneChip?? Rhesus Macaque Genome arrays, we analyzed gene expression profiles of doxifluridine after two weeks repeated administration in cynomolgus monkey. Kegg pathway analysis suggested that cytoskeletal rearrangement and cell adhesion remodeling were commonly occurred in colon, jejunum, and liver. However, expression of genes encoding extracellular matrix was distinguished colon from others. In colon, COL6A2, COL18A1, ELN, and LAMA5 were over-expressed. In contrast, genes included in same category were down-regulated in jejunum and liver. Interestingly, MMP7 and TIMP1, the key enzymes responsible for ECM regulation, were overexpressed in colon. Several studies were reported that both gene reduced cell sensitivity to chemotherapy-induced apoptosis. Therefore, we suggest they have potential as target for modulation of 5-FU action. In addition, the expression of genes which have been previously known to involve in 5-FU pathway, were examined in three organs. Particularly, there were more remarkable changes in colon than in others. In colon, ECGF1, DYPD, TYMS, DHFR, FPGS, DUT, BCL2, BAX, and BAK1 except CAD were expressed in the direction that was good response to doxifluridine. These results may provide that colon is a prominent target of doxifluridine and transcriptional profiling is useful to find new targets affecting the response to the drug.