• Applied Microscopy
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• v.39 no.2
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• pp.81-87
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• 2009

Diabetic retinopathy is one of major complications of diabetes mellitus, which is associated with the dysfunction of retina. It has been reported that the onset of diabetic retinopathy is related to the activation of renin-angiotensin system (RAS). Angiotensin converting enzyme (ACE), which converts angiotensin I into angiotensin II, is a key component of RAS. Among many growth factors, vascualr endothelial growth factor (VEGF) is an important cytokine in the neovasculization of retina, which is a characteristics of diabetic retinopathy. However, the relationship between ACE and VEGF was not elucidated in diabetic retinopathy. Thus, this study was conducted to examine the protective effect of captopril, an ACE inhibitor, in the retina of streptozotocin (STZ)-treated diabetic rats. In present study, STZ-treated diabetic rats exhibited the increase of VEGF levels in serum and retina. The serum levels of VEGF in STZ-treated diabetic rats was not blocked by the treatment of captopril. However, the retina levels of VEGF in STZ-treated diabetic rats was blocked by the treatment of captopril, suggesting the local action of captopril in retina. Immunohistochemical analysis also revealed that the retina of STZ-treated diabetic rats manifested the increase of ganglion cell layers, outer nuclear layers, and inner nuclear layers, which were also prevented by the treatment of captopril. In conclusion, captopril prevented the expression of VEGF in the retina of STZ-treated diabetic rats.

• Proceedings of the Korean Society of Food Hygiene and Safety Conference
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• 2004.11a
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• pp.42-49
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• 2004

본 연구는 선천선고혈압쥐(SHR)에서와 마찬가지로, 높은 정상혈압 및 중등 정도의 본태성고혈압 환자에서 Valyl-Tyrosine(VY)의 항고혈압 효과 여부를 결정하기 위해 수행되었다. 29명의 지원자에 대하여 무작위 이중맹검 위약검사를 실시하였으며, 3 mg의 VY를 포함하는 100-ml 음료와 100ml-위약 음료를 조제하여 사용하였다. 연구대상은 VY (남16/여1, 45.5${\pm}$3.2세, 146.4${\pm}$2.3/90.5${\pm}$1.8 mmHg) 집단과 위약(P) (남11/여1, 48.8${\pm}$3.0 세, 145.5${\pm}$2.4/92.3${\pm}$1.8 mmHg) 집단으로 나누었다. 대조(C)기간 3주 째에 VY-음료 또는 P-음료를 하루 2번씩 투여하기 시작하여 4주 간의 실험(E)기간(BP)은 매주 측정되었으며, 아침에 앉은 자세에서 측정하였다. 혈액 표본은 C기간과 E기간의 마지막 날 채취하였다. VY집단에서, 수축기(S) 및 이완기(D) 혈압의 감소는 첫째 주에 각각 9.7 및 5.3 mmHg (P < 0.001)이었으며, E기간의 시작에 따른 넷째 주에는 각각 9.3 및 5.2 mmHg (P < 0.001)이었다. P 집단에서는 SBP와 DBP 모두 변하지 않았다. VY 집단의 혈압은 회복기간의 끝까지 점진적으로 증가하였다. VY집단에서, 혈장 안지오텐신(Ang) I과 VY의 농도는 현저히 증가한 반면 Ang II와 알도스테론은 VY 투여 후에 현저히 감소하였다. VY는 SHR에서와 마찬가지로 중등 정도의 고혈압 환자에서도 Ang I-전환효소 억제를 통하여 현저한 항고혈압 효과를 가지는 것으로 보이며, 어떤 부작용도 검출되지 않았다.

• Childhood Kidney Diseases
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• v.8 no.1
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• pp.18-25
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• 2004

Purpose : Alport syndrome is clinically characterized by hereditary progressive nephritis causing ESRD with irregular thickening of the GBM and sensory neural hearing loss. The mutations of type IV collagen gene(COL4A5) located on the long arm of X chromosome is considered responsible for most of the structural abnormalities in the GBM of Alport patients. Since no definite clinical prognostic predictor has been reported in the disease yet, we designed this study to evaluate the significance of genetic polymorphism of the angiotensin converting enzyme in children with Alport syndrome as a prognostic factor for disease progression. Methods : ACE I/D genotype were examined by PCR amplification of the genomic DNA in 12 patients with Alport syndrome and 12 of their family members. Alport patients were divided into two groups; the conservative group, those who had preserved renal function for more than 10 years of age, the early CRF group, those who had progressed to CRF within 10 years of age. Results : The mean age of onset was $3.45{\pm}2.4$ years in the conservative group, $4.4{\pm}1.2$ years in the early CRF group. Sex ratios were 5:3 and 2:1 in each group. Among 12 cases of patients, 4 cases were in early CRF group and their mean duration of onset to CRF was 4.5 yews(8.9 years of age). Eight patients(67%) were in the conservative group and they had normal renal function for more than 10 years of age(mean duration of renal preservation was 10.6 years). The incidence of II type ACE gene were in 25.0%(3 cases), ID type in 41.7%(5 cases), DD type in 33.3%(4 cases). There was no significant difference between Alport patient and normal control(II type 44.3%, ID type 40.9%, DD type 14.8%). The incidence of DD type of early CRF group were higher than that of the conservative group(75% vs 12.5%)(p<0.05). There was no difference in ACE gene polymorphism between normal Alport family members and control group. Conclusion : Even though there was no significant difference of ACE polymorphism between Alport patients and the normal control group, the incidence of DD type is significantly increased in early CRF group which means DD type of ACE polymorphism has a possibility of being a predictor for early progression to CRF in Alport patients.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.241-250
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• 1999

Background: Persistent nonproductive cough is a major adverse effect encountered with ACE inhibitor treatment and the most frequent reason for withdrawal of the drug. The mechanism of cough was postulated to be associated with accumulation of bronchial irritants which are substrates of ACE. It has been speculated that occurrence of this adverse effect is genetically predetermined ; in particular, variants of the genes encoding ACE. To investigate this relationship, we determined ACE gene Insertion/Deletion polymorphism in subjects with and without a history of ACE inhibitor-induced cough. Methods: Among the 339 patients with ACE inhibitor treatment, subjects who developed cough that resolved when not taking medication were designated to cough group and other subjects who did not complain cough were designated to non-cough group. Clinical characteristics of the patients were collected by review of medical records. ACE genotypes were determined by PCR amplification of DNA from peripheral blood and agarose gel electrophoresis. Results: 37 patients complained of dry cough(cough group) and 302 patients did not complained of cough(non-cough group). The incidence of ACE inhibitor induced dry cough was 10.9%. There was a preponderance of females in the cough group (M : F=24.3% : 75.7%) compared to the non-cough group (M : F=49.7% : 50.3%, p=0.004). There was no significant difference in mean age, underlying diseases, and kinds and frequencies of ACE inhibitors and their mean dosage between the both groups. ACE genotypic frequencies were I/I : I/D : D/D=16.2% : 18.9% : 64.9% in the cough group and 18.9% : 18.2% : 62.9% in the non-cough group which showed no significant difference between the both groups(p=0.926). Allelic frequencies were I : D = 25.7% : 74.3% and 28.0% : 72.0% in the cough and non-cough group respectively and the difference was not significant(p = 0.676). Conclusion: The incidence of ACE inhibitor-induced cough are 10.9%, and women are more susceptible to ACE inhibitor-induced cough. ACE inhibitor-induced dry cough is not associated with ACE gene Insertion/Deletion polymorphism.

• Korean Journal of Food Science and Technology
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• v.30 no.6
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• pp.1476-1479
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• 1998

Effect of chitosan oligosaccharides on the ACE (angiotensin I converting enzyme) inhibition and antihypertension in SHR (Spontaneously hypertensive rat) was examined. The ACE inhibition activity was observed in all the chitosan oligosaccharides used in this study, and chitosan trimer exhibited the highest inhibitory activity $(IC_{50}=0.9{\mu}M)$ compared with other chitosan oligosaccharides $(IC_{50}\;:\;2.4{\sim}100\;{\mu}M)$. The results suggested that chitosan trimer was a good inhibitor of ACE in molecular level. When the single oral dose (2.14 mg/kg, similar to dose level of Captopril, known as strong ACE inhibitor) of chitosan trimer was given to 8 or 21 week aged SHR, the blood pressure reduction of both SHRs in 4hrs were $27{\pm}4.8\;mmHg\;and\;36{\pm}4.3\;mmHg$, respectively. Therefore, it was suggested that chitosan trimer could be applicable as natural ACE inhibitor related to antihypertension.

• Korean Journal of Medicinal Crop Science
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• v.15 no.6
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• pp.391-397
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• 2007

To develop new high valuable Gugija (Lycium chinensis), biofunctionalities of Gugija standard species and its hybrids were investigated and compared with each water extracts and methanol extracts from Lycii Fructus, Lycii Folium and buds and Lycii Cortex Radicis. Among various biofunctionalities of Gugija standard species, antioxidant activity was showed the highest in methanol extracts from buds of Cheongwoon species (93%) and antihypertensive angiotensin I-converting enzyme (ACE) inhibitory activity was 84.1% in the water extracts from Lycii Cortex Radicis of Cheongyang NO.7. Futhermore, methanol extracts from Lycii Cortex Radicis of Myungan A-2 hybrid showed 93.1% of antioxidant activity and 96.9% of ACE inhibitory activity was also showed in the methanol extracts from Lycii Fructus of DO148-72(A11) hybrid. However, fibrinolytic activity and anticholesteromia HMG-CoA reductase inhibitory activity were weak or not detected in almost of Gugija standard species and its hybrids. Therefore, we finally selected Cheongwoon Gugija standard species (buds) and Myungan A-2 hybrid (Lycii Cortex Radicis) as good antioxidant sources and also DO148-72 (A11) hybrid (Lycii Fructus) as excellent antihypertensive ACE inhibitior sources for manufacturing functional food product.