• Childhood Kidney Diseases
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• v.4 no.2
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• pp.127-135
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• 2000

Purpose: Cyclosporine(CsA) is a potent immunosuppressant but the use of CsA is associated with various side effects, especially nephrotoxicity. In tile kidney, salt depletion activates tile renin-angiotensin-aldosteron(RAS) system and accentuates chronic CsA nephropathy. We postulate that angiotensin converting enzyme inhibitors(ACEI) can prevent chronic CsA nephropathy, since ACEI may inhibit this cascades. This study was aimed to assess the effect of ACEI on chronic cyclosporin nephropathy in salt depleted rats. Methods: 36 Fischer-344 rats were divided into 6 goups. Group I received normal salt diet(NSD). Group II received a low salt diet(LSD). Group III received CsA with a NSD. Group IV received CsA with a LSD. Group V received NSD+CsA with ACEI. Group VI received LSD+CsA with ACEI. Rats were sacrificed after six weeks and the glomerular filtration rate(GFR), serum sodium, potassium and whole blood cyclosporine levels were measured. Renal tissues me sampled for the observation of histological changes. Results: No differences in blood CsA level & serum sodium were found between groups during the course of this experiment. Serum potassium in group VI was significantly increased compared with group IV and V (P<0.05). In groups treated with CsA only and in those where CsA was combined with ACEI, GFR was found to be significantly more decreased in LSD than NSD, and GFR in group V was significantly decreased in comparison with group III (P<0.05). Renal histologic lesions associated with CsA which consisted of cortical interstitial fibrosis, tubular atrophy and hyalinization of arterioles were more severe in tile LSD group. But, no differences were observed between tile groups treated with CsA and ACEI, and the groups treated with only CsA. Conclusion: Salt depletion associated with the activation of the RAS system accentuated chronic CsA nephrotoxicity, but, ACEI could not reduce the functional and morphological changes of salt depleted kidneys, in which nephropathy can be exacerbated in spite of the blocking of the angiotensin II pathway. further studies are required to elucidate whether Am ameliorated the effect of salt-depleted CsA nephrotoxicity upon the effective renal blood flow.

• Food Science of Animal Resources
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• v.42 no.1
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• pp.46-60
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• 2022

In this study, angiotensin-I-converting enzyme inhibitory (ACEI) activity was evaluated in fermented goat milk fermented by lactic acid bacteria (LAB) from fermented foods and breast milk. Furthermore, the potential for ACEI peptides was identified in fermented goat milk with the highest ACEI activity. The proteolytic specificity of LAB was also evaluated. The 2% isolate was inoculated into reconstituted goat milk (11%, w/v), then incubated at 37℃ until pH 4.6 was reached. The supernatant produced by centrifugation was analyzed for ACEI activity and total peptide. Viable cell counts of LAB and titratable acidity were also evaluated after fermentation. Peptide identification was carried out using nano liquid chromatography mass spectrometry (LC-MS/MS), and potential as an ACEI peptide was carried out based on a literature review. The result revealed that ACEI activity was produced in all samples (20.44%-60.33%). Fermented goat milk of Lc. lactis ssp. lactis BD17 produced the highest ACEI activity (60.33%; IC₅₀ 0.297±0.10 mg/mL) after 48 h incubation, viable cell counts >8 Log CFU/mL, and peptide content of 4.037±0.27/mL. A total of 261 peptides were released, predominantly derived from casein (93%). The proteolytic specificity of Lc. lactis ssp. lactis BD17 through cleavage on the amino acid tyrosine, leucine, glutamic acid, and proline. A total of 21 peptides were identified as ACEI peptides. This study showed that one of the isolates from fermented food, namely Lc. lactis ssp. lactis BD17, has the potential as a starter culture for the production of fermented goat milk which has functional properties as a source of antihypertensive peptides.

• Fisheries and Aquatic Sciences
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• v.4 no.2
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• pp.84-87
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• 2001

Multimeric angiotensin-converting-enzyme-inhibitor (ACE}) containing a trypsin cleavable linker peptide between ACEI was constructed. We made synthetic DNA coding for the ACEI peptide with asymmetric and complementary cohesive ends of linker nucleotides. A tandemly repeated DNA cassette for the expression of concatameric short peptide multimers was constructed by ligating the basic units. The resultant multimeric peptide expressed as soluble and trypsin treated peptide was shown at the same retention time with chemically synthetic ACEI by HPLC. The present results showed that the technique developed for the production of the ACEI multimers with trypsin cleavable linker peptides can be generally applicable to the production of short peptide.

• Korean Journal of Clinical Pharmacy
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• v.21 no.4
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• pp.364-375
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• 2011

Given that single blockade with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) can achieve only partial and undurable suppression of the Renin Angiotensin System (RAS), it has been hypothesized that dual blockage would be more beneficial in the management of blood pressure (BP) reduction and prevention of progressive chronic kidney disease (CKD) than either agent alone. Thus, it has been suggested that the combination of an ACEI and an ARB might provide renal benefits to hypertensive patients over and above BP reduction. However, this might also expose patients to additive or synergistic side effects. We attempted to conduct a systematic review to evaluate the benefits and harms of combination therapy in hypertensive patients with or without kidney diseases. MEDLINE and KoreaMed were searched for relevant randomized clinical trials in adult hypertensive patients with or without diabetes (restricted to 1997, limited to trials published in English). Results were summarized using the random-effects model, and between-studies heterogeneity was estimated with $I^2$. A final analysis of ten trials (23,928 patients) revealed that the combination of an ACEI and an ARB reduced blood pressure (SBP/DBP) by 3.95/2.02 mmHg (95% confidence interval [CI], -4.38 to -3.53/-2.33 to -1.71) compared with ACEI monotherapy, and 2.83/2.64 mmHg (95% CI, -3.25 to -2.41/-4.95 to -0.33) compared with ARB monotherapy. Eight trials (391 patients) demonstrated a significant reduction in 24h-proteinuria (weighted mean difference, 0.16 g/day, 95% CI, -0.26-0.05), but they did not translate into an improvement in GFR. Tests for heterogeneity showed no difference in effect among the studies. The combination therapy reduced proteinuria by 30% (95% CI, 23% to 37%) and 39% (95% CI, 31% to 48%) compared with ACEI monotherapy and ARB monotherapy, respectively. However, in patients who had proteinuria more than 0.5 g/day, the combination therapy failed to show significant reduction in urinary protein excretion. The current cumulative evidence suggests that diabetic patients with proteinuria on dual RAS blockade have an increase risk of adverse events such as hyperkalemia, hypotension, and so on, compared with ACEI or ARB alone. It is, therefore, proposed that the combination therapy should not be routinely used for the treatment of hypertension with or without compelling indications.

• Journal of Microbiology and Biotechnology
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• v.22 no.8
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• pp.1133-1140
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• 2012

Ribonucleic acid interference (RNAi) inhibits the expression of target genes in a sequence-specific manner, and shows potential for gene knockdown in filamentous fungi, in which the locus-specific gene knockout occurs in low frequency. In this study, the function of the repressor of cellulase expression I (ACEI) was verified in Trichoderma koningii (T. koningii) YC01 through RNAi, and ace1-silenced strains with improved cellulase productivity were obtained. An expression cassette that transcribed the interfering double-stranded RNA (dsRNA) of ace1 was constructed and transformed into T. koningii, and the transformants, in which the expression of ace1 was successfully silenced, were selected. As a result of the ace1 gene silencing, the expression levels of the main cellulase and xylanase genes were elevated, and the enhanced production of total proteins, cellulase, and xylanase was observed in the cultivation. In addition, the down-regulation of ace1 resulted in an increasing expression of xyr1, but no clear variation in the expression of cre1, which suggested that ACEI acted as a repressor of the xyr1 transcription, but was not involved in the regulation of the cre1 expression. The results of this work indicate that ace1 is a valid target gene for enhancing enzyme production in T. koningii, and RNAi is an appropriate tool for improving the properties of industrial fungi.

• Journal of Veterinary Science
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• v.24 no.2
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• pp.26.1-26.11
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• 2023

Background: Angiotensin-converting enzyme inhibitor (ACEi) inhibits the catalysis of angiotensin I to angiotensin II and the degradation of substance P (SP) and bradykinin (BK). While the possible relationship between ACEi and SP in nociceptive mice was recently suggested, the effect of ACEi on signal transduction in astrocytes remains unclear. Objectives: This study examined whether ACE inhibition with captopril or enalapril modulates the levels of SP and BK in primary cultured astrocytes and whether this change modulates PKC isoforms (PKCα, PKCβI, and PKCε) expression in cultured astrocytes. Methods: Immunocytochemistry and Western blot analysis were performed to examine the changes in the levels of SP and BK and the expression of the PKC isoforms in primary cultured astrocytes, respectively. Results: The treatment of captopril or enalapril increased the immunoreactivity of SP and BK significantly in glial fibrillary acidic protein-positive cultured astrocytes. These increases were suppressed by a pretreatment with an angiotensin-converting enzyme. In addition, treatment with captopril increased the expression of the PKCβI isoform in cultured astrocytes, while there were no changes in the expression of the PKCα and PKCε isoforms after the captopril treatment. The captopril-induced increased expression of the PKCβI isoform was inhibited by a pretreatment with the neurokinin-1 receptor antagonist, L-733,060, the BK B1 receptor antagonist, R 715, or the BK B₂ receptor antagonist, HOE 140. Conclusions: These results suggest that ACE inhibition with captopril or enalapril increases the levels of SP and BK in cultured astrocytes and that the activation of SP and BK receptors mediates the captopril-induced increase in the expression of the PKCβI isoform.

• Review of Culture and Economy
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• v.17 no.2
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• pp.185-216
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• 2014

It has been two years since the national certificate of Arts & Culture Education Instructor(ACEI) was implemented the 2012 amendment to the Arts & Culture Education Act. Separate from the initial policy goals, students who attend the program to achieve ACEI certificate share various expectations, motivations and intents. The purpose of the research is to understand the collective identity of future ACEIs to evaluate the initial policy implementation during the period when the collective professional identity has not been fully formed yet. This research studies the data that were collected from 172 students who were attending one of the official ACEI institutes in Seoul area. As one of qualitative research methods, Questionnaire Method was employed to conduct this phenomenological study. James E Marcia's theory provides the theoretical framework for the data analysis of this study. The research results indicate that many students'identity status are between Identity Diffusion and Moratorium, which raises concerns for both arts and cultural fields as well as the policy success. Therefore, this research will relate these findings to the larger arts and culture infrastructure in order to better prepare them as arts and cultural professionals and also to stress the importance of the job market development and social environment that can accept them.

• Korean Journal of Clinical Pharmacy
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• v.27 no.3
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• pp.136-142
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• 2017

Background: Dementia is one of important social and economic healthcare issues in the aging age. Therefore, it signifies to analyze the relationship between chronic disease or cardiovascular drug use and the incidence of dementia to establish a basis for increasing or preventing the risk of dementia. The purpose of this study was to investigate the correlation between the prevalence of chronic diseases and the use of cardiovascular drugs in patients diagnosed with dementia. Methods: In this study, we used data from sample of elderly patients from the Health Insurance Review and Assessment Service. We analyzed by logistic regression analysis with age, gender, and medication as covariates. KCD-7 was used to diagnosis of the disease, and drugs were analyzed using ATC codes and Korean standardized drug classification codes. Results: A total of 1,276,331 patients were analyzed in the sample of the elderly population, of which 532,075 (41.7%) were male and 744,256 (58.3%) were female. The patients have the higher risk of dementia in the older, women, and lower socioeconomically status. Cerebral infarction and ischemic heart disease increases risk of dementia. Patients taking statins, angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor antagonists (ARB) showed low incidence of dementia. Conclusion: This study has been shown that ACEI, ARB, and statin drugs may associate with lower incidence of Alzheimer's and other dementia except vascular dementia.

• YAKHAK HOEJI
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• v.56 no.5
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• pp.309-313
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• 2012

Antiobesity, hypotriglyceridemic and antihypertensive activities of isoflavone-free peptide mixture (black soybean peptide, BSP) were reported in our previous experiments. In the present study, angiotensin converting enzyme inhibitory (ACEi) activity was decreased in the aorta tissues of spontaneously hypertensive rats (SHRs) treated with BSP (1% in drink water) for 4 weeks, but not in serum. BSP administration significantly decreased ACE activity by 17.5% (from $33.2{\pm}4.5$ to $27.4{\pm}1.96$ mUnit/mg, p=0.0013) in aorta tissue hydrolysate. BSP treatment also decreased significantly mean blood pressure (BP) (from $213.0{\pm}16.96$ to $184.0{\pm}6.53$ mmHg, p<0.0001) as expected. These results indicate that BSP has antihypertensive activity as well as ACEi activity.

• Childhood Kidney Diseases
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• v.26 no.1
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• pp.31-39
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• 2022

Alport syndrome (AS) is a progressive hereditary nephritis that is often accompanied by sensorineural hearing loss and ocular abnormalities. It is inherited in three modes of X-linked AS (XLAS), autosomal recessive AS (ARAS), and autosomal dominant AS (ADAS). XLAS is caused by pathogenic variants in COL4A5, while ARAS and ADAS are caused by those in COL4A3 or COL4A4. There is currently no curative treatment for AS; however, angiotensin-converting enzyme inhibitors (ACEi) can improve the outcome of AS. In the past decade, multiple studies have shown that early intervention with ACEi upon isolated microscopic hematuria or microalbuminuria could delay disease progression, and early diagnosis is crucial for early treatment. Therefore, a new classification of AS based on molecular diagnoses has been proposed, including the paradigm shift of re-classifying female "carriers" to "patients" and "thin basement membrane nephropathy" to "ADAS." In addition, with the detection of COL4A mutations in some patients with biopsy-confirmed IgA nephropathy, focal segmental glomerulosclerosis, and chronic kidney disease of unknown origin, it is suggested that the phenotype of AS should be expanded. In this review, we highlight the landmark studies and guidelines published over the past decade and introduce strategies for early diagnosis and treatment to improve the outcomes of AS.