Effect of extraction solvent on total flavonoid content of andaliman fruit (Zanthoxylum acanthopodium DC): PENGARUH EKSTRAKSI DENGAN PELARUT PADA TOTAL FAVONOID BUAH ADALIMAN (Zanthoxylum acanthopodium DC)

Hypertension is a disease where blood pressure increases chronically beyond normal limits. Hypertension needs to be watched out because it includes asymptomatic diseases and can cause complications. One alternative treatment for hypertension that has been proven effective in the pharmaceutical industry is the use of ACE-I (Angiotensin-I Converting Enzyme Inhibitors). At present, ACE-I synthesis has been produced commercially as an antihypertensive drug, for example captopril, enalapril, alcacepril, and lisinopril. However, there are many studies that show the existence of ACE-I synthesis side effects for its users, both physiological and non-physiological effects such as coughing, angioedema, and disorders in pregnancy. ACE-I obtained naturally is safer than ACE-I synthesis. Research on ACE-I activity from natural ingredients is still very limited. Andaliman (Zanthoxylum acanthopodium DC) or better known as Batak Pepper has the potential as a natural source of ACE-I. Natural ACE-I in Andaliman can be obtained from the flavonoid content of Andaliman fruit extract. The purpose of this study was to determine total flavonoid content in andaliman fruit by comparing the types of solvents used for extraction. The solvents used were N-hexane, ethyl acetate, ethanol, and water. The extraction results were then compared using a completely randomized design (CRD) to determine the success of this study. Keywords: Antihypertensive, flavonoids, flavonoid, Zanthoxylum acanthopodium DC   ABSTRAK   Hipertensi adalah penyakit di mana tekanan darah meningkat secara kronis di luar batas normal. Hipertensi perlu diwaspadai karena termasuk penyakit tanpa gejala dan dapat menyebabkan komplikasi. Salah satu pengobatan alternatif untuk hipertensi yang telah terbukti efektif dalam industri farmasi adalah penggunaan ACE-I (Angiotensin-I Converting Enzyme Inhibitors). Saat ini, sintesis ACE-I telah diproduksi secara komersial sebagai obat antihipertensi, misalnya captopril, enalapril, alcacepril, dan lisinopril. Namun, ada banyak penelitian yang menunjukkan adanya efek samping sintesis ACE-I bagi penggunanya, baik efek fisiologis dan non-fisiologis seperti batuk, angioedema, dan gangguan pada kehamilan. ACE-I yang diperoleh secara alami lebih aman daripada sintesis ACE-I. Penelitian tentang aktivitas ACE-I dari bahan-bahan alami masih sangat terbatas. Andaliman (Zanthoxylum acanthopodium DC) atau lebih dikenal dengan sebutan Batak Lada berpotensi sebagai sumber alami ACE-I. ACE-I alami di Andaliman dapat diperoleh dari kandungan flavonoid dari ekstrak buah Andaliman. Tujuan dari penelitian ini adalah untuk menentukan total flavonoid dalam buah andaliman dengan membandingkan jenis pelarut yang digunakan untuk ekstraksi. Pelarut yang digunakan adalah N-heksana, etil asetat, etanol, dan air. Hasil ekstraksi kemudian dibandingkan dengan menggunakan desain acak lengkap (CRD) untuk menentukan keberhasilan penelitian ini. Kata kunci: Antihipertensi, flavonoid, flavonoid, Zanthoxylum acanthopodium D

Significant correlation of angiotensin converting enzyme and glycoprotein IIIa genes polymorphisms with unexplained recurrent pregnancy loss in north of Iran

Background: Spontaneous abortion is considered as the most complex problem during pregnancy. Thrombophilia is resumed as a cause of recurrent pregnancy loss (RPL). Glycoprotein IIIa (GPIIIa) gene is involved in thrombosis and abortion. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II and is involved in thrombosis. The most common polymorphism in this gene is the insertion/deletion (I/D). Objective: In this study, we analyzed the association between ACE I/D and GPIIIa c.98C >T polymorphisms in women with unexplained RPL from the north of Iran. Materials and Methods: Sample population consisted of 100 women with unexplained RPL and 100 controls. The ACE I/D and GPIIIa c.98C>T polymorphisms were genotyped by TETRA-ARMS PCR. The association between genotypes frequency and RPL were analyzed using χP2P and exact fisher tests. Associated risk with double genotype combinations was also investigated by binary logistic regression. Results: There was significant association between ACE DD genotype and RPL (OR=2.04; 95% CI=0.94-4.44; p=0.036). ACE D Allele was also significantly associated with the RPL (OR=1.59; 95% CI=1.05-2.41; p=0.013). No significant association was observed between GPIIIa c.98C>T polymorphism and RPL. Conclusion: ACE I/D polymorphism may probably be a prognostic factor in female family members of women with the history of recurrent abortion. © 2016, Research and Clinical Center for Infertitlity. All Rights Reserved

Perceived barriers for treatment of chronic heart failure in general practice; are they affecting performance?

BACKGROUND: The aim of this study is to determine to what extent barriers perceived by general practitioners (GPs) for prescribing angiotensin-converting enzyme inhibitors (ACE-I) in chronic heart failure (CHF) patients are related to underuse and underdosing of these drugs in actual practice. METHODS: Barriers were assessed with a semi-structured questionnaire. Prescribing data were extracted from GPs' computerised medical records for a random sample of their CHF patients. Relations between barriers and prescribing behaviour were assessed by means of Spearman rank correlation and multivariate regression modelling. RESULTS: GPs prescribed ACE-I to 45% of their patients and had previously initiated such treatment in an additional 3.5%, in an average standardised dose of 13.5 mg. They perceived a median of four barriers in prescribing ACE-I or optimising ACE-I dose. Many GPs found it difficult to change treatment initiated by a cardiologist. Furthermore, initiating ACE-I in patients already using a diuretic or stable on their current medication was perceived as barrier. Titrating the ACE-I dose was seen as difficult by more than half of the GPs. No significant relationships could be found between the barriers perceived and actual ACE-I prescribing. Regarding ACE-I dosing, the few GPs who did not agree that the ACE-I should be as high as possible prescribed higher ACE-I doses. CONCLUSION: Variation between GPs in prescribing ACE-I for CHF cannot be explained by differences in the barriers they perceive. Tailor-made interventions targeting only those doctors that perceive a specific barrier will therefore not be an efficient approach to improve quality of care

Effect of angiotensin converting enzyme inhibitors on periprocedural myocardial infarction in patients with metabolic syndrome

Background: Metabolic syndrome (MetS) has been reported as a risk factor for cardiovascular events. The aim of the present study is to investigate the association between chronic angiotensin-converting enzyme inhibitors (ACE-I) therapy and the rate of periprocedural myocardial infarction (PMI) after elective coronary stenting among patients with MetS. Methods: The inclusion criteria were MetS and plan for elective percutaneous coronary intervention. To assess the effect of ACE-I treatment on the incidence of PMI, measurements of cardiac biomarkers (CK-MB mass and troponin I) were performed at baseline and 24 h after the procedure. Results: A total of 459 patients fulfilling the inclusion criteria were recruited to chronic ACE-I treatment and ACE-I naive groups in a 2/1 ratio. Baseline troponin I and CK-MB levels were similar in both treatment groups, whereas they were significantly lower in ACE-I group 24 h after the procedure. Univariate analysis identified body mass index (BMI), LDL cholesterol, nitrate and ACE-I use as significant factors for the development of PMI. Multivariate regression model revealed that body mass index increased and use of nitrate and ACE-I decreased the probability of PMI independent from confounding factors (OR 1.14, 95% CI 1.05–1.23, p = 0.002 for BMI; OR 0.26, 95% CI 0.14–0.48, p = 0.01 for nitrate use, OR 0.51, 95% CI 0.27–0.93, p = 0.03 for ACE-I use). Conclusions: This prospective observational cohort trial demonstrated that chronic ACE-I therapy was an independent predictor for reduced PMI among patients with MetS who underwent elective coronary intervention

Gastrointestinal endogenous proteins as a source of bioactive peptides : Doctor of Philosophy in Nutritional Sciences at Riddet Institute, Massey University, Palmerston North, New Zealand

Gastrointestinal endogenous proteins (GEP) were investigated as a source of bioactive peptides. In silico and in vitro methods were used singly or in combination to study GEP-derived peptides after simulated digestion. The presence of bioactive peptides after in vivo digestion was determined using a porcine model. Bioactivity of the peptides was assessed using selected in vitro bioactivity assays, and peptides were characterised using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and mass spectrometry. In the in silico study, twenty six different GEP and seven dietary proteins were subjected to simulated in silico gastrointestinal (SIGIT) digestion. The predicted resultant peptides possessing amino acid sequences identical to those of known bioactive peptides were identified by screening them against an online database of bioactive peptides (BIOPEP). The predicted number of bioactive peptides released after the SIGIT digestion of GEP ranged from 1 (secretin) to 39 (mucin-5AC), while those for dietary proteins ranged from 1 (gliadin) to 55 (myosin). Angiotensin-I-converting enzyme (ACE-I) inhibitory peptide sequences were found in abundance in both GEP and dietary proteins. The GEP mucin-5AC and the dietary protein myosin were predicted to release the highest number of ACE-I inhibitory peptides (38 and 49 peptides respectively), and were found to be comparable in their potential to release ACE-I inhibitory peptides. Following SIGIT digestion of eleven representative GEP, nineteen novel GEP-derived peptide sequences were selected by applying quantitative structure-activity relationship rules, and were chemically synthesised. Two novel peptides with the amino acid sequences RPCF and MIM, showing dipeptidyl peptidase IV (DPP-IV) inhibitory activity and five novel antioxidant (2,2-diphenyl-1-picrylhydrazyl (DPPH)- inhibitory and, or ferric reducing antioxidant power (FRAP) activity) peptides with amino acid sequences CCK, RPCF, CRPK, QQCP and DCR were identified. These results indicate that GEP may contain novel bioactive peptide sequences. The potential release of bioactive peptides, from four GEP (trypsin, lysozyme, mucin, and serum albumin) and a dietary protein (chicken albumin), in the gastrointestinal tract (GIT) was investigated using an in vitro digestion model. The in vitro digests were screened for ACE-I-, renin-, platelet-activating factor acetylhydrolase (PAF-AH)-, and DPP-IV-inhibition, and antioxidant activity. All four in vitro GEP digests showed ACE-I inhibition comparable to that of the positive control captopril. In comparison to the unfractionated digests, the enriched fractions (<3 and <10 kDa) of lysozyme and serum albumin showed greater renin-, PAF-AH-, and DPP-IV-inhibition, and antioxidant potential. Over 190 peptide sequences were identified from these fractions using mass spectrometry. Stomach chyme (SC) and jejunal digesta (JD) were collected from growing pigs that were fed a protein-free diet for a period of 3 days. The peptides extracted from SC and JD samples were characterized by SDS-PAGE, and their ACE-I-, DPPH-, and microsomal lipid peroxidation (MLP)- inhibition, FRAP activity determined. Potential bioactive peptides responsible for bioactivity were identified using mass spectrometry. SDS-PAGE analysis showed that all of the samples contained a heterogeneous mixture of peptides. Porcine JD samples inhibited ACE-I and DPPH, while SC samples inhibited MLP. Characterization studies identified over 180 peptide sequences from the enriched fractions of SC and JD samples that showed the highest activity. Further, a porcine serum albumin peptide sequence (FAKTCVADESAENCDKS) was found to be a sub-sequence of a larger sequence identified in the in vitro digest of human serum albumin. There was considerable inter-animal variation for the bioactivities. This may be attributed to sampling effects and, or natural variations in the gut contents, thus underlining the complexity involved in in vivo release of bioactive peptides. Together, the results indicate: 1) GEP contain abundant encrypted bioactive peptide sequences; 2) GEP-derived bioactive peptides display a range of bioactivities; 3) GEP-derived bioactive peptides are released during gastrointestinal digestion in pigs; 4) GEP may contain numerous novel bioactive peptide sequences encoded within their primary sequence. In conclusion, the evidence reported here suggests that, like the dietary proteins, GEP are also a potentially rich source of exogenously-derived bioactive peptides in the gastrointestinal tract. Beyond their primary functions, GEP may act as an important cryptomic source of bioactive peptides, given that the amount of GEP secreted into the gut is equal to or greater than the dietary protein ingested per day, and that up to 80% of GEP are known to be digested

Hypertensive Management for African American Patients

Abstract Background: The rates of angioedema amongst African American patients using angiotensin- converting- enzyme- inhibitors (ACE-I) are five times greater than non-African American counterparts (01.-07 percent vs. 0.5-3.5 percent). Although ACE-I agents are widely prescribed, they have less therapeutic control in hypertension amongst this group of patients and high incidences of life threating side effects. Methods: The purpose of this quality improvement (QI) project was to assess provider knowledge related to established guidelines from the Joint National Committee (JNC) on hypertension management, as well as their knowledge of the side effects of ACE-I for African American patients. A pre interventions survey was conducted to assess knowledge of established guidelines for hypertension management and risks associated with use of ACE-I in African American patients. The staff was then educated on current guidelines as well as where to access them, and also on the risks of ACE-I and alternative options for African American patients and a post intervention survey was issued to assess knowledge gained from the intervention. Results: Following the educational intervention, all participants were able to identify resources related to guidelines for hypertensive management. However, only 75% of staff were able to recall potential adverse side effects of ACE-I use in African American patients. Conclusion: The results of this QI project support the effectiveness of an educational program addressing ethnic considerations in the prescribing of ACE-I for African American patients. Keywords: African American, angioedema, hypertension, ACE-

Impact of left ventricular ejection fraction on the effect of renin-angiotensin system blockers after an episode of acute heart failure: From the KCHF Registry

Objective: This observational study aimed to examine the prognostic association of angiotensin-converting enzyme inhibitors (ACE-I)/angiotensin receptor blockers (ARB) in different left ventricular ejection fraction (LVEF) categories. Methods: In 3717 patients enrolled in the KCHF Registry, a multicentre registry including consecutive patients hospitalized for acute heart failure (HF), we assessed patient characteristics and association between ACE-I/ARB and clinical outcomes according to LVEF. In the three LVEF categories (reduced LVEF [HFrEF], mid-range LVEF [HFmrEF] and preserved LVEF [HFpEF]), we compared the patients with ACE-I/ARB as discharge medication and those without, and assessed their 1-year clinical outcomes. We defined the primary outcome measure as a composite of all-cause death and HF hospitalization. Results: The 1-year cumulative incidences of the primary outcome measure were 36.3% in HFrEF, 30.1% in HFmrEF and 33.8% in HFpEF (log-rank P = 0.07). The adjusted risks of the ACE-I/ARB group relative to the no ACE-I/ARB group for the primary outcome measure were significantly lower in HFrEF and HFmrEF (HR 0.66 [95%CI 0.54–0.79], P<0.001, and HR 0.61 [0.45–0.82], P = 0.001, respectively), but not in HFpEF (HR 0.95 [0.80–1.14], P = 0.61). There was a significant interaction between the LVEF category and the ACE-I/ARB use on the primary outcome measure (Pinteraction = 0.01). Conclusions: ACE-I/ARB for patients who were hospitalized for acute HF was associated with significantly lower risk for a composite of all-cause death and HF hospitalization in HFrEF and HFmrEF, but not in HFpEF. ACE-I/ARB might be a potential treatment option in HFmrEF as in HFrEF

Angiotensin II-inhibition:effect on Alzheimer's pathology in the aged triple transgenic mouse

Reducing excessive accumulation of amyloid-β (Aβ) in Alzheimer's disease (AD) is a key objective of most AD therapies, and inhibition of angiotensin-converting enzyme (ACE) may delay onset or progression of AD. The effects of an ACE-inhibitor (ACE-I) and an angiotensin II receptor blocker (ARB) on Aβ and tau pathology in a triple transgenic (3xTGAD) mouse model of AD were investigated. 9-10month 3xTGAD mice were treated with ARB, ACE-I or vehicle for 6 months. Mean arterial blood pressure (MABP) was measured periodically and mice were assessed behaviourally. Aβ, phospho-tau, amyloid precursor protein (APP) and ACE activity were analysed. MABP was significantly reduced at 2 weeks and 3 months in the ACE-I group and at 3 months in the ARB group, compared to vehicle. Neither drug altered performance of 3xTGAD mice in Morris Water Maze or T-maze, nor were Aβ, tau immunolabelling or APP levels altered. ACE-I significantly reduced ACE activity in kidney. Prolonged treatment with ACE-I or ARB does not affect Aβ or phospho-tau accumulation in brains of aged 3xTGAD mice

Different Effects of Angiotensin Converting Enzyme Inhibitors on Endothelin-1 and Nitric Oxide Balance in Human Vascular Endothelial Cells: Evidence of an Oxidant-Sensitive Pathway

Angiotensin converting enzyme inhibitors (ACE-I) are able to reduce the formation of the potent vasoconstrictor endothelin-1 and increase nitric oxide bioavailability in human vascular endothelial cells (HUVECs). We tested the effects of two sulfhydryl-containing ACE-I, zofenoprilat, and captopril, and two nonsulfhydryl containing ACE-I, enalaprilat and lisinopril, on endothelin-1/nitric oxide balance and oxidative stress in HUVECs. All the four tested ACE-I reduced endothelin-1 secretion and increased nitric oxide metabolite production by HUVECs. However, zofenoprilat (−42% after 8 hours of incubation) was more effective (P < .05) than enalaprilat (−25%), lisinopril (−21%), and captopril (−30%) in reducing endothelin-1 secretion. Similarly, zofenoprilat (+110% after 8 hours of incubation) was more effective (P < .05) than enalaprilat (+64%), lisinopril (+63%), and captopril (+65%) in increasing nitric oxide metabolite production. The effect of ACE-I on endothelin-1 and nitric oxide metabolite production is mediated by the activation of bradykinin B2 receptor being counteracted, at least in part, by a specific antagonist. Zofenoprilat and, to a lesser extent, captopril also reduced oxidative stress in HUVECs. In conclusion, among the four tested ACE-I, zofenoprilat was more effective in improving endothelin-1/nitric oxide balance in HUVECs likely because of its greater antioxidant properties