Serum Angiotensin-converting Enzyme Activity Research Articles

A-083 Performance evaluation of Sentinel Diagnostics’ ACE assay on the Abbott Alinity c system and ARCHITECT c16000 System

Abstract Background The analytical performances of the Angiotensin Converting Enzyme (ACE) assay for quantitative determination of ACE activity in human serum and plasma have been evaluated on the Abbott Alinity c system and ARCHITECT c16000 System. ACE (dipeptidyl carboxypeptidase) is a glycoprotein peptidyldipeptide hydrolase that cleaves histidylleucine dipeptide from angiotensin I, a relatively inactive decapeptide. The latter is converted to the potent vasoconstrictor, angiotensin II. ACE also inactivates bradykinin. Elevated levels of ACE activity occur in serum of patients with active sarcoidosis, and occasionally in premature infants with respiratory distress syndrome, in adults with tuberculosis, Gaucher’s disease, leprosy, and in many other pathologic conditions involving lung and liver diseases. Methods ACE hydrolyses urylacryloylphenylalanine-glycylglycine (FAPGG) to furylacryloylphenylalanine (FAP) and glycylglycine. Hydrolysis of FAPGG results in a decrease in absorbance at 340 nm. The ACE activity in the sample is determined by comparing the sample reaction rate to that obtained with the Sentinel ACE calibrator. Performances evaluation have been done following the latest CLSI guidelines protocols available. Results Summary of the analytical performances for the tested assay is reported in table below. Conclusions Analytical performances of Sentinel Diagnostics’ ACE assay demonstrate that quantitative determination of ACE activity in human serum and plasma are suitable for the routine measurement of the analyte on Abbott Alinity c system and ARCHITECT c16000 System.

Development of Pomegranate Aloe Vera Juice: Pomalo

Abstract: Pomegranate juice is a good source of polyphenols and has good antioxidant potential, whereas, the studies on pomegranate juice have shown that it possesses antiatherogenic, antioxidant, antihypertensive, and anti-inflammatory properties. The literature also reported the major decrease in atherosclerotic lesion region in immune-deficient mice and intima media thickness in cardiac patients on medications, due to consumption of pomegranate juice. Whereas, in patients with type 2 diabetes, a reduction in lipid peroxidation was observed and in hypertensive patients, a systolic blood pressure and serum angiotensin converting enzyme activity was determined. Therefore, the study showed the potential cardioprotective advantages of pomegranate juice and suggests the inclusion of this juice in a diet for a healthy living. the composition of aloe vera and its role in development of functional foods. The colorless and watery gel-like consistency are the characteristics of aloe vera gel that makes it better option for blend beverages. The functional characteristics render aloe vera with broad range of application in the pharmaceutical, cosmetics and food sectors. The presence of antioxidants and hormones (auxins and gibberellins) in aloe vera, are responsible for preventing chronic diseases and wound healing properties by inducing the cell propagation, thus providing anti-inflammatory action, respectively. Saponins and salicylic acid present in it, provides antibacterial and antiseptic activity. The literature also reveals that emidine and aloin are the compounds present in aloe that act as antiviral, antibacterial and analgesic agent. Whereas, it also contains vitamins E, C and minerals such as, copper, selenium and zinc, along with enzyme brady kinase, fatty acids and sugar, essential and non-essential amino acids, 12 anthraquinones phenolic compounds. The most abundant monosaccharide and polysaccharides found in aloe vera are Mannose-6-phosphate, and glucomannans, respectively.

Mathematical modelling of the influence of ACE I/D polymorphism on blood pressure and antihypertensive therapy

The angiotensin-converting enzyme (ACE) gene (ACE) insertion/deletion (I/D) polymorphism raises the possibility of personalising ACE inhibitor therapy to optimise its efficiency and reduce side effects in genetically distinct subgroups. However, the extent of its influence among these subgroups is unknown. Therefore, we extended our computational model of blood pressure regulation to investigate the effect of the ACE I/D polymorphism on haemodynamic parameters in humans undergoing antihypertensive therapy. The model showed that the dependence of blood pressure on serum ACE activity is a function of saturation and therefore, the lack of association between ACE I/D and blood pressure levels may be due to high ACE activity in specific populations. Additionally, in an extended model simulating the effects of different classes of antihypertensive drugs, we explored the relationship between ACE I/D and the efficacy of inhibitors of the renin–angiotensin–aldosterone system. The model predicted that the response of cardiovascular and renal parameters to treatment directly depends on ACE activity. However, significant differences in parameter changes were observed only between groups with high and low ACE levels, while different ACE I/D genotypes within the same group had similar changes in absolute values. We conclude that a single genetic variant is responsible for only a small fraction of heredity in treatment success and its predictive value is limited.

Effects of Roasting and Extrusion Puffing on the Antihypertensive Activity of Blended Grains in Spontaneously Hypertensive Rats

We investigated the effects of processing (roasting and extrusion puffing) on the antihypertensive activity of blended grains both in vitro and in vivo. The blended grains were composed of sorghum (Sorghum bicolor), adzuki bean (Vigna angularis), and finger millet (Eleusine coracana). In the in vitro studies, total phenolic content (TPC), total flavonoid content (TFC), and angiotensin-converting enzyme (ACE) inhibitory activity of blended grains were evaluated. The results showed a significant decreasing trend in TPC, TFC, and ACE inhibitory activity in the following order: nonprocessed blended grains (NPBG) > roasted blended grains (RBG) > extrusion puffed blended grains (EPBG). Spontaneously hypertensive rats (SHRs) were fed a diet containing 40% blended grains (replacing the standard diet) for 8 weeks. None of the blended grains had any effects on feed intake, liver function, and serum lipid profile. Notably, NPBG showed the greatest reduction in systolic blood pressure compared to the model control (MC), followed by RBG, and EPBG, whereas diastolic blood pressure was significantly decreased in NPBG and RBG. Serum ACE activity and angiotensin II levels significantly decreased in all blended grains, with NPBG and RBG showing the most significant decrease in angiotensin II levels. Moreover, the mRNA expression of renin, a hormone involved in hypertension, was significantly decreased in NPBG and RBG. Only NPBG ameliorated aortic vascular remodeling compared to the MC. These results suggest that NPBG exhibited the most potent antihypertensive activity; however, roasting could be an effective processing method for maintaining antihypertensive effects compared to extrusion puffing.

Ratiometric fluorescence detection of the angiotensin-converting enzyme via single-excitation and double-emission biomass-derived carbon quantum dots

Efficient and rapid detection of angiotensin-converting enzyme (ACE) activity is important for preventing hypertension and the discovery of new angiotensin-converting enzyme inhibitors (ACEI). In this work, a single-excitation and double-emission biomass-derived carbon quantum dots (CQDs) was prepared and applied for ratiometric fluorescence detection of ACE. Fresh banyan leaves were extracted with ethanol and acetone, and the extracted solution was used as the precursor to produce the carbon quantum dots (BL-CQDs) with single-excitation and double-emission properties. The synthesized BL-CQDs is about 1.7 nm, has a graphene-like structure, contains a variety of hydrophilic functional groups on the surface, and has good fluorescence properties. Its fluorescence intensity ratio (I677/I460) is linear with ACE activity in the range of 0.02–0.8 U l−1. The regression equation is △F=2.5371 C ACE -0.0311. The method was successfully applied to the determination of ACE activity in pig lung and human serum, and the inhibitory efficiency of the flavonoid extract and captopril tablets on ACE activity was also investigated, which can be applied to the screening of ACEI. The survival rate and fluorescence imaging of Bel-7404 cells under the condition of high concentration BL-CQDs showed BL-CQDs had low cytotoxicity and good biocompatibility. These results indicate that the BL-CQDs can be used as an excellent fluorescent probe, providing a new method for screening ACE activity and plant-derived ACEI.

Increasing angiotensin-converting enzyme concentrations and absent angiotensin-converting enzyme activity are associated with adverse kidney outcomes in pediatric septic shock

BackgroundSepsis-induced endothelial dysfunction is proposed to cause angiotensin-converting enzyme (ACE) dysfunction and renin–angiotensin–aldosterone system (RAAS) derangement, exacerbating vasodilatory shock and acute kidney injury (AKI). Few studies test this hypothesis directly, including none in children. We measured serum ACE concentrations and activity, and assessed their association with adverse kidney outcomes in pediatric septic shock.MethodsA pilot study of 72 subjects aged 1 week–18 years from an existing multicenter, observational study. Serum ACE concentrations and activity were measured on Day 1; renin + prorenin concentrations were available from a previous study. The associations between individual RAAS components and a composite outcome (Day 1–7 severe persistent AKI, kidney replacement therapy use, or mortality) were assessed.Results50/72 subjects (69%) had undetectable ACE activity (< 2.41 U/L) on Day 1 and 27/72 (38%) developed the composite outcome. Subjects with undetectable ACE activity had higher Day 1 renin + prorenin compared to those with activity (4533 vs. 2227 pg/ml, p = 0.017); ACE concentrations were no different between groups. Children with the composite outcome more commonly had undetectable ACE activity (85% vs. 65%, p = 0.025), and had higher Day 1 renin + prorenin (16,774 pg/ml vs. 3037 pg/ml, p < 0.001) and ACE concentrations (149 vs. 96 pg/ml, p = 0.019). On multivariable regression, increasing ACE concentrations (aOR 1.01, 95%CI 1.002–1.03, p = 0.015) and undetectable ACE activity (aOR 6.6, 95%CI 1.2–36.1, p = 0.031) retained associations with the composite outcome.ConclusionsACE activity is diminished in pediatric septic shock, appears uncoupled from ACE concentrations, and is associated with adverse kidney outcomes. Further study is needed to validate these findings in larger cohorts.

Relevance of oxidative stress biomarkers, hemoglobin A1c, troponin-I, and angiotensin-converting enzyme metabolism to blood pressure in acute myocardial infarction: a case-control study

ABSTRACTThe aim was to investigate this relationship by calculating 1) the correlation between peak troponin-C (peak-cTnI), levels of oxidative stress biomarkers, including lipid peroxidation products (malondialdehyde (MDA), conjugated dienes (CD)), and antioxidant enzyme activity (glutathione peroxidase (GPx)), and HbA1c and 2) the correlation between HbA1c and serum angiotensin-converting enzyme (ACE) activity, and its impact on the rate pressure product (RPP) in acute myocardial infarction (AMI). A case-control study was performed in 306 AMI patients having undergone coronary angiography and on 410 controls. GPx activity was reduced in association with increased MDA and CD in patients. Peak-cTnI was positively correlated with HbA1c, MDA, and CD levels. Serum ACE activity was negatively correlated with GPx. HbA1c was positively correlated with ACE activity and RPP. Linear regression analysis showed that peak-cTnI, ACE activity and HbA1c are significant predictors of AMI. Elevated HbA1c and peak-cTnI levels are associated with RPP elevation causing AMI. In conclusions, patients with elevated HbA1c, elevated ACE activity and cTnI are at increased risk of AMI with increasing RPP. Patients at risk of AMI can be identified at an early stage if the biomarkers HbA1c, ACE activity, and cTnI are measured and preventive measures are taken in a targeted manner.

The ACE rs1799752 Variant Is Associated with COVID-19 Severity but Is Independent of Serum ACE Activity in Hospitalized and Recovered Patients.

This paper assesses the association of the insertion/deletion ACE (angiotensin-converting enzyme) variant (rs1799752 I/D) and the serum ACE activity with the severity of COVID-19 as well as its impact on post-COVID-19, and we compare these associations with those for patients with non-COVID-19 respiratory disorders. We studied 1252 patients with COVID-19, 104 subjects recovered from COVID-19, and 74 patients hospitalized with a respiratory disease different from COVID-19. The rs1799752 ACE variant was assessed using TaqMan® Assays. The serum ACE activity was determined using a colorimetric assay. The DD genotype was related to risk for invasive mechanical ventilation (IMV) requirement as an indicator of COVID-19 severity when compared to the frequencies of II + ID genotypes (p = 0.025, OR = 1.428, 95% CI = 1.046-1.949). In addition, this genotype was significantly higher in COVID-19 and post-COVID-19 groups than in the non-COVID-19 subjects. The serum ACE activity levels were lower in the COVID-19 group (22.30 U/L (13.84-32.23 U/L)), which was followed by the non-COVID-19 (27.94 U/L (20.32-53.36 U/L)) and post-COVID-19 subjects (50.00 U/L (42.16-62.25 U/L)). The DD genotype of the rs1799752 ACE variant was associated with the IMV requirement in patients with COVID-19, and low serum ACE activity levels could be related to patients with severe disease.

Lacto-Fermented and Unfermented Soybean Differently Modulate Serum Lipids, Blood Pressure and Gut Microbiota during Hypertension

Soy consumption may reduce hypertension but the impact of food processing on the antihypertensive effect is unclear. Hence, we ascertained the effects of lacto-fermented (FSB) and unfermented soybean (USB) consumption on serum atherogenic lipids, hypertension and gut microbiota of spontaneous hypertensive rats (SHR). FSB displayed a strong in vitro angiotensin converting enzyme (ACE) inhibitory ability of 70 ± 5% while USB inhibited 5 ± 3% of the enzyme activity. Consumption of USB reduced serum ACE activity by 19.8 ± 12.85 U while FSB reduced the enzyme activity by 47.6 ± 11.35 U, respectively. FSB significantly improved cholesterol levels and reduced systolic and diastolic blood pressures by 14 ± 3 mmHg and 10 ± 3 mmHg, respectively, while USB only had a marginal impact on blood pressure. Analysis of FSB showed the abundance of ACE inhibitory peptides EGEQPRPFPFP and AIPVNKP (which were absent in USB) and 30 phenolic compounds (only 12 were abundant in USB). Feeding SHR with FSB promoted the growth of Akkermansia, Bacteroides, Intestinimonas, Phocaeicola, Lactobacillus and Prevotella (short chain fatty acid producers) while USB promoted only Prevotellamassilia, Prevotella and Intestimonas levels signifying the prebiotic ability of FSB. Our results show that, relative to USB, FSB are richer in bioactive compounds that reduce hypertension by inhibiting ACE, improving cholesterol levels and mitigating gut dysbiosis.

Une sarcoïdose difficile à diagnostiquer

AbstractAbout a case of pulmonary granulomatosis disease first diagnosed as a tuberculosis from thoracic X ray examination; anamnesis, thoracic scanner and biological analyses established diagnosis of sarcoidosis which could be confirmed by pathological analysis of cutaneous lesions found after deep physical examination. Biological analyses showed that intern organs were also injured; corticoid therapy easily cured the disease with normalized biological values. The increase in serum angiotensin converting enzyme activity (ACE) is not specific for sarcoidosis but guides the physician toward diagnosis in this case and can follow efficacy of the therapy. Serum ACE activity is determined by spectrophotometric methods developed on biochemistry automates.

Small conductance calcium-activated potassium channels and nitric oxide/cGMP pathway mediate cardioprotective effects of Croton urucurana Baill. In hypertensive rats

Ethnopharmacological relevanceCroton urucurana Baill. (Euphorbiaceae), popularly known as ‘sangue de dragão’ is a Brazilian species widely used in traditional medicine for cardiovascular ailments. AimTo investigate the cardiovascular effects of the C. urucurana extract in spontaneously hypertensive rats (SHRs). Materials and methodsLeaves from C. urucurana were collected and morphoanatomically characterized. The ethanol-soluble fraction (ESCU) was obtained and analyzed by LC-DAD-MS. Using female Wistar rats we investigated the acute toxicity of ESCU. Then, SHRs (six months old) received vehicle, hydrochlorothiazide (25 mg/kg), or ESCU (30, 100, 300 mg/kg) for 28 days. At the beginning and at the end of treatments, urine samples were obtained to assess renal function. At the end of the trial period, the blood pressure, mesenteric vascular beds (MVBs) reactivity, and electrocardiographic profile were evaluated. Serum angiotensin-converting enzyme activity, as well as urea, creatinine, sodium, potassium, nitrite, malondialdehyde, nitrotyrosine, and aldosterone levels were determined. Relative organ weights and histopathological analysis were performed. Finally, the cardiac function on a Langendorff system, as well as the molecular mechanisms involved in the vasodilator effects of ESCU in MVBs were also investigated. ResultsThe compounds annotated from ESCU by LC-DAD-MS included mainly phenylpropanoid derivatives, alkaloids, O-glycosylated megastigmanes, glycosylated flavonoids, flavan-3-ols, and others, such as quercetin O-deoxyhexosyl-hexoside, magnoflorine, reticuline, and taspine. None of the animals showed any signs of toxicity. Male SHRs treated only with the vehicle showed important cardiovascular changes, including a reduction in renal function, increase in serum oxidative stress, and hemodynamic, electrocardiographic, and morphological changes typical of hypertensive disease. Moreover, parameters of cardiac function, including left ventricular developed pressure, peak rate of contraction, peak rate of relaxation, and the rate pressure product were significantly altered, showing a significant impairment of ventricular function. All ESCU-doses presented a significant cardioprotective effect in SHRs rats. The 28-day treatment normalized the hemodynamic, electrocardiographic, morphological, and renal impairments, as well as reversed the changes in ventricular function induced by hypertension. In MVBs with an intact endothelium, ESCU (0.1, 0.3, and 1 mg) dose-dependently induced vasodilation. Endothelium removal or the inhibition of nitric oxide synthase prevented the vasodilatory effect of ESCU. Perfusion with a physiological saline solution that contained KCl, tetraethylammonium, or apamin also abolished the vasodilatory effect of ESCU. ConclusionProlonged ESCU-treatment showed significant cardioprotective effects in SHRs. Moreover, the data showed the role of nitric oxide and calcium-activated small conductance potassium channels in the cardiovascular effects of ESCU.

High Angiotensin-Converting Enzyme and Low Carboxypeptidase N Serum Activity Correlate with Disease Severity in COVID-19 Patients.

(1) Background: Angiotensin-converting enzyme 2 (ACE2) is a functional receptor of SARS-CoV-2 and counter-balances ACE in the renin–angiotensin system (RAS). An imbalance of the RAS could be associated with severe COVID-19 progression. (2) Methods: Activities of serum proteases angiotensin-converting enzyme (ACE) and carboxypeptidase N (CPN) for 45 hospitalized and 26 convalescent COVID-19 patients were investigated vs. healthy controls using labeled bradykinin (DBK) degradation with and without inhibition by captopril as a read-out. Data were correlated to clinical parameters. (3) Results: DBK degradation and CPN activity were significantly reduced gender-independently in COVID-19 and returned to normal during convalescence. ACE activity was over-active in severe disease progression; product DBK1-5 was significantly increased in critically ill patients and strongly correlated with clinical heart and liver parameters. ACE inhibitors seemed to be protective, as DBK1-5 levels were normal in moderately ill patients in contrast to critically ill patients. (4) Conclusions: CPN and ACE serum activity correlated with disease severity. The RAS is affected in COVID-19, and ACE could be a therapeutic target. Further proof from dedicated studies is needed.

Angiotensin-Converting Enzyme Activity May Predict Disease Severity in Psoriasis

Psoriasis is a multifactorial disease, with many genetic risk factors, one of which seems to be the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. ACE activity has been shown to be higher in psoriatic patients and it suggests an oxidative stress state, as seen in many cardiovascular disorders. We aimed to explore the association between ACE activity and polymorphisms and cardiovascular risk amongst psoriatic patients. We included 64 psoriatic patients and 1091 controls and compared ACE I/D polymorphism genotype and serum activity for both groups. ACE genotypes were similar in psoriatic patients and controls. Notably, serum ACE activity was higher in psoriatic patients (19.09 ± 2.86 U/mL) compared to controls (11.85 ± 0.40 U/mL), p = 0.015. Non-HDL cholesterol was significantly lower in II polymorphism (p = 0.037). Psoriatic activity (PASI) was associated with a higher cardiovascular risk estimated by lower HDL concentrations (r = −0.496, p = 0.007), and higher triglyceride levels (r = 0.421, p = 0.020) and TC/HDL and LDL/HDL ratios (r = 0.612, p &lt; 0.001 and r = 0.437, p = 0.023, respectively). Patients with psoriasis have higher ACE activity levels, independent of ACE genotype. Moreover, disease activity correlated with cardiovascular risk. This could support the eventual role of ACE as a possible biomarker for disease severity and cardiovascular risk in psoriasis patients.

High serum angiotensin-converting enzyme 2 activity as a biomarker of frailty in nursing home residents.

Angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) are two of the main components of the renin-angiotensin system (RAS). Imbalanced RAS showing lower ACE2 has been associated with increased cardiovascular risk, muscular pathologies, sarcopenia, frailty, other age-related pathologies and a poorer health status. However, its role in aging remains unclear. Thus, the aim of this work was to analyze the serum enzymatic activity of ACE and ACE2, the ACE/ACE2 ratio and its association with anthropometric parameters, blood pressure, physical function, dependence and frailty in older people living in nursing homes. This study is a secondary analysis of baseline data from two randomized clinical trials in a population of 228 older individuals living in nursing homes (Spain). Serum ACE and ACE2 enzymatic activities were measured by fluorimetry. Variables linked to cardiovascular risk, physical function, dependence and frailty were measured using validated tests, indexes and scales. Association between ACE, ACE2 serum activities, the ACE/ACE2 ratio and the rest of the quantitative variables were assessed by Pearson's correlations and by partial correlations controlled by age and sex. The association between serum ACE and ACE2 activities, the ACE/ACE2 ratio and frailty scores was analyzed by generalized linear models with and without controlling for sex and age. Differences in enzymatic activities between sexes and between frail and non-frail individuals were analyzed using Student's t-test and general linear models to control analysis by age and sex. We found that higher serum ACE2 activity was associated with a higher body mass index, worse physical function, greater dependence and increased frailty. This association is consistent with the elevation of circulating ACE2 in certain pathological conditions and in line with RAS deregulation in muscular dystrophies. Serum ACE2 activity, in combination with other molecules, could be proposed as a biomarker of poor physical function, higher dependence and frailty.

Genistein alleviates renin-angiotensin system mediated vascular and kidney alterations in renovascular hypertensive rats

Genistein is a bioflavonoid mainly found in soybean. This study evaluated the effect of genistein on vascular dysfunction and kidney damage in two-kidney, one-clipped (2K1C) hypertensive rats. Male Sprague–Dawley-2K1C hypertensive rats were treated with genistein (40 or 80 mg/kg) or losartan 10 mg/kg (n = 8/group). Genistein reduced blood pressure, attenuated the increase in sympathetic nerve-mediated contractile response and endothelial dysfunction in the mesenteric vascular beds and aorta of 2K1C rats. Increases in the intensity of tyrosine hydroxylase (TH) in the mesentery and plasma norepinephrine (NE) were alleviated in the genistein-treated group. Genistein also improved renal dysfunction, hypertrophy of the non-clipped kidney (NCK) and atrophy of the clipped kidney (CK) in 2K1C rats. Upregulation of angiotensin II receptor type I (AT1R), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunit 4 (Nox4) and Bcl2-associated X protein (BAX) and downregulation of B-cell lymphoma 2 (Bcl2) protein found in CK were restored by genistein. It also suppressed the overexpression of AT1R, transforming growth factor beta I (TGF-β1), smad2/3 and p-smad3 in NCK. Genistein reduced serum angiotensin converting enzyme (ACE) activity and plasma angiotensin II (Ang II) in 2K1C rats. Low levels of catalase activity as well as high levels of superoxide generation and malondialdehyde (MDA) in 2K1C rats were restored by genistein treatment. In conclusion, genistein suppressed renin-angiotensin system-mediated sympathetic activation and oxidative stress in 2K1C rats. It alleviated renal atrophy in CK via modulation of AT1R/NADPH oxidase/Bcl-2/BAX pathways and hypertrophy in NCK via AT1R/TGF-β1/smad-dependent signalling pathways.

Investigation of The Effect of Aminoglycosides on Angiotensin Converting Enzyme (ACE)

Objective: The research attention to nephrotoxicity from antibiotics (as aminoglycosides), non-steroidal anti-inflammatory drugs, and antifungals, angiotensin-converting enzyme (ACE) inhibitors. Several drugs have resulted in produce an adverse effect on kidneys. Angiotensin-converting enzyme (ACE) is a component of the renin-angiotensin system (RAS), which leads to the conversion of angiotensin-I to angiotensin-II in vascular tissues. The present study aimed to determine serum ACE activity in rats with an aminoglycosine.&#x0D; &#x0D; Material-Method: In this study, two different groups formed, the control group (10 rats/Wistar-albino female) and the experimental group (30 rats/Wistar-albino female) administered aminoglycosine (Amikacin). Aminoglycosine was administered intraperitoneally to the experimental group at a single dose of 15 mg/kg body weight at the same time each day for 14 days. The control group implemented physiological water instead of aminoglycosine at the same rate. &#x0D; &#x0D; Result: When the groups compared according to the statistic results, it is observed that there was a significant increase in the experimental group according to the control group (p˂0.001).&#x0D; &#x0D; Conclusion: As a result, it was determined that aminoglycosin administered increased serum ACE activity and it was concluded that it may be useful to investigate the possibilities to evaluate it as a risk factor and indicator in the development of hypertension

Substance P Serum Degradation in Complex Regional Pain Syndrome – Another Piece of the Puzzle?

In a previous study, we demonstrated that the serum peptidase system might be less efficient in complex regional pain syndrome (CRPS). Since the neuropeptide substanc P (SP) contributes to inflammation in CRPS, we now investigated the metabolism of SP in CRPS specifically. An SP metabolism assay was performed in 24 CRPS patients, which constitute a subgroup of our previous investigation on BK degradation. In addition, we included 26 healthy controls (24 newly recruited plus 2 from our previous investigation), and 13 patients after limb trauma, who did not fulfil the CRPS diagnostic criteria (trauma controls, TC) were included. We adapted a thin layer chromatography assay (TLC) to quantify SP disappearance after incubation with 7.5 µL of serum. These results were compared with bradykinin (BK) metabolization to BK1-8 and BK1-5 fragments from our previous study. In addition, TC were clinically and quantitative sensory testing (QST) phenotyped; the phenotyping of CRPS patients was retrieved from our existing database. SP metabolism was less efficient in CRPS and TC patient serum vs human control (HC) serum (P < .03) suggesting reduced activity of the neutral endopeptidase (NEP) and/or the angiotensin converting enzyme (ACE). Together with the decreased occurrence of BK1-5 fragment in CRPS and TC, this suggests a reduced activation of the angiotensin converting enzyme (ACE). There was no clear clinical phenotype related to impaired SP degradation; duration of disease and gender were also not associated. Most importantly, results in TC did not differ from CRPS. Collectively, our current and previous experimental results suggest that limb trauma reduces serum peptidase metabolism of SP ex vivo, specifically serum ACE activity. However, this finding is not CRPS-specific and seems to be rather a long-term consequence of the trauma itself. PerspectiveThe experimental data from this study further support the hypothesis that impaired metabolism of inflammatory peptides potentially contribute to the development of posttraumatic pain in CRPS or limb trauma patients.

Clitoria ternatea (Linn.) flower extract attenuates vascular dysfunction and cardiac hypertrophy via modulation of Ang II/AT1 R/TGF-β1 cascade in hypertensive rats.

Clitoria ternatea (CT) (the Fabaceae family) has been reported to elicit several biological responses, such as anti-inflammation and anti-depression effects. This study evaluated the effect of CT flower extract on blood pressure, vascular function, and left ventricular hypertrophy in a two-kidney, one-clip (2K-1C) rat model. Hypertensive rats were treated with CT extract at various doses (100, 300, or 500 mg kg-1 day-1 ) or losartan (10mg kg-1 day-1 ) for 4 weeks (n=8/group). CT extract reduced blood pressure in a dose-dependent manner, and CT extract at a dose of 300 mg kg-1 was an effective concentration (P < 0.05). Augmentation of contractile responses to electrical field stimulation and impairment of vascular responses to acetylcholine in mesenteric vascular beds and aortic rings of 2K-1C rats were suppressed by treatment with CT extract or losartan (P < 0.05). Serum angiotensin-converting enzyme activity and plasma angiotensin II concentration were high in 2K-1C rats but alleviated by CT extract or losartan treatment (P < 0.05). Increases in superoxide production and lipid peroxidation were attenuated in 2K-1C rats treated with CT extract or losartan compared with the untreated group (P < 0.05). Increased plasma concentration of nitric oxide metabolites was found in hypertensive rats that received CT extract or losartan. CT extract or losartan suppressed the overexpression of Ang II receptor subtype I (AT1 -R) and transforming growth factor-β1 (TGF-β1) in 2K-1C rats. CT extract had antihypertensive effects that were associated with improving vascular function and cardiac hypertrophy in 2K-1C rats. The mechanisms involved suppression of the renin-angiotensin system, of oxidative stress, and of the AT1 R/TGF-β1 cascade. © 2021 Society of Chemical Industry.

Bradykinin and angiotensin-converting enzyme in serum of patients with diabetic retinopathy and the prognosis of diabetic macular edema development (pilot study)

Diabetic macular edema (DME) is a microvascular complication of diabetic retinopathy. One of the key roles in the pathogenesis of DME may belong to the components of rennin-angiotensin and kallikrein-kinin systems: bradykinin (Bk) and angiotensin-converting enzyme (ACE). To determine the Bk and ACE concentration and ACE activity in serum of patients with proliferative diabetic retinopathy (PDR) and to estimate the significance of these parameters for the early diagnostic and prognosis of DMO. Serum was collected from the 2 groups of patients with II type diabetes. Group I (n=9) had DME, group II (n=27) had PDR without DME. Control group (n=14) consisted of adult volonteers without diabetes and ophthalmic diseases. Concentration of Bk and ACE was measured using ELISA kits, ACE activity was determined enzymatically with specific fluorogenic substrate. Concentration of Bk in serum of patients without DME did not differ from one in controls (12,00 (9,70; 12,40) pg/ml) while all patients with DME had Bk level of 14,69 (13,68; 16,78) pg/ml that was significantly higher (p&lt;0,01). In patients without DME ACE concentration (88,60 (77,30; 97,45) ng/ml) and ACE activity (6,8 (5,1;7,1) nmol/min·ml) were higher than normal (p&lt;0,01) while in the case of DME concentration of ACE increased (77,36 (70,24; 86,29 ng/ml, p&lt;0,01) and activity remained normal. The Bk/ACE concentrations ratio decreased in patients without DME and increased in those having DME. Patients with DME have increased Bk concentration along with nearly normal ACE concentration that indicate predominance of Bk synthesis over its degradation that may lead to the DME development. The Bk/ACE ratio decrease in patients with uncomplicated PDR and increase significantly in ones with DME. It means that determination of Bk in serum of patients with PDR may be used for the prediction of DME development. The Bk/ACE concentrations ratio may be even more informative.

Reduced serum protease activity in Complex Regional Pain Syndrome: The impact of angiotensin-converting enzyme and carboxypeptidases

Complex Regional Pain Syndrome (CRPS) occurs in about 2% of patients after fracture of the limbs. In an earlier clinical study with 102 probands we have shown that the serum protease network in CRPS might be less effective. Based on these results we hypothesized that angiotensin-converting enzyme (ACE) and carboxypeptidase N (CPN) activity contribute to the differences of labeled bradykinin (DBK) degradation by patients’ sera. Details of the enzymatic processes remained however unclear. The contributions of ACE and CPN in the serum degradation of DBK were studied using specific inhibitors. CPN1-ELISA was performed in serum. It was confirmed that the majority of DBK was degraded by ACE and CPN. The data delivered proof that the ACE serum activity was lowered in CRPS. High-resolution mass spectrometry was additionally used for protein expression analysis of sera of above study cohort (CRPS vs. healthy probands). According to principal component analysis of these data, significant differences between CRPS and control samples only occurred in sera of females younger than 46 years. In these CRPS patients, a number of defence / immunity-related proteins and members of the renin-angiotensin system (RAS) protein network were regulated. The impact of CPN in CRPS pathophysiology is subject to further investigation. The data support the hypothesis that both the RAS and the innate immune system might be affected in CRPS. A database of regulated serum proteins was established for future research.