Serum Angiotensin-converting Enzyme Research Articles

ACE Phenotyping in Human Blood and Tissues: Revelation of ACE Outliers and Sex Differences in ACE Sialylation.

Angiotensin-converting enzyme (ACE) metabolizes a number of important peptides participating in blood pressure regulation and vascular remodeling. Elevated ACE expression in tissues (which is generally reflected by blood ACE levels) is associated with an increased risk of cardiovascular diseases. Elevated blood ACE is also a marker for granulomatous diseases. Decreased blood ACE activity is becoming a new risk factor for Alzheimer's disease. We applied our novel approach-ACE phenotyping-to characterize pairs of tissues (lung, heart, lymph nodes) and serum ACE in 50 patients. ACE phenotyping includes (1) measurement of ACE activity with two substrates (ZPHL and HHL); (2) calculation of the ratio of hydrolysis of these substrates (ZPHL/HHL ratio); (3) determination of ACE immunoreactive protein levels using mAbs to ACE; and (4) ACE conformation with a set of mAbs to ACE. The ACE phenotyping approach in screening format with special attention to outliers, combined with analysis of sequencing data, allowed us to identify patient with a unique ACE phenotype related to decreased ability of inhibition of ACE activity by albumin, likely due to competition with high CCL18 in this patient for binding to ACE. We also confirmed recently discovered gender differences in sialylation of some glycosylation sites of ACE. ACE phenotyping is a promising new approach for the identification of ACE phenotype outliers with potential clinical significance, making it useful for screening in a personalized medicine approach.

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.

Correlation of Mantoux Test and Serum Angiotensin-Converting Enzyme (ACE) Levels with Clinically and Radiologically Diagnosed Ocular Tuberculosis and Ocular Sarcoidosis

Abstract Aim: To evaluate the role of combined Mantoux test and serum angiotensin-converting enzyme (ACE) levels in the diagnosis of ocular tuberculosis (TB) and ocular sarcoidosis. Materials and Methods: A prospective and observational study including patients with bilateral granulomatous uveitis diagnosed both radiologically and clinically as ocular TB or ocular sarcoidosis within a six-month period. CT Thorax/CT abdomen was done, and findings were noted. Mantoux test and serum ACE levels were recorded, and findings were correlated. Results: The study included a total of 60 patients: 32 patients with ocular TB and 28 patients with ocular sarcoidosis. Using Mantoux test, 84.4% in the TB group tested positive and were correctly identified (sensitivity), and 96.4% in the sarcoid group tested negative and were correctly identified as sarcoidosis. Hence, the association between Mantoux test and diagnoses was statistically significant (P < 0.001). In the TB group, 25 subjects had normal and seven had elevated serum ACE levels. In the sarcoidosis group, 22 subjects had elevated and six had normal serum ACE levels. Hence, 78.1% were correctly identified with normal serum ACE levels (sensitivity) in the TB group and 78.6% were identified with elevated serum ACE levels in the sarcoidosis group, and the proportion difference was statistically significant (P < 0.001). Conclusion: Mantoux test and serum ACE levels are cost-effective investigations and can be used for the diagnosis of ocular TB and sarcoidosis when combined with clinical and radiological evidence. The combined use of serum ACE and Mantoux test is useful in differentiating between sarcoidosis and TB.

БИОЛОГИЧЕСКИЕ МАРКЕРЫ ФИБРОЗООБРАЗОВАНИЯ У БОЛЬНЫХ САРКОИДОЗОМ ЛЕГКИХ

Introduction. Sarcoidosis-associated pulmonary fibrosis still lacks biomarkers to predict progression. Whole-genome association studies and other genetic research over the past few years have identified several single nucleotide polymorphisms that are associated with an increased risk of developing pulmonary fi brosis. In sarcoidosis, relatively reliable predictors of the disease activity include serum angiotensin-converting enzyme, soluble interleukin-2 receptor (sIL-2R) and chitotriosidase. Levels of inetrleukin-5 and, possibly, interleukin-7 were found to be elevated in patients with a fibrotic phenotype. Aim. In the present study, we sought to find the relationship between serum non- coding RNA- microRNA expression in patients with pulmonary sarcoidosis and the likelihood of pulmonary fibrosis developing in these patients. Materials and Methods. A total of 52 research subjects (sarcoidosis patients with/without fibrosis and healthy subjects) were included in the study. RNA samples from two groups of sarcoidosis patients (with and without fibrosis) and the control group were analyzed using the PCR Array. TaqMan QRT-PCR Assay was used for data verification. Results and Discussion. A significant decrease in the lung diffusion capacity was detected in 12 of 15 patients with chest-CT fibrosis signs. Lung diffusion capacity was normal in 17 patients without any fibrosis signs. There was a significant negative correlation among miR-15a, miR-150, and the level of lung diffusion capacity. Сonclusions. A set of non-coding RNA- microRNAs, i. e., miR-15a, miR-22, miR-106b, miR-107, and miR-150, was identified that can be further used as diagnostic markers for sarcoidosis fibrosis.

Abstract P130: Higher Circulating Angiotensin Converting Enzyme 2 (ACE2) and ACE2 to ACE Ratio Are Associated With Lower COVID-19 Mortality: A Mechanistic Substudy of the ACTIV-4 Host Tissue Trials

Background: SARS-Cov-2 targets the peptidase ACE2, a key component of the renin-angiotensin system (RAS), which directly regulates the balance of the vasoconstrictor/inflammatory peptide Ang II and the vasodilator/anti-inflammatory peptide Ang-(1-7). Few studies have quantified the circulating elements of the RAS longitudinally in SARS-Cov-2 infection and their association with COVID-19 outcomes. Objective: Evaluate the association of circulating RAS enzymes with mortality in critically ill patients with COVID-19. Methods: We quantified serum ACE and ACE2 concentrations by ELISA among 111 patients hospitalized for confirmed SARS-Cov-2 infection with new onset hypoxemia who were randomized to the placebo arm of the ACTIV-4 Host Tissue trials investigating RAS pathway interventions. Serum was collected at baseline/randomization (Day 0) and 1, 3, and 5 days after randomization. We used multivariable Cox regression to estimate the association of baseline and longitudinal ACE and ACE2 with 90-day mortality. Hazard ratios (HR) for RAS enzyme concentrations were adjusted for age, sex, race/ethnicity, baseline level of O 2 support, obesity, hypertension, RAS inhibitor use prior to admission, and vasopressor use within 7 days of admission. Results: Participants were aged 18-90 (mean [SD] = 55 [14]) years, 62% male, 42% non-White, with 58% and 48% prevalence of obesity and hypertension, respectively. There were 22 (20%) deaths over 90 days of follow-up (median [25%, 75%] time to event = 16 [9, 29] days). Relative to participants with values below the sample median, those with higher Day 0 ACE2 (>4.9 pM; adjusted HR [95% CI] = 0.07 [0.02, 0.33]) and ACE2/ACE ratio (>6.0*10 -3 ; adjusted HR = 0.08 [0.01, 0.39]) had significantly lower mortality. Similarly, when analyzed as continuous, log 2 -normalized, time-varying predictors from Day 0 to Day 5, two-fold increments in ACE2 (adjusted HR = 0.81 [0.69, 0.96]) and ACE2/ACE ratio (adjusted HR = 0.78 [0.64, 0.96]) over this period were associated with lower mortality. Results did not differ by hypertension status (interaction p=0.385 and 0.278 for Day 0 ACE2 and ACE2/ACE ratio, respectively, and p=0.714 and 0.457 for time-varying ACE2 and ACE2/ACE ratio, respectively). In contrast, neither ACE levels at Day 0 (>1.3 nM; adjusted HR = 1.23 [0.41, 3.67]) nor time-varying ACE (adjusted HR = 1.21 [0.75, 1.95]) were associated with mortality. Conclusions: Higher baseline and longitudinal serum ACE2 levels, but not ACE, were associated with markedly reduced mortality among hospitalized patients with COVID-19, consistent with a protective role for ACE2. Whether serum ACE2 levels arise from tissue ACE2 shedding, thus binding less virus to tissue, should be explored further. A better understanding of the RAS timecourse in severe COVID-19 illness could identify patients at greater risk for adverse outcomes and inform targeted treatment strategies.

Anti-Diabetic Potentials ofLactobacillus Strains by Modulating Gut Microbiota Structure and β-Cells Regeneration in the Pancreatic Islets of Alloxan-Induced Diabetic Rats.

Diabetes mellitus, a most common endocrine disorder of glucose metabolism, has become a global epidemic and poses a serious public health threat with an increased socio-economic burden. Escalating incidence of diabetes is correlated with changes in lifestyle and food habits that cause gut microbiome dysbiosis and β-cells damage, which can be addressed with dietary interventions containing probiotics. Hence, the search for probiotics of human origin with anti-diabetic, anti-AGE, and anti-ACE potentials has gained renewed interest for the effective management of diabetes and its associated complications. The present study used an alloxan (AXN)-induced diabetic rat model to investigate the effects of potential probiotic Lacticaseibacillus casei MKU1, Lactiplantibacillus pentosus MKU3, and Lactiplantibacillus plantarum MKU7 administration individually on physiochemical parameters related to diabetic pathogenesis. Experimental animals were randomly allotted into six groups viz. NCG (control), DCG (AXN), DGM (metformin), DGP1 (MKU1), DGP2 (MKU3), and DGP3 (MKU7), and biochemical data like serum glucose, insulin, AngII, ACE, HbA1c, and TNF-α levels were measured until 90days. Our results suggest that oral administration with MKU1, MKU3, or MKU7 significantly improved serum insulin levels, glycemic control, glucose tolerance, and body weight. Additionally, β-cell mass was increased by preserving islet integrity in Lactobacillus-treated diabetic rats, whereas TNF-α (~40%), AngII (~30%), and ACE levels (~50%) were strongly inhibited and enhanced sIgA production (5.8 folds) abundantly. Furthermore, Lactobacillus administration positively influenced the gut microbiome with a significant increase in the abundance of Lactobacillus species and the beneficial Bacteroides uniformis and Bacteroides fragilis, while decreased the pathogenic Proteus vulgaris and Parabacteroides distasonis. Among the probiotic treatment groups, L. pentosus MKU3 performed greatly in almost all parameters, indicating its potential use for alleviating diabetes-associated complications.

Get reliable laboratory findings- how to recognize the deceptive effects of angiotensin-converting enzyme inhibitor therapy in the laboratory diagnostics of sarcoidosis?

Serum angiotensin-converting enzyme (ACE) is the only biomarker routinely used in the laboratory diagnostics of sarcoidosis, and ACE inhibitor (ACEi) drugs are among the most prescribed drugs worldwide. Taking ACEi can mislead medical teams by lowering ACE activity, delaying diagnosis and giving a false impression of disease activity of sarcoidosis. We aimed to develop a simple method to detect the presence of ACEi drugs in samples, to investigate the ACEi medication-caused interference and consequences in a retrospective study. ACE activity and the level of ACE inhibition were determined for 1823 patients with suspected sarcoidosis. These values were compared with the therapeutic information at the first and follow-up visits. A total of 302 patients had biochemical evidence of an ACEi drug effect during diagnostic ACE activity testing. In their case, ACE activity was significantly lower (median(IQR): 4.41 U/L(2.93-6.72)) than in patients not taking ACEi (11.32 U/L(8.79-13.92), p<0.01). In 62 sarcoidosis patients, the ACEi reduced ACE activity to the reference range or below. Only in 40 % of the cases was the medication list recorded in the outpatient chart and only in 3 cases was low ACE activity associated with ACEi use. 67 % of the repeated ACE activity measurements were also performed during ACEi therapy. Our study revealed that the use of ACEi is common in patients with suspected sarcoidosis. The ACE activity lowering effect of ACEi drugs may escape the attention of medical teams which can lead to diagnostic errors and unnecessary tests. Nevertheless, these pitfalls can be avoided by using a method suggested by our team.

Soluble mannose receptor: A potential biomarker in Gaucher disease.

Soluble mannose receptor (sMR) relates to mannose receptor expression on macrophages, and is elevated in inflammatory disorders. Gaucher disease (GD) has altered macrophage function and utilises mannose receptors for enzyme replacement therapy (ERT) endocytosis. sMR has not previously been studied in GD. sMR was measured by ELISA and correlated with GD clinical features including spleen and liver volume, haemoglobin and platelet count, bone marrow burden (BMB) scores and immunoglobulin levels. sMR was compared with biomarkers of GD: chitotriosidase, lyso-GL1, PARC, CCL3, CCL4, osteoactivin, serum ACE and ferritin. Median sMR in untreated GD patients was 303.0 ng/mL compared to post-treatment 190.9 ng/mL (p = .02) and healthy controls 202 ng/mL. Median sMR correlated with median spleen volume 455 mL (r = .70, p = .04), liver volume 2025 mL (r = .64, p = .04), BMB 7 (r = .8, p = .03), IgA 1.9 g/L (r = .54, p = .036), IgG 9.2 g/L (r = .57, p = .027), IgM 1.45 g/L (r = .86, p < .0001), with inverse correlation to median platelet count of 125 × 109/L (r = -.47, p = .08) and haemoglobin of 137 g/L (r = -.77, p = .0008). sMR correlated with established biomarkers: osteoactivin 107.8 ng/mL (r = .58, p = .0006), chitotriosidase 3042 nmol/mL/h (r = .52, p = .0006), PARC 800 ng/mL (r = .67, p = .0068), ferritin 547 μg/L (r = .72, p = .002) and CCL3 50 pg/mL (r = .67, p = .007). sMR correlates with clinical features and biomarkers of GD and reduces following therapy.

O03 Sarcoidosis in a Boy with Severe Eczema on Dupilumab

Abstract Sarcoidosis, a systemic granulomatous disease of unknown aetiology, is rare in children. Presentation varies according to the extent and severity of organ involvement and is typically multisystem in older children. Drug induced sarcoidosis-like reaction (DISR) has recently been reported in patients taking Dupilumab. We describe a patient who developed sarcoidosis while on Dupilumab and question whether this was caused by the drug. A 14-year-old boy with severe eczema developed widespread cutaneous nodules and papules after 30 months on Dupilumab. Histology showed non-caseating granulomas. A raised serum angiotensin converting enzyme level, asymptomatic coarse interstitial markings on chest x-ray and small lung nodules on CT scan were also consistent with sarcoidosis. Dupilumab was stopped and hydroxychloroquine and methotrexate commenced. Joint and liver involvement developed 4 months later so systemic glucocorticoids were and the methotrexate was changed to mycophenolate mofetil. To our knowledge there have been 3 previous reports of DISR on Dupilumab. The clinical picture is almost indistinguishable from sarcoidosis. In this case continuing evolution of sarcoidosis 4 months after stopping Dupilumab argues against DISR. However, as Dupilumab becomes more widely used, it is important to be alert to the possibility of new adverse reactions.

Rare manifestations of sarcoidosis in a young boy

Sarcoidosis is a chronic multisystem granulomatous disease of unknown etiology. It is rare in young children. A 9-year-old boy presented with failure to thrive, skin rashes, persistent fever and respiratory symptoms since 5 years of age. Blood investigations done showed elevated serum calcium and angiotensin converting enzyme (ACE) levels and biopsy of the rashes on the left shin revealed non-caseating granulomatous lesion. Computed tomography (CT) of chest revealed interstitial lung disease (ILD) and examination of eyes showed bilateral uveitis. He also had sensorineural hearing impairment, nephrocalcinosis and short stature. The patient was treated with oral steroids and mycophenolate mofetil. At follow up there was improvement in his systemic features including rashes and arthritis. Early detection, diagnosis and appropriate treatment of sarcoidosis are vital for disease control and to avoid morbidity.

The association of ACE gene polymorphism and serum ACE levels with diabetic nephropathy-a cross-sectional study

Diabetic nephropathy (DN) is the microvascular complication of type-2 diabetes that leads to end-stage renal disease. The angiotensin-converting enzyme gene that is a part of the renin-angiotensin-aldosterone system is considered one of the candidate genes responsible for the genetic predisposition of DN. To compare serum angiotensin converting enzyme (ACE) levels, the pattern of ACE gene polymorphism in patients with type-2 diabetes with or without nephropathy, to find the association between ACE gene polymorphism and various stages of DN, the association between serum ACE levels and various stages of DN. We enrolled 108 patients diagnosed with type-2 diabetes and 108 DN patients. Serum levels were estimated by ELISA and gene polymorphism was performed with gene sequencing. It was found that the serum ACE levels were higher in DN patients than in type-2 diabetics although the p-value was not significant. There was no significant association between serum ACE levels and various stages of nephropathy. The wild (GG genotype) distribution was more predominant in type-2 diabetic patients than in DN patients. There was a significant difference in the frequency of genotype with various stages of nephropathy and estimated glomerular filtration rate which was statistically significant (p = 0.0018). In summary, the study did not find a significant association between serum ACE levels and DN, nor did it observe a substantial impact of ACE gene polymorphism on serum ACE levels in DN patients. The findings also indicated that the ACE gene polymorphism might not have a direct influence on albuminuria stages. However, the wild-type genotype showed a trend toward protection against albuminuria development, while the carrier patients had a higher prevalence of severe albuminuria. Further research with larger sample sizes and longitudinal studies may provide deeper insights into the role of serum ACE levels and ACE gene polymorphism in the development and progression of DN.

The Relationship between Serum ACE Level and Disease Severity in Patients Hospitalized Due To COVID-19 pneumonia

The Relationship between Serum ACE Level and Disease Severity in Patients Hospitalized Due To COVID-19 pneumonia

The role of serum and bronchoalveolar lavage fluid chitotriosidase activity on diagnosis, disease characteristics and prognosis of sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease with an unpredictable clinical course. Chitotriosidase is a chitinase mainly expressed by activated macrophages. Increased chitotriosidase activity has been reported in serum and bronchoalveolar lavage (BAL) of sarcoidosis patients compared to healthy controls. This study aims to evaluate the role of serum and BAL chitotriosidase activity on diagnosis, disease characteristics, and prognosis of sarcoidosis. Patients referred with suspected sarcoidosis or other interstitial lung disease were prospectively included in the study. All patients underwent bronchoscopy with BAL. Serum and BAL chitotriosidase activity, BAL differential cell counts, and lymphocyte phenotypes were determined. Sarcoidosis patients were followed up regularly. Forty-two sarcoidosis and 28 non-sarcoidosis patients were included in the study. Serum chitotriosidase activity was higher in sarcoidosis group 247.5 (2.78-461) vs 108 (2.78-272) nmol/h/mL (p< 0.001). BAL chitotriosidase activity tended to be higher in sarcoidosis group 11 (2-308) vs 6.95 (2.27-44) nmol/h/mg but was not found to be statistically significant (p= 0.11). Serum and BAL chitotriosidase activities were correlated with each other (p= 0.023, r= 0.355). No significant difference was found between the diagnostic performance of BAL CD4/CD8 ratio and serum chitotriosidase activity (p= 0.079). Serum chitotriosidase and ACE activities were correlated with each other (p= 0.004, r= 0.457). No significant difference was found between serum or BAL chitotriosidase activity and stage or extrapulmonary involvement. Serum chitotriosidase activity was higher in patients who needed systemic therapy at diagnosis (p= 0.046). However, no significant difference was found between serum or BAL chitotriosidase activities and disease progression (p= 0.395 and p= 0.723, respectively). Serum chitotriosidase activity can be helpful in the differential diagnosis of sarcoidosis with a similar diagnostic performance with BAL CD4/CD8 ratio. Although serum chitotriosidase activity at diagnosis does not predict progressive disease, it is associated with the need for systemic therapy at diagnosis. Serial chitotriosidase measurements may be useful in monitoring disease progression during follow-up.

Evaluation of Renin Level and Some Hormones in Patients with Polycystic Ovarian Syndrome

Polycystic Ovarian Syndrome (PCOS) is one of the most frequent gynecological endocrinopathy that occurs in premenopausal females. This study aimed to investigate the relationship between PCOS and Renin Angiotensin Aldosteron system, by measuring the levels of renin, ACE, Kallikren5, FSH and LH in follicular and luteal phase, in addition to evaluating the level of kallikrein 5, which belongs to the kallikrein-kinin system associated with the renin system. The renin-angiotensin system (RAS) is well known as regulator of electrolytes and blood pressure. Renin is previously considered a major enzyme in this system. The study included 90 blood samples for married women of childbearing age between (18-45) years. These samples included 70 samples for women with polycystic ovary syndrome, which were divided into two groups (35 samples in each one), the first was withdrawn in the follicular phase, named PA, and the second in the luteal phase of the menstrual cycle named PB. As for the remaining 20 samples, they represented the control group of healthy women, which were also divided into two groups (CA and CB) as happened with the patient group. In this study, the levels of serum Renin, ACE, LH, FSH and Kallikren5 were evaluated in PCOS patients and compared with the control group in both phases. The results were analyzed by T-Test and ROC. There were no significant differences between patients and the control group in terms of ACE activity or FSH (P&gt;0.05). The results demonstrated that LH, Renin, and Kallikren5 were higher in patient group in both phases (P&lt;0.05). Renin Angiotensin system was affected by PCOS.

Prognosis of sarcoidosis and factors affecting prognosis.

Sarcoidosis is a multi-system disease of unknown etiology characterized by non-caseating granulomatous inflammation. Determining the characteristics and prognosis of sarcoidosis cases and revealing the factors that may affect the prognosis are important for approach to patient. This study was planned to obtain prognosis data for our country and to determine the factors affecting the prognosis. 188 patients, followed regularly for three years or more, admitted to Ankara University Faculty of Medicine, Department of Chest Diseases between 2012-2017 were evaluated retrospectively. Increased radiological findings, functional impairment and any of the clinical conditions requiring initiation/modification of treatment were accepted as progression. Clinical status of the patients at the last follow-up was defined as remission with treatment, spontaneous remission, stable disease, progression, chronic case and recurrence. Spontaneous remission and remission with treatment, regression, stable disease, and recurrence that followed without treatment and didn't cause symptom or functional impairment were accepted in good prognosis group. Progression, chronic cases that couldn't be followed without treatment and recurrence requiring treatment were included in poor prognosis group. 58% of patients was accepted in good prognosis and 42% had poor prognosis group. During follow-up, spontaneous remission rate was 20.2%, pulmonary hypertension development rate was 10.6% and mortality rate was 4.25%. Low radiological stage, high spirometry and diffusion capacity values, being asymptomatic and having no previous treatment were associated with spontaneous remission and good prognosis. Increase in serum angiotensin converting enzyme and C-reactive protein and decrease in spirometry parameters and diffusion capacity values were associated with progression.

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) &gt; roasted blended grains (RBG) &gt; 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.

Concurrent features of sarcoidosis and hypersensitivity pneumonitis in two patients exposed to fungal antigens

BackgroundSarcoidosis and hypersensitivity pneumonitis (HP) are two distinct clinical entities that share granulomatous inflammation, although each of them has specific clinical, radiologic and pathologic profiles. Coexistence of the two diseases have been described, suggesting, at least in some cases, a common biologic background.Case presentationWe describe two patients showing the concurrent diagnosis of sarcoidosis and hypersensitivity pneumonitis. Case 1: a 51-year old never smoker man had a history of occupational exposure, episodes of acute exacerbations and positive serum precipitins to Penicillium spp suggestive of HP, while the positivity of serum angiotensin converting enzyme (ACE) favored sarcoidosis. Case 2: a 42-year old non-smoker woman with occasional finding of enlarged mediastinal lymph nodes had a history of domestic exposure to molds and positive serum precipitins to Aspergillus spp suggestive of HP.In both cases high resolution computed tomography (HRCT) together with broncoscopy findings allowed to maintain both the diagnoses: HRCT showed both enlarged hilar/mediastinal limph nodes and intersitial lung involvement typical of HP; bronchoalveolar lavage presented marked lymphocytosis and granulomatous nodal lesions were observed at transbronchial needle aspiration.ConclusionsSarcoidosis and HP share some clinical findings and the differential diagnosis may be difficult. Our cases suggest that a common trait may be responsible for the concurrent diagnosis of sarcoidosis and hypersensitivity pneumonitis in the same patient.

Increased circulating interleukin-23 level in patients with sarcoidosis

BackgroundSarcoidosis is a Th1-mediated chronic inflammatory disease characterized by non-caseating granulomas. Its pathogenesis is not yet clear, but the possible role of various proinflammatory cytokines is being discussed. AimThis study aims to determine serum cytokine (IL-6, IL-12, IL-17, and IL-23) levels in patients with sarcoidosis, and to determine a possible correlation with clinical and laboratory findings of the disease. Material and methodForty-four biopsy-proven sarcoidosis patients followed up at a single centre and 41 healthy volunteers were included in the study. Demographic, clinical, laboratory, and radiological data of all patients were recorded. Serum samples from the patients and the control group were taken and IL-6, IL-12, IL-17, IL-23 were measured by ELISA method. ResultsOf the 44 sarcoidosis patients, 13(29.5%) were male and 31(70.5%) were female. Average patient age was 47.4 years, mean disease duration was 3.2 years. Twenty-one (47.7%) patients had erythema nodosum, three (6.8%) had uveitis, 40(90.9%) had arthralgia, 23(52.3%) had ankle arthritis, 15(34.1%) had enthesitis. Laboratory evaluation showed increased serum ACE levels in 24(54.5%) patients, increased serum calcium levels in 11 (25%) patients, increased serum D3 levels in 5(11.4%) patients, increased ESR and CRP levels in 22(50%) and 23(52.3%) patients, respectively. Compared with the control group higher serum IL-23 levels were found in the patients with sarcoidosis (p=.01). Serum IL-23 was associated with ankle arthritis (p=.02). Serum IL-6, IL-12, and IL-17 levels were similar in the sarcoidosis patients and the control group (p=.128, p=.212, p=.521 respectively). ConclusionIn our study, we found increased serum IL-23 in patients with sarcoidosis, while serum IL-6, IL-12, and IL-17 were detected as normal. Although our results are somewhat contradictory to other studies in the literature, the question should still be whether sarcoidosis is a Th1/Th17 disease. Multicentre studies are needed in this regard.

Serum Level of Ceruloplasmin, Angiotensin-Converting Enzyme and Transferrin as Markers of Severity in SARS-CoV-2 Infection in Patients with Type 2 Diabetes

The aim of this study was to analyze other possible new markers of severity, at hospital admission, that can be assessed in patients with type 2 diabetes and a SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. Our study included 90 subjects: 45 patients with type 2 diabetes mellitus infected with the SARS-CoV-2 virus, and 45 healthy persons as controls. The serum level of ceruloplasmin at hospital admission was statistically significant and directly correlated with the severity of COVID-19 (coronavirus disease) (p = 0.037) and with the serum level of IL-6 (interleukin 6) (p = 0.0001). Ceruloplasmin was statistically significant and inversely correlated with the serum iron level (p = 0.0001). However, we observed that ACE (angiotensin-converting enzyme) decreased in severe forms of SARS-CoV-2 infections in patients with type 2 diabetes (p = 0.001). Moreover, the decrease in ACE levels was correlated with an increase in IL-6 levels in these patients (p = 0.001). IL-6 increases were statistically significant and inversely correlated with serum iron, transferrin, and ACE levels. There was a noticed decreasing tendency of the transferrin depending on the severity of the COVID-19 infection (p = 0.0001). In addition to the known severity factors in the context of infection with the new coronavirus, increased concentrations of ceruloplasmin and decreased concentrations of ACE and transferrin may represent new markers of COVID-19 severity in patients with type 2 diabetes. These parameters, if analyzed upon admission to the hospital, could better inform health professionals about the evolution towards more severe forms of SARS-CoV-2 infections.

Effect of tofacitinib therapy on angiotensin converting enzyme activity in rheumatoid arthritis.

The Renin-Angiotensin-Aldosterone system (RAAS) has been implicated in the regulation of the cardiovascular system and linked to rheumatoid arthritis (RA). Little information has become available on the effects of Janus kinase (JAK) inhibition on RAAS. Here we studied the effects of 12-month tofacitinib treatment on angiotensin converting enzyme (ACE), ACE2 production and ACE/ACE2 ratios in RA along with numerous other biomarkers. Thirty RA patients were treated with tofacitinib in this prospective study. Serum ACE concentrations were assessed by ELISA. ACE2 activity was determined by a specific quenched fluorescent substrate. ACE/ACE2 ratios were calculated. We also determined common carotid intima-media thickness (ccIMT), brachial artery flow-mediated vasodilation (FMD) and carotid-femoral pulse-wave velocity (cfPWV) by ultrasound. C-reactive protein (CRP), rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPA) were also determined. All measurements were performed at baseline, as well as after 6 and 12 months of tofacitinib treatment. After the dropout of 4 patients, 26 completed the study. Tofacitinib treatment increased ACE levels after 6 and 12 months, while ACE2 activity only transiently increased at 6 months. The ACE/ACE2 ratio increased after 1 year of therapy (p < 0.05). Logistic regression analyses identified correlations between ACE, ACE2 or ACE/ACE2 ratios and RF at various time points. Baseline disease duration also correlated with erythrocyte sedimentation rate (ESR) (p < 0.05). One-year changes of ACE or ACE2 were determined by tofacitinib treatment plus ACPA or RF, respectively (p < 0.05). JAK inhibition increases serum ACE and ACE/ACE2 ratio in RA. Baseline inflammation (ESR), disease duration and ACPA, as well as RF levels at various time points can be coupled to the regulation of ACE/ACE2 ratio. The effect of tofacitinib on RAAS provides a plausible explanation for the cardiovascular effects of JAK inhibition in RA.