Elevated 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.

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.

Chronic hypoxia impairs skeletal muscle repair via HIF-2α stabilization.

Chronic hypoxia and skeletal muscle atrophy commonly coexist in patients with COPD and CHF, yet the underlying physio-pathological mechanisms remain elusive. Muscle regeneration, driven by muscle stem cells (MuSCs), holds therapeutic potential for mitigating muscle atrophy. This study endeavours to investigate the influence of chronic hypoxia on muscle regeneration, unravel key molecular mechanisms, and explore potential therapeutic interventions. Experimental mice were exposed to prolonged normobaric hypoxic air (15% pO2, 1atm, 2weeks) to establish a chronic hypoxia model. The impact of chronic hypoxia on body composition, muscle mass, muscle strength, and the expression levels of hypoxia-inducible factors HIF-1α and HIF-2α in MuSC was examined. The influence of chronic hypoxia on muscle regeneration, MuSC proliferation, and the recovery of muscle mass and strength following cardiotoxin-induced injury were assessed. The muscle regeneration capacities under chronic hypoxia were compared between wildtype mice, MuSC-specific HIF-2α knockout mice, and mice treated with HIF-2α inhibitor PT2385, and angiotensin converting enzyme (ACE) inhibitor lisinopril. Transcriptomic analysis was performed to identify hypoxia- and HIF-2α-dependent molecular mechanisms. Statistical significance was determined using analysis of variance (ANOVA) and Mann-Whitney U tests. Chronic hypoxia led to limb muscle atrophy (EDL: 17.7%, P<0.001; Soleus: 11.5% reduction in weight, P<0.001) and weakness (10.0% reduction in peak-isometric torque, P<0.001), along with impaired muscle regeneration characterized by diminished myofibre cross-sectional areas, increased fibrosis (P<0.001), and incomplete strength recovery (92.3% of pre-injury levels, P<0.05). HIF-2α stabilization in MuSC under chronic hypoxia hindered MuSC proliferation (26.1% reduction of MuSC at 10 dpi, P<0.01). HIF-2α ablation in MuSC mitigated the adverse effects of chronic hypoxia on muscle regeneration and MuSC proliferation (30.9% increase in MuSC numbers at 10 dpi, P<0.01), while HIF-1α ablation did not have the same effect. HIF-2α stabilization under chronic hypoxia led to elevated local ACE, a novel direct target of HIF-2α. Notably, pharmacological interventions with PT2385 or lisinopril enhanced muscle regeneration under chronic hypoxia (PT2385: 81.3% increase, P<0.001; lisinopril: 34.6% increase in MuSC numbers at 10 dpi, P<0.05), suggesting their therapeutic potential for alleviating chronic hypoxia-associated muscle atrophy. Chronic hypoxia detrimentally affects skeletal muscle regeneration by stabilizing HIF-2α in MuSC and thereby diminishing MuSC proliferation. HIF-2α increases local ACE levels in skeletal muscle, contributing to hypoxia-induced regenerative deficits. Administration of HIF-2α or ACE inhibitors may prove beneficial to ameliorate chronic hypoxia-associated muscle atrophy and weakness by improving muscle regeneration under chronic hypoxia.

Sarcoidosis Masquerading as Miliary Tuberculosis: A Case Report

A miliary nodular pattern of the lungs is an unusual presentation of sarcoidosis. Diagnosis of this condition can be challenging and requires exclusion of other lung pathology. A 47-year-old African American male presented to his doctor with a complaint of unintentional weight loss, exertional dyspnea and cough. The patient had a history of chronic smoking as well as recent incarceration. A miliary nodular pattern was found on CT scan of the lungs in a random distribution (with prominent peri-lymphatic distribution). HIV was ruled out. Tuberculosis (TB) and fungal infections were ruled out by tissue specimens and cultures from bronchoalveolar washings. Non-caseating granulomas on tissue specimens, peripheral smear lymphopenia and an elevated angiotensin converting enzyme (ACE) level were the positive findings on pathology and labs. The patient responded to a tapering course of oral steroids. This case demonstrates one of the unusual clinical presentations of sarcoidosis. Sarcoidosis is an autoimmune condition with predilection for middle aged African American patients.

Exposure to low dose of Bisphenol A (BPA) intensifies kidney oxidative stress, inflammatory factors expression and modulates Angiotensin II signaling under hypertensive milieu.

Humans are constantly exposed to low concentrations of ubiquitous environmental pollutant, Bisphenol A (BPA). Due to the prevalence of hypertension (one of the major risk factors of cardiovascular disease [CVD]) in the population, it is necessary to explore the adverse effect of BPA under hypertension associated pathogenic milieu. The current study exposed the Nω-nitro-l-arginine methyl ester (L-NAME) induced hypertensive Wistar rats to low dose BPA (50 μg/kg) for 30 days period. In tissue samples immunohistochemistry, real-time quantitative polymerase chain reaction and enzymatic assays were conducted. Moreover, studies on primary kidney cell culture were employed to explore the impact of low dose of BPA exposure at nanomolar level (20-80 nM range) on renal cells through various fluorescence assays. The observed results illustrate that BPA exposure potentiates/aggravates hypertension induced tissue abnormalities (renal fibrosis), oxidative stress (ROS generation), elevated angiotensin-converting enzyme activity, malfunction of the antioxidant and tricarboxylic acid cycle enzymes, tissue lipid abnormalities and inflammatory factor expression (both messenger RNA and protein level of TNF-α and IL-6). Further, in vitro exposure of nM levels of BPA to primary kidney cells modulates oxidative stress (both superoxide and total ROS), mitochondrial physiology (reduced mitochondrial transmembrane potential-∆ψm) and lipid peroxidation in a dose dependent manner. In addition, angiotensin II induced ROS generation was aggravated further by BPA during coexposure in kidney cells. Therefore, during risk assessment, a precise investigation on BPA exposure in hypertensive (CVD vulnerable) populations is highly suggested.

A Rare Case of Sarcoidosis Presenting as an Isolated Breast Mass and Pain: A Case Report and Literature Review.

BACKGROUND Sarcoidosis is a benign systemic granulomatous disorder of unknown etiology that affects multiple organs. Patients diagnosed with sarcoidosis usually present with nonspecific symptoms: fatigue, fever, weight loss, and respiratory symptoms such as cough and dyspnea; 50% of the patients are asymptomatic at the time of diagnosis. In 90% of patients, sarcoidosis targets hilar and mediastinal lymph nodes. In rare cases, it presents solely in the breast with no other symptoms. The diagnosis is established based on compatible clinical and radiological findings and supported by histological evidence in 1 or more organs of non-caseating epithelioid cell granulomas in the absence of organisms or particles. CASE REPORT We herein present a unique case of a 27-year-old woman who presented with pain and swelling in her left breast. On examination, the left breast revealed multiple, firm-hard, and tender masses. Breast ultrasound showed large loculated focally dilated ducts with significant periductal vascularity and inflammation. Fine-needle aspiration (FNA) showed an inflammatory process with granulomatous formation. An ultrasound-guided core biopsy, which was histologically consistent with granulomatous mastitis, and elevated angiotensin-converting enzyme (ACE) levels confirmed a diagnosis of sarcoidosis. The patient was started on IV steroids followed by oral prednisolone and azathioprine. During treatment, the mass size decreased and the pain substantially improved. CONCLUSIONS It is important to consider sarcoidosis in a patient who presents with only pain and swelling in the breast to ensure early diagnosis and initiate treatment, improving the patient's overall prognosis.

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.

Serum Angiotensin-Converting Enzyme Methylation Level and Its Significance in Patients With Comorbid Major Depressive Disorder and Hypertension.

Major depressive disorder (MDD) often coexists with hypertension (HYT). DNA methylation has elicited vital functionality in their development. Angiotensin-converting enzyme (ACE) is a vital enzyme in blood pressure. This study investigated the effect of ACE methylation on depression and HYT severity in patients with comorbid MDD and HYT (MDD + HYT). A total of 119 patients (41 men, 78 women, average age: 56.8 ± 9.1 years) with MDD + HYT were enrolled, with 89 healthy subjects (29 men, 60 women, average age: 57.4 ± 9.7 years) were enrolled. The Hamilton Depression Rating Scale-17 and self-rating depression scale scoring scales were used to assess the depression degree of patients, serum ACE methylation level in MDD + HYT patients was measured by means of bisulfite sequencing polymerase chain reaction, with subsequent analysis of the diagnostic efficacy of ACE methylation for MDD + HYT. The independent risk factors for sMDD + HYT were explored. Serum ACE methylation levels were significantly increased in MDD + HYT patients. The area under the curve of serum ACE methylation level for accurate diagnosis of MDD + HYT was 0.8471, and the cut-off value was 26.9 (sensitivity 83.19%, specificity 73.03%). ACE methylation was an independent risk factor for sMDD + HYT (P = 0.014; odds ratio, 1.071; 95% confidence interval = 1.014-1.131). The elevated serum ACE methylation level (P < 0.001) in patients with MDD + HYT elicited definite diagnostic values for MDD + HYT, and ACE methylation level was independently correlated with sMDD + HYT (P < 0.05).

Blood ACE Phenotyping for Personalized Medicine: Revelation of Patients with Conformationally Altered ACE.

Background: The angiotensin-converting enzyme (ACE) metabolizes a number of important peptides participating in blood pressure regulation and vascular remodeling. Elevated blood ACE is a marker for granulomatous diseases and elevated ACE expression in tissues is associated with increased risk of cardiovascular diseases. Objective and Methodology: We applied a novel approach -ACE phenotyping-to find a reason for conformationally impaired ACE in the blood of one particular donor. Similar conformationally altered ACEs were detected previously in 2-4% of the healthy population and in up to 20% of patients with uremia, and were characterized by significant increase in the rate of angiotensin I hydrolysis. Principal findings: This donor has (1) significantly increased level of endogenous ACE inhibitor in plasma with MW less than 1000; (2) increased activity toward angiotensin I; (3) M71V mutation in ABCG2 (membrane transporter for more than 200 compounds, including bilirubin). We hypothesize that this patient may also have the decreased level of free bilirubin in plasma, which normally binds to the N domain of ACE. Analysis of the local conformation of ACE in plasma of patients with Gilbert and Crigler-Najjar syndromes allowed us to speculate that binding of mAbs 1G12 and 6A12 to plasma ACE could be a natural sensor for estimation of free bilirubin level in plasma. Totally, 235 human plasma/sera samples were screened for conformational changes in soluble ACE. Conclusions/Significance: ACE phenotyping of plasma samples allows us to identify individuals with conformationally altered ACE. This type of screening has clinical significance because this conformationally altered ACE could not only result in the enhancement of the level of angiotensin II but could also serve as an indicator of free bilirubin levels.

Utility of angiotensin-converting enzyme and serum calcium levels in cutaneous sarcoidosis.

Sarcoidosis is a granulomatous disease of unknown etiology but is theorized to result from immune overactivity in the setting of an environmental or genetic trigger. It most commonly affects the lungs and lymph nodes but can affect other organ systems, with cutaneous involvement in 30% of patients. The granulomas associated with sarcoidosis lead to increased activity of angiotensin-converting enzyme (ACE) and 1α-hydroxylase resulting in an uncontrolled synthesis of 1,25-dihydroxyvitamin D3 by macrophages, along with elevated serum ACE and calcium levels. Serum ACE and calcium levels are frequently ordered when a patient is diagnosed with cutaneous sarcoidosis. However, their clinical utility in this setting remains unknown. In this retrospective chart review, we assessed serum ACE and calcium levels in 19 patients with cutaneous sarcoidosis diagnosed by histopathology without preceding evidence of systemic involvement. Serum ACE and calcium levels were also investigated as markers in the progression from mono-organ cutaneous sarcoidosis to systemic sarcoidosis. No patients with biopsy-proven cutaneous sarcoidosis had abnormal levels of serum calcium at presentation in a cohort of 17 patients at a single institution. An abnormally elevated ACE level was only seen in one of 13 patients presenting with cutaneous sarcoidosis. Our data suggest that serum ACE and calcium levels are not reliable markers of either cutaneous sarcoidosis or the progression to systemic sarcoidosis.

RF30 | PSAT177 A Case of Hypercalcemia Related to Immune Checkpoint Inhibitor-Induced Sarcoidosis-like Granuloma

Abstract Background Immune checkpoint inhibitor (ICI) is an essential part of the treatment of various advanced cancers, but its use can be associated with a number of side effects, including hypercalcemia. The mechanism through which hypercalcemia arises is not well established. One proposed mechanism is through sarcoidosis-like reactions. Here we present an illustrative case. Clinical Case A 75-year-old female with past medical history notable for stage IV endometrial adenocarcinoma treated with surgery plus adjuvant chemotherapy, presently on pembrolizumab for 9 months, hypertension, and diabetes was admitted with generalized fatigue, difficulty ambulating, slow movements, and slow speech. Stroke was ruled out with negative neurologic imaging. Blood work revealed elevated calcium 13.8 mg/dL (8.6-10.4 mg/dL) and ionized calcium 1.64 mmol/L (1.09-1.29 mmol/L). Additional workup showed suppressed PTH 7 pg/mL (11-51 pg/mL), 25-OH vitamin D 19 ng/mL (20-50 ng/mL), elevated 1,25(OH)2 vitamin D of 114 pg/mL (19.9-79.3 pg/mL), elevated angiotensin converting enzyme (ACE) level 90 U/L (12-69 U/L), and normal PTHrP, suggestive of PTH-independent hypercalcemia mediated by 1,25(OH)2D as seen in sarcoidosis. Two months prior to admission and seven months after starting pembrolizumab, surveillance CT found improvement in tumor burden but new intrathoracic lymphadenopathy. Lymph node biopsy via bronchoscopy identified non-caseating granulomas suggestive of a sarcoidosis-like reaction. The patient's moderate hypercalcemia was treated with intravenous fluids, calcitonin, and zoledronic acid 4 mg with normalization of calcium levels. Glucocorticoid therapy was initially deferred to avoid counteracting the effect of pembrolizumab, however prednisone 10 mg daily was started 1 month after discharge when calcium rose again to 11.1 mg/dL. Prednisone was tapered off over 8 weeks as her calcium and 1,25(OH)2D levels normalized. She then restarted pembrolizumb, but after the third month she had recurrence of hypercalcemia (calcium 10.8 mg/dL) with elevated 1,25(OH)2D (89.5 pg/mL). She was again treated with prednisone 10 mg daily which was tapered off over 6 weeks with resolution of hypercalcemia. Her calcium levels remained normal off pembrolizumab. The temporal correlation in our case strongly suggests that ICI administration caused sarcoidosis-like granulomas and hypercalcemia. Conclusion Immune checkpoint inhibitors are known to occasionally cause hypercalcemia, although the mechanisms are not well established. In our case, moderate hypercalcemia was likely caused by ICI-induced sarcoid-like granulomas that responded promptly to glucocorticoids and interruption of ICI-therapy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.

ODP593 Thyroid sarcoidosis: case study and literature review

Abstract Introduction Sarcoidosis is a disorder characterized by noncaseating granulomas, most commonly in the lungs, lymph nodes, and skin. Patients often present with cough, skin or eye changes, enlarged lymph nodes, fatigue, or are found to have incidental findings on chest imaging. While any organ can be involved, thyroid involvement is rare, reportedly seen postmortem in 4.2 to 4.6% of sarcoidosis cases. We describe the case of a young adult male with thyroid sarcoidosis in addition to neurosarcoidosis. Case Presentation A 37-year old African American male was found to have a goiter on routine examination. Work up revealed an elevated TSH level of 11.1 uIU/mL (0.4-4. 0) with a free T4 of 0.91 ng/dL (0.7-1.9). Thyroid ultrasound demonstrated a dominant right-sided thyroid mass measuring 5.5×3.1×4.1 cm. Fine needle aspiration cytology reported polymorphic lymphocytes, few lymphohistiocytic aggregates, scant hurthle cells, and multinucleated giant cells. Thyroidectomy was recommended; intra-operatively the right thyroid lobe contained a 5-cm firm, hard, whitish mass in the mid inferior portion which could not be excised due to extensive fibrosis. Incisional biopsy was performed demonstrating fibrotic lymphocytic thyroiditis and non-caseating granulomas with no evidence of malignancy. He presented to the ER six weeks later with confusion, headaches, retro-orbital pain, and periodic involuntary movements in all extremities. MRI of the brain showed dural-based lesion in the right lateral and inferior temporal fossa. He underwent craniotomy and excisional biopsy of the lesion, which showed granulomatous inflammation, favoring a diagnosis of neurosarcoidosis. In a future admission, he was found to have dural venous sinus occlusion and new granulomas on brain MRI. It was then noted that previous thyroid biopsy revealed granulomatous disease, which was then linked to his sarcoidosis. He was discharged on prednisone and methotrexate with eventual further neurological complications. Discussion Thyroid sarcoidosis is very rare and because of this, it is frequently misdiagnosed initially and fine needle aspiration of the thyroid is frequently nondiagnostic. Histopathology is usually necessary to rule out malignancy and identify non-caseating granulomas. In some reported cases, thyroid sarcoidosis shared clinical, ultrasonographic, and even cytologic features with papillary thyroid cancer. Our case was unique for several reasons. Firstly, although not immediately noted, incisional thyroid biopsy was the first diagnostic clue of sarcoidosis. More commonly, patients are already diagnosed with systemic sarcoidosis. Additionally, typical findings such as mediastinal hilar adenopathy, hypercalcemia, and elevated angiotensin converting enzyme levels were absent. Although sarcoidosis of the thyroid is rare and often benign, it is important to consider this differential diagnosis while ruling out more likely causes as early detection can lead to early treatment and prevent adverse outcomes. The ideal treatment remains unclear, regarding whether to treat pharmacologically or concurrently with surgical intervention. Presentation: No date and time listed

UNCOMMON CAUSES OF RECURRENT UNILATERAL PLEURAL EFFUSIONS

UNCOMMON CAUSES OF RECURRENT UNILATERAL PLEURAL EFFUSIONS

Asthma and COVID-19 pandemic: focus on the eosinophil count and ACE2 expression.

Currently, the world is engaged with a coronavirus disease 2019 (COVID-19) caused by acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection. The Center for Disease Control and Prevention (CDC) has proposed moderate to severe asthma as a risk factor for COVID-19 susceptibility and severity. However, current evidences have not identified asthma in the top 10 comorbidities associated with COVID-19 fatalities. It raises the question that why patients with different type of asthma are not more vulnerable to SARS-CoV-2 infection like other respiratory infection. Increased number of eosinophils and elevated angiotensin-converting enzyme 2 (ACE2) expressions in asthma are supposed as two mechanisms which associated with decreased COVID-19 susceptibility in asthmatics. Some studies have been performed to evaluate two mentioned factors in asthmatic patients compared with healthy individuals. Herein, we address these mechanisms and investigate whether ACE2 and eosinophil could protect asthmatic patients against SARS-CoV-2 infection.

Elevated angiotensin-converting enzyme 2 (ACE2) expression in cats with hypertrophic cardiomyopathy

Angiotensin-converting enzyme 2 (ACE2) is an enzyme within the renin-angiotensin-aldosterone system that plays a role in regulating blood pressure. However, it is also a cellular receptor for infection with SARS coronaviruses. Although most cats develop subclinical or mild disease following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) acquired from human patients, a previous study has suggested hypertrophic cardiomyopathy (HCM) is a potential risk factor for the development of severe disease in the cat. Herein we investigate the ACE2 protein expression in the lung, heart, and kidney from a small subset of cats with (n = 10) and without HCM (n = 10) by immunohistochemistry. The abundance and intensity of ACE2 expression is slightly elevated in alveoli (p = 0.09; 0.07, respectively) and bronchioles (p = 0.095; 0.37, respectively). However, statistically elevated abundance and intensity of ACE-2 expression was only evident in the heart of cats with HCM (p = 0.032; p = 0.011, respectively). Further investigation did not demonstrate a statistical correlation between the ACE2 expression in the heart in relation to the heart weight to body weight ratio, and the ventricular wall ratio. Current findings suggest an overexpression of ACE2 in HCM cases but follow up study is warranted to understand the pathophysiological process.

A rare presentation of neurosarcoidosis as the superior orbital fissure syndrome

We are reporting a rare case of neurosarcoidosis that presented with superior orbital fissure syndrome. A 51-year-old Indian woman who suffered from 2 weeks duration, insidious onset gradually progressive left sided headache limited to forehead, left periorbital pain, diplopia on looking toward left, and numbness on the left forehead was referred to our hospital. Ophthalmic findings included left oculomotor nerve, trochlear nerve and abducens nerve palsies, absent corneal reflex, and loss of touch, pain and temperature sensation in V1 distribution. Brain and orbit magnetic resonance imaging (MRI) showed contrast enhancing area at the left orbital apex with normal optic nerve. Normal CSF analysis. High ESR, and chest x-ray showing non-homogenous patchy opacities in bilateral lung fields leaded us for neoplastic screening. Chest computed tomography (CT) revealed multiple ill-defined irregular lung parenchymal nodular opacities of varying sizes involving bilateral lungs with enlarged mediastinal and bilateral axillary lymph nodes. Elevated angiotensin converting enzyme level was found. Biopsy of the axillary lymph node showed non-caseating granulomatous lymphadenitis with giant cells containing schaumann bodies and asteroid bodies in the cytoplasm. These findings indicating an inflammatory response induced by sarcoidosis. After the initiation of steroid treatment, the patient experienced complete remission without any recurrence. When examining a case presenting with superior orbital fissure syndrome with contrast enhancing MRI lesion at the orbital apex, the additional chest CT to exclude neoplastic lesions can detect pulmonary sarcoidosis and extraneural lesions. These may avoid delays in the diagnosis and management of neurosarcoidosis.

Overexpressed angiotensin-converting enzyme in neutrophils suppresses glomerular damage in crescentic glomerulonephritis.

While angiotensin-converting enzyme (ACE) regulates blood pressure by producing angiotensin II as part of the renin-angiotensin system, we recently reported that elevated ACE in neutrophils promotes an effective immune response and increases resistance to infection. Here, we investigate if such neutrophils protect against renal injury in immune complex (IC)-mediated crescentic glomerulonephritis (GN) through complement. Nephrotoxic serum nephritis (NTN) was induced in wild-type and NeuACE mice that overexpress ACE in neutrophils. Glomerular injury of NTN in NeuACE mice was attenuated with much less proteinuria, milder histological injury, and reduced IC deposits, but presented with more glomerular neutrophils in the early stage of the disease. There were no significant defects in T and B cell functions in NeuACE mice. NeuACE neutrophils exhibited enhanced IC uptake with elevated surface expression of FcγRII/III and complement receptor CR1/2. IC uptake in neutrophils was enhanced by NeuACE serum containing elevated complement C3b. Given no significant complement activation by ACE, this suggests that neutrophil ACE indirectly preactivates C3 and that the C3b-CR1/2 axis and elevated FcγRII/III play a central role in IC elimination by neutrophils, resulting in reduced glomerular injury. The present study identified a novel renoprotective role of ACE in glomerulonephritis; elevated neutrophilic ACE promotes elimination of locally formed ICs in glomeruli via C3b-CR1/2 and FcγRII/III, ameliorating glomerular injury.NEW & NOTEWORTHY We studied immune complex (IC)-mediated crescentic glomerulonephritis in NeuACE mice that overexpress ACE only in neutrophils. Such mice show no significant defects in humoral immunity but strongly resist nephrotoxic serum nephritis (less proteinuria, milder histological damage, reduced IC deposits, and more glomerular neutrophils). NeuACE neutrophils enhanced IC uptake via increased surface expression of CR1/2 and FcgRII/III, as well as elevated serum complement C3b. These results suggest neutrophil ACE as a novel approach to reducing glomerulonephritis.

Epidemiological characterization of patients with sarcoidosis in a high complexity hospital in southwestern Colombia

IntroductionEpidemiological studies on sarcoidosis in Colombia are scarce, and although recent reports from the north of the country have been published, clinical-epidemiological associations are not clear. Our aim was to characterize patients with sarcoidosis diagnosed at Fundación Valle del Lili in Cali, Colombia. MethodsA retrospective study of a series of sarcoidosis cases was conducted between 2011 and 2019. Demographic, clinical, laboratory, imaging, histopathological, and treatment variables were analyzed. ResultsA total of 34 patients with a diagnosis of sarcoidosis were found. The majority were women (n=25; 73%), and the mean age was 50 years. The main symptoms of onset were erythema nodosum (n=11; 33%), arthritis (n=10; 30%), and cough (n=9; 27%). In 64% of the cases, there was pulmonary involvement, with pulmonary nodules, mediastinal adenopathy, and interstitial lung disease found in 54%, 50%, and 36% of cases, respectively. In 85% of cases, there were extrapulmonary manifestations, mainly cutaneous (50%). Angiotensin-converting enzyme (ACE) was elevated in 62% of the cases in which it was measured (n=16; 47%). During the diagnostic process, 23 biopsies were performed, of which 95% showed granulomas with noncaseating necrosis. Most of the patients (76%) were controlled with prednisolone, at an average dose of 20mg (7.5–50mg) per day. ConclusionsSarcoidosis was more frequent in women and mestizos, and it presented earlier in men. Elevated ACE was not associated with extrapulmonary involvement. Calcium-phosphorus profile and antinuclear antibodies were not useful to establish the diagnosis.

Elevated ACE Levels Indicate Diabetic Nephropathy Progression or Companied Retina Impaired.

Renin-angiotensin-aldosterone system plays important roles in the development of diabetic nephropathy (DN), and angiotensin converting enzyme (ACE) is the key factor in the process from angiotensin I to angiotensin II, but the variation and roles of serum ACE in DN patients are still unclear. Forty-four type 2 diabetes mellitus (T2DM) patients, 75 DN patients, and 36 age-gender-matched healthy volunteers were recruited who attended Xiangya Hospital of Central South University in this case control study. Serum ACE levels and other indexes were tested with commercial kit. ACE levels in DN were significantly higher than T2DM and controls (F = 9.66, P < 0.001). Serum ACE levels significantly correlated with UmALB (r = 0.3650, P < 0.001), BUN (r = 0.3102, P < 0.001), HbA1c (r = 0.2046, P = 0.0221), ACR (r = 0.4187, P < 0.001), ALB (r = -0.1885, P = 0.0192), and eGFR (r = -0.3955, P < 0.001), and we got an equation that Y = 2.839 + 0.648X1 + 2.001X2 + 0.003X3 - 6.637X4 +0.416X5 - 0.134X6 (Y: ACE; X1: BUN; X2: HbA1C; X3: UmALB; X4: gender; X5: ALB; X6: eGFR, R2 = 0.655). When DN patients were divided into advanced-stage and early-stage with or without DR, ACE levels would increase when early-stage DN develops into advanced-stage or companied with DR. Elevated serum ACE levels may hint DN progression or retina impaired of DN patients.

Spinal cord sarcoidosis in Japan: utility of cerebrospinal fluid examination and nerve conduction study for diagnosis and prognosis prediction.

Spinal cord sarcoidosis (SCS) is rare, and its diagnosis is challenging. We examined clinical, laboratory, and imaging features in patients with SCS to obtain useful clues for diagnosis and prognosis. Eleven consecutive patients (four males, seven females) at a single Japanese institution were investigated. Median age at onset was 66years old. The most frequent site affected, other than the nervous system, was the respiratory system. While histological confirmation of non-caseating granulomas was often found there, no patient had respiratory symptoms. Peripheral nerve involvement was detected in 64% of patients. Soluble IL-2 receptor (sIL-2R) levels in serum and cerebrospinal fluid (CSF) were elevated in 64% and 45% of patients, respectively, and this finding was more common than elevation of angiotensin-converting enzyme (ACE). 18F-fluorodeoxyglucose (FDG) positron emission tomography showed abnormally high uptake in spinal lesions of all examined patients. Although corticosteroids were administrated to all patients, and immuno-suppressants were prescribed to six (55%), the modified Rankin Scale was unchanged or worsened in four (36%) patients during the follow-up period. Neurological exacerbation of myelopathy was seen in four (36%) patients. Complete response rate was only seen in 9%. High levels of cell count, protein, ACE, and sIL-2R in CSF were significantly more frequent in patients with a marked improvement after immunotherapy than in the other patients. These results suggest that high serum and CSF sIL-2R, high uptake of FDG, and peripheral nerve involvement are indicative of SCS. Given that SCS is commonly intractable, CSF abnormalities may predict efficacy of immunotherapies.