Serum Angiotensin-converting Enzyme Levels Research Articles

6564 A Case of Severe Hypercalcemia in Carney's Complex

Abstract Disclosure: J. Chippior: None. M. Rayan: None. L. Wright: None. L.S. Kirschner: Grant Recipient; Self; Medpace, Sparrow, Corcept Therapeutics, Corcept, Spruce, CinCor, Crinetics, Adrenas. S.W. Ing: Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx, Amolyt, Bridge Bio. Carney complex is a rare syndrome with fewer than 750 reported cases, characterized by lentigniosis, myxomas, and the occurrence of both endocrine and non-endocrine tumors. An inactivating mutation PRKAR1A, which encodes for the type 1A regulatory subunit of Protein kinase A, is responsible for over 70% of familial cases and 37% of sporadic cases. A 31-year-old female with a history of Carney complex, Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD), facial lentigines, spinal Schwannomas, and recent ischemic stroke secondary to embolization of a cardiac atrial myxoma, was transferred to our medical center for hyperemesis and severe hypercalcemia. Albumin-corrected serum calcium measured 15.4 mg/dL (8.6-10.5 mg/dL), ionized calcium 7.8 mg/dL (4.6-5.3 mg/dL) associated with suppressed PTH, normal PTH-related protein, and elevated bone turnover markers, C-telopeptide 4,273 pg/ml (150-635) and Procollagen Type 1 N-terminal Propeptide 222 mcg/L (19-83). Evaluation for etiology of hypercalcemia revealed elevated 1,25 dihydroxy vitamin D at 107.0 pg/ml (20-79) and elevated interleukin-6 at 11 pg/ml (<6.4). IL-6 is expressed by cardiac myxomas. Serum angiotensin-converting enzyme level was 50 U/L (16-85) and infectious workup was negative for potential granulomatous causes of elevated calcitriol (including testing for tuberculosis, histoplasma, blastomyces, bartonella, and coccidioides). CT angiogram of the abdomen and pelvis (completed in preparation of atrial myxoma resection) revealed ground-glass opacities in bilateral posterior lung fields and multiple pulmonary nodules, with the largest measuring 8 mm. After treatment with aggressive intravenous fluid resuscitation, intramuscular calcitonin, and intravenous zoledronic acid, corrected calcium normalized to 9.4 mg/dL at discharge. Urinary cortisol was 6.2 mcg per 24-hr (3.5-45), for which she started hydrocortisone 20 mg daily to treat suspected adrenal insufficiency as excess cortisol secretion in PPNAD may be episodic. Thus remission of hypercortisolism may have unmasked an underlying hypercalcemia, and adrenal insufficiency itself may have contributed to this finding. She had excision of left atrial myxoma and has continued to exhibit normal calcium levels on steroid replacement therapy. Repeat chest CT to further characterize these pulmonary findings is planned. This case illustrates a unique constellation of endocrine features associated with severe hypercalcemia in Carney complex. Presentation: 6/1/2024

6564 A Case Of Severe Hypercalcemia In Carney's Complex

Abstract Disclosure: J. Chippior: None. M. Rayan: None. L. Wright: None. L.S. Kirschner: Grant Recipient; Self; Medpace, Sparrow, Corcept Therapeutics, Corcept, Spruce, CinCor, Crinetics, Adrenas. S.W. Ing: Grant Recipient; Self; Alexion Pharmaceuticals, Inc., Amgen Inc, Radius Health, Inc, Takeda, Ultragenyx, Amolyt, Bridge Bio. Carney complex is a rare syndrome with fewer than 750 reported cases, characterized by lentigniosis, myxomas, and the occurrence of both endocrine and non-endocrine tumors. An inactivating mutation PRKAR1A, which encodes for the type 1A regulatory subunit of Protein kinase A, is responsible for over 70% of familial cases and 37% of sporadic cases. A 31-year-old female with a history of Carney complex, Cushing syndrome due to primary pigmented nodular adrenocortical disease (PPNAD), facial lentigines, spinal Schwannomas, and recent ischemic stroke secondary to embolization of a cardiac atrial myxoma, was transferred to our medical center for hyperemesis and severe hypercalcemia. Albumin-corrected serum calcium measured 15.4 mg/dL (8.6-10.5 mg/dL), ionized calcium 7.8 mg/dL (4.6-5.3 mg/dL) associated with suppressed PTH, normal PTH-related protein, and elevated bone turnover markers, C-telopeptide 4,273 pg/ml (150-635) and Procollagen Type 1 N-terminal Propeptide 222 mcg/L (19-83). Evaluation for etiology of hypercalcemia revealed elevated 1,25 dihydroxy vitamin D at 107.0 pg/ml (20-79) and elevated interleukin-6 at 11 pg/ml (<6.4). IL-6 is expressed by cardiac myxomas. Serum angiotensin-converting enzyme level was 50 U/L (16-85) and infectious workup was negative for potential granulomatous causes of elevated calcitriol (including testing for tuberculosis, histoplasma, blastomyces, bartonella, and coccidioides). CT angiogram of the abdomen and pelvis (completed in preparation of atrial myxoma resection) revealed ground-glass opacities in bilateral posterior lung fields and multiple pulmonary nodules, with the largest measuring 8 mm. After treatment with aggressive intravenous fluid resuscitation, intramuscular calcitonin, and intravenous zoledronic acid, corrected calcium normalized to 9.4 mg/dL at discharge. Urinary cortisol was 6.2 mcg per 24-hr (3.5-45), for which she started hydrocortisone 20 mg daily to treat suspected adrenal insufficiency as excess cortisol secretion in PPNAD may be episodic. Thus remission of hypercortisolism may have unmasked an underlying hypercalcemia, and adrenal insufficiency itself may have contributed to this finding. She had excision of left atrial myxoma and has continued to exhibit normal calcium levels on steroid replacement therapy. Repeat chest CT to further characterize these pulmonary findings is planned. This case illustrates a unique constellation of endocrine features associated with severe hypercalcemia in Carney complex. Presentation: 6/1/2024

The Antihypertensive Potential of Aqueous extract of Peristrophe Bivalvis (L.) Merr. is via Up-regulation of Cyclic Guanosine Monophosphate and Down-regulation of the Renin-angiotensin System.

Hypertension is a major risk factor for cardiovascular diseases. Peristrophe bivalvis (PB) is used for the treatment of hypertension, painful sprains, skin diseases, tuberculosis, acute bronchitis, anti-inflammatory conditions, hepatitis, and diabetes. Its antihypertensive potential has been investigated and documented. This study investigated the antihypertensive mechanism of aqueous extract of PB leaf (APB) on L-NAME-induced hypertension. Thirty male wistar rats (150-170 g) were grouped into five (n=5). Group 1 received 10 mL/kg of distilled water (control), while groups 2-5 were administered 60 mg/kg of L-NAME (L-- NAME60) orally for eight weeks to induce hypertension. After eight weeks, groups 2-5 received L-NAME60+distilled water (HNT), distilled water (HRE), L-NAME60+APB (200 mg/kg, [HAPB]), and L-NAME60+ramipril (10 mg/kg, [HRA]), respectively, for five weeks. The BP was measured by the tail-cuff method. The blood sample was obtained under anesthesia, and tissue samples were obtained after euthanasia. Serum renin, ACE, angiotensin-II, endothelin-1, and cyclic guanosine monophosphate (cGMP) levels were measured using ELISA techniques. Malondialdehyde, superoxide dismutase (SOD), and reduced glutathione (GSH) levels were measured by spectrophotometry. Data were analyzed using ANOVA at α0.05. The BP significantly decreased in HAPB compared to HNT. Renin, ACE, and angiotensin-II levels significantly decreased while cGMP levels increased in the HAPB group compared to HNT. Malondialdehyde levels significantly decreased, and SOD and GSH levels increased compared to HNT. Peristrophe bivalvis aqueous leaf extract reduced blood pressure in hypertensive rats by modulating the cGMP signalling pathway and the renin-angiotensin system.

Risk factors for uveitis in a Finnish sarcoid population.

To evaluate possible risk factors for uveitis among Finnish sarcoidosis patients. Patient charts of patients with sarcoidosis, with (n = 97) or without (n = 255) uveitis, and with a comprehensive eye examination from January 2014 to January 2021 at Tays Eye Centre, Tampere University Hospital, Finland were studied. Sarcoidosis patients with uveitis had higher rate of lymphocytopenia (43% vs. 29%, p = 0.041) and lower serum lysozyme levels (2.0 mg/L vs. 2.3 mg/L, p = 0.049; 95% CI, -0.692 to -0.002). Lysozyme level or lymphocytopenia did not have a statistically significant effect on the probability of uveitis in a binary logistic regression analysis. No other differences in the potential risk factors with p-values ≤0.05 were found, including bilateral hilar lymphadenopathy, serum angiotensin-converting enzyme (ACE) levels, sex, age and history of smoking. Lymphocytopenia and lower serum lysozyme levels present as possible risk factors for uveitis among patients with sarcoidosis. Systematic measurement of lymphocyte and lysozyme levels in sarcoidosis is needed to further understand their role as potential risk factors.

A Case of Ocular Sarcoidosis with an Atypical Presentation of Subretinal Mass

Purpose: To describe a case of ocular sarcoidosis manifesting as an atypical subretinal mass.Case summary: A 59-year-old woman reported reduced visual acuity in her left eye lasting for 1 month. Her best corrected visual acuity in the left eye had diminished to 0.3. A fundus examination revealed a whitish elevated lesion, approximately one disc diameter in size, in the perimacular area of the left eye. Optical coherence tomography identified a hyporeflective oval-shaped mass in the choriocapillaris region accompanied by subretinal fluid. Initial assessment suggested choroidal osteoma with choroidal neovascularization. Consequently, the patient underwent two intravitreal bevacizumab injections, which did not lead to improvement. To rule out systemic diseases, including syphilis, tuberculosis, and sarcoidosis, further radiologic and laboratory tests were conducted. A chest computed tomography highlighted mediastinal lymph node enlargement and pervasive nodules in both lung parenchymata, and serum angiotensin-converting enzyme levels were elevated to 77 U/L. Based on these findings, a diagnosis of sarcoidosis was confirmed, and the patient commenced treatment with oral prednisolone. Eight weeks after treatment, the subretinal lesion and fluid had resolved, and the best corrected visual acuity in the patient’s left eye had improved to 0.9.Conclusions: Ocular sarcoidosis can manifest as a subretinal mass. This presentation should be differentiated from other subretinal lesions.

#68 Novel clinical application of urinary angiotensin-converting enzyme assay in renal sarcoidosis: a retrospective observational study

Abstract Background and Aims Renal manifestations of sarcoidosis are observed in approximately 1–5% and characterized mainly by granulomatous interstitial nephritis, which could lead to kidney failure. Angiotensin-converting enzyme (ACE) reflects the presence of granuloma; hence, serum ACE and tubular injury markers are measured in renal sarcoidosis (RS); however, they either have low sensitivity or low specificity. Although its practicality has not been established, the use of ACE levels in cerebrospinal fluid has been reported for neuro-sarcoidosis. Therefore, we hypothesized that urinary ACE could reflect granuloma presence in the kidneys and could be a disease-specific marker for RS. Method This was a single-center, retrospective observational study. We evaluated clinical characteristics and kidney biopsy findings from electronic medical record surveys and kidney biopsy specimens. The control groups included sarcoidosis without renal involvement (SAR-control) and tubulointerstitial nephritis without a sarcoidosis etiology (TIN-control). Serum and urinary ACE levels were measured, and urinary fractional excretion of ACE (FEACE) was investigated. Serum ACE assay and urinary ACE levels were measured using the colorimetric method with p-hydroxybenzoyl-glycyl-L-histidyl-L-leucine. A total of six patients (three with RS; one with sarcoidosis as controls; and two with TIN controls) with undetectable urinary ACE levels were excluded from the urinary ACE and FEACE analyses. Tubulointerstitial lesions were visually assessed for essentially normal (%), inflammatory cell infiltrates (%), tubular atrophy (%), and interstitial fibrosis (%) by several board-certified nephrologists, and analyzed the correlation of these lesions with each marker. Results This study included 18 patients with RS, 18 as SAR-control, and 10 as TIN-control. Serum ACE, urinary ACE, and FEACE levels in the RS group were significantly higher than those in the control groups. Receiver operating characteristic analysis identified FEACE and serum ACE levels as useful biomarkers for diagnosing RS among patients with both controls, respectively. In the RS group, FEACE was positively correlated with the degree of tubulointerstitial injury (r = 0.69, P = 0.0045), and the cutoff value of FEACE for diffuse tubulointerstitial injury (50.0% or more) was 0.39%, with a sensitivity and specificity of 100.0%. Furthermore, obvious positive correlations were observed among FEACE, inflammatory cell infiltrates (r = 0.53, P = 0.044), and interstitial fibrosis (r = 0.56, P = 0.029) in the RS group but not in the TIN-control. Conclusion Combination with serum and urinary ACE could help diagnose and assess disease severity among patients with RS.

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.

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.

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.

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

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.

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.

Re-evaluating serum angiotensin-converting enzyme in sarcoidosis.

Sarcoidosis is a systemic inflammatory disease of unknown etiology, which mainly affects the lungs and lymph nodes, as well as extrapulmonary organs. Its incidence, and prevalence rate, and disease course largely vary with regions and populations globally. The clinical manifestations of sarcoidosis depend on the affected organs and the degree of severity, and the diagnosis is mainly based on serum biomarkers, radiographic, magnetic resonance, or positron emission tomography imaging, and pathological biopsy. Noncaseating granulomas composing T cells, macrophages, epithelioid cells, and giant cells, were observed in a pathological biopsy, which was the characteristic pathological manifestation of sarcoidosis. Angiotensin-converting enzyme (ACE) was first found in the renin-angiotensin-aldosterone system. Its main function is to convert angiotensin I (Ang I) into Ang II, which plays an important role in regulating blood pressure. Also, an ACE insertion/deletion polymorphism exists in the human genome, which is involved in the occurrence and development of many diseases, including hypertension, heart failure, and sarcoidosis. The serum ACE level, most commonly used as a biomarker in diagnosing sarcoidosis, in patients with sarcoidosis increases. because of epithelioid cells and giant cells of sarcoid granuloma expressing ACE. Thus, it serves as the most commonly used biomarker in the diagnosis of sarcoidosis and also aids in analyzing its therapeutic effect and prognosis in patients with sarcoidosis.

Curcumin Nanoemulsion: Unveiling Cardioprotective Effects via ACE Inhibition and Antioxidant Properties in Hypertensive Rats.

Background and Objectives: Curcumin, derived from Curcuma longa, is a well-known traditional medicinal compound recognized for its therapeutic attributes. Nevertheless, its efficacy is hampered by limited bioavailability, prompting researchers to explore the application of nanoemulsion as a potential alternative. Materials and Methods: This study delves into the antihypertensive effects of curcumin nanoemulsion (SNEC) by targeting the renin-angiotensin-aldosterone system (RAAS) and oxidative stress in deoxycorticosterone acetate (DOCA) salt-induced hypertensive rats. To gauge the cardio-protective impact of SNEC in DOCA salt-induced hypertension, molecular docking was undertaken, uncovering curcumin's high affinity and adept binding capabilities to the active site of angiotensin-converting enzyme (ACE). Additionally, the investigation employed uninephrectomized rats to assess hemodynamic parameters via an AD instrument. Serum ACE, angiotensin II, blood urea nitrogen (BUN), and creatinine levels were quantified using ELISA kits, while antioxidant parameters were evaluated through chemical assays. Result: The outcomes of the molecular docking analysis revealed robust binding of curcumin to the ACE active site. Furthermore, oral administration of SNEC significantly mitigated systolic, diastolic, and mean arterial blood pressure in contrast to the DOCA-induced hypertensive group. SNEC administration also led to a reduction in left ventricular end-diastolic pressure (LVEDP) and an elevation in the maximum rate of left ventricular pressure rise (LV (dP/dt) max). Moreover, SNEC administration distinctly lowered serum levels of ACE and angiotensin II compared to the hypertensive DOCA group. Renal markers, including serum creatinine and BUN, displayed a shift toward normalized levels with SNEC treatment. Additionally, SNEC showcased potent antioxidant characteristics by elevating reduced glutathione, catalase, and superoxide dismutase levels, while decreasing the concentration of thiobarbituric acid reactive substances. Conclusions: Collectively, these findings underscore that curcumin nanoemulsion exerts noteworthy cardio-protective effects through ACE activity inhibition and remarkable antioxidant properties.

OA12 Grimey granulomas of sarcoidosis

Abstract Introduction Sarcoidosis affects approximately 1% of the population. There are two situations where it came become life threatening: seizures secondary to neuro-sarcoidosis and arrhythmias due to cardiac infiltration. Currently there are limited licenced therapies for the treatment of sarcoidosis. We describe a case of cutaneous and neuro-sarcoidosis who developed subsequent multi-system sarcoidosis. Case description A previously fit and well 50-year-old presented to his local hospital with tonic clonic seizures. He worked as a mortgage broker and never smoked. There was no pro-drome and on examination it was noted he had erythema nodosum on his shins. He was investigated with a CT head and subsequent MRI demonstrating enhancement of his leptomeninges, mid brain parenchyma, hypothalamus and pituitary gland. A lumbar puncture was performed with an elevated protein level of 934g with a normal glucose and lymphocyte level. The CSF was negative for TB. A CT of his chest was performed demonstrating bilateral hilar lymphadenopathy and subsequent histology of these lymph nodes demonstrated non-necrotising, non-caseating epithelioid granulomas. A diagnosis of sarcoidosis was made and he was commenced on mycophenolate. His disease remained quiescent for 5 years before the eruption of further skin lesions. He developed multiple subdermal nodules on his fingers, wrists, elbows which were biopsied demonstrating cutaneous sarcoidosis. Neurological examination demonstrated brisk lower limb reflexes with upgoing plantars. He was commenced on a tapering course of prednisolone and an evaluation for extra-cutaneous disease was made. An IL2Ra was 4719ng/L (423-1843) with a normal ACE. Pituitary axis testing revealed a slightly raised prolactin (326 mIU/L). A CT-PET was performed demonstrating extensive metabolic activity in his skin, central nervous system, liver, spleen, salivary glands, skeletal uptake in both humeral heads alongside myocardial uptake. An urgent cardiac MRI was performed demonstrating active myocardial disease. An ECG did not demonstrate any conduction abnormalities. A diagnosis of multi-system sarcoidosis was made warranting an urgent MDT discussion given the progression of his disease. Discussion In this particular case, it had been assumed that his sarcoidosis was inactive until the emergence of the skin lesions. It was the skin lesions that lead to an assessment for multi-system sarcoidosis. It is common for the serum ACE level to be normal, as seen in up to 50% of cases and it was the Il2Ra elevation that prompted the CT-PET request. Given the extent and progression of disease despite treatment with mycophenolate, this gentlemen was given a tapering regime of prednisolone (starting at 20mg) and his mycophenolate was switched to methotrexate which has shown to have superior efficacy to mycophenolate for sarcoidosis. Furthermore, infliximab at a dose of 5mg/kg was commenced shortly after to control the increasing CNS lesions. Infliximab is a well recognised treatment for sarcoidosis; however, due to limited clinical trial data, it remains unlicenced for use in sarcoidosis with the exception of neuro-sarcoidosis (following the failure of DMARD therapy). To date, the patient remains well with no further worsening in his disease. Key learning points Sarcoidosis is a clinical entity with no one specific test. The diagnosis should be constructed using multiple parameters including radiographic findings, biochemical and histological proof. We advocate that suspected cases of sarcoidosis should have a thorough assessment and discussion in the MDT. When isolated skin disease is suspected or confirmed, baseline testing for extra-cutaneous involvement should be sent including NT-proBNP, troponin I and T, creatinine kinase, a full pituitary profile, ACE and cytokine assessment for Il2Ra, amongst other routine blood tests. An ECG is of paramount importance as arrhythmias are common cardiac features of sarcoidosis. Should there be ongoing suspicion of multiple organ involvement, a CT-PET should be performed at baseline. Isolated lymph node disease does not commonly warrant treatment; however, this cohort of patients should be closely monitored. The management of sarcoidosis in the acute setting is commonly prednisolone, but steroid sparing therapies should be considered in patients needing recurrent, prolonged courses of corticosteroids or those with evidence of critical organ involvement such as CNS, cardiac or lung disease. Life threatening disease or disease refractory to DMARD therapy should be considered for anti-TNF therapy with infliximab or adalimumab. More recently, tofacitinib has been promising as a treatment for sarcoidosis with clinical trials in Yale and Portland. Newer therapies in development include the GM-CSF inhibitor namilumab, and efzofitimod, a neuropilin 2 inhibitor.

SACE and IL-2R as serum biomarkers for evaluation of multi-organ involvement and prognosis of sarcoidosis

BackgroundSerum biomarkers in the evaluation of organ involvement and prognostic monitoring of sarcoidosis have not been determined. The purpose of this study was to identify common biomarkers that could be used to assess organ involvement and monitor outcomes in sarcoidosis patients.MethodsFrom Mar 2013 to Sep 2021, patients with newly diagnosed pulmonary sarcoidosis were enrolled in this study in Shanghai Pulmonary Hospital. The information from medical records was retrospectively collected including diagnosis, organ involvement, laboratory tests and follow up data. Differences of continuous variables between groups were analyzed by unpaired Student’s t-test. Multivariate logistic regression model was performed to identify potential independent factors associated with multiple organ involvement.ResultsA total of 832 patients were included in the study. There were 339 (40.7%) patients with single organ pulmonary involvement, while 493 (59.3%) patients had two to seven organs involved. Among the routine serum tests, only the serum angiotensin converting enzyme (SACE) level was an independent factor of multiple organ involvement. Compared to those patients without involvement, SACE levels were higher in patients with extra-thoracic lymph node, skin, or spleen involvement as well as abnormal calcium metabolism. Interleukin-2 receptor (IL-2R) levels were higher in patients with extra-thoracic lymph node, spleen involvement and abnormal calcium metabolism than in those without it. The mean levels of SACE and IL-2R showed upward trends paralleling the increase on number of organs involved. In follow up, SACE and IL-2R levels were both decreased in an improved patient group, while there was no obvious difference was noticed before and after treatment in patients with persistent disease.ConclusionSACE and IL-2R were useful as serum biomarkers in the initial evaluation of organ involvement as well as monitoring prognosis in sarcoidosis.

A case report of a patient with panuveitis following COVID-19 infection

Introduction: Panuveitis is intraocular inflammation of all layers of the uvea and may be isolated or associated with systemic inflammatory diseases affecting one eye or both eyes. Uveitis and conjunctivitis are noted in coronavirus disease 2019 (COVID-19) infection but have been listed as a major adverse event in case reports for COVID-19. Importance: To describe the clinical profile of a Syrian patient presenting with panuveitis following COVID-19 infection. Case presentation: A 32-year-old Syrian computer programmer, a previously healthy nonsmoker male, presented with pain, photophobia, and red eye with no irritation or discharge in eyes, decreased vision, and seeing floaters for 5 days. His only notable mention on review of systems was a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection 8 weeks prior. Ocular examination revealed panuveitis involvement. No muscle weakness or neurological positive findings were found. There was no relevant medical history or previous personal or family history. Laboratory tests, including QuantiFERON-TB, immune profile, and viral serology, were negative. Serum angiotensin-converting enzyme levels were normal. Interleukin-1 receptor was negative. Human leukocyte antigen B51/B27 typing was negative. Chest radiograph was normal. Thoracic, abdominal, and pelvic computerized tomography were normal. Based on the negative review of systems and the first panuveitis event, the presumptive diagnosis was isolated bilateral SARS-CoV-2-induced panuveitis. Clinical discussion: In December 2019, COVID-19 became a global health issue. Studies assumed that ocular manifestations of COVID-19 were rare and ranged between 3 and 30%. Moreover, it rarely happened as an initial manifestation of the disease, and it was reported during the following weeks. To our knowledge, in the literature review, panuveitis was reported after COVID infection only in our case and in Benito-Pascual et al.’s case, which described panuveitis and optic neuritis after COVID-19 infection. Conclusion: We must be aware of the possible panuveitis manifestations following COVID-19 infection.

Effect of Coffee-Corn Mix on Hypertensive Mice on Biomarkers of Nitric Oxide, eNOS, Sodium, and ACE Serum Levels

Hypertension is a major determinant of morbidity and mortality worldwide. Hypertension is the most common cause of death in Southeast Asia. The pathophysiology of hypertension is complex and not fully understood. Increased oxidative stress is considered one of the main mechanisms involved in the pathogenesis of endothelial dysfunction leading to hypertension. Therefore, antioxidant therapy can be an alternative option to prevent endothelial damage and hypertension. Robusta coffee and corn are high sources of antioxidants. This study aimed to analyze the effect of the coffee-corn mixture on NO, eNOS, sodium, and ACE serum levels in hypertensive rats. This research is an experimental laboratory study with a post-test only control group design. Robusta coffee and yellow corn samples were roasted at 180°C for 10 minutes. Rats were induced by DOCA salt and given a mixture of coffee-corn in a ratio of 75%: 25% and 50%: 50% for two weeks. After treatment, the levels of NO, eNOS, ACE, and F2-isoprostane from blood serum were measured. The results showed that there was no significant difference in serum Nitric Oxide levels in the negative, positive control group and the treatment group after treatment. There was a significant increase in eNOS levels and a significant decrease in serum sodium, ACE, and F2-isoprostane levels in the negative, positive, and treatment groups. In the path analysis, it was found that the administration of the coffee-corn mixture (50%:50%) can reduce blood pressure through two pathways, namely a decrease in the level of F2-isoprostane, which causes a decrease in sodium levels and a direct decrease in sodium levels.