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1.
Comput Math Methods Med ; 2022: 4657502, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35242207

RESUMO

OBJECTIVE: To investigate the diagnostic and staging value of serum angiotensin-converting enzyme (sACE) in sarcoidosis. METHODS: Patients with suspected sarcoidosis treated in the Department of Pulmonary and Critical Care Medicine of the China-Japan Friendship Hospital from 2010 to 2020 were included. The data of sACE, erythrocyte sedimentation rate (ESR), complete blood count (CBC), lung function, bronchoalveolar lavage, and biopsy were collected. The differences between the sarcoidosis group and the nonsarcoidosis group and between different stages of sarcoidosis were compared. The receiver operating characteristic (ROC) curve analysis was used for the diagnostic test of sACE in sarcoidosis. RESULTS: A total of 84 cases with suspected sarcoidosis were included, among which 70 cases were confirmed to be sarcoidosis by biopsy. The mean value of sACE in sarcoidosis patients was 56.61 ± 30.80 U/L, which was significantly higher than that in nonsarcoidosis patients (28.07 ± 14.11 U/L, P = 0.001). The level of sACE in sarcoidosis patients with peripheral superficial lymph nodes and multiple system involvement was significantly higher than that in intrathoracic sarcoidosis patients (P = 0.009); the percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) of sarcoidosis patients was 45.39 ± 22.87%, which was significantly higher than that of nonsarcoidosis patients (P < 0.001). There was no correlation between sACE and ESR (correlation coefficient = -0.167). According to ROC curve analysis, when sACE ≥ 44.0 U/L, the sensitivity of sarcoidosis diagnosis was 61.4%, the specificity was 92.9%, and the AUC was 0.819. CONCLUSION: sACE has a good specificity in the diagnosis of sarcoidosis. sACE values in patients with sarcoidosis with systemic involvement were higher than those with simple intrathoracic sarcoidosis.


Assuntos
Peptidil Dipeptidase A/sangue , Sarcoidose/sangue , Adulto , Idoso , Biomarcadores/sangue , Sedimentação Sanguínea , Biologia Computacional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Especificidade de Órgãos , Estudos Prospectivos , Sarcoidose/classificação , Sarcoidose/diagnóstico
2.
Biomed Pharmacother ; 144: 112323, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34656062

RESUMO

The prevalence of cardiovascular disease among type-2 diabetic patients has become a source of major concern world over. This study explored the protective effect of kolaviron, a bioflavonoid, against oxidative cardiovascular injury in fructose- streptozotocin-induced type 2 diabetic male Sprague Dawley rats. After acclimatization, induction, and confirmation of type-2 diabetes, kolaviron was administered for 28days, after which the animals were anesthetized with Isofor and euthanized. Blood from each rat were collected, and blood samples were then centrifuged for serum and plasma. Cardiac troponin I (cTnI), creatine kinase myocardial band (CK-MB), Creatine phosphokinase (CK), and insulin levels were immediately determined in serum, while remaining samples (serum, plasma, and organs) were stored in the bio-freezer at - 80 °C and 10% formalin for enzyme-link immunosorbent assay (ELISA), biochemical, molecular, and histopathological studies. The results show that type-2 diabetes induction with fructose and streptozotocin led to increased blood glucose levels, decreased insulin levels and cardiac antioxidant enzyme activities, increased malondialdehyde levels, cardiac biomarkers and pro-inflammatory cytokines levels, resulted in abnormal lipid profile, increased blood pressure and angiotensin-converting enzyme (ACE) activity, and decreased plasma endothelial nitric oxide synthase (eNOS) concentration. The histopathological examination of the cardiac tissue revealed severe lesion, hypertrophy, and myofibrils degeneration. However, administration of kolaviron for 28days remarkably improved these conditions. Hence the result from the study validates the potency of kolaviron, and suggests it could serve as an alternative to existing remedy in ameliorating or protecting against cardiovascular injury in type-2 diabetes.


Assuntos
Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Cardiomiopatias Diabéticas/prevenção & controle , Flavonoides/farmacologia , Mediadores da Inflamação/sangue , Miócitos Cardíacos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/metabolismo , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Cardiomiopatias Diabéticas/patologia , Frutose , Insulina/sangue , Lipídeos/sangue , Masculino , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Peptidil Dipeptidase A/sangue , Ratos Sprague-Dawley , Estreptozocina
3.
PLoS One ; 16(9): e0257016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34478478

RESUMO

BACKGROUND: Activation of the immune system is implicated in the Post-Acute Sequelae after SARS-CoV-2 infection (PASC) but the mechanisms remain unknown. Angiotensin-converting enzyme 2 (ACE2) cleaves angiotensin II (Ang II) resulting in decreased activation of the AT1 receptor and decreased immune system activation. We hypothesized that autoantibodies against ACE2 may develop after SARS-CoV-2 infection, as anti-idiotypic antibodies to anti-spike protein antibodies. METHODS AND FINDINGS: We tested plasma or serum for ACE2 antibodies in 67 patients with known SARS-CoV-2 infection and 13 with no history of infection. None of the 13 patients without history of SARS-CoV-2 infection and 1 of the 20 outpatients that had a positive PCR test for SARS-CoV-2 had levels of ACE2 antibodies above the cutoff threshold. In contrast, 26/32 (81%) in the convalescent group and 14/15 (93%) of patients acutely hospitalized had detectable ACE2 antibodies. Plasma from patients with antibodies against ACE2 had less soluble ACE2 activity in plasma but similar amounts of ACE2 protein compared to patients without ACE2 antibodies. We measured the capacity of the samples to inhibit ACE2 enzyme activity. Addition of plasma from patients with ACE2 antibodies led to decreased activity of an exogenous preparation of ACE2 compared to patients that did not have antibodies. CONCLUSIONS: Many patients with a history of SARS-CoV-2 infection have antibodies specific for ACE2. Patients with ACE2 antibodies have lower activity of soluble ACE2 in plasma. Plasma from these patients also inhibits exogenous ACE2 activity. These findings are consistent with the hypothesis that ACE2 antibodies develop after SARS-CoV-2 infection and decrease ACE2 activity. This could lead to an increase in the abundance of Ang II, which causes a proinflammatory state that triggers symptoms of PASC.


Assuntos
Autoanticorpos/sangue , COVID-19/imunologia , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/sangue , Angiotensina II/sangue , Angiotensina II/imunologia , Enzima de Conversão de Angiotensina 2/genética , Autoanticorpos/imunologia , Autoanticorpos/isolamento & purificação , COVID-19/sangue , COVID-19/virologia , Feminino , Humanos , Masculino , Peptidil Dipeptidase A/sangue , Receptor Tipo 1 de Angiotensina/sangue , Receptor Tipo 1 de Angiotensina/genética , Receptor Tipo 1 de Angiotensina/imunologia , Sistema Renina-Angiotensina/genética , Sistema Renina-Angiotensina/imunologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Glicoproteína da Espícula de Coronavírus/isolamento & purificação
4.
Cells ; 10(7)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34359878

RESUMO

Objective: Inhibitors of the angiotensin converting enzyme (ACE) are the primarily chosen drugs to treat heart failure and hypertension. Moreover, an imbalance in tissue ACE/ACE2 activity is implicated in COVID-19. In the present study, we tested the relationships between circulating and tissue (lung and heart) ACE levels in men. Methods: Serum, lung (n = 91) and heart (n = 72) tissue samples were collected from Caucasian patients undergoing lung surgery or heart transplantation. ACE I/D genotype, ACE concentration and ACE activity were determined from serum and tissue samples. Clinical parameters were also recorded. Results: A protocol for ACE extraction was developed for tissue ACE measurements. Extraction of tissue-localized ACE was optimal in a 0.3% Triton-X-100 containing buffer, resulting in 260 ± 12% higher ACE activity over detergent-free conditions. SDS or higher Triton-X-100 concentrations inhibited the ACE activity. Serum ACE concentration correlated with ACE I/D genotype (II: 166 ± 143 ng/mL, n = 19, ID: 198 ± 113 ng/mL, n = 44 and DD: 258 ± 109 ng/mL, n = 28, p < 0.05) as expected. In contrast, ACE expression levels in the lung tissue were approximately the same irrespective of the ACE I/D genotype (II: 1423 ± 1276 ng/mg, ID: 1040 ± 712 ng/mg and DD: 930 ± 1273 ng/mg, p > 0.05) in the same patients (values are in median ± IQR). Moreover, no correlations were found between circulating and lung tissue ACE concentrations and activities (Spearman's p > 0.05). In contrast, a significant correlation was identified between ACE activities in serum and heart tissues (Spearman's Rho = 0.32, p < 0.01). Finally, ACE activities in lung and the serum were endogenously inhibited to similar degrees (i.e., to 69 ± 1% and 53 ± 2%, respectively). Conclusion: Our data suggest that circulating ACE activity correlates with left ventricular ACE, but not with lung ACE in human. More specifically, ACE activity is tightly coordinated by genotype-dependent expression, endogenous inhibition and secretion mechanisms.


Assuntos
Peptidil Dipeptidase A/metabolismo , Idoso , Feminino , Humanos , Pulmão/metabolismo , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Peptidil Dipeptidase A/análise , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Processamento de Proteína Pós-Traducional
5.
J Med Virol ; 93(10): 5908-5916, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34138483

RESUMO

The main entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 interactions with ACE2 may increase ectodomain shedding but consequences for the renin-angiotensin system and pathology in Coronavirus disease 2019 (COVID-19) remain unclear. We measured soluble ACE2 (sACE2) and sACE levels by enzyme-linked immunosorbent assay in 114 hospital-treated COVID-19 patients compared with 10 healthy controls; follow-up samples after four months were analyzed for 58 patients. Associations between sACE2 respectively sACE and risk factors for severe COVID-19, outcome, and inflammatory markers were investigated. Levels of sACE2 were higher in COVID-19 patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < .0001. sACE2 was higher in men than women but was not affected by other risk factors for severe COVID-19. sACE2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < .0001, but remained higher than in healthy controls, p = .012. sACE was marginally lower during COVID-19 compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p = .008. Levels of sACE2 and sACE did not differ depending on survival or disease severity. sACE2 during COVID-19 correlated with von Willebrand factor, factor VIII and D-dimer, while sACE correlated with interleukin 6, tumor necrosis factor α, and plasminogen activator inhibitor 1. Conclusions: sACE2 was transiently elevated in COVID-19, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 differed in correlations with markers of inflammation and endothelial dysfunction, suggesting release from different cell types and/or vascular beds.


Assuntos
Enzima de Conversão de Angiotensina 2/sangue , COVID-19/sangue , Adulto , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/sangue , Sistema Renina-Angiotensina , Fatores de Risco , SARS-CoV-2
6.
J Appl Lab Med ; 6(5): 1179-1191, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34097042

RESUMO

BACKGROUND: 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 ACE in blood) is associated with increased risk of cardiovascular diseases. Elevated ACE in blood is also a marker for granulomatous diseases. METHODS: We applied our novel approach-ACE phenotyping-to characterize serum ACE in 300 unrelated patients and to establish normal values for ACE levels. ACE phenotyping includes (a) determination of ACE activity with 2 substrates (Z-Phe-His-Leu [ZPHL] and Hip-His-Leu [HHL]), (b) calculation of a ratio for hydrolysis of ZPHL and HHL, and (c) quantification of ACE immunoreactive protein levels and ACE conformation with a set of monoclonal antibodies (mAbs) to ACE. RESULTS: Only a combination of ACE activity determination with 2 substrates and quantification of the amount of ACE immunoreactive protein with mAbs 1G12 and 9B9 allows for the unequivocal detection of the presence of ACE inhibitors in the blood. After excluding such subjects, we were able to establish normal values of ACE in healthy populations: 50%-150% from control pooled serum. This ACE phenotyping approach in screening format with special attention to outliers can also identify patients with various mutations in ACE and may help to identify the as yet unknown ACE secretase or other mechanistic details of precise regulation of ACE expression. CONCLUSIONS: ACE phenotyping is a promising new approach with potential clinical significance to advance precision medicine screening techniques by establishing different risk groups based on ACE phenotype.


Assuntos
Inibidores da Enzima Conversora de Angiotensina , Peptidil Dipeptidase A/genética , Medicina de Precisão , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Angiotensinas , Humanos , Peptídeos , Peptidil Dipeptidase A/sangue , Fenótipo
7.
Diabetes Care ; 44(6): 1377-1384, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33827803

RESUMO

OBJECTIVE: The deletion (D) allele of the ACE insertion/deletion (I/D) polymorphism is a risk factor for diabetic kidney disease. We assessed its contribution to long-term kidney outcomes and all-cause death in patients with long-standing type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 1,155 participants from three French and Belgian cohorts were monitored for a median duration of 14 (interquartile range 13) years. The primary outcome was the occurrence of end-stage kidney disease (ESKD) or a 40% drop in the estimated glomerular filtration rate (eGFR). Secondary outcomes were the individual components of the primary outcome, rapid decline in eGFR (steeper than -3 mL/min/1.73 m2 per year), incident albuminuria, all-cause death, and a composite ESKD or all-cause death. Hazard ratios (HRs) for XD versus II genotype and for baseline plasma ACE levels were computed by Cox analysis. Genotype performance in stratifying the primary outcome was tested. RESULTS: Genotype distribution was 954 XD and 201 II. The primary outcome occurred in 20% of XD and 13% of II carriers: adjusted HR 2.07 (95% CI 1.32-3.40; P = 0.001). Significant associations were also observed for rapid decline in eGFR, incident albuminuria, ESKD, all-cause death, and ESKD or all-cause death. Baseline plasma ACE levels were higher in XD carriers and significantly associated with an increased risk of the primary outcome. The ACE genotype enhanced net reclassification improvement (0.154, 95% CI 0.007-0.279; P = 0.04) and integrated discrimination improvement (0.012, 95%CI 0.001-0.021; P = 0.02) for primary outcome stratification. CONCLUSIONS: The D-allele of the ACE I/D polymorphism was associated with an increased risk of major kidney events and all-cause death in patients with long-standing type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , Peptidil Dipeptidase A , Albuminúria/genética , Diabetes Mellitus Tipo 1/genética , Nefropatias Diabéticas/genética , Taxa de Filtração Glomerular , Humanos , Rim , Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/genética
8.
J Biochem ; 170(2): 245-253, 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33768251

RESUMO

Angiotensin converting enzyme (ACE) has a significant role in the angiogenesis of ovarian endothelium and the resumption of meiosis and folicular growth. However, there is no any study concerning ACE polymorphism and unexplained infertility (UI). The main aim of this study is that both identify ACE polymorphism and measure the serum ACE, anti-Mullerian hormone (AMH) and inhibin-B (INHB) levels in UI patients and controls in Turkish population. Forty-seven UI patients and 41 controls were involved in this study. To determine the ACE polymorphisms, DNA isolation and PCR were performed. Then, serum ACE, AMH and INHB levels were measured spectrophotometrically. Patients with UI had significantly higher serum INHB levels compared with controls (P < 0.05). Serum ACE levels were decreased, compared to controls; however, the decrease was not significant. Serum AMH levels did not significantly differ from controls. When the relationship was analysed between ACE insertion/deletion (I/D) polymorphism and infertility risk, and ID genotype was chosen as reference, it was found to be 2.33 times more risk of UI than the women have DD genotype [DD versus ID: odds ratio = 2.33, 95% confidence interval (0.88-6.19); P = 0.086]. This finding indicates that DD genotype may be high risk for UI. Further studies are warranted to confirm this finding, especially with a larger population.


Assuntos
Hormônio Antimülleriano/sangue , Infertilidade/genética , Inibinas/sangue , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Adulto , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Infertilidade/sangue , Peptidil Dipeptidase A/sangue , Turquia
9.
JAMA Psychiatry ; 78(6): 623-631, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33688928

RESUMO

Importance: Observational studies have reported associations between antihypertensive medication and psychiatric disorders, although the reported direction of association appears to be dependent on drug class. Objective: To estimate the potential effect of different antihypertensive drug classes on schizophrenia, bipolar disorder, and major depressive disorder. Design, Setting, and Participants: This 2-sample mendelian randomization study assessed the association between a single-nucleotide variant (SNV) and drug target gene expression derived from existing expression quantitative trait loci (eQTL) data in blood (sample 1) and the SNV-disease association from published case-control genome-wide association studies (sample 2). Significant associations were corroborated using published brain eQTL and protein QTL data. Participants included 40 675 patients with schizophrenia and 64 643 controls, 20 352 patients with bipolar disorder and 31 358 controls, and 135 458 patients with major depressive disorder and 344 901 controls. Blood eQTL levels were measured in 31 684 individuals from 37 cohorts (eQTLGen consortium); prefrontal cortex eQTLs were measured from the PsychENCODE resource in 1387 individuals; and protein QTLs were measured in cerebral spinal fluid from 544 individuals and plasma from 818 individuals. Data were collected from October 4, 2019, to June 1, 2020, and analyzed from October 14, 2019, to June 6, 2020. Exposures: Expression levels of antihypertensive drug target genes as proxies for drug exposure, and genetic variants robustly associated with the expression of these genes as mendelian randomization instruments. Main Outcomes and Measures: Risk for schizophrenia, bipolar disorder, and major depressive disorder. Results: A 1-SD lower expression of the angiotensin-converting enzyme (ACE) gene in blood was associated with lower systolic blood pressure of 4.0 (95% CI, 2.7-5.3) mm Hg, but increased risk of schizophrenia (odds ratio [OR], 1.75; 95% CI, 1.28-2.38; P = 3.95 × 10-4). A concordant direction of association was also observed between ACE expression in prefrontal cortex (OR, 1.33; 95% CI, 1.13-1.56) and ACE protein levels in cerebral spinal fluid (OR per 1-SD decrease, 1.12; 95% CI, 1.05-1.19) and plasma (OR per 1-SD decrease, 1.04; 95% CI, 1.01-1.07). We found no evidence for an association between genetically estimated SBP and schizophrenia risk. Conclusions and Relevance: Findings suggest an adverse association of lower ACE messenger RNA and protein levels with schizophrenia risk. These findings warrant greater pharmacovigilance and further investigation into the effect of ACE inhibitors, particularly those that are centrally acting, on psychiatric symptoms in patients with schizophrenia, as well as the role of ACE inhibitor use in late-onset schizophrenia.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Transtorno Bipolar/genética , Transtorno Depressivo Maior/genética , Análise da Randomização Mendeliana , Peptidil Dipeptidase A/genética , Farmacovigilância , Esquizofrenia/genética , Transtorno Bipolar/sangue , Transtorno Depressivo Maior/sangue , Estudo de Associação Genômica Ampla , Humanos , Peptidil Dipeptidase A/sangue , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/sangue , RNA Mensageiro/metabolismo , Esquizofrenia/sangue
11.
Eur J Endocrinol ; 184(4): 543-552, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33539316

RESUMO

OBJECTIVE: While evidence on the interface between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the renin-angiotensin-aldosterone-system (RAAS) is accumulating, clinical data on RAAS peptide alteration among coronavirus disease-19 (COVID-19) patients is missing. DESIGN AND METHODS: In this exploratory study, we prospectively included adult patients (aged ≥ 18 years) admitted between February 26 and April 30, 2020 to a tertiary care hospital in Switzerland. We assessed the association of an underlying SARS-CoV-2 infection and equilibrium serum levels of RAAS peptides in hospitalized COVID-19 patients 1:1 propensity-score matched with patients suffering from SARS-CoV-2-negative respiratory infections. Subgroup analyses involved stratification for taking RAAS inhibitors. RESULTS: COVID-19 patients had about 50% lower equilibrium serum RAAS peptide levels as compared with matched controls (angiotensin I: 31.6 vs 66.8 pmol/L, -52.7% (95%CI: -68.5% to -36.9%); angiotensin II: 37.7 vs 92.5 pmol/L, -59.2% (95%CI: -72.1% to -46.3%); angiotensin (1-5): 3.3 vs 6.6 pmol/L, -49.7% (95%CI: -59.2% to -40.2%); angiotensin (1-7): 4.8 vs 7.6 pmol/L, -64.9% (95%CI: -84.5% to -45.3%)). While the plasma renin activity was lower in COVID-19 patients (88.6 vs 207.9 pmol/L, -58.5% (95%CI: -71.4% to -45.6%)), there was no difference of angiotensin-converting enzyme (ACE) and ACE2 plasma activity between the groups. Subgroup analyses revealed a pronounced RAAS peptide profile depression in COVID-19 patients among those not on RAAS inhibitors. CONCLUSIONS: As compared with SARS-CoV-2-negative patients, we found a downregulated RAAS in presence of a SARS-CoV-2 infection. Whether the lower levels of the protective angiotensin (1-5) and (1-7) are linked to adverse outcomes in COVID-19 warrants further investigation.


Assuntos
Angiotensina II/sangue , Angiotensina I/sangue , Enzima de Conversão de Angiotensina 2/sangue , COVID-19/sangue , Fragmentos de Peptídeos/sangue , Peptidil Dipeptidase A/sangue , Renina/sangue , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema Renina-Angiotensina , SARS-CoV-2
12.
Scand J Clin Lab Invest ; 81(2): 160-165, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33474994

RESUMO

Angiotensin-converting enzyme (ACE)/Angiotensin (Ang) II pathway has crucial regulatory effects on circulatory hemostasis and immune responses. This pathway has a major role in the development of acute lung injury and acute respiratory distress syndrome (ARDS), which is a devastating complication of SARS-CoV-2 infection. The aim of this study is to investigate the serum ACE activity and its correlation with clinical features and the disease severity in patients with COVID-19. Patients with confirmed COVID-19 by detecting SARS-CoV-2 nucleic acid RT-PCR were included in the study. Demographic data, clinical features, laboratory and radiologic investigations were recorded. Patients were classified by disease severity; asymptomatic, mild, and severe pneumonia. The serum ACE activity was evaluated with an autoanalyzer based on a spectrophotometric method. Fifty-five patients (50.9% female) and 18 healthy subjects (33.3 % female) were enrolled in the study. The median age of patients was 40 years, ranging from 22 to 81 years. Eighteen healthy subjects were served as the control group. The baseline characteristics were comparable between groups. The median serum ACE activity of patients and controls (38.00 [IQR 21] U/L and 32.00 [IQR 24] U/L, respectively) and of between patients grouped by disease severity (38.5 [IQR 19], 36 [IQR 25], and 38 [IQR 22] U/L, asymptomatic, mild and severe pneumonia group, respectively) were similar. There was no correlation between the serum ACE activity and conventional inflammatory markers. In this study, we did not find an association between serum ACE activity and COVID-19 and serum ACE activity on admission did not reflect disease severity.


Assuntos
COVID-19/enzimologia , COVID-19/fisiopatologia , Peptidil Dipeptidase A/sangue , SARS-CoV-2 , Índice de Gravidade de Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiotensina II/metabolismo , Biomarcadores/sangue , Comorbidade , Feminino , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade
13.
Biosci Rep ; 41(2)2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33442728

RESUMO

The outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a global catastrophe. The elderly and people with comorbidity are facing a serious complication of the disease. The entry and infection strategy of SARS-CoV-2 in a host cell is raised by an amazing way of angiotensin-converting enzyme (ACE) 2 (ACE2) receptor recognition and imbalance of ACE/ACE2 in various organs, especially in the lungs. Here it has been discussed the role of interferon and protease during the receptor recognition (begining of infection) and followed by the impact of cytokine and hypoxia in the context of the balance of ACE/ACE2. It has also very concisely delineated the biochemistry and mechanism of ACE/ACE2 balance in different stages of infection and its role in comorbidity.


Assuntos
Enzima de Conversão de Angiotensina 2/sangue , COVID-19/epidemiologia , COVID-19/etiologia , Peptidil Dipeptidase A/sangue , SARS-CoV-2/patogenicidade , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , COVID-19/tratamento farmacológico , Comorbidade , Citocinas/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Sistema Renina-Angiotensina/fisiologia , Internalização do Vírus
14.
Ocul Immunol Inflamm ; 29(5): 902-905, 2021 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-31944169

RESUMO

Permanent make-up tattooing as a cosmetic procedure is gaining popularity especially among women. Although it is considered a relatively safe intervention, the ink used can rarely be a trigger of sarcoidosis. Uveitis can occur as part of this inflammatory process. In this study, we describe two ladies presented with tattoo-associated uveitis as the first manifestations of systemic sarcoidosis. They developed intermediate uveitis shortly after skin inflammation several months after permanent make-up tattooing of eyebrows. Lung involvement, high ACE levels, and negative PPD were present. Skin granuloma formation was diffuse over the area of tattoo in one patient and localized in the other one. This is the first report of uveitis following make-up tattoo.


Assuntos
Sobrancelhas , Granuloma de Corpo Estranho/etiologia , Sarcoidose Pulmonar/diagnóstico , Tatuagem/efeitos adversos , Uveíte Intermediária/etiologia , Feminino , Angiofluoresceinografia , Granuloma de Corpo Estranho/diagnóstico , Humanos , Pessoa de Meia-Idade , Oftalmoscopia , Peptidil Dipeptidase A/sangue , Radiografia Torácica , Vasculite Retiniana/diagnóstico , Tomografia Computadorizada por Raios X , Uveíte Intermediária/diagnóstico , Acuidade Visual/fisiologia
16.
Biomed Pharmacother ; 133: 110938, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33171402

RESUMO

We investigated oxidative stress and RAAS biomarkers, as well as their association, in chronic heart failure (CHF) patients on optimized medical therapy, stratified by disease severity or by renal function. Since vitamin D has been shown to attenuate RAAS activation and oxidative stress, we further evaluated the relationship between vitamin D, RAAS and oxidative stress in CHF patients with or without renal impairment. Sixty CHF outpatients were included and stratified by disease severity or by renal function. We quantified urinary hydrogen peroxide, plasma and urinary isoprostanes, plasma total antioxidant status, urinary angiotensinogen (intrarenal RAAS activation biomarker) and plasma angiotensinogen, plasma renin and aldosterone concentration, serum angiotensin-converting enzyme (ACE) activity, plasma angiotensin peptides, and serum total 25-hydroxyvitamin D (S-total 25(OH)D). Severe CHF patients had higher urinary isoprostanes (p = 0.002) and lower S-total 25(OH)D (p = 0.006) compared to mild-to-moderate patients, but no differences were observed for other redox or RAAS biomarkers. Patients with impaired renal function (iRF) had higher urinary angiotensinogen (p = 0.003) and lower S-total 25(OH)D (p = 0.028) compared to those with normal renal function (nRF), while no differences were observed for the remaining RAAS and redox parameters. Several positive correlations between oxidative stress and RAAS biomarkers were detected in iRF patients, while in patients with nRF these correlations were primarily inverse. In CHF-iRF patients, S-25(OD)D was inversely associated with urinary isoprostanes, which in turn were positively associated with plasma angiotensinogen and serum ACE. In conclusion, CHF patients with renal function impairment have increased intrarenal RAAS activation and lower vitamin D values and might benefit from the combination of RAAS blockers with vitamin D and/or antioxidants.


Assuntos
Taxa de Filtração Glomerular , Insuficiência Cardíaca/fisiopatologia , Nefropatias/fisiopatologia , Rim/fisiopatologia , Estresse Oxidativo , Sistema Renina-Angiotensina , Idoso , Angiotensinogênio/sangue , Angiotensinogênio/urina , Biomarcadores/sangue , Biomarcadores/urina , Doença Crônica , Feminino , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/metabolismo , Humanos , Isoprostanos/sangue , Isoprostanos/urina , Nefropatias/complicações , Nefropatias/metabolismo , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/sangue , Índice de Gravidade de Doença , Vitamina D/análogos & derivados , Vitamina D/sangue
17.
Transl Res ; 230: 5-20, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32726712

RESUMO

An elevated blood angiotensin I-converting enzyme (ACE) supports diagnosis of sarcoidosis and Gaucher disease. However, some ACE mutations increase ACE shedding, and patients with these mutations are therefore at risk of being incorrectly diagnosed with sarcoidosis because of elevated serum ACE levels. We applied a novel approach called "ACE phenotyping" to identify possible ACE mutations in 3 pulmonary clinic patients that had suspected sarcoidosis based on elevated blood ACE levels. Conformational fingerprinting of ACE indicated that these mutations may be localized in the stalk region of the protein and these were confirmed by whole exome sequencing. Index patient 1 (IP1) had a mutation (P1199L) that had been previously identified, while the other 2 patients had novel ACE mutations. IP2 had 2 mutations, T887M and N1196K (eliminating a putative glycosylation site), while IP3 had a stop codon mutation Q1124X (eliminating the transmembrane anchor). We also performed a comprehensive analysis of the existing database of all ACE mutations to estimate the proportion of mutations increasing ACE shedding. The frequency of ACE mutations resulting in increased blood ACE levels may be much higher than previously estimated. ACE phenotyping, together with whole exome sequencing, is a diagnostic approach that could prevent unnecessary invasive and/or costly diagnostic procedures, or potentially harmful treatment for patients misdiagnosed on the basis of elevated blood ACE levels.


Assuntos
Peptidil Dipeptidase A/sangue , Peptidil Dipeptidase A/genética , Polimorfismo Genético , Sarcoidose/sangue , Sarcoidose/diagnóstico , Idoso , Biomarcadores/sangue , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Simulação de Acoplamento Molecular , Mapeamento de Peptídeos , Ligação Proteica , Conformação Proteica
18.
Mod Rheumatol Case Rep ; 5(1): 167-171, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32967569

RESUMO

A 41-year-old man presented with itching of the skin surrounding his tattoos, blurred vision, fever, general fatigue, and arthralgia. Physical examination revealed skin bulges confined to the tattoo ink lines. Histological analyses of the skin revealed non-caseating granulomas surrounding the tattoo inks. Together with other clinical manifestations including uveitis, lymph nodes swelling, and elevated serum angiotensin-converting enzyme and lysozyme, he was diagnosed with systemic sarcoidosis. The administration of prednisolone alleviated the sarcoidosis-related symptoms, including skin changes. This case illustrates that skin changes on tattoos can be a presenting manifestation of systemic sarcoidosis and that skin biopsy is useful in early diagnosis.


Assuntos
Granuloma/etiologia , Sarcoidose/complicações , Pele/patologia , Tatuagem/efeitos adversos , Uveíte/etiologia , Adulto , Biópsia , Granuloma/diagnóstico , Humanos , Masculino , Muramidase/sangue , Peptidil Dipeptidase A/sangue , Prurido/etiologia , Sarcoidose/diagnóstico , Uveíte/diagnóstico
20.
Cells ; 11(1)2021 12 23.
Artigo em Inglês | MEDLINE | ID: mdl-35011591

RESUMO

Angiotensin-converting enzyme-1 (ACE1) and apolipoproteins (APOs) may play important roles in the development of Alzheimer's disease (AD) and cardiovascular diseases (CVDs). This study aimed to examine the associations of AD, CVD, and endocrine-metabolic diseases (EMDs) with the levels of ACE1 and 9 APO proteins (ApoAI, ApoAII, ApoAIV, ApoB, ApoCI, ApoCIII, ApoD, ApoE, and ApoH). Non-Hispanic white individuals including 109 patients with AD, 356 mild cognitive impairment (MCI), 373 CVD, 198 EMD and controls were selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset. Multivariable general linear model (GLM) was used to examine the associations. ApoE ε4 allele was associated with AD, as well as ApoAIV, ApoB and ApoE proteins, but not associated with CVD and EMD. Both AD and CVD were associated with levels of ACE1, ApoB, and ApoH proteins. AD, MCI and EMD were associated with levels of ACE1, ApoAII, and ApoE proteins. This is the first study to report associations of ACE1 and several APO proteins with AD, MCI, CVD and EMD, respectively, including upregulated and downregulated protein levels. In conclusion, as specific or shared biomarkers, the levels of ACE1 and APO proteins are implicated for AD, CVD, EMD and ApoE ε4 allele. Further studies are required for validation to establish reliable biomarkers for these health conditions.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/enzimologia , Apolipoproteínas/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/enzimologia , Peptidil Dipeptidase A/sangue , Idoso , Análise por Conglomerados , Feminino , Humanos , Modelos Lineares , Masculino , Análise Multivariada
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