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1.
Insulin autoimmune syndrome in an occidental woman: a case report and literature review.
Reis, MZR, Fernandes, VO, Fontenele, EGP, Sales, APAM, Montenegro Junior, RM, Quidute, ARP
Archives of endocrinology and metabolism. 2018;(5):566-570
Abstract
Insulin autoimmune syndrome (IAS, Hirata's disease) is a rare hypoglycemic disorder characterized by spontaneous hypoglycemia associated with extremely high circulating insulin levels and positive anti-insulin antibody results. Thus far, most cases have been reported in Asian countries, notably Japan, with few cases reported in western countries. As a possible cause, it is associated with the use of drugs containing sulfhydryl radicals, such as captopril. This report refers to a 63-year-old female Brazilian patient with a history of postprandial hypoglycemia. After extensive investigation and exclusion of other causes, her hyperinsulinemic hypoglycemia was considered to have likely been induced by captopril. Most cases of IAS are self-limiting. However, dietary management, corticosteroids, plasmapheresis, and rituximab have already been used to treat patients with IAS. In our case, after discontinuation of captopril, an initial decrease in insulin autoantibody levels was observed followed by improvement in episodes of hypoglycemia. Although it is a rare disease, IAS should be considered in the differential diagnosis of endogenous hyperinsulinemic hypoglycemia. Patients with suspected IAS must be screened for autoimmunity-related drugs for insulin. Initial clinical suspicion of IAS can avoid unnecessary costs associated with imaging examinations and/or invasive surgical procedures.
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Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease.
Sasongko, TH, Nagalla, S, Ballas, SK
The Cochrane database of systematic reviews. 2015;(6):CD009191
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Abstract
BACKGROUND Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in people with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. This is an update of a Cochrane Review first published in 2013. OBJECTIVES To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects. SEARCH METHODS The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 03 June 2015. SELECTION CRITERIA Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen. DATA COLLECTION AND ANALYSIS Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments. MAIN RESULTS Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (seven males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow up of three months) with captopril or placebo. The overall quality of the outcomes reported was high, since most aspects that may contribute to bias were regarded to be of low risk, although allocation concealment was not reported. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure. AUTHORS' CONCLUSIONS There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study.
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3.
Dietary flavonoids added to pharmacological antihypertensive therapy are effective in improving blood pressure.
de Jesús Romero-Prado, MM, Curiel-Beltrán, JA, Miramontes-Espino, MV, Cardona-Muñoz, EG, Rios-Arellano, A, Balam-Salazar, LB
Basic & clinical pharmacology & toxicology. 2015;(1):57-64
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Abstract
Epidemiological studies have suggested that the daily intake of flavonoids is associated with a decreased risk of developing cardiovascular disease. Our purpose was to evaluate the effect of the addition of dietary flavonoids (DF) to antihypertensive treatment (AHT), based on telmisartan (Tms) or captopril (Cpr), on blood pressure (BP), body mass index (BMI), waist/hip ratio, leptin, lipid profile and inflammation in hypertensive young patients. An open-label, randomized, controlled trial was performed among 79 patients aged 20-55 years with grade I or grade II systemic arterial hypertension. The subjects were assigned to one of four groups for AHT plus DF during 6 months: Cpr (n = 14), Cpr + DF (n = 19), Tms (n = 25) and Tms + DF (n = 21). DF consisted of dark chocolate, dehydrated red apple and green tea in an infusion to obtain a daily dose of 425.8 ± 13.9 mg epicatechin equivalents. The BP and anthropometric parameters were measured every 2 weeks. Lipid profile, leptin and hsCRP were determined by standard methods. The combination AHT-DF produced an additional and significant reduction in (i) SBP/DBP of -5/-4 mmHg, being -7/-5 for Cpr + DF and -4/-3 for Tms + DF; (ii) triglyceride levels (-30.6%) versus AHT alone (-9.6%); and (iii) leptin: Cpr + DF versus Tms + DF (p < 0.005). Finally, C-reactive protein plasma levels were reduced significantly in all groups independently of the applied treatment. We conclude that the addition of flavonoids to pharmacological antihypertensive therapy shows additional benefits on BP, lipid profile, leptin, obesity and inflammation.
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Human interventions to characterize novel relationships between the renin-angiotensin-aldosterone system and parathyroid hormone.
Brown, JM, Williams, JS, Luther, JM, Garg, R, Garza, AE, Pojoga, LH, Ruan, DT, Williams, GH, Adler, GK, Vaidya, A
Hypertension (Dallas, Tex. : 1979). 2014;(2):273-80
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Abstract
Observational studies in primary hyperaldosteronism suggest a positive relationship between aldosterone and parathyroid hormone (PTH); however, interventions to better characterize the physiological relationship between the renin-angiotensin-aldosterone system (RAAS) and PTH are needed. We evaluated the effect of individual RAAS components on PTH using 4 interventions in humans without primary hyperaldosteronism. PTH was measured before and after study (1) low-dose angiotensin II (Ang II) infusion (1 ng/kg per minute) and captopril administration (25 mg×1); study (2) high-dose Ang II infusion (3 ng/kg per minute); study (3) blinded crossover randomization to aldosterone infusion (0.7 µg/kg per hour) and vehicle; and study (4) blinded randomization to spironolactone (50 mg/daily) or placebo for 6 weeks. Infusion of Ang II at 1 ng/kg per minute acutely increased aldosterone (+148%) and PTH (+10.3%), whereas Ang II at 3 ng/kg per minute induced larger incremental changes in aldosterone (+241%) and PTH (+36%; P<0.01). Captopril acutely decreased aldosterone (-12%) and PTH (-9.7%; P<0.01). In contrast, aldosterone infusion robustly raised serum aldosterone (+892%) without modifying PTH. However, spironolactone therapy during 6 weeks modestly lowered PTH when compared with placebo (P<0.05). In vitro studies revealed the presence of Ang II type I and mineralocorticoid receptor mRNA and protein expression in normal and adenomatous human parathyroid tissues. We observed novel pleiotropic relationships between RAAS components and the regulation of PTH in individuals without primary hyperaldosteronism: the acute modulation of PTH by the RAAS seems to be mediated by Ang II, whereas the long-term influence of the RAAS on PTH may involve aldosterone. Future studies to evaluate the impact of RAAS inhibitors in treating PTH-mediated disorders are warranted.
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5.
Angiotensin-converting enzyme (ACE) inhibitors for proteinuria and microalbuminuria in people with sickle cell disease.
Sasongko, TH, Nagalla, S, Ballas, SK
The Cochrane database of systematic reviews. 2013;(3):CD009191
Abstract
BACKGROUND Sickle cell disease is a group of disorders characterized by deformation of erythrocytes. Renal damage is a frequent complication in sickle cell disease as a result of long-standing anemia and disturbed circulation through the renal medullary capillaries. Due to the improvement in life expectancy of people with sickle cell disease, there has been a corresponding significant increase in the incidence of renal complications. Microalbuminuria and proteinuria are noted to be a strong predictor of subsequent renal failure. There is extensive experience and evidence with angiotensin-converting enzyme (ACE) inhibitors over many years in a variety of clinical situations for patients who do not have sickle cell disease, but their effect in patients with this disease is unknown. It is common practice to administer ACE inhibitors for sickle nephropathy due to their renoprotective properties; however, little is known about their effectiveness and safety in this setting. OBJECTIVES To determine the effectiveness of ACE inhibitor administration in people with sickle cell disease for decreasing intraglomerular pressure, microalbuminuria and proteinuria and to to assess the safety of ACE inhibitors as pertains to their adverse effects. SEARCH METHODS The authors searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Hameoglobinopathies Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings.Date of the most recent search: 05 July 2012. SELECTION CRITERIA Randomized or quasi-randomized controlled trials of ACE inhibitors designed to reduce microalbuminuria and proteinuria in people with sickle cell disease compared to either placebo or standard treatment regimen. DATA COLLECTION AND ANALYSIS Three authors independently applied the inclusion criteria in order to select studies for inclusion in the review. Two authors assessed the risk of bias of studies and extracted data and the third author verified these assessments. MAIN RESULTS Five studies were identified through the searches, only one met our inclusion criteria. The included study randomized 22 participants (7 males and 15 females) having proteinuria or microalbuminuria with sickle cell disease and treated the participants for six months (median length of follow-up of three months) with captopril or placebo. At six months, the study reported no significant difference in urinary albumin excretion between the captopril group and the placebo group, although the mean urinary albumin excretion in the captopril group was lower by a mean difference of -49.00 (95% confidence interval -124.10 to 26.10) compared to that of placebo. However, our analysis on the absolute change score showed significant changes between the two groups by a mean difference of -63.00 (95% confidence interval -93.78 to -32.22). At six months albumin excretion in the captopril group was noted to decrease from baseline by a mean of 45 ± 23 mg/day and the placebo group was noted to increase by 18 ± 45 mg/day. Serum creatinine and potassium levels were reported constant throughout the study. The potential for inducing hypotension should be highlighted; the study reported a decrease of 8 mmHg in systolic pressure and 5 mmHg in diastolic and mean blood pressure. AUTHORS' CONCLUSIONS There is not enough evidence to show that the administration of ACE inhibitors is associated with a reduction of microalbuminuria and proteinuria in people with sickle cell disease, although a potential for this was seen. More long-term studies involving multiple centers and larger cohorts using a randomized-controlled design are warranted, especially among the pediatric age group. Detailed reporting of each outcome measure is necessary to allow a clear cut interpretation in a systematic review. One of the difficulties encountered in this review was the lack of detailed data reported in the included study.
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Oxyhalogen-sulfur chemistry: kinetics and mechanism of oxidation of captopril by acidified bromate and aqueous bromine.
Kapungu, GP, Rukweza, G, Tran, T, Mbiya, W, Adigun, R, Ndungu, P, Martincigh, B, Simoyi, RH
The journal of physical chemistry. A. 2013;(13):2704-17
Abstract
By nature of their nucleophilicity, all thiol-based drugs are oxidatively metabolized in the physiological environment. The key to understanding the physiological role of a hypertension drug, (2S)-1-[(2S)-2-methyl-3-sulfanylpropanoyl]pyrrolidine-2-carboxylic acid, medically known as captopril is through studying its oxidation pathway: its reactive intermediates and oxidation products. The oxidation of captopril by aqueous bromine and acidified bromate has been studied by spectrophotometric and electrospray ionization techniques. The stoichiometry for the reaction of acidic bromate with captopril is 1:1, BrO3(-) + (C4H6N)(COOH)(COCHCH3CH2)-SH → (C4H6N)(COOH)(COCHCH3CH2)-SO3H + Br(-), with reaction occurring only at the thiol center. For the direct reaction of bromine with captopril, the ratio is 3:1; 3Br2 + (C4H6N)(COOH)(COCHCH3CH2)-SH + 3H2O → (C4H6N)(COOH)(COCHCH3CH2)-SO3H + 6HBr. In excess acidic bromate conditions the reaction displays an initial induction period followed by a sharp rise in absorbance at 390 nm due to rapid formation of bromine. The direct reaction of aqueous bromine with captopril was much faster than oxidation of the thiol by acidified bromate, with a bimolecular rate constant of (1.046 (±0.08) × 10(5) M(-1) s(-1). The detection of thiyl radicals confirms the involvement of radicals as intermediates in the oxidation of Captopril by acidified BrO3(-). The involvement of thiyl radicals in oxidation of captopril competes with a nonradical pathway involving 2-electron oxidations of the sulfur center. The oxidation product of captopril under these strong oxidizing conditions is a sulfonic acid as confirmed by electrospray ionization mass spectrometry (ESI-MS), iodometric titrations, and proton nuclear magnetic resonance ((1)H NMR) results. There was no evidence from ESI-MS for the formation of the sulfenic and sulfinic acids in the oxidation pathway as the thiol group is rapidly oxidized to the sulfonic acid. A computer simulation analysis of this mechanism gave a reasonably good fit to the experimental data.
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7.
New Delhi metallo-β-lactamase I: substrate binding and catalytic mechanism.
Zheng, M, Xu, D
The journal of physical chemistry. B. 2013;(39):11596-607
Abstract
Metallo-β-lactamases can hydrolyze and deactivate lactam-containing antibiotics, which is the major mechanism for causing drug resistance in the treatment of bacterial infections. This has become a global concern because of the lack of clinically approved inhibitors so far. The emergence of New Delhi metallo-β-lactamase I (NDM-1) makes the situation even more serious. In this work, first, the structure of NDM-1 in complex with the inhibitor molecule l-captopril is investigated by both density functional theory (DFT) and hybrid quantum mechanical/molecular mechanical (QM/MM) methods, and the theoretical results are in good agreement with the X-ray structure. The Michaelis structure with an antibiotic compound (ampicillin) bound in the active site is constructed from a recent X-ray structure of the NDM-1 enzyme with hydrolyzed ampicillin. It is further simulated using a QM/MM molecular dynamics method. One of the interesting binding features of ampicillin in the NDM-1 active site is that the conserved C3 carboxylate group is not ligated with Zn2 but rather is only hydrogen-bonded with N220 and K211. A bridging hydroxide ion is suggested to connect two zinc cofactors. This hydroxide ion is also hydrogen-bonded with D124. Subsequent reaction path calculations indicate that the initial step of lactam ring-opening occurs through a concerted step in which the cleavage of the C-N bond and the transfer of the hydrogen bond to D124 are nearly concerted. The ligand bond between Zn2 and the C3 carboxylate group forms after the first step of nucleophilic addition. The calculated activation energy barrier height is about 19.4 kcal/mol for the hydrolysis of ampicillin, which can be compared with the experimental value of 15.8 kcal/mol derived from kcat = 15 s(-1). The overall mechanism is finally confirmed by a subsequent DFT study of a truncated active-site model.
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8.
The new approach for captopril detection employing triangular gold nanoparticles-catalyzed luminol chemiluminescence.
Chen, Q, Bai, S, Lu, C
Talanta. 2012;:142-8
Abstract
In this work, we utilize the triangular gold nanoparticles (AuNPs) prepared by trisodium citrate reduction of HAuCl(4) in presence of nonionic fluorosurfactant (FSN) as a novel chemiluminescence (CL) probe for the determination of captopril. Captopril can induce a sharp decrease in CL intensity from the triangular AuNPs-catalyzed luminol system. Under the selected experimental conditions, a linear relationship was obtained between the logarithm of CL intensity and the logarithm of concentration of captopril in the range of 23.0-920 nM, and the detection limit at a signal-to-noise ratio of 3 for captopril was 4.6 nM. The as-prepared triangular AuNPs were easier to synthesize, stable at a wider pH range and high ionic strength, and exhibited a high selectivity and an excellent sensitivity toward captopril. The applicability of the proposed method has been validated by determining captopril in commercial pharmaceutical formulations and human urine samples with satisfactory results. The recoveries for captopril in spiked samples were found to be between 95.0% and 103.5%. The method shows promise for routine control analysis of pharmaceutical preparations and human urine samples. Moreover, based on the CL spectra, UV-vis spectra and transmission electron microscope (TEM) measurements, a possible CL mechanism was proposed. The mechanism of high selectivity toward captopril is supposed to originate from the tight binding of the sulphydryl groups of captopril to the active site of the as-prepared triangular AuNPs, leading to oxygen-related radicals cannot easily be generated from H(2)O(2) on the surface of triangular AuNPs.
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9.
[Clinical observation on treatment of early diabetic nephropathy by milkvetch injection combined with captopril].
Liu, YH, Yang, L, Liu, J
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine. 2005;(11):993-5
Abstract
OBJECTIVE To investigate the therapeutic effect of milkvetch injection (MI) combined with Captopril on early diabetic nephropathy (EDN). METHODS A total of 69 EDN patients were randomly divided into three groups, with 23 in each group. Besides the conventional hypoglycemic therapy, patients in Group A Captopril, in Group B MI plus Captopril and in Group C MI were given respectively. The therapeutic course for all was 3 months. The related indices of EDN before and after treatment were measured and compared. RESULTS After treatment, the blood pressure significantly lowered after treatment in Group A and B (P<0.01), but unchanged in Group C; the levels of blood glucose and HbA1c significantly decreased in Group B and C (P < 0.05 or P<0.01), and significant difference was shown in comparison of Group B with Group A (P<0.05); levels of 24hrs urinary albumin excretion (UAER), blood urea nitrogen (BUN) and serum creatinine (SCr) significantly decreased in all 3 groups, and the decrement in Group B was more significant than that in the other two groups (P <0.05). CONCLUSION MI combined with Captopril can not only decrease blood pressure, blood glucose and HbA1c, but also significantly decrease the UAER in treating EDN.
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10.
Renoprotective effect of diltiazem in hypertensive type 2 diabetic patients with persistent microalbuminuria despite ACE inhibitor treatment.
Pérez-Maraver, M, Carrera, MJ, Micaló, T, Sahun, M, Vinzia, C, Soler, J, Montanya, E
Diabetes research and clinical practice. 2005;(1):13-9
Abstract
The aim of the study was to evaluate the effects of the non-dihydropyridine calcium antagonist (NDCA) diltiazem on the development of urinary albumin excretion (UAE) in type 2 hypertensive diabetic patients with persistent microalbuminuria despite ACE inhibitor treatment. Thirty-six type 2 diabetic hypertensive patients with microalbuminuria persisting after at least 1 year of treatment with ACE inhibitors were randomized to receive captopril (n=22) or combined therapy with captopril and 120 mg diltiazem (n=14) for 2 years. Captopril dose was individualized according to blood pressure. Changes in UAE, blood pressure, and metabolic control were monitored to analyze the influence of the addition of diltiazem on progression of diabetic nephropathy. In patients treated with captopril and diltiazem, absolute UAE did not change during the study (baseline: 101 mg/24 h, range 39-298; 2 years after randomization: 74 mg/24 h, range 12-665). In contrast, UAE increased in patients treated with captopril monotherapy (baseline: 118 mg/24 h, range 32-282; 2 years after randomization: 164 mg/24 h, range 15-1161, p<0.05). In addition, fewer patients in the captopril/diltiazem group progressed to macroalbuminuria (eight patients in captopril group and one in captopril/diltiazem group, p<0.05). The beneficial effects of the addition of diltiazem were independent of blood pressure and metabolic control. We suggest that the combination of ACE inhibitors and NDCA should be considered in type 2 microalbuminuric patients at high risk for progression to established diabetic nephropathy.