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1.
Wiad Lek ; 74(9 cz 1): 2087-2093, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34725281

RESUMO

OBJECTIVE: The aim: To increase the treatment effectiveness of CHF patients after MI with stenting by using magnesium and potassium salts of gluconic acid, eplerenone, and rivaroxaban in complex therapy. PATIENTS AND METHODS: Materials and methods: The research was performed at the premises of Ivano-Frankivsk Regional Clinical Cardiology Centre, Ukraine. 84 patients with CHF after past MI were examined. RESULTS: Results and conclusions: A more pronounced anti-ischemic effect has been linked to the use of combination therapy with rivaroxaban on the background of basic therapy (BT) in patients with CHF after MI, compared with the use of magnesium and potassium salts of gluconic acid or eplerenone. The use of eplerenone in the complex treatment of these patients on the background of BT has been proven to provide a pronounced reverse remodeling of the left myocardium in the postinfarction period.


Assuntos
Insuficiência Cardíaca , Infarto do Miocárdio , Eplerenona , Gluconatos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Magnésio , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Miocárdio , Potássio , Rivaroxabana/uso terapêutico , Sais , Espironolactona/uso terapêutico
2.
Kardiologiia ; 61(10): 99-103, 2021 Oct 30.
Artigo em Russo | MEDLINE | ID: mdl-34763644

RESUMO

The article presents recent data on possibilities of a broader use of mineralocorticoid receptor antagonists for existing indications and of expanding indications for the use of this pharmaceutical group in the context of the novel coronavirus infection COVID-19. The authors discussed prospects for expanded detection of aldosteronism using a new diagnostic approach, including an additional evaluation of blood pressure response to spironolactone.


Assuntos
COVID-19 , Hipertensão , Prova Pericial , Humanos , Antagonistas de Receptores de Mineralocorticoides , SARS-CoV-2 , Espironolactona
3.
Arterioscler Thromb Vasc Biol ; 41(11): 2740-2755, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34615372

RESUMO

Objective: MR (mineralocorticoid receptor) activation associates with increased risk of cardiovascular ischemia while MR inhibition reduces cardiovascular-related mortality and plaque inflammation in mouse atherosclerosis. MR in myeloid cells (My-MR) promotes inflammatory cell infiltration into injured tissues and atherosclerotic plaque inflammation by unclear mechanisms. Here, we examined the role of My-MR in leukocyte trafficking and the impact of sex. Approach and Results: We confirm in vivo that My-MR deletion (My-MR-KO) in ApoE-KO mice decreased plaque size. Flow cytometry revealed fewer plaque macrophages with My-MR-KO. By intravital microscopy, My-MR-KO significantly attenuated monocyte slow-rolling and adhesion to mesenteric vessels and decreased peritoneal infiltration of myeloid cells in response to inflammatory stimuli in male but not female mice. My-MR-KO mice had significantly less PSGL1 (P-selectin glycoprotein ligand 1) mRNA in peritoneal macrophages and surface PSGL1 protein on circulating monocytes in males. In vitro, MR activation with aldosterone significantly increased PSGL1 mRNA only in monocytes from MR-intact males. Similarly, aldosterone induced, and MR antagonist spironolactone inhibited, PSGL1 expression in human U937 monocytes. Mechanistically, aldosterone stimulated MR binding to a predicted MR response element in intron-1 of the PSGL1 gene by ChIP-qPCR. Reporter assays demonstrated that this PSGL1 MR response element is necessary and sufficient for aldosterone-activated, MR-dependent transcriptional activity. Conclusions: These data identify PSGL1 as a My-MR target gene that drives leukocyte trafficking to enhance atherosclerotic plaque inflammation. These novel and sexually dimorphic findings provide insight into increased ischemia risk with MR activation, cardiovascular protection in women, and the role of MR in atherosclerosis and tissue inflammation.


Assuntos
Aorta Torácica/metabolismo , Doenças da Aorta/metabolismo , Aterosclerose/metabolismo , Adesão Celular , Migração e Rolagem de Leucócitos , Macrófagos Peritoneais/metabolismo , Glicoproteínas de Membrana/metabolismo , Monócitos/metabolismo , Receptores de Mineralocorticoides/metabolismo , Adulto , Animais , Aorta Torácica/patologia , Doenças da Aorta/genética , Doenças da Aorta/patologia , Doenças da Aorta/prevenção & controle , Aterosclerose/genética , Aterosclerose/patologia , Aterosclerose/prevenção & controle , Adesão Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Hipoglicemia/tratamento farmacológico , Hipoglicemia/genética , Hipoglicemia/metabolismo , Migração e Rolagem de Leucócitos/efeitos dos fármacos , Macrófagos Peritoneais/patologia , Masculino , Glicoproteínas de Membrana/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout para ApoE , Pessoa de Meia-Idade , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Monócitos/efeitos dos fármacos , Monócitos/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Mineralocorticoides/efeitos dos fármacos , Receptores de Mineralocorticoides/genética , Fatores Sexuais , Transdução de Sinais , Espironolactona/uso terapêutico , Transcrição Genética , Migração Transendotelial e Transepitelial , Resultado do Tratamento , Células U937 , Adulto Jovem
4.
Colloids Surf B Biointerfaces ; 208: 112101, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34517218

RESUMO

This study proposes developing a topical formulation based on poly-ε-caprolactone (PCL) or methacrylic acid/methyl methacrylate copolymer (EL100) nanoparticles to enable a safer and more effective therapy of alopecia and acne with spironolactone. The effect of the size of the nanoparticle on follicular-targeted drug delivery is also verified. Compatibility studies based on thermal analyses and complementary techniques showed a small interaction of the drug with excipients, which may not compromise the drug stability. PCL nanoparticles of 180.0 ±â€¯1.6 and 126.8 ±â€¯1.0 nm, and EL100 nanoparticles of 102.7 ±â€¯7.1 nm were then prepared. All nanoparticles entrapped more than 75 % of spironolactone, were physically stable, and stabilized the drug for at least 90 days. They were also non-irritant according to HET-CAM tests. Drug release from the nanoparticles was reduced in aqueous buffer media but fast when in contact with oil. Finally, in vitro skin penetration experiments revealed the largest nanoparticles (of 180 nm) targeted drug delivery to the hair follicles 5-fold (p < 0.05) more than the control solution, 2.1-fold (p < 0.05) more than nanoparticles produced with the same polymer (PCL) but with smaller size (123 nm), and 4.9-fold (p < 0.05) more than the 102-nm E100 nanoparticles. In conclusion, follicular targeting can be adjusted according to nanoparticle size, and this work succeeded in obtaining polymeric nanoparticles adequate to enable topical treatment of acne and alopecia with spironolactone.


Assuntos
Portadores de Fármacos , Nanopartículas , Sistemas de Liberação de Medicamentos , Tamanho da Partícula , Poliésteres , Polímeros , Espironolactona
5.
J Org Chem ; 86(18): 12831-12839, 2021 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-34477382

RESUMO

(+)- and (-)-talaromyoxaones A and B (1 and 2, respectively), two new oxaphenalenone derivatives with a hemiacetal frame and an unprecedented spirolactone frame of a 2'H,3H,4'H-spiro[isobenzofuran-1,3'-pyran]-3-one unit that show biosynthetic enantiodivergence, and two new oxaphenalenone analogues (±)-11-apopyrenulin (3) and (+)- or (-)-abeopyrenulin (4) were isolated from the marine-derived fungus Talaromyces purpureogenus SCSIO 41517. Their structures were elucidated by spectroscopic analysis, single-crystal X-ray diffraction, and quantum chemical calculations of ECD spectra. Compounds 1 and 2 showed selective inhibitory activity against phosphatases SHP1, SHP2, and MEG2 with IC50 values of 1.3-3.4 µM, and the potential modes of action for 1 were investigated by a preliminary molecular docking study.


Assuntos
Talaromyces , Simulação de Acoplamento Molecular , Monoéster Fosfórico Hidrolases , Espironolactona
6.
JACC Heart Fail ; 9(11): 795-802, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34509404

RESUMO

OBJECTIVES: This study investigated an enriched cohort of patients with heart failure and preserved ejection fraction (HFpEF) in TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) with an echocardiographic phenotype of cardiac amyloidosis. BACKGROUND: There is a high prevalence of increased interventricular septal (IVS) thickness and decreased mitral annular systolic (s') velocity in cardiac amyloidosis. In addition, clinical trials of neurohormonal blockade are missing in this population. METHODS: TOPCAT randomized patients with HFpEF to spironolactone or placebo therapy with a primary endpoint of cardiovascular death, HF hospitalization, or aborted cardiac arrest. Patients with IVS and s' velocity measurements were included, and adjusted Cox models assessed the effect of echocardiographic variables and spironolactone on the primary endpoint. RESULTS: Among 590 patients, mean s' velocity was 6.4 ± 2.1 cm/s and IVS thickness was 1.2 ± 0.2 cm. The enriched cohort with characteristics of cardiac amyloidosis (s' velocity ≤6 cm/s and IVS thickness ≥1.2 cm) included 135 patients (23% of the cohort). After a median follow-up of 2.6 years (1.5-3.9 years), these patients had the worst prognosis (adjusted HR: 2.10; 95% CI: 1.26-3.50; P = 0.004). Both s' velocity and IVS thickness were individually associated with the primary endpoint, and abnormalities in these parameters were additive as lower s' velocity was particularly prognostic in those with greater IVS thickness (interaction: P = 0.013). Spironolactone was associated with improved outcomes in the overall cohort (P = 0.024), and patients in the enriched cohort had a benefit similar to that in other groups (interaction: P = 0.382). CONCLUSIONS: An enriched subset of patients with structural and functional echocardiographic features of cardiac amyloidosis had the worst prognosis in the TOPCAT study, but they benefitted similarly from spironolactone therapy. Future studies of mineralocorticoid receptor antagonists in patients with cardiac amyloidosis are warranted.


Assuntos
Amiloidose , Insuficiência Cardíaca , Amiloidose/diagnóstico por imagem , Amiloidose/tratamento farmacológico , Ecocardiografia , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Fenótipo , Espironolactona/uso terapêutico , Volume Sistólico , Resultado do Tratamento
7.
ESC Heart Fail ; 8(5): 3495-3503, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34369088

RESUMO

AIMS: The TOPCAT trial showed no benefit for spironolactone in heart failure patients with preserved ejection fraction (HFpEF). Post-hoc, spironolactone helped participants from the Americas, but not Eastern Europe. Determining which patients with HFpEF could respond like TOPCAT's responders should help guide their care. We aimed to develop a TOPCAT Trial Score (TS) as a composite metric to identify such patients. METHODS AND RESULTS: From the TOPCAT individual-level data, we calculated a TS of age, body mass index, systolic blood pressure, heart rate, creatinine, potassium, glucose, left ventricular ejection fraction, and left atrial volume for each participant as a weighted distance in multidimensional space from the theoretical perfectly average Americas participant. Logistic regression was used to measure TS and spironolactone as predictors of TOPCAT's primary outcome. The relationship between TS and the H2 FPEF score was also determined in TOPCAT and a registry cohort of real-world patients in the U.S. with HFpEF. A bimodal distribution of TS separated American (n = 1766) and Eastern European (n = 1,677) participants. Those with lower TS showed no significant response to spironolactone. Spironolactone's benefit rose with rising TS [ßinteraction  = -0.28 (P < 0.01)]. Significantly more American participants had benefit from spironolactone based on higher TS (> 1.14), in addition to higher likelihood of HFpEF based on higher H2 FPEF scores (≥3). The cohort of real-world patients with HFpEF had even higher TS than American TOPCAT participants. CONCLUSIONS: Patients with HFpEF can be quantified by the TS to capture the likelihood of benefit from spironolactone.


Assuntos
Insuficiência Cardíaca , Espironolactona , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Antagonistas de Receptores de Mineralocorticoides , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
8.
BMJ Open ; 11(8): e053876, 2021 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-34446504

RESUMO

INTRODUCTION: Acne is one of the most common inflammatory skin diseases worldwide and can have significant psychosocial impact and cause permanent scarring. Spironolactone, a potassium-sparing diuretic, has antiandrogenic properties, potentially reducing sebum production and hyperkeratinisation in acne-prone follicles. Dermatologists have prescribed spironolactone for acne in women for over 30 years, but robust clinical study data are lacking. This study seeks to evaluate whether spironolactone is clinically effective and cost-effective in treating acne in women. METHODS AND ANALYSIS: Women (≥18 years) with persistent facial acne requiring systemic therapy are randomised to receive one tablet per day of 50 mg spironolactone or a matched placebo until week 6, increasing to up to two tablets per day (total of 100 mg spironolactone or matched placebo) until week 24, along with usual topical therapy if desired. Study treatment stops at week 24; participants are informed of their treatment allocation and enter an unblinded observational follow-up period for up to 6 months (up to week 52 after baseline). Primary outcome is the Acne-specific Quality of Life (Acne-QoL) symptom subscale score at week 12. Secondary outcomes include Acne-QoL total and subscales; participant acne self-assessment recorded on a 6-point Likert scale at 6, 12, 24 weeks and up to 52 weeks; Investigator's Global Assessment at weeks 6 and 12; cost and cost effectiveness are assessed over 24 weeks. Aiming to detect a group difference of 2 points on the Acne-QoL symptom subscale (SD 5.8, effect size 0.35), allowing for 20% loss to follow-up, gives a sample size of 398 participants. ETHICS AND DISSEMINATION: This protocol was approved by Wales Research Ethics Committee (18/WA/0420). Follow-up to be completed in early 2022. Findings will be disseminated to participants, peer-reviewed journals, networks and patient groups, on social media, on the study website and the Southampton Clinical Trials Unit website to maximise impact. TRIAL REGISTRATION NUMBER: ISRCTN12892056;Pre-results.


Assuntos
Acne Vulgar , Espironolactona , Acne Vulgar/tratamento farmacológico , Adulto , Ensaios Clínicos Fase III como Assunto , Método Duplo-Cego , Feminino , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Espironolactona/uso terapêutico , Resultado do Tratamento
9.
Neuropsychopharmacology ; 46(12): 2140-2147, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34341493

RESUMO

There is a need to increase the armamentarium of pharmacotherapies for alcohol use disorder (AUD). Recent research suggests that mineralocorticoid receptor (MR) antagonism via spironolactone may represent a novel pharmacological treatment for AUD. We conducted a pharmacoepidemiologic retrospective cohort study (June 1, 2014 to May 31, 2018) to examine whether spironolactone dispensation (≥90 continuous days), for any indication, is associated with changes in weekly alcohol use about 6 months later. We compared 523 spironolactone-treated adults and 2305 untreated adults, matched on high-dimensional propensity scores created from a set of predefined (sociodemographic and health characteristics, diagnoses, and service utilization) and empirical electronic health record-derived covariates. The sample was 57% female and 27% non-White with a mean age of 59.2 years (SD = 19.3). Treated patients reduced their weekly alcohol use by 3.50 drinks (95% CI = -4.22, -2.79), while untreated patients reduced by 2.74 drinks (95% CI = -3.22, -2.26), yielding a significant difference of 0.76 fewer drinks (95% CI = -1.43, -0.11). Among those who drank >7 drinks/week at baseline, treated patients, compared to untreated patients, reported a greater reduction in weekly alcohol use by 4.18 drinks (95% CI = -5.38, -2.97), while there was no significant difference among those who drank less. There was a significant dose-response relationship between spironolactone dosage and change in drinks/week. Pending additional evidence on its safety and efficacy in individuals with AUD, spironolactone (and MR blockade, at large) may hold promise as a pharmacotherapy for AUD.


Assuntos
Consumo de Bebidas Alcoólicas , Espironolactona , Adulto , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Espironolactona/uso terapêutico
10.
AAPS PharmSciTech ; 22(5): 204, 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34258696

RESUMO

Hirsutism is a dermatological condition that refers to the excessive growth of hair in androgen-sensitive areas in women. Recently, the enhancement of the visible signs of a hairy female has taken special concern that affected the quality of life. The present study was developed to compare the follicular targeting effect of topical spironolactone (SP) or progesterone (PG)-loaded nanostructured lipid carrier (NLC) on the management of hirsutism. Four NLC formulations were prepared using cold homogenization techniques and pharmaceutically evaluated. SP-NLC and PG-NLC topical hydrogels were prepared to explore their pharmacological effect on letrozole induced polycystic ovarian syndrome (PCOS) in rats. Inflammatory mediators, antioxidant, and hormonal parameters were assayed. Additionally, histopathological examination was carried out to confirm the successful induction of PCOS. Results confirmed that all NLC formulations have a spherical shape with particle size ranged from 225.92 ± 0.41 to 447.80 ± 0.66 nm, entrapment efficiency > 75%, and zeta potential (- 31.4 to - 36.5 mV). F1 and F3 NLCs were considered as selected formulations for SP and PG, respectively. Female Wistar rats treated with F1 formulation for 3 weeks displayed better outcomes as manifested by the measured parameters as compared to the other tested groups. A significant reduction in hair follicle diameter and density was observed after topical application of SP or PG nano-gels. Finally, the outcomes pose a strong argument that the development of topically administered SP-NLC can be explored as a promising carrier over PG-NLC for more effectual improvement in the visible sign of hirsutism.


Assuntos
Portadores de Fármacos/administração & dosagem , Hirsutismo/sangue , Hirsutismo/tratamento farmacológico , Nanoestruturas/administração & dosagem , Progesterona/administração & dosagem , Espironolactona/administração & dosagem , Animais , Portadores de Fármacos/síntese química , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Hidrogéis/administração & dosagem , Hidrogéis/síntese química , Inflamação/tratamento farmacológico , Inflamação/patologia , Nanoestruturas/química , Tamanho da Partícula , Progesterona/síntese química , Ratos , Ratos Wistar , Espironolactona/síntese química
11.
Int J Mol Sci ; 22(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34281272

RESUMO

Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disease with a highly variable phenotypic expression, ranging from asymptomatic to drug refractory heart failure (HF) presentation. Pharmacological therapy is the first line of treatment, but options are currently limited to nonspecific medication like betablockers or calcium channel inhibitors, with frequent suboptimal results. While being the gold standard practice for the management of drug refractory HCM patients, septal reduction therapy (SRT) remains an invasive procedure with associated surgical risks and it requires the expertise of the operating centre, thus limiting its accessibility. It is therefore with high interest that researchers look for pharmacological alternatives that could provide higher rates of success. With new data gathering these past years as well as the development of a new drug class showing promising results, this review provides an up-to-date focused synthesis of existing medical treatment options and future directions for HCM pharmacological treatment.


Assuntos
Cardiomiopatia Hipertrófica/tratamento farmacológico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Animais , Bloqueadores dos Canais de Cálcio/uso terapêutico , Cardiomiopatia Hipertrófica/fisiopatologia , Fármacos Cardiovasculares/uso terapêutico , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Humanos , Miosinas/antagonistas & inibidores , Bloqueadores dos Canais de Sódio/uso terapêutico , Espironolactona/uso terapêutico , Vasodilatadores/uso terapêutico
12.
J Sex Med ; 18(7): 1299-1307, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34274044

RESUMO

BACKGROUND: Spironolactone and cyproterone acetate are commonly used in feminizing hormone therapy to achieve the goal of female range testosterone level; however, the data on the efficacy comparing between these two anti-androgens are scarce. AIM: To compare the anti-androgenic effects between spironolactone and cyproterone acetate as the component of feminizing hormone therapy among transgender women population. METHODS: The study was single-blinded randomized controlled trial involved 52 transgender women from two transgender health clinics. Each participant received oral estradiol valerate 4 mg/day combined with anti-androgen, spironolactone 100 mg/day or cyproterone acetate 25 mg/day, depending on which group they were randomized to. Clinical and biochemical variables were obtained at baseline and at 12 weeks of feminizing hormone therapy. MAIN OUTCOME MEASURES: The change of testosterone level from baseline. Other changes including free testosterone, estradiol, prolactin and lipid profile after the therapy. RESULTS: After a 12 weeks of feminizing hormone therapy, the change of testosterone level in the cyproterone acetate group [558.0 ng/dL (IQR 352.0 to 783.3)] was significantly higher than the spironolactone group [226.2 ng/dL (IQR,-4.3 to 480.1)](p value <0.001). Testosterone and calculated free testosterone in the cyproterone acetate group were significantly lower than the spironolactone group. Consequently, a proportion of the participants who achieved the female range testosterone (<50 ng/dL) was significantly higher in cyproterone acetate group (90%) compared to the spironolactone group (19%). Serious adverse effects observed in cyproterone acetate users were drug-induced liver injury and asymptomatic hyperprolactinemia. CLINICAL IMPLICATIONS: The data on the differences between the two anti-androgen could be benefit for the transgender health-care providers in medication selection and adverse-effects counseling. STRENGTHS & LIMITATIONS: The study design was randomized controlled trial and controlled the estrogen component by prescribed the same type and dose for each participant. However, the study was suffered from the confound feminizing effects from previous hormone therapy and the high drop-out rate. CONCLUSION: For feminizing hormone therapy, cyproterone acetate had a higher testosterone suppression efficacy than spironolactone. Burinkul S, Panyakhamlerd K, Suwan A, et al. Anti-Andorgenic Effects Comparison Between Cyproterone Acetate and Spironolactone in Transgender Women: A Randomized Controlled Trial. J Sex Med 2021;18:1299-1307.


Assuntos
Pessoas Transgênero , Transexualidade , Antagonistas de Androgênios/uso terapêutico , Ciproterona , Acetato de Ciproterona/uso terapêutico , Feminino , Humanos , Espironolactona/uso terapêutico , Testosterona , Transexualidade/tratamento farmacológico
13.
Bull Cancer ; 108(10): 963-980, 2021 Oct.
Artigo em Francês | MEDLINE | ID: mdl-34304865

RESUMO

Alopecia, although long considered an unavoidable consequence of cancer therapy, currently presents a multifaceted challenge. The knowledge of the physiology of the hair and consequently of the pathophysiology of alopecia has led to show that there is not one but several types of alopecia. Transposed to the world of oncology, different types of alopecia and subsequently molecular pathways have been characterized, allowing a better understanding of the underlying mechanisms. Thus, in patients with cancer, alopecia can be iatrogenic (chemotherapies, endocrine therapies, targeted therapies, immunotherapies, radiotherapy, surgery) or directly the consequence of the disease itself (malnutrition, scalp metastases, paraneoplastic syndromes). Knowledge of the incriminated mechanism(s) could thus make it possible to deploy an appropriate care component, whether on the preventive or curative sides or in terms of supportive care. These are particularly essential regarding the psychological repercussions caused by alopecia, with significant consequences on the quality of life of patients and with a potential impact on treatment compliance. On the preventive side, the last few years have seen the advent of the automated scalp cooling therapy, supported by several randomized clinical trials. On the curative side, several therapeutic proposals are currently deployed or under development in order to provide relevant treatments.


Assuntos
Alopecia/etiologia , Doença Iatrogênica , Neoplasias/complicações , Neoplasias/terapia , Alopecia/prevenção & controle , Alopecia/psicologia , Alopecia/terapia , Anti-Hipertensivos/uso terapêutico , Antineoplásicos/efeitos adversos , Bimatoprost/uso terapêutico , Cabelo/fisiologia , Cabelo/transplante , Folículo Piloso/fisiologia , Humanos , Imunoterapia , Minoxidil/uso terapêutico , Terapia de Alvo Molecular/efeitos adversos , Qualidade de Vida , Radioterapia/efeitos adversos , Dermatoses do Couro Cabeludo/complicações , Espironolactona/uso terapêutico
14.
Clin Cardiol ; 44(8): 1120-1127, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34076288

RESUMO

At present, the question of whether radiofrequency ablation (RFA) combined with spironolactone can reduce the levels of plasma angiotensin II (AngII) and aldosterone (ALD) in patients with atrial fibrillation (AF) and reduce the recurrence of AF has not been reported. HYPOTHESIS: The present study evaluates the effect of spironolactone as an ALD antagonist on the short-term and long-term recurrence of AF after RFA. A total of 203 patients were enrolled in the present study, with 102 patients in the spironolactone therapy group (Group PVI/SP) and 101 patients in the control group (Group PVI alone). The AngII and ALD levels and the size of the left atrium in patients with AF were observed in order to evaluate the relationship between the combination therapy of spironolactone with RFA and the success rate in AF treatment. After therapy, the levels of AngII (52.8 vs. 64.3 pg/ml, p < .001), ALD (45.7 vs. 60.6 pg/ml, p = .016), and N-terminal of B-type natriuretic peptide (NT-proBNP) (73.5 vs. 110 pg/ml, p = .016), along with the size of the left atrium (35.8 vs. 37.2 mm, p = .007), were all significantly lower in Group PVI/SP compared with Group PVI alone. The cumulative AF-free survival rate was higher in Group PVI/SP than in Group PVI alone after treatment (85.3% vs.73.3%, p = .033). In RFA combined with spironolactone treatment, spironolactone can directly antagonize the effects of ALD and AngII and the recurrence of AF and improve left ventricular function.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Átrios do Coração , Humanos , Veias Pulmonares/cirurgia , Recidiva , Espironolactona/efeitos adversos , Resultado do Tratamento
15.
Int J Pharm ; 604: 120773, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34090990

RESUMO

Impaired wound healing in patients receiving glucocorticoid therapy is a serious clinical concern: mineralocorticoid receptor (MR) antagonists can counter glucocorticoid-induced off-target activation of MR receptors. The aim of this study was to investigate the cutaneous delivery of the potent MR antagonist, spironolactone (SPL), from polymeric micelle nanocarriers, prepared using a biodegradable copolymer, methoxy-poly(ethylene glycol)-di-hexyl-substituted-poly(lactic acid). Immunofluorescent labelling of the MR showed that it was principally located in the pilosebaceous unit (PSU), justifying the study rationale since polymeric micelles accumulate preferentially in appendageal structures. Cutaneous biodistribution studies under infinite and finite dose conditions, demonstrated delivery of pharmacologically relevant amounts of SPL to the epidermis and upper dermis. Preferential PSU targeting was confirmed by comparing amounts of SPL in PSU-containing and PSU-free skin biopsies: SPL nanomicelles showed 5-fold higher delivery of SPL in the PSU-containing biopsies, 0.54 ± 0.18 ng/mm2vs. 0.10 ± 0.03 ng/mm2, after application of a hydrogel in finite conditions. Canrenone, an active metabolite of SPL, was also quantified in skin samples. In addition to being used for the treatment of delayed cutaneous wound healing by site-specific antagonism of the MR, the formulation might also be used to treat pilosebaceous androgen-related skin diseases, e.g. acne vulgaris, since SPL is a potent androgen receptor antagonist.


Assuntos
Micelas , Espironolactona , Glucocorticoides , Humanos , Receptores de Mineralocorticoides/metabolismo , Distribuição Tecidual , Cicatrização
16.
Cells ; 10(5)2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-34068720

RESUMO

BACKGROUND: Pharmacological targeting aberrant activation of epidermal growth factor receptor tyrosine kinase signaling is an established approach to treating lung adenocarcinoma. Osimertinib is a tyrosine kinase approved and effective in treating lung adenocarcinomas that have one of several common activating mutations in epidermal growth factor receptor. The emergence of resistance to osimertinib after a year or two is the rule. We developed a five-drug adjuvant regimen designed to increase osimertinib's growth inhibition and thereby delay the development of resistance. Areas of Uncertainty: Although the assembled preclinical data is strong, preclinical data and the following clinical trial results can be discrepant. The safety of OPALS drugs when used individually is excellent. We have no data from humans on their tolerability when used as an ensemble. That there is no data from the individual drugs to suspect problematic interaction does not exclude the possibility. DATA SOURCES: All relevant PubMed.org articles on the OPALS drugs and corresponding pathophysiology of lung adenocarcinoma and glioblastoma were reviewed. Therapeutic Opinion: The five drugs of OPALS are in wide use in general medicine for non-oncology indications. OPALS uses the anti-protozoal drug pyrimethamine, the antihistamine cyproheptadine, the antibiotic azithromycin, the antihistamine loratadine, and the potassium sparing diuretic spironolactone. We show how these inexpensive and generically available drugs intersect with and inhibit lung adenocarcinoma growth drive. We also review data showing that both OPALS adjuvant drugs and osimertinib have data showing they may be active in suppressing glioblastoma growth.


Assuntos
Acrilamidas/administração & dosagem , Adenocarcinoma de Pulmão/tratamento farmacológico , Compostos de Anilina/administração & dosagem , Quimioterapia Adjuvante/métodos , Reposicionamento de Medicamentos , Glioblastoma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Azitromicina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Ciproeptadina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Humanos , Loratadina/administração & dosagem , Camundongos , Metástase Neoplásica/tratamento farmacológico , Pirimetamina/administração & dosagem , Espironolactona/administração & dosagem
17.
Circ Heart Fail ; 14(6): e008075, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34129365

RESUMO

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) and insulin-treated diabetes have a high risk of cardiovascular complications. Mineralocorticoid receptor antagonists may mitigate this risk. We aim to explore the effect of eplerenone on cardiovascular outcomes and all-cause mortality in HFrEF patients with diabetes, including those treated with insulin in the EMPHASIS-HF trial (Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms). METHODS: The primary outcome was the composite of heart failure hospitalization or cardiovascular death. Cox models with treatment-by-diabetes subgroup interaction terms were used. RESULTS: The median follow-up was 21 (10-33) months. Of the 2737 patients included, 623 (23%) had non-insulin-treated diabetes, 236 (9%) had insulin-treated diabetes and 1878 did not have diabetes. Patients with insulin-treated diabetes were younger, more often women, with higher body mass index, waist circumference, more frequent ischemic heart failure cause, impaired kidney function, and longer diabetes duration. Compared with patients without diabetes, those with insulin-treated diabetes had a 2-fold higher risk of having a primary outcome event. The hazard ratio (95% CI) for the effect of eplerenone, compared with placebo, on the primary outcome was 0.31 (0.19-0.50) in insulin-treated diabetes, 0.69 (0.50-0.93) in non-insulin-treated diabetes, and 0.72 (0.58-0.88) in patients without diabetes; interaction P=0.007. The annualized number needed-to-treat-to-benefit with regards to the primary outcome was 3 (95% CI, 3-4) in patients with insulin-treated diabetes, 16 (13-19) in patients with diabetes not receiving insulin, and 26 (24-28) in patients without diabetes. CONCLUSIONS: Patients with insulin-treated diabetes experienced a greater benefit from eplerenone than those with diabetes not treated with insulin and people without diabetes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00232180.


Assuntos
Eplerenona/farmacologia , Insuficiência Cardíaca Sistólica/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Idoso , Diabetes Mellitus/tratamento farmacológico , Feminino , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca Sistólica/fisiopatologia , Humanos , Insulinas/uso terapêutico , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Espironolactona/uso terapêutico , Resultado do Tratamento
18.
J Vet Intern Med ; 35(4): 1673-1687, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34028078

RESUMO

BACKGROUND: The renin-angiotensin-aldosterone system (RAAS), when chronically activated, is harmful and RAAS-suppressive drugs are beneficial in the treatment of congestive heart failure (CHF). Mineralocorticoid receptor antagonists are widely used in the treatment of CHF in people. HYPOTHESIS/OBJECTIVES: To determine if a mineralocorticoid receptor antagonist (spironolactone) is beneficial and safe in CHF due to myxomatous mitral valve disease (MMVD) of varying severity, we hypothesized that, when combined with furosemide, a combination product (S+BNZ) containing the ACE inhibitor (ACE-I), benazepril, and spironolactone, would be superior to benazepril alone. ANIMALS: Five hundred and sixty-nine client-owned dogs, with MMVD and CHF (ACVIM Stage C) of ≤10-days' duration. METHODS: After initial stabilization, dogs were randomized into a positive-controlled, double-blind, multicenter trial, to receive furosemide plus S+BNZ or furosemide plus benazepril. The primary outcome variable was the percentage of dogs reaching cardiac endpoint before Day 360. Cardiac endpoint was defined as cardiac death or euthanasia, recurrence of pulmonary edema, necessity for nonauthorized cardiac drug(s) or a furosemide dosage >8 mg/kg/d. RESULTS: A significantly lower percentage of dogs treated with S+BNZ reached the primary outcome variable by Day 360 (OR = 0.56; 95% CI, 0.32-0.98; P = .04) and risk of dying or worsening from cardiac causes, was significantly reduced (HR = 0.73; 95% CI = 0.59-0.89, P = .002) vs benazepril alone. Adverse events, potentially associated with treatment, were rare and equal between groups. CONCLUSION AND CLINICAL IMPORTANCE: The combination of S+BNZ is effective, safe, and superior to benazepril alone, when used with furosemide for the management of mild, moderate or severe CHF caused by MMVD in dogs.


Assuntos
Doenças do Cão , Insuficiência Cardíaca , Animais , Benzazepinas , Doenças do Cão/tratamento farmacológico , Cães , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/veterinária , Valva Mitral , Espironolactona/uso terapêutico , Resultado do Tratamento
19.
J Formos Med Assoc ; 120(10): 1811-1820, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33906783

RESUMO

The aim of this study was to update the information on internationally acceptable standards and clinical practice recommendations for the management of patients with primary aldosteronism (PA). The Taiwan Society of Aldosteronism (TSA) Task Force acknowledged the novel issues of PA and reached a group consensus on PA in Taiwan by collecting the best available evidence and conducting one group meeting, several conference calls, and multiple e-mail communications. Unilateral adrenalectomy is the preferred treatment for patients with aldosterone-producing adenoma (APA). For medical treatment with mineralocorticoid receptor antagonists (MRAs), spironolactone is the first-line treatment, and eplerenone is a reasonable alternative in PA patients intolerant or contraindicated to spironolactone. The dose of MRAs can be titrated according to plasma renin activity (PRA). For screening PA-related comorbidities, we suggest albuminuria to predict a post-treatment decline in renal function, echocardiography as cardiac evaluation, bone mineral density scan for osteoporosis, and obstructive sleep apnea. In tissue and genetic surveys, we suggest immunohistochemical staining and somatic mutation screening for post-operative adrenal specimens in APA patients. With this consensus, we hope to update the information on PA for clinical physicians to facilitate better identification, management and treatment of patients with PA.


Assuntos
Hiperaldosteronismo , Hipertensão , Adrenalectomia , Humanos , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/terapia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Espironolactona , Taiwan
20.
Eur J Pain ; 25(8): 1739-1750, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33909330

RESUMO

BACKGROUND: Spironolactone (SPL) is a reversible mineralocorticoid receptor (MR) and androgen receptor (AR) antagonist which attracts pharmacotherapeutic interest not only because of its beneficial effects in heart failure but also because of the pathogenetic roles of MR and AR activities in neuropsychiatric diseases. Recently, beneficial and rapid-onset effects of SPL have been documented in a case series of women with fibromyalgia syndrome (FMS). To reaffirm this observation, we performed a double-blind placebo-controlled randomized clinical trial (RCT). METHODS: A total of 69 patients were screened, 56 patients were eligible and randomized to SPL or placebo (each n = 28). Forty-three patients completed the clinical trial to the last visit (n = 21 and n = 22). After a run-in phase of 50 and 100 mg/day, 200 mg/day SPL or placebo were applied between days 7 and 28. Primary outcome was the change in the FIQ-G score (Fibromyalgia Impact Questionnaire, German version). Secondary outcome parameters were the changes in pain (numeric rating scale, NRS), mood (ADS), quality of life (SF-36) and change in FIQ scores 14 days after the end of the medication. RESULTS: SPL of 200 mg/day did not change significantly either the primary or the secondary end points. SPL evoked a transient rise in serum potassium and a transient fall in GFR maximal after 2 weeks, but without clinical relevance. CONCLUSIONS: SPL at 200 mg/day does not improve symptoms in women with FMS, but was considered not to cause harm. SIGNIFICANCE: The mineralocorticoid receptor and androgen receptor antagonist spironolactone is repeatedly tested for its therapeutic effectivity against neuropsychiatric disorders. The present RCT demonstrated that 200 mg spironolactone does not change the symptoms of the fibromyalgia syndrome (FMS) in adult women. Between 2 and 4 weeks, spironolactone evokes a transient decrease in GFR and increase in serum potassium. Spironolactone cannot be recommended for the treatment of FMS.


Assuntos
Fibromialgia , Espironolactona , Adulto , Método Duplo-Cego , Feminino , Fibromialgia/tratamento farmacológico , Humanos , Dor , Espironolactona/uso terapêutico , Resultado do Tratamento
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