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James C Folk - One of the best experts on this subject based on the ideXlab platform.
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oral Mineralocorticoid Antagonists for recalcitrant central serous chorioretinopathy
Clinical Ophthalmology, 2015Co-Authors: Eric K Chin, David R P Almeida, Nathaniel C Roybal, Philip I Niles, Karen M Gehrs, Elliott H Sohn, Culver H Boldt, Stephen R Russell, James C FolkAbstract:PURPOSE: To evaluate the effect and tolerance of oral Mineralocorticoid Antagonists, eplerenone and/or spironolactone, in recalcitrant central serous chorioretinopathy. METHODS: Retrospective consecutive observational case series. Primary outcome measures included central macular thickness (CMT, μm), macular volume (MV, mm(3)), Snellen visual acuity, and prior treatment failures. Secondary outcomes included duration of treatment, treatment dosage, and systemic side effects. RESULTS: A total of 120 patients with central serous chorioretinopathy were reviewed, of which 29 patients were treated with one or more Mineralocorticoid Antagonists. The average age of patients was 58.4 years. Sixteen patients (69.6%) were recalcitrant to other interventions prior to treatment with oral Mineralocorticoid Antagonists, with an average washout period of 15.3 months. The average duration of Mineralocorticoid Antagonist treatment was 3.9±2.3 months. Twelve patients (52.2%) showed decreased CMT and MV, six patients (26.1%) had increase in both, and five patients (21.7%) had negligible changes. The mean decrease in CMT of all patients was 42.4 μm (range, -136 to 255 μm): 100.7 μm among treatment-naive patients, and 16.9 μm among recalcitrant patients. The mean decrease in MV of all patients was 0.20 mm(3) (range, -2.33 to 2.90 mm(3)): 0.6 mm(3) among treatment-naive patients, and 0.0 mm(3) among recalcitrant patients. Median visual acuity at the start of therapy was 20/30 (range, 20/20-20/250), and at final follow-up it was 20/40 (range, 20/20-20/125). Nine patients (39.1%) experienced systemic side effects, of which three patients (13.0%) were unable to continue therapy. CONCLUSION: Mineralocorticoid Antagonist treatment had a positive treatment effect in half of our patients. The decrease in CMT and MV was much less in the recalcitrant group compared to the treatment-naive group. An improvement in vision was seen only in the treatment-naive group. Systemic side effects, even at low doses, may limit its usage in some patients.
Eric K Chin - One of the best experts on this subject based on the ideXlab platform.
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oral Mineralocorticoid Antagonists for recalcitrant central serous chorioretinopathy
Clinical Ophthalmology, 2015Co-Authors: Eric K Chin, David R P Almeida, Nathaniel C Roybal, Philip I Niles, Karen M Gehrs, Elliott H Sohn, Culver H Boldt, Stephen R Russell, James C FolkAbstract:PURPOSE: To evaluate the effect and tolerance of oral Mineralocorticoid Antagonists, eplerenone and/or spironolactone, in recalcitrant central serous chorioretinopathy. METHODS: Retrospective consecutive observational case series. Primary outcome measures included central macular thickness (CMT, μm), macular volume (MV, mm(3)), Snellen visual acuity, and prior treatment failures. Secondary outcomes included duration of treatment, treatment dosage, and systemic side effects. RESULTS: A total of 120 patients with central serous chorioretinopathy were reviewed, of which 29 patients were treated with one or more Mineralocorticoid Antagonists. The average age of patients was 58.4 years. Sixteen patients (69.6%) were recalcitrant to other interventions prior to treatment with oral Mineralocorticoid Antagonists, with an average washout period of 15.3 months. The average duration of Mineralocorticoid Antagonist treatment was 3.9±2.3 months. Twelve patients (52.2%) showed decreased CMT and MV, six patients (26.1%) had increase in both, and five patients (21.7%) had negligible changes. The mean decrease in CMT of all patients was 42.4 μm (range, -136 to 255 μm): 100.7 μm among treatment-naive patients, and 16.9 μm among recalcitrant patients. The mean decrease in MV of all patients was 0.20 mm(3) (range, -2.33 to 2.90 mm(3)): 0.6 mm(3) among treatment-naive patients, and 0.0 mm(3) among recalcitrant patients. Median visual acuity at the start of therapy was 20/30 (range, 20/20-20/250), and at final follow-up it was 20/40 (range, 20/20-20/125). Nine patients (39.1%) experienced systemic side effects, of which three patients (13.0%) were unable to continue therapy. CONCLUSION: Mineralocorticoid Antagonist treatment had a positive treatment effect in half of our patients. The decrease in CMT and MV was much less in the recalcitrant group compared to the treatment-naive group. An improvement in vision was seen only in the treatment-naive group. Systemic side effects, even at low doses, may limit its usage in some patients.
Alejandro F De Nicola - One of the best experts on this subject based on the ideXlab platform.
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transformation and nuclear translocation of brain type i corticosteroid receptors complexed with the Mineralocorticoid Antagonist zk 91587 aldosterone or dexamethasone
The Journal of Steroid Biochemistry and Molecular Biology, 1992Co-Authors: Claudia Grillo, Santiago Vallee, Gerardo Piroli, Bruce S Mcewen, Alejandro F De NicolaAbstract:Abstract Type I corticosteroid receptors were determined in cytosol from hippocampus (HIPPO) and amygdala (AMYG), using [3H]aldosterone (ALDO), [3H]dexamethasone (DEX) or the Mineralocorticoid Antagonist [3H]ZK 91587 as ligands. Incubations with the first two compounds also contained the pure glucocorticoid RU 28362 to block type II receptors. Binding of the three ligands was comparable in cytosol from HIPPO and it was slightly higher for [3H]DEX in AMYG. However, after heat-induced receptor transformation, binding to DNA-cellulose was observed for [3H]ALDO-receptor complex obtained from HIPPO or AMYG, whereas it was negligible for [3H]ZK 91587. Receptors charged with [3H]DEX or [3H]ALDO showed similar retention on DNA-cellulose columns in the case of the AMYG, while binding to the polynucleotide was higher for [3H]ALDO in the HIPPO. Finally, only [3H]ALDO was taken up to a significant extent in purified cell nuclei prepared from slices of HIPPO and AMYG previously incubated with the three ligands. It is concluded that binding of a natural agonist steroid may be a prerequisite for type I receptor transformation and translocation from the cytoplasm into the nuclear fraction. DEX binding to type I receptors resembles a partial agonist with Antagonist properties, whereas Antagonists such as ZK 91587 are bound and retained in cytoplasm, without further translocation.
Robert W Schrier - One of the best experts on this subject based on the ideXlab platform.
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sodium retention in heart failure and cirrhosis potential role of natriuretic doses of Mineralocorticoid Antagonist
Circulation-heart Failure, 2009Co-Authors: Shweta Bansal, Joann Lindenfeld, Robert W SchrierAbstract:Patients with cirrhosis and heart failure (HF) share the pathophysiology of decreased effective arterial blood volume because of splanchnic vasodilatation in cirrhosis and decreased cardiac output in HF, with resultant stimulation of the renin-angiotensin-aldosterone system. Hyperaldosteronism plays a major role in the pathogenesis of ascites and contributes to resistance to loop diuretics. Therefore, the use of high doses of aldosterone Antagonist (spironolactone up to 400 mg/day) is the main therapy to produce a negative sodium balance in cirrhotic patients with ascites. Hyperaldosteronism also has increasingly been recognized as a risk factor for myocardial and vascular fibrosis. Therefore, low-dose aldosterone Antagonists are being used in patients with HF for cardioprotective action. However, the doses (25 to 50 mg/day) at which they are being used in cardiac patients as reported in the Randomized Aldactone Evaluation Study are not natriuretic. It is likely, therefore, that the mortality benefit relates primarily from their effect on cardiac and vascular fibrosis. Resistance to commonly used loop diuretics is frequently present in patients with advanced HF. In patients with decompensated HF with volume overload who are loop diuretic resistant, ultrafiltration may be the only available option. This is, however, an invasive procedure. For these patients, natriuretic doses of aldosterone Antagonists (spironolactone >50 mg/day) may be a potential option. The competitive natriuretic response of aldosterone Antagonists is related to activity of the renin-angiotensin-aldosterone system: the higher the renin-angiotensin-aldosterone system activity, the higher the dose of aldosterone Antagonist required to produce natriuresis. This article will discuss the potential use of natriuretic doses of aldosterone Antagonists in patients with HF, including the potential side effect of hyperkalemia.
Martin Reincke - One of the best experts on this subject based on the ideXlab platform.
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differential effects of reduced Mineralocorticoid receptor activation by unilateral adrenalectomy vs Mineralocorticoid Antagonist treatment in patients with primary aldosteronism implications for depression and anxiety
Journal of Psychiatric Research, 2021Co-Authors: Harald Murck, Christian Adolf, Anna Schneider, Lena Schlageter, Daniel A Heinrich, Katrin Ritzel, Lisa Sturm, Marcus Quinkler, Felix Beuschlein, Martin ReinckeAbstract:Abstract The Mineralocorticoid receptor (MR) and its ligand aldosterone have been found to play a major role in the pathophysiology of depression. Both could be targets of therapeutic interventions. We analyzed laboratory data and questionnaires evaluating anxiety (using GAD-7 questionnaire) and depression (using PHQD questionnaire) of up to 210 patients with primary aldosteronism (PA) (82 females, 54.7 ± 12.0yrs; 128 males, 48.7 ± 12.8yrs) before and one year after initiation of specific treatment of PA by either adrenalectomy (ADX) or treatment with Mineralocorticoid receptor Antagonists (MRA). After ADX normalization of aldosterone excess was observed. This was associated with a significant reduction of depressive symptoms, but no significant change in GAD-7 score. MRA treatment was accompanied with persistent high aldosterone levels, but led to a significant improvement of anxiety, but no significant changes in PHQD scores. These data suggest different mechanistic pathways for depression and anxiety mediated via the MR. For treatment of depression a reduction of aldosterone levels might be relevant at CNS locations specific for aldosterone, whereas MRA targets MR more broadly, including areas, where cortisol is the main ligand. MRA may be useful in treatment of anxiety related behavior.