- Hyperkalaemia in people with diabetes: occurrence, risk factors and outcomes in a Danish population-based cohort study. [Journal Article]
- DMDiabet Med 2018 May 23
- CONCLUSIONS: One in six newly diagnosed people with diabetes experienced a hyperkalaemic event, which was associated with severe clinical outcomes and death. This article is protected by copyright. All rights reserved.
- Elevated Potassium Levels in Patients With Congestive Heart Failure: Occurrence, Risk Factors, and Clinical Outcomes: A Danish Population-Based Cohort Study. [Journal Article]
- JAJ Am Heart Assoc 2018 May 22; 7(11)
- CONCLUSIONS: Almost 4 in 10 patients with HF develop hyperkalemia, and many patients have recurrent hyperkalemia episodes. Hyperkalemia risk is strongly associated with degree of reduced kidney function and use of spironolactone. Hyperkalemia is associated with severe clinical outcomes and death in HF.
- The Effect of Spironolactone on the Incidence of Contrast-Induced Nephropathy in Patients Undergoing Cardiac Catheterization: Study Design and Rationale. [Journal Article]
- CTCardiol Ther 2018 May 21
- Patients undergoing coronary catheterization are at high risk of developing contrast-induced nephropathy (CIN) acute kidney injury (AKI). Several approaches have been supposed to limit such an effect...
Patients undergoing coronary catheterization are at high risk of developing contrast-induced nephropathy (CIN) acute kidney injury (AKI). Several approaches have been supposed to limit such an effect but with mixed results or non-practical methods. Spironolactone is supposed to be effective as a nephroprotective agent in animal studies. This study will try to measure the effect of spironolactone on the incidence of CIN-AKI in patients undergoing coronary catheterization (angiography angioplasty).
- Study of Acute Kidney Injury on 309 Hypertensive Inpatients with ACEI/ARB - Diuretic Treatment. [Journal Article]
- JNJ Natl Med Assoc 2018; 110(3):287-296
- CONCLUSIONS: Chronic kidney disease and poor cardiac function are major risk factors for AKI in hypertensive inpatients using ACEI/ARB + diuretic therapy. The combination of thiazide diuretic and aldosterone antagonist had a higher risk of AKI than other single diuretics or diuretic combinations.
- Hormetic effects by exercise on hippocampal neurogenesis with glucocorticoid signaling. [Journal Article]
- BPBrain Plast 2015 Oct 09; 1(1):149-158
- Exercise enhances adult hippocampal neurogenesis (AHN), although the exact nature of how this happens remains controversial. The beneficial effects of exercise vary depending upon the exercise condit...
Exercise enhances adult hippocampal neurogenesis (AHN), although the exact nature of how this happens remains controversial. The beneficial effects of exercise vary depending upon the exercise condition, especially intensity. Most animal studies, however, have used wheel running, which only evaluates running distance (exercise volume) and does not consider intensity. In our rat model, we have found that exercise-induced neurogenesis varies depending on the intensity of the exercise and have found that exercise-enhanced neurogenesis is more pronounced with mild exercise than with moderate and/or intense exercise. This may be due, at least in part, to increased glucocorticoid (CORT) secretion. To test this hypothesis, we used our special exercise model in mice, with and without a stress response, based on the lactate threshold (LT) in which moderate exercise above the LT increases lactate and adrenocorticotropic hormone (ACTH) release, while mild exercise does not. Adult male C57BL/6J mice were subjected to two weeks of exercise training and AHN was measured with a 5-Bromo-2-deoxyuridine (BrdU) pre-injection and immunohistochemistry. The role of glucocorticoid signaling was examined using intrapertioneal injections of antagonists for the glucocorticoid receptor (GR), mifepristone, and the mineralocorticoid receptor (MR), spironolactone. We found that, while mild exercise increased AHN without elevating CORT blood levels, both MR and GR antagonists abolished mild-exercise-induced AHN, but did not affect AHN under intense exercise. This suggests a facilitative, permissive role of glucocorticoid and mineralocorticoid receptors in AHN during mild exercise (234/250).
- Development and validation of a fast and sensitive UHPLC-ESI-MS method for the simultaneous quantification of spironolactone and its metabolites in ocular tissues. [Journal Article]
- BCBiomed Chromatogr 2018 May 16; :e4287
- Glucocorticoids are a mainstay for the treatment of immune-mediated conditions and inflammatory diseases. However, their chronic use causes numerous side-effects including delays in corneal and cutan...
Glucocorticoids are a mainstay for the treatment of immune-mediated conditions and inflammatory diseases. However, their chronic use causes numerous side-effects including delays in corneal and cutaneous wound healing. This is attributed to off-target agonism of the mineralocorticoid receptor, which can be reduced by co-administration of a mineralocorticoid receptor antagonist such as spironolactone. The aim of this study was to develop a fast, selective and sensitive UHPLC-ESI-MS method for the simultaneous quantification of spironolactone, its active metabolites - 7α-thiomethylspironolactone and canrenone, the latter's water-soluble prodrug potassium canrenoate, and the synthetic glucocorticoid, dexamethasone, in corneal samples (17α-methyltestosterone served as an internal standard). A one-step extraction procedure using MeOH:H2 O (1:1) was validated and employed to recover the analytes from the corneal tissue. Extracts were centrifuged and the supernatant analyzed under isocratic conditions. Compounds were detected using SIR mode. The method satisfied FDA guidelines with respect to selectivity, precision and accuracy and displayed linearity from 5 to 1000 ng/mL for all the analytes. The LLOQ of the method was 5 ng/mL making it sufficiently sensitive for quantification of the analytes in samples from in vivo studies.
- Hormonal Treatment of Transgender Women with Oral Estradiol. [Journal Article]
- THTransgend Health 2018; 3(1):74-81
- Purpose: Maintaining cross-sex hormone levels in the normal physiologic range for the desired gender is the cornerstone of transgender hormonal therapy, but there are limited data on how to achieve ...
Purpose: Maintaining cross-sex hormone levels in the normal physiologic range for the desired gender is the cornerstone of transgender hormonal therapy, but there are limited data on how to achieve this. We investigated the effectiveness of oral estradiol therapy in achieving this goal. Methods: We analyzed data on all transgender females seen in our clinic since 2008 treated with oral estradiol. We looked at the success of achieving serum levels of testosterone and 17-β estradiol in the normal range on various doses of estradiol (with and without antiandrogens spironolactone and finasteride). Results: There was a positive correlation between estradiol dose and 17-β estradiol, but testosterone suppression was less well correlated. Over 70% achieved treatment goals (adequate 17-β estradiol levels and testosterone suppression) on 4 mg daily or more. Nearly a third of patients did not achieve adequate treatment goals on 6 or even 8 mg daily of estradiol. Spironolactone, but not finasteride, use was associated with impairment of obtaining desired 17-β estradiol levels. Spironolactone did not enhance testosterone suppression, and finasteride was associated with higher testosterone levels. Conclusions: Oral estradiol was effective in achieving desired serum levels of 17-β estradiol, but there was wide individual variability in the amount required. Oral estradiol alone was not infrequently unable to achieve adequate testosterone suppression. Spironolactone did not aid testosterone suppression and seemed to impair achievement of goal serum 17-β estradiol levels. Testosterone levels were higher with finasteride use. We recommend that transgender women receiving estradiol therapy have hormone levels monitored so that therapy can be individualized.
- Severe renal failure and thrombotic microangiopathy induced by malignant hypertension successfully treated with spironolactone. [Journal Article]
- ACAnn Cardiol Angeiol (Paris) 2018 May 09
- Malignant hypertension can cause thrombotic microangiopathy (TMA) characterized by hemolytic anemia and thrombocytopenia. On the other hand, severe hypertension is sometimes associated with hemolytic...
Malignant hypertension can cause thrombotic microangiopathy (TMA) characterized by hemolytic anemia and thrombocytopenia. On the other hand, severe hypertension is sometimes associated with hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). Distinguishing these entities is important because of therapeutic implications. Plasmapheresis should be initiated as soon as possible if we are dealing with TTP. We describe the case of a 30-year-old man referred to our hospital with malignant hypertension, severe renal failure and TMA: haemoglobin=9g/dL, total bilirubin=0.4mg/dL, haptoglobin≤10mg/dL, platelet count=59,000/μL and schistocytes on peripheral smear. He required initiation of hemodialysis. Additionally, we considered that the possible cause of TMA was malignant hypertension according to the presence of hypertensive retinopathy and thrombocytopenia which remitted only with blood pressure control, hence, plasmapheresis was not given. Renal function did not improve and the patient remained chronic hemodialysis. Intensive therapy for hypertension with a combination of antihypertensive drugs including spironolactone successfully lowered his blood pressure without developing hyperkalemia.
- Effects of Different Doses of Irbesartan Combined With Spironolactone on Urinary Albumin Excretion Rate in Elderly Patients With Early Type 2 Diabetic Nephropathy. [Journal Article]
- AJAm J Med Sci 2018; 355(5):418-424
- CONCLUSIONS: Our results indicate high-dose irbesartan combined with spironolactone may be more efficient in reducing UAER in elderly patients with early DN, but this treatment could cause hyperkalemia. Low-dose irbesartan combined with spironolactone was shown to be safer and more effective in decreasing UAER compared to high-dose irbesartan.
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- Evaluation of spironolactone solid dispersions prepared by co-spray drying with Soluplus® and PVP and influence of tableting on drug release. [Journal Article]
- JPJ Pharm Sci 2018 May 09
- Solid dispersions of spironolactone with Soluplus® and PVP were prepared by spray drying according to a mixture experimental design and evaluated for moisture content, particle size, drug solubility,...
Solid dispersions of spironolactone with Soluplus® and PVP were prepared by spray drying according to a mixture experimental design and evaluated for moisture content, particle size, drug solubility, crystallinity (PXRD and DSC) and physicochemical interactions (FTIR, Raman). In vitro dissolution was evaluated for the spray dried product itself and after compression into tablets and prediction models were derived using multiple linear regression analysis. The spray dried products consisted of amorphous drug, indicated by the absence of crystalline PXRD peaks. Amorphization and interactions impacted changes in the FTIR spectra in the ranges 2900-3000 cm-1 (C-H) and 1600-1800 cm-1 (C=O) and caused merging at 1690 cm-1 (C=O of lactone) and 1670 cm-1 (C=O of thioacetyl group). In the Raman spectra amorphization and interactions resulted in disappearance of peak at 1690 cm-1 (C=O) and merging of peaks at 582 and 600 cm-1 (C-S). Hydrogen bonding between the thioacetyl group of the drug with the hydroxyl groups of Soluplus® caused marked suppression of the peak at 1190 cm-1 (R-C(=O)-S vibration). Amorphization and interactions resulted in improved solubility and dissolution which was greatest for drug/Soluplus® ratio 1:4 and was also demonstrated in the corresponding tablets.