Enhancement of chemotherapy by prevention of tumor cell repair

The body naturally tries to repair lesions in the DNA of tumor cells, and thus reduces the efficacy of chemotherapy. Blocking the mechanisms for DNA repair would help to potentiate chemotherapy by reducing the resistance of cells to treatment. A team of scientists has discovered a new drug that inhibits repair: spironolactone, which seems likely to be used in the very short term as an adjuvant to chemotherapy. (Source: ScienceDaily Headlines)

Combined therapies versus monotherapies for the first variceal bleeding in patients with high�risk varices: A meta�analysis of randomized controlled trials

ConclusionsBased on the available evidences, no combined therapy can be recommended as the first�line treatment for the primary prevention of variceal bleeding currently. Further studies with large sample sizes and long�term follow up are warranted. (Source: Journal of Gastroenterology and Hepatology)

SPIRONOLACTONE Tablet, Film Coated [American Health Packaging]

Updated Date: Feb 14, 2014 EST (Source: DailyMed Drug Label Updates for the last seven days (since May 20, 2007 EST))

SPIRONOLACTONE Tablet, Film Coated [Aidarex Pharmaceuticals LLC]

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Spironolactone Reduces Cardiovascular and Cerebrovascular Morbidity and Mortality in Hemodialysis Patients

ConclusionsAldosterone receptor blockade using spironolactone may substantially reduce the risk of both CCV morbidity and death among HD patients; however, larger-scale studies are recommended to further confirm its efficacy. (Effects of Spironolactone on Cardio- and Cerebrovascular Morbidity and Mortality in Hemodialysis Patients; NCT01687699) (Source: Journal of the American College of Cardiology: Cardiovascular Interventions)

A Small Molecule Screen Identifies an Inhibitor of DNA Repair Inducing the Degradation of TFIIH and the Chemosensitization of Tumor Cells to Platinum.

Authors: Alekseev S, Ayadi M, Brino L, Egly JM, Larsen AK, Coin F Abstract Nucleotide excision repair (NER) removes DNA lesions resulting from exposure to UV irradiation or chemical agents such as platinum-based drugs used as anticancer molecules. Pharmacological inhibition of NER is expected to enhance chemosensitivity but nontoxic NER inhibitors are rare. Using a drug repositioning approach, we identify spironolactone (SP), an antagonist of aldosterone, as a potent NER inhibitor. We found that SP promotes a rapid and reversible degradation of XPB, a subunit of transcription/repair factor TFIIH. Such degradation depends both on ubiquitin-activating enzyme and on the 26S proteasome. Supplementation of extracts from SP-treated cells with purified TFIIH restored TFIIH-dependent repa...

Effect of intensified diuretic therapy on overnight rostral fluid shift and obstructive sleep apnoea in patients with uncontrolled hypertension

Objectives:Fluid displacement from the lower extremities to the upper body during sleep is strongly associated with obstructive sleep apnoea in hypertensive patients. The present pathophysiological study tests the hypothesis that intensified diuretic therapy will reduce the apnoea-hypopnoea index and blood pressure of uncontrolled hypertensive patients with obstructive sleep apnoea in proportion to the reduction in overnight change in leg fluid volume. Methods:Uncontrolled treated hypertensive patients underwent overnight polysomnography and measurement of overnight changes in leg fluid volume and neck circumference. Those with an apnoea-hypopnoea index at least 20 events per hour (nâ??=â??16) received metolazone 2.5â??mg and spironolactone 25â??mg daily for 7 days after which the daily do...

Rationale and design of the Mineralocorticoid Receptor Antagonists in End-Stage Renal Disease Study (MiREnDa)

Conclusions MiREnDa will investigate CV efficacy and safety of spironolactone in haemodialysis patients [clinical trials.gov NCT01691053]. (Source: Nephrology Dialysis Transplantation)

Aldosterone synthase inhibitors in cardiovascular and renal diseases

Aldosterone is involved in various cardiovascular pathologies, including hypertension, heart failure, atherosclerosis and fibrosis. Mineralocorticoid receptor (MR)-dependent and -independent, genomic and non-genomic processes mediate its complex effects. Spironolactone and eplerenone, both MR antagonists, are the only commercially available compounds targeting directly the actions of aldosterone. However, due to the poor selectivity (spironolactone), low potency (eplerenone) and the fact that only MR-dependent effects of aldosterone can be inhibited, these drugs have limited clinical use. An attractive approach to abolish potentially all of aldosterone-mediated pathologies is the inhibition of aldosterone synthase. This review summarizes current knowledge on the complex effects mediated by...<div id="medworm"><p><b><i>MedWorm Sponsor Message:</i></b> Find the best <a href="http://www.thejanuarysales.com/">Christmas Sales</a>, <a href="http://www.thejanuarysales.com/">Boxing Day Sales</a> and <a href="http://www.thejanuarysales.com/">January Sales</a> <a href="http://www.thejanuarysales.com/">here</a>.</p></div>

Anti-inflammatory properties of kaempferol via its inhibition of aldosterone signaling and aldosterone-induced gene expression.

Authors: Liu ZK, Xiao HB, Fang J Abstract Osteopontin (OPN), also called cytokine Eta-1, is a pro-inflammatory cytokine. Recent studies have shown that aldosterone increases OPN gene expression in endothelial cells. As a flavonoid compound, kaempferol has potent anti-inflammatory properties, but whether kaempferol regulates aldosterone signaling and aldosterone-induced gene expression is still unknown. Human umbilical vein endothelial cells (HUVECs) were pretreated with kaempferol (0, 1, 3, or 10 ÎŒmol/L) for 1 h prior to exposure to aldosterone (10(-6) mol/L) for 24 h. Aldosterone induced generation of reactive oxygen species; OPN and cluster of differentiation 44 gene expression; phospho-p38 MAPK and NF-ÎșB binding activity. The effect of aldosterone was abrogated by kaempferol a...

[Mineralocorticoid receptor antagonists as treatment option for acute and chronic central serous chorioretinopathy].

CONCLUSION: For further assessment of this treatment controlled clinical trials are urgently required as this therapy would offer a new approach for patients with chronic CSCR and no tendency towards recovery. PMID: 24510173 [PubMed - in process] (Source: Der Ophthalmologe)

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