Renal function and neurohormonal changes following intravenous infusions of nitroglycerin versus nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Rises in serum creatinine and efficacy have been reported as dose-related effects of nesiritide and nitroglycerin in acute decompensated heart failure (ADHF). However, no study has evaluated the comparative safety, efficacy, and biomarkers of optimally dosed nesiritide versus nitroglycerin in ADHF. METHODS AND RESULTS: Eighty-nine ADHF patients were prospectively randomized to receive either nesiritide (0.01 µg kg(-1) min(-1) ± bolus) or nitroglycerin (maximally tolerated doses by standard protocol). Blood urea nitrogen (BUN), and creatinine were obtained during 48 hours of intravenous infusion. B-Type natriuretic peptide (BNP) and N-terminal (NT) proBNP concentrations were measured during hospitalization. There were no significant differences in BUN, serum creatinine, creatinine clearance, or hospitalization and mortality. Although concentrations of BNP and NT-proBNP were significantly decreased over time, the comparative reductions between the 2 vasodilators were similar. CONCLUSIONS: Nesiritide and nitroglycerin produce similar hemodynamic effects, do not worsen markers of renal function, and produce significant, yet similar, reductions in neurohormones over time. Both nitroglycerin at maximally titrated doses and nesiritide at standard doses are safe and effective in patients with ADHF who require vasodilator therapy.

Thyroid hormone regulates endogenous amyloid-beta precursor protein gene expression and processing in both in vitro and in vivo models.

Thyroid hormone negatively regulates the amyloid-beta precursor protein (APP) gene in thyroid hormone receptor (TR)-transfected neuroblastoma cells. A negative thyroid hormone response element (nTRE) that mediates this regulation has been identified in the first exon of the APP gene. We demonstrate in an in vivo system that expression of APP mRNA, APP protein, and APP secretase cleavage products in mouse brain is influenced by thyroid status. Adult female mice were made hyperthyroid or hypothyroid for 3 weeks and compared to euthyroid mice. APP gene product expression was increased in hypothyroid mouse brain and reduced in hyperthyroid mouse brain, when compared to euthyroid controls. We observed similar effects of thyroid hormone on endogenous APP gene expression in human neuroblastoma cells. The incidence of hypothyroidism increases with age, and localized hypothyroidism of central nervous system has been reported in some patients with Alzheimer's disease (AD). Reduced action of thyroid hormone on the APP gene may contribute to AD pathology by increasing APP expression and the levels of processed APP products. These findings may be an underlying mechanism contributing to the association of hypothyroidism with AD in the elderly, as well as identifying a potential therapeutic target. Pharmacologic supplementation of thyroid hormone, or its analogs, may reduce APP gene expression and beta amyloid peptide accumulation.

Ginseng and anticancer drug combination to improve cancer chemotherapy: a critical review.

Ginseng, a well-known herb, is often used in combination with anticancer drugs to enhance chemotherapy. Its wide usage as well as many documentations are often cited to support its clinical benefit of such combination therapy. However the literature based on objective evidence to make such recommendation is still lacking. The present review critically evaluated relevant studies reported in English and Chinese literature on such combination. Based on our review, we found good evidence from in vitro and in vivo animal studies showing enhanced antitumor effect when ginseng is used in combination with some anticancer drugs. However, there is insufficient clinical evidence of such benefit as very few clinical studies are available. Future research should focus on clinically relevant studies of such combination to validate the utility of ginseng in cancer.

Modulation of novel cardiorenal and inflammatory biomarkers by intravenous nitroglycerin and nesiritide in acute decompensated heart failure: an exploratory study.

BACKGROUND: Modulation of novel cardiorenal and inflammatory markers may provide insight into the disease process and outcomes of patients with acute decompensated heart failure. METHODS AND RESULTS: In this open-labeled, prospective, randomized study, 89 patients received either nesiritide (NES) or nitroglycerin (NTG) infusion by standard protocol. The serum or plasma concentrations of cystatin-C and inflammatory markers (high-sensitivity C-reactive protein, tumor necrosis factor-α, transforming growth factor-ß1, and interleukin-6) were measured in 66 patients with acute decompensated heart failure at baseline and during drug infusion. Mean baseline values for demographics were not significantly different between NTG and NES groups; however, baseline inflammatory markers were elevated on admission. In NES compared with NTG groups, lower cystatin-C (1449 versus 2739 ng/mL, P<0.05) and IL-6 (25 versus 50 pg/mL, P<0.05) were observed. There were no significant differences in concentrations of high-sensitivity C-reactive protein, tumor necrosis factor-α, and transforming growth factor-ß1 between groups over time. CONCLUSIONS: The differential modulation effects of cystatin-C and interleukin-6 but not other inflammatory markers, in response to NES compared with NTG therapy, may provide important implications for vasodilator therapy. Further studies are warranted to confirm these findings. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00842023.