ABSTRACT
Cosmeceuticals are cosmetics formulated using compounds with medical-like benefits. Though the antiaging effect of carboxyethyl aminobutyric acid (CEGABA) has been discussed, its action mechanism in cosmeceuticals remains unclear. This study assessed the in vitro efficacy and safety of CEGABA. NHI-3T3 mouse fibroblast cell line was treated with two CEGABA concentrations (50 and 500 µmol/L) for 24 h, 48 h, and 72 h. Cytotoxicity and genotoxicity were evaluated by colorimetry (MTT) and the alkaline version of the comet assay, respectively. Flow cytometry and the scratch-wound assay were used to assess cell-cycle phase distributions and cell migration rates. Compared with the untreated control, CEGABA increased cell growth 1.6 times after 72 h, independent of dose. The compound also decreased cell replication time by 4 h. These findings seem to be related with the approximately 1.5-times increase in phase S cells numbers. Importantly, in vitro wound healing improved roughly 20% after treatment with CEGABA for 24 h and persisted after 48 h, indicating culture recovery. The time-dependent proliferation and migration of fibroblasts induced by CEGABA besides the fact that the compound is neither genotoxic nor cytotoxic makes it an ideal candidate in the development of cosmeceuticals in antiaging therapy.
Subject(s)
Aminobutyrates/adverse effects , Aminobutyrates/pharmacology , Cell Movement/drug effects , Cell Proliferation/drug effects , Cosmetics/adverse effects , Cosmetics/pharmacology , 3T3 Cells , Aging/drug effects , Animals , Cell Cycle/drug effects , Cell Line , Fibroblasts/drug effects , Mice , Mutagenicity TestsSubject(s)
Aminobutyrates/adverse effects , Angioedema/chemically induced , Angiotensin Receptor Antagonists/adverse effects , Heart Failure/drug therapy , Ileus/etiology , Tetrazoles/adverse effects , Aged , Angioedema/complications , Biphenyl Compounds , Conservative Treatment , Drug Combinations , Humans , Ileus/diagnostic imaging , Ileus/therapy , Intestine, Small/blood supply , Intestine, Small/diagnostic imaging , Intestine, Small/drug effects , Male , Tomography, X-Ray Computed , ValsartanABSTRACT
OBJECTIVE: Chronic heart failure with reduced ejection fraction (HF-REF) represents a major public health issue and is associated with considerable morbidity and mortality. We evaluated the cost-effectiveness of sacubitril/valsartan (formerly LCZ696) compared with an ACE inhibitor (ACEI) (enalapril) in the treatment of HF-REF from the perspective of healthcare providers in the UK, Denmark and Colombia. METHODS: A cost-utility analysis was performed based on data from a multinational, Phase III randomised controlled trial. A decision-analytic model was developed based on a series of regression models, which extrapolated health-related quality of life, hospitalisation rates and survival over a lifetime horizon. The primary outcome was the incremental cost-effectiveness ratio (ICER). RESULTS: In the UK, the cost per quality-adjusted life-year (QALY) gained for sacubitril/valsartan (using cardiovascular mortality) was £17 100 (20 400) versus enalapril. In Denmark, the ICER for sacubitril/valsartan was Kr 174 000 (22 600). In Colombia, the ICER was COP$39.5 million (11 200) per QALY gained. Deterministic sensitivity analysis showed that results were most sensitive to the extrapolation of mortality, duration of treatment effect and time horizon, but were robust to other structural changes, with most scenarios associated with ICERs below the willingness-to-pay threshold for all three country settings. Probabilistic sensitivity analysis suggested the probability that sacubitril/valsartan was cost-effective at conventional willingness-to-pay thresholds was 68%-94% in the UK, 84% in Denmark and 95% in Colombia. CONCLUSIONS: Our analysis suggests that, in all three countries, sacubitril/valsartan is likely to be cost-effective compared with an ACEI (the current standard of care) in patients with HF-REF.
Subject(s)
Aminobutyrates/economics , Aminobutyrates/therapeutic use , Cardiovascular Agents/economics , Cardiovascular Agents/therapeutic use , Drug Costs , Heart Failure/drug therapy , Heart Failure/economics , Stroke Volume/drug effects , Tetrazoles/economics , Tetrazoles/therapeutic use , Ventricular Function, Left/drug effects , Aminobutyrates/adverse effects , Biphenyl Compounds , Cardiovascular Agents/adverse effects , Chronic Disease , Clinical Trials, Phase III as Topic , Colombia , Cost-Benefit Analysis , Denmark , Drug Combinations , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Quality-Adjusted Life Years , Randomized Controlled Trials as Topic , Recovery of Function , Tetrazoles/adverse effects , Time Factors , Treatment Outcome , United Kingdom , ValsartanABSTRACT
We compared the systolic blood pressure (SBP)-lowering efficacy and safety of crystalline valsartan/sacubitril (LCZ696, an angiotensin receptor blocker-neprilysin inhibitor) 400 mg daily against valsartan (320 mg once daily) alone or coadministered with placebo or increasing doses of free sacubitril (50, 100, 200, or 400 mg once daily) to identify the optimal antihypertensive combination dose. This multicenter, double-blinded, 7-arm parallel-group study recruited patients with mild-to-moderate systolic hypertension (office SBP 150-179 mm Hg). Primary-dependent variable was change in office SBP from baseline to week 8. At entry (n = 907), mean age was 61.5 years, sitting office BP 160/90.2 mm Hg, and mean 24-hour ambulatory BP 142/82.1 mm Hg; 852 participants completed the study. At week 8, there were greater reductions in sitting office SBP and 24-hour ambulatory SBP with LCZ696 400 mg than with valsartan 320 mg (-5.7 and -3.4 mm Hg, respectively, P < 0.05 each). The SBP reduction with LCZ696 400 daily was similar to coadministered free valsartan 320 mg and sacubitril 200 mg. Effects were similar in those older and younger than 65 years, and active therapies had adverse event rates similar to placebo. We conclude that crystalline valsartan/sacubitril 400 mg daily (1) is superior to valsartan 320 mg daily for lowering SBP, (2) has similar efficacy to the combination of free valsartan 320 mg plus free sacubitril 200 mg, (3) represents the optimal dosage for systolic hypertension in patients of any age, and (4) is safe and well tolerated.