Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.

Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1 (men) or ≤50 mg dl-1 (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. RESULTS: The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1 , 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 μg ml-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.info:eu-repo/semantics/publishedVersio

Neuroendocrine Regulation of Metabolism

Given the current environment in most developed countries, it is a challenge to maintain a good balance between calories consumed and calories burned, although maintenance of metabolic balance is key to good health. Therefore, understanding how metabolic regulation is achieved and how the dysregulation of metabolism affects health is an area of intense research. Most studies focus on the hypothalamus, which is a brain area that acts as a key regulator of metabolism. Among the nuclei that comprise the hypothalamus, the arcuate nucleus is one of the major mediators in the regulation of food intake. The regulation of energy balance is also a key factor ensuring the maintenance of any species as a result of the dependence of reproduction on energy stores. Adequate levels of energy reserves are necessary for the proper functioning of the hypothalamic-pituitary-gonadal axis. This review discusses valuable data presented in the 2015 edition of the International Workshop of Neuroendocrinology concerning the fundamental nature of the hormonal regulation of the hypothalamus and the impact on energy balance and reproduction.Fil: Cornejo, María Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Hentges, S.T.. State University of Colorado - Fort Collins; Estados UnidosFil: Maliqueo, M.. Universidad de Chile; ChileFil: Coirini, Hector. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Becu Villalobos, D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Elias, C. F.. University of Michigan; Estados Unido

Conjugated linoleic acid reduces permeability and fluidity of adipose plasma membranes from obese Zucker rats

NOTICE: this is the author’s version of a work that was accepted for publication in Biochemical and Biophysical Research Communications. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochemical and Biophysical Research Communications. July 2010; 398 (2): 199-204.Conjugated linoleic acid (CLA) is a dietary fatty acid frequently used as a body fat reducing agent whose effects upon cell membranes and cellular function remain unknown. Obese Zucker rats were fed atherogenic diets containing saturated fats of vegetable or animal origin with or without 1% CLA, as a mixture of cis(c)9,trans(t)11 and t10,c12 isomers. Plasma membrane vesicles obtained from visceral adi- pose tissue were used to assess the effectiveness of dietary fat and CLA membrane incorporation and its outcome on fluidity and permeability to water and glycerol. A significant decrease in adipose membrane fluidity was correlated with the changes observed in permeability, which seem to be caused by the incor- poration of the t10,c12 CLA isomer into membrane phospholipids. These results indicate that CLA supple- mentation in obese Zucker rats fed saturated and cholesterol rich diets reduces the fluidity and permeability of adipose membranes, therefore not supporting CLA as a body fat reducing agent through membrane fluidification in obese fat consumers

FUSE Observations of the Dwarf Novae UU Aql, BV Cen, and CH UMa in Quiescence

We report on FUSE spectra of three U Gem-type, long period, dwarf novae, UU Aql, BV Cen and CH UMa taken during their quiescence intervals. We discuss the line identifications in their spectra and attempt to characterize the source(s) of their FUV flux distribution. Archival IUE spectrum of CH UMa and BV Cen in quiescence were identified as having a matching flux level with the FUSE spectra and these were combined with each FUSE spectrum to broaden the wavelength coverage and further constrain model fits. Multi-component synthetic spectral fits from our model grids, consisting of single temperature white dwarfs, two-temperature white dwarfs, accretion disks and white dwarfs plus accretion disks, were applied to the FUSE spectra alone and to the combined FUSE + IUE spectra. We present the results of our model analyses and their implications.Comment: accepted in AJ, 26 pages, 6 tables, 8 figures (5 color, 3 b/w

Peripapillary Retinal Nerve Fiber Layer Thickness and Peripheral Microcirculation in Raynaud’s Disease

Purpose: Normal-tension glaucoma has been associated with systemic vascular diseases such as peripheral vasospasm. This study aims to evaluate the influence of peripheral vasospasm on the thickness of the retinal nerve fiber layer (RNFL) in Raynaud's disease (RD), and the correlation between global RNFL and peripheral microcirculation features in RD patients. Methods: Observational cross-sectional study of 18 patients (35 eyes) with a diagnosis of RD followed in our clinic, and 20 healthy controls (39 eyes). RNFL parameters were obtained using spectral domain optical coherence tomography (SD-OCT Spectralis®, Heidelberg). Global and sectorial peripapillary RNFL thickness were registered. Age, gender, refractive error, best-corrected visual acuity and intraocular pressure were determined, and slit-lamp biomicroscopy and fundus examination were performed. Nailfold videocapillaroscopy (NC) was performed in the RD group to characterize capillary morphology and blood flow. Mann-Whitney and Fisher's exact tests were used for statistical analysis. Statistical significance level was set at p<0.05 (two-sided). Results: There was no significant difference in the global RNFL between RD patients and the control group (p=0.35). The presence of avascular areas in NC was associated with a lower global RNFL thickness (p=0.026). Conclusion: The association between avascular areas in NC and the lower global RNFL thickness in RD patients suggests that systemic vasospasm severity may be related to optic nerve damage propensity. Therefore, its presence in NC may identify RD patients at risk for optic nerve head damage. A larger sample with a long-term study is needed to support the clinical and therapeutic implications of our findings.info:eu-repo/semantics/publishedVersio