Monocyte cAMP content is decreased in patients with stable angina.
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Aged↗
Biomedical subjects
Pablo Gonzalez
Publications and source records attributed to Pablo Gonzalez.
Bias in estimation of transporter kinetic parameters from overexpression systems: Interplay of transporter expression level and substrate affinity.
The objective was to investigate the interplay between transporter expression levels and substrate affinity in controlling the influence of aqueous boundary layer (ABL) resistance on transporter kinetics in an over-expression system. Taurocholate flux was measured across human apical sodium-dependent bile acid transporter (hASBT)-Madin-Darby canine kidney monolayers on different occasions and kinetic parameters estimated with and without considering ABL. In error-free simulation/regression studies, flux values were generated across a range of J max, Kt, and substrate concentrations. Similar evaluation was performed for transport inhibition studies. Additionally, simulation/regression studies were performed, incorporating 15% random error to estimate the probability of successfully estimating Kt. Across different occasions, experimental J max and Kt estimates for taurocholate were strongly associated (p < 0.001; r2 = 0.82) when ABL was not considered. Simulation/regression results indicate that not considering ABL caused this association, such that Kt estimates were highly positively biased at high hASBT expression. In reanalyzing taurocholate flux data using the ABL-present model, Kt was relatively constant across occasions (approximately 5 microM) and not associated with J max (p = 0.24; r2 = 0.13). Simulations suggest that J max and Kt collectively determined ABL influence, which is most prominent under conditions of low monolayer resistance. Additionally, not considering ABL lead to negatively biased Ki estimates, especially at high J max. Error-inclusive simulation/regression studies indicated that the probability of successfully estimating Kt depended on the contribution of ABL resistance to flux; when flux became increasingly ABL-limited, probability of success decreased. Results indicate that ABL resistance can bias Kt and Ki estimates from overexpression systems, where the extent of bias is determined by transporter expression level and substrate affinity.
Animals↗
Atherogenesis takes place in cholesterol-fed rabbits when circulating concentrations of endogenous cortisol are increased and inflammation suppressed.
Atherosclerosis is an inflammatory disease, but the response of the endogenous anti-inflammatory system during this process has not been evaluated previously. Cortisol is the end product of this anti-inflammatory system, but is also able to activate cellular processes that induce atherogenesis; however, it is unknown whether atherogenesis occurs when circulating concentrations of endogenous cortisol are increased or when they are decreased. We have evaluated the counter-regulatory responses of cortisol and interleukin-1beta (IL-1beta) during the short- and long-term responses to vascular injury in rabbits fed a 2% cholesterol diet. In the short-term group (n=18), serum cortisol and IL-1beta concentrations were measured after 10, 20 and 30 days. Rabbits developed hypercholesterolemia and hypercortisolemia, with only modest increases in IL-1beta. Although inflammation was low-grade, atherogenesis took place, with subintimal lipid accumulation evident on day 30. In the second group (n=18), we evaluated variables after 40, 60 and 90 days. This group developed hypercholesterolemia, but serum cortisol concentrations were inappropriately normal, while IL-1beta concentrations were elevated 8.6-fold; advanced atherosclerotic plaques were evident on days 60 and 90. These results show that atherogenesis occurs when high endogenous cortisol levels are suppressing inflammation, and are consistent with a promotion of early atherogenesis by high cortisol concentrations.
Animals↗
Cobb syndrome: case report.
We present a 7-year-old boy in whom cutaneous hemangioma and intramedullary and paraspinal arteriovenous malformations were associated. Magnetic resonance arteriography revealed the presence of the two arterovenous malformations, and the selective intercostal arteriography demonstrated that the intraspinal and paraspinal arteriovenous malformations were supplied by the same intercostal arteries. Rubbing the back was required to detect the cutaneous changes, which were only suspected by casual inspection.
Abnormalities, Multiple↗