Coronary flow-induced inotropism is modulated by binding of dextrans to the endothelial luminal surface

In isolated perfused guinea pig hearts, coronary flow causes a positive inotropic effect [positive coronary flow-induced effect (+CFIE)] that could be altered by dextrans (Dx) in the coronary perfusion solution. To test this possibility, Dx of 20, 40, 70, and 500 kDa were infused and found to modulate +CFIE; however, when Dx infusion was terminated, the effect persisted, i.e., was irreversible/nonwashable, suggesting that Dx may bind to luminal endothelial lectinic structures. This hypothesis was tested when Dx [with fluorescent traces (D*)] bound to the vessel wall was hydrolyzed by dextranase infusion and washout of D* fragments completely reverted the +CFIE, and it was found that bound D* to be displaced by free Dx required concentrations 50-100 times that used during binding. In addition, dose-response curves for Dx on +CFIE show that the higher the Dx molecular mass, the lesser the concentration required to have an effect. Because a large Dx molecule has a greater number polymeric glucose branches, it can bind to a larger number of endothelial lectinic sites, requiring a lower concentration to affect +CFIE. Our results suggest that luminal endothelial lectinic structures are part of the flow-sensing assembly.     

Comparative biology and pathology of oxidative stress in Alzheimer and other neurodegenerative diseases: beyond damage and response

In this review, we consider comparative aspects of the biology and pathology of oxygen radicals in neurodegenerative disease and how these findings have influenced our concept of oxidative stress. The common definition of oxidative stress is a breach of antioxidant defenses by oxygen radicals leading to damage to critical molecules and disrupted physiology. Inherent in this definition is that oxidative stress is an unstable situation, for if there is net damage, viability of the system decreases with time, leading to disequilibria and death. While this circumstance defines acute conditions, such as stroke and head trauma which result in dysfunction and death, it does not fit physiological situations or chronic diseases closely aligned to normal physiology. Therefore, we propose that oxidative modifications in Alzheimer disease may actually serve as a homeostatic response to stress resulting in a shift of neuronal priority from normal function to basic survival. This phenomenon is comparable to normal physiological conditions of metabolic decrease, such as those seen in hibernation and estivation. Thus, Alzheimer disease could be seen as part of normal aging that includes additional pathology due to inadequate homeostatic response.     

Effects of caecal ligation and saline acclimation on plasma concentration and organ mass in male and female Pekin ducks,Anas platyrhynchos

Summary The intestinal caeca reabsorb urinary sodium chloride (NaCl) and water (Rice and Skadhauge 1982). Free water may be generated if the reabsorbed NaCl is secreted via salt gland secretion (Schmidt-Nielsen et al. 1958). Therefore ceacal ligation should (a) reduce hingut NaCl and water reabsorption, (b) enhance the increase in plasma osmolality during saline acclimation, and (c) affect drakes more than ducks. Twelve Pekin drakes and 13 Pekin ducks, Anas platyrhynchos, were caecally ligated or sham operated before acclimation to 450 mmol · 1 NaCl. Body mass, hematocrit, plasma osmolality, and inonic concentrations of plasma, cloacal fluid, and salt gland secretion were measured after each increase in drinking water salinity. Osmoregulatory organ masses were determined. Caecal ligation did not effect plasma osmolality or ion concentrations of plasma, cloacal fluid, or salt gland secretion, but reduced salt gland size in ducks. Drakes and ducks drinking fresh water had the same hematocrit, plasma osmolality, and plasma concentrations of Na⁺ and Cl^–. In both sexes exposure to 75 mmol · 1^-1 NaCl significantly decreased plasma [Na⁺] and doubled cloacal fluid [Na⁺]. Exposure to 450 mmol · 1^-1 NaCl decreased body mass and increased hematocrit, plasma [Na⁺], [Cl^–], and plasma osmolality (more in drakes than in ducks); cloacal fluid osmolality nearly doubled compared to freshwater-adapted ducks, due mainly to osmolytes other than Na⁺ and Cl^–. The [Cl^–] in salt gland secretion only slightly exceeded drinking water [Cl^–].Abbreviations AVT antiduretic hormone - CF cloacal fluid - ECFV extraoellular fluid volume - FW freshwater acclimated - Hct hematocrit - MDWE mean daily water flux - [Na ⁺]_cf cloacal fluid sodium concentration - [Na ⁺]_pl plasma sodium concentration - Osm _cf cloacal fluid osmolality - Osm _pl plasma osmolality - SGS salt gland secretion - TBW total body water