Dialysis dementia: the role of dialysate pH in altering the dialyzability of aluminum.
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Biomedical subjects
Publications and source records attributed to D L Fry.
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Parenteral Evans blue dye (EBD) binds to albumin and thus can indicate transvascular protein flux. A model was developed to relate the arterial surface accumulation of EBD to the light refected from the opened vessel surface. The accumulation, M (nmol cm-2), was related to the optical "absorbance" (rho) of the surface by the equation, M = 3.92 rho + 0.80 rho3, where rho = -ln(I/I0) and I and I0 are the intensities of light reflected from the surface in the stained and unstained state, respectively. The validity of the model was examined in two ways, 1) by comparing the value of the optical absorption coefficient for EBD predicted by the model to the measured value: the predicted value was 0.128 +/- SD 0.015 cm2 nmol-1, the measured value was 0.125 +/- SD 0.005 cm2 nmol-1; and 2) by comparing predicted changes in vessel wall stretch to measured values: the percentage changes (Y) in area predicted by the model from changes in M were linearly related to the directly measured percentage area changes (X) by Y = 0.09 + 1.01X, +/- SD 2.54, with a correlation coefficient of 0.994.
The simultaneous transport of Evans blue dye (EBD) and 125I-labeled canine albumin (IALB) across normal and injured endothelial surface was measured by determining the intimal accumulation of EBD (ME) by a reflectometric method and accumulation of equimolar concentrations of EBD and IALB, ME was related to MI by ME = 0.092 + 5.04 MI - 0.508 MI2 for injured and ME = 0.002 + 0.435 MI (nmol-cm-2) for normal surfaces. Both ME and MI varied nonlinearly with exposure time for injured and linearly with time for normal surfaces, giving apparent permeability coefficients of 0.92 X 10(-8) cm-sec-1 for EBD and 2.00 X 10(-8) cm-sec-1 for albumin. These results show that the transvascular flux of EBD can be related to that of albumin by empirical equations, which is of practical importance but also implies unique underlying physical laws. Study of these physical laws will provide deeper insight into transvascular macromolecular transport processes.
The wall shear stress pattern was measured in a rigid plastic cast of a canine artery during steady flow by means of an electrochemical technique. The topographic distribution of shear stress is very nonuniform, with regions of high and low shear in close proximity. The steady shear stresses are highest at the leading edge of flow dividers and at the entrance regions to branch vessels. The shapes of the shear stress curves in the celiac branch are primarily a function of the ratio of branch flow to total aortic flow. However, the shapes of the shear stress curves in the adjacent anterior mesenteric branch remain the same for different anterior mesenteric branch flow ratios, although the shear increases with the branch flow ratio. An unstable pattern of flow separation and reattachment is found at the anterior mesenteric flow divider lip and remains localized to that region. A correlation is suggested between sites of high shear stress, extremes in the range of stress, and unstable stress patterns and sites at which atherosclerosis has been shown to develop.
The kinetics of the cyanate-hemoglobin reaction in normal whole blood have been investigated. The mechanism was found to be second order, irreversible, bimolecular. The influence of the temperature, pH, Po2, and Pco2 on the reaction rate constant was examined. A temperature change from 37 degrees to 42 degrees C, resulted in a 50 percent increase in the rate constant. The rate constant increased in proportion to the pH decrease, and deoxygenated whole blood was carbamylated approximately twice as fast as oxygenated blood. Carbon dioxide pressures had no influence on rates of carbamylation when a constant pH was maintained. A maximum rate constant of 3.7 M-U min.-u was obtained with conditions which were compatible with the red blood cells. This knowledge of the reaction mechanism and the influence of important system parameters on the reaction rate constant may be applied to the development of an extracorporeal system for the treatment of sickle cell anemia.
Dogs maintained for 1 year on a semisynthetic diet containing hydrogenated coconut oil and cholesterol developed hypercholesterolemia. In those cases where plasma cholesterol levels exceeded 750 mg/100 ml, the animals also developed severe atherosclerosis. This atherogenic hyperlipoproteinemia was characterized by the presence of beta very low density lipoproteins (B-VLDL), increased levels of low density lipoproteins (LDL), and the occurrence of the HDLc lipoproteins. In all of these cholesterol-rich lipoproteins the arginine-rich apoprotein (ARP) was prominent. Moreover, the HDLc (d = 1.006-1.02) contained the ARP as the only detectable apoprotein. The atherosclerosis involved the abdominal aorta, coronary and cerebrovascular arteries, and many of the peripheral arteries. Histologically, the aortic lesions were characterized by a variable intimal proliferative response and extensive medial lipid deposition. In the peripheral, coronary, and cerebral arteries, the lesions were more extensive and involved primarily the media of the vessel wall, with little intimal reaction in many cases. The correlation between the in vivo disease process and the response of aortic smooth muscle cells (SMC) grown in tissue culture to the various cholesterol-induced lipoproteins was examined. B-VLDL, LDL, and HDLc (but not HDL2) caused a marked accumulation of free and esterified cholesterol in the SMC. The cholesterol accumulation was found to be more extensive in canine SMC than in swine smooth muscle cells or smooth muscle cells of other species in response to a similar lipoprotein cholesterol concentration. The enhanced sterol uptake appeared to be a property of canine smooth muscle cells rather than a property of the canine lipoproteins. These in vitro results may be related to the observed propensity for the development of medical disease that was demonstrated in the in vivo studies.
Fibrous intimal proliferation severe enough to produce occlusion has been observed in vein segments used for aorta-coronary bypass grafts. In an attempt to improve graft patency and decrease intimal fibrous thickening, animals with vein grafts were treated with dipyridamole or methylprednisolone for 8 to 12 weeks. Femoral vein segments were used to bypass the femoral artery in 36 dogs. Thirty-four of these grafts were patent at 8 weeks, with no statistically significant differences between control and drug treatment groups. Intimal thickness measurements were taken at three different points along the graft: proximal (upstream end), middle,and distal (downstream end). Dogs treated with methylprednisolone had significantly less intimal thickening (214 versus 125 mu, p less than 0.05) than did control animals in the middle of the veins but there was no difference in thickness measurements at the proximal and distal ends. Dipyridamole-treated animals did not differ from control dogs. Although these data show decreasing intimal thickening in the middle of grafts with methylprednisolone therapy, the intimal thickness was still considerably greater than normal. The lack of response near the anastomotic sites suggests that clinical application of either agent to improve long-term patency is unwarranted.
The distribution, severity, and complications of diet-induced atherosclerosis in dogs can be altered by changing the source of fat in the diet. Thrombosis and thromboembolic disease associated with atherosclerosis occurred with diets containing beef tallow and lard of coconut oil but were absent in dogs fed cottonseed oil as a source of fat. Experiemtnal animals with and without thrombosis are of value as models in elucidating the role of platelets and thrombostatic mechanisms in atherosclerosis.
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