Acute Kidney Injury

Simple acid-base disorders are defined by changes in pH and the initial change in 1 of the 2 variables, serum bicarbonate (HCO3-) and PCO2. Low pH indicates acidosis, and high pH indicates alkalosis. If 1 of the 2 components (HCO3-or PCO2) decreases, the other component also decreases (a compensatory change that minimizes the change in the ratio and the pH) and vice versa, as shown in the Henderson-Hasselbalch equation. Emphasis has been placed on the Henderson-Hasselbalch equation because the equation describes the 4 acid-base disorders and their compensatory changes.

R439 – Effect of Resistance-Compliance Changes in Fluidic Systems

Problem Previous work has established the relationship of resistance and compliance in a bench-top model of 2 parallel fluid systems representing endolymph and perilymph. The R-C Product is mathematically proportional to the time to equilibrium. Increasing the resistance to fluid movement in the “endolymph” significantly increased the time to hydrostatic equilibrium between the systems. The current study was designed to test whether a compensatory change in the R-C Product on the “perilymphatic” side would reduce the time to steady state. Methods As previously described, 2 parallel tubular systems with symmetric resistance and compliance members were perturbed by rotating the model from a horizontal, equilibrium condition to an upright, disequilibrium condition. Time to steady state was video recorded in 4 resistance conditions. The primary test was whether increased resistance to flow on the “endolymph” limb would be negated by an equal increase to resistance to flow on the “perilymph” limb. Results All 4 resistance conditions exhibited differences in time to steady state by ANOVA (p = 3.4 × 10E-12). Mean time to a steady state was reduced when a compensatory change in resistance was applied to the “perilymph” limb (1.0 + 1.1 sec) when compared to high resistance in the “endolymph” alone (2.5 + 1.3 sec, p = .01). Conclusion Compensatory changes in the R-C Product can reduce time to equilibrium. Significance Improved treatment of vertigo may be possible by application of principles that can affect resistance (fluid pathway diameter or viscosity) or compliance (stiffness of the oval or round window) of the systems. Support University of Minnesota Biomedical Engineering Institute Otolaryngology Interest Group Fund.

Identification of a Compensatory Mutant (lpg2−REV) of Leishmania major Able To Survive as Amastigotes within Macrophages without LPG2-Dependent Glycoconjugates and Its Significance to Virulence and Immunization Strategies

ABSTRACT Different Leishmania species rely to different extents on abundant glycoconjugates, such as lipophosphoglycan (LPG) and related molecules, in mammalian infections. Previously, we showed that Leishmania major deletion mutants lacking the Golgi GDP-mannose transporter LPG2, which is required for assembly of the dominant phosphoglycan (PG) repeats of LPG, were unable to survive in macrophages. These lpg2 − mutants, however, retained the ability to generate asymptomatic, persistent infections in mice. In contrast, Ilg and colleagues showed that Leishmania mexicana LPG2 mutants retained virulence for mice. Here we identified a partial revertant population of the L. major lpg2 − mutants (designated lpg2 − REV) that had regained the ability to replicate in macrophages and induce disease pathology through a compensatory change. Like the lpg2 parent, the lpg2 − REV revertant was unable to synthesize LPG2-dependent PGs in the promastigote stage and thus remained highly attenuated in the ability to induce infection. However, after considerable delay lpg2 − REV revertant-infected mice exhibited lesions, and amastigotes isolated from these lesions were able to replicate within macrophages despite the fact that they were unable to synthesize PGs. Thus, in some respects, the lpg2 − REV amastigotes resemble L. mexicana amastigotes. Future studies of the gene(s) responsible may shed light on the mechanisms employed by L. major to survive in the absence of LPG2-dependent glycoconjugates and may also improve the potential of the lpg2 − L. major line to serve as a live parasite vaccine by overcoming its tendency to revert toward virulence.