To investigate whether dysfunction of the proximal tubule underlies maleic acid-(MA) induced type II ("proximal") renal tubular acidosis (RTA II), we intravenously administered either MA or acetazolamide to eight conscious trained dogs undergoing water diuresis and examined the relationship between fractional solute-free water clearance (Ch2o/GFR), a measure of NaCl reabsorption in the post-proximal nephron, and either fractional urine flow (V/GFR), a measure of total solute rejected by the proximal tubule, or the sum of fractional excretion of Cl- and Ch2o/GFR [(Ccl + Ch2o)/GFR], a measure of proximally rejected solute that is potentially reabsorbable by the thick ascending limb. When MA or acetazolamide induced brisk bicarbonaturia at normal plasma bicarbonate concentrations: 1) V/GFR, (Ccl + Ch20)GFR, and Ch2o/GFR increased strikingly; 2) at any increment of Ch2o/GFR ws not; 3) the increments of V/GFR correlated positively with those of fractional excretion of bicarbonate (P less than 0.001); 4) during hyperchloremic acidosis, MA-induced bicarbonaturia was greatly attenuated; the increment in V/GFR was halved and approximated that in Ch20/GFR, which was unchanged; 5) when plasma bicarbonate was abruptly increased, bicarbonaturia increased strikingly and V/GFR increased further but Ch20/GFR and aminoaciduria did not. We conclude that MA induces a reduction in the net rate at which the proximal tubule reabsorbs HCO-3, Na+, and Cl-. This dysfunction underlies RTA II and evokes greatly increased reabsorption of Cl- and Na+ in the post-proximal tubule.
ABSTRACT. The phagocytic and bactericidal capacities of ovine bronchoalveolar lavage (BAL) cells were investigated as a function of postnatal age. In addition, age-related changes in the elaboration by alveolar macrophages of chemotaxins for neutrophils, concentrations of BAL fluid and serum immunoglobulins, and serum opsonic capacity were determined. BAL cells exhibited major changes in morphology, composition, and in vitro proliferation during the 1st postnatal wk. Studies in germ-free lambs indicated that the antigenic burden of the ambient environment markedly influenced the concentration of BAL neutrophils but had no effect on the influx, phagocytic, and proliferative activities of alveolar macrophages. Phagocytic and bactericidal functions of BAL cells improved rapidly during the 1st postnatal wk, then declined, and did not reattain adult levels until day 180. The capacity of alveolar macrophages to elaborate chemotaxins for neutrophils was deficient at day 8, but not at subsequent ages. The concentration of BAL IgG, increased until day 8, fell at day 21, and then continued to increase gradually. IgA was not detected in BAL until day 21 and increased rapidly thereafter. Serum opsonic capacity at days 1 and 4 was comparable to that of adult serum, but sera from days 8 to 42 showed a marked reduction in opsonic capacity. Pulmonary antimicrobial defenses in neonatal sheep were thus found to be deficient to some degree throughout the first 3 months of life. It was not until day 180 that the parameters investigated in this study approximated those of adult sheep.
To determine if there is a rationale for compartmentalized immunostimulation, we have carried out a series of experiments to evaluate whether intratracheal delivery of interferon-gamma (rRatIFN-gamma) can activate rat bronchoalveolar lavage cells (BAL) for in vitro expression of tumoricidal activity against xenogeneic P815 tumor cells and enhanced in vitro microbicidal activity against the intracellular protozoan Toxoplasma gondii. Treatment of rat alveolar macrophages in vitro activates them for both of these activities as well as enhanced production of superoxide anion. We found that a single intratracheal dose of 5,000-10,000 units of rRatIFN-gamma activated rat BAL for both microbicidal and tumoricidal activity. To determine the duration of activation, microbicidal activity was determined 1, 2, 3, 5, and 7 days after a single intratracheal dose of 5,000 units of IFN. Enhanced microbicidal activity was maintained through day 3 but returned to control levels by day 5. Alveolar macrophages always accounted for the majority of cells in the lavage populations. However, intratracheal IFN caused an increase in the number of polymorphonuclear leukocytes and lymphocytes in the lavageable cells and, although these cells were always in the minority, they may have contributed to both the tumoricidal and microbicidal activity of the lavage cells. These studies demonstrate that local administration of an immunostimulant can activate pulmonary defense cells and may be a feasible route of drug delivery for prophylaxis against pulmonary infections.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.