801 research outputs found
Rosemary Kinne, Physiology
John Curtin School of Medical Research - Research Scholars - R. B. Vaughan, V. K. Whittaker, Mrs. J. Beatty, Rosemary Kinne, J. W. Phillis, R. Barry, J. A. Broomhead, R. G. Webster, Miss Janet Atkinson, W. J. O'Sullivan, Dr. D. G. Gasliek, B. McDougall, Dr. D. D. Perri
Brush border and basal lateral membranes in the action of thyroid hormone on the proximal tubule
Regulation of volume reabsorption by thyroid hormones in the proximal tubule of rat: Minor role of luminal sodium permeability
In order to investigate whether changes in luminal membrane sodium permeability can explain the increase in isotonic fluid reabsorption (Jv) found in proximal tubules of thyroidectomized rats (TX) treated with tri-iodothyronine (T3), experiments were carried out on TX rats and TX rats treated for 3 days (TX+T3) with physiological doses (10 μg/kg body wt) of T3. Two sets of experiments were performed: 1) in vivo, using the micropuncture technique for the measurements of Jv; 2) in vitro, using isolated brush border membrane vesicles for the direct measurement of Na+ permeability. In micropuncture studies a 65% increase in Jv of TX rats was observed after treatment with T3. Luminal perfusion of proximal tubules of TX rats with Amphotericin B (10 μg/ml), to increase luminal sodium permeability, enhanced Jv only by 15%. Brush border membrane vesicles isolated from TX and TX+T3 rats showed the same sodium permeability in uptake or efflux experiments. These results were confirmed by the fact that sodium gradient dependent histidine transport into brush border membrane vesicles did not change after T3 treatment. Finally, measuring the amiloride sensitive sodium uptake, it was also found that the Na+−H+ exchange was also only slightly affected by T3. These micropuncture and vesicle data indicate that the large effect of T3 on the trans-cellular sodium transport and volume reabsorption in the proximal tubule, cannot be explained by an action of T3 on the sodium entry step across the brush border membrane. © 1985, Springer-Verlag. All rights reserved
Thyroid hormones and renal transport: Cellular and biochemical aspects
The thyroid hormones tri-iodothyronine (T3) and thyroxine (T4) are found in all vertebrates, but it is only in the homeothermic animals that most of the effects are observed [1]. These include stimulation of O2 consumption, effects on growth and maturation, regulations of sugar, and lipid metabolism. The hormones furthermore influence mineral metabolism and the distribution of water and electrolytes between body fluid compartments. This paper will review the action of thyroid hormones on the kidney with particular emphasis on the biochemical and biophysical aspects of thyroid hormones action on transport processes of well–defined tubular segments and cell membranes. Moreover, we will discuss the role of thyroid hormones in regulating renal cell growth and differentiation. Finally we will outline a working hypothesis for the action of thyroid hormones on the kidney with specific indication of their role in modulating trans-epithelial transport processes.For an in depth analysis of the clinical aspects of the effect of thyroid hormones on kidney function and electrolyte metabolism, the reader is referred to other reviews [2–4] which have been published recently
Determinazione in situ ed in vivo del pH intracellulare di singole cellule tubulari mediante microscopia laser confocale
I-123-antileukoproteinase scintigraphy reveals microscopic cartilage alterations in the contralateral knee joint of rats with "monarticular" antigen-induced arthritis
Objective, To assess the involvement of the contralateral knee joint in monarticular antigen-induced arthritis (AIA) by scintigraphy with the cationic (pI >10),I-123-labeled, serine proteinase inhibitor antileukoproteinase (I-123-ALP) and to compare the scintigraphic findings with those of radiography and high-resolution ex vivo magnetic resonance imaging (MRI). Methods, Lewis rats with chronic AIA were examined 2.5 months following arthritis induction (injection of 500 mu g of methylated bovine serum albumin/saline into the ipsilateral [arthritic] knee joint and injection of phosphate buffered saline into the contralateral knee joint following systemic immunization). I-123-ALP was injected intravenously into normal rats (n = 4) or rats with AIA (n = 6), The ipsilateral and contralateral knee joints and both ankles were examined by scintigraphy and radiography, Joint cartilage was examined by high-resolution ex vivo MRI, histopathology, and measurement of tissue radioactivity. Results. ALP accumulation (typically observed in normal articular cartilage) was lost in both the ipsilateral and the contralateral knee joints, but not in the clinically unaffected ankles of rats with ALA, In both knee joints, I-123-ALP target:background ratios and cartilage radioactivity correlated negatively with the loss of toluidine blue staining in cartilage, which documents the depletion of charged matrix molecules. Findings of histopathology confirmed mild alterations in the ipsilateral knee joint and even milder alterations in the contralateral knee joint, while the ankles were normal. Radiography and high-resolution ex vivo MRI failed to detect abnormalities in the contralateral knee joint. Conclusion. Loss of ALP accumulation appears to document proteoglycan depletion, even in the microscopically altered cartilage of the contralateral knee joint in AIA, These findings underscore the high sensitivity of I-123-ALP for in vivo detection of biochemical cartilage alterations in arthritis, and furthermore, question the use of the contralateral knee joint as a normal control in AIA
The use of micropuncture, isolated tubule, and vesicle technique in the study of the action of thyroid hormones on the proximal tubule function
In hypothyroid rats (TX), the isotonic fluid reabsorption (Jv), that is closely linked to the transepithelial sodium transport (JNa), is unpaired. The administration of physiological doses (10 μg/kg body weight per day) of tri-iodothyronine (T3) doubles Jv in three days (TX+T3J. This phenomenon could be explained by several mechanisms: (i) a direct stimulation of Na-K-A TPase, (ii) an increase in the Na+ entry step, (iii) changes in the permeability properties of the luminal and/or basal lateral membranes. Using a kinetic microassay, Na-K-ATPase activity was measured in early (S1) and late (S2) proximal tubules segments isolated from control, TX, and TX+3T3 animals. In TX rats the enzyme activity was lower (70%) in both segments versus control rats, it remained unchanged after 3 days, and it increased after 7 days of T3 substitution. The Na+ permeability of brush border membrane (BBM) vesicles isolated from TX and TX+T3 rats was identical. However the valuation of the K+ membrane permeability by in vivo perfusion of the lumen and peritubular space of proximal tubules of TX rats, with perfusate containing the K+ ionophore valinomycin (1 μg/ml), induced a significant increase in Jv that accounted for 40% of that elicited by T3. Taken together, the in vivo and in vitro experiments suggest that the early effect on Jv of physiological doses of T3 cannot be explained by a direct action of T3 either on the Na+ entry step across the BBM or on the Na+ exit step (i.e., the Na-K-ATPase), but rather by an increase in K+ permeability of proximal tubular cell membranes. This latter effect would explain the increase in Jv through an increase in the driving force for sodium. © 1985 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted
Amphotericin B and Amphotericin B methylester: Effect on brush border membrane permeability
In order to explain the nephrotoxicity of polyene antibiotics such as Amphotericin B (AM), an effect on the tubule membrane permeability has been postulated. However, studies on the action of AM have been complicated by the use of sodium deoxycholate (DOC), a membrane dissociating detergent as a solvent. Recently, a derivative, the methylester aspartate salt of Amphotericin B (AME) has been synthesized, which is highly water soluble in the absence of organic solvents. We have tested the action of AM, DOC, and AME on the sodium permeability of brush border (BBM) vesicles isolated from rat kidney cortex. It was found that both AM and AME increased the 22Na uptake as measured by a rapid filtration technique. However, a large fraction of the AM action was due to the effect of DOC on the BBM sodium permeability. We also investigated the time- and dose-dependent action of AME on 22Na and 3H-D-mannitol efflux from BBM vesicles. After 15 sec of exposure, efflux from 22Na-preloaded vesicles was unchanged in the presence of 1 μg AME/mg protein compared to control vesicles. With 10, 50, and 100 μg AME/mg protein, the efflux increased 16, 25, and 35% respectively; 260 μg AME/mg protein did not elicit a further increment in the 22Na efflux. In the same membrane vesicles 3H-D-mannitol efflux did not change. After preincubation of the membranes for 60 min with different concentrations of AME, the 15 sec 22Na efflux increased 26% in the presence of 1 μg/mg protein AME with no change in the 3H-D-mannitol efflux. At higher concentrations of AME (200 and 300 μg/mg protein), an increase in 22Na efflux (36%), but also an increased 3H-D-mannitol efflux (26 and 63% respectively) was observed. These studies demonstrate that AME increases the Na permeability of BBM in a time- and dose-dependent manner. At higher concentrations and with longer incubation periods, AME additionally affects the overall membrane permeability. The increase in sodium permeability and the breakdown in membrane barrier may be among the factors responsible for the nephrotoxocity of Amphotericin B and its derivatives
ORMONI TIROIDEI E TRASPORTO TUBULARE PROSSIMALE DI SODIO I: VARIAZIONI DELL'ATTIVITÀ DELLA NA+-K+-ATPASI DETERMINATA SU SINGOLI NEFRONI
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