Aminoglycosides and renal magnesium homeostasis in humans.
(73/1587)
BACKGROUND: The use of aminoglycosides has been linked with hypomagnesaemia in scattered reports. The objective of the study was to measure prospectively the effect of treatment with the aminoglycoside amikacin on renal magnesium homeostasis. METHODS: Twenty-four cystic fibrosis patients (aged 9-19 years) admitted because of exacerbation of pulmonary symptoms caused by Pseudomonas aeruginosa were treated with the aminoglycoside amikacin and the cephalosporin ceftazidime for 14 days. Renal values and plasma and urinary electrolytes were measured before and at the end of the systemic anti-pseudomonal therapy. RESULTS: In the patients with cystic fibrosis, treatment with amikacin and ceftazidime did not modify plasma creatinine or urea and plasma or urinary sodium, potassium and calcium. Treatment with amikacin and ceftazidime significantly decreased both plasma total magnesium (from 0.77 (0. 74-0.81) to 0.73 (0.71-75) mmol/l; median and interquartile range) and ionized magnesium (from 0.53 (0.50-0.55) to 0.50 (0.47-0.52) mmol/l) concentration and increased fractional urinary magnesium excretion (from 0.0568 (0.0494-0.0716) to 0.0721 (0.0630-0.111)) and total urinary magnesium excretion (from 30.7 (26.5-38.0) to 38.5 (31. 5-49.0) micromol/l glomerular filtration rate). CONCLUSIONS: The present study demonstrates that systemic therapy with amikacin plus ceftazidime causes mild hypomagnesaemia secondary to renal magnesium wasting even in the absence of a significant rise in circulating creatinine and urea. (+info)
Airway surface liquid composition in mice.
(74/1587)
Airway surface liquid (ASL) lines the conducting airways of the respiratory tract. We collected small samples of this liquid from the lower tracheae of anesthetized C57BL/6 mice and determined its ionic composition (in mM: 87.2 Na(+), 4.7 K(+), and 57.0 Cl(-)). Intravenous methacholine produced significant increases in the concentrations of Na(+), K(+), and Cl(-) within ASL. A limited analysis of liquid from cystic fibrosis transmembrane conductance regulator (CFTR) knockout mice revealed no significant differences compared with littermate controls; however, Pseudomonas aeruginosa infection led to an increase in the salt concentration of ASL in cftr(+/+) mice. Morphometric measurements of tracheal submucosal gland volume revealed significant differences between inbred mouse strains, corresponding to ease of ASL collection. We conclude that although submucosal glands may be responsible for the production of some ASL, the ionic composition of this liquid is actively regulated by the underlying epithelial cells. (+info)
Effect of temperature on pH and electrolyte concentration in air-breathing ectotherms.
(75/1587)
The aim of this study was to determine the effects of temperature upon pH, protein charge and acid-base-relevant ion exchange in air-breathing ectotherms. Plasma and skeletal muscles in cane toads (Bufo marinus) and bullfrogs (Rana catesbeiana) were examined at 30, 20 and 10 degrees C. In addition, skeletal muscle ion concentrations were examined in black racer snakes (Coluber constrictor) at 30 and 10 degrees C. Cooling the amphibians produced a reduction in most of the plasma ion concentrations (Na(+), K(+), Ca(2+), Cl(-), SO(4)(2)(-)) and in protein concentration because of increased hydration. Between 30 and 10 degrees C, total plasma osmolality fell by 14 % in the toads and by 5 % in the frogs. Plasma protein charge, calculated using the principle of electroneutrality, was unaffected by temperature, except possibly for the toads at 10 degrees C. The in vivo skeletal muscle capdelta pHi/ capdelta T ratio, where pHi is intracellular pH and T is temperature, between 30 and 20 degrees C averaged -0.014 degrees C(-)(1) in the toads and -0.019 degrees C(-)(1) in the frogs. Between 20 and 10 degrees C, there was no change in pHi in the toads and a -0.005 degrees C(-)(1) change in the frogs. The in vitro skeletal muscle capdelta pHi/ capdelta T averaged -0.011 degrees C(-)(1) in both toads and frogs. In all three species, skeletal muscle inulin space declined with cooling. Intracellular ion concentrations were calculated by subtracting extracellular fluid ion concentrations from whole-muscle ion concentrations. In general, temperature had a large effect upon intracellular ion concentrations (Na(+), K(+), Cl(-)) and intracellular CO(2) levels. The relevance of the changes in intracellular ion concentration to skeletal muscle acid-base status and protein charge and the possible mechanisms producing the adjustments in intracellular ion concentration are discussed. It is concluded that ion-exchange mechanisms make an important contribution to adjusting pH with changes in temperature. (+info)
Hierarchical self-assembly of F-actin and cationic lipid complexes: stacked three-layer tubule networks.
(76/1587)
We describe a distinct type of spontaneous hierarchical self-assembly of cytoskeletal filamentous actin (F-actin), a highly charged polyelectrolyte, and cationic lipid membranes. On the mesoscopic length scale, confocal microscopy reveals ribbonlike tubule structures that connect to form a network of tubules on the macroscopic scale (more than 100 micrometers). Within the tubules, on the 0.5- to 50-nanometer length scale, x-ray diffraction reveals an unusual structure consisting of osmotically swollen stacks of composite membranes with no direct analog in simple amphiphilic systems. The composite membrane is composed of three layers, a lipid bilayer sandwiched between two layers of actin, and is reminiscent of multilayered bacterial cell walls that exist far from equilibrium. Electron microscopy reveals that the actin layer consists of laterally locked F-actin filaments forming an anisotropic two-dimensional tethered crystal that appears to be the origin of the tubule formation. (+info)
The inhibition of cholera toxin-induced 5-HT release by the 5-HT(3) receptor antagonist, granisetron, in the rat.
(77/1587)
1. The secretagogue 5-hydroxytryptamine (5-HT) is implicated in the pathophysiology of cholera. 5-HT released from enterochromaffin cells after cholera toxin exposure is thought to activate non-neuronally (5-HT(2) dependent) and neuronally (5-HT(3) dependent) mediated water and electrolyte secretion. CT-secretion can be reduced by preventing the release of 5-HT. Enterochromaffin cells possess numerous receptors that, under basal conditions, modulate 5-HT release. 2. These include basolateral 5-HT(3) receptors, the activation of which is known to enhance 5-HT release. 3. Until now, 5-HT(3) receptor antagonists (e.g. granisetron) have been thought to inhibit cholera toxin-induced fluid secretion by blockading 5-HT(3) receptors on secretory enteric neurones. Instead we postulated that they act by inhibiting cholera toxin-induced enterochromaffin cell degranulation. 4. Isolated intestinal segments in anaesthetized male Wistar rats, pre-treated with granisetron 75 microg kg(-1), lidoocaine 6 mg kg(-1) or saline, were instilled with a supramaximal dose of cholera toxin or saline. Net fluid movement was determined by small intestinal perfusion or gravimetry and small intestinal and luminal fluid 5-HT levels were determined by HPLC with fluorimetric detection. 5. Intraluminal 5-HT release was proportional to the reduction in tissue 5-HT levels and to the onset of water and electrolyte secretion, suggesting that luminal 5-HT levels reflect enterochromaffin cell activity. 6. Both lidocaine and granisetron inhibited fluid secretion. However, granisetron alone, and proportionately, reduced 5-HT release. 7. The simultaneous inhibition of 5-HT release and fluid secretion by granisetron suggests that 5-HT release from enterochromaffin cells is potentiated by endogenous 5-HT(3) receptors. The accentuated 5-HT release promotes cholera toxin-induced fluid secretion. (+info)
Potassium depletion increases proton pump (H(+)-ATPase) activity in intercalated cells of cortical collecting duct.
(78/1587)
Intercalated cells (ICs) from kidney collecting ducts contain proton-transporting ATPases (H(+)-ATPases) whose plasma membrane expression is regulated under a variety of conditions. It has been shown that net proton secretion occurs in the distal nephron from chronically K(+)-depleted rats and that upregulation of tubular H(+)- ATPase is involved in this process. However, regulation of this protein at the level of individual cells has not so far been examined. In the present study, H(+)-ATPase activity was determined in individually identified ICs from control and chronically K(+)-depleted rats (9-14 days on a low-K(+) diet) by monitoring K(+)- and Na(+)-independent H(+) extrusion rates after an acute acid load. Split-open rat cortical collecting tubules were loaded with the intracellular pH (pH(i)) indicator 2', 7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein, and pH(i) was determined by using ratiometric fluorescence imaging. The rate of pH(i) recovery in ICs in response to an acute acid load, a measure of plasma membrane H(+)-ATPase activity, was increased after K(+) depletion to almost three times that of controls. Furthermore, the lag time before the start of pH(i) recovery after the cells were maximally acidified fell from 93.5 +/- 13.7 s in controls to 24.5 +/- 2.1 s in K(+)-depleted rats. In all ICs tested, Na(+)- and K(+)-independent pH(i) recovery was abolished in the presence of bafilomycin (100 nM), an inhibitor of the H(+)-ATPase. Analysis of the cell-to-cell variability in the rate of pH(i) recovery reveals a change in the distribution of membrane-bound proton pumps in the IC population of cortical collecting duct from K(+)-depleted rats. Immunocytochemical analysis of collecting ducts from control and K(+)-depleted rats showed that K(+)-depletion increased the number of ICs with tight apical H(+)ATPase staining and decreased the number of cells with diffuse or basolateral H(+)-ATPase staining. Taken together, these data indicate that chronic K(+) depletion induces a marked increase in plasma membrane H(+)ATPase activity in individual ICs. (+info)
Comparison of enalapril and valsartan in cyclosporine A-induced hypertension and nephrotoxicity in spontaneously hypertensive rats on high-sodium diet.
(79/1587)
1. We compared the effects of the angiotensin converting enzyme (ACE) inhibitor enalapril and the angiotensin AT(1) receptor antagonist valsartan in cyclosporine A (CsA)-induced hypertension and nephrotoxicity in spontaneously hypertensive rats (SHR). 2. SHR (8 - 9 weeks old) on high-sodium diet were given CsA (5 mg kg(-1)d (-1) s.c. ) for 6 weeks. The rats were treated concomitantly either with enalapril (30 mg kg(-1)d (-1) p.o.) or valsartan (3 or 30 mg kg(-1) d (-1) p.o.). To evaluate the role of bradykinin in the action of enalapril, some rats received a bradykinin B(2) receptor antagonist icatibant (HOE 140, 500 microg kg(-1) d (-1) s.c.) during the last 2 weeks of enalapril treatment. 3. Blood pressure was recorded every second week by tail cuff method. Renal function was measured by serum creatinine, creatinine clearance and urinary excretion of proteins at the end of the experiment. The activity of the renal kallikrein-kinin system was estimated by urinary kallikrein excretion. 4. CsA caused hypertension, impaired renal function and induced morphological nephrotoxicity with glomerular damage and interstitial fibrosis. Enalapril and the lower dose of valsartan attenuated the CsA-induced hypertension to the same extent, while the higher dose of valsartan totally abolished it. Icatibant did not reduce the antihypertensive effect of enalapril. Urinary kallikrein excretion was similar in all groups. 5. Enalapril and valsartan equally prevented the CsA-induced deterioration of kidney function and morphology. 6. The renin-angiotensin but not the kallikrein-kinin system plays a crucial role in CsA-toxicity during high intake of sodium in SHR. (+info)
IGF-I treatment in adults with type 1 diabetes: effects on glucose and protein metabolism in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp.
(80/1587)
Type 1 diabetes is associated with abnormalities of the growth hormone (GH)-IGF-I axis. Such abnormalities include decreased circulating levels of IGF-I. We studied the effects of IGF-I therapy (40 microg x kg(-1) x day(-1)) on protein and glucose metabolism in adults with type 1 diabetes in a randomized placebo-controlled trial. A total of 12 subjects participated, and each subject was studied at baseline and after 7 days of treatment, both in the fasting state and during a hyperinsulinemic-euglycemic amino acid clamp. Protein and glucose metabolism were assessed using infusions of [1-13C]leucine and [6-6-2H2]glucose. IGF-I administration resulted in a 51% rise in circulating IGF-I levels (P < 0.005) and a 56% decrease in the mean overnight GH concentration (P < 0.05). After IGF-I treatment, a decrease in the overnight insulin requirement (0.26+/-0.07 vs. 0.17+/-0.06 U/kg, P < 0.05) and an increase in the glucose infusion requirement were observed during the hyperinsulinemic clamp (approximately 67%, P < 0.05). Basal glucose kinetics were unchanged, but an increase in insulin-stimulated peripheral glucose disposal was observed after IGF-I therapy (37+/-6 vs. 52+/-10 micromol x kg(-1) x min(-1), P < 0.05). IGF-I administration increased the basal metabolic clearance rate for leucine (approximately 28%, P < 0.05) and resulted in a net increase in leucine balance, both in the basal state and during the hyperinsulinemic amino acid clamp (-0.17+/-0.03 vs. -0.10+/-0.02, P < 0.01, and 0.25+/-0.08 vs. 0.40+/-0.06, P < 0.05, respectively). No changes in these variables were recorded in the subjects after administration of placebo. These findings demonstrated that IGF-I replacement resulted in significant alterations in glucose and protein metabolism in the basal and insulin-stimulated states. These effects were associated with increased insulin sensitivity, and they underline the major role of IGF-I in protein and glucose metabolism in type 1 diabetes. (+info)