The transport of calcium and sodium ions across bilayers induced by neutral synthetic ligands used in specific electrodes

Neutral synthetic ligands of calcium and sodium which enter into the liquid membrane composition of the selective electrodes of these ions have been incorporated within the bilayer. The membrane conductance measured shows that each of these two ligands behave as ion carriers for calcium or sodium ions. The selectivities with respect to the other alcaline or alcaline earth ions are similar to those observed by potentiometric measurements with thick liquid membrane selective electrodes.     

Nomograms for the estimation of the saturation of urine with calcium oxalate, calcium phosphate, magnesium ammonium phosphate, uric acid, sodium acid urate, ammonium acid urate and cystine

The effects on respiratory frequency of preoptic heating during slow-and fast-wave sleep were studied in freely moving cats. During slow-wave sleep, at neutral ambient temperature, the subliminal range of preoptic temperature for thermal polypnea extends to 0.2-0.4 degrees C above control preoptic temperature. During fast-wave sleep, at neutral ambient temperature, the subliminal range of preoptic temperature for thermal polypnea increases beyond 0.9-1.0 degrees C above control preoptic temperature. Moreover, the polypneic response is weak and unstable. The results show the suspension of a precise thermoregulatory control during fast-wave sleep in a homoiothermic species.     

Methodological studies of the estimation of loss of sodium, potassium,calcium and magnesium through the skin during a 10 km run

An estimation of the electrolytic losses through the skin was evaluated in a run over a distance of 10 km on a 400 m Tartan-trac. Na, K, Ca, and Mg excreted by the skin were collected in standardised clothing and thereafter washed out. The remaining electrolytes on the skin were collected by washing the body with deionized water. In addition, the concentrations of hormones and metabolites in blood before and after the race were ascertained. Mean ambiant temperature and relative humidity amounted to 21 degrees C and 35%, respectively. The mean performance was 40.5 min. and the average body weight loss was 1.45 kg. The only significant changes in the serum concentrations were the increases of free fatty acids and glycerol. This can be explained, together with a slight increase of glucose and a decrease of insulin, by a higher sympathoadrenergic activity. In the mean 20 mg calcium, 5 mg magnesium, 200 mg potassium, and 800 mg sodium were lost by the skin per kg body weight loss. Those amounts compared well with corresponding data found in literature. The described method can be proposed for further experiments.     

雾化气流量对ICP-AES测定钾长石中钾、钠、钙、镁、铝、铁和钛的影响

采用氢氟酸、盐酸、硝酸、高氯酸分解样品,电感耦合等离子体原子发射光谱法(ICP-AES)同时测定钾长石中CaO、MgO、Al₂O₃、Fe₂O₃、TiO₂、K₂O、Na₂O。在选择待测元素的分析谱线及背景校正方式基础上,考察了雾化气流量分别在1.0、 0.6、 0.5、0.4 L/min时对钾、钠、钙、镁、铝、铁、钛等元素的谱线强度、测定结果的精密度以及校准曲线线性影响。当雾化气流量为0.4 L/min和0.5 L/min时各元素测定结果的精密度最好,校准曲线线性相关系数均大于0.999;但雾化气流量为0.5 L/min时各元素谱线强度最高,因此选择雾化气流量为0.5 L/min。根据确定的雾化气流量,用ICP-AES对GBW03116钾长石标准物质中上述6种组分进行测定,测定值与认定值的相对误差(RE)在-3.64%~4.26%之间, RSD(n=11)为0.76%~4.2%。     

The participation of chloride and sodium channels in the realization of the effects of superhigh-frequency electromagnetic fields in the centimeter range on the active transport of sodium ions across the cell membrane

The main reason institutions reuse single use medical devices is to save money. Most hospitals are reusing disposables in varying degrees, but few have thoroughly investigated the issues surrounding reuse. Are there true savings to be realized? What are the risks to patients and coworkers? What are the legal and liability hazards to our employers and to ourselves? Professional nurses have a responsibility as patient advocates and employees to question the validity of the reuse of medical devices which are manufactured to be used only once. By reusing disposables are we really cutting costs, or are we cutting corners?     

Cell membrane fatty acid composition in type 1 (insulin-dependent) diabetic patients: relationship with sodium transport abnormalities and metabolic control

We have studied the fatty acid composition of erythrocyte membrane phospholipids in nine Type 1 (insulin-dependent) diabetic patients and nine healthy control subjects. Cell membranes from the diabetic patients showed a marked decrease in the total amount of polyunsaturated fatty acids (19.0% +/- 2.2 vs 24.6% +/- 1.4, p < 0.0001) mainly at the expense of docosahexaenoic acid C22:6(n3) (2.9% +/- 1.1 vs 5.3% +/- 1.3, p < 0.001), and arachidonic acid C20:4n6 (12.0% +/- 1.6 vs 15.1% +/- 0.6, p < 0.0005). Conversely, the total amount of saturated fatty acids was significantly increased (p < 0.05) and the polyunsaturated/saturated ratio was decreased in the Type 1 diabetic patients (p < 0.00 005). Neither the time from diagnosis, nor C-peptide levels, correlated with parameters indicating a poor metabolic control of Type 1 diabetes. However, C22:6(n-3) and total n-3 content significantly correlated with HbA1c (r = -0.79 and r = -0.88, respectively, p < 0.01), fructosamine (r = -0.71 and r = -0.74, respectively, p < 0.05), and Na+-K+ ATPase activity (maximal rate/Km quotient) (r = 0.78 and r = 0.71, respectively, p < 0.05). In conclusion we have found marked alterations of cell membrane lipid composition in Type 1 diabetic patients. These cell membrane abnormalities in lipid content were related to sodium transport systems and to poor metabolic control. Either diet, or the diabetic state, might be responsible for the observed cell membrane abnormalities. A dietary intervention study might differentiate the role of diet and diabetes in the reported cell membrane alterations.     

Hypertension development in Dahl S and R rats on high salt-low potassium diet: calcium, magnesium and sympathetic nervous system

Dietary combination of high salt with low potassium (HSLK) exacerbates hypertension development in Dahl salt-sensitive (S) rats, and produces a mild degree of hypertension in otherwise salt-resistant (R) rats. Increased blood pressure in both strains is associated with increased urinary excretion of calcium and magnesium. The objective of this study was to determine the effect of blood pressure on body balance of these ions in Dahl rats on HSLK diet. Two groups of S and two groups of R weanlings were all placed on HSLK diet (NaCl=8%, K=0.2%) for eight weeks. One group of each strain was subjected to chemical sympathectomy with 6-hydroxydopamine (6-OHDA) to counteract hypertension development. Urinary norepinephrine was used to determine efficacy of 6-OHDA treatment. Systolic blood pressures of conscious animals were measured daily throughout the study. The last three days on the diet were used to determine total dietary intake and urinary as well as fecal excretion of sodium, calcium and magnesium. At the end of the study, extracellular fluid volume, serum aldosterone and parathyroid hormone were analyzed. Final systolic blood pressures in the 4 groups were as follows: S=235+/-9 mmHg (n=9); R=155+/-3 mmHg (n=8); 6-OHDA S=151+/-6 mm Hg (n=8); 6-OHDA R=117+/-6 mm Hg. Chemical sympathectomy decreased blood pressure in both S and R rats. There was no indication of sodium accumulation in S rats. Associated with reduced parathyroid hormone levels the S strain had significantly less positive balance for calcium than the R strain, primarily due to increased urinary excretion. A less positive balance for magnesium was also observed, due mainly to relatively reduced intestinal absorption of the ion. We conclude that the HSLK diet is associated with inappropriate activation of the sympathetic nervous system and increased arterial pressure in both strains. In addition, since divalent cations may influence blood pressure, we suggest that the observed abnormalities in calcium and magnesium metabolism might independently promote hypertension development in the S strain.     

Inter-relationships of carbonate, phosphate, monohydrogen phosphate, calcium, magnesium and sodium in uraemic bone: comparison of dialysed and non-dialysed patients

1. Chemical and morphological features of uraemic bone disease were studied by comparison of bone composition in 44 patients with uraemia (12 dialysed and 32 non-dialysed) and 36 control subjects. The significant changes included decreased bone mineral carbonate associated with calcium, a concomitant increase in phosphate, and an increase in magnesium. There was also an increase in osteoid and a reduction in the specific gravity of the compact bone. 2. The most marked changes in bone composition were observed in patients with uraemia of more than 1 year's duration, who had been dialysed. Bone mineral sodium concentrations were not significantly altered in any group. 3. The changes in bone mineral composition appeared to be the result of several simultaneous and/or successive mechanisms: (i) loss of fixed base, calcium carbonate; (ii) replacement of carbonate by phosphate; (iii) the addition of immature bone mineral, which contains high concentrations of phosphate and relatively low concentrations of carbonate. 4. These observations are consistent with earlier views of the bone salt as an indefinite calcium/phosphate/carbonate complex. Variations in bone composition may arise from a reciprocal relationship between phosphate and carbonate. The bone mineral analogue that best explains these variations in bone composition is octacalcium phosphate carbonate [Ca4 (PO4)2(HPO4)x(CO3)1-x,zH2O].     

Interaction of calcium channel antagonists with calcium: structural studies on nicardipine and its Ca2+ complex

Conformational features of nicardipine in acetonitrile, in the absence and presence of Ca2+, were investigated by one-dimensional NMR and difference absorption spectroscopy techniques. The data show that in acetonitrile solution the antiperiplanar form of nicardipine is dominant. The addition of Ca2+ to the drug solution caused marked changes in the difference absorbance spectra in the 200-400 nm region and in many of its 1H and 13C NMR resonances. The changes were most significant up to a ratio of 0.5 Ca2+:drug. Analysis of the binding data showed the predominant species to be a 2:1 drug:Ca2+ "sandwich" complex with an estimated dissociation constant of 100 microM at 25 degrees C. One-dimensional nuclear Overhauser effect (NOE) experiments revealed through-space connectivities in the drug before and after Ca2+ binding. These changes in conjunction with the changes in 1H and 13C chemical shifts suggest a structure in which the 4-aryl ring substitute of the pyridine moiety moves closer to the C3-side chain in the presence of Ca2+. This attraction is achieved via the chelation of the Ca2+ ion by the oxygen atoms in the m-NO2 of the aryl group and the COOCH2 group in the side chain of the dihydropyridine ring, and gives rise to a stable synperiplanar conformation. A preference for this conformation was also observed in the Ca2+ complex of nifedipine in acetonitrile as inferred from the rather limited NOE data obtained. Our study provides a detailed solution structure for nicardipine and also leads to a suggestion of a role for Ca2+ in the action of this and possibly other dihydropyridines.     

Interaction of calcium channel antagonists with calcium: structural studies on verapamil and its Ca2+ complex

The conformation of the calcium channel antagonist verapamil has been determined in acetonitrile, in the absence and presence of Ca2+, using two-dimensional 1H-NMR and molecular modeling techniques. Interproton connectivities in the drug molecule were identified from the observed NOESY cross peaks and interproton distances were estimated from the magnitudes of the volume integrals of the cross peaks. The molecular modeling program utilized the Monte Carlo simulation to generate a random ensemble of conformers complying with the NOESY-derived distance constraints. The energies of these conformers were subsequently computed. The minimum-energy structure of the free drug obtained in this manner exhibited some significant differences from the structure of verapamil determined by X-ray crystallography. In particular, the torsional angles in the middle region of the molecule containing the aliphatic "backbone" were such that the two aromatic rings at either end of the drug molecules were moved farther apart from each other in solution than in the crystal structure. The nearly perpendicular orientation of the aromatic rings seen in the crystal was, however, maintained in the solution structure as well. The addition of Ca2+ to a solution of verapamil in acetonitrile caused marked changes in the difference absorbance of the drug in the 200-300-nm region and in many of its 1H-NMR resonances. The changes were most significant up to a mole ratio of about 0.5 Ca2+:drug. Analysis of the binding data at 25 degrees C showed the presence of both 2:1 and 1:1 drug:Ca2+ complexes in equilibrium, the former "sandwich" complex being dominant at the lower cation concentrations with an estimated dissociation constant of about 300 microM. All of the NOESY cross peaks of the free drug remained on addition of 0.5 mol ratio of Ca2+ to verapamil in deuterated acetonitrile and only two new connectivities were observed. Using the interproton distances calculated from these NOESY data, molecular modeling of the 2:1 drug:Ca2+ complex was carried out to yield the minimum-energy conformer. In this conformer, Ca2+ was coordinated to two methoxy oxygens from each of the two drug molecules. The implications of the verapamil-Ca2+ interaction are discussed in terms of available experimental data on the binding of verapamil to the dihydropyridine-sensitive channel and in terms of a hypothesis on the formation of a drug-Ca(2+)-receptor complex in the lipid bilayer environment.     

Inactivation of rat brain Na+ K+ ATPase by sodium dodecylsulfate: effect of pH, magnesium ions and temperature

The relative stabilities to SDS inactivation of the rat brain Na(+)-ATPase catalytic subunit isoforms in the conditions of the surface charge modulation and temperature modification of the physical state of the membrane lipids were examined. The higher sensitivity of the Na+,K(+)-ATPase a1-isoform than a+ to SDS inactivation occurs under the conditions of the detergent treatment of microsomes at pH 7.5 and room temperature. The decrease in pH in ATP-free medium up to 6.2 or temperature elevation up to 37 degrees C eliminates the differences in SDS sensitivity of the Na+,K(+)-ATPase isoforms. The enhancement of the SDS binding with a subunit due to changes in membrane surface charge in the first case or increase of accessibility of the protein intramembrane regions for detergent due to the decrease of the packing density of the boundary lipids in the second case are supposed.     

Evidence for a sodium ion exchange carrier linked with glucose transport across the brush border of a flatworm (Hymenolepis diminuta, Cestoda)

The manner in which the flatworm, Hymenolepis diminuta (Cestoda), regulates the transport of glucose and Na+ across the brush border was examined. While the presence of an unstirred region in the brush border may favor the reabsorption of leaked glucose, some leaked glucose was lost to the ambient medium. This loss was markedly enhanced by preloading the worms with glucose and by removing Na+ from the incubation medium. Since glucose and Na+ influxes are coupled, glucose leakage stimulated the influx of 22Na+. However, this 22Na+ influx was balanced by a simultaneous increased 22Na+ efflux. The presence of phlorizin inhibited both unidirectional fluxes of 22Na+ indicating that efflux of 22Na+ occurred by countertransport; countertransport of [14C] glucose appeared to be negligible. A model has been proposed in which the transport of glucose and compensating transfers of Na+ across the membrane occur via the same carrier.     

Interaction of calcium channel antagonists with calcium: spectroscopic and modeling studies on diltiazem and its Ca2+ complex

Using spectral techniques, the solution conformation of diltiazem was studied in acetonitrile with special reference to the effect of Ca2+ on the drug structure. Complete assignment of the proton resonances in the 1H-NMR spectrum of the drug was made using one-and two-dimensional spectral analyses. A two-dimensional 1H-NOESY spectrum (in the phase-sensitive mode) was obtained to identify the interproton connectivities in the drug molecule. A molecular modeling program involving Monte Carlo simulation and energy minimization was employed to arrive at the structure of the drug. The program was run with and without the input of the interproton distances derived from the NOESY cross peaks. Both the protocols led to a structure of the drug which was generally similar to that reported from X-ray diffraction data on crystalline diltiazem hydrochloride (Kojic-Prodic, et al. Helv. Chim. Acta 1984, 67, 916-926). However, significant differences between the two structures were seen in the orientations of the substituent groups attached to the benzothiazepine ring. Substantial changes in the circular dichroic (CD) and 1H-NMR spectra of diltiazem were observed on addition of Ca2+ up to a mole ratio of 0.5 Ca2+ per drug. Relatively large changes were seen in 1H resonances of the N-methyl protons and the methylene protons attached to the heterocyclic nitrogen. Analysis of the binding isotherms from CD data at 22 +/- 1 degrees C indicated a 2:1 drug:Ca2+ "sandwich" complex with an estimated dissociation constant of 140 microM. One-dimensional difference NOE and two-dimensional NOESY spectra revealed interproton connectivities between two drug molecules that were compatible with the sandwich complex formation. The interproton distances derived from the volume integrals of the NOESY cross peaks were used as geometrical constraints in modeling the Ca(2+)-bound conformation of diltiazem. The minimum-energy conformation corresponded to the sandwich complex where Ca2+ was coordinated to three oxygens in each of the two drug molecules. Combined with our earlier data on the ability of diltiazem to translocate Ca2+ across the lipid bilayer in synthetic liposomes (Ananthanarayanan, V.S.; Taylor, L.; Pirritano, S.Biochem. Cell Biol. 1992, 70, 608-612), the structural data presented here point to a role for Ca2+ in the interaction of diltiazem with its membrane-bound receptor.     

Uphill permeation model of gold(III) and its separation from base metals using thiourea derivatives as ionophores across a liquid membrane

This work deals with carrier-facilitated membrane transport of Au(III) from chloride media across a polymer-immobilised liquid membrane (PILM) using as organic reagents N-(thiocarbamoyl)benzamide derivatives and N-benzoylthiourea derivatives, denoted as 2a–c and 3a–f, respectively. Both the composition of the organic membrane solvent and the type of carrier have a marked effect on gold permeation. Recovery and permeability of gold using 2a–c and 3a–f across a PILM proceed in the following order: 3e≈3d≈3c?3f>3b≈3a≈2a≈2b≈2c. In view of the performance of these carriers, 3c was selected as a metal receptor for detailed studies of Au(III) in permeation. A model is presented for the permeation of Au(III) (61 μM) in 0.5 M Cl⁻ at pH 2.5 using 3c as a membrane carrier. The mathematical equations describing the rate of permeation are derived to correlate the membrane permeability coefficient with diffusional and equilibrium parameters. The mass transfer coefficient was calculated from the described model as 1.1×10⁻⁵ m s⁻¹, and the thickness of the aqueous boundary was later calculated to be 65 μm. Several polymeric supports were tested for impregnation of the organic extractant, and Durapore (Millipore) afforded the maximum flux for Au(III), yielding a value of 1.1×10⁻¹⁴ mol m⁻² s. The relationship between flux and support characteristics is derived and a mathematical equation is presented. Of the several diluents used, cumene had the most satisfactory performance in terms of PILM stability and metal transport. Of the different reagents used, 0.5 M sodium thiocyanate in 0.5 M NaCl at pH 2.5 served most efficiently as the stripping agent. More than 80% of the Au(III) could be readily separated using 3c in the presence of various metals such as Cu(II), Fe(III) and Zn(II).