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The influence of suxamethonium on cardiovascular and respiratory function in the anaesthetized horse.

1. In horses anaesthetized with halothane the intravenous administration of suxamethonium chloride, at a dose level of 0.2 mg/kg, produced a short-lived period of hypoventilation, which was associated with increases in arterial blood PCO(2) levels and in plasma concentrations of bicarbonate, sodium and potassium ions, and reductions in arterial blood pH and PO(2) values.2. The respiratory depressant action of suxamethonium chloride 0.2 mg/kg was accompanied by increases in blood pressure and heart rate. Doses of suxamethonium chloride 0.4 mg/kg produced similar but quantitatively greater changes in cardiovascular and respiratory function. These effects were not accompanied by cardiac arrhythmias, with the exception of one animal, in which an unusually prolonged period of apnoea occurred.3. The cardiovascular effects of suxamethonium during halothane anaesthesia were diminished but not abolished when the respiratory depressant action of suxamethonium was prevented by applying positive pressure ventilation.4. The cardiovascular effects of suxamethonium in horses anaesthetized with halothane were partially antagonized by propranolol and completely antagonized by hexamethonium. It is suggested that the cardiovascular effects of suxamethonium are mediated by two distinct mechanisms: reflexly mediated increases in heart rate and sympathetic vasoconstrictor tone due to the respiratory depression, and a direct stimulant action of suxamethonium on peripheral, autonomic ganglia.5. Much less pronounced changes in cardiovascular function, but not in respiratory function, were recorded when suxamethonium was administered to horses anaesthetized with ether.6. A slight degree of tachyphylaxis to the cardiovascular and respiratory effects of suxamethonium was recorded in horses anaesthetized with halothane.7. Some atypical effects of suxamethonium on respiration are described.

Anesthesia, Inhalation↗

Developmental changes in proximal tubule tight junction proteins.

We demonstrated previously that neonatal proximal tubules have a lower passive paracellular permeability to chloride ions and higher resistance than that of adult proximal tubules. In addition, administration of thyroid hormone to neonates, before the normal maturational increase in serum thyroid hormone levels, prematurely accelerates the developmental increase in chloride permeability to adult levels. To test the hypothesis that there is a maturational change in tight junction proteins and that thyroid hormone mediates these changes, we examined the two known tight junction proteins present in proximal tubules, occludin and claudin 2. Using immunoblot and immunohistochemistry, we demonstrated that claudin 2 has a 4-fold greater abundance in neonatal proximal tubules than in adult tubules. Occludin, however, has a 4-fold greater expression in adult tubules than in neonatal tubules. Administration of thyroid hormone to neonates did not affect claudin 2 expression, occludin expression, or the transepithelial resistance in rat proximal tubule cells in vitro. In conclusion, there are postnatal maturational changes in tight junction proteins. The factors that cause these maturational changes are unknown but unlikely to be due solely to the maturational increase in thyroid hormone.

Age Factors↗

Interleukin 10 modulates ion transport in rat small intestine.

BACKGROUND & AIMS: It has been proposed that the anti-inflammatory cytokine interleukin (IL)-10 might be an effective therapeutic agent in the treatment of inflammatory bowel disease. This study examined the effects of human recombinant IL-10 on ileal sodium and chloride transport in Sprague-Dawley rats. METHODS: Unidirectional fluxes of sodium and chloride and tissue electrical parameters were measured under voltage-clamped conditions in ussing chambers. Intracellular levels of adenosine 3',5'-cyclic monophosphate (cAMP) were measured in isolated enterocytes. RESULTS: Jejunal and ileal tissue responded to serosal addition of IL-10 with a transient decrease in short-circuit current reflecting an IL-10-induced increase in net sodium and chloride absorption because of an increase in mucosal to serosal ion movement. The IL-10-induced absorption was not prevented by tetrodotoxin but did show tachyphylaxis. IL-10 reversed, or markedly attenuated, forskolin- and carbachol-induced net chloride secretion. The effects of IL-10 on net secretion were accompanied by a reduction in forskolin-stimulated cAMP levels and a decrease in basal cAMP levels. An additional effect of IL-10 was its induction of bicarbonate secretion only in the presence of secretagogues. CONCLUSIONS: This study shows that IL-10 enhances intestinal electroneutral sodium and chloride absorption, inhibits stimulated chloride secretion, and under some secretory conditions stimulates bicarbonate secretion.

Animals↗

The role of potassium and chloride ions on the Na+/acidic amino acid cotransport system in rat intestinal brush-border membrane vesicles.

The Na+/L-glutamate (L-aspartate) cotransport system present at the level of rat intestinal brush-border membrane vesicles is specifically activated by the ions K+ and Cl-. The presence of 100 mM K+ inside the vesicles drastically enhances the uptake rate and the transient intravesicular accumulation (overshoot) of the two acidic amino acids. It has been demonstrated that the activation of the transport system depended only in the intravesicular K+ concentration and that in the absence of any sodium gradient, an outward K+ gradient was unable to influence the Na+/acidic amino acid transport system. It was also found that Cl- could specifically activate the Na+-dependent L-glutamate (L-aspartate) uptake either in the presence or in the absence of K+. Also the effect of Cl- was observed only in the presence of an inward Na+ gradient and it was noted to be higher when chloride ion was present on both sides of the membrane vesicles. No influence (activation or accumulation) was observed in the absence of the Na+ gradient and in the presence of chloride gradient. L-Glutamate uptake measured in the presence of an imposed diffusion potential and in the presence of K+ or Cl- did not show any translocation of net charge.

Amino Acids, Dicarboxylic↗

Cation effects on chloride fluxes and accumulation levels in barley roots.

Accumulation of Cl(-) by excised barley roots, as of K(+), approaches a maximum level at which the ion influx and efflux rates become equal. The rate of Cl(-) influx at this equilibrium is close to the initial rate while the efflux rate increases with time from zero to equality with influx. The Cl(-) fluxes are independent of simultaneous exchange flux of the cations, but depend on the nature and concentration of the salt solutions from which they originate. The Cl(-) content at equilibrium, however, is largely independent of the external concentrations. The approach to equilibrium reflects the presence of the cation. Cl(-) flux equilibrium is attained more rapidly in KCl than in CsCl or CaCl(2). This is presumably an effect of much slower distribution of Cs(+) and Ca(++) than of K(+) within the roots. Accumulated Cs(+) appears to form a barrier to ion movement primarily within the outermost cells, thereby reducing influx and ultimately efflux rates of both Cl(-) and cations. Slow internal mixing and considerable self-exchange of the incoming ions suggest internal transport over a series of steps which can become rate-limiting to the accumulation of ions in roots.

Biological Transport↗

Lack-of-fit testing of ion chromatographic calibration curves with inexact replicates.

Calibration studies involve the preparation and analysis of replicates for multiple concentrations of standards. Curves that are fitted through the data are evaluated for their adequacy of fit. A helpful test is a lack-of-fit procedure, which is performed easily by most statistical software. When coupled with Radj2, the procedure differentiates between data that are not linear and those that are simply noisy. The test requires data from exact replicates of the various standard levels involved. However, in ppt-level ion chromatography, the above condition may be impossible to meet. With the common anions (e.g., chloride, nitrite), the working standards must be prepared by mass and all liquids must be poured; transfer pipets contaminate at these concentrations. Since it is virtually impossible to pour out the desired mass exactly, final concentrations will vary slightly. Consequently, a different approach is needed for lack-of-fit testing. This paper discusses reasonable alternatives and applies them to actual data.

Analysis of Variance↗

Induction for the expression of yeast metallothionein gene, CUP1, by cobalt.

Induction for the expression of the metallothionein gene, CUP1, in the yeast Saccharomyces cerevisiae by cobalt was examined using a reporter gene with the promoter of this gene fused to the coding region of lacZ. The expression of the gene was induced by cobalt as well as by copper and silver ions. The activity of beta-galactosidase showed high levels after treatment with 1.0 mM cobalt chloride. It has been reported that the induction for the transcription of CUP1 by copper and silver is mediated by the Ace1 transcription factor. However, the expression of the gene by cobalt occurred in yeast cells lacking the Ace1 factor. These results suggest the presence of a novel cobalt-specific transcription factor for the CUP1 gene.

Carrier Proteins↗

[Effect of proteinuria on transport of sodium, potassium and chloride ions in renal tubules].

Functional and structural damages of tubulointerstitium are caused by proteinuria. The aim of this study was to assess the influence of different proteinuria levels on Na+, K+, Cl- tubular transport. We examined 50 patients (24 males, 26 females), mean age 46.50 +/- 13.08 years, with mean creatinine clearance of 87.29 +/- 31.17 mL/min. They were separated in three groups, depending on proteinuria value. The first group with proteinuria less than 0.3 g/24 h included 19 persons (7 males, 12 females), mean age 45.12 +/- 13.28 years, with mean creatinine clearance of 94.27 +/- 34.70 mL/min. The second group of 18 patients (8 males, 10 females), mean age 45.39 +/- 12.64 years, had proteinuria of 0.3-3.0 g/24 h and mean creatinine clearance of 90.07 +/- 31.89 mL/min. The third group had proteinuria level higher than 3.0 g/24 h and mean creatinine clearance of 73.25 +/- 20.44 mL/min. It included 13 patients (9 males, 4 females), mean age 50.08 +/- 13.73 years. As a parameter of proteinuria influence on tubular transport of Na+, K+ and Cl-, fractional excretion of these electrolytes, was studied. Student's T test, Mann Whitney U test and c2 test were used for statistical analysis. No statistically significant influence of proteinuria was found on Na+, K+ and Cl tubular transport.

Biological Transport, Active↗

Modulation of the ionic milieu of the airway in health and disease.

Airway surface liquid (ASL) is an integral part of lung defense mechanisms. Ion transport by airway epithelia regulates the volume and composition of this fluid. A better understanding of the mechanisms of ion transport will enable the development of new therapies for airway diseases associated with defects in these mechanisms. A useful model of a disease with abnormal airway epithelial ion transport is cystic fibrosis (CF), a distinct genetic syndrome of altered lung defense mechanisms characterized by chronic bacterial infection and a steady decline in lung function. Traditional therapies for CF include antibacterial drugs and augmentation of clearance of secretions, but investigators are now studying pharmacological approaches to target the more basic defect of the disease, i.e. abnormal sodium and chloride ion transport. Early treatment in childhood, prior to lung damage, might prevent or at least retard the decline in pulmonary function that remains the hallmark of CF. Ion transport dysfunction may also contribute to other airway diseases such as asthma and chronic bronchitis. Pharmacological intervention at this level may prove beneficial in these common lung diseases as well.

Animals↗

Electrolyte changes at 3500 m in males with and without high-altitude pulmonary edema.

Ten normal healthy male subjects between 20-30 years of age were initially examined at Delhi (200 m) and thereafter air-lifted to an altitude of 3,500 m. Excretion of sodium, potassium and chloride in urine and their plasma level were determined at sea level (SL) and daily at high altitude (HA) for 4 d. At HA, four subjects developed high-altitude pulmonary edema (HAPE), four remained normal, and two suffered from acute mountain sickness. The results on normals and HAPE are presented. There was increased excretion of potassium at HA in both groups resulting in reduction of plasma level. The sodium and chloride excretion was also increased in normals at HA irrespective of urine volume. In HAPE cases, the sodium and chloride excretion was related to urine output. With the retention of fluid, the excretion of these ions in urine was diminished without a parallel change in plasma levels.

Adult↗

Effects of cadmium and zinc ions on mitotic activity and protein synthesis in mouse liver.

OBJECTIVE: To evaluate the in vivo effects of cadmium and zinc ions on mitotic activity and protein synthesis in mouse liver. MATERIAL AND METHODS: White outbred mice were injected intraperitoneally with cadmium chloride solution (14 micromoles cadmium per 1 kg of body mass) and/or with zinc sulfate solution (48 micromoles zinc per 1 kg of body mass). Histological slides were examined by light microscopy. For each specimen, the number of mitotic cells was counted in 10 randomly selected reference areas. Protein synthesis was evaluated by incorporation of [14C]-labeled leucine into newly synthesized peptides and proteins. RESULTS: We found that the mitotic index of mouse liver cells was increased for periods of 2-8 h after cadmium chloride injection; after 24 h the mitotic index significantly diminished. These data indicate a possible increase in liver cell regeneration during the initial 8 h following acute cadmium exposure. Zinc ions did not affect liver mitotic activity, and, interestingly, decreased the mitotic index in the liver of cadmium-treated mice to control levels. An examination of the kinetics of protein synthesis in mouse liver over a 24 h period after cadmium chloride injection revealed that incorporation diminished by 38% at 2 h, then increased 51% by 8 h and again decreased by 32% at 24 h as compared to control. Zinc ions increased protein synthesis in mouse liver 8 h after zinc sulfate injection. In assessing the effects of cadmium and zinc ions in vivo, it appeared that zinc ions tended to protect protein synthesis in response to cadmium ions but only at 2 h after cadmium intoxication. CONCLUSIONS: Zinc ions are capable of normalizing an increase in the mitotic index of liver cells at the early stage of cadmium poisoning (up to 8 h) and to protect the liver translation machinery against inhibition by cadmium.

Animals↗

Numerical modeling of ferrous-ion oxidation rate in Acidithiobacillus ferrooxidans ATCC 23270: optimization of culture conditions through statistically designed experiments.

Statistically designed experimental strategy has been performed in order to evaluate and optimize nutritional and environmental parameters that affect ferrous ion oxidation rate in Acidithiobacillus ferrooxidans ATCC 23270. Plackett-Burman design was carried out to evaluate efficiently the biological significance of 10 culture conditions influencing ferrous-ion oxidation rate of A. ferrooxidans grown for 5 days in shake-flask batch mode on the newly modified 9-K media. Among ten fermentation factors examined, the most significant variables influencing ferrous-ion oxidation rate were statistically elucidated to be pH and calcium nitrate as positive contributors, whereas trace metals solution and potassium chloride were the most significant negative contributors. The optimal levels of the most significant three nutritional factors were further predicted from a polynomial model created from the data obtained from three level factorial design, a Box-Behnken design. Predicted optimal ferrous-ion oxidation rate Q(Fe2+) was recorded to be 0.148 (g Fe2+/l/hr). On verifying the predicted value, an experiment was performed under optimal predicted conditions and showed an actual experimental Q(Fe2+) of 0.152 g/l/hr, which was 2.7% over the predicted value. Our optimized medium formula gave overall five folds increase in ferrous-ion oxidation rates over the previously published data of standard 9-K medium on batch culture of A. ferrooxidans ATCC 23270 with higher mu(max) (hr(-1)) of 0.177 which was achieved within 75 h incubation in shake-flask culture.

Calcium Compounds↗

Unusual apparent hyperchloremia induced by long-term abuse of bromide-containing drugs.

Recently, we have observed 8 cases showing unusually high serum chloride (Cl-) levels of 282, 279, 257, 251, 213, 169, 123 and 120 mEq/l respectively, as measured by the ion selective electrical method (ISE). All of these cases showed almost normal Cl- levels by the coulometric method. Five of the patients had been taking Bromide (Br-)-containing drugs for a long period, and were found to have high serum levels of Br- ranging from 0.6 to 11.0 mEq/l (normal level: 0.1 mEq/l greater than). The cause of this abnormal elevation in serum Cl- as measured by ISE was investigated as follows. First, normal human pooled serum was mixed with NaBr solution to give increasing concentrations of Br- ions, which was then analyzed using the ISE method. Results showed that the selective response ratio of Br- against Cl- had values as high as 15.03 with ISE in contrast to values of 1.0 obtained by coulometry. Secondly, 7 healthy volunteers were given 4 commercially obtained Br(-)-containing tablets (Sedes A; Shionogi & Co., Ltd.) every day for 8 days. Their mean serum Cl- values measured by ISE gradually increased from 108 to 112 mEq/l, paralleling increments of mean Br- value from 0.1 to 0.6 mEq/l over 9 days. From these observations, it is concluded that serum chloride values obtained by ISE are easily interfered with by Br-. Paradoxically, however, this fact is often a good indicator of Br- intoxication. The authors therefore recommend clinicians to pay more attention to the Br- intoxication that often occurs from overdosage of Br(-)-containing drugs, some of which are commercially available without prescription.

Adult↗

Electrochemical detection of chloride by underpotentially deposited silver films on polycrystalline gold.

This paper describes an electrochemical method for measuring dilute levels of chloride using an underpotentially deposited (UPD) Ag adlayer on polycrystalline Au substrates as a sensing agent. Specifically, chloride ions adsorb onto the Ag UPD adlayer and effect changes in the electrochemical deposition and stripping characteristics of the silver film. Cyclic voltammograms (CVs) of the native Au/Ag(UPD) electrode in 0.1 M H2SO4(aq) exhibit a primary stripping peak for the Ag UPD adlayer at 550 mV vs Ag(+/0), and chloride adsorption onto the Au/Ag(UPD) surface effects a peak shift to approximately 600 mV vs Ag(+/0), depending on the amount of adsorbed Cl-, as affected by the Cl- concentrations and contact times employed in the derivatization. The chloride-treated electrodes also exhibit a stripping peak at 275 mV that is not observed on the native substrate and increases in intensity with Cl- concentration and derivatization time. The integrated charge density for this latter stripping peak relative to that for the primary stripping peak at 550-610 mV provides a useful metric for quantifying adsorbed Cl- levels, and these values allow measurement of Cl- concentrations in dilute aqueous solutions. For Cl- concentrations between 0.5 and 100 microM, the kinetics of Cl- adsorption followed a transient Langmuir adsorption model and allowed measured surface coverages to be used for determining Cl- solution concentrations. Using contact times of 1 min for Cl- adsorption, the electrodes showed a linear response across Cl- concentrations of 0.5-20 microM.

Adsorption↗

The role of sodium and calcium ions in the hypothalamus in the control of body temperature of the unanaesthetized cat.

1. Isolated regions of the anterior, posterior and other areas of the hypothalamus of the unanaesthetized cat were perfused by means of push-pull cannulae lowered through permanently implanted guide tubes. Each site was perfused for a 30 min interval at a rate of 50 mul./min. Concentrations of sodium, calcium, potassium and magnesium ions in the perfusate were altered selectively.2. Sodium ions in a concentration which varied from 13.6 to 68.0 mM in excess of the level in extracellular fluid caused a steep rise in the temperature of the cat when the solution was perfused at sites located within the posterior hypothalamic area. Shivering, vasoconstriction, and piloerection accompanied the increase in temperature. When the chloride was replaced in the perfusate by the toluene-p-sulphonate salt of sodium, the hyperthermia was equally intense. Solutions containing excess sodium ions perfused within the anterior and other hypothalamic areas produced either a slight fall or rise in temperature as well as other physiological changes.3. Calcium ions in a concentration which varied from 2.6 to 10.4 mM in excess of the physiological level perfused at the same sites within the posterior region of the hypothalamus produced a sharp fall in body temperature, which was accompanied by vasodilatation and a decrease in the activity of the cat. When solutions containing excess calcium were perfused in the anterior and other hypothalamic areas, no consistent change in temperature occurred.4. Potassium or magnesium ions in concentrations which varied from two to ten times the level in extracellular fluid had virtually no effect on the temperature of the cat when they were perfused in the anterior, posterior or other areas of the hypothalamus.5. We conclude that the constancy in the ratio between sodium and calcium ions in the posterior hypothalamus may be the inherent mechanism by which the set-point for body temperature is determined.

Animals↗

Determination of perchlorate in drinking water by ion chromatography using macrocycle-based concentration and separation methods.

Macrocycle-based ion chromatography provides a convenient, reliable method for the determination of perchlorate ion, which is currently of great interest to the environmental community. This study shows that effective perchlorate determinations can be made using standard conductimetric detection by combining an 18-crown-6-based mobile phase with an underivatized reversed-phase mobile phase ion chromatography (MPIC) column. One unique feature of this method is the flexibility in column capacity that is achieved through simple variations in eluent concentrations of 18-crown-6 and KOH, facilitating the separation of target analyte anions such as perchlorate. Using a standard anion exchange column as concentrator makes possible the determination of perchlorate as low as 0.2 ug/L in low ionic strength matrices. Determination of perchlorate at the sub-ug/L level in pure water and in spiked local city hard water samples with high background ion concentrations can be achieved this way. However, like other IC techniques, this method is challenged to achieve analyses at the ug/L level in the demanding high ionic strength matrix described by the United States Environmental Protection Agency (EPA) (1,000 mg/L chloride, sulfate and carbonate). We approached this challenge by use of the Cryptand C1 concentrator column, provided by Dionex Corporation, to effectively preconcentrate perchlorate while reducing background ion concentrations in the high ionic strength matrix. The retention characteristics of the concentrator column were studied in order to maximize its effectiveness for perchlorate determinations. The method makes possible the determination of perchlorate at the 5 ug/L level in the highest ionic strength matrix described by the EPA.

Chromatography, Ion Exchange↗