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Interrelationships of chloride, bicarbonate, sodium, and hydrogen transport in the human ileum.

Using a triple-lumen constant perfusion system, the following observations were made in normal subjects. First, chloride, bicarbonate, and sodium were found to exhibit net movement across ileal mucosa against electrochemical gradients. Second, during perfusion with a balanced electrolyte solution simulating plasma, the ileum generally absorbed, but sometimes secreted fluid. A reciprocal net movement of chloride and bicarbonate was noted when sodium movement was zero. Increasing rates of sodium absorption were associated with decreasing bicarbonate secretion rates and finally bicarbonate absorption. Even when bicarbonate was absorbed ileal contents were alkalinized (by contraction of luminal volume). Third, net chloride movement was found to be sensitive to bicarbonate concentration in ileal fluid. For instance, chloride was absorbed from solutions containing 14 or 44 mEq/liter of bicarbonate, but was secreted when ileal fluid contained 87 mEq/liter of bicarbonate. Fourth, when chloridefree (sulfate) solutions were infused, the ileum absorbed sodium bicarbonate and the ileal contents were acidified. Fifth, when plasma-like solutions were infused, the potential difference (PD) between skin and ileal lumen was near zero and did not change when chloride was replaced by sulfate in the perfusion solution. These results suggest that ileal electrolyte transport occurs via a simultaneous double exchange, Cl/HCO2 and Na/H. In this model neither the anion nor the cation exchange causes net ion movement; net movement results from the chemical reaction between hydrogen and bicarbonate. No other unitary model explains all of the following observations: (a) human ileal transport in vivo is essentially nonelectrogenic even though Na, Cl, and HCO3 are transported against electrochemical gradients, (b) the ileum can secrete as well as absorb, (c) ileal contents are alkalinized during absorption of or during secretion into a plasma-like solution, and (d) the ileum acidifies its contents when sulfate replaces chloride. Data obtained with a carbonic anhydrase inhibitor support the proposed model.

Acetazolamide↗

Regulation of release from isolated adrenergic secretory vesicles by ATP-mediated changes in transmembrane potential and anion permeability.

Isolated chromaffin granules release their contents when exposed to calcium, magnesium, ATP, and high levels of chloride ions. The mechanism of release is not well-understood, but changes in anion permeability may be involved. We found that another anion, thiocyanate (SCN-), also activated release in a fashion similar to chloride, while isethionate (HO-CH2-CH2SO3-) an impermeant anion, was inactive. Mg++-ATP was found to activate the uptake of 36Cl and 14C-SCN, leading us to conclude that activation of anion uptake might be involved in the release process. The 36Cl and the 14C-SCN compartments were then compared by studying displacement of the trace anions by excess cold mass. Chloride and SCN displaced large amounts of both 36Cl and 14C-SCN, while isethionate displaced little of either tracer anion. We suggest, on the basis of these data, that ATP-mediated anion uptake may be the basis for the release mechanism. Release may occur as a consequence of anion and subsequent water uptake into granules, resulting in osmotic imbalance and osmotic shock. This may also be of physiologic importance, and we propose a cellular model for secretion based on the biochemical properties of the isolated chromaffin granule.

Adenosine Triphosphate↗

Plasticizer-level study of poly(vinyl chloride) ion-selective membranes.

Highly plasticized poly(vinyl chloride) (PVC) membranes (200 per hundred resin [phr]) form the basis of one class of ion-selective electrodes (ISEs). In previous work on the mechanical properties of membranes, the optimal ratio of plasticizer level employed to minimal level required for complete plasticization (phr(exp)/phrmin) was found to be 2.0. The current study was designed to determine whether this ratio is necessary or sufficient for proper ISE function. Dynamic mechanical analysis (DMA) was used to examine the effects of five plasticizers on the dynamic mechanical properties of membranes at three frequencies (110, 11.0, and 1.1 Hz) as a function of temperature (-100 degrees C to +100 degrees C); dioctyl sebacate (DOS), epoxidized propylene glycol dioleate (PGDO), ortho-nitrophenyl octyl ether (o-NPOE), epoxidized soybean oil (ESO), and epoxidized linseed oil (ELO). The glass transition temperature of PVC, which was found to be +77.1 degrees C at 11.0 Hz, was depressed by the addition of 200 phr of each plasticizer from a high of -1.4 degrees C (PGDO at 110 Hz) to a low of -70.2 degrees C (DOS at 1.1 Hz). DMA and electromotive-force (EMF) measurements on membranes plasticized with o-NPOE through a range of phr(exp)/phrmin from 0.5 to 9.3 indicated that a "transition window" occurs between phr(exp)/phrmin of 2.0 and 3.3 in which the membranes change from minimally plasticized polymer films to predictable ion-selective membranes, coinciding with the optimal mechanical properties observed previously. Based on dynamic mechanical properties and EMF response data, the optimal phr(exp)/phrmin++ ratios for membranes as a function of plasticizer were proposed: 0.8 for ESO and ELO, 1.3 for PGDO, 1.7 for DOS, and 3.0 for o-NPOE.

Elasticity↗

Steroid hormones and receptors of the GABAA supramolecular complex. II. Progesterone and estrogen inhibitory effects on the chloride ion channel receptor in different forebrain areas of the female rat.

The inhibitory effect of female sex steroid hormones on the binding of [35S]t-butylbicyclophosphorothionate [35S]TBPS to the chloride ion channel receptor in different forebrain areas of the female rat proved to be of a differential nature. The in vivo administration of estradiol and estradiol+progesterone were responsible for substantially lower chloride ion channel receptor levels in brain areas that contain elevated steroid receptors, such as the medial preoptic area, the cortico-medial amygdala nucleus, the vertical limb diagonal band-medial septal nucleus and the cortex lamina V. The administration of progesterone alone reduced receptor levels in the oriens-pyramidalis CA1 layer of the hippocampus, caudate putamen, cortex lamina VI (brain areas that contain little if any steroid receptors) and in the lateral and basolateral amygdala nucleus (brain sites that contain noninducible progesterone receptors). On the basis of the progesterone-inhibitory activity on the chloride ion channel receptors, it was important to investigate whether progesterone per se or whether the potent progesterone metabolites 3 alpha-hydroxy-5 alpha-dihydroprogesterone (3 alpha, 5 alpha-THP) and 3 beta-hydroxy-5 beta-dihydroprogesterone (3 beta,5 beta-THP) were involved in the binding level changes, and to establish the specific brain sites where these steroid effects occur. In fact, in vitro addition of the 5 alpha-reduced progesterone metabolite produced even greater depressive effects on [35S]TBPS binding not only in the same brain areas as the in vivo progesterone replacement therapy but also in some sites that provided significant receptor level changes following the sequential administration of estradiol+progesterone. However, when the 5 beta-reduced metabolite was tested on the binding of [35S]TBPS to the chloride ion channel receptor, only the basolateral amygdala nucleus, the cortex lamina VI and the dorsolateral septal nucleus exhibited changes. Because the steroid-mediated chloride ion flux is regulated in a GABA-dependent manner, we next checked for the type of GABA effects on the chloride ion channel receptor levels and found that GABA not only intensified the 3 alpha,5 alpha-THP inhibitory effects but, together with this progesterone metabolite, was also involved in binding changes in the vertical limb diagonal band-medial septal nucleus. It is interesting to note that the GABA effects on 5 beta-metabolite-induced receptor changes were not of the enhancing type, but tended, rather, to be inhibitory.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Determination of N,N-dimethylaminoethyl chloride and the dimethylaziridinium ion at sub-ppm levels in diltiazem hydrochloride by LC-MS with electrospray ionisation.

An LC-MS method is described for the determination of the synthetic reagent N,N-dimethylaminoethyl chloride (DMC) in the drug substance diltiazem hydrochloride, for which the permissible limit is not more than 1 ppm (microgram g-1). The N,N-dimethylaziridinium ion (DMA), the reactive intermediate formed by cyclisation of DMC, is also detected. A column switching arrangement is used: diltiazem hydrochloride is trapped on a reversed-phase HPLC column, and the polar analytes are separated by ion exchange chromatography. Ionisation is effected by positive-ion electrospray, and the quadrupole filter mass spectrometer is operated in the selected ion recording mode. The detection limit (peak height-to-baseline noise ratio = 3) for DMC varies from day to day in the range < 0.05 to 0.1 ppm. The response for DMC is linear (r > 0.999) over the concentration range 0.2-10 ppm, and the repeatability is better than 7% (relative standard deviation) at 1.0 ppm. Concentrations of DMC in diltiazem hydrochloride from the manufacturing facility under study ranged from undetectable to about 0.07 ppm. An indirect TLC method has been published for the determination of DMC in mepyramine maleate, but it lacks the necessary sensitivity and specificity. The LC-MS method presented is direct, straightforward and suitable for routine use.

Alkylating Agents↗

Acid-base balance parameters and ionic composition of arterial, venous and capillary blood in goats.

The aim of the present study was to compare the acid-base balance parameters of arterial, venous and capillary blood in clinically healthy goats, and to determine the electrolyte content of venous and arterial blood. The experiment was performed on ten adult goats. It was found that the acid-base balance parameters of venous blood differed from those of arterial blood, whereas the parameters of capillary and arterial blood were similar. The levels of sodium and chloride ions in arterial and venous blood were similar, whereas the level of potassium ions was higher in venous blood.

Animals↗

The effect of propofol on acid-base balance and ionic composition of venous and arterial blood in goats.

The aim of the present study was to determine the effect of propofol on acid-base balance and ionic composition of arterial and venous blood in clinically healthy goats. The experiment was performed on ten adult goats. Propofol was administered intravenously at bolus dose of 6 mg/kg bw. The heart and breath rate, acid-base balance (pH, pCO2, pO2, HCO3-, BE, O2SAT, ctCO2) and ionic composition (Na+, K+, Cl-) of arterial and venous blood were measured before injection and 3, 6 and 15 min. after. The propofol infusion induced increase of heart rate, decrease of breath rate and compensated respiratory acidosis in venous and arterial blood. It was found that changes of acid-base balance parameters in arterial blood arose faster than in venous blood. The levels of sodium and chloride ions in both types of blood were similar, whereas the level of potassium ions was higher in venous blood during entire experiment.

Acid-Base Equilibrium↗

Secretion by the mandibular gland of the red kangaroo (Macropus rufus) during isoprenaline infusion.

Intracarotid infusion of isoprenaline, either alone or in combination with acetylcholine infusion was used to stimulate salivation by the mandibular glands of anaesthetized red kangaroos. Isoprenaline alone (0.20-1.25 eta mol.kg-1.min-1) elicited flow rates ranging from 0.014 to 0.239 ml.min-1 (1.21-28.1 microliters.g gland-1.min-1). Salivary concentrations of sodium, chloride, phosphate and urea were negatively correlated with flow, whereas potassium, calcium, magnesium, hydrogen ion, bi-carbonate, protein, and osmolality were poorly correlated with flow. Relative to cholinergic saliva produced at equivalent flow rates, isoprenaline-evoked saliva had higher osmolality, saliva/plasma urea ratios and concentrations of protein, potassium, magnesium, bicarbonate, and phosphate, but lower sodium, chloride and hydrogen ion levels. At a steady salivary flow (0.5 ml.min-1), superim-position of isoprenaline infusion (0.15 eta mol.kg-1.min-1) on a pre-existing acetylcholine infusion reduced the rate of acetylcholine administration necessary to maintain flow, increased osmolality and the concentrations of protein, urea, potassium, calcium, magnesium, bicarbonate and phosphate and decreased sodium, chloride and hydrogen ion in the saliva. Salivary amylase activity was low and highly variable and the amylase activity/protein ratio fell substantially during isoprenaline stimulation. These results support the conclusion that the enzyme is of extrinsic origin. The response of the kangaroo mandibular gland to isoprenaline stimulation was very similar to that reported for rat mandibular gland, suggesting that the same ion transport phenomena underlie mandibular secretion in both species and probably in therian mammals generally.

Acetylcholine↗

Degradation of pentachlorophenol by the white rot fungus Phanerochaete chrysosporium grown in ammonium lignosulphonate media.

Removal and degradation of pentachlorophenol (PCP) by Phanerochaete chrysosporium in static flask cultures was studied using ammonium lignosulphonates (LS), a waste product of the papermill industry, as a carbon and nitrogen source. After 3 days, cultures of P. chrysosporium grown in either a 2% LS (nitrogen-sufficient) medium or a 0.23% LS and 2% glucose (nitrogen-deficient) medium removed 72 to 75% of PCP, slightly less than the 95% removal seen using nitrogen-deficient glucose and ammonia medium. PCP dehalogenation occurred despite the fact that extracellular enzyme (LiP) activity, measured by a veratryl alcohol oxidation assay and by PCP disappearance in cell-free extracts, was inhibited by LS. This inactivation of LiP likely contributed to the lower percent of PCP dehalogenation observed using the LS media. In order to better understand the relationship between PCP disappearance and dehalogenation, we measured the fate of the chlorine in PCP. After 13 days, only 1.8% of the initial PCP added was recoverable as PCP. The remainder of the PCP was either mineralized or transformed to breakdown intermediates collectively identified as organic halides. The largest fraction of the original chlorine (58%) was recovered as organic (non-PCP) halide, most of which (73%) was associated with the cell mass. Of the remaining chlorine, 40% was released as chloride ion, indicating a level of dehalogenation in agreement with previously reported values.

Basidiomycota↗

Effect of dietary chloride on aldosterone synthase induction and angiotensin II receptors in rat adrenals.

Effects of dietary chloride ions on the levels of both cytochrome P-450aldo (CYP11B2) and angiotensin II receptors were examined in rat adrenals. Capsular adrenal CYP11B2 protein levels significantly increased in previously chloride-depleted animals treated with either ammonium- or choline chloride. No changes in CYP11B2 protein levels were detected in previously chloride-depleted rats replenished with either ammonium acetate or choline bromide. The induction of CYP11B2 by chloride-repletion was not concurrent with either increased plasma renin activity or elevated serum potassium levels. None of the above dietary manipulations affected angiotensin II receptor number and affinity, respectively. Treatment of chloride-repleted animals with an angiotensin II receptor antagonist (TCV116) significantly attenuated the increase of CYP11B2 protein levels. In addition, chloride-repletion of previously chloride-depleted animals increased mRNA levels encoding angiotensin II type 1B receptor, but decreased mRNA levels encoding the type 1A form of the receptor. Thus, the presented data are supportive of the notion that the regulation of CYP11B2 expression in the capsular portion of the rat adrenal is, in part, mediated via induction of the angiotensin II type 1B receptor.

Adrenal Glands↗

Depression of sodium, chloride and calcium ions in the plasma of goldfish (Carassius auratus) and immature freshwater- and seawater-adapted eels (Anguilla anguilla L.) after acute administration of salmon calcitonin.

Goldfish showed a significant reduction in their plasma sodium and calcium levels 1 h after receiving 50 i.u. calcitonin per kg body weight. When 100 i.u. calcitonin were injected there was a significant fall in circulating levels of both sodium and calcium and also of chloride ions compared with those found in untreated control animals. Administration of calcitonin to immature eels adapted to either freshwater or seawater conditions showed no significant change in plasma ion composition at doses of 10 i.u. per kg body weight or less. However, doses of 50 and 100 i.u. caused significant reductions in plasma sodium, chloride and calcium ion levels compared with sham-injected control animals. When immature eels were given 100 i.u. calcitonin per kg body weight there were significant reductions in the plasma levels of sodium, chloride and calcium ions but the timing of these changes was slightly different. In freshwater-adapted eels, the depression of plasma sodium was seen after 30 min and lasted for up to 2 h, whilst depression of plasma chloride and calcium was not seen until 1 h after injection. In addition, whilst the lowering of plasma chloride ions lasted up to 2 h after injection, the plasma calcium had returned to the preinjection control level by this time. In seawater-adapted eels the depression of sodium, chloride and calcium levels was seen at 30 min and the effect continued for up to 2 h after injection when the depression was no longer apparent.

Anguilla↗

The catalytic role of aspartate in a short strong hydrogen bond of the Asp274-His32 catalytic dyad in phosphatidylinositol-specific phospholipase C can be substituted by a chloride ion.

Phosphatidylinositol-specific phospholipase C from Bacillus thuringiensis catalyzes the cleavage of the phosphorus-oxygen bond in phosphatidylinositol. The focus of this work is to dissect the roles of the carboxylate side chain of Asp(274) in the Asp(274)-His(32) dyad, where a short strong hydrogen bond (SSHB) was shown to exist based on NMR criteria. A regular hydrogen bond (HB) was observed in D274N, and no low field proton resonance was detected for D274E and D274A. Comparison of the activity of wild type, D274N, and D274A suggested that the regular HB contributes significantly (approximately 4 kcal/mol) to catalysis, whereas the SSHB contributes only an additional 2 kcal/mol. The mutant D274E displays high activity similar to wild type, suggesting that the negative charge is sufficient for the catalytic role of Asp(274). To further support this interpretation and rule out possible contribution of regular HB or SSHB in D274E, we showed that the activity of D274G can be rescued by exogenous chloride ions to a level comparable with that of D274E. Comparison between different anions suggested that the ability of an anion to rescue the activity is due to the size and the charge of the anion not the property as a HB acceptor. In conclusion, a major fraction of the functional role of Asp(274) in the Asp(274)-His(32) dyad can be attributed to a negative charge (as in D274E and D274G-Cl(-)), and the SSHB in the wild type enzyme provides minimal contribution to catalysis. These results represent novel insight for an Asp-His catalytic dyad and for the mechanism of phosphatidylinositol-specific phospholipase C.

Anions↗

Effect of chronic treatment of ethanol on benzodiazepine and picrotoxin sites on the GABA receptor complex in regions of the brain of the rat.

Ethanol has been shown to enhance gamma-aminobutyric acid (GABA)ergic transmission. In this study an examination was made of the effect of chronic treatment with ethanol and its withdrawal at 24 h on the binding of [3H]flunitrazepam and [35S]t-butylbicyclophosphorothionate (TBPS) to brain regions in rat. Rats were rendered tolerant to, and dependent on, ethanol by an intragastric intubation method. The affinity (KD) or the binding capacity (Bmax) of [3H]flunitrazepam or [35S]TBPS was not altered by chronic treatment with ethanol or during withdrawal from ethanol. Neither the enhancing effect of GABA on the binding of [3H]flunitrazepam nor its inhibitory effect on the binding of [35S]TBPS were affected by chronic treatment with ethanol or its withdrawal at 24 h. These results suggest that the sensitivity of benzodiazepine and picrotoxin sites on the oligomeric GABA receptor complex is not affected during tolerance to, or withdrawal from ethanol. It is suggested that the effects of ethanol on GABAergic transmission may be produced at the level of coupled chloride ion channels.

Animals↗

[Effect of different types of nutrition on various biochemical indicators in the blood of calves during the first 4 months of life. I. Mineral components and hematological indicators of the blood].

The experiment was conducted on 3 groups of calves. Each group composed of 6 calves from 2-16 weeks of age. In the first group the calves were fed whole milk--milk replacer "Mlekomiks", in the second--whole milk and in the third group--milk replacer "Mlekomiks". Throughout the experiment ale calves were fed good meadow hay and concentrate ad libitum. Analysis of the obtained results showed significant (P less than or equal to 0.01) influence of used feeding method on level of sodium, chloride ions, calcium, phosphorus inorganic and indices of blood hematocrit, ferrum, glucose and amylase as well. There was not observed the relationship in the case of hemoglobin and potassium.

Age Factors↗

[Detection of the G551D mutation in a patient with nasal polyps].

Atypical forms of cystic fibrosis can be manifested by a mild affection of the airways in adult age. They are the phenotypic manifestation of less frequent mutations for CF. The authors present the case-history of a man who developed the first symptoms of respiratory disease at the age of 16 years. He had relapsing nasal polyps, sinusitis, bronchial asthma, intolerance of acetylsalicylic acid. Bacteriological examination revealed repeatedly Pseudomonas aeruginosa on the respiratory mucosal membranes. The levels of the chloride ion in sweat were normal, genetic examination revealed a mutation of the gene for cystic fibrosis, G 551 D.

Adult↗

[The diagnostic value of measuring the electric conductivity of milk].

A positive correlation of the milk specific conductance (MSC) to the number of cells (r = 0.65) and to the content of chloride ions (r = 0.93) was found on the basis of an examination of 196 udder-quarter milk samples. As indicated by the closeness of the relationship to the number of cells, MSC measurement at a determination level of 41.8% has similar diagnostic effectiveness as the determination of the content of chloride ions (determination level 43.5%) and lactose content (determination level 42.8%), and much higher diagnostic effectiveness than the determination of titration acidity (determination level 23.4%). As indicated by the closeness of the relationship to the content of chloride ions, MSC measurement at a determination level of 86.7% has higher diagnostic effectiveness than the determination of lactose content (determination level 73.9%) and titration acidity (determination level 54.6%). In both comparisons, the highest diagnostic effectiveness was found in assessing the chlorine-sugar number (determination levels of 49.8% and 94.0%). The MSC value, corresponding to the cellulization of 500 . 10(3) cells per ml of milk, was determined from regression: 0.523 S . m-1. The diagnostic congruence of MSC with the number of cells in milk was 81.25%, and with the findings of mastitis test-NK only 54.0%. The variability of the measurements of MSC renders it impossible to use this measurement to indirect multi-step screening of milk cellulization. It is only realistic to distinguish two classes of the measured MSC values: negative and positive.

Animals↗

[Determining the levels of selected pesticides, nitrates, nitrites, ammonium ions, sulfates, chlorides and urea in surface and underground waters. VII].

The subjects of the study was determination of the residues of pesticides: lindane, metoxychlor and chlorphenvinphos, nitrates, nitrites, ammonium ions, sulphates, chlorides and urea in surface waters and underground waters in the southeastern part of the Province of Szczecin in 1983-1988. The certain pesticides and urea in none of determined samples of waters were present. The concentrations of nitrates, ammonium and chlorides below the permitted value have been. Nitrites in surface waters and in underground waters in 48 per cent and 82 percent of the samples have been respectively.

Chlorfenvinphos↗