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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated the effects of acidic stimuli upon [Ca2+]i in isolated carotid body type I cells from the neonatal rat using indo-1 (AM-loaded). Under normocapnic, non-hypoxic conditions (23 mM HCO3-, 5% CO2 in air, pHo = 7.4), the mean [Ca2+]i for single cells was 102 +/- 5.0 nM (SEM, n = 55) with 58% of cells showing sporadic [Ca2+]i fluctuations. A hypercapnic acidosis (increase in CO2 to 10%-20% at constant HCO3-, pHo 7.15-6.85), an isohydric hypercapnia (increase in CO2 to 10% at constant pHo = 7.4) and an isocapnic acidosis (pHo = 7.0, constant CO2) all increased [Ca2+]i in single cells and cell clusters. The averaged [Ca2+]i response to both hypercapnic acidosis and isohydric hypercapnia displayed a rapid rise followed by a secondary decline. The averaged [Ca2+]i response to isocapnic acidosis displayed a slower rise and little secondary decline. The rise of [Ca2+]i in response to all the above stimuli can be attributed to no single factor other than to a fall of pHi. The hypercapnia-induced rise of [Ca2+]i was almost completely abolished in Ca(2+)-free solution, suggesting a role for Ca2+ influx in triggering and/or sustaining the [Ca2+]i response. These results are consistent with a role for type I cell [Ca2+]i in mediating pH/PCO2 chemoreception.
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PMID:Effects of acidic stimuli on intracellular calcium in isolated type I cells of the neonatal rat carotid body. 827 80

In this study, we evaluated the effect of long-term administration of daily calcium carbonate (2-4 g/day) and intermittent high oral doses of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3, 3-4 micrograms, given twice a week] in conjunction with a 3-mEq/1 calcium concentration in the dialysate for the treatment of severe secondary hyperparathyroidism in 6 hemodialysis patients. All patients had reduced serum levels of 1,25-(OH)2D3, which increased significantly (p < 0.005) reaching the maximum level in the 4th month. Serum total and ionized calcium levels significantly increased also, in relation to those before treatment. No patients developed hypercalcemia. Serum phosphorus did not significantly change during the study. Initial serum intact parathyroid hormone (PTH) (1,241 +/- 233 pg/ml, mean +/- SEM) markedly decreased after starting treatment with 1,25-(OH)2D3, being 542 +/- 174 pg/ml in the 5th month and 477 +/- 174 pg/ml in the 8th month. These changes are statistically significant (p < 0.05 and < 0.007, respectively). Alkaline phosphatase behavior was similar to that of intact PTH. A constant direct correlation between intact PTH and alkaline phosphatase and an inverse significant correlation between intact PTH and 1,25-(OH)2D3 was evidenced by us. We conclude that oral 1,25-(OH)2D3 pulse therapy is very effective in suppressing PTH secretion. The administration of calcium carbonate and the use of dialysate with a reduced calcium concentration would allow to prevent hyperphosphatemia and the administration of high oral doses of 1,25-(OH)2D3 without concomitant hypercalcemia.
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PMID:Treatment of severe secondary hyperparathyroidism with administration of calcium carbonate, intermittent high oral doses of 1,25-dihydroxyvitamin D3 and dialysate with 3 mEq/1 calcium concentration. 834 82

Physical, chemical, and mineralogical investigations of mineral concretions found in the human pineal gland were performed by means of optical microscopy and modern techniques of analytical electron microscopy and x-ray powder diffraction (OM,SEM + EDS,TEM + EDS,XRD). The mineral concretions were found to be nano-crystalline carbonate-hydroxyapatite with a mean Ca/P molar ratio equal to 1.65, very close to the theoretical value of 1.67. TEM and XRD showed that this is the only inorganic phase present in the concretions without the presence of amorphous phosphate as precursor. SEM and EDS, performed on cross-sectioned samples, showed a concentric layered distribution of the inorganic phase permeated by organic matter, within the concretions, with a slight increasing of the Ca/P molar ratio in their internal part.
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PMID:Physical, chemical, and mineralogical characterization of carbonate-hydroxyapatite concretions of the human pineal gland. 838 51

Impulse inhibition by local anesthetics (LAs) is potentiated by extracellular solutions containing HCO3-. CO2 (BC), relative to the inhibition in BC-free solutions at the same pH. We studied the mechanistic basis of this potentiation by assaying compound action potential amplitudes in desheathed frog sciatic nerves with the sucrose-gap method. We compared the potencies of 12 different impulse-blocking agents in Ringer's buffered with BC (BC-R) and in Ringer's containing only atmospheric CO2 and buffered by a zwitterionic compound (3-(N-morpholino)propanesulfonic acid-Ringer's). The relative inhibition produced by an agent in BC divided by the inhibition produced in 3-(N-morpholino)propanesulfonic acid, was defined as the potentiation factor (PF). The organic guanidinium blockers of sodium channels, tetrodotoxin and saxitoxin, which act at a different site from that for LAs, were, by our definition, nominally potentiated (PF = 1.33 +/- 0.04, mean +/- SEM, n = 4, and 1.24 +/- 0.07, n = 10, respectively), implying that BC induces a decrease in the safety margin for impulse conduction, a decrease that cannot itself alone account for the much larger potentiation (PF = 5-8) by BC observed with certain LAs. Only nominal potentiations occurred with charged LAs (PF = 1.15), showing that little direct potentiation of the cationic LA species per se occurs. Inhibition by the permanently neutral LA benzocaine had a significantly larger than nominal potentiation (PF = 1.8) showing that BC can potentiate neutral LAs. Among the tertiary amine LAs, potentiation of ester-linked drugs (procaine, RAG505; PF = 3.9, 5.4, respectively), exceeded that of their amide-linked homologues (procainamide, lidocaine; PF = 1.3, 2.8, respectively) which have higher pKa values. This result is consistent with an ion trapping mechanism whereby CO2 acidifies the axoplasm and thereby increases the concentration of protonated LA inside the nerve fibers. However, slight differences in the molecular structure of 3 degrees-amine LAs with similar pKa values resulted in significantly different potentiations (e.g., procaine, PF = 3.9; 2-chloroprocaine, PF = 8.7), suggesting that the HCO3- or CO2 molecules interact specifically with the LA molecule or with LA binding sites in the nerve membrane. Spectrophotometric measurements of the free [Ca2+] in Ringer's showed it to be similar (+/- 0.03 mM) for both buffers, obviating changes in extracellular Ca2+ as a mechanism of BC potentiation. The resting potential of the nerve was slightly more negative (approximately -4 mV) in BC-R, so membrane depolarization cannot explain the potentiation.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:On the mechanisms of potentiation of local anesthetics by bicarbonate buffer: drug structure-activity studies on isolated peripheral nerve. 841 14

Possible mechanisms of primary fluid formation by macropodine parotid glands were investigated in anaesthetized red kangaroos using ion transport inhibitors. Carotid plasma amiloride concentrations of 0.05-0.5 mmol.l-1 progressively reduced a stable acetylcholine-evoked half-maximal flow rate of 2.0 +/- 0.04 to 0.22 +/- 0.024 ml.min-1 (mean +/- SEM). Concurrently, saliva bicarbonate concentration and secretion fell (135 +/- 1.6 to 67 +/- 1.7 mmol.l-1 and 272 +/- 7.6 to 15 +/- 2.6 mumol.min-1, respectively); [phosphate], [chloride] and [sodium] rose and [potassium] and osmolality were unaltered. High-rate cholinergic stimulation did not increase saliva flow beyond 11 +/- 1.0% of that for equivalent pre-amiloride stimulation. Equipotent levels of amiloride and methazolamide given concurrently were no more effective at blocking flow and bicarbonate secretion than when given separately. Furosemide (up to 2 mmol.l-1), bumetanide (up to 0.2 mmol.l-1) and ethacrynate (1 mmol.l-1) in carotid plasma had no effect on salivary flow or ion concentrations. During methazolamide blockade, furosemide did not curtail the concurrent increase in salivary [chloride]. Chlorothiazide at 0.25-1.0 mmol.l-1 caused progressive depression of saliva flow and [bicarbonate], and elevation of [chloride]. 4-acetamido-4'-isothiocyanatostilbene-2,2'disulphonic acid at 0.1 mmol.l-1 was without effect, whereas at 0.5 mmol.l-1 it stimulated fluid secretion and increased saliva [protein], [sodium], [potassium], [bicarbonate] and osmolality. Concurrently, mean arterial blood pressure and pulse pressure fell and heart rate, haematocrit and carotid artery plasma flow rose. These responses were absent if saliva flow was kept constant by reduction in cholinergic stimulation during 4-acetamido-4-isothiocyanatostilbene-2,2'disulphonic acid administration. It is concluded that secretion of primary fluid by the kangaroo parotid is initiated mainly (> 90%) by secretion of bicarbonate which is formed in the endpiece cells from CO2 delivered by the circulation. No evidence was found for initiation of fluid secretion by chloride transport involving basolateral Na(+)-K(+)-2Cl- symports, Na(+)-Cl- symports or Cl-/HCO3- antiports.
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PMID:Mechanisms of fluid and ion secretion by the parotid gland of the kangaroo, Macropus rufus, assessed by administration of transport-inhibiting drugs. 857 52

We investigated whether intestinal calcium absorption and serum 1,25-dihydroxycholecalciferol (calcitriol) concentrations are higher in women during lactation and after weaning to compensate for calcium lost in breast milk. Measurements were obtained at 4.6 mo postpartum in 24 lactating women and 24 nonlactating women, at 9.6 mo postpartum in 24 lactating women (2.6 mo after complete weaning) and 24 nonlactating women. One-half of the women in each group were randomly assigned to receive 1 g supplemental Ca/d as calcium carbonate. Fractional calcium absorption was measured by using stable isotopic tracers 42Ca and 44Ca. Fractional absorption was 0.32+/-0.02 (+/-SEM) in both lactating and nonlactating women, but was higher in lactating women after weaning (0.37+/-0.02) compared with nonlactating postpartum control subjects (0.31+/-0.02). These effects were independent of calcium intake. Changes in serum calcitriol paralleled changes in fractional absorption. There were no differences in calcitriol concentrations between lactating and nonlactating women, but calcitriol was greater in women after weaning compared with postpartum control subjects. Lactating women who had resumed menses had higher fractional absorption and serum calcitriol than did lactating women who had not. Serum calcium and phosphorus concentrations were greater in lactating compared with nonlactating women; there were no differences between groups after weaning. We conclude that lactation stimulates increases in fractional calcium absorption and serum calcitriol, but the responses are only apparent after weaning or the resumption of menses.
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PMID:Intestinal calcium absorption of women during lactation and after weaning. 859 16

We have employed two independent techniques to measure the intracellular pH (pHi) in giant glial cells of the leech Hirudo medicinalis, using the fluorescent dye 2',7'-bis-(2-carboxyethyl)-5,6-carboxyfluorescein (BCECF) and double-barreled neutral-carrier, pH-sensitive microelectrodes, which also record the membrane potential. We have compared two procedures for calibrating the ratio of the BCECF signal, excited at 440 nm and 495 nm: 1) the cell membrane was H(+)-permeabilized with nigericin in high-K+ saline at different external pH (pHo) values, and 2) the pHi of intact cells was perturbed in CO2/HCO3(-) -buffered saline of different pH, and the BCECF ratio was calibrated according to a simultaneous microelectrode pH reading. As indicated by the microelectrode measurements, the pHi did not fully equilibrate to the pHo values in nigericin-containing, high-K+ saline, but deviated by -0.12 +/- 0.02 (mean +/- SEM, n = 37) pH units. In intact cells, the microelectrode readings yielded up to 0.15 pH unit lower values than the calibrated BCECF signal. In addition, larger dye injections into the cells (> 100 microM) caused an irreversible membrane potential loss indicative of some damage to the cells. The amplitude and kinetics of slow pHi changes were equally followed by both sensors, and the dye ratio recorded slightly higher amplitudes during faster pHi shifts as induced by the addition and removal of NH4+.
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PMID:Simultaneous measurements of intracellular pH in the leech giant glial cell using 2',7'-bis-(2-carboxyethyl)-5,6-carboxyfluorescein and ion-sensitive microelectrodes. 880 22

We examined the effects of sodium bicarbonate (BIC) and sodium citrate (CIT) ingestion on distance running performance. Seven male runners [mean VO2max = 61.7 (SEM 1.7) ml.kg-1.min-1] performed three 30-min treadmill runs at the lactate threshold (LT) each followed by a run to exhaustion at 110% of LT. The runs were double-blind and randomly assigned from BIC (0.3 g.kg body mass-1), CIT (0.5 g.kg body mass-1) and placebo (PLC, wheat flour, 0.5 g.kg body mass-1). Venous blood samples were collected at 5, 15 and 25 min during the run and immediately post-exhaustion (POST-EX) and analysed for pH, and the concentrations of lactate ([la-]b) and bicarbonate ([HCO3-]). Performance was measured as running time to exhaustion at 110% of LT (TIME-EX). The pH was significantly higher (P < or = 0.05) for the BIC and CIT trials during exercise, but not POST-EX compared to PLC. The [la-]b was significantly higher (P < or = 0.05) for the CIT trial compared to PLC during exercise, and for both CIT and BIC compared to PLC at POST-EX. Blood [HCO3-] was significantly higher (P < or = 0.05) during exercise for BIC compared to PLC. TIME-EX was not significantly different among treatments: BIC 287 (SEM 47.4)s; CIT 172.8 (SEM 29.7)s; and PLC 222.3 (SEM 39.7)s. Despite the fact that buffer ingestion produced favourable metabolic conditions during 30 min of high intensity steady-state exercise, a significant improvement in the subsequent maximal exercise run to exhaustion did not occur.
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PMID:The effects of buffer ingestion on metabolic factors related to distance running performance. 885 7

We have hypothesized that a major role of the apical H(+)-pump in mitochondria-rich (MR) cells of amphibian skin is to energize active uptake of Cl- via an apical Cl-/HCO3(-)-exchanger. The activity of the H+ pump was studied by monitoring mucosal [H+]-profiles with a pH-sensitive microelectrode. With gluconate as mucosal anion, pH adjacent to the cornified cell layer was 0.98 +/- 0.07 (mean +/- SEM) pH-units below that of the lightly buffered bulk solution (pH = 7.40). The average distance at which the pH-gradient is dissipated was 382 +/- 18 microns, corresponding to an estimated "unstirred layer" thickness of 329 +/- 29 microns. Mucosal acidification was dependent on serosal pCO2, and abolished after depression of cellular energy metabolism, confirming that mucosal acidification results from active transport of H+. The [H+] was practically similar adjacent to all cells and independent of whether the microelectrode tip was positioned near an MR-cell or a principal cell. To evaluate [H+]-profiles created by a multitude of MR-cells, a mathematical model is proposed which assumes that the H+ distribution is governed by steady diffusion from a number of point sources defining a set of particular solutions to Laplace's equation. Model calculations predicted that with a physiological density of MR cells, the [H+] profile would be governed by so many sources that their individual contributions could not be experimentally resolved. The flux equation was integrated to provide a general mathematical expression for an external standing [H+]-gradient in the unstirred layer. This case was treated as free diffusion of protons and proton-loaded buffer molecules carrying away the protons extruded by the pump into the unstirred layer; the expression derived was used for estimating stationary proton-fluxes. The external [H+]-gradient depended on the mucosal anion such as to indicate that base (HCO3-) is excreted in exchange not only for Cl-, but also for Br- and I-, indicating that the active fluxes of these anions can be attributed to mitochondria-rich cells.
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PMID:Proton pump activity of mitochondria-rich cells. The interpretation of external proton-concentration gradients. 899 67

Hydroxyapatites precipitated at pH 7.0 and 9.0 with and without carbonate and with different amounts of magnesium were studied. Mg uptake, Ca/P ratios, and lattice constant data indicate that Mg is incorporated into the apatite lattice. IR spectra demonstrate the formation of B-type carbonate apatites with carbonate substituting for phosphate. Decomposition of carbonate-containing apatites at elevated temperatures up to 1000 degrees C is more gradual for apatites prepared at pH 9.0 than for those prepared at pH 7.0 for which an abrupt loss of carbonate occurs after 600 degrees C. Compounds synthesized without added carbonate partially transform to beta Ca3(PO4)2 (TCP) at about 700 degrees C. Greater transformation to TCP occurs as the Mg incorporation is increased, indicating the insertion of Mg into TCP and consequent stabilization of the TCP. SEM micrographs show increases in the size of crystallites when apatites are precipitated with Mg (in the 0.2-1.5% range), providing further evidence for Mg incorporation into the apatite structure.
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PMID:Magnesium-containing carbonate apatites. 907 68


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