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Biomedical subjects

A Roos

Publications and source records attributed to A Roos.

At least 73 records · Page 4Linked to original sources
PubMed1986

Projection of tooth pulp afferents to the thalamus of the cat. II. Distribution and characteristics of single units.

Single unit activity was recorded extra- and intracellularly in the thalamus of the cat following electrical stimulation of tooth pulp afferents. Cells activated by noxious stimuli were found in the basal ventromedial nucleus (VMB), the marginal zones of the arcuate and external nuclei of the ventrobasal complex (VBA and VBX) and the intralaminar complex. Cells found in any of these locations showed a variety of properties; they were activated at different latencies and had different patterns of input. However, cells with responses of short latency and low convergence were with few exceptions found in or close to VMB. Stimulation of tooth pulp evoked both EPSP's and IPSP's in these cells. A subpopulation of cells were found that responded to stimulation of either right or left tooth pulp afferents. 22 units, mainly located in VMB, were found that responded exclusively to stimulation of tooth pulp afferents. In the laterodorsal part of VMB cells influenced by tooth pulp stimulation were found to be antidromically activated by stimulation of the cortical tooth pulp projection area. No such cells were seen at other locations. The results of this study is in agreement with the conclusions in the companion paper (Rydenhag et al. 1986a) that VMB and the border zone between VMB and VBA are the most likely relay nuclei between tooth pulp nociceptive afferents and the cortex. The intralaminar complex is suggested to be important in the cortical arousal reactions and direction of attention following a painful stimulus.

Afferent Pathways↗
PubMed1986

Properties of the intracellular pH-regulating systems of frog skeletal muscle.

1. The properties of the systems that regulate intracellular pH (pHi) in frog muscle (Rana pipiens) were studied in semitendinosus fibres using pH-sensitive micro-electrodes. All experiments were done at 22 degrees C and at external pH (pHo) 7.35. 2. Normally polarized fibres acidified to pHi approximately 6.8 by an NH4Cl pre-pulse (nominal absence of CO2) recovered at a rate of 0.26 +/- 0.04 delta pHi h-1 (n = 10). This corresponds to a net equivalent H ion efflux, JH, of 5.0 pmol cm-2 s-1. This rate was not affected by depolarizing the fibres to -20 mV in 50 mM-K, constant Cl (0.29 +/- 0.03 delta pHi h-1, JH = 4.9 pmol cm-2 s-1, n = 13). Amiloride (1 mM) reduced recovery by almost 90%, while 4-acetamido-4'-isothiocyanostilbene-2,2'-disulphonic acid (SITS, 0.1 mM) reduced recovery by only 18%. Removal of external Na (substitution by N-methyl-D-glucammonium) abolished recovery. Thus, Na-H exchange is responsible for most of the recovery from acidification induced by an NH4Cl pre-pulse. 3. The rate of recovery after an NH4Cl pulse increased linearly as pHi was reduced from 7.25 to 6.55. The dependence of this recovery upon external Na (at pHi 6.90) can be described by Michaelis-Menten kinetics; the apparent Michaelis constant (Km) is 12 +/- 3 mM. 4. Recovery of normally polarized fibres from acidification induced by 5% CO2 is very slow (about 0.03 delta pHi h-1). This recovery could be converted into an acidification of 0.06-0.07 delta pHi h-1 either by removal of Na (as previously described) or by amiloride. We ascribe this acidification of the polarized fibres to HCO3- efflux. 5. In fibres depolarized in 50 mM-K, at constant external Cl concentration, recovery from CO2 acidification was brisk (0.28 +/- 0.01 delta pHi h-1, JH = 9.4 pmol cm-2 s-1, n = 66). It was reduced by about 50% with either SITS or amiloride, and abolished by removal of Na. In the absence of Cl (substituted by gluconate), recovery was also reduced by about 50% and was unaffected by SITS, but nearly abolished by amiloride. Thus, in depolarized fibres, in addition to Na-H exchange, there is an active, SITS-sensitive component of recovery that requires Na, Cl and HCO3.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1986

Effect of calcium and other divalent cations on intracellular pH regulation of frog skeletal muscle.

1. We examined, in frog semitendinosus muscle, the effect of calcium release, induced by depolarization or caffeine, on intracellular pH (pHi) recovery from an acid load applied at least 40 min later. We also studied the effect of external Ca and other divalent cations on recovery. We used pH-sensitive micro-electrodes; the external pH (pHo) was always 7.35. 2. In fibres depolarized by 50 mM-K, constant [K] X [Cl] in the presence of 1 mM-tetracaine (which blocks Ca release), the rate of pHi recovery from 5% CO2-induced acidification was 0.15 +/- 0.02 delta pHi h-1 (n = 7), whereas in depolarized fibres that had never been exposed to the drug, the rate of recovery was 0.27 +/- 0.01 delta pHi h-1 (n = 5). Yet, when Ca release was not blocked and the depolarized fibres were exposed to tetracaine shortly before CO2 exposure, a similar slow rate of 0.14 +/- 0.03 delta pHi h-1 (n = 7) was observed. When Ca release was blocked by tetracaine, but the drug washed out before recovery, the rate was again 0.27 +/- 0.02 delta pHi h-1 (n = 6). 3. In fibres first depolarized to about -23 mV in 50 mM-K, constant [K] X [Cl] (recovery of 0.23 +/- 0.03 delta pHi h-1, n = 6), and then repolarized to -79 mV in 2.5 mM-K, the slow rate of recovery was the same (0.03 +/- 0.02 delta pHi h-1) as that in fibres without a history of depolarization and thus of Ca release. 4. In fibres depolarized to -50 mV (15 mM-K, constant Cl) and then exposed to caffeine (4 mM) which releases Ca from intracellular stores, the recovery was the same (0.07 +/- 0.03 delta pHi h-1, n = 5) as in depolarized fibres not exposed to caffeine (0.09 +/- 0.01 delta pHi h-1, n = 5). 5. We conclude that in frog muscle transient Ca release induced by either depolarization or caffeine does not affect the rate of subsequent pHi recovery. Tetracaine reversibly inhibits pHi recovery, but this inhibition is not due to its blocking of Ca release. 6. Recovery from CO2-induced acidification of fibres depolarized to -21 mV in 50 mM-K, constant Cl was halved, from 0.31 +/- 0.04 delta pHi h-1 (n = 10) to 0.15 +/- 0.01 delta pHi h-1 (n = 13), when external Ca was raised from 4 to 10 mM.(ABSTRACT TRUNCATED AT 400 WORDS)

Ammonium Chloride↗
PubMed1985

Regulation of intracellular pH in human neutrophils.

The intracellular pH (pHi) of isolated human peripheral blood neutrophils was measured from the fluorescence of 6-carboxyfluorescein (6-CF) and from the equilibrium distribution of [14C]5,5-dimethyloxazolidine -2,4-dione (DMO). At an extracellular pH (pHo) of 7.40 in nominally CO2-free medium, the steady state pHi using either indicator was approximately 7.25. When pHo was suddenly raised from 7.40 to 8.40 in the nominal absence of CO2, pHi slowly rose by approximately 0.35 during the subsequent hour. A change of similar magnitude in the opposite direction occurred when pHo was reduced to 6.40. Both changes were reversible. Intrinsic intracellular buffering power, determined by using graded pulses of CO2 or NH4Cl, was approximately 50 mM/pH over the pHi range of 6.8-7.9. The course of pHi obtained from the distribution of DMO was followed during and after imposition of intracellular acid and alkaline loads. Intracellular acidification was brought about either by exposing cells to 18% CO2 or by prepulsing with 30 mM NH4Cl, while pHo was maintained at 7.40. In both instances, pHi (6.80 and 6.45, respectively) recovered toward the control value at rates of 0.029 and 0.134 pH/min. These rates were reduced by approximately 90% either by 1 mM amiloride or by replacement of extracellular Na with N-methyl-D-glucamine. Recovery was not affected by 1 mM SITS or by 40 mM alpha-cyano-4-hydroxycinnamate (CHC), which inhibits anion exchange in neutrophils. Therefore, recovery from acid loading is probably due to an exchange of internal H for external Na. Intracellular alkalinization was achieved by exposing the cells to 30 mM NH4Cl or by prepulsing with 18% CO2, both at a constant pHo 7.40. In both instances, pHi, which was 7.65 and 7.76, respectively, recovered to the control value. The recovery rates (0.033 and 0.077 pH/min, respectively) were reduced by 80-90% either by 40 mM CHC or by replacement of extracellular Cl with p-aminohippurate (PAH). SITS, amiloride, and ouabain (0.1 mM) were ineffective.(ABSTRACT TRUNCATED AT 400 WORDS)

Ammonium Chloride↗
PubMed1984

Pharmacokinetics of the antirheumatic proquazone in healthy humans.

The pharmacokinetics of the antirheumatic proquazone and its conjugated and unconjugated m-hydroxy metabolites were investigated in five healthy male volunteers after both intravenous (75 and 122 mg) and peroral (300 and 900 mg via capsules) administration. For adequate intravenous dosing of the poorly water-soluble proquazone, advantage was taken of the high degree of protein binding of the drug. Proquazone was admixed with 40% sterile human albumin, and these proteinaceous drug-containing solutions were injected. The pharmacokinetics of proquazone and of the measured metabolites after intravenous administration and after the 300-mg po dose were first order, whereas deviations from linear kinetics were observed at the 900-mg dose level. The apparent half-lives of the alpha, beta, and gamma phases of proquazone in plasma were 2, 14, and 76 min, respectively, on intravenous administration. The total clearance of proquazone was 700 mL/min, which indicated a high hepatic extraction. The apparent volume of distribution at steady state was 40 L, implying extensive binding or partitioning of the lipophilic drug in the tissues. Unchanged proquazone (less than 0.001%), the m-hydroxy metabolite (less than 1.0%), and the conjugated m-hydroxy metabolite (20%) were renally excreted after intravenous administration. The extent of absorption of proquazone was approximately 7% and was entirely the result of a large first-pass effect. Digital computer analysis of the data after intravenous administration was performed with a linear three-compartment model. A model-independent approach was used in the analysis of the peroral data.

Administration, Oral↗
PubMed1983

Activity in cortical cells after stimulation of tooth pulp afferents in the cat. Intracellular analysis.

The projection of tooth pulp afferents to cortical cells was studied in intracellular recordings. In a small region of the coronal gyrus, cells in lamina IV were responding at stimulation of contralateral tooth pulp afferents with short latency, steeply rising EPSPs, and one or two action potentials followed by an IPSP. These cells received convergence from skin afferents. In a large cortical area in the coronal, anterior suprasylvian and anterior ectosylvian gyri, tooth pulp stimulation elicited long latency, long lasting EPSPs not succeeded by hyperpolarization mainly in superficial cortical cells. These EPSPs could elicit trains of spikes. A complex type of responses consisted of a short latency EPSP with one or two spikes followed by hyperpolarization which in part was counteracted by a second, long latency EPSP of long duration. Stimulation of low threshold contralateral skin afferents usually gave short latency EPSPs with spikes followed by long lasting hyperpolarization. A common feature of many cells was a high convergence from tooth pulp afferents and bilateral low threshold skin afferents. The response characteristics at tooth pulp stimulation compared to low threshold input are discussed in relation to cortical mechanisms of pain.

Action Potentials↗
PubMed1983

Activity in cortical cells after stimulation of tooth pulp afferents in the cat. Extracellular analysis.

The cortical projection of tooth pulp afferents has been investigated by extracellular recordings in lightly chloralose anaesthetized cats. The results indicate two different projection systems from the tooth pulp afferents terminating on the cortical cells. One system appears to be specific with topographical distribution and activates cells mainly in lamina IV in a restricted region of the coronal gyrus. The cells in this area receive excitation also from restricted cutaneous fields. At stimulation of the tooth pulps with single electrical pulses cells are activated with high discharge probability and with a stable latency. The other system projects mainly to cells in the superficial cortical laminae in a much larger area. These cells receive input from large bilateral cutaneous fields but show less discharge probability and require often temporal summation to discharge at tooth pulp stimulation.

Action Potentials↗
PubMed1983

The intracellular pH of frog skeletal muscle: its regulation in isotonic solutions.

The behaviour of intracellular pH (pHi) was studied with micro-electrodes in frog semitendinosus muscle which was superfused with Ringer solution and with depolarizing solutions. The electrodes were introduced into the depolarized muscle about 40 min after contracture had subsided. All studies were done at external pH (pHo) of 7.35 and at 22 degrees C. The pHi in normal Ringer solution buffered with HEPES was 7.18 +/- 0.03 (S.E. of mean) (n = 10); the membrane potential, Vm, was -88 +/- 1.8 mV. When pHi was lowered to about 6.8 by replacing the HEPES by 5% CO2, 24 mM-HCO3 (constant pHo), it recovered at a very slow rate of 0.025 +/- 0.011 delta pHi h-1 (n = 6). When all the Na was replaced by N-methyl-D-glucamine (initial pHi 7.20 +/- 0.04, initial Vm -89 +/- 1.5 mV, n = 8), this slow alkalinization was converted into a slow acidification at a rate of 0.069 +/- 0.024 delta pHi h-1. In muscle depolarized in 15 mM-K (Vm approximately -50 mV), the rate of recovery from CO2 acidification was not increased above that in normal Ringer solution (2.5 mM-K). When, however, the muscle was depolarized in 50 mM-K to about -20 mV, the rate of recovery increased to 0.33 +/- 0.07 delta pHi h-1 (n = 6) when external Cl was kept constant, or to 0.21 +/- 0.03 (n = 9) when [K]. [Cl] product was kept constant. In the absence of Na, pHi recovery rate in 50 mM-K was reduced by at least 90%. Enhanced recovery from CO2-induced acidification was also observed in 2.5 mM-K when the fibres were depolarized to about -20 mV in one of two ways: (a) by previous exposure for 60 min to 50 mM-K at constant Cl, or (b) by reduction of external Cl to 5.9 mM in the presence of 0.5 mM-Ba. When pHi of depolarized fibres (50 mM-K) was lowered to about 6.8 by the weak acid dimethyl-2,4-oxazolidinedione (DMO), it recovered at a rate of 0.12 delta pHi h-1 in two experiments. In fibres depolarized in 50 mM-K and constant Cl, either 0.1 mM-SITS or 0.5 mM-amiloride slowed pHi recovery from CO2 exposure by about 50%. When the depolarization was achieved at constant [K]. [Cl] product, amiloride slowed pHi recovery by about 50%, while SITS had, at most, only a slight effect.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed1983

The intracellular pH of frog skeletal muscle: its regulation in hypertonic solutions.

Intracellular pH (pHi) was followed with micro-electrodes in frog semitendinosus muscle, superfused at 22 degrees C with hypertonic solutions (external pH, pHo, 7.35) containing 2.5, 15 or 50 mM-K. Tonicity was doubled by addition of 250 mM-mannitol or, in a few cases, 125 mM-extra NaCl. Tripling of tonicity was accomplished by adding 500 mM-mannitol. Because of the ability of hypertonicity to minimize contracture, the course of pHi could be followed from the start of depolarization. The pHi of fibres after about 40 min in Ringer solution (2.5 mM-K, HEPES buffer) of twice normal tonicity was 7.40 +/- 0.04 (S.E. of mean) (n = 17), about 0.2 higher than at normal tonicity. The membrane potential, Vm, was -87.7 +/- 1.3 mV. When the muscle was depolarized in 50 mM-K to about -30 mV, the pHi rapidly fell by 0.3-0.5 unit (n = 9), and then promptly returned. This recovery was followed by a much slower and progressive rise to above control. Removing Na from the medium did not affect the degree of acidification, but the pHi recovered at a slightly slower rate, did not reach control value and showed no progressive rise. A less pronounced transient acidification was also observed when the muscle was depolarized in 15 mM-K to about -60 mV. When contracture was prevented either by 1-2 mM-tetracaine under isotonic conditions or by raising tonicity 3-fold, 50 mM-K produced no transient acidification. When the pHi of resting fibres in Ringer solution (2.5 mM-K) of twice normal tonicity was reduced by 5% CO2 from 7.40 to 7.12 +/- 0.07 (n = 3), it recovered at a slow rate (0.06 +/- 0.03 delta pHi h-1). Depolarization by 15 or 50 mM-K enhanced recovery rate 4-6-fold. These solutions of twice normal tonicity, as compared to those of normal tonicity, shifted the curve relating pHi recovery rate and membrane potential along the potential axis in the direction of hyperpolarization. This shift may be due to increased ionic shielding of fixed negative charges at the inner membrane surface. At twice normal tonicity, the very slow pHi recovery of resting fibres from CO2-induced acidification, as well as the more rapid recovery in depolarized fibres, could be abolished by 1 mM-amiloride or by removing Na. The application of amiloride during pHi recovery in 50 mM-K was not associated with an observable change in Vm. SITS had no significant effect on recovery.(ABSTRACT TRUNCATED AT 400 WORDS)

Amiloride↗
PubMed1982

Cortical responses evoked by tooth pulp stimulation in the cat. Surface and intracortical responses.

In lightly chloralose-anaesthetized cats selective stimulation of tooth pulp afferents elicited responses in coronal, anterior suprasylvian and adjacent cortical gyri. In the lateral part of coronal gyrus the potentials evoked from the contralateral canine tooth pulps were initially positive. Such responses from the upper and lower teeth had different cortical distribution suggesting a topographical organization. In the regions adjacent to those with initially positive responses stimulation of the same tooth pulp evoked initially negative potentials. Stimulation of ipsilateral tooth pulp afferents elicited almost exclusively initially negative potentials with a similar distribution as the responses of contralateral teeth but with longer latency. Laminar analysis showed that the region with initial positivity in the response to stimulation of the tooth pulp coincided with an intracortical negative focal potential of maximum amplitude mainly in lamina IV. In areas with initially negative responses the maximum of the focal potential following tooth pulp stimulation was obtained in superficial cortical layers. It is postulated that the projection system underlying the initially positive cortical responses has a topographically arranged cortical projection terminating mainly in lamina IV. The projection system eliciting the initially negative potentials, has a widespread cortical distribution and produces excitation predominantly in the superficial laminae.

Afferent Pathways↗
PubMed1981

Protein binding and erythrocyte partitioning of the antirheumatic proquazone.

The kinetics of proquazone, a new nonacidic nonsteroidal anti-inflammatory drug, were investigated by equilibrium dialysis and red blood cell partitioning methods on human blood and its subcompartments: erythrocytes, plasma, and plasma water. The binding of this lipophilic compound to plasma proteins and albumin was high (98%) and was not concentration dependent or altered in the presence of large concentrations of metabolites. The plasma protein binding of proquazone increased with increasing pH. The apparent solubility of the hydrophobic drug was largely increased in buffers in which albumin was admixed in high concentrations. Albumin as a biological solubilizer permits intravenous administration of significantly larger amounts of the drug. The erythrocyte--buffer partition coefficient averaged 5.5 and was pH dependent. Equilibrium between red blood cells and the buffer was obtained quickly after drug addition (less than 2 min). The erythrocyte--plasma partition coefficient value of 0.09 indicated that only unbound drug partitions into red cells.

Anti-Inflammatory Agents↗
PubMed1981

Membrane permeability to the molecular and ionic forms of DMO in barnacle muscle.

The time course of the intracellular pH (pHi) of barnacle muscle fibers was followed using microelectrodes while the fibers were exposed to 15 mM of the weak acid 5,5-dimethyloxazolidine-2,4-dione (DMO) at pH 6.5. The rapid initial fall in pHi was used to determine the membrane permeability to the DMO molecule, while the much slower fall during the subsequent plateau phase yielded the permeability to the DMO ion. This experimental approach and the mathematical treatment of the data can be used to obtain the membrane permeabilities to other weak acids or bases. We found values of 1.9 X 10(-4) cm/s for the permeability to the DMO molecule and 1.5 X 10(-7) cm/s for the permeability to the ion, assuming the fiber to be a cylinder. Thus the permeability of the neutral form is about 10(3) times that of the ionized form. At commonly encountered conditions of pHi = 7.3, outside pH = 7.5, and membrane potential = -52 mV, this permeability ratio introduces an error of only -0.01 to -0.02 into the determination of pHi based on the distribution of DMO.

Animals↗
PubMed1981

pH regulation in barnacle muscle fibers: dependence on extracellular sodium and bicarbonate.

Intracellular pH (pHi) regulation was studied in barnacle muscle fibers with pH-sensitive microelectrodes. The cells were acid loaded, and the subsequent recovery of pHi was monitored. The rate of recovery was reduced by one-third when external Na+ ([Na+]o) was replaced by Li+, but recovery was completely abolished when Na+ was replaced by choline or N-methyl-D-glucamine. In other experiments, varying amounts of Na+ were replaced by choline, and the acid extrusion rate, derived from the recovery rate of pHi, was calculated at a single value of pHi, 6.80. The dependence of the acid extrusion rate on [Na+]o could be described by Michaelis-Menten kinetics; at pHo (extracellular) = 8.0 and [HCO3-]o (extracellular) = 10 mM, the apparent Km and Vmax were 59 mM and 1.3 mmol x l(-1) x min-1. When [HCO3-]o was reduced to 2.5 mM at the same pHo, Km did not change significantly, but Vmax was substantially reduced. On the other hand, when pHo was reduced to 7.4 at constant [HCO3-]o, Vmax changed only slightly, but Km increased substantially. In similar experiments, we examined the dependence of the acid extrusion rate on [HCO3-]o. At pHo = 8.0 and [Na+]o = 440 mM, the apparent Km and Vmax were 4.1 mM and 2.1 mmol x 1-1 x min-1. When pHo was reduced to 7.4, Vmax was not altered, but Km substantially increased. The kinetic data are discussed in terms of the role of pHo, [Na+]o, and [HCO3-]o in the pHi-regulating system.

Acid-Base Equilibrium↗
PubMed1980

An evaluation of a model ecosystem with DDT.

The reproducibility, variability, and reliability of a simple aquatic-terrtestrial model ecosystem experiment was tested with p,p'-DDT. The variation among the model replicates as well as within the units was studied by using hierarchal analysis of variance. the complete budget of the chemical was calculated and a theoretical transport model was constructed. The degradation and accumulation of DDT was followed by gas chromatographic residue analysis, which showed good reproducibility of the experimental design. The degradation of DDT in the model was similar to that found in the field, but the determination of concentration factors was questionable. The material balance tables revealed that the soil and bottom substrates were the main contributors, which regulated the fate of the chemical in the model. The usefulness of the model is presented in this report.

Animals↗
PubMed1980

The buffer value of weak acids and bases: origin of the concept, and first mathematical derivation and application to physico-chemical systems. The work of M. Koppel and K. Spiro (1914).

A translation is offered of a paper by M. Koppel and K. Spiro, published in 1914, and entitled: 'On the action of moderators (buffers) in the shift of the acid-base equilibrium of biological fluids'. In this work, which appeared in Vol. 65 of the Biochemische Zeitschrift, the authors introduced the modern concept of buffer value and, for the first time, quantified the buffering power of weak acids and bases, ampholytes, dibasic acids, and mixtures of buffers. The circumstances that surround the eclipse of this trailblazing research have been critically examined, and biographical details have been provided.

Acid-Base Equilibrium↗