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Biomedical subjects

M E Morris

Publications and source records attributed to M E Morris.

At least 55 records · Page 3Linked to original sources
PubMed1998

Performance on clinical tests of balance in Parkinson's disease.

BACKGROUND AND PURPOSE: Due to the high incidence of falls in people with idiopathic Parkinson's disease (PD), the assessment of standing balance is a key component of physical therapist evaluation. This study investigated performance on clinical tests of standing balance in subjects with and without PD. SUBJECTS: The subjects were 10 persons with PD who had a history of falls (age range = 60-80 years), 10 persons with PD who had no history of falls (age range = 63-79 years), and 10 persons with no known neurological impairment (age range = 60-78 years) who served as a comparison group. METHODS: Subjects were tested on their ability to maintain stability in 3 conditions: (1) steady standing (feet apart, feet together, tandem stance, step stance, and single-limb stance), (2) in response to perturbations generated by self-initiated movements (arm raise, functional reach, bend-reach, and step tests), and (3) in response to an external perturbation to upright stance (shoulder tug). Balance was measured at peak dosage in the levodopa medication cycle (in the morning) and 7 days later. RESULTS: The mean Hoehn and Yahr Disability Scale score was 3.0 for the fallers with PD and 2.5 for the nonfallers with PD. Performance on the tandem stance, single-limb stance, functional reach, and shoulder tug tests demonstrated differences between the subjects with PD and the comparison group and between the fallers and nonfallers with PD. The results of these tests were highly repeatable over 7 days (ICC = .61-.94). CONCLUSION AND DISCUSSION: Although there was a small sample size, performance was highly consistent across 7 days when testing occurred during peak dosage of levodopa. A small battery of tests were sensitive enough to discriminate between people with PD who fall and those with no history of falls.

Accidental Falls↗
PubMed1998

Changes in [K+]o evoked by baclofen in guinea pig hippocampus.

K(+)-sensitive microelectrodes were used to record changes evoked by baclofen in extracellular potassium concentration ([K+]o) and field potentials in the stratum pyramidale (SP) and stratum radiatum (SR) in the CA1b region of guinea pig hippocampal slices in vitro. Bath applications of (+/-)-baclofen (1 microM-3 mM for approximately 5 min) evoked changes in [K+]o, which were in most cases sustained throughout agonist application and reversed during washout. The maximal (Rmax) values for curves fitted to the concentration-response data were for SP and SR, respectively, 0.59 +/- 0.03 and 0.65 +/- 0.03 mM, and EC50 values were 39.7 and 39.4 microM, respectively. The evoked K+ and field potential changes were significantly correlated and could be blocked by 2-OH-saclofen (50 microM) and CGP 35348 (50 microM). In < or = 10% of experiments baclofen (10-50 microM) induced either a decrease or a transient increase (< or = 1 min duration) in [K+]o; in some slices with concentrations > or = 20 microM an initial decrease preceded a progressive increase. Pressure ejection of baclofen (100 microM for 100-900 ms) evoked increases in [K+]o and field potentials, which were larger in SR than in SP. In < or = 10% of slices brief and (or) sustained application of baclofen (by either bath perfusion or pressure ejection) also evoked synchronous, repetitive interictal and ictal discharges at frequencies approximately 1/s and 1/12 s, respectively, an observation that affirms a proconvulsant capacity. It is concluded that (i) although increases in [K+]o evoked by baclofen in SR compared with SP are slightly larger, they are not significantly different, (ii) GABAB receptor subtype(s) in SR and SP appear similar, as they have identical affinities, and (iii) [K+]o accumulations evoked by GABA likely include a contribution from a GABAB receptor activated K+ conductance, especially in dendritic regions.

Animals↗
PubMed1998

Cellular mechanisms of renal adaptation of sodium dependent sulfate cotransport to altered dietary sulfate in rats.

The renal transport and fractional reabsorption of inorganic sulfate is altered under conditions of sulfate deficiency or excess. The objective of this study was to examine the cellular mechanisms of adaptation of renal sodium/sulfate cotransport after varying dietary intakes of a sulfur containing amino acid, methionine. Female Lewis rats were divided into four groups and fed diets containing various concentrations of methionine (0, 0.3, 0.82 and 2.46%) for 8 days. Urinary excretion rates and renal clearance of sulfate were significantly decreased in the animals fed a 0% methionine diet or a 0.3% methionine diet, and significantly increased in the animals fed a 2.46% methionine diet when evaluated on days 4 and 7. Serum sulfate concentrations were unchanged by diet treatment in all animals. The fractional reabsorption of sulfate was significantly increased in the animals fed the 0% methionine diet and the 0.3% methionine diets, and decreased in the animals fed the 2.46% methionine diet. Increased mRNA and protein levels for the sodium/sulfate transporter (NaSi-1) were found in the kidney cortex following treatment with the 0 and 0.3% methionine diet groups. Sulfate homeostasis by renal reabsorption is maintained by an up-regulation of steady state levels of NaSi-1 mRNA and protein when the diet is low in methionine.

Animals↗
PubMed1998

Ibuprofen-induced changes in sulfate renal transport.

Nonsteroidal anti-inflammatory drugs (NSAIDs) increase sulfate renal clearance and decrease the fractional reabsorption of sulfate by the kidneys. The mechanism of this alteration of inorganic sulfate homeostasis is unknown. The objectives of this study were 1) to investigate if sulfate renal transport is altered in isolated membrane vesicles after pretreatment of animals in vivo with ibuprofen (IBU), and 2) to determine the cellular mechanism of changes in sulfate renal transport. Female Lewis rats received IBU at a i.v. dose of 27 mg/kg followed by an infusion of 33 microg/min for 4 hr. Sulfate transport was studied using brush border (BBM) and basolateral membrane (BLM) vesicles isolated from rat kidney cortex. The Vmax for the sodium-dependent sulfate cotransport (NaSi-1) in BBM was significantly lower in the IBU group compared with the control group (0.79 +/- 0.23 vs. 1.25 +/- 0.17 nmol/mg protein/10 sec, respectively; P <.05) with no change in Km. There were no significant differences between the study groups in sulfate anion exchange kinetics in BLM vesicles. NaSi-1 transporter mRNA level in kidney cortex and protein level in BBM were significantly lower in animals pretreated with IBU compared with that in control animals. There was no change in membrane fluidity of BBM and BLM isolated from IBU-treated animals as measured by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene. These results indicate that IBU treatment alters sodium-dependent sulfate cotransport by a downregulation of mRNA and protein of NaSi-1 transporter in BBM.

Animals↗
PubMed1997

Salicylic acid induces changes in the physical properties of model and native kidney membranes.

Salicylic acid (SA) can inhibit the facilitated transport of inorganic sulfate in the kidney, placenta, and erythrocytes. One mechanism of this inhibition could involve the interaction of SA with membranes, resulting in altered function of transporter protein(s) due to changes in membrane fluidity. Such membrane effects could result in altered membrane transport and consequently in changes in the pharmacokinetics and the therapeutic activity of both xenobiotics and endogenous substrates. We investigated the effect of SA on the fluidity of brush border membrane (BBM) and basolateral membrane (BLM) isolated from rat kidney and also on the physical properties (such as phase transition temperature and fluidity) of model membranes by fluorescence polarization and differential scanning calorimetry (DSC) techniques. SA decreased the lipid order parameter (S) of BBM and BLM membranes in a concentration-dependent manner, indicating that the addition of SA makes the membrane more fluid. The fluidizing effect of SA was more pronounced than that of benzyl alcohol. Studies were carried out with protein-free model membranes composed of dipalmitoylphosphatidylcholine (DPPC) to investigate the effects of SA on the bilayer membrane lipids. SA decreased the fluorescence polarization of DPH (1,6-diphenyl 1,3,5-hexatriene) incorporated in DPPC vesicles. DSC studies demonstrated that SA broadened the phase transition temperature of DPPC vesicles and suggested that SA is located in the C1-C8 region of the acyl chain. In protein-free model membranes, SA exerted fluidizing effects through its incorporation into the cooperative hydrophobic region of the bilayer. The perturbation of membrane physical properties induced by SA and its hydrophobic localization in the membrane bilayer may be important in the SA-induced alteration of sulfate membrane transport.

Animals↗
PubMed1997

Membrane transport in hepatic clearance of drugs. I: Extended hepatic clearance models incorporating concentration-dependent transport and elimination processes.

PURPOSE: The objective of the present study was to develop hepatic clearance models which incorporate a unidirectional carrier-mediated uptake and bidirectional diffusional transport processes for drug transport in the sinusoidal membrane of hepatocytes as well as nonlinear intrinsic elimination. METHODS: Two models were derived which view the liver as two separate compartments, i.e., sinusoid and hepatocyte. Model I assumes the instantaneous complete mixing of drugs within each compartment (similar to that of the "well-stirred" model), while model II assumes that the drug concentrations in both compartments decrease progressively in the direction of the hepatic blood flow path (similar to that of the "parallel-tube" model). Computer simulations were performed using a range of steady-state infusion rates for a substrate, while varying the Vmax (capacity) and Km (Michaelis-Menten constant) for the carrier-mediated uptake process, the diffusional clearance, the Vmax and Km for the intrinsic elimination process, blood flow and protein binding. RESULTS: Simulations in which Vmax and Km for the sinusoidal membrane transporter and the diffusional clearance were varied, demonstrated that these membrane transport processes could affect the clearance of drugs to a significant extent in both models. The estimates for clearance of substrates with the same pharmacokinetic parameters are always lower in model I than in model II, although the quantitative differences in parameter estimates between models varied, depending on the steady state infusion rates. CONCLUSIONS: These more general hepatic clearance models will be most useful for describing the hepatic clearance of hydrophilic compounds, such as organic anions or cations, which exhibit facilitated uptake and limited membrane diffusion in hepatocytes.

Biological Transport↗
PubMed1997

Membrane transport in hepatic clearance of drugs. II: Zonal distribution patterns of concentration-dependent transport and elimination processes.

PURPOSE: The objective of the present simulation study was to investigate the effects of hepatic zonal heterogeneity of membrane transporter proteins and intrinsic elimination activities on hepatic clearance (CL) and drug concentration gradient profiles in the sinusoidal blood and hepatocytes. METHODS: The model used in the simulations assumes an apparent unidirectional carrier-mediated transport and a bidirectional diffusion of substrates in the hepatic sinusoidal membrane as well as a nonlinear intrinsic elimination. Three different distribution patterns of the transporter and the metabolizing enzyme along the sinusoidal flow path were used for the simulations. The effects of changes in the Michaelis-Menten parameters for those nonlinear processes, and in the unbound fractions of the drug in blood and tissue components were investigated. RESULTS: Significant differences in CL occurred when the distribution patterns of the transporter and/or the metabolizing enzyme activities were altered under nonlinear conditions. The highest CL values were observed when the transporter and the metabolizing enzyme had similar distribution patterns within the liver acinus, while opposite distribution patterns produced the lowest CL values. Tissue concentration profiles were significantly affected by the distribution patterns of the transporter, but the changes in blood concentration profiles were relatively small. Altering protein binding in blood produced significant changes in CL, and blood and tissue concentration gradients, while altering protein binding in tissue affected only drug accumulation patterns within hepatocytes, regardless of the distribution patterns of the transporter or the metabolizing enzyme. CONCLUSIONS: The present simulations demonstrate that hepatic zonal heterogeneities in the transporter and the metabolizing enzyme activities can significantly influence hepatic clearance and/or drug concentration gradient profiles in the sinusoidal blood and hepatocytes.

Biological Transport↗
PubMed1996

Extracellular K+ accumulations and synchronous GABA-mediated potentials evoked by 4-aminopyridine in the adult rat hippocampus.

Transient changes in extracellular potassium concentration ([K+]o) and field potentials were evoked by 4-aminopyridine (4-AP; 50-100 microM) and recorded with ion-selective microelectrodes in CA1b, CA3b and dentate sectors of adult rat hippocampal slices. Long-lasting field potentials recurred at a frequency of approximately 1/60 s (0.016 +/- 0.003 Hz) in association with increases in [K+]o which were largest and most sustained in the dendritic regions where afferent fibers terminate (dentate > CA1 > CA3) and in the hilus. In stratum radiatum of CA1 or stratum moleculare of the dentate these fields had a peak amplitude of 1.4 +/- 0.29 mV, duration 8.3 +/- 1.6 s, and were accompanied by increases in [K+]o of 1.8 +/- 0.22 mM that lasted 32 +/- 5.5 s (n = 17 slices). Interictal epilentiform potentials, which were brief (< 0.2 s) and more frequent at approximately 1/3 s (0.30 +/- 0.02Hz) were also present in CA1, CA3 and the hilus and associated with small increases in [K+]o (< or = 0.5 mM, duration < or = 2 s). Interictal activity was blocked by 6-cyano-7-nitroquinoxalone-2,3-dione (CNQX; 5-20 microM); the slow, less frequent potentials were resistant to both CNQX and DL-2-amino-5-phosphonovaleric acid (APV; 50 microM) and reversibly blocked (or attenuated by approximately 80%) by bicuculline methiodide (BMI) (25-100 microM). The BMI-sensitive potentials were also abolished by baclofen (100 microM), an effect which was reversed by 2-OH-saclofen (100 microM). Focal application of KCI or GABA in the absence of 4-AP evoked long-lasting field and [K+]o potentials which were similar to those evoked by 4-AP but more sustained. The proportional relationship between the amplitudes of field and K+ potentials with GABA closely resembled that observed for 4-AP; in contrast the slope of KC1-evoked responses was lower. Our results demonstrate that in the adult rat hippocampus 4-AP induces in many different regions accumulations of [K+]o in synchrony with the long-lasting field potentials, which are known to correspond to an intracellular long-lasting depolarization of the pyramidal cells. These changes are smaller than those which occur in the immature rat hippocampus--which may be related to differences in Na-K-ATPase and susceptibility to seizures. These events involve the activation of GABAA receptors, are under the modulatory control of GABAB receptors, and likely arise from the activity of GABAergic interneuron and/or afferent terminals. The long-lasting field potentials appear to reflect mainly the direct depolarizing actions of GABA and to much more limited extent the associated accumulation of [K+]o.

4-Aminopyridine↗
PubMed1996

Hepatic conjugation/deconjugation cycling pathways. Computer simulations examining the effect of Michaelis-Menten parameters, enzyme distribution patterns, and a diffusional barrier on metabolite disposition.

Conjugation/deconjugation cycling plays an important role in the physiologic regulation of the concentration of endogenous compounds that form conjugated metabolites. Less is known concerning the deconjugation of xenobiotics. The model compound p-nitrophenol (pNP) is conjugated to sulfate and glucuronide metabolites which can also undergo hydrolysis, via separate enzyme systems, to regenerate pNP. In the present investigation, computer simulations were performed using literature values for the KM and Vmax for each of the four enzyme systems involved in net pNP conjugation. The apparent sulfation rate, apparent glucuronidation rate, and the extraction ratio (E) of pNP were each examined (i) as a function of pNP concentration, (ii) following alterations in the KM and Vmax values for the deconjugation enzymes, (iii) after modulating the enzyme distribution patterns along the liver flow path for both the conjugating and deconjugating enzymes, and (iv) in the presence of drug metabolite diffusional barriers for membrane transport. Results of these simulations demonstrated that changes in the KM or Vmax for deglucuronidation produced changes not only in net glucuronidation but also in net sulfation. Overall extraction (E) of the parent compound was only affected when glucuronidation was an important pathway, i.e., at higher pNP concentrations. Similar results were observed with changes in desulfation, with desulfation having the greatest effects at low pNP concentrations where sulfation represents the predominant metabolic pathway. Changes in the enzyme distribution patterns for the deconjugation pathways showed that the greatest influence on net conjugation rates occurred when hydrolase enzyme activity was distributed downstream from the respective forward reaction. In the presence of a diffusional barrier for metabolite transport (i.e., when the diffusional clearance was one tenth of blood flow), net metabolism of parent was diminished with E decreasing from 0.74, in the absence of a barrier, to 0.23, since the generated metabolite remained, to a great extent, within hepatocytes and underwent a more pronounced hydrolysis. In the presence of diffusional barriers for uptake of the conjugated metabolites, the lowest drug extraction and metabolite formation rates were observed when the distribution of the conjugation and deconjugation pathways across the liver were the same. Therefore, the effects of deconjugation on hepatic drug removal and metabolite formation are highly dependent on the enzymatic parameters of both the forward and reverse reactions, the parent drug concentration, the enzyme distribution patterns, and the presence of diffusional barriers for metabolite membrane transport. Since a change in the deconjugation of one metabolite can influence the net formation of not only itself but also other metabolites, and overall drug extraction, evaluation of conjugation/deconjugation cycling represents an important consideration in pharmacokinetic studies involving physiological-, pathological-, or pharmacological-induced alterations in conjugate formation.

Computer Simulation↗
PubMed1996

Inhibitors of P-glycoprotein-mediated daunomycin transport in rat liver canalicular membrane vesicles.

P-glycoprotein (P-gp), the multidrug resistance (MDR) gene product, is exclusively located on the canalicular membrane of hepatocytes. Recent studies using isolated rat canalicular liver plasma membrane (cLPM) vesicles indicate that daunomycin (DNM) is a substrate for the ATP-dependent P-gp efflux system in the rat liver. The isoforms of P-gp present in cLPM and in cancer cell lines differ in that the major form present in the liver represents the gene product of mdr2 in mice (MDR3 in humans; class III) while the isoform of P-gp in cancer cells is the gene product of mdr1 in mice (MDR1 in humans, class I). The objective of this study was to examine the inhibitory effects of various organic compounds, most of which have been studied previously in MDR cancer cells, on P-gp-mediated [3H]DNM uptake into cLPM. Also, the stereospecificity of P-gp for its substrates was investigated by comparing the inhibitory effects of the enantiomers and the racemic mixtures of verapamil and propranolol. DNM exhibited ATP-dependent active transport into rat liver cLPM with a Km of 26.8 +/- 13.4 microM and a Vmax of 4.9 +/- 0.8 nmol/45 s/mg of protein (n = 4). ADP, AMP, and a nonhydrolyzable ATP analogue did not increase DNM transport over the control value. Thirty-one potential inhibitors were examined; only acridine orange, doxorubicin, verapamil, propranolol, phosphatidylcholine, beta-estradiol glucuronide, and DNM itself showed statistically significant inhibition of [3H]DNM uptake into cLPM. These results suggest that only a limited number of substrates bind to or are transported across the hepatic canalicular membrane via P-gp. Phosphatidylcholine, a substrate for the gene product of the class III P-gp gene, produced significant inhibition of [3H]DNM transport (30.6% at a 10-fold-higher substrate concentration), suggesting that transport may be mediated, at least in part, by this P-gp gene product. There were no statistically significant differences in the inhibitory effects of the enantiomers and racemate of verapamil on [3H]DNM transport into cLPM, but the enantiomers of propranolol exhibited stereospecific inhibition of DNM transport. (R)-(+)-Propranolol produced a statistically significant inhibition of [3H]DNM transport similar to that observed with the racemic mixture, while (S)(-)-propranolol showed no inhibition. These findings suggest that bile canalicular P-gp may exhibit stereospecificity of binding or transport for its substrates.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Stride length regulation in Parkinson's disease. Normalization strategies and underlying mechanisms.

Results of our previous studies have shown that the slow, shuffling gait of Parkinson's disease patients is due to an inability to generate appropriate stride length and that cadence control is intact and is used as a compensatory mechanism. The reason for the reduced stride length is unclear, although deficient internal cue production or inadequate contribution to cortical motor set by the basal ganglia are two possible explanations. In this study we have examined the latter possibility by comparing the long-lasting effects of visual cues in improving stride length with that of attentional strategies. Computerized stride analysis was used to measure the spatial (distance) and temporal (timing) parameters of the walking pattern in a total of 54 subjects in three separate studies. In each study Parkinson's disease subjects were trained for 20 min by repeated 10 m walks set at control stride length (determined from control subjects matched for age, sex and height), using either visual floor markers or a mental picture of the appropriate stride size. Following training, the gait patterns were monitored (i) every 15 min for 2 h; (ii) whilst interspersing secondary tasks of increasing levels of complexity; (iii) covertly, when subjects were unaware that measurement was taking place. The results demonstrated that training with both visual cues and attentional strategies could maintain normal gait for the maximum recording time of 2 h. Secondary tasks reduced stride length towards baseline values as did covert monitoring. The findings confirm that the ability to generate a normal stepping pattern is not lost in Parkinson's disease and that gait hypokinesia reflects a difficulty in activating the motor control system. Normal stride length can be elicited in Parkinson's disease using attentional strategies and visual cues. Both strategies appear to share the same mechanism of focusing attention on the stride length. The effect of attention appears to require constant vigilance to prevent reverting to more automatic control mechanisms.

Aged↗
PubMed1996

Temporal stability of gait in Parkinson's disease.

BACKGROUND AND PURPOSE. Evaluation of physical therapy for gait disorders in patients with Parkinson's disease (PD) requires an under-standing of how the patients' medication cycle affects function. Four experiments were conducted to investigate stability of gait variables. METHODS AND RESULTS. In experiment 1, 15 subjects with idiopathic PD and 15 subjects without PD performed two sets of gait trials spaced 30 minutes apart, with the initial trial conducted with the subjects at a peak dose of medication. Strong correlations, as determined by intraclass correlation coefficients (ICC[2,1]), occurred between repeat measures of speed (ICC = .92), cadence (ICC = .92), stride length (ICC = .94), and time spent in double support (DS) (ICC = .93). In experiment 2, 16 subjects with PD were tested at the same time on two consecutive days. There was good repeatability for speed (ICC = .88), cadence (ICC = .85), stride length (ICC = .84), and DS (ICC = .80). When we assessed the repeatability of measurements taken at peak dose and at end of dose, there were low correlations for speed (ICC = -.54), cadence (ICC = -.07), stride length (ICC = -.35), and DS (ICC = -.38). In a final experiment on 16 subjects with PD, we used time-series analysis to examine the stability of measurements taken every 15 minutes for 2 1/2 hours. Slopes of regression models, standard deviations, and residual autocorrelations were negligible, indicating that the measurements were stable. CONCLUSION AND DISCUSSION. The parkinsonian gait pattern is reproducible across either brief time intervals or 24 hours when peak medication prevails. At the end of dose, however, marked changes in gait occur, apparently related to depletion of medication.

Aged↗
PubMed1996

Pectoralis tendon avulsion in the skeletally immature.

Pectoralis tendon avulsion is a rare injury typically occurring in skeletally mature men. The diagnosis can be difficult to make and is often delayed. We report a case of a complete bony avulsion of the pectoralis tendon at the site of its humeral insertion in a skeletally immature male. The palpable and radiographic evidence of ossification at the injury site made the diagnosis in this adolescent case uniquely obvious.

Adolescent↗
PubMed1996

Hepatic uptake of choline in rat liver basolateral and canalicular membrane vesicle preparations.

Choline, an endogenous quaternary ammonium ion, is transported into the liver by both saturable and nonsaturable processes. The objective of the present investigation was to determine the driving force(s) for uptake of choline in rat liver basolateral membrane (blLPM) and canalicular membrane (cLPM) vesicles. Choline is transported into an osmotically sensitive intravesicular space in both blLPM and cLPM. Uptake of [3H]choline into both blLPM and cLPM exhibited temperature dependence (0 degree C vs. 37 degrees C). A valinomycin-induced inside-negative K+ diffusion potential significantly stimulated initial uptake of [3H]choline in both vesicles. Choline uptake in blLPM and cLPM was not stimulated in the presence of an inwardly directed sodium gradient or an outwardly directed H+ gradient, and ATP did not enhance choline uptake in cLPM. Choline itself and structurally similar derivatives, such as hemicholinium-3 and succinylcholine, inhibited [3H]choline uptake 11 to 92% (at 10-fold higher concentrations) in blLPM and cLPM. Other cations, including N1-methylnicotinamide, thiamine and d-tubocurarine, and cardioglycosides did not inhibit choline transport in either vesicle preparation. In addition, [3H]choline uptake into both blLPM and cLPM was enhanced when vesicles were preloaded with nonradiolabeled choline (trans-stimulation). Kinetic studies indicated that choline was transported into blLPM by both saturable and passive processes and into cLPM predominantly by a saturable process. These results suggest that the transport of choline is likely mediated by a potential-sensitive conductive pathway in both blLPM and cLPM. The electrogenic pathway in cLPM may play a role in the reabsorption of choline from bile.

Animals↗
PubMed1995

Correlation of anoxic neuronal responses and calbindin-D28k localization in stratum pyramidale of rat hippocampus.

Immunohistochemical staining for the calcium-binding protein calbindin-D28k (CaBP) was combined with Lucifer Yellow (LY) identification and intracellular recording of changes in membrane parameters of pyramidal neurons in CA2, CA1, and the subiculum of rat hippocampal slices during brief exposure (4.0 +/- 0.19 min) to N2. Anoxia evoked either a depolarization or hyperpolarization of membrane potential (VM) (+21.5 +/- 2.79 mV above VM = -70.5 +/- 1.50 mV, n = 30 and -7.2 +/- 0.72 mV below VM = -68.2 +/- 1.34 mV, n = 24, respectively) and a fall in membrane resistance of approximately 20%. Differences in the response could be correlated with the presence or absence of CaBP and the localization of neurons in different layers of stratum pyramidale and sectors of the hippocampus. For neurons immunopositive for calbindin (CaBP(+)), depolarization was observed more frequently (83%) than hyperpolarization (17%); in contrast, 44% of responses of calbindin-negative (CaBP(-)) neurons were depolarizing and 56% were hyperpolarizing. Depolarizations of CaBP(+) neurons were more gradual in slope, and more rapidly reached a plateau in comparison with those recorded in CaBP(-) neurons. Responses of neurons in the superficial layer of stratum pyramidale (in which 79% of CaBP(+) pyramidal neurons were situated) were mainly depolarizing (91%), while for those in the deep layer (which contained 89% of the CaBP(-) cells) such responses were observed less often (45%). Depolarization was also more common than hyperpolarization for cells located in CA2/CA1c/CA1b (63%) than in the CA1a/subicular region (37%). The depolarizing response of the majority of pyramidal neurons which are CaBP(+), superficial, and closer to CA3 may reflect an efficient buffering of intracellular Ca2+, which maintains a low [Ca2+]i, steep gradient for Ca2+ influx and may facilitate the movement of Ca2+ away from points of entry. The neurons which are CaBP(-), deep, and closer to subiculum and in which N2 evokes hyperpolarization, on the other hand, may have a sustained elevation/accumulation of cytosolic Ca2+ which could activate K+ conductance, inhibit Ca2+ influx, and stabilize the membrane potential. These experiments provide a functional correlate for CaBP and suggest that it may have a significant role in Ca2+ homeostasis and the determination of selective neuronal vulnerability.

Animals↗
PubMed1995

Effects of acute caffeine ingestion and menopause on sulfate homeostasis in women.

Inorganic sulfate is a physiological anion which is utilized in the metabolism of both endogenous compounds and xenobiotics. Its homeostasis is maintained predominantly by facilitated reabsorptive processes in the kidneys. The objectives of the present investigation were to evaluate the effects of menopausal status and caffeine ingestion on the serum concentrations and clearance of inorganic sulfate. Thirty-nine women who were classified as premenopausal, postmenopausal with or without estrogen treatment, and postmenopausal with osteoporosis participated in the study. The women were studied on two separate occasions following the ingestion of a decaffeinated beverage to which 6 mg caffeine/kg lean body mass or no caffeine was added. All women were habitual caffeine users (mean ingestion of 588 mg caffeine per day) but abstained from all caffeine sources for 2 weeks prior to the control study day. Postmenopausal women with estrogen supplementation exhibited significantly lower sulfate serum concentrations (0.24 +/- 0.02 mM vs. 0.32 +/- 0.04 mM in premenopausal women, mean +/- SD, p < 0.05) and a decreased renal reabsorption of sulfate for the control (no caffeine) period. There was no difference in serum sulfate or sulfate reabsorption in estrogen supplemented postmenopausal women, compared with women not taking estrogen. Postmenopausal women with osteoporosis had significantly lower creatinine and sulfate clearances than postmenopausal women with estrogen supplementation which may be related to their older age, or factors related to the disease process. The 6 mg/kg dose of caffeine caused a diuresis, but no change in GFR, as indicated by urine volume and creatinine clearance values, respectively. Caffeine administration resulted in an increase in the sulfate excretion rate; there was no change in sulfate serum concentrations. The results of this investigation indicate that menopause results in decreased sulfate serum concentrations that may be the consequence of a decreased renal reabsorption of sulfate. Secondly, this investigation demonstrated that caffeine ingestion increases the urinary excretion of sulfate, an effect that may be related to the diuretic effect of caffeine or due to a caffeine-induced alteration in the renal reabsorption of sulfate.

Adult↗