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PubMed1981

Proton Fluxes Associated with Sugar Uptake in Vicia faba Leaf Tissues.

Vicia faba leaf fragments bring the pH of their incubation medium to about 4.7, whatever the initial pH value. At this pH, addition of 20 millimolar sucrose causes a transient (20 to 40 minutes) alkalinization (0.05 to 0.10 pH unit) of the medium. The alkalinization is not observed in the presence of p-chloromercuribenzenesulfonic acid which blocks the sucrose carrier involved in phloem loading without affecting the ATPase (Delrot, Despeghel, Bonnemain 1980 Planta 149: 144-148). Addition of 20 millimolar glucose, fructose, or 3-O-methylglucose induces weaker alkalinization than sucrose. Sequential additions of sugars show that: (a) sucrose- and hexose-induced proton fluxes are nearly saturated at 20 millimolar sugar (b) there is no competition between sucrose and hexoses for inducing proton influxes whereas (c) glucose and 3-O-methylglucose are competing for a common system.Autoradiographs performed under the conditions used for the observation of proton fluxes show a slight accumulation of [(14)C]sucrose into the veins within 2 minutes of uptake, whereas [(14)C]glucose and 3-O-methyl [(14)C]glucose are localized in the mesophyll. These data support the proton-sucrose cotransport hypothesis of phloem loading and show that mesophyll cells are able to take up hexoses by symport with protons.The apparent sucrose/proton stoichiometry is constant below 5 millimolar sucrose (about 1.9 sucrose per proton taken up) but increases up to 6 sucrose per proton, between 5 and 15 millimolar sucrose. This confirms our previous study indicating that above 5 millimolar sucrose, a system which exhibits little pH dependence is involved in the uptake.Simultaneous measurements of H(+) and K(+) fluxes indicate that sucrose uptake is accompanied by a reduction of K(+) uptake rate, thus suggesting that sucrose and K(+) uptake can compete in dissipating the protonmotive force.

Journal Article↗

PubMed1985

Preparation of Membrane Vesicles Enriched in ATP-Dependent Proton Transport from Suspension Cultures of Tomato Cells.

Membranes enriched in ATP-dependent proton transport were prepared from suspension cultures of tomato cells (Lycopersicon esculentum Mill cv VF36). Suspension cultures were a source of large quantities of membranes from rapidly growing, undifferentiated cells. Proton transport activity was assayed as quench of acridine orange fluorescence. The activity of the proton translocating ATPase and of several other membrane enzymes was measured as a function of the cell culture cycle. The relative distribution of the enzymes between the 3,000, 10,000, and 100,000g pellets remained the same throughout the cell culture cycle, but yield of total activity and activity per gram fresh weight with time had a unique profile for each enzyme tested. Maximal yield of the proton translocating ATPase activity was obtained from cells in the middle logarithmic phase of growth, and from 50 to 90% of the activity was found in the 10,000g pellet. The proton translocating ATPase activity was separable from NADPH cytochrome c reductase and cytochrome c oxidase on a sucrose gradient. Proton transport activity had a broad pH optimum (7.0-8.0), was stimulated by KCl with a K(m) of 5 to 10 millimolar, stimulation being due to the anion, Cl(-), and not the cation, K(+), and was not inhibited by vanadate, but was inhibited by NO(3) (-). The activity is tentatively identified as the tonoplast ATPase.

Journal Article↗

PubMed1989

Intact Chloroplasts Show Ca-Gated Switching between Localized and Delocalized Proton Gradient Energy Coupling (ATP Formation).

Intact chloroplasts were compared to isolated thylakoids as to whether storage of the organelle in high KCl medium caused the energy coupling reactions to show a delocalized or a localized proton gradient energy coupling response. With isolated thylakoids, the occurrence of one or the other energy coupling mode can be reversibly controlled by the concentration of mono- and divalent cations used for the thylakoid storage media. Calcium was shown to be the key ion and previous evidence suggested a Ca(2+)-controlled gating of H(+) fluxes in the thylakoid membrane system (G Chiang, RA Dilley [1987] Biochemistry 26: 4911-4916). Isolated, intact chloroplasts, which retained the outer envelope membranes during the 30 min or longer storage treatments in various concentrations of KCl and CaCl(2) (with sorbitol to maintain iso-osmotic conditions), were osmotically burst in a reaction cuvette and within 3 minutes were assayed for either a localized or a delocalized proton gradient energy coupling (ATP formation) mode. The intact chloroplast system was analogous to isolated thylakoids, with regard to the effects of KCl and CaCl(2) on the energy coupling mode. For example, adding 100 millimolar KCl to the intact organelle storage medium resulted in the subsequent ATP formation assay showing delocalized proton gradient coupling just as with isolated thylakoids. Adding 5 millimolar CaCl(2) to the 100 millimolar KCl storage medium resulted in a localized proton gradient coupling mode. Suspending thylakoids in stromal material previously isolated from intact chloroplast preparations and testing the energy coupling response showed that the stromal milieu has enough Ca(2+) to cause the localized coupling response even though there was about 80 millimolar K(+) in the intact chloroplasts used in this study (determined by atomic absorption spectrophotometry). Extrapolating the intact chloroplast data to the whole leaf level, we suggest that proton gradient energy coupling is normally of the localized mode, but under certain conditions it could be either localized or delocalized, depending on factors that affect the putative Ca(2+)-regulated proton flux gating function.

Journal Article↗

PubMed1991

Comparison of Temperature Dependency of Tonoplast Proton Translocation between Plants Sensitive and Insensitive to Chilling.

Proton transport activities in isolated tonoplast vesicles were measured as quenching of fluorescence of acridine orange. A marked difference in the temperature dependency of two types of tonoplast proton transports, i.e. ATP- and pyrophosphate-driven, was observed between two leguminous plants sensitive (mung bean, Vigna radiata [L.] Wilczek) and insensitive (pea, Pisum sativum L.) to chilling. In tonoplast vesicles isolated from hypcotyls of mung bean seedlings that were germinated for 3.5 days at 26 degrees C in the dark, the total amount of fluorescence quenching at the steady state in both types of proton pumps, as a measurement of the inside-acidic pH gradient across the membrane vesicles, was markedly suppressed under temperatures below 10 degrees C. In tonoplast vesicles isolated from epicotyls of pea seedlings, which were germinated for 7 days at 18 degrees to 23 degrees C in the dark, no suppression occurred in the formations of the pH gradient in either type of proton pump, even at 0 degrees C. The cause of the low temperature-induced suppression of the proton pumps in mung bean tonoplasts seems to be not an increased permeability of the membrane vesicles to protons or accompanying anions and cations, but instead a marked inhibition in the catalytic activity of both enzymes under low temperatures.

Journal Article↗

PubMed1980

Unified mechanism for proton-transfer reactions affecting the catalytic activity of liver alcohol dehydrogenase.

The effect of pH on substrate binding to liver alcohol dehydrogenase has been examined over the pH range 6--10 by transient-state and steady-state kinetic methods. The results provide evidence that there is no significant effect of pH on benzaldehyde binding to the enzyme. Benzyl alcohol association to the binary enzyme . NAD+ complex requires protonation of an ionizing group with a pKa of 7.6 in the binary complex. Substrate dissociation from the enzyme . NAD+ . alcohol complex is regulated by an ionizing group with a pKa of 6.6 (6.4) in the complex formed with naphthyl alcohol (benzyl alcohol). Alcohol desorption from the ternary complex occurs exclusively when the ionizing groups is in the protonated form. A reaction mechanism is proposed which accounts for all major effects of pH on liver alcohol dehydrogenase catalysis over the investigated pH range. The reactivity of the enzyme . NAD+ (enzyme . NAD+ . alcohol) complex is suggested to be regulated by the ionization state of a water (alcohol) molecule bound at the catalytic zinc atom of the enzyme. Zinc-bound water does not function as a binding site for substrates or as a mediator of catalytic proton transfer from substrate to solution at the binary-complex level. Catalytic proton transfer takes place at the ternary-complex level, probably through an alcohol/alcoholate ion interconversion of the enzyme-bound substrate. This proton transfer step can be envisaged to serve the purpose of facilitating hydride transfer during alcohol oxidation and alcohol desorption during aldehyde reduction. The kinetics of proton uptake/release during naphthaldehyde reduction at pH 6 are shown to be consistent with the proposed mechanism of enzyme action.

Alcohol Oxidoreductases↗

PubMed1980

Optical study of the light-induced protonation changes associated with the metarhodopson II intermediate in rod-outer-segment membranes.

The kinetics of the protonation changes and of the formation of the metarhodopsin II intermediate are measured in the presence of the pH indicator dye bromocresol purple after two consecutive flashes on the same suspension of right-side-out vesicles from cattle rod-outer-segment membranes. A rapid proton binding followed by partial proton release is observed. The formation of metarhodopsin II is found to be biphasic. The rapid phase of metarhodopsin II formation is slightly faster than the proton binding, and the kinetics of the slow phase are similar to that of the proton release. The protein groups which are protonated and deprotonated are shown to be situated on the outside of the vesicles. These results provide evidence that a structural change of the protein involving pK changes occurs without spectral modification before the formation of metarhodopsin III (half-time of the order of seconds).

Animals↗

PubMed2005

Sequential proton transfer through water bridges in acid-base reactions.

The proton transfer mechanism between aqueous Brønsted acids and bases, forming an encounter pair, has been studied in real time with ultrafast infrared spectroscopy. The transient intermediacy of a hydrated proton, formed by ultrafast dissociation from an optically triggered photoacid proton donor ROH, is implicated by the appearance of an infrared absorption marker band before protonation of the base, B-. Thus, proton exchange between an acid and a base in aqueous solution is shown to proceed by a sequential, von Grotthuss-type, proton-hopping mechanism through water bridges. The spectra suggest a hydronium cation H3O+ structure for the intermediate, stabilized in the Eigen configuration in the ionic complex RO-...H3O+...B-.

Journal Article↗

PubMed2004

Long-term calorie restriction reduces proton leak and hydrogen peroxide production in liver mitochondria.

Calorie restriction (CR) without malnutrition increases maximal life span in diverse species. It has been proposed that reduction in energy expenditure and reactive oxygen species (ROS) production could be a mechanism for life span extension with CR. As a step toward testing this theory, mitochondrial proton leak, H2O2 production, and markers of oxidative stress were measured in liver from FBNF1 rats fed control or 40% CR diets for 12 or 18 mo. CR was initiated at 6 mo of age. Proton leak kinetics curves, generated from simultaneous measures of oxygen consumption and membrane potential, indicated a decrease in proton leak after 18 mo of CR, while only a trend toward a proton leak decrease was observed after 12 mo. Significant shifts in phosphorylation and substrate oxidation curves also occurred with CR; however, these changes occurred in concert with the proton leak changes. Metabolic control analysis indicated no difference in the overall pattern of control of the oxidative phosphorylation system between control and CR animals. At 12 mo, no significant differences were observed between groups for H2O2 production or markers of oxidative stress. However, at 18 mo, protein carbonyl content was lower in CR animals, as was H2O2 production when mitochondria were respiring on either succinate alone or pyruvate plus malate in the presence of rotenone. These results indicate that long-term CR lowers mitochondrial proton leak and H2O2 production, and this is consistent with the idea that CR may act by decreasing energy expenditure and ROS production.

Animals↗

PubMed1990

Proton-gated sodium current in parasympathetic ganglion cells of frog heart.

1. The proton-gated current was investigated in whole-cell configuration of the neurons isolated from bullfrog heart parasympathetic ganglia with the use of the "concentration-clamp" technique, which combines intracellular perfusion and extremely rapid exchange of external solution within 1-2 ms, under a single-electrode voltage-clamp condition. 2. In all isolated neurons, a "step" decrease in extracellular pH (pHo) induced a transient inward current that was followed by a complete inactivation within 1 s. 3. The proton-gated current increased in a sigmoidal fashion as pHo decreased. In the external solution containing 2 mM Ca2+, the threshold of current activation was at pHo 7.4, and the maximum response appeared at pHo 6.5-5.5. The dissociation constant (Kd) and Hill coefficient were 7.1 and 3.2, respectively. 4. The proton-gated current was reduced by decreasing the extracellular Na+ concentration. In the absence of K+, the current produced by reduced extracellular pH reversed at the Na+ equilibrium potential (ENa), indicating that the current was carried by Na+. 5. Kinetics of both the activation and inactivation phases of proton-induced current were single exponential. The time constants of activation (tau a) and inactivation (tau i) had no potential dependence but decreased slightly by decreasing pHo. 6. In the inactivation curve of the proton-induced current obtained by decreasing pHo from various conditioning pHos to 6.5, the half-maximum inactivation occurred at pHo 7.75. 7. The proton-gated current was suppressed as the extracellular Ca2+ concentration [( Ca2+]o) increased from 0.1 to 10 mM, and the half inhibition occurred at greater than 10 mM [Ca2+]o.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1997

Lactate-proton cotransport in skeletal muscle.

Skeletal muscle and most other tissues possess a membrane transport system mediating a coupled lactate and H+ translocation. Muscle possesses several lactate-proton transporter isoforms of which two have been cloned; however, the main isoform remains to be identified. The isoforms may have different properties and functional roles, but these have not been specifically characterized. The distribution of lactate-proton transport capacity in skeletal muscle is fiber type dependent, with a higher capacity in slow-twitch fibers compared with fast-twitch fibers. During intense muscle activity and in the recovery period, the lactate and H+ effluxes are mainly mediated by the lactate-proton transporter, which reduces the accumulation of lactate in muscle as well as the drop in internal pH suggested to be involved in muscle fatigue. Thus the lactate-proton transporter is of functional importance for pH regulation in association with muscle activity. This carrier is also important for lactate uptake into resting muscle and other tissues; therefore, the carrier distribution is important for the fate of lactate in the body. In addition, the capacity of the lactate-proton transporter can be increased by intense training and is reduced by inactivity; thus the lactate-proton transporter can undergo adaptive changes.

Animals↗

PubMed2006

Combined proton beam radiotherapy and transpupillary thermotherapy for large uveal melanomas: a randomized study of 151 patients.

INTRODUCTION: Exudation from the tumour scar and glaucoma can be major problems after proton beam irradiation of uveal melanoma and can sometimes lead to secondary enucleation. We conducted a randomized study to determine whether systematic transpupillary thermotherapy (TTT) after proton beam radiotherapy could have a beneficial effect. PATIENTS AND METHOD: Between February 1999 and April 2003, all the patients treated by proton beam radiotherapy for uveal melanomas >/=7 mm thick or >/=15 mm in diameter were included in this study after giving their informed consent. One half of the patients received proton beam radiotherapy alone (60 Gy in 4 fractions) and the other half received the same dose of proton beam radiotherapy followed by TTT at 1, 6 and 12 months. All the information concerning the initial tumour parameters, treatments and follow-up was recorded and a statistical analysis was performed. RESULTS: We randomized 151 patients. The median follow-up was 38 months. The 2 groups of patients were similar in terms of age, gender and tumour characteristics. The patients treated with TTT showed a greater reduction of tumour thickness (p = 0.06), less retinal detachment at the latest follow-up (p = 0.14) and a lower secondary enucleation rate (p = 0.02). DISCUSSION: The present study is the first randomized analysis to demonstrate a significant decrease in the secondary enucleation rate in patients treated with TTT after proton beam radiotherapy. Further studies should be performed to determine whether TTT could be beneficial to smaller tumours and to define its optimal dose.

Adult↗

PubMed1989

Sodium-lithium exchange and sodium-proton exchange are mediated by the same transport system in sarcolemmal vesicles from bovine superior mesenteric artery.

Several laboratories have reported that Na+-Li+ countertransport activities are increased in red blood cells from patients with essential hypertension. It has been proposed that the activity of this red blood cell transport system might reflect the activity of a similar system in vascular smooth muscle. We previously demonstrated Na+-Li+ exchange in sarcolemmal vesicles from canine artery and proposed that this transport function might be mediated by the Na+-H+ exchanger. In the present studies, however, we were unable to demonstrate Na+-Li+ countertransport in canine red blood cells. Since bovine red blood cells have a vigorous Na+-Li+ exchanger and we previously demonstrated Na+-H+ exchange in sarcolemmal vesicles from bovine artery, we wished to determine whether bovine sarcolemmal vesicles mediate Na+-Li+ exchange and whether this transport function is mediated via the Na+-H+ exchanger. We found that an outwardly directed proton or Li+ gradient stimulated 22Na+ uptake in sarcolemmal vesicles from bovine superior mesenteric artery. Li+ gradient-stimulated Na+ uptake was not due to electrical coupling between the two ions, was not affected by a change in membrane potential, and could not be explained by the parallel operation of Li+-H+ and Na+-H+ exchange. External Li+ inhibited proton gradient-stimulated Na+ uptake, and external protons inhibited Li+ gradient-stimulated Na+ uptake. Na+ efflux from vesicles was stimulated by inwardly directed gradients for Li+ or protons, and these effects were not additive. Proton efflux from vesicles was stimulated by inwardly directed gradients for Na+ or Li+, and these effects were not additive. Finally, Na+-H+ exchange and Na+-Li+ exchange in sarcolemmal vesicles were inhibited by 5-(N-ethyl-N-isopropyl)amiloride in an identical dose-dependent manner. In conclusion, Na+-Li+ countertransport could not be demonstrated in canine red blood cells, but as is the case with bovine red blood cells, sarcolemmal vesicles from bovine artery mediate Na+-Li+ countertransport. This transport function and sarcolemmal Na+-H+ exchange are mediated via a single 5-(N-ethyl-N-isopropyl)amiloride-sensitive cation exchanger with affinity for Na+, Li+, and protons. The cow, as opposed to the dog, may be a good animal model to test whether the activity of red blood cell Na+-Li+ countertransport is predictive of the activity of Na+-Li+ (and Na+-H+) exchange in vascular smooth muscle.

Amiloride↗

PubMed1993

Hypertensive sodium-proton exchanger phenotype persists in immortalized lymphoblasts from essential hypertensive patients. A cell culture model for human hypertension.

An enhancement of sodium-proton exchange activity is a frequently observed ion transport abnormality in essential hypertension. The cellular basis for this has not yet been elucidated. Due to the lack of a specific cell culture system it has been impossible to distinguish between intrinsic cellular abnormalities and influences exerted by the hypertensive neurohumoral milieu. Using Epstein-Barr virus we have immortalized lymphocytes from controls and from patients with essential hypertension that exhibited enhanced sodium-proton exchanger activity. Sodium-proton exchanger activity was determined in cells loaded with the fluorescent cytosolic pH indicator 2'7'-biscarboxyethyl-5,6-carboxyfluorescein acetoxymethylester (BCECF) after pretreatment with 250 nM of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate for 10 min. Cell lines from hypertensive patients displayed higher Vmax values of sodium-proton exchange than those from normotensive controls (129.6 +/- 30.0 vs. 77.1 +/- 13.2 mmol H+/min.; P < 0.001). Hill coefficients for H+ were distinctly lower in hypertension compared to normotension (1.12 +/- 0.12 vs. 1.50 +/- 0.14; P < 0.0001). The enhanced antiporter activity in cell lines from hypertensive patients was not accompanied by a corresponding increase in steady-state NHE-1 mRNA transcript levels, which argues against overexpression of antiporter protein in hypertension. The cells from hypertensive patients with high sodium-proton exchange activity proliferated distinctly faster than those from normotensive controls. These human cell lines represent a novel model to study the mutual interaction between sodium-proton exchange and cell proliferation, and may provide insights into the alterations in ion transport observed in a group of patients with essential hypertension.

Adult↗

PubMed1991

Proton MR spectroscopy in multiple sclerosis: value in establishing diagnosis, monitoring progression, and evaluating therapy.

MR imaging is currently the technique of choice for evaluating brain lesions in patients with multiple sclerosis (MS). In addition to MR imaging, proton MR spectroscopy has shown potential in diagnosing MS and monitoring the progression of treatment. Spatially localized proton spectroscopy has been used to evaluate changes in choline, creatine, N-acetyl aspartate (NAA), lipids, and lactate in MS patients and in animal models of MS. The main spectroscopic findings are a decrease in the NAA:creatine ratio and an increase in the choline:creatine ratio in brain regions that include plaques defined by MR imaging. Proton MR spectroscopy along with MR imaging may be helpful in distinguishing those early lesions that might respond to therapy from late irreversible lesions. Preliminary evidence suggests that although the proton spectra acquired from patients with various brain diseases are similar (high choline, low NAA), there are differences in other resonances (lipids, lactate, glutamate, inositol) that could potentially help in diagnosing MS. Changes in proton metabolites potentially can be used to differentiate between the different stages of the MS lesion (hyperacute and edematous lesions, demyelinated lesions, and subacute to chronic plaques). It is hypothesized that successful treatment of demyelination and neuronal damage will be accompanied by changes in the proton spectrum (high choline:creatine ratio will lower to normal values and low NAA:creatine values will rise to normal values).

Animals↗

PubMed1987

Equipment for radiation surgery using narrow 185 MeV proton beams. Dosimetry and design.

The purpose of the present work was to optimize and standardize irradiation conditions and dosimetry methods in order to investigate the prerequisites for the routine use of narrow high energy proton beams for cerebral radiation surgery. Particular importance was laid on the design of the arrangements for defining and controlling the path of the beam in the laboratory in view of the desirability of working with well-defined parallel beams containing a minimal contribution of scattered and secondary radiation. At the same time it was intended that this apparatus should be used to adjust the beam reproducibly onto an ideal beam path prior to each irradiation session. It was also considered desirable to be able to supervise the centering and the structure of the beam during the irradiations in view of the variations which can arise due to varying running conditions in the synchrocyclotron. The beam was collimated and led to the place where the irradiations were to be performed, 25 metres from the synchrocyclotron, with a system of focusing quadrupole magnets and bending magnets. Final collimation of the beam penetrating the object was arranged with a system of accurately aligned cylindrical and plane-parallel metal apertures. The energy of the protons in the beam was 185 +/- 0.2 MeV and the maximum total fluence was 5 X 10(10) protons/s. A method of 11C activation dosimetry was developed with which an absolute determination of the fluence and the dose in the proton beam could be made with good accuracy. These determinations were performed by irradiating small polystyrene cylinders placed along the beam axis at the isocentre. The activity induced in the cylinders by the protons was measured in a well-type crystal detector. The efficiency of the detector for the detection of annihilation photons was determined before each measurement by means of calibration with standardized activities of 22Na and 60Co. The overall uncertainty in the dose determinations using 11C activation dosimetry was +/- 8 per cent. Monitoring of the dose during irradiation was performed with an ionization chamber. Since it was most important to minimize the scattering of the protons, this chamber was designed as a 'free air chamber' with the electrodes parallel to the beam. The chamber could not be used for absolute measurements, however, since there was a contribution to the ionization in the chamber from scattered protons and secondary radiation from the walls of the collimator defining the cross section of the ionization volume.(ABSTRACT TRUNCATED AT 400 WORDS)

Energy Transfer↗

PubMed1990

Assignment of proton endor resonances of nitroxyl spin-labels in frozen solution.

Spin-label nitroxyl derivatives of tetramethylpyrroline and tetramethylpyrrolidine in frozen solutions of perdeuterated methanol have been characterized by electron nucleus double resonance (ENDOR spectroscopy). With use of selectively deuterated derivatives of 2,2,5,5-tetramethylpyrroline-1-oxyl-3-carboxamide, proton ENDOR resonance features have been assigned to the vinylic proton in the five membered pyrrolinyl ring and to the methyl groups. The ENDOR resonance features were analyzed on the basis of their dependence on H0. Two pairs of resonance features were assigned to the vinylic proton and were shown to correspond to parallel and perpendicular hyperfine coupling (hfc) components. Six pairs of resonance features were ascribed to the methyl groups. The proton ENDOR spectra of the 3-carboxylic acid spin-label derivatives of tetramethylpyrroline and of tetramethylpyrrolidine compounds exhibited comparable features with nearly identical line splittings. From the observed ENDOR splittings, we have estimated the isotropic hfc component of the vinylic proton in 2,2,5,5-tetramethylpyrroline-1-oxyl-3-carboxamide to be -1.81 +/- 0.04 MHz in frozen methanol. On the basis of the anisotropic dipolar hfc components, the electron-to-vinylic proton distance is estimated as 3.78 +/- 0.01 A, in excellent agreement with that of 3.79 A calculated from X-ray defined coordinates.

Cyclic N-Oxides↗

PubMed1995

Measurement of serum isopropanol and the acetone metabolite by proton nuclear magnetic resonance: application to pharmacokinetic evaluation in a simulated overdose model.

The purpose of this investigation was to 1) compare the performance of proton nuclear magnetic resonance spectroscopy to gas chromatography head-space analysis in the measurement of serum isopropanol and its metabolite, acetone, obtained during a simulated overdose, and 2) compare pharmacokinetic parameters obtained using the two analytical techniques. Three healthy volunteers ingested 0.6 mL/kg of 70% isopropanol and blood samples were obtained at baseline, 0.16, 0.33, 0.66, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, and 24.0 hours post-ingestion. Resulting sera were analyzed by gas chromatography head-space analysis and proton nuclear magnetic resonance spectroscopy for determination of isopropanol and acetone concentrations. A correlation between concentrations quantitated by gas chromatography head-space analysis versus proton nuclear magnetic resonance spectroscopy was determined using linear regression. Pharmacokinetic disposition parameters were determined from serum concentration-time data and compared using analysis of variance. For isopropanol, the linear regression equation which describes the relationship between gas chromatography head-space analysis and proton nuclear magnetic resonance spectroscopy was y = 1.041x - 2.180 (r2 = 0.995, p < 0.0001); for acetone, y = 1.022x - 0.946 (r2 = 0.984, p < 0.0001). Pharmacokinetic disposition parameters derived from the two analytical methods were comparable. Proton nuclear magnetic resonance spectroscopy can be used to rapidly quantitate serum isopropanol and acetone concentrations in the same sample when gas chromatography head-space analysis is unavailable. Also, proton nuclear magnetic resonance spectroscopy can be used to follow serial serum concentrations during an ingestion for the purpose of pharmacokinetic analysis.

1-Propanol↗

PubMed1999

Proton chemical shift imaging of the hippocampus in patients with complex partial seizures.

BACKGROUND: Cerebral metabolites can be evaluated non-invasively using in vivo proton magnetic resonance spectroscopy (MRS). Decreased N-acetylaspartate (NAA) and increased choline-containing compounds (Cho) and creatine-phosphocreatine (Cr) have been found in the hippocampus of patients with complex partial seizures (CPS). METHODS: We prospectively studied hippocampal proton MRS of 10 patients with CPS and 12 control subjects by using the chemical shift imaging (CSI) technique. The spectral data were analyzed in terms of the ratio between the integral peak area of NAA and that of (Cho + Cr). RESULTS: Compared with the control group, patients with CPS showed a significantly lower NAA/(Cho + Cr) ratio, both in the anterior and posterior hippocampus (p value = 0.001 and 0.002, respectively). Metabolic abnormalities of the hippocampus were detected using proton CSI in all the patients with normal MRI results (4 patients) and those with normal EEG results (3 patients). Lateralizations using proton CSI were obtained in all the 10 patients in this study, including concordant lateralization in the 6 patients with MRI-detectable abnormalities. CONCLUSION: The hippocampal abnormalities in patients with CPS can be detected early using proton CSI than using MRI or surface EEG. Lateralization of the seizure focus using proton CSI is possible, but further correlation with the surgical outcome in a larger study group is necessary.

Adolescent↗