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Cell inactivation and double-strand breaks: the role of core ionizations, as probed by ultrasoft X rays.

The large RBE (approximately 7) measured for the killing of Chinese hamster V79 cells by 340 eV ultrasoft X rays, which preferentially ionize the K shell of carbon atoms (Hervé du Penhoat et al., Radiat. Res. 151, 649-658, 1999), was used to investigate the location of sensitive sites for cell inactivation and the physical modes of action of radiation. The enhancement of the RBE above the carbon K-shell edge either may indicate a high intrinsic efficiency of carbon K-shell ionizations (due, for example, to a specific physical or chemical effect) or may be related to the preferential localization of these ionizations on the DNA. The second interpretation would indicate a strong local (within 3 nm) action of K-shell ionizations and consequently the importance of a direct mechanism for radiation lethality (without excluding an action in conjunction with an indirect component). To distinguish between these two hypotheses, the efficiencies of core ionizations in DNA atoms (phosphorus L-shell, carbon K-shell, and oxygen K-shell ionizations) to induce damages were investigated by measuring their capacities to produce DNA double-strand breaks (DSBs). The effect of photoionizations in isolated DNA was studied using pBS plasmids in a partially hydrated state. No enhancement of the efficiency of DSB induction by carbon K-shell ionizations compared to oxygen K-shell ionizations was found, supporting the hypothesis that it is the localization of these carbon K-shell events on DNA which gives to the 340 eV photons their high killing efficiency. In agreement with this interpretation, cell inactivation and DSB induction, which do not appear to be correlated when expressed in terms of yields per unit dose in the sample, exhibit a rather good correlation when expressed in terms of efficiencies per core event in the DNA. These results suggest that core ionizations in DNA, through core-hole relaxation in conjunction with localized effects of spatially correlated secondary and Auger electrons, may be the major critical events for cell inactivation, and that the resulting DSBs (or a constant fraction of these DSBs) may be a major class of unrepairable lesions.

Animals↗

Incidence and prognostic value of low plasma ionized calcium concentration in cats with acute pancreatitis: 46 cases (1996-1998).

OBJECTIVE: To determine the incidence and prognostic significance of low plasma ionized calcium concentration in cats with clinical signs of acute pancreatitis (AP). DESIGN: Retrospective study. ANIMALS: 46 cats with AP and 92 control cats with nonpancreatic diseases. PROCEDURE: Medical records were reviewed, and results of clinicopathologic testing, including plasma ionized and total calcium concentrations, acid-base values, and electrolyte concentrations, were recorded. Cats with AP were grouped on the basis of outcome (survived vs died or were euthanatized), and plasma ionized calcium concentrations, acid-base values, and electrolyte concentrations were compared between groups. RESULTS: Serum total calcium concentration was low in 19 (41%) cats with AP, and plasma ionized calcium concentration was low in 28 (61%). Cats with AP had a significantly lower median plasma ionized calcium concentration (1.07 mmol/L) than did control cats (1.12 mmol/L). Nineteen (41%) cats with AP died or were euthanatized; these cats had a significantly lower median plasma ionized calcium concentration (1.00 mmol/L) than did cats that survived (1.12 mmol/L). Ten of the 13 cats with AP that had plasma ionized calcium concentrations < or = 1.00 mmol/L died or were euthanatized. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that low plasma ionized calcium concentration is common in cats with AP and is associated with a poorer outcome. A grave prognosis and aggressive medical treatment are warranted for cats with AP that have a plasma ionized calcium concentration < or = 1.00 mmol/L.

Acid-Base Equilibrium↗

Total and ionized calcium in parturient dairy cows and their calves.

Ionized Ca in blood, standard ionized Ca, pH, and total Ca in plasma were measured in 33 Holstein-Friesian dairy cows and their calves. Blood was taken immediately postpartum and at 12, 24, 48, and 72 h after calving. Cows and their calves were grouped according to parity. Concentrations of ionized and total Ca consistently were higher in neonates than in the dams. Parity differences were significant for maternal ionized Ca and total Ca. However, parity was not significant for ionized or total Ca in the blood of corresponding calves. Changes in ionized Ca concentration in calves of first lactation cows largely were attributable to perinatal acidosis. In contrast to total Ca concentrations, the ionized Ca and standard ionized Ca concentrations in dams and calves were relatively stable throughout the study, suggesting that ionized Ca concentration in blood is indicative of the Ca status of the dairy animal.

Animals↗

Foscarnet-induced changes in plasma concentrations of total and ionized calcium and magnesium in HIV-positive patients.

The time course and magnitude of foscarnet-induced changes in plasma concentrations of total and ionized calcium and magnesium were investigated in 13 male HIV-positive patients who had no active cytomegalovirus-associated disease. The patients had a mean age of 36 years (range 25-49 years) and a mean CD4 cell count of 550 cells/mm3 (range 130-1280 cells/mm3). Peak (mean +/- SD) plasma concentrations of foscarnet (0.89+/-0.10 mmol/l) were seen at the end of the period of drug infusion (90 mg/kg of foscarnet was infused over 2 hours) and declined with a terminal half-life of 5.7+/-0.7 hours. Plasma concentrations of total calcium declined over an 8-hour period, with the lowest concentration occurring after 4 hours (baseline: 2.29+/-0.09 mmol/l; lowest: 2.18+/-0.07 mmol/l; P < 0.001). By contrast, the lowest plasma concentration of ionized calcium occurred after 2 hours (baseline: 1.25+/-0.04 mmol/l; lowest: 0.99+/-0.05 mmol/l; P < 0.001), before gradually recovering to baseline levels over the next 10 hours. The mean maximal decrease in total calcium was 0.11+/-0.06 mmol/l, compared with 0.26+/-0.04 mmol/l for ionized calcium (P < 0.001). Plasma concentrations of total magnesium declined from 0.79+/-0.06 mmol/l (baseline) to 0.74+/-0.04 mmol/l (P < 0.05) after 4 hours and remained at this level after 8 hours. However, plasma concentrations of ionized magnesium fell steeply from 0.56+/-0.03 mmol/l to 0.39+/-0.03 mmol/l at 2 hours (P < 0.001), followed by a gradual recovery over the next 10 hours. The mean maximal decrease in total magnesium was 0.05+/-0.08 mmol/l, compared with 0.18+/-0.03 mmol/l (P < 0.001) for ionized magnesium. In summary, we found that foscarnet-induced changes in the plasma concentrations of total calcium and magnesium were dissociated from the corresponding changes in ionized calcium and magnesium. The maximal decreases in the plasma concentrations of total calcium and magnesium were smaller in magnitude and occurred much later than did the changes in ionized calcium and magnesium. The relative changes in the plasma concentration of ionized magnesium were greater than those of ionized calcium, indicating that foscarnet binds preferentially to the magnesium ion.

Adult↗

[Ionized calcium and magnesium as interdependent variables in blood pressure origin in healthy adolescents].

INTRODUCTION: Growing evidence indicates that diet divalent cations--ionized calcium (Ca) and magnesium (Mg)--and MN blood group polymorphism may be associated with essential arterial hypertension. OBJECTIVES: To assess a possible relationship between serum ionized Ca and Mg and MN blood group polymorphism with blood pressure (BP) and body mass index (BMI). POPULATION AND METHODS: The study group consisted of 173 healthy adolescents, 96 female (55.5%) and 77 male (44.5%), with mean age of 13.0 +/- 1.7 years. Serum ionized Ca and Mg were determined by standardized methods based on detection by specific electrodes. MN blood group polymorphism was determined by immunoaglutination of erythrocytes with monoclonal antibodies. BP was evaluated based on AHA recommendations. BMI was calculated as weight divided by squared height (Kg/m2). The statistical method used was the Pearson correlation. RESULTS: In this population no significant correlation was found from serum ionized Ca (mean: 1.07 +/- 0.06 mmol/L) and Mg (mean: 1.15 +/- 0.97 mmol/L) with systolic BP (mean: 113.1 +/- 10.7 mmHg) and diastolic BP (mean: 66.1 +/- 10.1 mmHg). In contrast there was an inverse correlation between the quotient ionized Mg/ionized Ca (0.45 +/- 0.05) and diastolic BP (p = 0.029; r = -0.381). A positive correlation was found between BMI (20.57 +/- 3.24 Kg/m2) and systolic BP (p = 0.007; r = 0.24) and diastolic BP (p = 0.016; r = 0.22). No correlation was found between ionized Ca, ionized Mg and BP with MN blood group polymorphism. CONCLUSIONS: In this population of healthy adolescents there was a dependence between diastolic BP and serum ionized Mg/ionized Ca. There was no interindividual BP and ionized Ca and Mg variation dependent from genetic variation.

Adolescent↗

[2+1, 1+1 and 1+1+1 multiphoton resonant ionization of manganese atom].

Resonance ionization spectroscopy (RIS) is an important technique for trace analyses. In the present paper, based on the population rate equations, "2+1", "1+1" and "1+1+1" multiphoton resonant ionization processes of Mn atom are studied by computer simulation. The phenomena and the threshold condition of saturated excitation and ionization processes are discussed. The threshold laser intensities for saturated ionization of Mn atom with different RIS schemes are calculated. With the typical Q-switched laser duration of 10 ns, the obtained saturation threshold laser intensity for the ionization steps in all the resonant ionization processes of Mn is about 10(8) W x cm(-2) with the exception of the "1+ 1" resonant ionization of Mn which is 3 orders of magnitude lower. The obtained threshold laser intensity for the saturated excitation steps is about 10(2)-10(3) W x cm(-2) in "1+1" and "1+1+1" ionization processes. It is also shown that the threshold laser intensity required for saturated excitation and ionization processes turns smaller with the laser duration prolonged.

English Abstract↗

Comparative studies of total and ionized serum calcium values in normal subjects and patients with renal disorders.

One hundred fourteen nondialyzed azotemic adult patients (creatinine connentration 1.2 to 17.6 mg/dl), 78 stable renal transplant recipients (creatinine less than 1.9 mg/dl), 50 patients with idiopathic nephrolithiasis, 36 patients with surgically proven primary hyperparathyroidism, and 62 normal volunteers were studied with simultaneous serum ionized calcium, total calcium, parathyroid hormone (PTH), phosphorus, and creatinine measurements. Ionized calcium could not be reliably predicted from total calcium. Although in all patient groups values for serum ionized calcium correlated significantly with those for total calcium, the scatter around the regression line was such that a direct interpretation was not precise. With respect to reference values, significant differnces were found between ionized and total calcium in 26% of all studied patients. When compared with total serum calcium, ionized calcium appeared to be a more sensitive index of calcium metabolism. All correlations with ionized calcium had a higher r value compared with those with total serum calcium. Two findings were particularly rewarding. In patients with chronic renal failure, serum PTH showed a negative correlation with serum ionized calcium, indicating that the latter may have been largely responsible for the secondary increase in PTH; in patients after a successful transplant, serum PTH showed a positive correlation with serum ionized calcium, indicating that in the presence of normal kidney function the previously hypertrophied parathyroid glands may be largely responsible for the daily study of a large number of specimens, determinations of serum ionized calcium should be encouraged in all patients suspected of having abnormalities of renal calcium metabolism.

Adult↗

Two-photon ionization thresholds of matrix-assisted laser desorption/ionization matrix clusters.

Direct two-photon ionization of the matrix has been considered a likely primary ionization mechanism in matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. This mechanism requires that the vertical ionization threshold of matrix materials be below twice the laser photon energy. Because dimers and larger aggregates may be numerous in the early stages of the MALDI plume expansion, their ionization thresholds are important as well. We have used two-color two-photon ionization to determine the ionization thresholds of jet cooled clusters of an important matrix, 2,5-dihydroxy benzoic acid (DHB), and mixed clusters with the thermal decomposition product of DHB, hydroquinone. The thresholds of the clusters were reduced by only a few tenths of an eV compared to the monomers, to an apparent limit of 7.82 eV for pure DHB clusters. None of the investigated clusters can be directly ionized by two nitrogen laser photons (7.36 eV), and the ionization efficiency at the thresholds is low.

Biopolymers↗

Effect of air ionization on heart rate and perceived exertion during a bicycle exercise test. A double-blind cross-over study.

The influence of ionization of air on heart rate (HR) and ratings of perceived exertion (RPE) during bicycle exercise was studied in nine healthy medical students selected according to a randomized schedule from the class of 90 students. The exercise tests were performed both under negative and positive ionization. The study was made with a double-blind, cross-over design. The body surface exposed to ionic current was made large by reducing the clothing of the subject. A significant overall tendency to lower HR and RPE values under negative ionization was observed (p less than 0.01, sign tests). The RPE values were significantly lower (p less than 0.01, paired t-test and the Wilcoxon test) under negative than under positive ionization at the maximal work load level but not at other relative load levels. However, when separately tested at each relative load level HR values did not differ significantly in negative and positive ionization. The results of this pilot study indicate that ionic composition of the air can modify the RPE and possibly also HR during exercise; negative air ionization seems to be beneficial compared with positive ionization. The mechanisms involved are obscure, but we suggest that negative ionization of air may increase oxidative metabolism through generation of a superoxide radical (O2-) that is reduced to H2O2 by superoxide dismutases.

Adult↗

Effects of ionization on the percutaneous absorption of drugs: partitioning of nicotine into organic liquids and hydrated stratum corneum.

To gain further insight into the disposition of ionizable drugs in the stratum corneum, the partitioning of nicotine as a function of pH was studied in excised, hydrated, human stratum corneum (SC) and the organic liquids n-butanol, n-octanol, isopropyl myristate, and Miglyol 812. Partitioning in n-octanol, isopropyl myristate, and Miglyol 812 was consistent with the pH-partition hypothesis, while partitioning in n-butanol agreed with agreed with a model for the partitioning of the free base and an ion pair which dissociates in the organic phase. The results in SC also suggested the partitioning of ion pairs. Binding studies indicated that neither the un-ionized nor the ionized species is bound significantly in the stratum corneum. Trichloroacetate (TCA) anion increased partitioning of ionized nicotine in n-butanol, but had no effect in stratum corneum. Delipidization of the stratum corneum decreased the partition coefficient for the free base, but had no effect on the ionized species. Thermodynamic parameters determined from van't Hoff plots were consistent with the entry of un-ionized nicotine into ordered lipids. These results suggest that the un-ionized form is found within the lipid regions of the stratum corneum, while the ionized form is located in aqueous regions.

Chemical Phenomena↗

Ionized hypocalcemia during out-of-hospital cardiac arrest and cardiopulmonary resuscitation is not due to binding by lactate.

OBJECTIVE: To determine the relationship between ionized calcium concentrations and blood lactate levels during cardiac arrest and cardiopulmonary resuscitation (CPR). DESIGN: A prospective cohort study. SETTING: Emergency department (ED) and general intensive care unit in a city hospital (tertiary care center). PATIENTS AND PARTICIPANTS: 32 patients with out-of-hospital cardiac arrest; 14 of the patients had a return of spontaneous circulation (ROSC) and 18 of the patients died. INTERVENTIONS: Basic and advanced life support. MEASUREMENTS AND RESULTS: Concentrations of ionized and total calcium, bicarbonate, lactate, and pyruvate and pH were simultaneously determined immediately upon arrival at the ED, and at 30 and 60 min. Upon arrival at the ED, all patients had ionized hypocalcemia (1.09 +/- 0.02 mmol/l). Ionized and total calcium concentrations progressively decreased during and after CPR, but pH and bicarbonate concentrations did not show any significant changes. In patients who had ROSC, a significant, but perhaps not clinically relevant, relationship was observed between the ionized calcium concentrations and pH (r2 = 0.152, p = 0.0117). In the patients who died, there were significant correlations between ionized calcium and pH (r2 = 0.382, p = 0.0001) and bicarbonate concentrations (r2 = 0.298, p = 0.0006). No definite correlations were demonstrated when comparing ionized calcium concentrations with lactate and pyruvate concentrations. CONCLUSIONS: Ionized hypocalcemia during out-of-hospital cardiac arrest and CPR is not due to binding by both lactate and pyruvate, but may be partly due to complexing by bicarbonate, with some modifications due to variations in pH.

Aged↗

Plasma ionized magnesium in tubular disorders with and without total hypomagnesemia.

Selective electrodes have been designed for determining plasma ionized magnesium. In kidney disease the relationship between ionized and total circulating magnesium is often altered. Hence plasma ionized magnesium (ETH 7025 membrane) was determined in 25 patients with primary renal tubular disorders; 6 patients had total hypomagnesemia. Total plasma magnesium was never reduced in the remaining 19 patients. Plasma ionized magnesium values were low in the 6 patients with total hypomagnesemia. In 18 of the 19 patients without total hypomagnesemia plasma ionized magnesium values were not reduced. Ionized hypomagnesemia was noted in a patient with normal total plasma magnesium in the context of hypercalciuric nephrocalcinosis of unknown origin. The study demonstrates an excellent concordance between plasma total and ionized magnesium in tubular disorders associated with total hypomagnesemia and a good concordance in tubular disorders that are not linked with total hypomagnesemia. The determination of circulating ionized magnesium is of little value in the diagnostic work-up of the vast majority of renal tubular disorders. The determination might perhaps disclose latent hypomagnesemia in nephrocalcinosis of unknown cause.

Adolescent↗

Effects of extracellular ionized calcium, diltiazem and cAMP on motility of human spermatozoa.

In order to elucidate the effects of ionized calcium and calcium channel blockers on human sperm motility, an in vitro study was conducted looking at the effects of exogenous calcium, ethylene diamine tetraacetic acid (EDTA), diltiazem and dibutyrl cyclic adenosine monophosphate (db-cAMP) on per cent motility and mean velocity of human sperm. Washed spermatozoa from 21 fertile donors were incubated with ionized calcium (zero, five, 10 and 50 mM), EDTA (one and 10 mM), diltiazem (one, 10, 100 microM and one mM) and cAMP (five mM). Per cent motility and mean velocity determinations were made at 10 and 120 min. by computerized analysis of videomicrographs. Over a wide range of extracellular ionized calcium concentrations (50 microM to 50 mM), per cent motility and mean velocity of human sperm were not stimulated or inhibited. At ionized calcium concentration less than 1 microM, achieved by addition of EDTA (10 mM), per cent motility decreased by 68% and 79% and mean velocity decreased by 44% and 48% compared to controls at 10 and 120 min. respectively (p less than 0.001). The decrease in mean velocity was reversible by addition of calcium to the EDTA (10 mM) sample to return ionized calcium to control concentration (0.5 mM). This reversibility suggests EDTA did not have a direct toxic effect on spermatozoa and that its action was mediated by changes in ionized calcium concentration. Diltiazem (one mM) decreased sperm mean velocity by 26% and 28% compared to controls at 10 and 120 min. respectively (p less than 0.01), but had no effect at lower concentrations (one, 10 or 100 microM). Db-cAMP (five mM) increased per cent motility by 25% and 20% and mean velocity by 36% and 34% compared to controls at 10 and 120 min. respectively (p less than 0.05). These results indicate that a minimum level of extracellular ionized calcium is essential to normal sperm motility and suggest that sperm are more dependent on the intracellular translocation of calcium ions for the regulation of motility than on the extracellular ionized calcium concentration. While db-cAMP does significantly increase per cent motility and mean velocity of human sperm, its clinical usefulness for the treatment of male infertility remains to be demonstrated.

Bucladesine↗

Nuclear factor kappa B dependent induction of gamma glutamylcysteine synthetase by ionizing radiation in T98G human glioblastoma cells.

Glioblastoma is one of the most malignant of all neoplasms, and often shows resistance to chemotherapy and radiation therapy. Ionizing radiation activates transcriptional factors, such as nuclear factor kappa-B (NF-kappa B). Previously we found that glutathione (GSH) synthesis is induced by cytokines mediated by NF-kappa B (Urata et al. J. Biol. Chem., 1996). Here, we present direct evidence that NF-kappa B activated by ionizing radiation induces the expression of gamma-glutamylcysteine synthetase (gamma-GCS), the rate limiting enzyme of GSH synthesis, using T98G human glioblastoma cells. T98G cells have approximately 14-times the level of intracellular GSH of NB9 cells, radiation-sensitive neuroblastoma cells. In T98G cells, 30-Gy of ionizing radiation was required for the activation of NF-kappa B on an electrophoretic mobility shift assay and the induction of gamma-GCS mRNA on Northern blots and a nuclear run-on assay. However, when T98G cells were treated with buthionine sulfoximine, 3-Gy of ionizing radiation stimulated the DNA-binding activity of NF-kappa B and the expression of gamma-GCS. We constructed chimeric genes containing various regions of gamma-GCS promoter gene and the coding region for Luciferase. T98G cells transiently transfected with a plasmid containing the gamma-GCS promoter-luciferase construct showed increased luciferase activity when treated with ionizing radiation. The luciferase activity stimulated by ionizing radiation was found in the gamma-GCS promoter containing the NF-kappa B binding site, whereas not in that containing its mutated site. These results suggest that GSH synthesis is upregulated by ionizing radiation mediated by NF-kappa B and a high concentration of GSH in T98G cells causes downregulation of the NF-kappa B-DNA binding activity in response to ionizing radiation. The irresponsiveness of the intracellular signal transduction cascade to irradiation may be a factor in the resistance of T98G cells to radiation therapy.

Acetylcysteine↗

Characterization and relative ionization efficiencies of end-functionalized polystyrenes by matrix-assisted laser desorption/ionization mass spectrometry.

The properties and relative ionization efficiencies of a series of polystyrenes (PS) with hydroxyl, hydrogen, tertiary amine, and quaternary amine end-functionalities were examined by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS). The hydrogen and hydroxyl functionalized PS ionized via attachment of a single Ag(+) cation, as expected. However, tertiary amine PS oligomers were found in (M - H)(+) and (M + H)(+) forms, in addition to M + Ag(+), while the quaternary amine PS oligomers only ionized to the M(+) form. Analysis of tertiary amine PS spectra revealed varying ratios of the three ionic forms depending on the oligomer length, pointing to a change in ionization efficiency. When the bulk samples were compared, the quaternary amine end-functionalized PS gave a ten-fold higher ionization efficiency over all others studied, likely because of the preexisting charge on the functionality. Samples with hydroxyl and hydrogen functionalities had similar ionization efficiencies, with the tertiary amine slightly higher, depending on the molecular weight. Changes in molecular weight affected the relative ionization efficiencies in varying fashion depending on the end functionality, though average molecular weight measurements were largely unaffected by end-functionality. Quantification of end-functionalized polystyrenes with different ionization efficiencies was found to be possible if due care was taken.

Journal Article↗

Control of local ionization and charge transfer in the bifunctional molecule 2-phenylethyl-N,N-dimethylamine using Rydberg fingerprint spectroscopy.

Local photoionization pathways and charge-transfer dynamics of 2-phenylethyl-N,N-dimethylamine (PENNA) are explored using the recently developed Rydberg fingerprint spectroscopy. PENNA, a molecule that derives its biological significance from its relation to neurotransmitters, has two ionization centers that are separated by an ethyl group. We ionize the molecule in various multiphoton ionization processes using different laser wavelengths. The Rydberg fingerprint spectrum reveals the local nature of the ionization process and identifies the center of charge. We discovered that the laser wavelength provides substantial control over the activation of the individual ionization centers. The resonant (2+1) ionization with 400-nm radiation is dominated by the ejection of an electron from the amine moiety. In contrast, the resonant (1+1) ionization with 266-nm radiation leads predominantly to an ion with the charge in the phenyl group. The clean separation of the two ionization processes allows the exploration of ultrafast charge-transfer dynamics ensuing from a specific starting state characterized by a charged phenyl moiety. The width of the corresponding spectral features suggests that the charge transfer proceeds on a femtosecond time scale, suggesting a strong coupling between the two lowest-energy electronic surfaces of the PENNA cation.

Journal Article↗

An approach to modelling radiation damage by fast ionizing particles.

This paper presents a statistical approach to modelling the damaging effects of radiation by fast heavy ionizing particles in small biological structures such as enzymes, viruses, and some cells. Irreparable damage is assumed to be caused by the occurrence of ionizations within sensitive regions of a structure. For structures containing double-stranded DNA, one or more ionizations occurring within each strand of the DNA will cause inactivation; for simpler structures without double-stranded DNA a single ionization within the structure will be sufficient for inactivation. Damaging ionizations occur along tracks of primary irradiating particles or along tracks of secondary particles released at primary ionizations. An inactivation probability is derived for each damage mechanism, and is expressed in integral form in terms of the radius of the biological structure (assumed spherical), the rate of ionization along primary tracks, and the maximum energy for secondary particles. The performance of each model is assessed by comparing results from the model with results derived from data from various experimental studies extracted from the literature. For the simpler structures, where a single ionization is sufficient for inactivation, the model gives qualitatively promising results. However, for larger more complex structures containing double-stranded DNA, the model requires some further refinements.

DNA↗

Correction of ionized plasma magnesium during cardiopulmonary bypass reduces the risk of postoperative cardiac arrhythmia.

UNLABELLED: We conducted this randomized controlled trial to determine whether the intraoperative measurement and correction of ionized plasma magnesium can reduce the risk of cardiac arrhythmia after cardiopulmonary bypass. Eighty-five patients presenting for coronary artery bypass grafting were randomly assigned either to the magnesium-corrected group, which received magnesium sulfate on the basis of measured levels of ionized plasma magnesium (n = 43), or to the control group, in which magnesium levels were identified but not corrected (n = 42). Ionized magnesium was determined with an ion-selective electrode with minimal delay, and further samples were taken for laboratory analysis of total plasma magnesium. All patients had Holter electrocardiogram monitoring for 72 h after surgery. Total hypomagnesemia (45 patients; 53% of all patients) was more common than ionized hypomagnesemia (11 patients; 13%) before cardiopulmonary bypass. Both total and ionized magnesium levels declined further during the course of cardiopulmonary bypass in the control group. The incidence of ventricular tachycardia in the first 24 h was less frequent in the magnesium-corrected group (3 patients; 7%) than the control group (12 patients, 30%; P < 0.01). Patients in the magnesium-corrected group were more likely to display continuous sinus rhythm (Lown Grade 0) in the first 24 h (14 patients; 34%) than patients in the control group (2 patients, 5%; P < 0.001). Our results suggest that the intraoperative correction of ionized magnesium is associated with a reduction in postoperative ventricular arrhythmia in cardiac surgical patients. IMPLICATIONS: In this study the correction of ionized plasma magnesium during cardiopulmonary bypass was guided by measurements from an ion-selective electrode. This intervention resulted in a reduction in the incidence of postoperative ventricular tachycardia and an increased frequency of continuous sinus rhythm. Ion-selective electrodes constitute a convenient near-patient test, providing a basis for the targeted replacement of ionized plasma magnesium.

Aged↗