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PubMedDate not supplied

Combined radiation sensitizing and anti-angiogenic effects of ionizing radiation and the protease inhibitor ritonavir in a head and neck carcinoma model.

Ritonavir, a protease inhibitor, has been successfully applied in the treatment of HIV infection. Reports of dramatic improvement of AIDS-related cancers, such as primary central system lymphoma after radiation therapy as well as Kaposi's sarcoma, led to the recent discovery of the "non viral" antitumor activity of HIV protease inhibitors. This study was designed to detect the antitumor effect of Ritonavir when combined with ionizing radiation both in vitro and in vivo in the HEP-2 head and neck carcinoma model. Inhibition of tumor growth was observed when mice were treated with Ritonavir alone and this effect was enhanced when combined with ionizing radiation. No adverse effect or significant toxicity in the hosts' body weights was seen between the different treatment and control groups throughout the experiments. A marked antiproliferation effect of the combination was observed in vitro. A marked reduction of angiogenesis was detected within the tumor sections from the Ritonavir combined with irradiation group as compared with the Ritonavir or irradiation alone groups. Western blot analysis showed that apoptosis was induced by an increased expression of Bax and decreased expression of Bcl-2 after treatment with Ritonavir and ionizing radiation. Thus, the antitumor effect of the latter combination is associated with the enhancement of radiation-induced apoptosis and inhibition of angiogenesis. These data suggested that Ritonavir could clinically improve the tumor response to radiation therapy, especially in head and neck carcinoma.

Animals↗
PubMed2005

Assessment of serum ionized magnesium levels in healthy volunteers, in patients with coronary artery disease and/or hypertension and in hypertension alone.

We examined ionized magnesium concentration by blood analysis in patients with hypertonia arterialis, ischemic heart diseases, both of them and in a control group. Slighty lower mean serum ionized magnesium concentration was found in the study group hypertonia arterialis when compared to the control group. In patients both group "B" with coronary artery diseases and group "C" with hypertonia arterialis + ischemic heart diseases, mean serum ionized magnesium concentrations were higher then in the control group, the differences were statistically significant.

Comorbidity↗
PubMed2006

Dosimetric properties of the liquid ionization chamber electronic portal imaging device (EPID).

In the relation between the pixel values of the electronic portal imaging device (EPID) and dose rate, pixel values have been reported to be proportional to the square roots of the dose rates although some researchers have reported that each EPID pixel value was almost proportional to the dose rates when they were more than 1 Gy/min. To resolve this contradiction, in this study we have investigated the dosimetric properties of the liquid ionization chamber EPID based on a two-dimensional matrix of liquid- filled ionization chambers. Our results show that the pixel values of this EPID were proportional to the square roots of the dose rates when they were less than 0.5 Gy/min, and the values were proportional to the dose rates when they were more than that. In addition, the survival time of electrons in the liquid of the EPID is reportedly dependent on the amount of impurities in the liquid ionizing chamber of EPID. The pixel values of the EPID acquired in rapid succession, increased. In the results, the pixel values were constantly increased to approximately 0.2% of pre-images for less than 15 s of the rest interval. When changes in the sensitivity of each pixel value were approximately 1%, approximately 5% changes were observed against the transformed dose rate. To avoid this difference, we developed the following formula relating the pixel value, P, and dose rate, D. P=a D + b radicalD - k h (a, b, h: constants, k : variable).

Diagnostic Imaging↗
PubMed2007

Enhanced lung cancer cell killing by the combination of selenium and ionizing radiation.

Selenium has been associated with anticancer activity by affecting multiple cellular processes. We reasoned that the simultaneous modulation of multiple radioresponse regulators by selenium should increase radiosensitivity if selenium is combined with radiation in cancer therapy. Therefore, we explored the possibility of whether we could obtain an enhancement of radiosensitivity by the combination of selenium and ionizing radiation. We used two human lung cancer cell lines, NCI-H460 and H1299, as well as a human diploid lung fibroblast, WI-38, as the normal cell counterpart. The combined treatment of the cancer cell lines with Seleno-methionine and ionizing radiation resulted in increased cell killing as assessed by clonogenic survival assay whereas it had little effect on the normal diploid WI-38 cells. The increased radiosensitivity in the cancer cells was correlated with the attenuation of the key proteins involved in either cell survival signaling [Akt, EGFR (epidermal growth factor receptor), ErbB2 and Raf1] or DNA damage response (Mre11, Rad50, Nbs1, Ku80, 53BP1 and DNAPK). The attenuation of the proteins by the selenium compound was possibly caused by the effect on transcription and on protein stability since selenium treatment decreased both the RNA transcript and the protein stability of EGFR and DNAPK. By contrast, Seleno-L-methionine had no effect on the protein profile of a normal diploid fibroblast which is consistent with an intact radiosensitivity. These data provide possible clinical applications, as selenium selectively enhanced the radiosensitivity of the tumor cells whereas that of the normal cells was unaffected. Moreover, the selective decrease of cell proliferation signaling in tumor cells but not in normal cells should facilitate the repopulation of normal cells required for healing during radiation therapy. On the whole, the results suggest that the cancer preventive activity of selenium can be combined with ionizing radiation to improve the control of lung cancer.

Cell Line, Tumor↗
PubMed1991

[The ionized calcium fraction of the blood: dependence on different methodical factors].

In the present study the influence of different methodical factors (analyzer with ion-selective electrodes used, anticoagulation of blood samples with heparin, storing of samples at different temperatures) on the concentration of ionized calcium in blood was investigated. It could be shown that nowadays' systems for analysis of ionized calcium (ORION SS-20, AVL 980, NOVA 2 and 8, ICA 1) yield reproducible values for human as well as canine blood. System-related differences point to a varying degree of interferences on the ion-selective electrodes used. The concentration of ionized calcium is strongly dependent on different preanalytic factors. Heparin leads to a concentration-related reduction of calcium ions in blood. This negative impact of heparin can be overcome by substitution of the solvent for CaCl2 (2.5 mmol.l-1) without meaningful falsification of the measured values. At 4 degrees C blood samples can be stored without detectable changes in Ca++ concentration for 8 hours.

Animals↗
PubMed1991

Lignin peroxidase of Phanerochaete chrysosporium. Evidence for an acidic ionization controlling activity.

The active site amino acid residues of lignin peroxidase are homologous to those of other peroxidases; however, in contrast to other peroxidases, no pH dependence is observed for the reaction of ferric lignin peroxidase with H2O2 to form compound I (Andrawis, A., Johnson, K.A., and Tien, M. (1988) J. Biol. Chem. 263, 1195-1198). Chloride binding is used in the present study to investigate this reaction further. Chloride binds to lignin peroxidase at the same site as cyanide and hydrogen peroxide. This is indicated by the following. 1) Chloride competes with cyanide in binding to lignin peroxidase. 2) Chloride is a competitive inhibitor of lignin peroxidase with respect to H2O2. The inhibition constant (Ki) is equal to the dissociation constant (Kd) of chloride at all pH values studied. Chloride binding is pH dependent: chloride binds only to the protonated form of lignin peroxidase. Transient-state kinetic studies demonstrate that chloride inhibits lignin peroxidase compound I formation in a pH-dependent manner with maximum inhibition at low pH. An apparent pKa was calculated at each chloride concentration; the pKa increased as the chloride concentration increased. Extrapolation to zero chloride concentration allowed us to estimate the intrinsic pKa for the ionization in the lignin peroxidase active site. The results reported here provide evidence that an acidic ionizable group (pKa approximately 1) at the active site controls both lignin peroxidase compound I formation and chloride binding. We propose that the mechanism for lignin peroxidase compound I formation is similar to that of other peroxidases in that it requires the deprotonated form of an ionizable group near the active site.

Benzyl Alcohols↗
PubMed1991

Induction of tissue-type plasminogen activator by ionizing radiation in human malignant melanoma cells.

Two differently timed extracellular and intracellular enzymatic and mRNA peaks of tissue-type plasminogen activator (t-PA) were induced following ionizing radiation. The first peak appeared within 10 min following X-irradiation but rapidly declined. The appearance of early t-PA mRNA transcripts and enzymatic activity were not prevented by actinomycin D treatment. In contrast, cycloheximide prevented the early, minor enzymatic induction peak of t-PA. Stabilization of t-PA mRNA transcripts appears to be an early initial response of human cells to ionizing radiation, since the synthesis of new mRNA transcripts within the first 30 min was not observed via nuclear run-on analyses. Nearly 12 h following X-irradiation, a second major enzymatic peak of t-PA was observed. Cycloheximide or actinomycin D treatments blocked the later t-PA response. t-PA mRNA levels were induced greater than 100-fold in 4 h by ionizing radiation as assayed via Northern or nuclear run-on analyses. During the major induction period, t-PA mRNA transcripts reached their maximum levels at 4-8 h, and intracellular enzyme levels accumulated 6-8 h after X-irradiation. Unirradiated U1-Mel cells demonstrated only low basal levels of t-PA mRNA and enzymatic activity. Similar induction responses were found following UV-irradiation or 12-O-tetradecanoyl-phorbol-13-acetate (PMA) treatments. Normal human fibroblast (i.e., GM 2936B, GM2907A, and IMR-90) cells also demonstrated the induction of t-PA, although only one later enzymatic peak was detected. The induction of t-PA mRNA levels and intracellular and extracellular enzymatic activities for these cells were 50-fold lower than with U1-Mel cells given equitoxic doses of X-rays. Differential expression of t-PA in some tumor as compared to normal tissues may be utilized in future chemotherapeutic regimens.

DNA↗
PubMed1990

Ionized calcium and cyclic AMP in plasma and urine. Biochemical evaluation in calcium metabolic disease.

Measurement of ionized calcium and cAMP in plasma and urine are used as sensitive parameters for the evaluation of calcium disorders. Ionized calcium is accepted as the biologically active form of calcium in the extracellular fluid, while urine cAMP provides an in vivo receptor assay for the biologically active parathyroid hormone. When urine is included as part of the calcium metabolic investigation it usually requires 24 h urine collection with a variety of different laboratory tests. Ionized calcium and cAMP are described in the literature in terms of several derived quantities, nomenclatures, and units which are rather unsystematic. The author developed reliable techniques and proposed systematic names and symbols and reference values for these quantities. Due to the lack of guidelines for the collection of urines in calcium metabolic evaluation, the author presented a simplified protocol (4 h standardized urine collection). In clinical investigation plasma and urine cAMP have been used to differentiate idiopathic hypoparathyroidism from pseudohypoparathyroidism (PsHP) based on the results of i.v. injection of parathyroid hormone (PTH). Nephrogenous cAMP has also been used for the detection of primary and secondary hyperparathyroidism with a high nosographic sensitivity (90%) (Broadus). The author showed that measurement of cAMP after i.v. PTH was a reliable and sensitive test to establish the diagnosis of PsHP, and that the urinary cAMP was useful for the diagnosis of secondary hyperparathyroidism in patients with jejunoileal bypass, but could not confirm the high nosographic sensitivity for the diagnosis of primary hyperparathyroidism. Further data are needed for proper conclusion. Although pursued vigorously the research into idiopathic stone formation using different protocols has not prevented stone recurrence nor indicated where further progress might be made. For the evaluation of recurrent calcium disease, the author proposed a simplified 4 h standardized urine collection with plasma albumin, urinary pH, standardized excretion rate of calcium, plasma phosphate glomerular filtration rate, and nephrogenous cAMP as the most important parameters. In this way the author obtained a sensitivity of 93% and specificity of 95.6% for the diagnosis of recurrent stone former. The test may therefore be of value for predicting the risk of recurrent stone formation in the single stone former.

Calcium↗
PubMedDate not supplied

[The effect of fenigidin (nifedipine) and verapamil on renin activity, the levels of ionized calcium and aldosterone in the blood plasma and on the hemodynamic indices of rats with spontaneous hypertension].

Nifedipine and verapamil (10 mg/kg orally) were found to induce a significant increase of renin activity, a decrease of aldosterone and ionized calcium levels in blood plasma in spontaneously hypertensive rats. A preliminary administration of a hypertonic solution of sodium chloride decreased renin activity, ionized calcium and aldosterone levels that contributed to the enhancement of the hypotensive effect of calcium antagonists. It was established that nifedipine by its effect on the parameters of hemodynamics and the condition of renin-angiotensin system as well as the blood plasma ionized calcium level is superior to verapamil.

Aldosterone↗
PubMed1979

Spectral evidence for tyrosine ionization linked to a conformational change in liver alcohol dehydrogenase ternary complexes.

Resonance energy transfer from Trp-314 to ionized Tyr-286 was proposed (Laws, W. R., and Shore, J. D. (1978) J. Biol. Chem. 253, 8593-8597) as the mechanism for the observed decrease in protein fluorescence of liver alcohol dehydrogenase seen with alkaline pH, or with the formation of a ternary complex with NAD+ and trifluoroethanol. In the present study, ultraviolet difference spectra confirm the presence of ionized tyrosine not only in these two cases but also in the ternary complex with NADH and isobutyramide. Our results indicate that ternary complex formation, with either oxidized or reduced coenzyme, causes a conformational change leading to partial ionization of tyrosine residues in regions of the enzyme far from the active site.

Alcohol Oxidoreductases↗
PubMed1990

[Identification of bis-quaternary ammonium compounds using mild ionization mass spectrometry].

Ethonium, an antimicrobial chemotherapeutic agent, was investigated by mass spectrometry (MS) under various ionization conditions: electron impact, field ionization, field desorption (FD) and fast atom ionization. FDMS was found to be the most suitable procedure for ethonium identification. Relation of the ED mass spectra to the distance between the nitrogen atoms in bis-quaternary ammonium compounds is discussed. It was shown that the most intensive ions with m/z 499, 315 in the FD mass spectra corresponded to the ethonium specific fragmentation and their occurrence in the spectra could serve as a sufficient criterion useful in qualitative and quantitative assay of the drug in the sample.

Chemical Phenomena↗
PubMedDate not supplied

Comparative study of sodium, potassium, ionized calcium, urea and creatinine circadian rhythm documented in samples of capillary and venous blood from healthy subjects.

Circadian rhythms of sodium, potassium, ionized calcium, creatinine and urea concentrations were determined in venous and capillary blood of practically healthy volunteers (10 women and 8 men). Electrolytes were determined on the ionoselective analyzer Microlyte (KONE, Finland). Circadian rhythmicity of parameters was revealed in venous and capillary blood by means of group-mean cosinor analysis. Acrophases of the rhythms occurred in the late evening (Na) or in the first (K, venous ionized Ca) and in the second half (creatinine, urea) of sleep. Circadian rhythms of electrolytes (except ionized Ca rhythm) and final products of nitrous metabolism in capillary blood turned out to be the markers of the corresponding indices rhythms of venous blood.

Adult↗
PubMed1989

Effects of oral base therapy on serum ionized calcium, phosphorus and parathyroid hormone in chronic hemodialysis patients.

The purpose of this study was to evaluate the effects of oral base therapy on selected chemical parameters in chronic hemodialysis patients. Oral base supplements were administered to 20 acidotic chronic hemodialysis patients for one month. Serum bicarbonate levels rose from 18.6 +/- 2.9 to 22.5 +/- 4.0 mEq/L (p less than 0.0005) and pH rose from 7.35 +/- 0.03 to 7.39 +/- 0.04 (p less than 0.0005). Serum ionized calcium levels fell from 5.03 +/- 0.37 to 4.83 +/- 0.34 mg/dL (1.25 +/- 0.09 to 1.21 +/- 0.08 mmol/L) (p less than 0.01), while intact parathyroid hormone (PTH) levels rose from 547 +/- 697 to 619 +/- 776 pg/mL (p less than 0.05). Base therapy did not result in significant changes in serum levels of total calcium, phosphorus, alkaline phosphatase, urea nitrogen, creatinine, total protein, albumin or potassium. If empiric therapy with exogenous base is given to dialysis patients, ionized calcium levels should be closely monitored since changes in calcium supplement or vitamin D therapy may be required to maintain ionized calcium and parathyroid hormone values at the pre-treatment levels.

Acidosis↗
PubMed1989

Critical analytical and clinical aspects of ionized calcium in neonates.

Clinical diagnosis in neonates is often based primarily on biochemical data, because clinical symptoms are difficult to assess and inconclusive. A knowledge of the validity of the data would therefore seem very important. Practical technical assessments lead me to conclude that measurement of ionized calcium at actual pH in anaerobic capillary samples of whole blood, currently practicable, is an easy and optimal laboratory analysis when biologically significant data are required for assessment of acute disturbances in calcium homeostasis of neonates. Values are given for ionized calcium, describing the relations in cord and maternal blood in uncomplicated pregnancies at term. Recent published cross-sectional and longitudinal reference values for ionized calcium, measured during the first weeks in healthy full-term and preterm neonates, seem to provide a new basis for the diagnosis and management of early neonatal hypocalcemia.

Adult↗
PubMed1989

Significance of ionized calcium during liver transplantation.

In liver transplant patients low plasma protein, acid base abnormalities and high citrate concentrations in the blood affects the binding of ionized calcium. In the present study plasma ionized calcium as well as serum total plasma calcium were measured in ten patients undergoing liver transplantation because of end-stage liver failure. During the operation, ionized calcium fell to as low as 0.46 mmol/l although calcium chloride was administered frequently at doses of 10 mg/kg. Serum total calcium concentration values did not fall but rose well above normal at the end of the operation. The measuring of total serum calcium may thus be dangerously misleading in patients undergoing liver transplantation.

Calcium↗
PubMed1986

Ionizing radiation promotes protozoan reproduction.

This experiment was performed to determine whether ionizing radiation is essential for maximum growth rate in a ciliated protozoan. When extraneous ionizing radiation was reduced to 0.15 mrad/day, the reproduction rate of Tetrahymena pyriformis was significantly less (P less than 0.01) than it was at near ambient levels, 0.5 or 1.8 mrad/day. Significantly higher growth rates (P less than 0.01) were obtained when chronic radiation was increased. The data suggest that ionizing radiation is essential for optimum reproduction rate in this organism.

Background Radiation↗
PubMed1987

Ionized calcium levels during liver transplantation.

Plasma ionized calcium and total calcium concentrations were measured during 26 liver transplant operations. The level of ionized calcium decreased during the early part of the operation, reaching its lowest point during the anhepatic period, but rose again after revascularization of the new liver. Calcium chloride was given with the aim of reversing these decreases, which were associated with the use of blood products preserved in citrate-phosphate-dextrose anti-coagulant-containing adenine (CPD-A). Ionic hypocalcaemia is a result of intra-operative citrate loading in the presence of poor or absent (during the anhepatic phase) liver function; aggressive correction of low ionized calcium levels, especially during the early stages of the operation, is required to prevent this effect.

Adult↗
PubMed1988

The ionization and distribution behavior of oleic acid in chylomicrons and chylomicron-like emulsion particles and the influence of serum albumin.

A reproducible, fairly narrow-sized population of rat lymph chylomicrons, approximately 100 nm, was isolated by centrifugation and combined with low levels of [1-13C]oleic acid for NMR studies. The carboxyl chemical shift was monitored as a function of aqueous pH to characterize the ionization behavior of the fatty acid in these particles. The titration curves were very similar to those for oleic acid in equivalent-sized emulsion particles composed of egg phosphatidylcholine and triolein. A simple partition-ionization model was fitted to the data to derive values for apparent ionization constant, expressed as pKapp, of 7.4-7.5 and the "true" surface to core partition coefficient of approximately 7 for oleic acid in chylomicrons. The fatty acid in chylomicrons thus appeared to be largely associated with the surface regions of these particles. Addition of bovine serum albumin to the samples showed that near physiologic pH much of the fatty acid was bound to the albumin at fatty acid to albumin-binding stoichiometries as high as 5.1 and with mass ratios of greater than 2 in favor of the lipid or lipoprotein particles. Lowering the pH of the medium shifted the distribution of fatty acid away from albumin so that at pH 5 with the emulsion, virtually all the fatty acid was associated with the lipid. The behavior observed under physiologic conditions is consistent with the rapid clearance and redistribution of fatty acid generated in these particles by lipolytic processes. However, under conditions of severe acidosis, hyperlipidemia, and hypoalbuminemia a significant portion of fatty acids might be retained in triglyceride-rich lipoproteins and their remnants and affect subsequent metabolism.

Algorithms↗