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PubMed1988

Cardiac arrest and blood ionized calcium levels.

Blood ionized and total calcium levels, and pH values were obtained in 12 patients who were being ventilated and given external cardiac massage after having had an out-of-hospital cardiac arrest. On admission they had marked ionized hypocalcemia, with mean ionized calcium levels of 0.67 +/- 0.22 mmol/L, (range, 0.26 to 0.89), but normal total calcium levels. There was a positive correlation between pH and ionized calcium levels (r = 0.71). Of the six patients who were successfully resuscitated, four were discharged and two died; the other six could not be resuscitated and died. By comparison, ionized and total calcium levels obtained within 3 minutes of cardiac arrest were normal in 9 patients who had cardiac arrests in the intensive care unit or during surgery. All were discharged. These data are the first to document the occurrence of severe ionized hypocalcemia after out-of-hospital cardiac arrest. Hypocalcemia appears to be time-dependent and due essentially to extracellular complexing of calcium. Further work is needed to determine whether patients who have out-of-hospital cardiac arrests can benefit from calcium administration.

Adult↗

PubMed1999

[Changes in ionized magnesium concentrations during general anesthesia].

The change in ionized magnesium (Mg) was investigated during isoflurane-nitrous oxide-oxygen anesthesia. The patients were divided into two groups by induction method of anesthesia. Group 1 was induced with thiamylal 4 mg.kg-1 and Group 2 was induced with ketamine 1 mg.kg-1. The ionized Mg concentration was recorded by NOVA 8 analyzer and observed during anesthesia. We also recorded the serum concentration of total Mg after administration of thiamylal. During induction of anesthesia and surgery, ionized Mg concentration decreased significantly in both groups. The ionized Mg concentration after administration of thiamylal was significantly lower than that after administration of ketamine. The serum total Mg concentration did not decrease throughout the anesthesia course. The ionized calcium concentration decreased, but the concentration of Na and K remained essentially unchanged. We conclude, therefore, that ionized Mg concentration decreases during surgery under general anesthesia, in part, possibly by the effect of anesthetic agent on the cell membrane itself.

Adult↗

PubMed2000

Antitumor activity of combined treatment of human cancer cells with ionizing radiation and anti-epidermal growth factor receptor monoclonal antibody C225 plus type I protein kinase A antisense oligonucleotide.

Recent studies have suggested that selective inhibition of mitogenic pathways may improve the antitumor activity of ionizing radiation. The epidermal growth factor receptor (EGFR) is overexpressed and is involved in autocrine growth control in the majority of human carcinomas. Protein kinase A type I (PKAI) plays a key role in neoplastic transformation and is overexpressed in cancer cells in which an EGFR autocrine pathway is activated. We used two specific inhibitors of EGFR and PKAI that are under clinical evaluation in cancer patients: C225, an anti-EGFR chimeric human-mouse monoclonal antibody (MAb); and a mixed-backbone antisense oligonucleotide targeting the PKAI RIalpha subunit (PKAI AS). We tested in human colon cancer (GEO) and ovarian cancer (OVCAR-3) cell lines the antiproliferative activity of MAb C225 and/or PKAI AS in combination with ionizing radiation. In vivo antitumor activity was evaluated in nude mice bearing established GEO xenografts. Dose-dependent inhibition of soft agar growth was observed in both cancer cell lines with ionizing radiation, C225, or PKAI AS oligonucleotide. A cooperative antiproliferative effect was obtained when cancer cells were treated with ionizing radiation followed by MAb C225 or PKAI AS oligonucleotide. This effect was observed at all doses tested in both GEO and OVCAR-3 cancer cell lines. A combination of the three treatments at the lowest doses produced an even greater effect than that observed when two modalities were combined. Treatment of mice bearing established human GEO colon cancer xenografts with radiotherapy (RT), MAb C225, or PKAI AS oligonucleotide produced dose-dependent tumor growth inhibition that was reversible upon treatment cessation. A potentiation of the antitumor activity was observed in all mice treated with RT in combination with MAb C225 or PKAI AS oligonucleotide. Long-term GEO tumor growth regression was obtained following treatment with ionizing radiation in combination with MAb C225 plus PKAI AS oligonucleotide, which produced a significant improvement in survival compared with controls (P < 0.001), the RT-treated group (P < 0.001), or the group treated with MAb C225 plus PKAI AS oligonucleotide (P < 0.001). All mice of the RT + MAb C225 + PKAI AS group were alive 26 weeks after tumor cell injection. Furthermore, 50% of mice in this group were alive and tumor-free after 35 weeks. This study provides a rationale for evaluating in cancer patients the combination of ionizing radiation and selective drugs that block EGFR and PKAI pathways.

Animals↗

PubMed2003

[Ionizing radiation-regulated killing of human hepatoma cells by liposome-mediated CDglyTK gene delivery].

EGR-1 gene promoter and CDglyTK gene were used to construct the pcDNA3-EGR-CDglyTK recombinant vector, in which CDglyTK gene expression was under the control of EGR-1 gene promoter. Cationic liposome LipofectAMINE was used to transfect plasmids into human hepatoma 7402 cell line. Subsequently, the transfected cells were treated with different doses of gamma-ray. Northern blot and Western blot showed that ionizing radiation can induce CDglyTK gene expression drived by EGR-1 promoter,in a dose-dependant manner. There was no ionizing radiation-inducible effect in pcDNA3-CMV-CDglyTK control group. Ionizing radiation also markedly enhanced the sensitivity of tumor cells transfected with pcDNA3-EGR-CDglyTK to prodrugs (GCV/5-FC) in tumor cell killing. The data indicated that EGR-1 promoter was inducible by ionizing radiation, whereas the CMV promoter was not. There was a synergetic effect between GCV and 5-FC. The cytotoxic effect of the suicide gene-ionizing radiation combination was stronger than suicide gene alone or ionizing radiation alone.

Blotting, Northern↗

PubMed1992

[Alteration of the ionized calcium level in coronary sinus blood during coronary arteriography].

Injection of contrast medium into the coronary circulation produces a decrease in the concentration of ionized calcium in blood and thus causes a deterioration of myocardial contractility. In this study, changes in the ionized calcium level in the coronary sinus during coronary arteriography were compared for four different contrast media in human subjects. The contrast media used were meglumine sodium diatrizoate, iohexol, iopamidol and meglumine sodium ioxaglate. Blood samples were collected from the coronary sinus before and 5, 15 and 30 seconds after the first injection of contrast medium into the left coronary artery. The ionized calcium level of each specimen was measured using an ion specific electrode, and hematocrit was measured using the centrifuge method. Diatrizoate produced the greatest changes in both hematocrit and ionized calcium. The time concentration curve of hematocrit was similar for all four contrast media, but diatrizoate and ioxaglate produced a prolonged decrease in ionized calcium. The cause of this phenomenon is not clear, but it may be related to differences in the ionic status of the contrast media. Nonionic low-osmolality contrast media with added calcium may be preferable for coronary arteriography with respect to maintenance of the ionized calcium level.

Adult↗

PubMed2004

Highly sensitive screening method for nitroaromatic, nitramine and nitrate ester explosives by high performance liquid chromatography-atmospheric pressure ionization-mass spectrometry (HPLC-API-MS) in forensic applications.

A highly sensitive screening method based on high performance liquid chromatography atmospheric pressure ionization mass spectrometry (HPLC-API-MS) has been developed for the analysis of 21 nitroaromatic, nitramine and nitrate ester explosives, which include the explosives most commonly encountered in forensic science. Two atmospheric pressure ionization (API) methods, atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI), and various experimental conditions have been applied to allow for the detection of all 21 explosive compounds. The limit of detection (LOD) in the full-scan mode has been found to be 0.012-1.2 ng on column for the screening of most explosives investigated. For nitrobenzene, an LOD of 10 ng was found with the APCI method in the negative mode. Although the detection of nitrobenzene, 2-, 3-, and 4-nitrotoluene is hindered by the difficult ionization of these compounds, we have found that by forming an adduct with glycine, LOD values in the range of 3-16 ng on column can be achieved. Compared with previous screening methods with thermospray ionization, the API method has distinct advantages, including simplicity and stability of the method applied, an extended screening range and a low detection limit for the explosives studied.

Journal Article↗

PubMed1991

Heparinization of blood decreases ionized calcium concentration.

To evaluate whether heparin in the plasma sample may affect the ionized calcium level, we compared the ionized calcium levels of blood samples of three different heparin concentrations in 25 normal healthy volunteers: Group A contained no heparin (control group); Group B contained 4.7 IU/ml heparin; and Group C contained 37.5 IU/ml heparin. The result showed ionized calcium to be 4.99 +/- 0.28 mg/dl (Mean +/- SEM) in group A; 4.64 +/- 0.26 mg/dl (Mean +/- SEM) in group B and 4.25 +/- 0.24 mg/dl (Mean +/- SEM) in group C. These three values were significantly different (p less than 0.001). So, heparin might artificially lower the plasma ionized calcium concentration. It is concluded that: (1) samples for accurate ionized calcium measurement should contain no heparin; and (2) in spite of the careful measurement by conventional technique, an introduction of an excessive amount of heparin into the deadspace of the syringe may significantly reduce the ionized calcium concentration.

Adult↗

PubMed1989

Effect of sodium bicarbonate infusions on ionized calcium and total calcium concentrations in serum of clinically normal cats.

The effects of sodium bicarbonate (0.5 mEq/kg of body weight, 1.0 mEq/kg, 2.0 mEq/kg, and 4.0 mEq/kg) on ionized and total calcium concentrations were determined in clinically normal cats. Also, serum pH, whole blood pH, and serum albumin, serum total protein, and serum phosphorus concentrations were measured. Intravenous administration of sodium bicarbonate to awake cats decreased serum ionized calcium and serum total calcium concentrations. All dosages of sodium bicarbonate were associated with significant decreases of serum ionized calcium concentration. This effect lasted for greater than 180 minutes when cats were given 2.0 mEq/kg or 4.0 mEq/kg. When cats were given 4 mEq of sodium bicarbonate/kg, serum ionized calcium concentration was significantly decreased, compared with that when cats were given lower doses, but only at 10 minutes after infusion. After sodium bicarbonate infusion, serum total calcium concentration, measured by ion-specific electrode and colorimetry, was lower than baseline values at most of the times evaluated. Decreases in serum ionized calcium and serum total calcium concentrations can be attributed only in part to an increase in serum or whole blood pH and to a decrease in serum protein concentration. Serum total calcium concentrations measured by ion-specific electrode and by colorimetry were positively correlated, but the variability was high. Only 44% of the variability in serum ionized calcium concentration could be predicted when serum total calcium, albumin, total protein, phosphorus, and bicarbonate concentrations and pH were considered.

Animals↗

PubMed1989

[Ionized calcium, total calcium and albumin corrected calcium in the serum in 1213 patients with suspected calcium metabolic diseases. A prospective multicenter study].

The correlation between serum ionized calcium, serum total calcium and albumin corrected total calcium was investigated in a prospective multicentre investigation of 1,213 patients with suspected calcium metabolic disease. 31.0% of the patients were misclassified when serum total calcium was measured instead of serum ionized calcium. The diagnostic discrepancy between the two methods decreased with the calculation of albumin corrected total calcium or calculated ionized calcium (17.9%). On justing for the analytical error connected with the measurement of ionized calcium, 11.2% of the patients were still misclassified. It is not possible precisely to predict serum ionized calcium from the measurement of serum total calcium and we recommend measurement of serum ionized calcium in patients believed to have calcium metabolic disease.

Calcium↗

PubMed1989

Subcellular regulation of the ionized calcium pool in isolated growth-plate chondrocytes.

At a low total endogenous calcium content, as in the reserve and proliferative zone chondrocyte, cells buffer their ionized calcium pool at a low steady state between 150 and 300 nM. The endoplasmic reticulum appears to be primarily effective in the regulation of the ionized calcium pool under these conditions. With calcium loading of 20 to 30 nmol Ca+2/mg protein, as in the hypertrophic zone chondrocyte, the cells buffer their ionized calcium pool at a higher steady state between 600 and 700 nM. The mitochondria appear to be primarily effective in buffering the cytosolic ionized calcium pool after calcium loading. These data suggest that in the growth plate as the chondrocyte approaches the mineralization front, there is an accumulation of intracellular calcium that results in the saturation of the capacity of the endoplasmic reticulum to buffer the ionized calcium pool at a low steady state. Under these conditions of calcium loading, there is an increase in the intracellular ionized calcium concentration and a shift toward mitochondrial buffering of this calcium pool. This study has clinical relevance because in the cartilaginous tissues of the growth plate and in fracture callus, the matrix mineralizes as a prerequisite step in the formation of bone. Intracellular calcium accumulation and calcium release appear to play a role in matrix mineralization. An understanding of how the chondrocyte regulates intracellular calcium homeostasis in states of calcium accumulation is important in the overall understanding of bone development and fracture healing.

Animals↗

PubMed1986

Aqueous and serum-based materials compared for use as simulated calibrators for three ionized calcium analyzers.

To determine if bias between different ionized calcium analyzers could be decreased, we analyzed 10 control fluids during a study in which ionized calcium was measured in more than 150 serum and whole-blood samples. After calibrating three ionized calcium analyzers (Radiometer ICA 1, Nova 8, and AVL 980) with the manufacturers' respective calibrators, we used the between-instrument differences of the control fluids to simulate recalibration of the analyzers during each analytical run. A filtered human serum pool containing ionized calcium at 1 mmol/L concentration, with CO2 removed and having no added buffer, was the only material that consistently decreased between-analyzer bias of both serum and whole blood. Another human serum pool containing about 1.3 mmol of ionized calcium and about 10 mmol of bicarbonate per liter was even better at minimizing analyzer biases for serum samples, but was not as effective for whole-blood samples. Some additives used to buffer pH apparently adversely affected both the accuracy and precision of some, but not other, calcium ion electrodes. We conclude that if a reference material is developed for calibration of ionized calcium analyzers, it should be tested on several analyzers for use with both serum and whole blood, and it should be at least as effective as a human serum material, such as that used here.

Calcium↗

PubMed1984

Interaction of hemolysis and genotype on ionized calcium in bile of mice with hemolysis-induced gallstones.

In this study, we used an ion-selective membrane electrode to measure ionized calcium in hepatic bile of control +/+ mice and nb/nb mice with hereditary hemolytic anemia. We found that biliary concentrations of ionized, bound, and total calcium were significantly higher (p less than 0.001) and magnesium was significantly lower (p less than 0.001) in nb/nb mice than in control +/+ mice. To separate the hemolytic process from genotypic influences, we transplanted genetically defective bone marrow from nb/nb mice into histocompatible nonhemolytic recipients (W/Wv). After successful engraftment, transplanted W/Wv mice had significantly higher biliary concentrations of ionized calcium than their untreated W/Wv counterparts (p less than 0.001); but bound and total calcium and magnesium concentrations were not different from untreated W/Wv controls. When compared with nb/nb mice, transplanted W/Wv mice had lower ionized calcium (p less than 0.001) and higher bound calcium concentrations (p less than 0.001) in their biles. These data indicate that ionized calcium in hepatic bile is significantly influenced by genotypic factors and subsequently increased in chronic hemolysis; and further, that increased ionized calcium in bile of mice with hemolysis is a risk factor, but of limited predictive value for hemolysis-induced gallstone formation.

Anemia, Hemolytic, Congenital↗

PubMed1984

[Cutaneous epitheliomas induced by ionizing radiation during radiotherapy. Presentation of 35 cases].

Thirty five cases of carcinomas of the skin, presumably induced by ionizing radiation therapy are reported. There was a precise topographic relationship between the site of irradiation and that of onset of tumor; in 31 cases, there were multiple neoplastic foci in the skin area exposed to ionizing radiation; a sufficiently long period of time had elapsed from the time of exposure to ionizing radiation to the clinical diagnosis of induced tumor; cases in which there were cutaneous carcinomas in other parts of the body as well as in the skin area exposed to the radiation were excluded from the series. Almost all patients had been subjected to ionizing radiation for treatment of benign diseases and 29 for arthrosis. The median age of the patients at the time of exposure to the ionizing radiation was 33,33 years. The radiation dose to which the patients had been subjected varied from 10 to 25 Gy; this dose is rather low, however it is in this dose range, according to Gray, a relatively high incidence of induced tumor is verified. The median interval between exposure to ionizing radiation and clinical finding of the tumor was 18.5 years. The carcinomas were observed almost always in the trunk and like spontaneous carcinomas at this site they were almost exclusively basal cell type.

Adult↗

PubMed1984

Effects of storage temperature and time before centrifugation on ionized calcium in blood collected in plain vacutainer tubes and silicone-separator (SST) tubes.

We studied the stability of ionized calcium and pH in samples stored at either room temperature or 4 degrees C, in centrifuged and uncentrifuged blood-collection tubes and in centrifuged tubes containing a silicone-separator gel (SST tubes). At room temperature, in uncentrifuged blood from healthy individuals, mean ionized calcium usually increased no more than 10 mumol/L per hour; at 4 degrees C it did not change detectably for 70 h. This stability was fortuitous, however: the concentrations of both hydrogen and lactate ions in these samples increased, apparently with offsetting effects on the concentration of ionized calcium. Blood stored for 70 h at 4 degrees C in centrifuged SST tubes, although showing a slightly greater change in ionized calcium, had less change of pH and no change in the ionized calcium corrected to pH 7.4. In 11 heparinized whole-blood samples from eight patients in intensive care, the mean change per hour in ionized calcium and pH after storage at room temperature was +10 mumol/L and -0.04 units, respectively.

Acute Disease↗

PubMed1993

pH and drug ionization affects ocular pressure lowering of topical carbonic anhydrase inhibitors.

PURPOSE: To evaluate the effect of drug ionization on the ocular hypotensive activity of topical carbonic anhydrase inhibitors. METHODS: Ocular normotensive New Zealand albino and ocular hypertensive Dutch Belted pigmented rabbits were used. Tonometric intraocular pressure levels were taken after topical application of 50 microliters of drug (at various concentrations and pH values) to one eye with the contralateral eye used as an untreated control. The drugs tested were MK-927, L-662,583, and AHR-16329. Eye tissues were analyzed for drug by our enzymatic methods. RESULTS: In all cases, the more ionized the applied drug the greater the ocular hypotensive activity. Tissue distribution studies showed that there was more drug found in the eye after the ionized form of a drug was applied than that found after application of the less ionized forms. CONCLUSIONS: Increasing the ionization of three ampholyte topical carbonic anhydrase inhibitors increases their ocular hypotensive activity. These data taken with ocular disposition data suggest that ionized compounds of this type are more readily sequestered in the cornea, which serves as a drug depot for prolonged drug delivery and activity.

Animals↗

PubMed1997

Concentration of ionized calcium in plasma from cats with urethral obstruction.

OBJECTIVE: To measure ionized calcium concentration in plasma from cats with urethral obstruction and to correlate these values with results of clinical biochemical analyses and physical examinations. DESIGN: Prospective study. ANIMALS: 24 male cats. PROCEDURE: Blood samples were obtained from each cat on admission, and PCV, pH, and concentrations of ionized calcium, total calcium, glucose, total solids, sodium, potassium, BUN, creatinine, chloride, magnesium, albumin, and phosphorus were determined. Mentation, tissue perfusion, and ECG recordings were also assessed. RESULTS: 18 (75%) cats had low ionized calcium concentrations (reference range, 2.4 to 2.8 mEq/L). Hypocalcemia was considered mild (2.0 to 2.36 mEq/L) in 9 (37.5%) cats, moderate (1.6 to 1.98 mEq/L) in 6 (25%), and severe (< 1.6 mEq/L) in 3 (12.5%). Significant positive correlations were found between ionized calcium concentration and heart rate, pH, and concentrations of sodium, chloride, and total calcium. Significant negative correlations were found between ionized calcium concentration and concentrations of potassium, BUN, creatinine, and phosphorus. CLINICAL IMPLICATIONS: Most cats with urethral obstruction had a low concentration of ionized calcium. This may contribute to cardiac electrical and mechanical dysfunction in some severely affected cats. Although effects of i.v. administration of calcium were not evaluated, results of this study strengthen the rationale for its use in cats with urethral obstruction.

Animals↗

PubMed1996

Vascular effects of occupational exposure to low-dose ionizing radiation.

Damage to the microcirculation caused by high-dose ionizing radiation is well known but data concerning low-dose exposure are scant and contrasting. We employed capillary microscopy to study dermal microcirculation damage resulting from occupational exposure to ionizing radiation doses lower than 5 rem/year (maximum permissible dose in Italy). We studied 145 physicians (60.7% radiologists, 33.8% orthopedic specialists, 5.5% cardiologists) occupationally exposed to ionizing radiation and a control group of 106 subjects in comparable but different occupations not exposed to ionizing radiation or to other skin hazards. All subjects were administered a clinical protocol and underwent capillary microscopy of the fingernail-fold. Capillary microscopy alterations were classified as absent, mild, moderate, marked and severe. Our data confirm that occupational exposure to low-dose ionizing radiation can lead to morphological and functional alterations of the dermal microcirculation, which can be identified early by capillary microscopy.

Adult↗

PubMed2005

JNK/p53 mediated cell death response in K562 exposed to etoposide-ionizing radiation combined treatment.

The study of the ability of chemotherapeutic agents and/or ionizing radiation (IR) to induce cell death in tumor cells is essential for setting up new and more efficient therapies against human cancer. Since drug and ionizing radiation resistance is an impediment to successful chemotherapy against cancer, we wanted to check if etoposide/ionizing radiation combined treatment could have a synergic effect to improve cell death in K562, a well-known human erythroleukemia ionizing radiation resistant cell line. In this study, we examined the role played by JNK/SAPK, p53, and mitochondrial pathways in cell death response of K562 cells to etoposide and IR treatment. Our results let us suppose that the induction of cell death, already evident in 15 Gy exposed cells, mainly in 15 Gy plus etoposide, may be mediated by JNK/SAPK pathway. Moreover, p53 is a potential substrate for JNK and may act as a JNK target for etoposide and ionizing radiation. Thus further investigation on these and other molecular mechanisms underlying the cell death response following etoposide and ionizing radiation exposure could be useful to overcome resistance mechanisms in tumor cells.

Antineoplastic Agents, Phytogenic↗