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PubMed2000

Parenteral iron use in the management of anemia in end-stage renal disease patients.

Intravenous iron is required by most dialysis patients receiving erythropoietin (EPO) to maintain an adequate hematocrit. In the United States, there are currently two parenteral iron preparations, iron dextran and iron gluconate, approved for such use, and a third product, iron sucrose, is under development. This article reviews each of these products. Each of the iron products increases the efficacy of EPO use in anemia management. There is considerable experience in the United States and elsewhere with the use of iron dextran. Although it is clinically effective, iron dextran is also associated with significant morbidity from both dose-dependent and -independent side effects. The slow release of iron from this complex necessitates a delay in monitoring iron indices after the administration of large doses of iron dextran. Recommended doses of iron sucrose appear very safe with little risk of anaphylactic reactions. Adverse effects are uncommon and not life threatening. If approved for use in the United States, iron sucrose may be a safe and effective alternative to iron dextran. Iron dissociates from iron gluconate quite rapidly and may increase the production of ionized free iron. Iron gluconate may be a safe alternative to iron dextran for patients with severe reactions, including anaphylaxis. The risk of allergic reactions to iron gluconate is very low. The exact place in therapy for the newer iron complexes remains unclear. Currently available data suggest that iron sucrose and iron gluconate may have diminished adverse effect profiles when compared with iron dextran. Additional clinical experience will establish the role for these new iron products.

Anemia, Iron-Deficiency↗
PubMed2003

Comparison of antibacterial and toxic effects of various root canal irrigants.

AIM: To compare the antibacterial properties and toxicity of 5.25% sodium hypochlorite (NaOCl), 2% chlorhexidine gluconate and 0.2% chlorhexidine gluconate plus 0.2% cetrimide (Cetrexidin); Vebas, San Giuliano, Milan, Italy). METHODOLOGY: The antibacterial effects of the irrigants in vitro were examined after 5 min and 48 h in freshly extracted human teeth with single roots, whose canals were infected by Enterococcus faecalis ATCC 29212. In a separate in vivo study, bacterial culture samples were collected before treatment from the infected root canals of deciduous teeth containing necrotic pulp tissue. Irrigants were used to clean the canals which were then left empty for 48 h. Aerobic/facultative anaerobic and anaerobic bacterial growth were compared before and 48 h after irrigation. Finally, the toxic effects of the irrigants were assessed by injecting them into the subcutaneous tissues of rats. The inflammatory reactions that occurred 2 h, 48 h and 2 weeks after the injections were evaluated. RESULTS: In the laboratory study, the 2% chlorhexidine gluconate and Cetrexidin were significantly more effective on E. faecalis than the 5.25% NaOCl at 5 min (P < 0.05). Similarly, in the in vivo study, 2% chlorhexidine gluconate and Cetrexidin were significantly more effective on anaerobic bacteria than the 5.25% NaOCl at 48 h (P < 0.05). At the end of 2 weeks, the toxicity of the NaOCl solution was greater than that of the other irrigants (P < 0.05). CONCLUSIONS: Cetrexidin and 2% chlorhexidine gluconate were more effective, and had more residual antibacterial effects and lower toxicity than 5.25% NaOCl solution.

Animals↗
PubMed2000

Effects of anion substitution on hydration behavior and water uptake of the red-spotted toad, Bufo punctatus: is there an anion paradox in amphibian skin?

Amphibians absorb water osmotically across their skins and rely on chemosensory information from the skin to assess the suitability of hydration sources. The time spent with skin in contact with a moist surface provides a quantitative measure of their ability to perceive the ionic and osmotic properties of aqueous solutions. Dehydrated toads given hyperosmotic (250 mM) solutions of NaCl or Na-gluconate showed significantly longer periods of hydration behavior on the gluconate solution, but they lost water osmotically when immersed in either solution. Similarly, dehydrated toads given 250 mM solutions of NaCl, Na-acetate, Na-phosphate or Na-gluconate showed a progressively greater length of hydration time on solutions with the larger mol. wt anions. These results are consistent with the chemosensory phenomenon previously described in mammalian tongue as 'anion paradox'. On dilute (50 mM) solutions of NaCl or Na-gluconate, the hydration time was not different between anions, despite toads gaining water more rapidly when immersed in dilute NaCl than in Na-gluconate solutions. The differing behavioral results with hyperosmotic and hypoosmotic salt solutions suggest that chemosensory transduction through toad skin involves both transcellular and paracellular pathways.

Animals↗
PubMed2005

Update on adverse drug events associated with parenteral iron.

BACKGROUND: We previously compared the safety profile of three formulations of intravenous iron used during 1998-2000 and found higher rates of adverse drug events (ADEs) associated with the use of higher molecular weight iron dextran and sodium ferric gluconate complex compared with lower molecular weight iron dextran. Since that time, iron sucrose has become widely available and clinicians have gained additional experience with sodium ferric gluconate complex. METHODS: We obtained data from the United States Food and Drug Administration (FDA) on ADEs attributed to the provision of four formulations of intravenous iron during 2001-2003, including higher and lower molecular weight iron dextran, sodium ferric gluconate complex and iron sucrose. We estimated the odds of intravenous iron-related ADEs using 2 x 2 tables and the chi(2) test. RESULTS: The total number of reported parenteral iron-related ADEs was 1141 among approximately 30,063,800 doses administered, yielding a rate of 3.8 x 10(-5), or roughly 38 per million. Eleven individuals died in association with the ADE. Relative to lower molecular weight iron dextran, total and life-threatening ADEs were significantly more frequent among recipients of higher molecular weight iron dextran and significantly less frequent among recipients of sodium ferric gluconate complex and iron sucrose. The absolute rates of life-threatening ADEs were 0.6, 0.9, 3.3 and 11.3 per million for iron sucrose, sodium ferric gluconate complex, lower molecular weight iron dextran and higher molecular weight iron dextran, respectively. Based on differences in the average wholesale price of iron sucrose and lower molecular weight iron dextran in the US, the cost to prevent one life-threatening ADE related to the use of lower molecular weight iron dextran was estimated to be 5.0-7.8 million dollars. The cost to prevent one lower molecular weight iron dextran-related death was estimated to be 33 million dollars. CONCLUSIONS: The frequency of intravenous iron-related ADEs reported to the FDA has decreased, and overall, the rates are extremely low. This is the fourth report suggesting increased risks associated with the provision of higher molecular weight iron dextran. Life-threatening and other ADEs appear to be lower with the use of non-dextran iron formulations, although the cost per ADE prevented is extremely high.

Adverse Drug Reaction Reporting Systems↗
PubMed2006

Multivariate analysis of microarray data by principal component discriminant analysis: prioritizing relevant transcripts linked to the degradation of different carbohydrates in Pseudomonas putida S12.

The value of the multivariate data analysis tools principal component analysis (PCA) and principal component discriminant analysis (PCDA) for prioritizing leads generated by microarrays was evaluated. To this end, Pseudomonas putida S12 was grown in independent triplicate fermentations on four different carbon sources, i.e. fructose, glucose, gluconate and succinate. RNA isolated from these samples was analysed in duplicate on an anonymous clone-based array to avoid bias during data analysis. The relevant transcripts were identified by analysing the loadings of the principal components (PC) and discriminants (D) in PCA and PCDA, respectively. Even more specifically, the relevant transcripts for a specific phenotype could also be ranked from the loadings under an angle (biplot) obtained after PCDA analysis. The leads identified in this way were compared with those identified using the commonly applied fold-difference and hierarchical clustering approaches. The different data analysis methods gave different results. The methods used were complementary and together resulted in a comprehensive picture of the processes important for the different carbon sources studied. For the more subtle, regulatory processes in a cell, the PCDA approach seemed to be the most effective. Except for glucose and gluconate dehydrogenase, all genes involved in the degradation of glucose, gluconate and fructose were identified. Moreover, the transcriptomics approach resulted in potential new insights into the physiology of the degradation of these carbon sources. Indications of iron limitation were observed with cells grown on glucose, gluconate or succinate but not with fructose-grown cells. Moreover, several cytochrome- or quinone-associated genes seemed to be specifically up- or downregulated, indicating that the composition of the electron-transport chain in P. putida S12 might change significantly in fructose-grown cells compared to glucose-, gluconate- or succinate-grown cells.

Carbohydrate Metabolism↗
PubMed1982

Effect of phosphoglycerate mutase deficiency on heterotrophic and autotrophic carbon metabolism of Alcaligenes eutrophus.

Mutants of Alcaligenes eutrophus were isolated on the basis of their inability to grow on succinate as the sole source of carbon and energy. The mutants also failed to grow on other gluconeogenic substrates, including pyruvate, acetate, and citrate. Simultaneously, they had lost their capability for autotrophic growth. The mutants grew, but slower than the wild type, on fructose or gluconate. Growth retardation on gluconate was more pronounced. The mutants lacked phosphoglycerate mutase activity, and spontaneous revertants of normal growth phenotype had regained the activity. The physiological characteristics of the mutants indicate the role of phosphoglycerate mutase in heterotrophic and autotrophic carbon metabolism of A. eutrophus. Although the enzyme is necessary for gluconeogenesis during heterotrophic growth on three- or four-carbon substrates, its glycolytic function is not essential for the catabolism of fructose or gluconate via the Entner-Doudoroff pathway. The enzyme is required during autotrophic growth as a catalyst in the biosynthetic route leading from glycerate 3-phosphate to pyruvate. It is suggested that the mutants accomplish the complete degradation of fructose and gluconate mutase lesion. The catabolically produced triose phosphates are converted to fructose 6-phosphate which is rechanneled into the Entner-Doudoroff pathway. This carbon recycling mechanism operates less effectively in mutant cells growing on gluconate.

Alcaligenes↗
PubMed1990

Relative osmotic effects of raffinose, KCl, and NaCl across basolateral cell membrane.

Lumen-collapsed segments of rabbit S2 proximal tubule were bathed in isotonic medium and then exposed acutely to a medium made hypertonic by the addition of raffinose, NaCl, KCl, Na gluconate, K gluconate, or choline Cl. The result was a rapid efflux of water and a shrinking of the tubule, which could be measured by video techniques within the first 0.1 s. After reequilibration in isotonic medium, each tubule was then exposed to a second hypertonic medium to provide a direct comparison between two different solutes, either NaCl vs. KCl or raffinose vs. any one of the other solutes. Because raffinose is impermeant across the basolateral cell membrane, the ratio of its effect to that of another solute is a measure of the reflection coefficient (sigma) of that other solute. The following results were obtained: sigma KCl = 0.70 +/- 0.02, sigma K gluconate = 0.97 +/- 0.07, sigma Na gluconate = 0.84 +/- 0.06, and sigma choline Cl = 0.75 +/- 0.06. We previously have reported sigma NaCl = 0.56 +/- 0.07. If sigma of each salt is considered to be the arithmetic average of its component parts, and if gluconate and choline are considered to be impermeant, we also obtain sigma Na+ = 0.68, sigma K+ = 0.94, and sigma Cl- = 0.50.

Animals↗
PubMed1982

Experiments and ultrastructural investigations on the mouse embryo during early teratogen-sensitive stages.

The effect of iron gluconate on the mouse embryo was studied in early embryonic development before the chorioallantoic placenta was established. Iron gluconate is teratogenic to mouse embryos after intraperitoneal application to pregnant mice on the 8th and 9th days of gestation. The most pronounced defect is exencephaly. As seen with the electron microscopy, iron gluconate enters the cells of the yolk sac. The excessive uptake of iron gluconate in the cells of the yolk sac alters these cells for a short period. Iron gluconate is visible, neither in the cells of the head process nor in the cells of the neuroectoderm, but the neuroectodermal cells show necrotic degeneration. Two different types of necrosis can be found; these appear at a time (13-22 h after maternal treatment) when the yolk sac cells are normalized again.

Abnormalities, Drug-Induced↗
PubMed1985

Attenuation of aspirin analgesia by calcium loading in healthy subjects.

To clarify the mechanism of aspirin analgesia, the relationship among analgesic and hypocalcemic effects and pharmacokinetics of aspirin was investigated in 20 healthy subjects at 20-23 years old. Four experimental groups were made, that is, (1) aspirin 1.0 g, (2) aspirin 1.0 g + calcium gluconate 1.5 g X 2, (3) calcium gluconate 1.5 g X 2, (4) control (placebo). Calcium gluconate was administered orally twice, that is, 30 and 90 min after oral administration of aspirin. The experiments were carried out under a double blind method. As an analgesic test, the ultrasonic method was used. Aspirin (1.0 g) caused a significant analgesia, the effect reaching the maximum at 90 min and prolonging for about 3 h. Simultaneously, plasma calcium level significantly decreased and kept going down, at least, until 180 min after administration of aspirin. However, when calcium gluconate was loaded at 30 and 90 min after administration of aspirin, both the analgesic and hypocalcemic effects of aspirin were significantly inhibited. The plasma aspirin concentration reached a maximum 30-60 min after administration of aspirin in both groups: aspirin alone and aspirin with calcium gluconate. On the other hand, plasma salicylic acid concentration kept increasing up to 180 min after administration of aspirin in either group. The plasma aspirin and salicylic acid levels in both groups were similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1999

Iron management: innovative solutions to persistent challenges--focus on Ferrlecit.

The use of sodium ferric gluconate in sucrose injection (Ferrlecit) in the treatment of anemia in patients with end stage renal disease (ESRD) was the major topic at the symposium "Iron Management: Innovative Solutions to Persistent Challenges," held April 14, 1999 during the annual ANNA 30th National Symposium in Baltimore, Maryland. Chairperson Susan Vogel, MHA, RN, CNN, addressed the challenges of anemia management and the limitations of oral iron supplements. She described available intravenous (i.v.) iron therapies and reviewed clinical trial data that demonstrated an excellent safety and efficacy profile for the newly approved i.v. iron supplement, sodium ferric gluconate. Suzanne Schweitzer, RPh, MPH, discussed iron metabolism and the U.S. labeling for sodium ferric gluconate, with a focus on dosing and administration. In the final presentation, Suzanne Seiler, RN, described her clinic's experience with sodium ferric gluconate and provided an experimental dosing and monitoring protocol. Together, these presentations suggest that sodium ferric gluconate is an important new tool for meeting the challenges of iron management in ESRD patients.

Anemia, Iron-Deficiency↗
PubMed2005

Study of magnesium bioavailability from ten organic and inorganic Mg salts in Mg-depleted rats using a stable isotope approach.

Literature data on the bioavailability of various Mg forms provide scarce information on the best Mg salt to be used in animal and human supplementation. This study aimed to investigate the bioavailability of different forms of Mg in rats using Mg stable isotopes. Eighty male Wistar rats aged 6 weeks were fed a semi-purified Mg-depleted diet for three weeks. The rats were then randomised into ten groups and received, for two more weeks, the same diet repleted with Mg (550 mg Mg/kg) as: oxide, chloride, sulphate, carbonate, acetate, pidolate, citrate, gluconate, lactate or aspartate. After 10 days of Mg-repleted diet, the rats received orally 1.8 mg of an enriched 26Mg. Faeces and urine were then collected for 4 consecutive days. Isotope ratios in faeces and urine were determined. The Mg absorption values obtained varied from 50% to 67%. Organic Mg salts were slightly more available than inorganic Mg salts. Mg gluconate exhibited the highest Mg bioavailability of the ten Mg salts studied. Urinary 26Mg excretion varied from 0.20 mg to 0.33 mg, and feeding with the organic pidolate, citrate, gluconate and aspartate salts resulted in higher urinary 26Mg excretion than with inorganic salts. Ultimately, 26Mg retention was higher in the rats receiving the organic salts such as gluconate, lactate and aspartate than in those receiving the inorganic salts. Taken together, these results indicate that 26Mg is sufficiently bioavailable from the ten different Mg salts studied in the present experiment, although Mg gluconate exhibited the highest bioavailability under these experimental conditions.

Animals↗
PubMed2006

Bactericidal effect of Er,Cr:YSGG laser on Streptococcus mutans.

The aim of this study was to compare the antibacterial activities of Er,Cr:YSGG laser with two different power outputs against a chlorhexidine gluconate-based cavity disinfectant. A cavity tooth model test was used to determine the antibacterial activity. Four cylindrical cavities were prepared on the dentin surface of 10 bovine incisors and left in contact with Streptococcus mutans for 72 hours to allow bacterial invasion. Following which, Er,Cr:YSGG laser with 0.75 W and 1 W power outputs and a chlorhexidine gluconate-based cavity disinfectant were applied separately on one of the three infected cavities, whereas the fourth was left untreated for control. Standardized amounts of dentin chips were obtained from the cavity walls, and the number of bacteria recovered was counted. Statistical analysis was carried out using one-way ANOVA and Dunnett's C test (p=0.05). No significant differences were observed among the data obtained from the chlorhexidine gluconate-based cavity disinfectant and the two Er,Cr:YSGG laser groups (p>0.05). However, when compared to the control group, both Er,Cr:YSGG laser groups and the chlorhexidine gluconate-based cavity disinfectant resulted in significantly less bacterial recovery (p<0.05). In conclusion, the antibacterial activity on S. mutans demonstrated by Er,Cr:YSGG laser with both energy outputs was similar to that of the tested chlorhexidine gluconate-based cavity disinfectant.

Animals↗
PubMed1998

[Two patients with chlorhexidine allergy--anaphylactic reactions and eczema].

A 14 year-old girl experienced a combined delayed and immediate type of allergy to chlorhexidine. She first developed an eczematous reaction in the face following the long-term application of an antiacne preparation. Use test (repeated Open Application Test, ROAT) on the forearm was positive. Epicutaneous tests with 1% chlorhexidine gluconate and acetate were both positive. About six months later she developed an urticarial rash and syncope after cleansing the skin with chlorhexidine gluconate. Prick tests were positive to 0.05% chlorhexidine gluconate and to 0.01% of the acetate solution. A 30 year-old man developed anaphylactic symptoms following treatment with an antiseptic dental gel containing 1% chlorhexidine gluconate. Prick test was positive to the gel and to chlorhexidine gluconate 0.5%.

Adolescent↗
PubMed1977

Fermentation of glucose by Acetobacter melanogenus.

Growing cultures of Acetobacter melanogenus ATCC 9937 concerted D-glucose to 2,5-diketo-D-gluconic acid with D-gluconic acid and 5-keto-D-gluconic acid as intermediates. The 2,5-diketo-D-gluconic acid was isolated from the fermented medium by treatment with an anion exchange resin.

Acetobacter↗
PubMed1989

The influence of the culture pH value on the direct glucose oxidative pathway in Klebsiella pneumoniae NCTC 418.

Klebsiella pneumoniae NCTC 418 was cultured aerobically in chemostat cultures (D = 0.3 h-1; 35 degrees C) under respectively carbon-, phosphate-, potassium-, sulphate-, and ammonia-limited conditions with glucose as the sole carbon and energy source. The effect of the external pH value on glucose metabolism and on the enzymes of the direct glucose oxidative pathway was examined. The pH value of the medium had a profound influence on both the activity and the synthesis of the glucose dehydrogenase and the gluconate dehydrogenase. At pH values ranging from pH 5.5 to pH 6.0 maximal activity and synthesis of these enzymes resulted in a more than 80% conversion of the glucose consumed into gluconate and 2-ketogluconate under potassium- or phosphate-limited conditions. On the other hand, no gluconate and/or 2-ketogluconate production could be detected when K. pneumoniae was cultured at pH 8.0. Whereas the synthesis of gluconate dehydrogenase seemingly was completely repressed, still some glucose dehydrogenase was present. The lack of glucose dehydrogenase activity at pH 8.0 was shown not to be due to the dissociation of the cofactor PQQ from the enzyme.

Aerobiosis↗
PubMed1977

Energy conservation during aerobic growth in Paracoccus denitrificans.

Paracoccus denitrificans was aerobically grown in chemostat culture with succinate or gluconate as carbon source. Due to the presence of two phosphorylation sites in the respiratory chain and the absence of branching, theoretical P/O ratios of 1.71 and 1.82 were calculated for cells growing respectively with succinate and gluconate as carbon source. Using these data, 95% confidence intervals for the P/O ratio were determined, via a mathematical model, at 0.91-1.15 and 1.00-1.37 for sulphate-limited cultures, with respectively succinate and gluconate as carbon source. These results and measurements of P/O ratios in membrane particles and of proton translocation in whole cells have led to the conclusion that site I phosphorylation is affected under sulphate-limited conditions. Under conditions of carbon source-limitation the endogenous leads to H+/O ratio is about 7-8. Average values of 3.40 and 4.78 were respectively found for sulphate-limited succinate- and gluconate grown cells. For starved cells, oxidizing succinate as exogenous substrate, the leads to H+/O ratios were determined at about 3-4, independent of the growth limiting factor. It is concluded that the number of protons ejected per pair of electrons per energy-conserving site (leads to H+/site ratio) is about 3-4, instead of 2 as postulated by the chemiosmotic hypothesis.

Aerobiosis↗
PubMed1976

Permeability of sarcoplasmic reticulum membrane. The effect of changed ionic environments on Ca2+ release.

Permeability properties and the effects of a changed membrane potential on Ca2+ release of sarcoplasmic reticulum vesicles of rabbit skeletal muscle were investigated by Millipore filtration. The relative permeability of sarcoplasmic reticulum to solutes determined under conditions of isotope exchange at equilibrium and/or under conditions of net flow of solute and water into the vesicles was as follows: sucrose, Ca2+, Mn2+ less than gluconate-, choline+, Tris+ less than methanesulfonate- less than urea, glycerol, K+, Na+,Li+, Cl-. Transient membrane potentials were induced by rapidly changing the ionic environment of the vesicles. Knowledge of the relative permeation rates of the above ions allowed prediction of the direction and extent of membrane polarization. Osmotic effects in the polarization measurements due to the rapid influx of solute and water into the vesicles were minimized by using media containing a fast (K+ or Cl-) and a relatively slow (gluconate- or choline+) penetrating ion. 45Ca2+ efflux from vesicles derived from different parts of the sarcoplasmic reticulum structure was not appreciably changed when vesicles were made more positive inside (choline chloride leads to potassium gluconate) or more negative inside (potassium gluconate leads to choline chloride). These studies suggest that part or all of the ion-induced changes in sarcoplasmic reticulum membrane permeability, previously interpreted to indicate "depolarization" -induced Ca2+ release, may be due to osmotic effects.

Animals↗
PubMed2000

Successful treatments of lung injury and skin burn due to hydrofluoric acid exposure.

Recent growth in the electronics and chemical industries has brought about a progressive increase in the use of hydrofluoric acid (HF), along with the concomitant risk of acute poisoning among HF workers. We report severe cases of inhalation exposure and skin injury which were successfully treated by administering a 5% calcium gluconate solution with a nebulizer and applying 2.5% calcium gluconate jelly, respectively. Case 1: A 52-year old worker used HF for surface treatment after welding stainless steel, and was hospitalized with rapid onset of severe dyspnea. On admission to the critical care medical center he had widespread wheezing and crackles in his lungs. Chest radiograph showed a fine diffuse veiling over both lower pulmonary fields. Severe hypocalcemia with high concentrations of F in serum and urine were disclosed. He was immediately given 5% calcium gluconate solution by intermittent positive-pressure breathing (IPPB), utilizing a nebulizer. On the 21st hospital day, chest film and CT scan did not demonstrate any abnormality. He was discharged very much improved on the 22nd hospital day. Case 2: A 35-year old worker at an electronics factory was admitted to his local hospital with severe skin burn on his face and neck after exposure to 100% HF. Treatment began with immediate copious washing with water for 20 min. Calcium gluconate 2.5% gel (HF burn jelly) was applied to the area as a first-aid measure. Persistent high concentrations of serum and urinary F were disclosed for 2 weeks. After treatment with applications of HF burn jelly, he was confirmed as being completely recovered. The present cases and a review of published data suggest that an adequate method of emergency treatment for accidental HF poisoning is necessary.

Administration, Topical↗