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PubMed1981

The ultrastructure of renomedullary interstitial cells in hypercalcemia induced by calcium gluconate.

Under hypercalcemia induced by calcium gluconate the degranulation of renomedullary interstitial cells accompanied with the increase in volume of the rough and smooth surfaced endoplasmic reticulum and enlargement of the Golgi apparatus were observed. The ultrastructural changes can be regarded as an expression of the increase of a synthetic and secretory activity of these cells. Because the changes of renomedullary cells observed in hypercalcemia induced by calcium gluconate are not really different from that observed in hypercalcemia induced by vitamin D3 (Roszkiewicz et al. 1979) it can suppose that these changes may be connected solely with a calcium serum elevation and that the renomedullary interstitial cells rather do not play any important role in vitamin D3 metabolism.

Animals↗
PubMed1993

[Triggered activities in cat heart induced by combined administration of ouabain and calcium gluconate].

The pharmacological effects of i.v. a mixture of ouabain (Oua) (50 micrograms.kg-1) and calcium gluconate (Ca2+) (100 mg.kg-1) on the electric activities of the cat hearts (n = 19) were studied by using a contact electrode and a contact electrode catheter to record both epicardial and endocardial monophasic action potentials (MAP). The results showed that the 2 drugs together reduced the MAP amplitude, decreased Vmax, and lengthened the MAP duration. Ouabain induced triggered activities, eg, early afterdepolarization, early afterhyperpolarization, delayed afterdepolarization including oscillatory afterpotentials, and triggered arrhythmias, which were enhanced by calcium gluconate. Endocardium is more sensitive than epicardium to ouabain.

Action Potentials↗
PubMed1993

Effect of hypoxia on the accumulation of technetium-99m-glucarate and technetium-99m-gluconate by Chinese hamster ovary cells in vitro.

The accumulation of 99mTc-glucarate, an agent recently reported to localize in acutely infarcted myocardium, zones of acute cerebral injury and tumors, has been compared with 99mTc-gluconate in an in vitro system of cultured Chinese hamster ovary fibroblasts. The effects on accumulation of hypoxia and competition with fructose have been studied. Both labeled glucose analogs showed a two- to threefold enhanced accumulation in hypoxic cells relative to aerobic cells. No such enhanced accumulation under hypoxia was observed for the nonsugar tracers pertechnetate and 99mTc-DTPA. The presence of 20 mM fructose reduced the accumulation of 99mTc-glucarate by 30% (p = 0.067) and 99mTc-gluconate by 40% (p < 0.05) in hypoxic cells, but had no significant effect in aerobic cells. These results suggest that both compounds at least partially share a common mechanism of uptake and/or accumulation with fructose.

Animals↗
PubMed2000

Disinfection of eyelid specula with chlorhexidine gluconate (Hibiclens) after examinations for retinopathy of prematurity.

BACKGROUND: The preferred method of cleaning eyelid specula between examinations for retinopathy of prematurity is unknown. A previous study showed that disinfection with 70% isopropyl alcohol swabs fails to eliminate viruses and bacteria from the specula. OBJECTIVE: To determine if alternative sterilization procedures would allow multiple use of a single speculum without risking nosocomial infection. METHODS: In phase 1, 40 autoclave-sterilized eyelid specula were randomized into either "cleaned" or "patient control" groups after being used for routine retinopathy of prematurity examinations performed in the outpatient setting. Specula in the cleaned group were cleaned with chlorhexidine gluconate (Hibiclens). Specula in the patient control group were not cleaned after use. All study specula were placed into enriched culture media from which bacterial and fungal cultures were obtained. In phase 2, 20 autoclave-sterilized eyelid specula were inoculated with a clinically relevant dilution of adenovirus serovar 5 or herpes simplex type 2. Specula were randomized into either a cleaned or a control group, and cell cultures and immunofluorescence assays were used to document and confirm, respectively, viral growth. RESULTS: In phase 1, all 20 cultures from the patient control group grew bacteria compared with 0 (0%) of 20 cultures from the cleaned group and 0 (0%) of 5 from the cleaned control group. No fungi were isolated from any group. In phase 2, all 10 cultures from specula inoculated with adenovirus serovar 5 grew virus. None of the cultures from the 5 cleaned specula inoculated with herpes simplex type 2 grew virus. In contrast, all 5 cultures in the control group were positive for growth of herpes simplex type 2. CONCLUSIONS: Autoclave sterilization is the ideal method of sterilization of eyelid specula between neonate examinations. When an alternative disinfection technique is required, washing the speculum with chlorhexidine gluconate and tap water is preferred over wiping with a 70% isopropyl alcohol swab. Arch Ophthalmol. 2000;118:786-789

Adenoviruses, Human↗
PubMed2000

Molecular modeling of substrate binding in wild-type and mutant Corynebacteria 2,5-diketo-D-gluconate reductases.

2,5-diketo-D-gluconic acid reductase (2,5-DKGR; E.C. 1.1.1.-) catalyzes the Nicotinamide adenine dinucleotide phosphate (NADPH)-dependent stereo-specific reduction of 2, 5-diketo-D-gluconate (2,5-DKG) to 2-keto-L-gulonate (2-KLG), a precursor in the industrial production of vitamin C (L-ascorbate). Microorganisms that naturally ferment D-glucose to 2,5-DKG can be genetically modified to express the gene for 2,5-DKGR, and thus directly produce vitamin C from D-glucose. Two naturally occurring variants of DKGR (DKGR A and DKGR B) have been reported. DKGR B exhibits higher specific activity toward 2,5-DKG than DKGR A; however, DKGR A exhibits a greater selectivity for this substrate and significantly higher thermal stability. Thus, a modified form of DKGR, combining desirable properties from both enzymes, would be of substantial commercial interest. In the present study we use a molecular dynamics-based approach to understand the conformational changes in DKGR A as the active site is mutated to include two active site residue changes that occur in the B form. The results indicate that the enhanced kinetic properties of the B form are due, in part, to residue substitutions in the binding pocket. These substitutions augment interactions with the substrate or alter the alignment with respect to the putative proton donor group. Proteins 2000;39:68-75.

Amino Acid Substitution↗
PubMed1988

Mucosal injuries following intratympanic applications of chlorhexidine gluconate in the cat.

We investigated the morphological changes of the middle ear mucosa of the cat exposed to two different concentrations of the disinfectant, chlorhexidine gluconate. In the high concentration (2%) group, notable destructive changes were found on the mucosal surfaces in the tympanic cavity and were especially most severe in that area lined with few ciliated cells under normal conditions. Cilia were twisted and decreased in length in this site. At the tympanic orifice of the eustachian tube, cilia were distributed densely and showed little destructive changes on the surface. In the clinical concentration (0.05%) group, mucosal injuries generally seemed more slight when compared with those in the high concentration group. However, a decrease in the number of cilia or actual loss of cilia was one of the features in this group. Infrequent defects of the superstructures of the epithelial cells were noted on the mucosal surface, but these injuries appeared to spare the basal lamina. In both groups, there were no calcified pathologies seen and no complete obliterations by thickened mucosa or granulations. Deterioration of the ciliary system by chlorhexidine gluconate seems to produce subsequent cell destruction of the middle ear mucosa.

Animals↗
PubMed2005

Chlorhexidine gluconate: an ideal scolicidal agent in the treatment of intraperitoneal hydatidosis?

Hydatid disease is a parasitic disease that is treated primarily by surgery. The most important complication of surgical treatment is spillage of the contents of the cyst, leading to secondary dissemination. In this study, the effect of chlorhexidine gluconate (Chx-Glu) was investigated in the treatment of experimental intraperitoneal hydatidosis (IPH). IPH was reproduced in 100 Wistar albino rats by inoculation with 1 ml of a suspension contained approximately 1500 viable protoscolices of Echinococcus granulosus following determination of scolicidal activity of chlorhexidine gluconate in vitro. Five minutes after protoscolex inoculation, 5 ml of the scolicidal solution was instilled into the peritoneal cavity: 0.9% NaCl (control group), 4.0% Chx-Glu, 0.4% Chx-Glu, and 0.04% Chx-Glu. After 6 months of follow-up, the rats were sacrificed, and the number of isolated cysts, peroperative and postoperative deaths, and toxicity were evaluated. Cyst formation did not occur in any of the Chx-Glu groups compared to the control group (p < 0.05), whereas it was detected in all of the control rats. In addition, to 4.0% Chx-Glu was found to be more toxic and to cause a high mortality rate compared to the 0.4% and 0.04% Chx-Glu groups and the control group (p < 0.05). Chx-Glu 0.04% was found to be the most potent, nontoxic agent; it is easily available, inexpensive, and highly potent in a short period of time at the low concentration. Chx-Glu 0.04% can be used safely in the treatment of intraperitoneal hydatidosis and hydatid cyst.

Animals↗
PubMed1986

The pharmacodynamic response of the basal skin potential to quinidine gluconate.

The basal skin potential (BSP) was explored as an indirect means of continuously monitoring the cardiac response of quinidine gluconate. A method was developed to follow the BSP using a high impedance, recording polygraph and nonpolarizing calomel electrodes. Intravenous administration of quinidine gluconate caused time dependent changes in the BSP. Further studies showed that blood levels during the elimination phase and the QT interval of the electrocardiogram (ECG) over their entire time period were highly correlated with the BSP. Optimal correlation with the QT interval occurred when the BSP curve was shifted to earlier times by approximately 10 minutes, reflecting possible differences in the accessibility or mechanism of the respective pharmacologic compartments. Further application of the BSP for pharmacodynamic monitoring will require electrode refinements and an increased understanding of its mechanism of action.

Animals↗
PubMed2004

Gluconate dehydratase from the promiscuous Entner-Doudoroff pathway in Sulfolobus solfataricus.

An investigation has been carried out into gluconate dehydratase from the hyperthermophilic Archaeon Sulfolobus solfataricus. The enzyme has been purified from cell extracts of the organism and found to be responsible for both gluconate and galactonate dehydratase activities. It was shown to be a 45 kDa monomer with a half-life of 41 min at 95 degrees C and it exhibited similar catalytic efficiency with both substrates. Taken alongside the recent work on glucose dehydrogenase and 2-keto-3-deoxygluconate aldolase, this report clearly demonstrates that the entire non-phosphorylative Entner-Doudoroff pathway of S. solfataricus is promiscuous for the metabolism of both glucose and galactose.

Amino Acid Sequence↗
PubMed2005

Anaphylactoid reaction to intravenous sodium ferric gluconate complex during pregnancy.

We report the first case of a severe anaphylactic or anaphylactoid reaction to sodium ferric gluconate complex in a pregnant patient. Sodium ferric gluconate complex is felt to be one of the safest forms of iron therapy during pregnancy. This case highlights the need for extreme caution and vigilance in pregnant patients receiving any type of parenteral iron therapy.

Adult↗
PubMed2003

Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients.

Patients with controlled background pain associated with cancer frequently also experience episodes of moderate to severe intensity breakthrough pain. Opioid pharmacotherapy, particularly with oral morphine, remains the cornerstone for the management of cancer pain. Nasal administration of opioids provides a mechanism for more rapid drug absorption and more rapid onset of pain relief compared with oral dosing. This non-randomized, open-label, uncontrolled investigation evaluated the pharmacokinetics, safety and efficacy of a single 40 mg dose of nasal morphine gluconate, administered to cancer patients in response to an episode of breakthrough pain. Single dose nasal morphine gluconate administered to 11 patients was associated with effective plasma morphine concentrations (mean C(max) 64 ng/ml; range 33.8-121 ng/ml) and low plasma morphine metabolites (morphine-6-glucuronide mean C(max) 114 ng/ml; range 46-189 ng/ml; morphine-3-glucuronide mean C(max) 572 ng/ml; range 257-990 ng/ml). Side effects were minor and limited to nasal irritation. Patients reported rapid onset of pain relief (perceptible pain relief achieved in 10/11 patients, time to onset 2.4+/-2.1 min; and meaningful pain relief, achieved in five patients, 6.8+/-7.3 min to onset, mean t(max) 0.36 h). Pain intensity scores were significantly reduced at all times after dosing; pain relief scores were unchanged. Patient satisfaction ratings were high. These results show that nasal morphine has rapid absorption and apparent onset of effect. Additional multi-dose, dose-ranging and placebo-controlled studies of nasal morphine for cancer pain are warranted.

Administration, Intranasal↗
PubMed1998

Perioperative use of 0.12% chlorhexidine gluconate for the prevention of alveolar osteitis: efficacy and risk factor analysis.

OBJECTIVES: The purposes of this study were to evaluate the use of 0.12% chlorhexidine gluconate as a prophylactic therapy for the prevention of alveolar osteitis and to further examine subject-based risk factors associated with alveolar osteitis. STUDY DESIGN: The trial was a randomized, double-blind, placebo-controlled, parallel-group study conducted among 279 subjects, each of whom required oral surgery for the removal of a minimum of one impacted mandibular third molar. Subjects were instructed to rinse twice daily with 15 ml of chlorhexidine or placebo mouthrinse for 30 seconds for 1 week before and 1 week after the surgical extractions. This regimen included a supervised presurgical rinse. Alveolar osteitis diagnosis was based on the subjective finding of increasing postoperative pain at the surgical site that was not relieved with mild analgesics, supported by clinical evidence of one or more of the following: loss of blood clot, necrosis of blood clot, and exposed alveolar bone. RESULTS: In comparison with use of the placebo mouthrinse, prophylactic use of the chlorhexidine mouthrinse resulted in statistically significant (p < 0.05) reductions in the incidence of alveolar osteitis. With chlorhexidine therapy, the subject- and extraction-based incidences of alveolar osteitis in the evaluable subset (271 subjects) were reduced, relative to placebo, by 38% and 44%, respectively. The corresponding odds ratios that describe the increased odds of experiencing alveolar osteitis in the placebo group were 1.87 and 2.05 for subject- and extraction-based analyses, respectively. In comparison with nonuse of oral contraceptives, the use of oral contraceptives in female subjects was related to a statistically significant increase in the incidence of alveolar osteitis (odds ratio = 1.92, p = 0.035). Relative to male subjects, the observed incidence of alveolar osteitis for female subjects not using oral contraceptives was not statistically significant (odds ratio = 1.18, p = 0.64). Smoking did not increase the incidence of alveolar osteitis relative to not smoking (odds ratio = 1.20, p = 0.33). CONCLUSIONS: These data confirm that the prophylactic use of 0.12% chlorhexidine gluconate mouthrinse results in a significant reduction in the incidence of alveolar osteitis after the extraction of impacted mandibular third molars. In addition, oral contraceptive use in females was confirmed to be a risk factor for the development of alveolar osteitis.

Adolescent↗
PubMed1998

Crystal structure of 2,5-diketo-D-gluconic acid reductase A complexed with NADPH at 2.1-A resolution.

The three-dimensional structure of Corynebacterium 2, 5-diketo-D-gluconic acid reductase A (2,5-DKGR A; EC 1.1.1.-), in complex with cofactor NADPH, has been solved by using x-ray crystallographic data to 2.1-A resolution. This enzyme catalyzes stereospecific reduction of 2,5-diketo-D-gluconate (2,5-DKG) to 2-keto-L-gulonate. Thus the three-dimensional structure has now been solved for a prokaryotic example of the aldo-keto reductase superfamily. The details of the binding of the NADPH cofactor help to explain why 2,5-DKGR exhibits lower binding affinity for cofactor than the related human aldose reductase does. Furthermore, changes in the local loop structure near the cofactor suggest that 2,5-DKGR will not exhibit the biphasic cofactor binding characteristics observed in aldose reductase. Although the crystal structure does not include substrate, the two ordered water molecules present within the substrate-binding pocket are postulated to provide positional landmarks for the substrate 5-keto and 4-hydroxyl groups. The structural basis for several previously described active-site mutants of 2,5-DKGR A is also proposed. Recent research efforts have described a novel approach to the synthesis of L-ascorbate (vitamin C) by using a genetically engineered microorganism that is capable of synthesizing 2,5-DKG from glucose and subsequently is transformed with the gene for 2,5-DKGR. These modifications create a microorganism capable of direct production of 2-keto-L-gulonate from D-glucose, and the gulonate can subsequently be converted into vitamin C. In economic terms, vitamin C is the single most important specialty chemical manufactured in the world. Understanding the structural determinants of specificity, catalysis, and stability for 2,5-DKGR A is of substantial commercial interest.

Bacterial Proteins↗
PubMed2003

Origin of the 2-amino-2-deoxy-gluconate unit in Rhizobium leguminosarum lipid A. Expression cloning of the outer membrane oxidase LpxQ.

An unusual feature of the lipid A from the plant endosymbionts Rhizobium etli and Rhizobium leguminosarum is the presence of a proximal sugar unit consisting of a 2-amino-2-deoxy-gluconate moiety in place of glucosamine. An outer membrane oxidase that generates the 2-amino-2-deoxy-gluconate unit from a glucosamine-containing precursor is present in membranes of R. leguminosarum and R. etli but not in S. meliloti or Escherichia coli. We now report the identification of a hybrid cosmid that directs the overexpression of this activity by screening 1800 lysates of individual colonies of a R. leguminosarum 3841 genomic DNA library in the host strain R. etli CE3. Two cosmids (p1S11D and p1U12G) were identified in this manner and transferred into S. meliloti, in which they also directed the expression of oxidase activity in the absence of any chromosomal background. Subcloning and sequencing of the oxidase gene on a 6.5-kb fragment derived from the approximately 20-kb insert in p1S11D revealed that the enzyme is encoded by a gene (lpxQ) that specifies a protein of 224 amino acid residues with a putative signal sequence cleavage site at position 28. Heterologous expression of lpxQ using the T7lac promoter system in E. coli resulted in the production of catalytically active oxidase that was localized in the outer membrane. A new outer membrane protein of the size expected for LpxQ was present in this construct and was subjected to microsequencing to confirm its identity and the site of signal peptide cleavage. LpxQ expressed in E. coli generates the same products as seen in R. leguminosarum membranes. LpxQ is dependent on O(2) for activity, as demonstrated by inhibition of the reaction under strictly anaerobic conditions. An ortholog of LpxQ is present in the genome of Agrobacterium tumefaciens, as shown by heterologous expression of oxidase activity in E. coli.

Amino Acid Sequence↗
PubMed2001

Intravenous chlorhexidine gluconate causing acute respiratory distress syndrome.

CASE REPORT: A 67-year-old man undergoing a colectomy for colon cancer was unintentionally administered 0.8 mg of chlorhexidine gluconate intravenously and subsequently developed acute respiratory distress syndrome. The operation was discontinued immediately. Respiratory failure progressed despite three cycles of plasma exchange beginning on day 1. Extracorporeal membrane oxygenation for 72 h beginning on day 3 was associated with dramatic improvement. The patient showed complete recovery of intellectual function and subsequently underwent a colectomy with lymph node dissection for colon cancer. CONCLUSION: For acute respiratory distress syndrome secondary to chlorhexidine gluconate intoxication, consideration should be given to the treatment of initial respiratory distress and subsequent pneumonia. The benefit of extracorporeal membrane oxygenation and plasma exchange may merit further investigation.

Aged↗
PubMed2006

Randomized controlled trial of chlorhexidine gluconate for washing, intranasal mupirocin, and rifampin and doxycycline versus no treatment for the eradication of methicillin-resistant Staphylococcus aureus colonization.

BACKGROUND: Eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage may reduce the risk of MRSA infection and prevent transmission of the organism to other patients. METHODS: To determine the efficacy of decolonization therapy, patients colonized with MRSA were randomized (3:1 allocation) to receive treatment (2% chlorhexidine gluconate washes and 2% mupirocin ointment intranasally, with oral rifampin and doxycycline for 7 days), or no treatment. Follow-up samples for MRSA culture were obtained from the nares, perineum, skin lesions, and catheter exit sites monthly for up to 8 months. The primary outcome measure was detection of MRSA at 3 months of follow-up. Univariate and multivariable analyses were performed to identify variables associated with treatment failure. RESULTS: Of 146 patients enrolled in the study, 112 patients (87 treated; 25 not treated) were followed up for at least 3 months. At 3 months of follow-up, 64 (74%) of those treated had culture results negative for MRSA, compared with 8 (32%) of those not treated (P=.0001). This difference remained significant at 8 months of follow-up, at which time, 54% of those treated had culture results negative for MRSA (chi2=64.4; P<.0001, by log-rank test). The results of the multivariable analysis indicated that having a mupirocin-resistant isolate at baseline was associated with treatment failure (relative risk, 9.4; 95% confidence interval, 2.8-31.9; P=.0003), whereas decolonization therapy was protective (relative risk, 0.1; 95% confidence interval, 0.04-0.4; P=.0002). Mupirocin resistance emerged in only 5% of follow-up isolates. CONCLUSIONS: Treatment with topical mupirocin, chlorhexidine gluconate washes, oral rifampin, and doxycycline for 7 days was safe and effective in eradicating MRSA colonization in hospitalized patients for at least 3 months.

Administration, Intranasal↗
PubMedDate not supplied

Lack of reaction to ferric gluconate in hemodialysis patients with a history of severe reaction to iron dextran.

Iron deficiency is the most common cause of a poor response to recombinant human erythropoietin (rHuEPO) in patients receiving long-term dialysis, who are known to absorb oral iron preparations poorly. This retrospective case series reports our preliminary observation of five patients receiving long-term dialysis in a tertiary care university hospital who had responded poorly to rHuEPO because of iron deficiency. These patients also had a history of severe, potentially life-threatening reaction to intravenous iron dextran preparation, but they tolerated the newly available ferric gluconate complex in sucrose with no untoward effects. These results suggest that the parenteral administration of ferric gluconate can be safe for those who require iron therapy and who have had a severe reaction to iron dextran.

Adult↗