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Effects of 0.12% chlorhexidine gluconate on experimental gingivitis in non-human primates: clinical and microbiological alterations.

OBJECTIVE: This study examined the efficacy of 0.12% chlorhexidine gluconate (Peridex) to reduce gingival inflammation in the absence of mechanical hygiene and its effect on the oral microbial ecology in a non-human primate (NhP) model of gingivitis. DESIGN: Twelve NhP were stratified based on existing inflammation into two groups of six NhP per group. Oral hygiene was performed on both groups so as to reach a level of gingival health (BOP < or = 0.3) at the conclusion of the hygiene phase. One group received 30 ml of 0.12% chlorhexidine gluconate twice daily 7 days/week, and a second group received 30 ml of placebo (distilled water colored to match the active) using the same regimen for 10 weeks. MEASUREMENT OUTCOMES: Clinical parameters including plaque (PLI), pocket depth (PD), attachment level (AL), and bleeding on probing (BOP) were evaluated at 2-week intervals. Subgingival plaque samples were collected by paper point at 2-week intervals and cultured for predominant cultivable bacteria. RESULTS: By week 2, there was a difference in BOP between the groups, which reached statistical significance by week 4. This difference in BOP was maintained throughout the course of the study. Chlorhexidine gluconate (0.12%) had no significant effect on PLI, PD, or AL; although PD was greater in the placebo group after week 2 and throughout the study. Microbiologically, at week 4, the treatment group had a reduction in total bacterial counts, as well as Gram positive bacteria, and total black pigmented bacteria, compared to the placebo group. However, only the differences in Actinomyces spp. reached significance. Interestingly, when both groups received only one treatment/day on the weekends (i.e., day 6 and 7), an associated loss of statistically significant differences between the two groups was observed. Additional experiments dosing the non-human primates once daily, 5 days/week yielded no significant differences in clinical parameters, including bleeding, when compared with the placebo group. CONCLUSION: Non-human primates provided a model system of gingivitis for testing antimicrobial agent effects on the subgingival ecology and accompanying inflammatory responses. Chlorhexidine gluconate (0.12%), even in the absence of mechanical hygiene, was effective in inhibiting clinical signs of inflammation, associated with alterations in the subgingival microbial ecology, most notably Actinomyces spp.

Actinomyces↗

Effect of aluminum hydroxide gel on quinidine gluconate absorption.

The effect of aluminum hydroxide gel on quinidine gluconate bioavailability was studied in eight nonsmoking healthy male volunteers. Subjects were randomized to receive quinidine gluconate 648 mg with and without 30 mL of aluminum hydroxide gel. The mean area under the concentration-time curve (AUC) (23.11 +/- 5.21 mg.h/L), time to reach maximum concentration (tmax) (3.13 +/- 0.64 h), maximum serum concentration (1.44 +/- 0.41 mg/L), and elimination rate constant (0.069 +/- 0.010-h) observed during the control phase of the trial did not differ significantly (p greater than 0.05) from values obtained during the coadministration of aluminum hydroxide with quinidine gluconate (23.91 +/- 4.48 mg.h/L, 4.13 +/- 2.12 h, 1.53 +/- 0.34 mg/L, and 0.077 +/- 0.013-h, respectively). There was considerable individual variation in AUC with one subject demonstrating an increase of 35 percent and one subject demonstrating a decrease of 18 percent. There was a trend toward aluminum hydroxide delaying tmax with only one subject experiencing an earlier tmax with the coadministration of aluminum hydroxide. The results of this single-dose trial suggest that, although statistically the concurrent administration of aluminum hydroxide gel with quinidine gluconate does not significantly alter the extent of quinidine absorption, clinically significant individual variations may occasionally occur.

Adult↗

The impact of chlorhexidine gluconate on the relative cell surface hydrophobicity of oral Candida albicans.

OBJECTIVES: Adherence of Candida albicans has been implicated as the first step in the pathogenesis of oral candidosis, and its relative cell surface hydrophobicity (CSH) a contributory physical force. Chlorhexidine gluconate is by far the commonest antiseptic mouthwash prescribed in dentistry. The intra-oral concentrations of the retained chlorhexidine mouthwash fluctuate considerably due to the dilution effect of saliva and the cleansing action of the oral musculature. Hence the objective of the present study was to investigate the effect of brief exposure to sub-therapeutic concentrations of chlorhexidine gluconate on the relative CSH of C. albicans. DESIGN: The CSH of the isolates was assessed by a biphasic aqueous-hydrocarbon assay. RESULTS: A statistically significant reduction in CSH was observed following the exposure of Candida isolates to 0.005 and 0.0025% chlorhexidine gluconate. CONCLUSIONS: These results elucidate additional mechanisms by which chlorhexidine gluconate suppress candidal pathogenicity despite a brief period of transient exposure within the oral environment.

Adhesiveness↗

Weekly administration of high-dose sodium ferric gluconate is safe and effective in peritoneal dialysis patients.

This report describes the safety and efficacy of high-dose sodium ferric gluconate in 18 peritoneal dialysis (PD) patients. Nine patients received low-dose (125 mg) and 9 patients received high-dose (250 mg) sodium ferric gluconate once per week for 8 or 4 weeks, respectively, followed by a maintenance dose once every 4 weeks. Patients in both groups had low iron saturation before treatment (hemoglobin [Hgb] < 11 g/dl, transferrin saturation [TSAT] approximately 20%, and serum ferritin < 250 ng/ml). After treatment, TSAT and ferritin significantly increased in both the low-dose (ferritin 465 +/- 292 ng/ml and TSAT 33.5 +/- 6.9%) and high-dose (ferritin 622 +/- 339 ng/ml and TSAT 35.0 +/- 25.7%) groups compared to baseline. Hemoglobin levels also increased in both groups, but this was not statistically significant. No adverse reactions or transferrin oversaturation with high-dose sodium ferric gluconate were observed. In conclusion, high-dose sodium ferric gluconate was safe, convenient, and effective in treating iron deficiency in PD patients.

Anemia, Iron-Deficiency↗

Effects of daily oral care with 0.12% chlorhexidine gluconate and a standard oral care protocol on the development of nosocomial pneumonia in intubated patients: a pilot study.

PURPOSE: The purpose of this pilot study was to determine if a difference existed between nosocomial pneumonia rates for intubated critical care unit (CCU) patients who received twice-daily oral hygiene care with 0.12% chlorhexidine gluconate and those who received the standard oral care. METHODS: Over seven months (February to August), CCU patients were identified through screening and informed consent procedures, and randomized into 1 of 2 groups. Over the 7 months, due to the critically ill nature of the patients, only 5 subjects were enrolled. While in the study, twice-daily oral hygiene care consisted of brushing the cheeks, teeth, and endotracheal tube with a suctioning toothbrush using an FDA-approved 0.12% chlorhexidine gluconate antimicrobial agent with the experimental group (2 intubated patients in the CCU). The control group (3 intubated patients in the CCU) received the standard oral care 6 times per day utilizing a soft foam swab and half strength hydrogen peroxide. All oral care was performed by the nursing staff. The number of persons developing nosocomial pneumonia was monitored until hospital discharge. RESULTS: Results revealed that 1 person out of 3 in the control group was discharged from the hospital with a diagnosis of nosocomial (aspiration) pneumonia. Neither of the 2 subjects in the experimental group was diagnosed with nosocomial pneumonia. Preliminary findings suggest that twice-daily oral hygiene care with 0.12% chlorhexidine gluconate may reduce the risk of nosocomial pneumonia in intubated patients more than the 6-times daily standard oral care protocol. The standard oral care protocol does not include the use of an FDA-approved antimicrobial solution. However, the small size of the sample makes this finding inconclusive. CONCLUSION: Twice-daily oral hygiene care with 0.12% chlorhexidine gluconate may hold promise as a nosocomial pneumonia reduction strategy within hospital CCUs; however, its application requires further testing.

Adult↗

Anaphylactic symptoms due to chlorhexidine gluconate.

Six patients who developed urticaria, dyspnea, and anaphylactic shock due to topical application of chlorhexidine gluconate solution are described. Chlorhexidine gluconate was confirmed as the causative agent of type I hypersensitivity by intradermal, scratch, and epicutaneous tests. To prevent life-threatening adverse reactions, it seems important to use chlorhexidine gluconate on wound surfaces at a concentration of 0.05%, as recommended by the manufacturer; chlorhexidine gluconate may not be suitable for application to mucous membranes.

Adolescent↗

Purification and characterization of 2,5-diketo-D-gluconate reductase from Corynebacterium sp.

2,5-Diketo-D-gluconate reductase, a novel enzyme that catalyzes the stereospecific NADPH-dependent reduction of 2,5-diketo-D-gluconate to 2-keto-L-gulonate, has been purified to homogeneity by sequential anion exchange, Cibacron blue F3GA affinity, and gel permeation chromatography from Corynebacterium sp. ATCC 31090. Molecular weight of the native form, determined by gel permeation chromatography, is 35,000 +/- 2,000. The subunit molecular weight, determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis is 34,000; thus, the enzyme is active as a monomer. A pI value of 4.4 is measured for the enzyme. Amino- and carboxyl-terminal sequences are consistent with that predicted by the DNA sequence of the reductase gene. At 25 degrees C, pH 6.4, the turnover number is 500 min-1, and the apparent Km values for 2,5-diketo-D-gluconate and NADPH are 26 mM and 10 microM, respectively. The enzyme is specific for NADPH, but the sugar binding site will also accept 5-keto-D-fructose and dihydroxyacetone as substrates. The enzyme is active over a broad pH range (pH 5-8) for the reduction of 2,5-diketo-D-gluconate; a sharp optimum at pH 9.2 is observed for the oxidation of 2-keto-L-gulonate. A Keq value of 5.6 X 10(-13) M indicates that reduction of substrate by NADPH is highly preferred. An activation energy of 12.3 kcal mol-1 is measured. Enzyme turnover is slow relative to dehydration of the gem-diol at C-5 of the substrate.

2,3-Diketogulonic Acid↗

Bioavailability of two manufacturers' sustained-release quinidine gluconate tablets at steady state.

Steady-state bioavailability of sustained-release quinidine gluconate tablets manufactured by two companies was compared in a crossover study. The tablets were Quinaglute Dura-Tabs, manufactured by Berlex Laboratories, Inc., and generic quinidine gluconate tablets, manufactured by Bolar Pharmaceutical Company. Sixteen healthy male volunteers were given multiple doses of the two products in randomized sequence. Blood samples were obtained immediately before administration of the seventh dose (hour 72) and at 1, 2, 3, 4, 5, 6, 8, 10, and 12 hours after administration. Plasma samples were assayed for quinidine content by high-performance liquid chromatography. The tablets manufactured by Berlex provided statistically significantly higher plasma levels during the second half of the dosing interval (six to 12 hours postdose). A 29% difference in plasma levels was observed between the products at the end of the dosing interval. The Bolar quinidine gluconate tablets had a statistically significant lower area under the curve (AUC). The greatest difference in AUC occurred during the last six hours of the dosing period. The six- to 12-hour AUC for the Bolar tablets was 24% less than that for Berlex tablets. The generic tablets also achieved peak plasma level 31% sooner than did Quinaglute Dura-Tabs. The pharmacokinetic characteristics of the two products at steady state indicate that the Bolar quinidine gluconate tablet exhibited a more rapid onset of peak plasma levels and a more rapid decline to minimum plasma levels. In summary, the data from this multiple-dose study, performed using commercially available material, indicate that differences exist in pharmacokinetic performance of the products. However, the exact correlation between pharmacokinetic data and clinical effectiveness has not been established.

Biological Availability↗

[Effectiveness and tolerability of oral liquid ferrous gluconate in iron-deficiency anemia in pregnancy and in the immediate post-partum period: comparison with other liquid or solid formulations containing bivalent or trivalent iron].

UNLABELLED: From the early months of pregnancy and even more so later, women suffer a deficiency of iron along with a decline in their red blood cell count. It is also now clear that women who take iron supplements during pregnancy do not suffer the same post-natal reduction in hemoglobin and ferritin as those who don't make it. A study was therefore conducted on 40 women aged 20-35, with iron-deficiency anaemia during or immediately after pregnancy all of whom presented Hb < 10 gr/dl, Ht < 33% and serum iron < 60 micrograms/dl. All women with pregnancy-related pathological conditions, pre-existing on concomitant disease (Type I diabetes, heart diseases etc.) were excluded from the study. The women whose blood chemical parameters were largely homogeneous at the start of the study were divided into four treatment groups of 10 patients each and were treated as follows: Group A with oral liquid ferrous gluconate (75 mg per diem in 2 vials a day); Group B with solid ferrous gluconate (80 mg per diem in a single effervescent tablet); Group C with solid ferrous sulphate (105 mg per diem in a single tablet); and Group D with ferric protein succinylate (80 mg per diem in 2 vials a day). All were given iron treatment for 30 days. Treatment efficacy was analysed by comparing basal and final parameters using the T-test for paired dependent samples. The tolerance of the 4 treatment protocols was assessed by the analysis of any side effects such as nausea, vomiting, epigastric pain, diarrhoea, constipation or other disorders reported by patients during treatment. RESULTS: Analysis of the therapeutic efficacy parameters (red blood cells, hemoglobin, hematocrit and serum iron) showed significant improvements but no statistically significant differences between the groups. However, the Group A patients treated with oral doses of liquid ferrous gluconate received a significantly lower cumulative dose of iron elements than the other groups: in detail 150 mg (p < 0.05) less than Groups B and D; 900 mg (< 0.001) less than Group C. By the end of treatment the Group A patients revealed significant increases versus basal values in red blood cells (p < 0.001) 1,051,000 per mm3 or 33%, in Hb (p < 0.001) 2.83 gr/dl or 32%, in Ht (p < 0.001) 8.32% or 32%, in serum iron (p < 0.05) 19.5 micrograms/dl or 61%. The same group also showed an increase in Ferritin amounting to 7.8 micrograms/dl or 24% of the basal value. As to safety, only Group A patients reported no side effects and produced no drop-outs. Gastrointestinal and other aspecific side effects caused 1 drop-out each in Groups B and C and 2 drop-outs in Group D. CONCLUSION: Numerous preparations containing bivalent or trivalent iron are available for the treatment of iron-deficiency anaemia during or immediately after pregnancy. It has been shown that preparations containing ferrous salts (+2) are more easily absorbed than those containing ferric salts (+3) since the former can be immediately absorbed by the duodenal mucosa. The study reported here reveals that oral ferrous gluconate in liquid form is more effective and above all better tolerated than other solid or liquid formulations containing elementary iron.

Administration, Oral↗

Cutaneous calcinosis in a neonate following extravasation of calcium gluconate.

Cutaneous calcinosis following extravasation of calcium gluconate in a 6-day-old neonate is reported. After extravasation of a 10% calcium gluconate infusion, rapid and marked swelling, erythema, and signs of soft tissue necrosis developed over the dorsum of the right hand and wrist. Small eschars were soon formed on the skin surface and began to slough, the underlying base appearing necrotic. Through the small channels of the destroyed epidermis, tiny white pieces of calcific masses were eliminated spontaneously. Histologically, the dermal collagen was massively degenerated and the calcium deposits were found as amorphous masses throughout the dermis and subcutaneous adipose tissue, surrounded by mild lymphohistiocytic cell infiltration. This is a case which again warns of the danger of using 10% calcium gluconate intravenously in the neonate or young infant.

Calcinosis↗

Choice of calcium salt. A comparison of the effects of calcium chloride and gluconate on plasma ionized calcium.

Equimolar quantities of calcium chloride and calcium gluconate produced similar changes in plasma ionised calcium concentration when injected intravenously into anaesthetised ferrets or when added to human blood in vitro. In vivo changes were followed with a calcium electrode positioned in the animal's aorta, and this showed that the ionisation of calcium gluconate on its first pass through the circulation is as great as that of calcium chloride. This does not support the common suggestion that calcium chloride is preferable to calcium gluconate because of its greater ionisation.

Animals↗

Compatibility of calcium chloride and calcium gluconate with sodium phosphate in a mixed TPN solution.

The maximum concentrations of phosphate that will remain soluble in a parenteral nutrient solution containing various concentrations of calcium chloride or calcium gluconate were determined. Various concentrations of sodium phosphate were mixed with FreAmine II (McGaw Laboratories), and the resulting solutions were mixed with 50% dextrose solutions containing various concentrations of calcium chloride or calcium gluconate. The final solutions were sealed and stored at 30 degrees C for 24 hours and then were inspected visually for precipitate formation. It was found that higher equivalent concentrations of phosphate are attainable when calcium gluconate, instead of calcium chloride, is used as the calcium source. Factors found to influence the concentrations of calcium and phosphate that are compatible in amino acid solutions are the calcium salt used, temperature and duration of storage, dextrose concentration, amino acid composition, pH, and other additives.

Amino Acids↗

Toxicology of cupric salts on honeybees. IV--Gluconate and sulfate action on hemolymph trehalose activity in vivo and in vitro.

A biphasic increase of hemolymph glucose levels was observed following injection to bees of cupric gluconate or sulfate, both potent agents for the control of Varroa jacobsoni, a parasitic mite of hives. The simultaneous injection to bees of 0.3 microM BAYg5421 (an inhibitor of alpha-glucosidases) quenched the response, suggesting a direct effect of 2 nmol/bee cupric ions on trehaloses' activity. One nanomol of injected cupric gluconate increased the trehalose (Tre) activity by 233% in crude hemolymph extracts at 1 mM trehalose concentration, and exhibited biphasic dose-related effects with a maximum 15% increase at 0.5 mM cupric ion and a stabilized 20% inhibition from 4 mM, regardless of the anionic moiety. Upon partial purification of the enzyme complex, two fractions (FI = 75% and FII = 25% of total activity) were isolated that exhibited, respectively, less and more marked positive cooperatively than crude extract. Form I showed almost no susceptibility to either cupric derivatives, which indicated form II as the most likely target, with 68% and 72% increases with 0.25 mM cupric sulfate and 0.5 mM cupric gluconate, in presence of 16 mM trehalose.

Acarbose↗

Effect of hypothermia on intracellular Ca2+ in rabbit renal tubules suspended in UW-gluconate preservation solution.

Altered cellular calcium (Ca) homeostasis may be important in mediating hypothermic injury in preserved kidneys. In this study the effect of hypothermic (5 degrees C) storage on ionized intracellular Ca concentration ([Ca]i) in rabbit tubules was examined using Indo-1. Tubules were stored up to 250 min in UW-gluconate solution containing either 0.0, 0.5, 1.5, or 5.0 mM Ca (yielding about 3.6, 62, 371, and 1,010 microM ionized solution Ca (Ca2+) at 5 degrees C, respectively). [Ca]i increased to about 1,600 nM within 1 min after suspension in UW solution followed by a decrease in [Ca]i during the subsequent 60 min in all groups, suggesting mitochondrial Ca sequestration. Thereafter, [Ca]i either 1) increased in tubules incubated with 1.5 and 5.0 mM Ca to levels greater than 2,500 nM; 2) decreased to about 800 nM in tubules incubated with 0.5 mM Ca and then remained stable; or 3) continued to decrease in tubules incubated with 0.0 mM added Ca to reach an apparent steady-state concentration of about 175 nM after 180 min of incubation. The early spike in [Ca]i was unaffected by adding EGTA (solution Ca2+ = 50 nM). Ryanodine eliminated the [Ca]i spike, indicating that cooling in UW-gluconate solution caused release of endoplasmic reticulum Ca. This study shows that [Ca]i initially increases after exposure to UW-gluconate solution and appears to be transiently buffered through intracellular, probably mitochondrial, sequestration. Saturation of cellular buffer mechanisms resulted in a sustained dependence of [Ca]i on extracellular Ca2+. These results support the hypothesis that the effect of Ca on kidney viability is related to solution-induced alterations in [Ca]i.

Adenosine↗

Toxicology of cupric salts on honeybees. V. Gluconate and sulfate action on gut alkaline and acid phosphatases.

Some aspects of putative nontarget effects of cupric ions systemically fed to honeybees against their parasite mite Varroa jacobsoni have been investigated on the host phosphatases. The alkaline and acid forms extracted from the guts of worker bees exhibited substrate-inhibition features. Upon detailed kinetic analysis, cupric organic salts indicate activation effects at concentrations of about 1 mM. Concentrations up to 10 mM (alkaline form) and 25 mM (acid form) induced no important changes, except a partial quenching of the substrate-inhibition process, characterized by a wide increase in the constant of apparent inhibitory binding of substrate to the enzyme-substrate complex. Partial purification gave a single alkaline form with quite similar kinetic behavior in the absence of natural ions as in crude extracts. Cupric gluconate and sulfate demonstrated similar patterns, except an increase of the apparent Hill coefficient by sulfate only. The substrate constant of acid phosphatases was decreased at high cupric gluconate doses while its maximum velocity was biphasically increased (with observed maximum at 1 mM), resulting in a sustained activation. Chemiluminescence studies revealed that cupric ion activation is counteracted by oxygen radicals generated by cupric ions and also, in vitro, by the artificial substrate para-nitrophenylphosphate. The para-nitrophenol molecules released from the reaction are therefore responsible for biphasic effects selectively observed with gluconate salts. In apicultural practice, neither blockade of activity nor dramatic changes are to be expected at doses administered to bees against the parasite.

Acid Phosphatase↗

Production of gluconic acid and 2-ketogluconic acid by Klebsiella aerogenes NCTA 418.

2-Ketogluconic acid and, to a lesser extent, gluconic acid were found to be major products of glucose catabolism by phosphate-limited cultures of Klebsiella aerogenes NCTC 418, and together accounted for up to 46% of the glucose carbon that was metabolized. Although the concentrations of both acids increased substantially at low growth rates, their specific rates of synthesis decreased markedly, ad did the proportion of glucose converted into these products. Determination of the affinity constant, for glucose, of phosphate-limited organisms showed it ot be not significantly different from that of glucose-limited organisms (KS less than or equal to 50 muM), indicative of the phosphotransferase uptake system. And since these organisms possessed an active glucose 6-phosphate dehydrogenase, and had no detectable glucose dehydrogenase activity, it was concluded that gluconic acid and 2-keto-gluconic acid arose from their corresponding phosphorylated metabolites, and not directly from glucose.

Gluconates↗

Gluconic acid production by Penicillium puberulum.

Twenty-five Penicillium species isolated from Egyptian soil were examined for their ability to produce gluconic acid in surface culture. Of the eight species capable of producing gluconic acid, Penicillium puberulum gave the maximum yield (91% gluconic acid from glucose after 7 days of fermentation with 3% CaCO3). Peptone was the best nitrogen source for acid fermentation and glucose was superior to sucrose. Addition of low concentrations of KH2PO4 and MgSO4 - 7 H2O stimulated acid production. An initial pH of 6.1 was most favourable for acid accumulation and addition of CaCO3 was necessary for maximum acid production.

Calcium Carbonate↗

Biotransformation of glucose to 5-keto-D-gluconic acid by recombinant Gluconobacter oxydans DSM 2343.

For the conversion of glucose to 5-keto-D-gluconate (5-KGA), a precursor of the industrially important L-(+)-tartaric acid, Gluconobacter strains were genetically engineered. In order to increase 5-KGA formation, a plasmid-encoded copy of the gene encoding the gluconate:NADP-5 oxidoreductase (gno) was overexpressed in G. oxydans strain DSM 2434. This enzyme is involved in the nonphosphorylative ketogenic oxidation of glucose and oxidizes gluconate to 5-KGA. As the 5-KGA reductase activity depends on the cofactor NADP+, the sthA gene (encoding Escherichia coli transhydrogenase) was cloned and overexpressed in the GNO-overproducing G. oxydans strain. Growth of the sthA-carrying strains was indistinguishable from the G. oxydans wild-type strain and therefore they were chosen for the coupled overexpression of sthA and gno. G. oxydans strain DSM 2343/pRS201-gno-sthA overproducing both enzymes showed an enhanced accumulation of 5-KGA.

Bacterial Proteins↗