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Effects of edd and pgi disruptions on inosine accumulation in Escherichia coli.

Using an inosine-producing mutant of Escherichia coli, the contributions of the central carbon metabolism for overproducing inosine were investigated. Sodium gluconate instead of glucose was tested as a carbon source to increase the supply of ribose-5-phosphate through the oxidative pentose phosphate pathway. The edd (6-phosphogluconate dehydrase gene)-disrupted mutant accumulated 2.5 g/l of inosine from 48 g/l of sodium gluconate, compared with 1.4 g/l of inosine in the edd wild strain. The rpe (ribulose phosphate 3-epimerase gene)-disrupted mutant resulted in low cell growth and low inosine production on glucose and on gluconate. The disruption of pgi (glucose-6-phosphate isomerase gene) was effective for increasing the accumulation of inosine from glucose but resulted in low cell growth. The pgi-disrupted mutant accumulated 3.7 g/l of inosine from 40 g/l of glucose when 8 g/l of yeast extract was added to the medium. Furthermore, to improve effective utilization of adenine, the yicP (adenine deaminase gene)-disrupted mutant was evaluated. It showed higher inosine accumulation, of 3.7 g/l, than that of 2.8 g/l in the yicP wild strain when 4 g/l of yeast extract was added to the medium.

Adenine↗

The role of zinc lozenges in treatment of the common cold.

OBJECTIVE: To summarize and critique the medical literature on the use of zinc lozenges for treatment of the common cold. DATA SOURCES: MEDLINE searches (January 1966-June 1997) identified human clinical trials on the use of zinc lozenges for the treatment of the common cold. Bibliographies were also reviewed for relevant articles. STUDY SELECTION: Double-blind, placebo-controlled trials of zinc lozenges in adults for the treatment of the common cold, with the clinical end points of reduction in duration and/or severity of cold symptoms. DATA EXTRACTION: All double-blind placebo-controlled, human clinical trials on the use of zinc lozenges for the treatment of the common cold were included. DATA SYNTHESIS: The use of zinc lozenges in the treatment of the common cold has been suggested to reduce the duration and severity of cold symptoms. Of eight double-blind, placebo-controlled trials, four found zinc lozenges to be effective, while the other four reported no difference between zinc and placebo therapy. Potential reasons for the discrepancy between the results of these trials include inadequate placebo control, formulation of the lozenge, and the dose of zinc used. Common adverse effects include unpleasant taste, mouth irritation, and nausea. CONCLUSIONS: Treatment of the common cold with zinc gluconate lozenges, using adequate doses of elemental zinc, may be effective in reducing duration and severity of cold symptoms. The benefit appears to be maximal if the lozenges are started immediately after the onset of symptoms. The formulation of the lozenges also appears to be important because the addition of citric acid or tartaric acid may reduce efficacy due to chelation of zinc ion. Although zinc gluconate lozenges have dominated clinical trials thus far, further studies are needed to demonstrate the efficacy of zinc acetate lozenges and to determine whether their adverse effect profile is more favorable to that of zinc gluconate lozenges. Patients should play an important role in the decision-making process and must decide whether the benefit gained from treatment with zinc lozenges outweighs the potential adverse effects.

Common Cold↗

Independent effects of acetic acid and pH on survival of Escherichia coli in simulated acidified pickle products.

Our objective was to determine the effects of organic acids and pH on the rate at which selected strains of Escherichia coli O157:H7 die in acid solutions representative of acidified pickle products (pH < 4.6). We used gluconic acid/sodium gluconate (pKa = 3.7) as a noninhibitory buffer to maintain pH at selected values in the absence of other organic acids. This was possible because we found that the inhibitory effects of this acid on E. coli strains at pH 3.1 were independent of acid concentration over a range of 2 to 200 mM. By this method, the lethal effects of acetic acid solutions (100 to 400 mM) at selected pH values between 3.1 and 4.1 were compared with the effects of pH alone (as determined using gluconate buffer). We found D-values were two- to fourfold lower with acetic acid compared with the effect of pH alone for simulated pickle brines in this pH range. Glutamic acid, an amino acid that is known to enhance acid resistance in E. coli and is a component of pickle brines, protected the E. coli strains from the specific effects of acetic acid.

Acetic Acid↗

Influence of salt form and concentration on the absorption of magnesium in rat small intestine.

The influence of magnesium concentration and salt form on the absorption of this element in the rat small intestine was investigated. The following magnesium salts were studied: gluconate, fumarate, and chloride. At 1 and 5 mM concentrations absorption was most efficient from gluconate whereas at 10 mM absorption from fumrate was more efficient. Mg2+ absorption half-life (t50%) varied with salt and concentration. The Mg2+ absorption half-life for magnesium gluconate at 10 mM concentration was 42 times as long as at 1 mM concentration. The biggest area under the curve, which characterizes substance bioavailability, was observed for each of the investigated salts at 5 mM. Therefore, we may conclude that magnesium administration at 5 mM concentration would be optimal.

Animals↗

Drug resistance mechanisms in clinical isolates of Leishmania donovani.

Leishmania are protozoan parasites distributed worldwide. About 1.5-2.0 million cases are reported in the world annually from this disease and the death toll is estimated to be 57,000. Along with Brazil, Sudan and Bangladesh, India contributes to 90 per cent of the global burden of visceral leishmaniasis (VL). The absence of effective vaccines and vector control programmes, makes chemotherapy the most widely used tool against leishmaniasis. Chemotherapy based on pentavalent antimonials has been used for more than 50 years and remains the mainstay for treatment of leishmaniasis. Clinical resistance to pentavalent antimonials, in the form of sodium antimony gluconate (SAG), has become a major problem in the treatment of kala-azar (visceral leishmaniasis) in India. The mechanism of resistance is unclear in these clinical isolates although a lot of work has been carried out with Leishmania mutants selected in vitro by step-wise increasing drug concentration using the antimony related metal arsenic and more recently sodium antimony gluconate. We for the first time, investigated the molecular aspect of drug resistance in clinically confirmed sodium antimony gluconate resistant field isolates and found that the parasite evaded cytotoxic effects of therapy by enhanced efflux of drugs through overexpressed membrane proteins belonging to the superfamily of ABC (ATP-binding cassette) transporters. Additionally, our study also points towards cell surface changes in resistant isolates.

Animals↗

[Replacement therapy with pancreatic enzymes and the principle of reversible regulation of the enzyme-secreting activity of the pancreas].

In patients suffering from chronic pancreatitis (outside exacerbation) with initial enzyme-secretory pancreatic failure, the two-week intake of pancreatin as a replacement therapy brought about a decrease of the enzyme-secretory activity of the patient's own pancreas paralleled by the lowering of diurnal steatorrhea. This was confirmed by repeated pancreozymine tests. These data confirm the concept of a reverse relation between pancreatic enzymatic secretion and the concentration of the enzymes in the duodenal contents. Combined administration of pancreatin and calcium gluconate led to the preservation of the degree of steatorrhea by the enzymatic preparation. At the same time its inhibitory effect on the activity of the own pancreas was prevented. The effect of calcium gluconate is accounted for from the standpoint of the role Ca2+ plays in the maintenance of the function of the exocrine part of the pancreas. The combination with calcium gluconate is indicated in the clinical use of replacement therapy with preparations of pancreatic enzymes in patients with chronic pancreatitis.

Calcium Gluconate↗

Hydrofluoric acid dermal exposure.

A retrospective review of 237 consecutive cases of dermal exposure to dilute (6-11%) hydrofluoric acid (HF)- containing rust stain remover consumer products reported to the Rocky Mountain Poison and Drug Center during 1986 was done to evaluate the toxicity of these agents and the efficacy of topical treatment with calcium gluconate gel. In 148 cases (62%), failure to follow manufacturers' recommended safety procedures was the likely cause of exposure. 219 patients developed the following symptoms: dermal swelling, redness, or both (131, 55%); blistering (12, 5%); black discoloration under fingernails (12, 5%); or pain without reported dermal changes (64, 27%). Local complications were noted in 7 cases (3%) (infection, 4 cases; fingertip dermal necrosis, 3 cases). No systemic toxicity was noted. 116 patients (49%) received treatment with topical calcium gluconate gel; 53 were followed until complete resolution of symptoms. There appeared to be a relationship between earlier initial gel application and more rapid resolution of signs and symptoms. Some degree of dermal injury may be quite common following exposure to dilute (6-11%) HF-containing rust stain remover consumer products. Failure to follow manufacturers' recommended safety procedures may be responsible for many exposures. Treatment with topical calcium gluconate gel may be effective, and more rapid resolution of signs and symptoms may occur with earlier initiation of this therapy.

Calcium Gluconate↗

The alkalinizing effects of metabolizable bases in the healthy calf.

The alkalinizing effect of citrate, acetate, propionate, gluconate, L and DL-lactate were compared in healthy neonatal calves. The calves were infused for a 3.5 hour period with 150 mmol/L solutions of the sodium salts of the various bases. Blood pH, base excess, and metabolite concentrations were measured and the responses compared with sodium bicarbonate and sodium chloride infusion. D-gluconate and D-lactate had poor alkalinizing abilities and accumulated in blood during infusion suggesting that they are poorly metabolized by the calf. Acetate, L-lactate and propionate had alkalinizing effects similar to bicarbonate, although those of acetate had a slightly better alkalinizing effect than L-lactate. Acetate was more effectively metabolized because blood acetate concentrations were lower than L-lactate concentrations. There was a tendency for a small improvement in metabolism of acetate and lactate with age. Sodium citrate infusion produced signs of hypocalcemia, presumably because it removed ionized calcium from the circulation. D-gluconate, D-lactate and citrate are unsuitable for use as alkalinizing agents in intravenous fluids. Propionate, acetate and L-lactate are all good alkalinizing agents in healthy calves but will not be as effective in situations where tissue metabolism is impaired.

Acetates↗

Comparative effectiveness of topical treatments for hydrofluoric acid burns.

Hydrofluoric acid (HF) burns are characterized by progressive tissue necrosis and severe pain. Numerous topical treatments have been proposed, yet few have been studied experimentally. The present study was designed to examine the comparative efficacy of recommended treatments. Hair on the hind legs of rats was removed and 48 hours later 70% HF was applied. Calcium gluconate, Zephiran (benzalkonium chloride), A + D Ointment, aloe gel, and magnesium ointment were applied topically and burn development was monitored. Calcium gluconate significantly reduced burn size as early as one hour after application. Significant protection continued for seven days after the single application. The other treatments were not effective in decreasing or delaying HF burn development. The results indicated that calcium gluconate ointment was the most effective topical treatment for HF burns.

Aloe↗

Ionized calcium in exchange transfusion with THAM-buffered ACD blood.

In 20 exchange transfusions with THAM-buffered ACD blood 5 ml. of 2% calcium gluconate (8 mg. elemental calcium) was injected after each 100 ml. of blood exchanged. Plasma ionized calcium decreased significantly during the procedure, although after each injection of calcium gluconate, levels returned briefly to normal. Ten minutes after the end of exchange ionized calcium had returned to pre-exchange levels and remained there until at least 30 mins. postexchange.Total calcium also increased significantly. Short periods of extreme hypercalcemia (between 7 and 8 mEq./l.) were noted after each injection of calcium gluconate.The amount of calcium gluconate was insufficient to counteract the calcium-chelating effect of citrate. If no heparinized blood is available we suggest adding heparin and calcium chloride to THAM-buffered ACD blood to avoid the repeated sudden fluctuations between low and high calcium ion activity.

ABO Blood-Group System↗

Effect of 1-DOPA on calcitonin secretion by thyroid C cells.

After administering 1-DOPA for 7 d a decreased number of secretory granules as well as pronounced rough endoplasmic reticulum and Golgi apparatus were noted in C cells. A single dose of 1-DOPA did not inhibit C cell stimulation induced by a single dose of calcium gluconate. On the other hand, parallel administration of alpha-methyl-DOPA and calcium gluconate did not decrease the number of C cell secretory granules, which were observed after administration of calcium gluconate alone. The data suggest that the presence of DOPAmine (formed the 1-DOPA) in the secretory granules is a prerequisite for normal functioning of secretory processes in thyroid C cells.

APUD Cells↗

99mTc-labelled compounds prepared with sodium dithionite as reducing agent.

The paper deals with the applications of Na2S2O4 as reducing agent in the preparation of 99mTc-labelled compounds. The reduction of pertechnetate can advantageously be carried out in neutral solutions of pH 7. Using this procedure, DTPA, HEDSPA, MDP, gluconate, citrate and trypsin were successfully labelled. In HEDSPA and MDP labelling, a high as cumulation of 99mTc in rat bones (50%) was obtained. In gluconate labelling, under various reaction temperatures, two types of complexes were prepared. Complex I shows a 99mTc biodistribution which is comparable with the kidney diagnosticum 99mTc-Sn-gluconate (24% of 99mTc in kidneys). Complex II, on the other hand, exhibited a reduced affinity of 99mTc to kidneys (2.2%) which, however, increases in bone to 15.4%. The experimental results indicated that Tc(V) is bound in Complex I. In technetium complexing no "mixed complex" is formed technetium being complexed directly by chelate-forming groups on the labelled compound.

Animals↗

Effect of sugars, hydrogen ion concentration and ammonium nitrate on the formation of citric acid by Aspergillus niger.

Aspergillus niger Mulder strain when grown on a synthetic medium containing urea as the sole source of nitrogen at pH 5.2, formed a mixture of citric and gluconic acids. On growing the organism at pH 2.0 the gluconic acid content was reduced but citric acid yield remained low. Addition of NH4NO3 to the medium lowered the gluconic acid yields to undetectable levels with a simultaneous increase in the citric acid content. Of the sugars used for the production of citric acid, sucrose in an unautoclaved medium was found to be the best carbon source. Sucrose medium if autoclaved at pH 2.0, or a mixture of glucose and fructose instead of sucrose gave lower yields of citric acid. Under optimum conditions only citric acid was produced and the yield was 66-68 per litre after a growth period of about 10 days.

Aspergillus↗

The clinical effect of dentifrices containing stabilized stannous fluoride on plaque formation and gingivitis--a six-month study with ad libitum brushing.

The effects of stabilized 0.454% stannous fluoride dentifrices on supragingival plaque, gingival inflammation and gingival bleeding were studied in 549 adult male and female subjects who completed a six-month, double blind clinical study. Following an oral prophylaxis, subjects were randomly assigned to brush with one of the following dentifrices: 1) 0.454% SnF2 stabilized with 2.08% sodium gluconate, 2) 0.454% SnF2 stabilized with 4.16% sodium gluconate, 3) an experimental dentifrice, or 4) 0.243% NaF control dentifrice. Follow-up examinations were conducted at 3 and 6 months. Compared to the control dentifrice at 6 months, stannous fluoride dentifrices stabilized with 2.08% or 4.16% sodium gluconate significantly reduced gingivitis by 18.8% and 18.0%, respectively. There were no statistically significant differences between the two stabilized SnF2 groups with respect to their beneficial effects on gingival health. Gingival bleeding was also reduced, relative to the control dentifrice, for both stabilized SnF2 dentifrices. However, these differences were not statistically significant at p=0.05. The stabilized SnF2 dentifrices were not significantly different from the control dentifrice in their effects on supragingival plaque. No significant differences in adverse oral soft tissue effects were observed between the test and control groups. As expected, accumulation of extrinsic tooth stain increased in the stabilized SnF2 groups. However, the difficulty in removing accumulated dental stain was similar between the control and stabilized SnF2 dentifrices. Since use of SnF2 dentifrices has been reported to produce tooth stain, gingivitis examinations were done with and without custom-made tooth covers to evaluate the potential for examiner bias. Comparable gingivitis and gingival bleeding benefits were observed when the evaluations were conducted with or without the tooth covers. Results from this study support that 0.454% stabilized stannous fluoride dentifrices can provide an important adjunct to the prevention and control of gingivitis when used in combination with regular personal oral hygiene procedures and professional care.

Adult↗

Comparison of sustained-release quinidines given twice daily to patients with ventricular ectopy.

To compare the steady-state kinetic profiles and ectopy-suppression rates of two sustained-release forms of quinidine with those of a conventional quinidine preparation, 18 patients with ventricular ectopy were studied in randomized crossover fashion. The drugs were conventional quinidine sulfate 300 mg q6h, sustained-release quinidine sulfate 600 mg q12h, and sustained-release quinidine gluconate 648 mg q12h. Following baseline electrocardiographic ambulatory monitoring, each drug was given for three days, with repeat ambulatory monitoring and serial plasma drug level determinations performed on the third day. There were no washout periods between treatments. Plasma quinidine levels were assayed by both enzyme multiplied immunoassay technique (EMIT) and quinidine-specific high-performance liquid chromatography (HPLC) methods. Using actual steady-state HPLC values, there were no differences in the area under the plasma concentration-time curve (AUC) among the three treatments; the dose-corrected AUC was greater for quinidine gluconate than for the other two preparations. Using EMIT values, mean plasma quinidine levels from the conventional quinidine sulfate regimen were greater during the last five hours of the 12-hour study interval. A consistently strong inverse relationship between EMIT plasma quinidine levels and hourly ectopy rates was present in only one of eight (13%) responders. Diurnal variation of quinidine kinetics was observed after two days of each treatment; trough values at midnight were slightly lower than trough values at noon. Among patients demonstrating at least 70% suppression of premature ventricular contractions (PVCs), there were no differences in ectopy rates or ectopy-suppression rates among treatments. Dosing sustained-release quinidine sulfate 600 mg or quinidine gluconate 648 mg q12h was clinically acceptable in the small number of responders studied.

Adolescent↗

Metabolic engineering for the production of copolyesters consisting of 3-hydroxybutyrate and 3-hydroxyhexanoate by Aeromonas hydrophila.

Aeromonas hydrophila 4AK4 was able to synthesize copolyesters consisting of 3-hydroxybutyrate (3HB) and about 15 mol-% 3-hydroxyhexanoate (3HHx) (PHBHHx) when grown in long chain fatty acids such as dodecanoate regardless of growth conditions. To regulate the unit fraction in PHBHHx, phbA and phbB genes encoding beta-ketothiolase and acetoacetyl-CoA reductase in Ralstonia eutropha, were introduced into A. hydrophila 4AK4. When gluconate was used as cosubstrate of dodecanoate, the recombinant produced PHBHHx containing 3-12 mol-% 3HHx, depending on the gluconate concentration in media. Vitreoscilla hemoglobin gene, vgb, was also introduced into the above recombinant, resulting in improved PHBHHx content from 38 to 48 wt.-% in shake flask study. Fermentor studies also showed that increased gluconate concentration in medium containing dodecanoate promoted the recombinant strain harboring phbA and phbB genes to incorporate more 3HB unit into PHBHHx, resulting in reduced 3HHx fraction. Recombinant A. hydrophila harboring phbA, phbB and vgb genes demonstrated better PHBHHx productivity and higher conversion efficiency from dodecanoate to PHBHHx than those of the recombinant without vgb in fermentation study. Combined with the robust growth property and simple growth requirement, A. hydrophila 4AK4 appeared to be a useful organism for metabolic engineering.

3-Hydroxybutyric Acid↗

Modulation by anions of p-aminohippurate transport in bovine renal basolateral membrane vesicles.

In the presence of 10 microM 2-oxoglutarate (2-OG) and of an inward Na+ gradient, uphill [3H]p-aminohippurate (PAH) uptake occurs due to cooperation of the PAH/2-OG exchanger and the Na(+)-coupled 2-OG transporter in bovine renal basolateral membrane vesicles. Uphill PAH uptake is observed with Cl-, but not with gluconate as the bulk anion. To determine specificity and nature of this anion effect [3H]PAH uptake was measured in the presence of several anions without and with ionophores to distinguish indirect from direct effects on the PAH transporter. Na(+)-gradient plus 2-OG-stimulated [3H]PAH uptake is fast with Cl-, intermediate with F-, Br-, I-, NO3- and SCN-, and slow in the presence of gluconate, SO4(2-) and HPO4(2-). Stimulation by Cl-(as compared to gluconate) is attenuated but not abolished, by clamping electrical potential and pH differences to zero, suggesting a partial effect through charge compensation and a major effect of anions on the PAH transporter itself. Indeed, [3H]PAH/2-OG and [3H]PAH/PAH exchange rates under voltage- and pH-clamped condition depend on bulk anions although the anion effects are less pronounced than with Na(+)-gradient plus 2-OG-stimulated [3H]PAH uptake. Since an inward Cl- gradient does not drive [3H]PAH above or below equilibrium distribution, Cl- ions are most probably not translocated by the PAH transporter. We propose that anions modulate the PAH transporter by interacting with a site not directly related to anion transport.

Animals↗

The metabolism of several carboxylic acids by lactic acid bacteria.

The anaerobic metabolism of citrate, fumarate, gluconate, malate, 2-oxoglutarate and pyruvate by 137 strains of 23 species of lactic acid bacteria was investigated. The bacteria were from various sources (plant material, meat and dairy products, dough and wine) and belonged to the genera Lactobacillus, Leuconostoc, Pediococcus, and Streptococcus. The ability of metabolize the acids was determined by thin layer chromatography or by enzymatic analysis after growth of the strains in a glucose-containing medium. All strains metabolized pyruvate and only 12 mainly heterofermentative strains were malate negative. These strains were also unable to decompose citrate. This acid was fermented by 23 strains, all of which metabolized malate. Many lactic acid bacteria reduced 2-oxoglutarate to hydroxyglutarate. The strains of Lactobacillus plantarum did not metabolize 2-oxoglutarate whereas all strains of Leuconostoc oenos decarboxylated this acid and formed 4-hydroxybutyrate and succinate. Gluconate was fermented by 52 mainly heterofermentative strains. No correlation was observed between the ability to ferment citrate, malate or gluconate.

Bacteria↗