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A study on citric acid as a proposed replacement resorption inhibitor.

The material consisted of 36 one-rooted immature teeth in 6 mongrel dogs. 12 teeth were immediately replanted after extraction, while 24 teeth were extracted and stored dry for 120 min before re- or autotransplantation. Root planing and topical citric acid treatment of the root of dry-stored teeth did not prevent the development of progressive root resorption and ankylosis, not even when special care was taken to prevent damage to the superficial, demineralized layer of the root during and after the transplantation procedures in an experimental model, which included autotransplantation of teeth to sockets, which were much larger than their original sockets.

Alveolar Process↗

An electromyographic method of objectively assessing cough intensity and use of the method to assess effects of codeine on the dose-response curve to citric acid.

The integrated surface abdominal electromyogram (EMG) has been used as a simple measurement of cough intensity which correlates well with the volume, air flow and noise produced in different coughs. Using the integrated abdominal EMG as a measure of cough intensity, dose response curves to inhaled citric acid can be drawn which are highly reproducible. We have studied the effects of codeine (60 mg) on these curves, and have demonstrated a reduction in cough intensity. It is suggested that this method of testing the effects of an antitussive on such a dose-response curve may be a useful one.

Action Potentials↗

Synthesis of novel thiol-containing citric acid analogues. Kinetic evaluation of these and other potential active-site-directed and mechanism-based inhibitors of ATP citrate lyase.

ATP citrate lyase is an enzyme involved in mammalian lipogenesis and cholesterogenesis. Inhibitors of the enzyme represent a potentially novel class of hypolipidemic agents. Citric acid analogues 5-16 bearing electrophilic and latent electrophilic substituents were synthesized and evaluated as irreversible inhibitors of the enzyme. The design of these agents was based on the classical enzymatic mechanism where an active-site nucleophile (thiol) was believed to be critically involved in catalysis. Reversible inhibition (Ki's ranging from ca. 20 to 500 microM) was observed for compounds 5, 10, and 12-16. Compounds 6-9 and 11 had no appreciable affinity for enzyme (Ki > 1 mM). Time-dependent inactivation of the enzyme by 5-16 was not detected following long incubation times (> 1 h, 37 degrees C) at 2 mM inhibitor concentrations.

ATP Citrate (pro-S)-Lyase↗

A method for decalcification with citric acid.

Psammoma bodies and small calcifications are frequently seen in a wide variety of tissues. These deposits of calcium salts render tissues difficult to section. Conventional decalcification alters the tissues; consequently it is not advisable to decalcify tissues containing only small calcium deposits. A simple and rapid method to remove small amounts of calcium salts using citric acid alone is described. This method does not alter the antigenic properties of the substances studied.

Antigens↗

Anaplerosis of the citric acid cycle: role in energy metabolism of heart and skeletal muscle.

Efficient energy transfer in heart and skeletal muscle requires a series of moiety-conserved cycles. The intermediaries of the metabolic cycles are finely regulated to maintain a dynamic state of equilibrium. In heart muscle, depletion of the citric acid cycle (TCA cycle) through a block of 2-oxoglutarate dehydrogenase results in a rapid decline of contractile function, which is reversed by the addition of substrates promoting flux through the carboxylating enzymes, malic enzyme, pyruvate carboxylase and propionyl-CoA carboxylase. Anaplerosis describes a pathway, which replenishes a metabolic cycle. We show that enzymes for anaplerosis of the TCA cycle are expressed in heart and skeletal muscles. The role of anaplerosis of the TCA cycle in skeletal muscle is not entirely clear, but there is substantial evidence for its operational control during exercise. While the anaplerotic flux of carbon into the TCA cycle exceeds the removal of cycle intermediates, this process is only transient and reverses with prolonged exercise. It remains to be determined, however, whether the initial increase in TCA cycle intermediates is obligatory in order to attain high rates of TCA cycle flux, or primarily reflects a mass action phenomenon owing to increased substrate availability for anaplerotic pathways.

Animals↗

Inhibition of calcification with citric acid in pericardial bioprosthetic heart valve material: a preliminary report.

BACKGROUND AND AIM OF THE STUDY: Although current bioprosthetic heart valves have low thrombogenicity and favorable hemodynamic properties, their durability remains unsatisfactory. Valve failure usually occurs from calcific degeneration. The study aim was to investigate the effect of a chelating agent, citric acid (CA), on calcification in bovine pericardium. METHODS: Freshly excised bovine pericardium was dissected free from adhering fat tissue and cut into 1- cm2 pieces; these were rinsed in phosphate-buffered saline solution (PBS), transferred into +4 degrees C PBS containing 0.625% glutaraldehyde (GA) for initial fixation, and then allocated to two groups. Control samples received the same treatment in a fresh solution for 5 days. The other samples underwent an additional fixation step in PBS (pH = 7.4, 37 degrees C) containing 3.8% CA for a period of 48 h (30 ml/g tissue) and were then transferred into freshly prepared PBS + 0.625% GA solution at 37 degrees C for a further 3 days. To investigate calcification rate, pericardial patches were inserted into the dorsal pouches of 15 juvenile male Wistar rats for 42 days. Tissue calcium levels were measured with atomic absorption spectrophotometer, and also assessed histopathologically. RESULTS: The calcium content of CA-treated pericardium was significantly lower than that of controls (66.4 +/- 33.5 and 111.4 +/- 27.2 mg/g, respectively; p = 0.000). In general, the degree of calcification in histological sections agreed well with results of the chemical analyses. Control pericardial tissues showed moderate to severe solid mineral depositions, predominantly parallel to the implant surface, whereas only minor traces of calcium were found in CA-treated tissues. CONCLUSION: These preliminary data suggest that calcific degeneration in bovine pericardium may be reduced by using CA as a chelating agent.

Animals↗

Translational regulation of mammalian and Drosophila citric acid cycle enzymes via iron-responsive elements.

The posttranscriptional control of iron uptake, storage, and utilization by iron-responsive elements (IREs) and iron regulatory proteins (IRPs) provides a molecular framework for the regulation of iron homeostasis in many animals. We have identified and characterized IREs in the mRNAs for two different mitochondrial citric acid cycle enzymes. Drosophila melanogaster IRP binds to an IRE in the 5' untranslated region of the mRNA encoding the iron-sulfur protein (Ip) subunit of succinate dehydrogenase (SDH). This interaction is developmentally regulated during Drosophila embryogenesis. In a cell-free translation system, recombinant IRP-1 imposes highly specific translational repression on a reporter mRNA bearing the SDH IRE, and the translation of SDH-Ip mRNA is iron regulated in D. melanogaster Schneider cells. In mammals, an IRE was identified in the 5' untranslated regions of mitochondrial aconitase mRNAs from two species. Recombinant IRP-1 represses aconitase synthesis with similar efficiency as ferritin IRE-controlled translation. The interaction between mammalian IRPs and the aconitase IRE is regulated by iron, nitric oxide, and oxidative stress (H2O2), indicating that these three signals can control the expression of mitochondrial aconitase mRNA. Our results identify a regulatory link between energy and iron metabolism in vertebrates and invertebrates, and suggest biological functions for the IRE/IRP regulatory system in addition to the maintenance of iron homeostasis.

Aconitate Hydratase↗

High-performance liquid chromatographic analysis of citric acid, inositol and fructose in boar and bull seminal plasma.

The efficiency of ultrafiltration and high-performance liquid chromatography (HPLC) in the routine analysis of dialysable sugar alcohols, organic acids and carbohydrates in boar and bull seminal plasma is evaluated. Permitting a simple and rapid separation of protein-free samples, ultrafiltration reduces the time of HPLC analysis by 40 minutes as compared to protein precipitation by means of methanol. Under optimal flow-conditions the separation of citric acid, inositol and fructose is achieved in 16 minutes. Moreover, the use of silicon-oil for separating seminal plasma within seconds is described.

Animals↗

Citric acid production by Aspergillus niger using media containing low concentrations of glucose or corn starch.

By using an appropriate ratio of carbon source to mineral components, we obtained comparable citrate yields in media containing different concentrations of glucose. The enzyme system of inoculum passed on gradually from "growth" state to "production" state during the mould growth. In the starch medium, the critical factors of citric acid production are the aeration efficiency of the medium and the amylase formation of the strain. The air interruption exhibited a prolonged inhibition of the production rate but not of the citrate yield in glucose medium while those parameters in starch medium containing excessive urea were briefly but severely inhibited. After being affected by these unfavorable conditions, the production activity of Aspergillus niger could be restored by applying an appropriate fermentation process.

Aspergillus niger↗