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Citric acid increases viable epidermal thickness and glycosaminoglycan content of sun-damaged skin.

BACKGROUND: Recently, there has been an exponential increase in the use of alpha-hydroxy acids in dermatologic practice. Their inclusion in a myriad of cosmetic preparations underscores their popularity. Among the clinical effects of alpha-hydroxy acids are their ability to prevent the atropy resulting from potent topical corticosteroids, improve the appearance of photoaged skin, and correct disorders of keratinization. Despite this range of desirable effects, very little is known about the specific changes produced by various alpha-hydroxy acid preparations in the epidermis and dermal extracellular matrix. Previous work by others has demonstrated the ability of another alpha-hydroxy acid to increase viable epidermal thickness, and dermal glycosaminoglycans. OBJECTIVE: In this study, we examined the effect of 20% citric acid lotion, as compared with vehicle alone, on skin thickness, viable epidermal thickness, and dermal glycosaminoglycan content. Biopsy samples were harvested after 3 months of treatment. RESULTS: Image analysis of biopsy sections revealed increases in viable epidermal thickness and dermal glycosaminoglycans in treated skin. CONCLUSIONS: Topical citric acid produces changes similar to those observed in response to glycolic acid, ammonium lactate, and retinoic acid including increases in epidermal and dermal glycosaminoglycans and viable epidermal thickness. Further studies of citric acid and other alpha-hydroxy acids are warranted to clarify their clinical effects and mechanisms of action.

Administration, Cutaneous↗

Citric acid as excipient in multiple-unit enteric-coated tablets for targeting drugs on the colon.

Delivery of drugs to the large bowel has been extensively investigated during the last decade. The aim of this study was to investigate whether enteric-coated tablets could be made from enteric-coated matrix granules and drug release targeted to the colon. Whether in vitro drug release rate and in vivo absorption could be delayed by adding citric acid to the granules and/or to the tablet matrix was also studied. Ibuprofen was used as model drug because it is absorbed throughout the gastrointestinal tract. Eudragit S and Aqoat AS-HF were used as enteric polymers. Drug release rates were studied at different pH levels and drug absorption was studied in bioavailability tests. The conclusion was that citric acid retarded in vitro drug release when used in multiple-unit tablets. In vivo absorption of ibuprofen was markedly delayed when citric acid was included in both granules and tablet matrix. Further studies are needed to determine the optimal amount of citric acid in formulations.

Adult↗

The effect on healing of the application of citric acid during replaced flap surgery.

The aim of this double-blind controlled clinical trial was to assess the effect on healing following conditioning the root surface with citric acid during replaced flap surgery. Healing was assessed in 18 pairs of sites in 12 patients before surgery and after 3 months; healing was also assessed in 13 pairs of these sites in 10 of the patients after 9 months. During surgery, the root surface at 1 site from each pair was treated with citric acid pH 0.6 for 3 min and the contralateral site was exposed to sterile saline. Healing was assessed by measuring attachment levels, probing depths and recession; in addition, gingival crevicular fluid flow was measured, as was the degree of bleeding on probing. The mean gain of attachment (mm) in the acid and control groups were 1.0 and 1.2, respectively, at 3 months and 1.1 and 0.9 respectively, at 9 months. The results of this study indicate, both clinically and statistically, that the difference in healing between the acid and the non-acid sites is not significant. Thus no additional benefit is shown by using citric acid in conjunction with replaced flap surgery on anterior teeth.

Adult↗

Effect of citric acid and lyophilized autologous plasma on healing following periodontal flap surgery in monkeys.

The purpose of this histologic, histometric, and autoradiographic study was to examine the effect of citric acid conditioning and lyophilized autologous plasma (LAP) application on healing following periodontal flap surgery. Mucoperiosteal flaps were elevated in six rhesus monkeys using the modified Widman flap procedure. A total of 24 quadrants were treated, each included the first and second premolar and first and second molar teeth. Cementum was removed from the exposed root surfaces, and reference notches were inscribed into the roots at the alveolar bone margin. Two treatment modalities were employed: (1) surgery plus citric acid conditioning, to serve as control and (2) surgery plus citric acid followed by LAP application (400 mg/ml saline). Flaps were returned to their preoperative positions and sutured. Animal sacrifices were scheduled to provide observations 3, 7, 14, 21, 28, and 45 days after surgery. Each monkey received an intravenous injection of tritiated thymidine, 1 microCi/gm of body weight, 1 hour before it was killed. Tissue specimens were processed for evaluation following standard procedures. Histologically, tissue sections were examined for: (1) proliferation and attachment of epithelium, (2) organization and maturation of periodontal fibers, (3) inflammatory cell types, (4) presence or absence of new cementum deposition, and (5) degree of vascularity of the tissues. For histometric evaluation, the radicular notches were used as reference points. The distances examined histometrically were: (1) from the root surface notch to the alveolar bone crest, (2) from the root surface notch to the apical extent of the junctional epithelium, and (3) from the free gingival margin to the apical extent of the junctional epithelium. For autoradiographic evaluation labeled cells were counted in five spatial compartments at 400 X magnification: (1) oral epithelium, (2) crevicular area, (3) supracrestal connective tissue, (4) coronal periodontal membrane, and (5) coronal bone marrow. For each the histometric and autoradiographic evaluation involved a total of 36 tissue sections per quadrant (9 sections per tooth). Tooth and quadrant means were obtained for each monkey. The plasma-treated and control quadrants were compared at each time point by the paired t test. N = 2 monkeys were used for each comparison. Histologic results showed that in teeth that were acid-conditioned after root planing, the epithelium often migrated apically reaching the radicular notch. Those teeth that were conditioned and subsequently treated with LAP demonstrated fiber attachment to the planed root surface and little or no epithelial downgrowth.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Human enamel dissolution in citric acid as a function of pH in the range 2.30< or =pH< or =6.30--a nanoindentation study.

The objective of this study was to investigate the dissolution of human enamel in citric acid solutions over a wide range of pH. The in vitro conditions are considered to be relevant to soft drink-induced enamel erosion. Nanoindentation was used to investigate changes in the nanomechanical properties of polished enamel surfaces after exposure to citric acid solutions. Solutions used had 38.1 mmol l-1 citric acid and pH greater than 2.3 but less than 6.3 (2.30 < or = pH < or = 6.30). Samples were exposed to rapidly stirred, constant composition solutions for 120 s. Statistically significant changes in enamel hardness and reduced elastic modulus were observed after exposure to all solutions. There was an approximately linear dependence of enamel hardness on solution pH for 2.90 < or = pH < or = 6.30. Below pH 2.90, enamel is thought to have reached the lowest possible hardness value. The reduction in enamel dissolution caused by an increase in pH of a soft drink is likely to be small. Product modification to reduce the erosive potential of drinks may require additional methods such as addition of calcium salts.

Citric Acid↗

[Effects of citric acid and tetracycline HCL treatment on periodontal healing].

The aim of the present study was to examine if a new connective tissue attachment is established following citric acid and tetracycline HCI treatment of roots, surgically deprived of its attachment apparatus. The 2. and 3. premolars of three dogs were used. After elevation of mucoperiostal flaps alveolar bone was removed extending a level of 2/3 of the roots. Then, teeth were treated with %1 citric acid PH 1 and Tetracycline HCI (Aquas solution) for 3 minutes and 4 teeth were used as control. After the 21 days of healing period the groups were evaluated histopathologically. The results indicate that citric acid and tetracycline treatment increase the amount of new attachment, inhibit the down growth of the dento gingival epithelium, allowing more time for the repopulation of periodontal ligament cells on the root surfaces.

Alveolar Bone Loss↗

Structural study of very thin anodic alumina films on silicon by anodization in citric acid aqueous solution.

The formation of thin alumina films on a silicon substrate by anodization in a mild acid, specifically in 1% wt citric acid aqueous solution, is investigated by transmission electron microscopy (TEM). We present a comparative study between two cases of starting material: pure aluminum and an alloy of aluminum with 1% silicon. In both cases the thickness of the Al layer was less than 50 nm. It was observed that under exactly the same conditions, in the first case the anodization was stopping before anodizing the whole film and a remaining non-anodized Al layer was always present, while in the second case, the Al layer was fully anodized, resulting in an alumina matrix with a very high density of silicon nanocrystals of uniform sizes embedded in it. In both cases the alumina film was compact and amorphous.

Aluminum Oxide↗

Citric Acid cycle activity in mitochondria isolated from mung bean hypocotyls.

Citric acid cycle activity in mitochondria from mung bean (Phaseolus aureus var. Jumbo) hypocotyls were examined by surveying (a) characteristics of oxidation of cycle intermediates; (b) activities of cycle enzymes in mitochondrial extracts; (c) contents of cycle intermediates and electron transport components in isolated mitochondria; and (d) time-course changes of products formed during oxidation of succinate, malate, and citrate. Isolated mitochondria are deficient in thiamine pyro-phosphate and somewhat so in adenylates, but apparently sufficient in CoA, NAD, and electron transport carriers. Cycle activity in the mitochondria is not directly correlated with the activities of the enzymes measured in extracts. These studies led to the conclusion that the region between malate and citrate is an important regulatory area in citric acid cycle functioning in isolated mung bean mitochondria.

Journal Article↗

[On the contamination of the citric acid fermentation. I. The contamination by representatives of Enterobacteriaceae (author's transl)].

Among the most dangerous bacterial contaminations of the citric acid fermentation is the so-called brown contamination, which is called forth by non pathogenic representatives of Enterobacteriaceae like Escherichia coli, Aerobacter aerogenes, Enterobacter cloacae and Proteus vulgaris, while other bacteria do not produce the mentioned contamination. There is given a comprehensive characterization of the brown contamination. Enterobacteriaceae interrupt the growth of the mycelium of the mold Aspergillus niger and stop the production of citric acid, produce a characteristic repugnant smell and reduce nitrate to nitrite. In a case of weak contamination the phenomena of the brown contamination do not appear, but the yield of citric acid is rather low. The contamination may be transferred successfully within the first 24 hrs. of incubation. The effect of the bacteria is determined by their virulence and some other factors.

Aspergillus niger↗

Effect of volume of culture medium on enhanced citric acid productivity by a mutant culture of Aspergillus niger in stirred fermentor.

AIMS: The present study deals with the effect of volume of culture medium on enhanced citric acid productivity by a mutant culture of Aspergillus niger. METHODS AND RESULTS: A laboratory scale stirred fermentor of 15-l capacity was employed for all microbial cultivations. Blackstrap molasses, a by-product of sugar industries is easily and abundantly available for its exploitation as a carbon source in fermentation processes. The parental culture of A. niger was improved by mutation using ultraviolet radiations and N-methyl N-nitro N-nitroso guanidine, i.e. mutagen MNNG. Six MUV and eight MNNG-treated mutant strains were isolated after extensive screening and optimization. Mutant strain of A. niger MNNG-2 showed enhanced citric productivity (87.60 g l-1) over the parental strain BTL-45 (19.53 g l-1) and other mutant derivatives (49.85 g l-1 citric acid in case of mutant MUV-5 and 76.82 g l-1 in case of mutant MNNG-7). The optimal sugar level was found to be 150 g l-1 (optimum volume of the medium, 60%) after 6 days of inoculation, which is economically significant. Specific productivity of the mutant culture MNNG-2 (qp = 0.057 g/g cells h-1) was several folds higher than other strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of the present study are of commercial level. All kinetic parameters including yield coefficients and volumetric rates revealed the hyper-producibility of citric acid by mutant MNNG-2 using blackstrap molasses as the basal medium in stirred fermentor.

Aspergillus niger↗

Proteomic insights into hepatic responses to high soybean meal inclusion with citric acid supplementation in hybrid grouper (Epinephelus fuscoguttatus&#xa0;&#xd7;&#xa0;Epinephelus lanceolatus) juveniles.

This study evaluated the growth performance and hepatic proteomic responses of juvenile hybrid grouper (Epinephelus fuscoguttatus&#xa0;&#xd7;&#xa0;Epinephelus lanceolatus) juveniles fed diets containing 30% or 40% soybean meal (SBM), with or without 3% citric acid supplementation, and compared with a fishmeal (FM) control diet over a 10-week feeding trial. Fish fed 30% SBM (LSBM) showed a final body weight comparable to the FM group, whereas fish fed 40% SBM (HSBM) recorded significantly reduced growth and net protein utilization (NPU) (p&#xa0;<&#xa0;0.05). Supplementation of citric acid in the 40% SBM diet (HSBM + CA) significantly improved NPU and partially restored growth relative to HSBM. LC-MS/MS based quantitative proteomics identified 1544 hepatic proteins and showed clear dietary segregation. Differentially expressed proteins were predominantly associated with reduced abundance of proteins involved in lipid metabolism, amino acid metabolism, pyruvate metabolism, and the tricarboxylic cycle across all SBM diets, suggesting a shift in oxidative metabolic capacity. In contrast, LSBM induced upregulation of spliceosome-associated proteins and RNA processing components, suggesting adaptive post-transcriptional regulation under moderate SBM inclusion. In contrast, HSBM exhibited greater reduction in metabolic protein abundance without comparable upregulation of adaptive regulatory components, coinciding with reduced nutrient retention. Protein-protein interaction analysis further confirms the correlation between the regulation of spliceosomal clusters and mitochondrial lipid-catabolic modules. Citric acid supplementation did not markedly reverse hepatic metabolic protein changes but improved protein retention. Data are available via ProteomeXchange with identifier PXD081994. These findings suggest a tolerance limit between 30% and 40% SBM inclusion, with 30% inducing adaptive hepatic proteomic responses compatible with maintained growth performance.

Animals↗

Citric acid burnishing of dentinal root surfaces. A scanning electron microscopy report.

The integrity of formalin-fixed periodontally diseased root surfaces was assessed following root planing to dentin and citric acid application. Extracted human teeth (fixed in 10% formalin), with crowns removed, were vertically sectioned in half. A horizontal groove on each proximal surface marked the extent of attachment loss. The diseased root surface was vigorously root planed to expose dentin. Cotton pellets, soaked in a saturated solution of citric acid, were either "placed" (control) or "burnished" (vigorously rubbed using root planing pressure) (experimental) on the prepared root surface for 5 min. Pellets were changed 2 times/min. The teeth were fixed and prepared for scanning electron microscope viewing and photography. A representative print was selected for each specimen. To confirm differences between test and control groups, untrained raters were asked to perform 2 sorting exercises. First, they were asked to sort the representative photographs of each specimen into 2 piles based on surface characteristics. Second, they were asked to choose from pairs of photographs, representing matched specimens, the one photograph which appeared to have the greatest collagen surface area. The surfaces of experimental specimens revealed patent dentinal tubules and an intertubular area with a very distinct "shag carpet" appearance of deeply tufted collagen fibrils. Control samples also exhibited open dentinal tubules, yet the intertubular surface displayed a "matted collagen" surface. Results of the 2 sorting exercises confirm that burnishing of formalin-fixed dentin root surfaces for 5 min with cotton pellets soaked in a saturated solution of citric acid consistently produces a distinct tufted collagen fibril surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Topical↗

Responsivity to water regulatory challenges in rats adapted to fluids adulterated with quinine or citric acid.

Ad lib ingestive behavior and reactivity to water regulatory challenges were examined in rats adapted to citric acid- or to quinine-adulterated fluids. Quinine drinkers were unlike citric acid subjects in being unresponsive to fluid deprivation and to the hypovolemia produced by polyethylene glycol (PEG). The effect during hypovolemia was evident when subjects had access to adulterated physiological saline, a solution more responsive to the PEG-induced need state, and quinine group behavior was not easily explained in terms of the tastes of quinine and saline combined together nor in terms of a posttreatment malaise effect. Substances that degrade the taste of water therefore do not exert uniform effects; bitter quinine appears to have some unique property that remains to be specified.

Animals↗

Variation and evolution of the citric-acid cycle: a genomic perspective.

The presence of genes encoding enzymes involved in the citric-acid cycle has been studied in 19 completely sequenced genomes. In the majority of species, the cycle appears to be incomplete or absent. Several distinct, incomplete cycles reflect adaptations to different environments. Their distribution over the phylogenetic tree hints at precursors in the evolution of the citric-acid cycle.

Archaea↗

Reversibility of the mitochondrial isocitrate dehydrogenase reaction in the perfused rat liver. Evidence from isotopomer analysis of citric acid cycle intermediates.

The reversal of the mitochondrial isocitrate dehydrogenase reaction was investigated in rat livers perfused with [U-13C5]glutamate or [U-13C5]glutamine. The mass isotopomer distribution of citric acid cycle intermediates extracted from the livers was determined by gas chromatography-mass spectrometry. Citrate was enriched in an isotopomer containing five 13C. The formation of this isotopomer can only be explained by the reversal of the isocitrate dehydrogenase reaction. Calculation of kinetic parameters from the mass isotopomer data reveals a rapid interconversion of isocitrate and alpha-ketoglutarate. This interconversion results in an isotopic exchange between carbon 6 of citrate and mitochondrial CO2 that can affect the calculation of citric acid cycle kinetic parameters. Thus, the reversal of the isocitrate dehydrogenase reaction should be included in isotope labeling models of the citric acid cycle.

Animals↗

Burnished versus nonburnished application of citric acid to human diseased root surfaces: the effect of time and method of application.

Citric acid (pH = 1) was applied passively or by vigorous burnishing for 3 or 5 minutes to diseased human root surfaces following root planning in vitro. Control surfaces were similarly treated with saline only. Teeth were fixed in glutaraldehyde, dehydrated, freeze-dried, and sputter coated with gold for scanning electron microscopic viewing. Results suggested that optimal exposure of collagen and demineralization occurred with the burnishing application of citric acid for 3 minutes. Although somewhat similar results were found with passive application for 5 minutes, the result of the burnishing application for 5 minutes was that the root was overdemineralized or that the exposed collagen was completely obscured by an amorphous layer that was suggestive of protein denaturization.

Citrates↗

Changes in citric acid cycle flux and anaplerosis antedate the functional decline in isolated rat hearts utilizing acetoacetate.

To determine the temporal relationship between changes in contractile performance and flux through the citric acid cycle in hearts oxidizing acetoacetate, we perfused isolated working rat hearts with either glucose or acetoacetate (both 5 mM) and freeze-clamped the tissue at defined times. After 60 min of perfusion, hearts utilizing acetoacetate exhibited lower systolic and diastolic pressures and lower cardiac outputs. The oxidation of acetoacetate increased the tissue content of 2-oxoglutarate and glutamate and decreased the content of succinyl-CoA suggesting inhibition of citric acid cycle flux through 2-oxoglutarate dehydrogenase. Whereas hearts perfused with either acetoacetate or glucose were similar with respect to their function for the first 20 min, changes in tissue metabolites were already observed within 5 min of perfusion at near-physiological workloads. The addition of lactate or propionate, but not acetate, to hearts oxidizing acetoacetate improved contractile performance, although inhibition of 2-oxoglutarate dehydrogenase was probably not diminished. If lactate or propionate were added, malate and citrate accumulated indicating utilization of anaplerotic pathways for the citric acid cycle. We conclude that a decreased rate of flux through 2-oxoglutarate dehydrogenase in hearts oxidizing acetoacetate precedes, and may be responsible for, contractile failure and is not the result of decreased cardiac work. Further, anaplerosis play an important role in the maintenance of contractile function in hearts utilizing acetoacetate.

Acetoacetates↗