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Solubility and dissolution rate studies of ergotamine tartrate.

The solubility of ergotamine tartrate in aqueous solutions of tartaric acid, citric acid, hydrochloric acid, and caffeine and the dissolution rate of ergotamine tartrate in aqueous mixtures containing hydrochloric acid, caffeine, citric acid, or sodium acetate were studied. The Noyes-Whitney model of dissolution is useful for predicting the dissolution rate of ergotamine tartrate in most of the dissolution media. The relative slowness with which ergotamine chloride (a substance with low water solubility) precipitated when ergotamine tartrate was dissolved in 0.1 M HCl resulted in the solid dissolving faster in this medium than was predicted using the Noyes-Whitney equation.

Caffeine↗

The effects of organic species on the hygroscopic behaviors of inorganic aerosols.

Water-soluble organic compounds have recently received much attention because of their ability to absorb water and alter the hygroscopic properties of inorganic aerosols. The effects of glycerol, succinic acid, malonic acid, citric acid, and glutaric acid on the water cycles (water activities during particle evaporation and growth), crystallization relative humidities (CRH), and deliquescence relative humidities (DRH) of sodium chloride (NaCl) and ammonium sulfate (AS) were studied using an electrodynamic balance (EDB). The growth factors of these inorganic and organic mixtures were lower than those of the pure inorganic species. The presence of all these organics in the mixed particle reduce the water absorption of NaCl but enhance that of AS relative to that of the pure inorganic salts. Glycerol and succinic acid did not affect the deliquescence properties of NaCl and AS, although succinic acid increased the CRH of NaCl and AS. Malonic acid and citric acid, behaving as nondeliquescent species in single particle studies, caused NaCl and AS particles to absorb a significant amount of water before deliquescence. Glutaric acid caused NaCl and AS to deliquesce gradually, spanning a wide range of relative humidity. The ZSR model was found to be useful in predicting the water activity of the mixtures and the growth ratios. However, the detailed crystallization and deliquescence behaviors of the organic/inorganic mixtures cannot be easily predicted from the hygroscopic properties of the individual components.

Absorption↗

Occurrence and characterization of yeasts isolated from milks and dairy products of Apulia region.

One hundred and five strains of yeasts isolated from milk of different animal origin and from typical Apulian cheeses were studied to identify and characterize yeast strains for further selection as starter cultures for cheese production. The most prevalent isolates belonged to the species Trichosporon cutaneum (15.24%), Candida catenulata (10.48%) and Yarrowia lipolytica (8.57%). In order to evaluate the potential use as starter cultures, the occurrence of some selected properties, such as fermentation of glucose and lactose, assimilation of lactic acid, citric acid and lactose, growth at 4 degrees C and production of lipolytic and proteolytic enzymes in the strains belonging to the most frequent species was tested. C. catenulata and C. zeylanoides were positive for assimilation of lactic and citric acids and showed psychrotrophic aptitude. T. cutaneum was positive for all properties tested except for glucose and lactose fermentations. Y. lipolytica was endowed with remarkable lipolytic activity also at 4 degrees C and was positive for assimilation of lactic and citric acids, growth at 4 degrees C and proteolytic activity.

Animals↗

Effect of hyperprotidic diet associated or not with hypercalcic diet on calcium oxalate stone formation in rat.

The aim of this study was to determine whether protein, administered alone or simultaneously with a hypercalcic diet, was able to aggravate calcium oxalate stone formation in rats. Thirty-two male Wistar rats were randomly divided into four groups of 8 rats each and assigned a calcium oxalate lithogenic diet added to their drinking water for 3 weeks. One group, used as reference, received a standard diet prepared in our laboratory. The second was assigned the same diet but supplemented with 7.5 g animal proteins/100 g diet. The third received a diet containing 500 mg calcium more than the standard group. The diet given to the last group was supplemented with calcium and protein at the same doses indicated previously. One day before the end of treatment, each animal was placed in a metabolic cage to collect 24-hour urine samples and determine urinary creatinine, urea, calcium, magnesium, phosphate, uric acid, citric acid and oxalate levels. Immediately thereafter, aortic blood was collected to determine the same parameters as in urine. The kidneys were also removed to determine calcium oxalate deposits. Our results showed an increased 24-hour urinary excretion of calcium, oxalate and uric acid and decreased urinary citric acid excretion only in groups that received protein supplementation. At the same time, calcium oxalate deposits were found significantly higher in hyperprotidic diets than reference or calcium-supplemented groups. According to these findings, glomerular filtration, fractional excretion of urea and reabsorption of water, calcium and magnesium were found significantly lower in hyperprotidic diets compared to other groups. These results demonstrate that proteins could seriously aggravate calcium oxalate stones and cause renal disturbances.

Animals↗

Modulation of antioxidant compounds in organic vs conventional fruit (peach, Prunus persica L., and pear, Pyrus communis L.).

Despite the increasing interest in organic products, knowledge about how different levels of fertilization affect nutritionally relevant components is still limited. The concentration of polyphenols and the activity of polyphenoloxidase (PPO), together with the content in ascorbic acid, citric acid, and alpha- and gamma-tocopherol, were assayed in conventional and organic peach (Prunus persica L., cv. Regina bianca) and pear (Pyrus communis L., cv. Williams). 2-Thiobarbituric acid reactive substances and the tocopherolquinone/alpha-tocopherol ratio were used as markers of oxidative damage in fruits. A parallel increase in polyphenol content and PPO activity of organic peach and pear as compared with the corresponding conventional samples was found. Ascorbic and citric acids were higher in organic than conventional peaches, whereas alpha-tocopherol was increased in organic pear. The concentration of oxidation products in organic samples of both fruits was comparable to that of the corresponding conventional ones. These data provide evidence that an improvement in the antioxidant defense system of the plant occurred as a consequence of the organic cultivation practice. This is likely to exert protection against damage of fruit when grown in the absence of pesticides.

Antioxidants↗

Survival of Escherichia coli O157:H7 in synthetic gastric fluid after cold and acid habituation in apple juice or trypticase soy broth acidified with hydrochloric acid or organic acids.

Extreme acid tolerance of Escherichia coli O157:H7 has raised doubts about the safety of acidic foods. This study examined whether prior storage in acidic and/or cold conditions enhanced survival of E. coli O157:H7 in synthetic gastric fluid (SGF). Three E. coli O157:H7 strains were stored in trypticase soy broth (TSB; acidified with HCl, malic acid, citric acid, or lactic acid) or pH 3.5 and 6.5 (nonacidic control) apple juice at 4 and 21 degrees C for < or = 7 days and then were incubated in pH 2.5 SGF at 37 degrees C for 4 h. Cells survived better in apple juice than in TSB containing organic acids, suggesting that juice constituents other than organic acids protect E. coli O157:H7. Refrigeration combined with low pH best protected cells in apple juice and acidified TSB, but, compared to the nonacidic control, only acidified TSB enhanced subsequent survival in pH 2.5 SGF. Equal survival in SGF occurred after storage in pH 3.5 or 6.5 apple juice at 4 degrees C, suggesting that low temperature alone in apple juice enhanced acid tolerance. Two strains stored at 4 degrees C in TSB containing malic or citric acid subsequently survived better in SGF than cells stored in nonacidified TSB but poorer than cells stored in the presence of HCl. These differences reflect the higher pKa of these organic acids. However, subsequent survival of these strains in SGF was poorer after refrigerated storage in apple juice than in TSB containing citric or malic acids. Cells stored in lactic acid were most likely to be completely eliminated upon transfer to SGF. Differences in survival in storage media or SGF related to strain, storage conditions, or acidifier were consistent and often statistically significant (P < 0.05). Although the survival of E. coli O157:H7 in refrigerated acidic beverages may not be affected by the type of acidifier used, the subsequent survival in SGF of this pathogen may be critically dependent on this factor.

Beverages↗

The influence of dietary factors on the risk of urinary stone formation.

The action of various beverages and foods on the composition of the urine in the circadian rhythm and in the 24-hour urine has been investigated under standardized conditions. Orange juice leads to a significant increase of urinary pH and citric acid excretion. Black tea leads to a raised excretion of oxalic acid by only 7.9%. In the short term, beer increases diuresis, but afterwards leads to a compensatory antidiuresis with increased risk of stone formation. Depending on their composition, mineral waters have very different effects on the urinary constituents. Milk as well as cocoa beverage significantly increase calcium excretion; moreover, cocoa causes an increase in the oxalic acid excretion. The leafy vegetable foods containing oxalate, e.g., spinach and rhubarb, lead to peaks of oxalate excretion of 300-400% in the circadian excretion curve. Cheese leads to a significant rise of calcium excretion with acidification of the urine and lowering of citrate excretion. Calcium excretion is increased by 30% by sodium chloride. Foods containing purine result in an increased uric acid excretion over several days. Depending on their phytic acid content, brans bind calcium, but lead to an increased oxalic acid excretion. Analysis of the urine indicates that average diet in Germany entails a high risk of urinary stone formation. As a result of the change to a balanced mixed or vegetarian diet, according to the requirements, significant alterations in urinary pH, calcium, magnesium, uric acid, citric acid, cystine, and glycosaminoglycan excretion are measured, resulting in a drastic reduction in the risk of urinary stone formation.

Adult↗

Simultaneous determination of polycarboxylic acids by capillary electrophoresis with a copper electrode.

The simultaneous determination of polycarboxylic acids including oxalic acid, citric acid, malonic acid, malic acid, tartaric acid, aspartic acid and glutamic acid was achieved by capillary electrophoresis with a copper disk electrode (d = 200 microm). In the system. 0.2 mmol/l cetylpridinium bromide (CPB) was used as an electroosmotic flow (EOF) modifier to reverse the direction of EOF. The effects of the solution pH and CPB concentration on separation were evaluated to achieve the optimum separation conditions. At the working potential of +0.14 V (vs. saturated calomel electrode), the calibration curves for all polycarboxylic acids studied were linear with 2 approximately 3-orders of magnitude and all the detection limits (S/N = 3) were below 15 fmol except malonic acid. Furthermore, the oxalic and citric acids in urine were successfully separated and determined with high sensitivity.

Carboxylic Acids↗

Micropore to macropore structure-designed silicas with regulated condensation of silicic acid nanoparticles.

A new preparation method for porous silica particles was developed using activated silica sols which are called nano-silica solutions in this paper. Several kinds of organic and inorganic acids are employed to neutralize diluted sodium silicate solutions to form the nano-silica solutions: formic acid, acetic acid, propionic acid, oxalic acid, succinic acid, dl-malic acid, citric acid, and tricarballylic acid as carboxylic acids, and sulfuric acid and hydrochloric acid as inorganic acids. The effect of salts in the nano-silica solution is also studied. The products were investigated using a field emission scanning electron microscope, an X-ray diffractometer, the nitrogen adsorption technique, and a mercury porosimeter. Microporous silicas were produced when carboxylic acids were applied; the formation of micropores was influenced by the pH of the nano-silica solutions and molecular sizes of the carboxylic acids. Addition of a salt in a citric acid solution increased the mesopore volume. Macropores were formed when inorganic acids including salts were applied; the salt nanoparticles which were crystallized in silica spheres acted as templates. The anion types and salt concentrations in the nano-silica solutions affected the aggregation condition of silica nanoparticles, following the Schulze-Hardy rule.

Journal Article↗

Corrosion of aluminium in soft drinks.

The corrosion of aluminium (Al) in several brands of soft drinks (cola- and citrate-based drinks) has been studied, using an electrochemical method, namely potentiodynamic polarization. The results show that the corrosion of Al in soft drinks is a very slow, time-dependent and complex process, strongly influenced by the passivation, complexation and adsorption processes. The corrosion of Al in these drinks occurs principally due to the presence of acids: citric acid in citrate-based drinks and orthophosphoric acid in cola-based drinks. The corrosion rate of Al rose with an increase in the acidity of soft drinks, i.e. with increase of the content of total acids. The corrosion rates are much higher in the cola-based drinks than those in citrate-based drinks, due to the facts that: (1) orthophosphoric acid is more corrosive to Al than is citric acid, (2) a quite different passive oxide layer (with different properties) is formed on Al, depending on whether the drink is cola or citrate based. The method of potentiodynamic polarization was shown as being very suitable for the study of corrosion of Al in soft drinks, especially if it is combined with some non-electrochemical method, e.g. graphite furnace atomic absorption spectrometry (GFAAS).

Aluminum↗

[Zinc and chronic enteropathies].

In recent years the nutritional importance of zinc has been well established; its deficiency and its symptoms have also been recognized in humans. Furthermore, Acrodermatitis Enteropathica has been isolated, a rare but severe disease, of which skin lesions, chronic diarrhoea and recurring infections are the main symptoms. The disease is related to the malfunctioning of intestinal absorption of zinc and can be treated by administering pharmacological doses of zinc orally. Good dietary sources of zinc are meat, fish and, to a less extent, human milk. The amount of zinc absorbed in the small intestine is influenced by other nutrients: some compounds inhibit this process (dietary fiber, phytate) while others (picolinic acid, citric acid), referred to as Zn-binding ligands (ZnBL) facilitate it. Citric acid is thought to be the ligand which accounts for the high level of bioavailability of zinc in human milk. zinc absorption occurs throughout the small intestine, not only in the prossimal tract (duodenum and jejunum) but also in the distal tract (ileum). Diarrhoea is one of the clinical manifestations of zinc deficiency, thus many illnesses distinguished by chronic diarrhoea entail a bad absorption of zinc. In fact, in some cases of chronic enteropathies in infants, like coeliac disease and seldom cystic fibrosis, a deficiency of zinc has been isolated. Some of the symptoms of Crohn's disease, like retarded growth and hypogonadism, have been related to hypozinchemia which is present in this illness. Finally, it is possible that some of the dietary treatments frequently used for persistent post-enteritis diarrhoea (i.e. cow's milk exclusion, abuse and misuse of dietary fiber like carrot and carub powder, use of soy formula) can constitute a scarce supply of zinc and therefore could promote the persistency of diarrhoea itself.

Biological Availability↗

Different forms of heroin and their relationship to cook-up techniques: data on, and explanation of, use of lemon juice and other acids.

Recent reports of the use of lemon juice in the preparation of heroin for injection have failed to recognize the importance of the different forms of heroin (in the form of the salt or the base) and the impact of this on the chemical manipulation required before injection. One hundred and four opiate addicts in London were interviewed about the forms of heroin (white, brown, etc) and their relationship to cook-up techniques (use of heat and acid). White heroin was typically prepared with water and heat; brown heroin was prepared with acid (citric acid or Vitamin C (ascorbic acid) or lemon juice) and heat; pharmaceutical heroin was prepared with water only (i.e. neither acid nor heat). On the last occasion of heroin use, brown heroin had been the form most commonly used, with over 90% of the sample using citric acid or vitamin C. Lemon juice was rarely used, and heat was almost universally applied in conjunction with lemon juice.

Adult↗

Augmenting effect of acetic acid for acidification on bactericidal activity of hypochlorite solution.

AIMS: Bactericidal activity of chlorine solution is enhanced by weak acidification. We compared the effects of various acids on the bactericidal activity of hypochlorite solution to establish a method for safe and effective use of an acidic hypochlorite solution. METHODS AND RESULTS: The bactericidal activities of acidic hypochlorite solutions that had been adjusted to pH 5.0 with hydrochloric acid, acetic acid, citric acid, lactic acid, formic acid, phosphoric acid or sulphuric acid against Bacillus subtilis spores were compared. The acidic solutions prepared with hydrochloric acid and acetic acid showed the highest bactericidal activity, and all of the spores (5 x 106 cfu ml(-1)) were killed within 10 min. On the other hand, the solutions prepared with citric acid and lactic acid showed no bactericidal activity against any bacterial strains tested in this study despite the low pH. The amount of chlorine gas produced by the preparation using acetic acid was sixfold less than that produced from the preparation using hydrochloric acid. CONCLUSIONS: Acetic acid is the most suitable and safe acid for the preparation of an acidic hypochlorite solution. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study provide useful information for establishing a method for safe and effective use of an acidic hypochlorite solution.

Acetic Acid↗

Transport of tricarboxylic acids in Salmonella typhimurium.

Salmonella typhimurium possesses at least three inducible transport systems for the tricarboxylic acids (citric, isocitric, cis-aconitic, and tricarballylic). The first system was induced by citrate, isocitrate, or cis-aconitate, and transported citric acid and isocitric acid. The second system was also induced by the same acids as in the first system and transported cis-aconitic acid. This system required Mg(2+) ions and was stable at pH 8.4 but unstable at pH 7.0. The metal ion was replaced with Sr(2+) or Ca(2+) ions but not with Ba(2+) ions. The third system was induced by tricarballylate and transported citric acid, cis-aconitic acid, and tricarballylic acid.

Aconitum↗

Intraluminal transport of iron from stomach to small-intestinal mucosa.

Inorganic iron rarely exceeds 10(-4) molar concentration in the stomach after a meal. Natural sugars, ascorbic acid, citric acid, and amino-acids form iron complexes, and if they are present in the meal complexing occurs when the gastric contents are neutralized. In their absence an iron complex is formed with gastric mucopolysaccharide, which acts as a carrier, stable at neutral pH. Iron can be detached from this carrier at neutral pH by some low molecular weight substances, of which citric acid, ascorbic acid, and cysteine are particularly effective at low concentrations. Under normal circumstances most of the iron released from food in the stomach becomes bound to the mucopolysaccharide carrier.

Amino Acids↗

Enhanced phytoextraction: in search of EDTA alternatives.

Enhanced phytoextraction proposes the use of soil amendments to increase the heavy-metal content of above-ground harvestable plant tissues. This study compares the effect of synthetic aminopolycarboxylic acids [ethylenediamine tetraacetatic acid (EDTA), nitriloacetic acid (NTA), and diethylenetriamine pentaacetic acid (DTPA)] with a number of biodegradable, low-molecular weight, organic acids (citric acid, ascorbic acid, oxalic acid, salicylic acid, and NH4 acetate) as potential soil amendments for enhancing phytoextraction of heavy metals (Cu, Zn, Cd, Pb, and Ni) by Zea mays. The treatments in this study were applied at a dose of 2 mmol/kg(-1) 1 d before sowing. To compare possible effects between presow and postgermination treatments, a second smaller experiment was conducted in which EDTA, citric acid, and NH4 acetate were added 10 d after germination as opposed to 1 d before sowing. The soil used in this screening was a moderately contaminated topsoil derived from a dredged sediment disposal site. This site has been in an oxidized state for more than 8 years before being used in this research. The high carbonate, high organic matter, and high clay content characteristic to this type of sediment are thought to suppress heavy-metal phytoavailability. Both EDTA and DTPA resulted in increased levels of heavy metals in the above-ground biomass. However, the observed increases in uptake were not as large as reported in the literature. Neither the NTA nor organic acid treatments had any significant effect on uptake when applied prior to sowing. This was attributed to the rapid mineralization of these substances and the relatively low doses applied. The generally low extraction observed in this experiment restricts the use of phytoextraction as an effective remediation alternative under the current conditions, with regard to amendments used, applied dose (2 mmol/kg(-1) soil), application time (presow), plant species (Zea mays), and sediment (calcareous clayey soil) under study.

Biodegradation, Environmental↗

Studies on dissolution enhancement and mathematical modeling of drug release of a poorly water-soluble drug using water-soluble carriers.

Role of various water-soluble carriers was studied for dissolution enhancement of a poorly soluble model drug, rofecoxib, using solid dispersion approach. Diverse carriers viz. polyethylene glycols (PEG 4000 and 6000), polyglycolized fatty acid ester (Gelucire 44/14), polyvinylpyrollidone K25 (PVP), poloxamers (Lutrol F127 and F68), polyols (mannitol, sorbitol), organic acid (citric acid) and hydrotropes (urea, nicotinamide) were investigated for the purpose. Phase-solubility studies revealed AL type of curves for each carrier, indicating linear increase in drug solubility with carrier concentration. The sign and magnitude of the thermodynamic parameter, Gibbs free energy of transfer, indicated spontaneity of solubilization process. All the solid dispersions showed dissolution improvement vis-à-vis pure drug to varying degrees, with citric acid, PVP and poloxamers as the most promising carriers. Mathematical modeling of in vitro dissolution data indicated the best fitting with Korsemeyer-Peppas model and the drug release kinetics primarily as Fickian diffusion. Solid state characterization of the drug-poloxamer binary system using XRD, FTIR, DSC and SEM techniques revealed distinct loss of drug crystallinity in the formulation, ostensibly accounting for enhancement in dissolution rate.

Calorimetry, Differential Scanning↗

Gastrointestinal mucoadhesive patch system (GI-MAPS) for oral administration of G-CSF, a model protein.

A new gastrointestinal mucoadhesive patch system (GI-MAPS) has been designed for the oral delivery of protein drugs. The system consists of four layered films, 3.0 x 3.0 mm2, contained in an enteric capsule. The 40 microm backing layer is made of a water-insoluble polymer, ethyl cellulose (EC). The surface layer is made of an enteric pH-sensitive polymer such as hydroxypropylmethylcellulose phthalate (HP-55), Eudragit L100 or S100 and was coated with an adhesive layer. The middle layer, drug-containing layer. made of cellulose membrane is attached to the EC backing layer by a heating press method. Both drug and pharmaceutical additives including an organic acid, citric acid, and a non-ionic surfactant, polyoxyethylated castor oil derivative (HCO-60), were formulated in the middle layer. The surface layer was attached to the middle layer by an adhesive layer made of carboxyvinyl polymer (Hiviswako 103). Fluorescein (FL), 30mg, was first used as a model drug for oral administration of GI-MAPS having different surface layers in beagle dogs. The plasma FL concentration vs. time profiles demonstrated that the targeting of the systems was obtained, because the Tmax, the time when plasma FL concentrations reaches to its maximum lelev, was 2.33+/-0.82 h for HP-55 system, 3.33+/-0.41 h for Eudragit L100 system and 5.00+/-0.00 h for Eudragit S100 system. The same three kinds of GI-MAPSs containing 125 microg of recombinant human granulocyte colony-stimulating factor (G-CSF) were prepared and orally administered to dogs and the increase in total white blood cell (WBC) counts were measured as the pharmacological index for G-CSF. Comparison with the total increase of WBCs after iv injection of the same amount of G-CSF (125 microg) indicated the pharmacological availabilities (PA) of G-CSF were 23%, 5.5% and 6.0% for Eudragit L100, HP-55 and Eudragit S100 systems. By decreasing the amount of HCO-60 and citric acid, the PA of G-CSF decreased. These results suggest the usefulness of GI-MAPS for the oral administration of proteins.

Administration, Oral↗