Abstract  There are five U.S. manufacturers of propylene glycol ether derivatives shown in Table 1. This table also lists the trade names for these materials. The ethers of mono‐, di‐, tri‐, and polypropylene glycol are prepared commercially by reacting propylene oxide with the alcohol of choice in the presence of a catalyst. They may also be prepared by direct alkylation of the selected glycol with an appropriate alkylating agent such as a dialkyl sulfate in the presence of an alkali. The monoalkyl ethers of propylene glycol occur in two isomeric forms, the alpha or beta isomer. The alpha isomer is a secondary alcohol (on the middle carbon of the propane backbone) that forms the ether linkage at the terminal alcohol of propylyene glycol. This alpha isomer is predominant during synthesis. The beta isomer is a primary alcohol with the ether linkage formed at the secondary alcohol. The toxicological significance of the alpha and beta isomers of propylene glycol is discussed later in this narrative. The monoalkyl ethers of dipropylene glycol occur in four isomeric forms. The commercial product Dowanol® DPM Glycol Ether is believed to be a mixture of these but to consist to a very large extent of the isomer in which the alkyl group has replaced the hydrogen of the primary hydroxyl group of the dipropylene glycol, which is a secondary alcohol. The internal ether linkage is between the 2 position of the alkyl‐etherized propylene unit and the primary carbon of the other propylene unit, thus leaving the remaining secondary hydroxyl group unsubstituted. In the case of dipropylene glycol monomethyl ether, the primary isomer is 1‐(2‐methoxy‐1‐methylethoxy)‐2‐propanol. The monoalkyl ethers of tripropylene glycol can appear in eight isomeric forms. The commercial product Dowanol® TPM Glycol Ether, however, is believed to be a mixture of isomers consisting largely of the one in which the alkyl group displaces the hydrogen of the primary hydroxyl group of the tripropylene glycol and the internal ether linkages are between secondary and primary carbons. The known physical properties of the most common ethers are given in Tables 5 and 8. The methyl and ethyl ethers of these propylene glycols are miscible with both water and a great variety of organic solvents. The butyl ethers have limited water solubility but are miscible with most organic solvents. This mutual solvency makes them valuable as coupling, coalescing, and dispersing agents. These glycol ethers have found applications as solvents for surface coatings, inks, lacquers, paints, resins, dyes, agricultural chemicals, and other oils and greases. The di‐ and tripropylene series also are used as ingredients in hydraulic brake fluids. Occupational exposure would normally be limited to dermal and/or inhalation exposure. The toxicological activity of the propylene glycol‐based ethers generally indicates a low order of toxicity. Under typical conditions of exposure and use, propylene glycol ethers pose little hazard. As with many other solvents, appropriate precautions should be employed to minimize dermal and eye contact and to avoid prolonged or repeated exposures to high vapor concentrations. The propylene glycol ethers (PGEs), even at much higher exposure levels, do not cause the types of toxicity produced by certain of the lower molecular weight ethylene glycol ethers (EGEs). Specifically, they do not cause damage to the thymus, testes, kidneys, blood, and blood‐forming tissues as seen with ethylene glycol methyl and ethyl ethers. In addition, the propylene glycol ethers induce neither the development effects of certain of the methyl‐ and ethyl‐substituted ethylene glycol‐based ethers nor the hemolysis and associated secondary effects seen in laboratory animals with EGEs. Other propylene glycol ethers also exhibit a similar lack of toxicity. For example, propylene glycol ethyl ether (PGEE) and its acetate do not cause the critical toxicities of testicular, thymic, or blood injury and do not produce birth defects. Propylene glycol tertiary‐butyl ether (PGTBE) also has been tested and fails to elicit these toxicities or birth defects in rats exposed by inhalation to substantial concentrations. The methyl, ethyl, and n‐butyl ethers of butylene glycol considered herein are prepared by reacting the appropriate alcohol with the so‐called straight‐chain butylene oxide, consisting of about 80% 1,2 isomer and about 20% 2,3 isomer in the presence of a catalyst. They are colorless liquids with slight, pleasant odors. The methyl and ethyl ethers are miscible with water, but the butyl ether has limited solubility. All are miscible with many organic solvents and oils; thus, they are useful as mutual solvents, dispersing agents, and solvents for inks, resins, lacquers, oils, and greases. Industrial exposure may occur by any of the common routes. The common esters and diesters of the polyols are prepared commercially by esterifying the particular polyol with the acid, acid anhydride, or acid chloride of choice in the presence of a catalyst. Mono‐ or diesters result, depending on the proportions of each reactant employed. The ether esters are prepared by esterifying the glycol ether in a similar manner. Other methods can also be used. The acetic acid esters have remarkable solvent properties for oils, greases, inks, adhesives, and resins. They are widely used in lacquers, enamels, dopes, adhesives, and in fluids to dissolve plastics or resins as applied by lacquer, paint, and varnish removers. Generally speaking, the fatty acid esters of the glycols and glycol ethers, in either the liquid or vapor state, are more irritating to the mucous membranes than those of the parent glycol or glycol ethers. However, once absorbed into the body, the esters are hydrolyzed and the systemic effect is quite typical of the parent glycol or glycol ethers. It should be noted that the nitric acid esters of glycols are highly toxic and exert a physiological action quite different from that of the parent polyols. The nitric acid esters of glycols are not typical of the esters or ether esters of organic acids and are considered separately in this chapter. They are used as explosives, usually in combination with nitroglycerin, to reduce the freezing point. Industrial exposures of consequence are most likely to occur through the inhalation of vapors, but may also occur through contact with the eyes and skin. With the dinitrate, a serious hazard exists from absorption through the skin.

Abstract  Intense diffuse uptake of Tc-99m HMDP was seen in the gastrointestinal tract of a patient given liquid calcium gluconate. Bone scintigraphy was performed as a routine follow up 8 years after surgery for breast cancer. The gastrointestinal uptake disappeared when the administration of the liquid calcium gluconate was discontinued.

Abstract  Six-week-old male rats were placed on two high calcium regimens: one with calcium carbonate and monobasic calcium phosphate, with calcium content increased via calcium carbonate; and another with calcium phosphate and calcium gluconate, with calcium gluconate the source of increased calcium. Animals fed the gluconate-containing diets absorbed 29% of the ingested calcium over the entire calcium intake range, whereas those fed the calcium carbonate diets absorbed 25% over an intake range of 225 to 450 mg Ca/d, but at calcium intakes above 450 mg Ca/d their absorption reached a plateau at approximately 109 mg/d. Active calcium transport decreased with increased calcium intake in both the calcium carbonate- and calcium gluconate-fed groups. Nonsaturable transport was unchanged as a result of increasing calcium intake and did not differ among the diet groups. Because the absorptive processes were unaffected by the calcium source, events in the lumen must have been responsible for the observed differences. Because phosphate is nearly 18 times more soluble than carbonate, very little calcium of calcium carbonate origin can have been solubilized in the presence of phosphate and this, we conclude, accounts for the limit on calcium absorption observed in diets high in calcium carbonate. Moreover, when intake is expressed as soluble calcium, absorption approaches 50%, the value expected when intestinal transit time (approximately 3 h) is multiplied by 16%/h, the experimental value of nonsaturable absorption.

Abstract  Calcium carbonate, calcium gluconate and calcium citrate can be used as alternative phosphate binders to supplement aluminum hydroxide. The use of these substances reduces the amount of aluminum hydroxide needed to stabilize phosphate homeostasis in patients with renal failure and therefore the risk of aluminum intoxication. Patients treated with calcium citrate should be monitored very carefully, especially since citrate facilitates the absorption of aluminum by the gut. The phosphate level can be lowered best by calcium carbonate; calcium gluconate tends to produce an increase in serum calcium. Calcium gluconate also has to be carefully dosed, since gastrointestinal side effects can occur.

Abstract  To assess directly the effect of ionic dissociation on the bioavailability of calcium, we used the double isotope inverse convolution method to compare the absorption of calcium gluconate and calcium pyrrolidone carboxylate, an organic, highly dissociated salt. Two tests were performed at a 2 day interval, using in random sequence either salt as a carrier. Forty-eight subjects of various age and clinical condition were studied. The use of the more dissociated salt consistently and significantly increased fractional absorption in a rather constant ratio. Moreover, it slowed absorption in normal subjects whatever their age, and accelerated it in patients with chronic renal failure or osteoporosis, leading to inferences on the alteration of calcium absorption in these conditions.

Abstract  Calcium (Ca) preparations are widely used in the treatment of osteoporosis, usually as soluble salts. Tolerance might be improved by prescription of slowly dissolved Ca preparations, since Ca is also absorbed distally, even in the colon. In this regard the use of natural forms of Ca might be advantageous, but natural products cannot be labeled reliably for easy evaluation of their absorption. To study the intestinal absorption of an osseino-mineral complex (Ossopan) in comparison with Ca-gluconate, healthy males were investigated by means of conventional blood and urinary measurements before and after ingestion of either substance containing 1.58 g Ca. All subjects were placed on a standard diet 2 days before and during test day. Ca-gluconate (n = 7) evoked a marked and transient rise in plasma ionized calcium; total plasma calcium and urinary calcium followed a parallel course, while plasma and urinary phosphate decreased. After administration of osseino-mineral complex (n = 6), a slow but sustained elevation of plasma ionized calcium was observed while total calcium remained unchanged when corrected by the plasma proteins. Plasma phosphate and proteins increased, as did urinary phosphate. Comparing the 24-hour urine of the test day with that of the previous day, the rise in calcium excretion was slightly greater in the subjects treated by osseino-mineral complex than in those who were given Ca-gluconate, while phosphate excretion increased in the first group and decreased in the second. It is concluded that the bioavailability of Ca in osseino-mineral complex is as good as, if not better than, that of Ca-gluconate.(ABSTRACT TRUNCATED AT 250 WORDS)

Abstract  Under hypercalcemia induced by calcium gluconate the degranulation of renomedullary interstitial cells accompanied with the increase in volume of the rough and smooth surfaced endoplasmic reticulum and enlargement of the Golgi apparatus were observed. The ultrastructural changes can be regarded as an expression of the increase of a synthetic and secretory activity of these cells. Because the changes of renomedullary cells observed in hypercalcemia induced by calcium gluconate are not really different from that observed in hypercalcemia induced by vitamin D3 (Roszkiewicz et al. 1979) it can suppose that these changes may be connected solely with a calcium serum elevation and that the renomedullary interstitial cells rather do not play any important role in vitamin D3 metabolism.

Abstract  A stable isotope labeling (13C and D) was administered to 8 subjects in order to observe the short-term effect of phytosterols (Cytellin 9 g/day) or calcium (calcium gluconate 3 g/day) on the processes involved in cholesterol elimination in the feces. Under control conditions, the mean fraction of fecal cholesterol having a plasmatic origin was 69% and that of cholesterol secreted by the digestive tract 11%. The remaining fraction represented unabsorbed dietary cholesterol. While both treatments reduced the absorption of cholesterol, Cytellin enhanced the fecal excretion of plasma cholesterol and calcium lowered it. The change observed in the rate of intestinal external secretion did not follow the change in the fecal excretion of cholesterol.

Abstract  We have performed a first series of experiments using our stop flow technique to localize renal transport of calcium in dogs. Calcium is found to be actively reabsorbed in a far distal area but does not appear to be actively lowered in concentration in proximally derived samples. In a second series of dogs, elevation of plasma calcium by infusion of the salt CaCl2 caused a 43% reduction in the additional volume of water reabsorbed by the proximal tubule during stop flow. Calcium does not interfere with the active reabsorption of sodium in the distal area and does not cause significant increases in sodium excretion. In contrast calcium causes a considerable increase in potassium secretion at a far distal site. When calcium gluconate was employed, severe impairment of distal sodium and calcium reabsorption occurred in addition to the increased potassium secretion. We suggest that the gluconate anion restricts the movement of sodium, calcium and potassium electrostatically thus obligating cations to remain in the tubular urine depending upon their reabsorption potential.

Abstract  delta-D-Gluconolactone, delta-D-mannonolactone, and - for the first time - the thermodynamically unstable delta-D-galactonolactone have been prepared and isolated from DMF solution by oxidizing the corresponding sugars with Shvo's catalyst [(C4Ph4CO)(CO)(2)Ru](2) and a hydrogen acceptor. The preferred conformation of delta-D-galactonolactone in [D-6]DMSO solution has been determined by H-1 NMR spectroscopy experiments and DFT calculations to be H-4(3) and is compared to those of the previously established conformations of delta-D-gluconolactone (H-4(3)) and delta-D-mannonolactone (B-2,B-5). The conformations of the lactones suggest an explanation for their relative rates of isomerization to their respective 7-D-lactones by an intramolecular mechanism. (C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Abstract  In the present study, experiments were designed to investigate if supplementation with calcium during 4 weeks had an effect on blood parameters in sedentary male athletes at rest and exhaustion. Thirty healthy subjects of ages ranging from 18 to 22 years were included in the study. The subjects were separated into three groups, as follows: Group 1 consisted sedentary athletes receiving 35 mg/kg/day calcium gluconate. Group 2 included subjects equally supplemented with calcium training 90 min/day for 5 days/week. Group 3 were subject to the same exercise regime but did not receive calcium supplements. Blood parameters were determined in the experimental subjects at rest and after exhaustion. The leukocyte count (WBC) of athletes in groups 2 and 3 were significantly higher at exhaustion (p < 0.05). There were no significant differences in the WBC of the two supplemented groups. The erythrocyte count (RBC) was increased in the supplemented athletes after training (p < 0.05), but hemoglobin, hematocrit, and thrombocyte levels remained unchanged. The mean corpuscular volume increased in the calcium-supplemented group at rest (p < 0.05). These results suggest that calcium supplementation only causes increases in white and red blood cell counts in athletes after exhaustion while other hematological parameters remain unchanged.

Abstract  An indirect method to measure the reaction of glucono delta lactone with protein was developed. Glucono delta lactone reacts with lysine, tyrosine, threonine, arginine, and serine residues of protein, protecting them from attack by nitrous acid.

Abstract  The chloride channel blockers SITS (4-acetamido-4'-isothiocyanostibene-2,2'-disulphonic acid) and DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid) markedly suppressed progesterone production in the Rana temporaria and Xenopus laevis follicle-enclosed oocytes and oocyte maturation stimulated by the homologous pituitary suspension and hCG, respectively. Inhibition was dose-dependent and decreased with the increase of the hormone concentration. SITS did not affect progesterone production in the R. temporaria follicle-enclosed oocytes stimulated by dbcAMP. Substitution of sodium chloride for equimolar concentrations of sodium gluconate, methanesulfonate, glutamate, or formate significantly potentiated the gonadotropin-stimulated progesterone production and oocyte maturation in the both species. Possible involvement of chloride channels in progesterone production by the gonadotropin-stimulated amphibian follicle-enclosed oocytes is discussed. (C) 1997 Wiley-Liss, Inc.

Abstract  Part 28 includes a supplement purported to combat fatigue and enhance growth hormone (ornithine); a well-known ingredient (phenylalanine) of a well-known sweetener (aspartame); a possible energy enhancer via 2,3 diphosphoglycerate (phosphate); and a rather dubious supplement purported in the early 1940s to have a wide range of medicinal effects (pangamic acid). Of these, only phosphate appears to have some credible evidence to support the claims of an ergogenic effect.

Abstract  The effect of diet on metabolites found in rat urine samples has been investigated using nuclear magnetic resonance (NMR) and a new ambient ionization mass spectrometry experiment, extractive electrospray ionization mass spectrometry (EESI-MS). Urine samples from rats with three different dietary regimens were readily distinguished using multivariate statistical analysis on metabolites detected by NMR and MS. To observe the effect of diet on metabolic pathways, metabolites related to specific pathways were also investigated using multivariate statistical analysis. Discrimination is increased by making observations on restricted compound sets. Changes in diet at 24-h intervals led to predictable changes in the spectral data. Principal component analysis was used to separate the rats into groups according to their different dietary regimens using the full NMR, EESI-MS data or restricted sets of peaks in the mass spectra corresponding only to metabolites found in the urea cycle and metabolism of amino groups pathway. By contrast, multivariate analysis of variance from the score plots showed that metabolites of purine metabolism obscure the classification relative to the full metabolite set. These results suggest that it may be possible to reduce the number of statistical variables used by monitoring the biochemical variability of particular pathways. It should also be possible by this procedure to reduce the effect of diet in the biofluid samples for such purposes as disease detection.