Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rate constant for the catalytic transfer of the active-site PO3 group from rabbit muscle phosphoglucomutase to the hydroxyl group of a water molecule is about 3 x 10(-8) s-1 under optimal reaction conditions, but in the absence of the normal substrate, viz., at pH 7.5 and 30 degrees C, in the presence of saturating Mg2+; the corresponding constant for transfer to the 6-hydroxyl group of glucose 1-phosphate under analogous conditions, about 1000 s-1, is larger than this by some 3 x 10(10)-fold. Since no single factor appears to be capable of providing a rationale for a majority of this "substrate-induced rate effect" (Ray, jr., W.J., and Long, J.W. (1976), Biochemistry, the preceding paper in this issue), the change in the PO3-transfer rate produced by binding various parts of the phosphoglucosyl moiety to the enzyme, both separately and concurrently, was investigated. The rate of PO3 transfer to water is increased by up to 1000-fold by binding entities that provide the active site with a second PO3 group, e.g., ethyl phosphate or inorganic phosphite. Using an alcoholic acceptor further increases transfer efficiency (in the presence of bound phosphite): increase with methanol, about 2000-fold on a molar basis. The reactivities of ten other primary aliphatic alcohols vary by nearly 600-fold as the acidity of the PO3 acceptor is varied over a 4000-fold range. Although no straightforward relationship is observed between the efficiency of an alcohol as an acceptor and its acidity - presumably because of complications due to steric effects, for example - an increased transfer rate of 100-fold, relative to the water reaction, is estimated for a simple primary alcohol with a pKa similar to that expected for the 6-hydroxyl group of glucose 1-phosphate, when the alcohol is present at a concentration of 1 M. Joining an alcoholic acceptor and a PO3 group via five apparently inert bridging units changes PO3 transfer to an intramolecular process; in the case of 1,4-butanediol monophosphate the rate of transfer also increases by 240-fold, relative to the analogous reaction in the presence of 1 M propanol and bound inorganic phosphite. Comparable values also are obtained in comparisons of PO3 transfer rates for trans- 1,4-butenediol and 1,4-butynediol monophosphates relative to 1 M allyl and propargyl alcohols, respectively, in the presence of bound phosphite. An increased rate of transfer also is produced by binding the xylosyl part of the glucose ring, either when the acceptor is an hydroxyl group attached to the ring or when it is the hydroxyl group of a water molecule, e.g., as in the water reaction facilitated by bound xylose 1-phosphate. These and other results suggest that most of the differences between the rates of the water reaction and the glucose 1-phosphate reaction can be rationalized in terms of four fairly discrete factors whose approximate values are as follows: the PO4 factor, 1000-fold; the C-OH/H-OH factor, 100-fold; the nucleophile-binding factor, 250-fold; and the (CHOH)3-bridging factor, 200-fold...
Biochemistry 1976 Sep 07
PMID:An analysis of the substrate-induced rate effect in the phosphoglucomutase system. 96 19

Alterations in gastric physiology caused by selective embolization and vasopressin infusion of the left gastric artery were evaluated in 29 dogs. Gastric acidity was not significantly altered following Gelfoam embolization but decreased sharply with vasopressin infusion. These results suggest that the segmental occlusion caused by Gelfoam embolization permits significant collateral blood flow to the gastric mucosa, while the arteriolar and capillary constriction caused by vasopressin effectively decreases mucosal blood flow. These findings are consistent with the clincal observation that embolization is more effective in controlling bleeding ulcers, while vasopressin infusion is more effective for controlling hemorrhagic gastritis.
Radiology 1976 Sep
PMID:Alterations in gastric physiology caused by selective embolization and vasopressin infusion of the left gastric artery. 108 10

Incubation in 5% CO2 reduced the inhibition zones of piperacillin-tazobactam (75/10 micrograms) disks for Escherichia coli strains with TEM-1, TEM-2, and SHV-1 beta-lactamases. Similarly, MICs of piperacillin-tazobactam and other penicillin-sulfone combinations for TEM producers were up to 500-fold higher at pH 6.5 than at pH 8.0. This effect was greatest for organisms with high levels of enzyme activity. CO2 and mild acidity did not affect the susceptibility of beta-lactamase-negative strains to penicillin-sulfone combinations, and the effects of these conditions were variable for organisms with beta-lactamases other than TEM-1, TEM-2, and SHV-1. These last observations discounted acid-mediated inactivation of piperacillin or tazobactam. MICs of amoxicillin or piperacillin alone or with clavulanate for TEM and SHV producers were affected only less than or equal to 16-fold by 5% CO2 or acidity, indicating that the greater effects seen with the penicillin-sulfone combinations depended on the behavior of the sulfones and not on that of the penicillins. This pH effect was studied in detail for TEM-1 enzyme. Inhibition of this enzyme by sulfones but not clavulanate varied grossly with pH, with 50% inhibitory concentrations of tazobactam and sulbactam up to 300-fold higher at pH 6.5 than at 8.0. By contrast, the hydrolytic activity of TEM-1 enzyme for substrates and its level of production varied threefold or less between pH 6.5 and pH 8.0. Increased inhibition at pH 8.0 reflected sequestration of the enzyme into a secondary noncovalent complex rather than increased irreversible inactivation.
Antimicrob Agents Chemother 1992 Sep
PMID:Effects of CO2 and pH on inhibition of TEM-1 and other beta-lactamases by penicillanic acid sulfones. 132 33

Our objective was to compare the influence of dietary NaHCO3 and a multielement buffer on ruminal acid-base status and lactation performance of dairy cows. Five ruminally fistulated, primiparous and multiparous lactating Holstein cows averaging 123 +/- 21 d postpartum were assigned randomly to treatments in a 5 x 5 Latin square with 3-wk experimental periods. Treatments were a basal diet without supplemental buffers, with 1.5% NaHCO3 or 1.5% multielement buffer, or with NaHCO3 or multielement buffer solutions poured into the rumen via cannula at 2 h postfeeding. Addition of either buffer to the diet reduced ruminal fluid hydrogen ion concentration from 0 to 6 h postfeeding; only NaHCO3 reduced ruminal fluid acidity when dosed via the cannula. Addition of buffers via ruminal cannula appeared to retard the reduction in ruminal fluid acidity that normally occurs from 6 to 12 h postfeeding; this may have been related to a feedback mechanism inhibiting salivary buffer secretion. Buffering capacity of ruminal fluid tended to increase with buffer addition; the increase was greatest during infusion of NaHCO3. The ruminal fluid buffer value index increased by 4 units for control cows from early (0 to 6 h) to late (6 to 12) postfeeding; smaller increases were noted for addition of multielement buffer. This index was not different for NaHCO3 during these two intervals. Milk yield and DMI were not affected by buffer addition. Although milk fat content tended to be higher with the multielement buffer than with NaHCO3, it was not accompanied by the expected alterations in ruminal acid-base status. Therefore, this increase may be related to systemic effects of specific minerals in the multielement buffer rather than to a more stable ruminal environment. Based on the ruminal fluid buffer value index, NaHCO3 tended to maintain the most stable ruminal acid-base status.
J Dairy Sci 1992 Sep
PMID:Sodium bicarbonate or multielement buffer via diet or rumen: effects on performance and acid-base status of lactating cows. 133 97

By using the time hierarchy of the processes determining the fate of drugs in biosystems (absorption, transport, distribution, protein binding, and elimination), a one-compartment open model is formulated at a subcellular level for the disposition phase of pharmacokinetics. The resulting disposition function describes the kinetics of the intracellular disposition of drugs as determined by their hydrophobicity, acidity or basicity, affinity to proteins, and rate parameters of elimination. Structure-activity relationships, based on the function with incorporated extrathermodynamic relations, fit the literature data well (fixed-time bioactivity-hydrophobicity profiles, kinetics of microbial degradation of organic compounds, and kinetics of analgesic effects of fentanyl derivatives in rats). Application of the approach, creating a basis for the construction of model-based quantitative structure-time-activity relationship, to biosystems of varying complexity is discussed.
J Pharm Sci 1992 Sep
PMID:A time hierarchy-based model for kinetics of drug disposition and its use in quantitative structure-activity relationships. 143 27

Effect of pirenzepine, famotidine or a combination of both agents on gastric secretion during anesthesia and surgery was evaluated in 42 surgical patients ranged in age from 17 y to 70 y. They underwent orthopedic, ophthalmic, ENT, plastic, oral or non-abdominal surgery under either neuroleptanesthesia or enflurane anesthesia. They received either pirenzepine 10 mg, famotidine 20 mg or the combination of both agents intravenously just before the induction of anesthesia. Volume and acidity of gastric juice were measured during 3 hours after the administration of these agents. A continued decrease in volume and acidity of gastric juice was observed 3 hrs after the administration of the agents both in the pirenzepine group and in the famotidine group. Efficacy of the combination of pirenzepine and famotidine on gastric secretion tended to be more prominent than that of either pirenzepine or famotidine alone.
Masui 1992 Sep
PMID:[Effect of M1 blocker or H2 blocker on gastric secretion during anesthesia and surgery]. 143 78

A micellar electrokinetic capillary chromatographic method has been developed for the qualitative assay of amoxycillin and its degradation products and clavulanic acid. Together with amoxycillin the latter acid is an important constituent in the antibiotic Augmentin. The analytical procedure is fast and analytes can be identified both from their migration times and from changes in migration time observed either at different pH values or in electropherograms run in H2O and D2O based buffers of the same acidity.
Analyst 1992 Sep
PMID:Micellar electrokinetic capillary chromatography of amoxycillin and related molecules. 144 40

Saliva plays a central role in the formation of oral malodor. Such formation has as its basis bacterial putrefaction, the degradation of proteins, and the resulting amino acids by microorganisms. Saliva provides substrates that are readily oxidized and in the process facilitates oxygen depletion. This favors the reduced conditions conducive to production of odoriferous volatiles. At the same time, saliva is a major source of oxygen for the oral bacteria which generally is inhibitory of their formation. The pH is also critical to malodor development; acidity inhibits, whereas neutrality and alkalinity favor malodor production. Since the pH on oral mucosal surfaces where odor formation occurs is largely determined by the fermentative and putrefactive activities of the adhering bacteria, these acid-base processes are necessarily of major regulatory importance. Because oral malodor and periodontitis both involve excessive oral putrefaction, a better understanding of putrefaction could lead to more substantive methods of oral malodor treatment than exists today, as well as identifying new approaches to amelioration of the bacterial attack on the soft tissues leading to the destruction associated with periodontal disease.
J Periodontol 1992 Sep
PMID:Salivary and metabolic factors involved in oral malodor formation. 147 78

Esophageal pH-metry is the test of choice for diagnosing gastroesophageal reflux. However, although it allows acid refluxes to be distinguished, it is of limited value for identifying alkaline or mixed (acid mixed with alkaline material) refluxes. To evaluate the ability of dual pH-metry to identify alkaline or mixed refluxes, the gastric acidity and gastroesophageal reflux pattern were evaluated simultaneously in 64 patients with mild-moderate esophagitis, in 28 patients with severe or complicated esophagitis, and in 20 healthy subjects. A dual esophageal gastric pH-probe allowed three different types of esophageal reflux to be distinguished: (a) acid refluxes, defined as a drop in esophageal pH to values less than 4 together with a gastric pH less than 4; (b) mixed refluxes, defined as a drop in esophageal pH from baseline to values greater than 4 associated with rises in gastric pH to greater than 4 values; (c) alkaline refluxes, defined as a rise in esophageal pH to greater than 7 associated with a simultaneous increase in gastric pH to greater than 4. Gastric acidity was more significantly reduced in patients with severe or complicated esophagitis than it was in healthy subjects (P less than 0.01). The reflux pattern in both mild-moderate and severe esophagitis was characterized by mainly acid refluxes and a marked increase in the time the esophagus mucosa was exposed to acid (P less than 0.001). Pure alkaline refluxes were rare (less than 1%) in both healthy subjects and esophagitis patients. The number of mixed refluxes was considerably higher in severe esophagitis patients than it was in either mild-moderate esophagitis patients or controls (P less than 0.05). The finding of mixed refluxes in severe or complicated esophagitis suggests that biliary acids and/or pancreatic enzymes are involved in the pathogenesis of severe forms of esophagitis.
Gastroenterology 1992 Sep
PMID:Gastric acidity and gastroesophageal reflux patterns in patients with esophagitis. 844 Apr 52

Nine patients with duodenal ulcer were on separate occasions given omeprazole, 20 mg orally, 10 mg intravenously (IV), and 40 mg IV once daily for 5 days. On day 1, the median reduction of 24-hour intragastric acidity was 42.2% for the 20-mg oral dose and 54.8% and 88.4% for the two IV doses, respectively, but the between-patient variability was considerable for all three doses. On day 5, the degree of reduction had increased for all three doses to a median value of 99.9% for the 20-mg oral dose and 95.7% and 99.9% for the two IV doses, respectively. Plasma omeprazole concentrations increased significantly from day 1 to day 5 only for the 20-mg oral and 40-mg IV doses. Thus, the increased pharmacological effect of omeprazole during repeated once daily administration can only partly be explained by increased plasma concentrations, suggesting that some additional factor(s) must influence the degree of reduction of 24-hour intragastric acidity. Thus, when determining the optimal dose of omeprazole for acid inhibition, the route and duration of administration must be taken into consideration; after 5 days of once-daily administration of doses as low as 10 mg IV and 20 mg orally are effective and dependable in reducing 24-hour intragastric acidity in patients with duodenal ulcer. However, a daily dose of 40 mg IV omeprazole is not sufficient to keep intragastric pH above 4 in all patients during the first day of treatment.
Gastroenterology 1992 Sep
PMID:Effect of intravenous and oral omeprazole on 24-hour intragastric acidity in duodenal ulcer patients. 149 42


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