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

Ground mixture of N,N-dimethylcarbamoylmethyl alpha, 2-dimethyl-5H-[1]benzopyrano-[2,3-b]pyridine-7-acetate (1) with various pharmaceutical ingredients were prepared in order to investigate their dissolution behaviors and bioavailability. Taking into account the weakly basic property of 1, the dissolution rate was determined in the 2nd fluid (pH 6.8) of disintegration test, JP XI. Dissolution rates of the ground mixtures (1 : 1, w/w) of 1 with hydroxypropylcellulose-L (HPC-L), low substituted hydroxypropylcellulose (L-HPC) or lactose respectively, showed a significant increase compared with compound 1 alone. Three kinds of experimental fine granules were prepared; type A: produced from ground mixture of 1, HPC-L, L-HPC and lactose; type B: produced from physical mixture having the same composition as type A; type C: produced 1, L-HPC and lactose. In these fine granules, only type A exhibited pH-independent dissolution profiles. Bioavailability study was carried out in beagle dogs whose gastric acidity was controlled in advance to low levels by administration of omeprazole. The test was conducted in a cross over design. Reflecting their dissolution characteristics, type A granules showed better bioavailability than the others. These results suggest that grinding is useful for the improvement of the dissolution property and bioavailability of 1, a weakly basic compound.
 ...
PMID:[Dissolution properties and bioavailability of ground mixture of N,N-dimethylcarbamoylmethyl alpha, 2-dimethyl-5H-[1]benzopyrano[2,3-b]-pyridine-7-acetate with various pharmaceutical ingredients]. 263 Jun 36

This study was initiated to clarify whether the main hydrolytic enzymes of the pancreas are activated or inactivated when secreted into the stomach of patients who had undergone a pylorus-preserving pancreaticoduodenectomy (PPPD) and were given a pancreaticogastrostomy (PG) for the reconstruction. Seventeen such patients, 15 cancer patients and two pancreatic patients, who underwent PPPD-PG reconstruction were postoperatively followed up for 3 or more years to investigate the influence of the gastric acid on the p-type amylase and lipase activity. Results revealed that when the pH was < 3.0, both the p-type amylase and the lipase secretion remained inactivated, but when the pH was > 3.1, the activity of both enzymes increased proportionately. The pancreatic enzyme activity in the small intestine was also investigated in seven patients, six cancer cases and one case of pancreatitis, given a PPPD-PG reconstruction, and it was found that the pancreatic enzyme activity in the small intestine increased after milk loading. Further, the fecal pancreatic enzyme activity was investigated in 17 patients given a PPPD-PG reconstruction. Results reveal that the fecal p-type amylase, lipase, and chymotrypsin activity amounted to 21, 27, and 31% of the respective values seen in 10 healthy volunteers. However, the fecal pancreatic enzyme activity levels did not differ significantly from the levels seen in 20 pancreaticoduodenectomy patients given a pancreaticojejunostomy reconstruction. In conclusion, it was found that the main hydrolytic enzymes of the pancreas are activated when the gastric acidity is over pH 3.1, which normally occurs after ingestion of a meal.
 ...
PMID:Pancreatic enzyme activity after a pylorus-preserving pancreaticoduodenectomy reconstructed with pancreaticogastrostomy. 857 82

The role of cortisol in the prenatal development of digestive enzymes in the abomasum (prochymosin and pepsinogen) and pancreas (amylase, trypsin, chymotrypsin) has been investigated in the fetal lamb during late gestation. The abomasum and pancreas were collected from 22 unoperated control fetuses (99-145 days gestation; term, 145 +/- 2 days), from seven pairs of twins infused with either saline or cortisol for five days preceding delivery at 127-133 days, and from four 139-143-day-old fetuses adrenalectomized at 120-123 days. Developmental increases (2-8-fold) occurred in protease concentrations in the fetal abomasum and in amylase and chymotrypsin contents in the fetal pancreas. These increases paralleled the normal prepartum rise in fetal plasma cortisol. In addition, the enzyme values were significantly higher in cortisol-infused than in saline-infused fetuses (with the exception of pancreatic amylase) and were significantly lower in adrenalectomized fetuses than in control fetuses at term. The pH of abomasal fluid remained neutral (pH 6.8-8.0) during late gestation and was not affected by cortisol treatment or adrenalectomy. The results suggest that cortisol stimulates the development of the exocrine abomasum and pancreas in fetal sheep and may, thereby, increase the digestive capacity in neonatal lambs. Compared with the pig, another long-gestation species, the sheep has an early development of gastric pepsinogen but a late development of gastric acidity and pancreatic protease activities.
 ...
PMID:Maturational effects of cortisol on the exocrine abomasum and pancreas in fetal sheep. 860 79

Gastric and pancreatic lipases are enzymes that play a pivotal role in the digestion of dietary fat. Orlistat, a semisynthetic derivative of lipstatin, is a potent and selective inhibitor of these enzymes, with little or no activity against amylase, trypsin, chymotrypsin and phospholipases. It exerts its effect within the gastrointestinal (GI) tract. Orlistat acts by binding covalently to the serine residue of the active site of gastric and pancreatic lipases. When administered with fat-containing foods, orlistat partially inhibits hydrolysis of triglycerides, thus reducing the subsequent absorption of monoaclglycerides and free fatty acids. This effect can be measured using 24h faecal fat excretion as a representative pharmacodynamic parameter. Orlistat's pharmacological activity is dose-dependent and can be described by a simple Emax model which exhibits an initial steep portion of the dose-response curve with a subsequent plateau (approximately 35% inhibition of dietary fat absorption) for doses above 400 mg/d. At therapeutic doses (120 mg tid with main meals) administered in conjunction with a well balanced, mildly hypocaloric diet, the inhibition of fat absorption (approximately 30% of ingested fat) contributes to an additional caloric deficit of approximately 200 calories. Orlistat does not produce significant disturbances to GI physiological processes (gastric emptying and acidity, gallbladder motility, bile composition and lithogenicity) or to the systemic balance of minerals and electrolytes. Similarly, orlistat does not affect the absorption and pharmacokinetics of drugs with a narrow therapeutic index (phenytoin, warfarin, digoxin) or compounds frequently used by obese patients (oral contraceptives, glyburide, pravastatin, slow-release nifedipine).
 ...
PMID:Mode of action of orlistat. 922 72

Hydroxide-catalyzed exchange rate constants were determined for those amides of FK506-binding protein (FKBP12), ubiquitin, and chymotrypsin inhibitor 2 (CI2) that are solvent-accessible in the high-resolution X-ray structures. When combined with previous hydrogen exchange results for the rubredoxin from Pyrococcus furiosus, the acidity of these amides was calculated by continuum dielectric methods as a function of the nonpolarizable electrostatic parameter set, internal dielectric, and the charge distribution of the peptide anion. The CHARMM22 parameter set with an internal dielectric value of 3 and an ab initio-derived anion charge distribution yielded an rmsd value of 7 for the 56 amide exchange rate constants ranging from 10(0.67) to 10(9.0) M(-1) s(-1). The OPLS-AA parameter set yielded comparably robust predictions, while that of PARSE, AMBER parm99, and AMBER ff03 performed more poorly. The small value for the optimal internal dielectric, combined with the brief lifetime of the peptide anion intermediate and the uniformity of the correlation between predicted and observed amide acidities, is consistent with electronic polarizability providing the dominant contribution to dielectric shielding. By construction, nonpolarizable force fields do not model electric field attenuation by electronic polarizability. Accurate prediction of the total electrostatic energy by such force fields necessitates the hyperpolarization of the atomic charge values in order to match the average electric field energy density (1/2)epsilon(tau)E(2)(tau) when epsilon(tau) is set to the in vacuo dielectric value of 1. The resulting predictions of the experimental hydrogen exchange data demonstrate the substantial systematic errors in the predicted electrostatic potential that can arise when dielectric shielding due to electronic polarizability is neglected.
 ...
PMID:Polarization and polarizability assessed by protein amide acidity. 1950 27

Although the protein native state is a Boltzmann conformational ensemble, practical applications often require a representative model from the most populated region of that distribution. The acidity of the backbone amides, as reflected in hydrogen exchange rates, is exquisitely sensitive to the surrounding charge and dielectric volume distribution. For each of four proteins, three independently determined X-ray structures of differing crystallographic resolution were used to predict exchange for the static solvent-exposed amide hydrogens. The average correlation coefficients range from 0.74 for ubiquitin to 0.93 for Pyrococcus furiosus rubredoxin, reflecting the larger range of experimental exchange rates exhibited by the latter protein. The exchange prediction errors modestly correlate with the crystallographic resolution. MODELLER 9v6-derived homology models at ~60% sequence identity (36% identity for chymotrypsin inhibitor CI2) yielded correlation coefficients that are ~0.1 smaller than for the cognate X-ray structures. The most recently deposited NOE-based ubiquitin structure and the original NMR structure of CI2 fail to provide statistically significant predictions of hydrogen exchange. However, the more recent RECOORD refinement study of CI2 yielded predictions comparable to the X-ray and homology model-based analyses.
 ...
PMID:Assessing the chemical accuracy of protein structures via peptide acidity. 2318 63