The Effect of a Single Large Dose of Salicylate and Phenylbutazone on the Glucosamine-6-Phosphate Synthesis <i>in vivo</i> by the Liver and by the Gastric Mucosa of Rats

By use of an in vivo canine chambered stomach preparation in which the gastric mucosa was partitioned into two equal halves, the effect of topical 16,16-dimethyl PGE2 (DMPGE2) (1 microgram/ml of perfusate) and 8% and 40% ethanol on tissue levels of nonprotein sulfhydryl compounds was assessed. Both DMPGE2 and 8% ethanol significantly increased (P less than 0.005) mucosal levels of nonprotein sulfhydryls when compared with corresponding mucosa bathed with saline alone. In contrast, mucosa bathed with 40% ethanol showed significantly decreased levels. If mucosa was bathed with DMPGE2 or 8% ethanol prior to exposing the stomach to 40% ethanol, this depletion in sulfhydryl compounds was not observed. Since other experimental observations have shown that exogenously administered prostaglandins and mild irritants (such as low-dose alcohol) can prevent gastric mucosal damage by necrotizing agents (such as high-dose alcohol), our findings are consistent with the hypothesis that nonprotein sulfhydryls may play a role in mediating gastric mucosal protection.

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Dothiepin for depression: single nightly dosage

Drug and Therapeutics Bulletin ◽

10.1136/dtb.15.23.92 ◽

1977 ◽

Vol 15 (23) ◽

pp. 92-92

Keyword(s):

Single Dose ◽

Depressed Patient ◽

Large Dose ◽

Half Life ◽

Dosage Regimen ◽

The Body ◽

Dry Mouth ◽

Blurred Vision ◽

Depressed Patients ◽

Single Large Dose

Depressed patients tend to be forgetful, and for them a simple dosage regimen is particularly appropriate. The use of a single daily dosage depends on the drug having a relatively long (over 36 hours) half-life in the body and being tolerated in a single large dose. Many tricyclic anti-depressives fulfil these requirements provided that the single dose is given before the patient goes to bed. Unwanted effects such as dry mouth and blurred vision, which are troublesome during the day, are not a problem during sleep. The sedative actions of many of these drugs can help the insomniac depressed patient who might otherwise need a separate hypnotic.

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Design and Synthesis of Novel Ibuprofen Derivatives as Selective COX-2 inhibitors and potential anti-inflammatory agents: Evaluation of PGE2, TNF-α, IL-6 and histopathological study

Medicinal Chemistry ◽

10.2174/1573406417666210809162636 ◽

2021 ◽

Vol 17 ◽

Author(s):

Peter Amir Halim ◽

Hala Bakr El-Nassan ◽

Yara Sayed El-Dash

Keyword(s):

Carboxylic Acid ◽

Gastric Mucosa ◽

Docking Simulation ◽

Histopathological Study ◽

Acid Moiety ◽

Rat Serum ◽

Tnf Α ◽

Cox 2 ◽

Anti Inflammatory

Background: The reported binding mode of ibuprofen in the COX-2 binding site indicated that the carboxylic group binds with Arg-120 and Tyr-355 at the entrance of the cyclooxygenase channel and does not extend into the pocket. This accounted for the non-selectivity of ibuprofen. Based on this fact, we assumed that extending the length of the carboxylic acid moiety in ibuprofen and adding more bulky rigid groups as well as bulky groups carrying H-bonding functions might increase the selectivity and reduce the side effects of ibuprofen while maintaining its analgesic and anti-inflammatory activities. Objective: In this work, four series of ibuprofen derivatives were designed and prepared. The compounds were designed by increasing the length of the carboxylate group along with the incorporation of large hydrophobic groups. Method: Four series of ibuprofen derivatives were synthesized starting from ibuprofen. Their chemical structure was confirmed by spectral data. All the compounds were tested for their COX inhibitory activity. Results : The best COX-2 activity and selectivity were obtained with compounds 5c and 5d, which were subjected to further in vivo testing (carrageenan-induced paw edema, rat serum PGE2, TNF- α and IL-6, hot plate latency test) to investigate their anti-inflammatory and analgesic activities as well as their effects on the gastric mucosa. The anti-inflammatory activity of both compounds was comparable to that of ibuprofen, diclofenac, and indomethacin. Both compounds suppressed the production of PGE2 as well as the rat serum concentrations of both TNF-α and IL-6. This potent anti-inflammatory and analgesic behavior was not accompanied by any effect on the gastric mucosa. Docking simulation studies of the two compounds explained the higher selectivity for the COX-2 enzyme. Conclusion: Potent and selective ibuprofen derivatives can be successively obtained by extending the length of the carboxylic acid moiety in ibuprofen and adding more bulky rigid groups as well as bulky groups with H-bonding functions.

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Primary culture of secretagogue-responsive parietal cells from rabbit gastric mucosa

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1989.256.1.g254 ◽

1989 ◽

Vol 256 (1) ◽

pp. G254-G263 ◽

Cited By ~ 20

Author(s):

C. S. Chew ◽

M. Ljungstrom ◽

A. Smolka ◽

M. R. Brown

Keyword(s):

Gastric Mucosa ◽

Primary Culture ◽

Cultured Cells ◽

Single Cells ◽

Parietal Cells ◽

Ultrastructural Changes ◽

Long Term Effects ◽

H2 Receptor Antagonist ◽

Morphological Transformations

A new procedure for isolation and primary culture of gastric parietal cells is described. Parietal cells from rabbit gastric mucosa are enriched to greater than 95% purity by combining a Nycodenz gradient separation with centrifugal elutriation. Cells are plated on the basement membrane matrix, Matrigel, and maintained in culture for at least 1 wk. Parietal cells cultured in this manner remain differentiated, cross-react with monoclonal H+-K+-ATPase antibodies, and respond to histamine, gastrin, and cholinergic stimulation with increased acid production as measured by accumulation of the weak base, [14C]aminopyrine. When stimulated, cultured cells undergo ultrastructural changes in which intracellular canaliculi expand and numerous microvilli are observed. These ultrastructural changes are similar to those previously found to occur in vivo and in acutely isolated parietal cells. Morphological transformations in living cells can also be observed with differential interference contrast optics in the light microscope. After histamine stimulation, intracellular canaliculi gradually expand to form large vacuolar spaces. When the H2 receptor antagonist, cimetidine, is added to histamine-stimulated cells, these vacuoles gradually disappear. The ability to maintain hormonally responsive parietal cells in primary culture should make it possible to study direct, long-term effects of a variety of agonists and antagonists on parietal cell secretory-related activity. These cultured cells should also prove to be useful for the study of calcium transients, ion fluxes, and intracellular pH as related to acid secretion in single cells, particularly since morphological transformations can be used to monitor "physiological" responses at the same time within the same cell.

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