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Biomedical subjects

R L King

Publications and source records attributed to R L King.

13 recordsLinked to original sources

Nonsalicylate nonsteroidal antiinflammatory drugs augment prestimulated acid secretion in rabbit parietal cells. Investigation of the mechanisms of action.

The effects of nonsalicylate nonsteroidal antiinflammatory drugs on acid secretion were studied in isolated rabbit parietal cells. Indomethacin, naproxen, and carprofen (10(-6)-10(-4) mol/L) potentiated histamine-, forskolin-, 3-isobutyl-1-methylxanthine-, and dibutyryl cyclic adenosine monophosphate-stimulated acid secretion without affecting basal acid secretion. This augmentation of secretagogue-stimulated acid secretion was dependent on extracellular calcium because potentiation was abolished by calcium depletion of the medium or in the presence of the calcium antagonist lanthanum chloride. Potentiation was independent of the H2 and muscarinic receptors and did not appear to involve guanine nucleotide regulatory proteins. Proton pump activity was unaffected by indomethacin. Furthermore, nonsteroidal antiinflammatory drugs increased calcium efflux through the plasma membrane, as measured by calcium 45, and decreased endogenous prostaglandin E2 content. Exogenous dimethyl prostaglandin E2 inhibited the potentiating effect of these drugs on histamine-stimulated but apparently not on dibutyryl cyclic adenosine monophosphate-stimulated acid secretion. The data indicate that nonsalicylate nonsteroidal antiinflammatory drugs interacted at a postreceptor site between adenylate cyclase and the proton pump. The potentiating effects of these drugs were regulated by calcium and possibly modulated by prostanoids.

Animals

Aspirin potentiates prestimulated acid secretion and mobilizes intracellular calcium in rabbit parietal cells.

The effects of aspirin on gastric acid secretion were studied in isolated rabbit parietal cells (PC). Aspirin (10(-5) M) potentiated histamine-, dibutyryl cyclic AMP (dbcAMP)-, forskolin- and 3-isobutyl-1-methylxanthine-stimulated acid secretion without affecting basal acid secretion. Augmentation of secretagogue-stimulated acid secretion by aspirin was dependent on calcium (Ca2+) since potentiation was blocked by removal of extracellular Ca2+ ([Ca2+]o) or addition of the calcium antagonist lanthanum chloride. Using the Ca2+ probe fura-2, aspirin (10(-6) - 2 X 10(-5) M) rapidly increased intracellular free Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. The source of released Ca2+ was intracellular as demonstrated by depletion of intracellular Ca2+ and [Ca2+]o with EGTA washing. Aspirin did not affect several other signal transduction sites involved in stimulus-secretion coupling, including the H2 receptor, intracellular cyclic AMP (cAMP), inositol 1,4,5, triphosphate (IP3) and H+,K(+)-ATPase. Aspirin decreased PC prostaglandin E2 (PGE2) content by 98%. Exogenous dimethyl PGE2 (dmPGE2) inhibited both histamine-stimulated acid secretion and its enhancement by aspirin. In contrast, dmPGE2 abolished aspirin-induced potentiation of dbcAMP-stimulated acid secretion by augmenting the dbcAMP-stimulated response. These results indicate that aspirin acts at a site beyond the adenylate cyclase/cAMP system and before the proton pump, presumably by releasing Ca2+ from an IP3-independent intracellular storage pool and by inhibiting PGE2 generation.

Adenosine Triphosphatases

Mechanisms of gastric proton pump inhibition by calcium channel antagonists.

The inhibitory effects of Ca channel antagonists on gastric acid secretion [[14C]-aminopyrine (AP) uptake ratio] have been analyzed in isolated rabbit parletal cells (PC). Secretagogue-stimulated AP uptake was inhibited by verapamil and diltiazem in a dose-dependent manner with IC50 values of 15 and 100 microM, respectively, both in the presence and absence of extracellular Ca. In contrast, nifedipine had no effect on AP accumulation. Verapamil decreased histamine-stimulated respiration with the same IC50 as observed for AP uptake. Imidazole, a weak base, by buffering the acid spaces in PC, reversed the inhibitory effect of verapamil on respiration. In the bullfrog gastric mucosa, forskolin-stimulated proton transport was inhibited by verapamil (10(-4) M) from the luminal but not the serosal side. This inhibitory effect was reversed by either elevating KCl concentration in, or removing the drug from, the secretory solution. Verapamil inhibited gastric microsomal H+,K(+)-adenosine triphosphatase (H+,K(+)-ATPase) and PC K(+)-stimulated p-nitrophenyl phosphatase activities with a higher potency than diltiazem. Inhibition of these enzymes by verapamil and diltiazem was pH dependent. The drugs competed with K+ in both H+,K(+)-ATPase and K(+)-stimulated p-nitrophenyl phosphatase reactions. Our data suggest that inhibition of the gastric proton pump by verapamil or diltiazem is not due to their Ca channel antagonism but to their interaction with the luminal high affinity K(+)-site of the H+,K(+)-ATPase under acidic conditions.

Adenosine Triphosphatases

Stimulation of mono (ADP-ribosyl)ation by reduced extracellular calcium levels in human fibroblasts.

Lowering extracellular calcium in cultures of human diploid fibroblast-like cells caused a rapid depletion of NAD pools. This loss of NAD was reversed by restoring extracellular Ca2+ and was inhibited by 3-aminobenzamide, an inhibitor of ADP-ribosyl transfer reactions. The concentrations of 3-aminobenzamide needed to inhibit the loss of NAD were consistent with those required to inhibit cellular mono(ADP-ribosyl) rather than poly(ADP-ribosyl) reactions. Calcium depletion did not inhibit the biosynthesis of NAD. These results suggest that mono(ADP-ribosyl)ation is involved in the regulation of cellular Ca2+ levels.

Adenosine Diphosphate Ribose

Effectiveness of publicity campaign encouraging earlier referral of hearing loss in adults.

During 16,070 consultations in general practice 70 adults complained of difficulty with hearing. A simple poster displayed in the waiting areas together with an accompanying leaflet almost doubled the incidence of presentation of loss of hearing. Nevertheless, more than half of those complaining had failed to notice the prominently displayed personally relevant message, and the beneficial effect was lost almost as soon as the poster was removed.

Advertising

Fluorescent color factor calculation using dBASE-II.

A software system utilizing dBASE-II operating on a dual-drive Apple II+ computer is described. Color factors and retention times for 15 amino acids and epsilon-(gamma-glutamyl)lysine dipeptide are calculated following high performance liquid chromatography. The software package produces a listing of acceptable limits for these parameters calculated as plus and minus 2 standard deviations of the mean. The code is distributed in source form.

Algorithms

Use of videotape and phone teleconference in statewide extension program on milk quality and mastitis control.

Extension specialists used a 3-h videotape and phone teleconferences to teach dairy farmers how to produce quality milk and control mastitis. This 5-d effort reached approximately 20% of the state's commercial dairy farms in 22 meetings at 22 locations. A survey of approximately 170 dairy producers indicated those attending the program had less education, were younger, and more were enrolled in Dairy Herd Improvement program as compared with the average Maryland dairy farmer. Eighty percent reported they would like to see additional videotaped programs; 5% indicated no interest in viewing other topics on videotape. Scores on knowledge pretests and posttests were 66 and 76%, respectively. Only 1.7% were using all 13 mastitis management practices recommended in the educational program, and 11.2% said they would use all 13 practices after participating in the program.

Animal Husbandry

Medicaid, HMO, PSRO.

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Health Maintenance Organizations

A preliminary report on the supraoptic nucleus and control of intraocular pressure.

Four animals received unilateral optic nerve sections which ablated that eye's rise in intraocular pressure in response to water drinking. Bilateral supraoptic nucleus lesions in two animals resulted in ablation of the other eye's response to water drinking. Both animals showed histopathologic proof of the lesion site. Two animals received sham operations for the supraoptic nucleus lesions with no change in their differential response to water drinking. This report gives preliminary evidence of the hypothesis of a supraoptic nuclear control mechanism of intraocular pressure.

Animals