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Biomedical subjects

G R Brown

Publications and source records attributed to G R Brown.

At least 109 records · Page 6Linked to original sources
PubMed1988

The synthesis of a novel thromboxane receptor antagonist 4(Z)-6-(2-o-chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid ICI 192605.

The synthesis and summary pharmacology of a novel thromboxane receptor antagonist 4(Z)-6-(2-o-chlorophenyl-4-o-hydroxyphenyl-1, 3-dioxan-cis-5-yl) hexenoic acid (3) is reported. Compound 3 was competitive and selective with pA2 values of 8.0 +/- 0.1 (rabbit) and 8.4 +/- 0.05 (rat) on smooth muscle preparations and 8.16 +/- 0.01 on human platelets. In vivo activity of 3 was demonstrated in a Konzett Rossler guinea pig model at 0.01 mg/kg p.o.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

The role of a (Ca2+ + Mg2+)-ATPase of the rough endoplasmic reticulum in regulating intracellular Ca2+ during cholinergic stimulation of rat pancreatic acini.

Rough endoplasmic reticulum membranes, purified from isolated rat pancreatic acini stimulated by carbachol, had a decreased Ca2+ content and increased (Ca2+ + Mg2+)-ATPase activity. Ca2+ was regained and ATPase activity reduced to control levels only after blockade by atropine. The (Ca2+ + Mg2+)-ATPase was activated by free Ca2+ (half-maximal at 0.17 microM; maximal at 0.7 microM) over the concentration range which occurs in the cell cytoplasm. Pretreatment with EGTA, at a high concentration (5 mM), inhibited ATPase activity which, our results suggest, was due to removal of a bound activator such as calmodulin. The rate of (Ca2+ + Mg2+)-ATPase actively declined during the 10-min period over which maximal active accumulation of Ca2+ by membrane vesicles occurs. In the presence of ionophore A23187, which released actively accumulated Ca2+ and stimulated the (Ca2+ + Mg2+)-ATPase, this time-dependent decline in activity was not observed. Our data provide evidence that the activity of the Ca2+-transporting ATPase of the rough endoplasmic reticulum is regulated by both extra and intravesicular Ca2+ and is consistent with a direct role of this enzyme in the release and uptake of Ca2+ during cholinergic stimulation of pancreatic acinar cells.

Animals↗
PubMed1987

Rapid formation of inositol 1,4,5-trisphosphate in rat pancreatic acini stimulated by carbamylcholine.

Cholinergic stimulation of inositol phosphate formation was studied in isolated rat pancreatic acini, prelabelled with myo-[2-3H]inositol. Carbamylcholine increased incorporation of radioactivity into Ins(1,4,5)P3 and InsP4 within 5 s. Increases in [3H]Ins(1,3,4)P3 were delayed with marked stimulation occurring between 10 s and 1 min. Inositol polyphosphate formation was less sensitive to carbamylcholine concentration than was stimulation of amylase release. At a low (0.3 microM) carbamylcholine concentration, no increase in inositol polyphosphate formation was detected, whereas stimulation of amylase release, which was not dependent on extracellular calcium, was observed. Ins(1,4,5)P3 was shown to release actively accumulated 45Ca2+ from isolated rough endoplasmic reticulum membranes to a similar extent as that released from rough endoplasmic reticulum following cholinergic stimulation of pancreatic acini (Richardson, A.E. et al. (1984) Biochem. Soc. Trans. 12, 1066-1067). The data is consistent with Ins(1,4,5)P3 being produced rapidly enough to release sufficient calcium from the rough endoplasmic reticulum to cause an observed increases in cytoplasmic free Ca2+.

Amylases↗
PubMed1987

Intracellular Ca2+ in pancreatic acinar cells: regulation and role in stimulation of enzyme secretion.

Evidence for a primary role for intracellular Ca2+ in the stimulation of pancreatic enzyme secretion is reviewed. Measurements of cytoplasmic free Ca2+ concentration have allowed direct demonstration of its importance in triggering enzyme secretion and defined the concentration range over which membrane Ca2+ pumps must work to regulate intracellular Ca2+. Current evidence suggests a key role for the Ca2+, Mg-ATPase of rough endoplasmic reticulum in regulating intracellular Ca2+ and accumulating a Ca2+ store which is released by the action of inositol-1,4,5 trisphosphate following stimulation of secretion.

Animals↗
PubMed1987

Anorexia nervosa complicated by Mycobacterium xenopi pulmonary infection.

Pulmonary infection with a rare atypical mycobacterium, Mycobacterium xenopi, was discovered during the treatment of anorexia nervosa in a 21-year-old woman without preexisting pulmonary disease. Psychiatric treatment resulted in restoration of premorbid weight in the presence of active pulmonary disease and treatment with isoniazid and rifampin. Ethambutol was added for the final 12 months of the 18-month treatment course. Thirty-two-month follow-up indicated continued remission of both illnesses. Concurrence of M. xenopi infection and anorexia nervosa has not been previously reported.

Adult↗
PubMed1986

(S)-3-[(benzyloxy)methyl]morpholine hydrochloride: a nonstimulant appetite suppressant without conventional neurotransmitter releasing properties.

The synthesis and appetite-suppressant activity of (S)-3-[(benzyloxy)methyl]morpholine hydrochloride in dogs are reported. The oral ED50 for appetite suppression in dogs of 3 was 12 mg/kg, and it was tolerated up to 200 mg/kg. 3 had no inhibitory effect on the release or uptake of noradrenaline, dopamine, or serotonin at 10(-5) M. The (R) enantiomer of 3 was not anorexiant.

Animals↗
PubMed1986

ICI 180080, a novel selective thromboxane receptor antagonist: synthesis and relative activity.

The preparation of a novel potent thromboxane receptor antagonist ICI 180080, 5(Z)-7-[2,2-dimethyl-4-(2-hydroxyphenyl)-1,3-dioxan-cis-5-yl] heptenoic acid, is described together with its methyl ether and methyl ester. Thromboxane antagonist pA2 data against U 46619 is presented for rabbit thoracic aorta in-vitro (ICI 180080, pA2 = 7.5). The relative antagonist pA2 values obtained are discussed in terms of the chemical structure of the molecules. The potent activity of ICI 180080 is attributed to a specific orientation of the phenolic oxygen, due to an intramolecular hydrogen bond.

Animals↗
PubMed1986

Pharmacokinetics of cefixime (CL 284,635; FK 027) in healthy subjects and patients with renal insufficiency.

The pharmacokinetics of the extended-half-life, broad-spectrum oral cephalosporin cefixime (CL 284,635; FK 027) were studied in 7 healthy volunteers and 35 patients with various degrees of renal insufficiency, including patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and hemodialysis. Apparent total body, renal, and apparent nondialysis-nonrenal clearances and protein binding declined and elimination half-life increased with decreasing creatinine clearance. All of these alterations became statistically significant as the creatinine clearance fell below 20 ml/min per 1.73 m2. Cefixime concentrations in urine exceeded the MICs for most urinary tract pathogens for up to 24 h postdose, even in patients with severe renal insufficiency. CAPD removed an insignificant fraction of cefixime body burden over the 72-h study period (1.57 +/- 0.60% [mean +/- the standard error of the mean]). Area under the curve data suggested that hemodialysis similarly removed an insignificant fraction of the cefixime body burden. Volume of distribution at steady state was not altered significantly by renal insufficiency. It is recommended that standard doses of cefixime be administered at extended intervals, especially in patients with creatinine clearances less than 20 ml/min per 1.73 m2. In addition, supplemental doses are not necessary during CAPD and at the end of hemodialysis.

Adult↗
PubMed1986

Nifedipine serum concentrations following sublingual and oral doses.

Although nifedipine is commonly administered sublingually in the clinical setting, a comparison of the serum concentrations obtained by this route vs oral administration has not been previously made. Nifedipine serum concentrations were measured in 6 healthy subjects following sublingual or oral administration of one nifedipine 10 mg capsule. Serum nifedipine concentrations were measured at regular intervals and demonstrated that sublingual administration produced measurable nifedipine concentrations sooner than oral administration. Peak nifedipine serum concentrations were less following sublingual administration (41.9 +/- 24.9 ng/ml) than following oral administration (99.6 +/- 49.8 ng/ml, p less than 0.05). The time to peak nifedipine serum concentration was also longer following sublingual administration than with the oral dose (74 +/- 24 minutes vs 40 +/- 14 minutes, p less than 0.05). Despite these differences, the areas under the serum concentration-time curve of the two routes of administration were similar. These differences in nifedipine concentrations may be an important consideration when choosing the route of administration of nifedipine.

Administration, Oral↗
PubMed1986

Polymer resins with amino acid containing pendants for sorption of bilirubin. II. Polyamide resins with various basic amino acids.

Short peptides, three to eight amino acids in length, containing various combinations of alanine, arginine, lysine, histidine and tyrosine have been synthesized onto water-swellable polyamide resin by the solid phase peptide synthesis method. The amount of bilirubin adsorbed from aqueous buffer solution (pH = 7.8) by the resins increases with increasing basicity of the amino acids in the pendant. As the number of basic amino acids on the pendant is increased from one to five a 4.7 fold enhancement in the adsorption capacity is seen for arginine while a 9.3 fold enhancement is obtained for lysine. A corresponding increase in length for the non-basic histidine results in a 6 fold enhancement. With alanine the adsorption capacity is uneffected by an increase in pendant length.

Alanine↗
PubMed1985

Potentiation of fasciolicidal agents by benzoyl side chains. Synthesis of benzoylsalicylanilides.

The synthesis and potent fasciolicidal activity of novel salicylanilides, with benzoyl substituents in the salicyl ring, is described. Several compounds surpassed the activity of commercially used flukicides against Fasciola hepatica infections in rats. Compounds 10, 11, and 15 were poorly active against the parasite in sheep and inactive in infected calves. It is concluded that the benzoyl substituents potentiate antiparasitic action by virtue of their electron-withdrawing properties rather than by advantageous protein binding at parasite receptor sites. Poor activity in sheep is ascribed to in vivo reduction of the carbonyl in the benzoyl group of the anilides.

Animals↗
PubMed1984

Receptor binding sites of hypoglycemic sulfonylureas and related [(acylamino)alkyl]benzoic acids.

The blood glucose level lowering activity of [(acylamino)ethyl]benzoic acids, such as p-[2-(5-chloro-2-methoxy-benzamido)ethyl]benzoic acid (HB699, 2), is discussed in terms of binding at putative insulin-releasing receptor sites of pancreatic beta cells. The hypoglycemic potencies found for synthetic analogues of 2 indicate that high hypoglycemic activity is only found when a carboxyl group or a group that is readily oxidized to carboxyl in vivo, such as methyl, is attached to the aromatic ring of the phenethyl group. It is proposed that this carboxyl group is able to bind at the same receptor site as the SO2NHCONH group of the sulfonylurea drugs, such as tolbutamide (3). The role of the benzamide group in 2 was attributed to protein binding.

Animals↗
PubMed1984

Polymer resins with amino acid containing pendants for sorption of bilirubin. I. Comparison of Merrifield and polyamide resins.

Merrifield resins with various amino acid containing pendants and a water swellable polyamide resin with the peptide alanine-alanine-alanine-arginine as the pendant group have been prepared by solid phase peptide synthesis. Merrifield resins with either arginine or lysine pendants are capable of sorbing bilirubin from aqueous solution (pH = 7.8) but those with other amino acid pendants gave no indication of sorption. The polyamide-arginine resin showed, on a functional group basis, a higher capacity for bilirubin than does cholestyramine. It is proposed that the formation of salt linkages causes a strong interaction of bilirubin with arginine and lysine.

Adsorption↗
PubMed1983

Anticoccidial activity of crown polyethers.

Anticoccidial activity in vitro against Eimeria tenella is reported for crown polyethers with ring sizes from 14 to 30 atoms. The most potent compounds, 4 and 9, were found active at 0.33 ppm, but none were active in vivo. Test results are discussed in terms of lipophilic shielding of complexed cations.

Animals↗
PubMed1982

Avulsion of the innominate artery from the aortic arch associated with a posterior tracheal tear.

The management of a patient with avulsion of the innominate artery from the aortic arch associated with a longitudinal tear on the posterior aspect of the trachea is discussed. It is obviously important to make both diagnoses preoperatively to determine priorities in the surgical management. If the airway injury can be managed by tracheal intubation, then it is recommended that the vascular injury be repaired first. If there is a persistent air leak with respiratory distress, then it is necessary to repair the tracheal injury before performing the vascular procedure. In some patients it may be appropriate to treat the tracheal injury nonoperatively.

Accidents, Traffic↗
PubMed1982

[Changes in the transepithelial potential and spike responses of the ampullae of Lorenzini to temperature stimulation in the skate].

Electrical responses of the sensory epithelium of Lorenzinian ampullae as well as their nerve fibres frequency reactions to thermal stimulation were studied in Black Sea skates, Raja clavata. Electrically isolated ampullae with input resistance 500-800 K omega were used. They were loaded through a feedback circuit to a controllable resistance. Heating of the ampulla caused a lumen-negative shift of the transepithelial potential, its amplitude being approximately linearly dependent on the input resistance of the preparation (R1). Frequency responses of the nerve fibres were also dependent on R1. With R1 more (less) than 400-500 K omega there was an increase (decrease) in spike frequency during heating of the ampulla. Two temperature-dependent potential sources in sensory epithelium affecting spike frequency in the opposite ways are suggested.

Animals↗