PubMed Health⌕ Search

Biomedical subjects

J Bigelow

Publications and source records attributed to J Bigelow.

8 recordsLinked to original sources
PubMed1990

Luminal concentrations of orally ingested 4-aminosalicylic acid as determined by in-vivo equilibrium dialysis.

We measured 4-aminosalicylic acid (4-ASA) levels in faecal water by in-vivo equilibrium dialysis during oral ingestion of drug by two different dose protocols (A and B). In Protocol A, 5 normal subjects ingested 3 g of 4-ASA as the free acid and 20 mg of metaclopromide per day. On Day 5, small dialysis sacs filled with dextran 40 were ingested and the oral drug was continued until the sacs were retrieved from the stool. Protocol B followed the same format except that 3 g of 4-ASA was ingested twice daily and metaclopromide was omitted. In both protocols concentrations of 4-ASA and N-acetylated 4-ASA in sac contents were measured by HPLC. In-vitro dialysis studies showed bi-directional equilibrium was reached within 120 min. During Protocol A, intraluminal concentrations of total 4-ASA ranged from 14.0 to 32.2 mmol/L with a mean of 20.6 mmol/L. With Protocol B, total 4-ASA levels ranged from 20.1 to 41.3 mmol/L with a mean of 33.9 mmol/L. From 90 to 99% of the drug in the dialysates was N-acetylated. These concentrations of total 4-ASA are similar to those of 5-ASA after ingestion of therapeutic doses of sulphasalazine or absorption-resistant formulations of 5-ASA. Thus, oral 4-ASA could have a role in the treatment of inflammatory bowel disease.

Acetylation↗
PubMed1986

Mechanism of binding of a benzomorphan opiate to the acetylcholine receptor from Torpedo electroplaque.

The mechanism of binding of the benzomorphan opiate, (-)-N-allylnormetazocine [(-)-ANMC], to Torpedo acetylcholine receptor (AcChR)-rich membranes was investigated. Using a centrifugation assay, two equilibrium binding affinities were observed with KD values of 0.4 and 2 microM. The KD and the apparent Bmax of the higher affinity component were decreased by cholinergic agonists and antagonists but not by alpha-bungarotoxin alone. The high affinity binding site (KD = 0.4 microM) was found to be distinct from the binding site for tetracaine, a noncompetitive blocker. The apparent association rate constant was essentially independent of receptor concentration both in the presence and absence of the cholinergic agonist, carbamoylcholine. When carbamoylcholine was equilibrated with the AcChR prior to (-)-[3H]ANMC addition, the association rate constant was 2- to 3-fold greater than in the absence of cholinergic effectors. When carbamoylcholine and (-)-[3H]ANMC were added simultaneously to AcChR-rich membranes, association was too rapid to resolve manually and binding measured at 5 sec was greater than the equilibrium level both in the presence and absence of carbamoylcholine. Binding decreased as a function of time, reaching its equilibrium level with a time constant of approximately 1 min. This effect appeared to be agonist specific since it was not observed when the antagonist, d-tubocurarine, replaced carbamoylcholine. In the absence of cholinergic ligands, dissociation of (-)-ANMC was biphasic (t1/2 values of less than 5 sec and approximately 2.5 min) and, in the presence of cholinergic ligands, was monophasic (t1/2 of 40 sec). The simultaneous addition of carbamoylcholine and (-)-[3H]ANMC to the membranes initially results in a biphasic dissociation (t1/2 of 5 and 30 sec) which becomes monophasic with increasing times of incubation. A mechanism is proposed involving an isomerization of the receptor-ligand complex which agrees quantitatively and qualitatively with the data.

Affinity Labels↗
PubMed1983

Male mouse (Mus musculus) ultrasonic vocalizations to female urine: why is heterosexual experience necessary?

Previous research was consistent with the hypothesis that urinary chemosignals from female mice (Mus musculus) serve as a conditioned stimulus (CS) for the elicitation of male ultrasonic courtship vocalizations while some other unknown aspect of the female serves as an unconditioned stimulus (US). According to this hypothesis adult heterosexual experience is necessary for males to pair the urinary CS with the US. Three experiments further examined this hypothesis. Experiment 1 demonstrated that the hypothesized US was not female behavior. Experience with anesthesized males and females was just as effective as experience with awake conspecifics. Experiments 2 and 3, however, question the primacy of the Classical Conditioning hypothesis. In both experiments sexually naive males were allowed contact with either normal females or female surrogates. The female surrogates were neonatally castrated males (Experiment 2) or hypophysectomized females (Experiment 3), both of which appeared to possess the hypothesized US but not the urinary CS on the basis of previous research. While exposure to normal females caused the highest level of vocalization to urine from normal females, exposure to the two classes of female surrogates also resulted in vocalizations to the urine of normal females. Thus under some circumstances, males do not require experience with a normal female to emit ultrasounds to urine from normal females. Factors in addition to Classical Conditioning must be operating to account fully for the role of adult heterosexual experience in causing female urine to come to elicit male courtship vocalization.

Animals↗