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Biomedical subjects

S B Freedman

Publications and source records attributed to S B Freedman.

123 records · Page 7Linked to original sources
PubMed1982

Influence of sodium and sulphydryl groups on [3H]sulpiride binding sites in rat striatal membranes.

The effect of thiol reagents on the specific binding of the atypical neuroleptic, sulpiride, to rat striatal membranes are examined. Pretreatment of membranes with N-ethylmaleimide (NEM), but not with iodoacetamide or dithiothreitol (DTT), diminishes [3H]sulpiride binding. The effect is dependent on time, temperature, and the concentration of NEM. The reaction proceeds with pseudo-first-order rate kinetics, indicating the involvement of a single essential SH group in the binding of [3H]sulpiride to striatal membranes sites. Both sodium and sulpiride, but not nucleotides, protect the [3H]sulpiride sites from NEM inactivation in a dose-dependent fashion. As sodium is essential for [3H]sulpiride binding it is possible that in the presence of sodium and sulpiride a conformational change takes place that makes the essential SH group less accessible to alkylation.

Animals↗
PubMed1981

Verapamil kinetics in normal subjects and patients with coronary artery spasm.

Verapamil kinetics after intravenous and single and long-term oral dosing were studied in 12 patients with coronary artery spasm and four normal subjects. The decline in plasma concentration after intravenous doses was described by triexponential decay equation, with a terminal half-life (t1/2) of 5 hr. After a single oral dose the bioavailability was only 24%, probably because of the first-pass metabolism. During long-term oral doses of 80 mg every 6 hr, mean peak and trough concentrations were 255 +/- 90 and 105 +/- 38 ng/ml, and mean time at which peak concentration occurred was 1.2 +/- 0.5 hr. Norverapamil, the major active metabolite of verapamil, cumulated during oral dosing and may account for a small proportion of the overall pharmacologic effect. Mean elimination t1/2 during long-term oral dosing was longer than after a single dose (9.6 and 5.7 hr, P less than 0.05). Also, during long-term dosing the area under the curve was more than double that of a single dose, and the apparent oral clearance fell from 4.2 to 1.8 l/min (P less than 0.01). These changes may partly be explained by reduction in presystemic metabolism during long-term therapy. Kinetic predictions based on single doses will not give reliable estimates for long-term oral dosage. Less frequent dose schedule may be possible for prolonged therapy.

Administration, Oral↗
PubMed1981

Effect of guanine nucleotides on dopaminergic agonist and antagonist affinity for [3H]sulpiride binding sites in rat striatal membrane preparations.

[3H]Sulpiride bound to rat striatal membrane preparations with a saturable, high affinity component. This binding was displaced potently by dopamine antagonists (both classic neuroleptics and the benzamide, sulpiride) and less potently by dopamine agonists. GTP and its stable analogue Gpp(NH)p did not affect [3H]sulpiride binding to the membranes but altered the affinity for dopaminergic agonists. This effect was specific in that antagonist binding was not affected and only GTP, GDP, and Gpp(NH)p produced the effect. Similar alterations in ligand binding affinity caused by guanine nucleotides have been observed for binding sites linked to an adenylate cyclase. Such an interpretation for the case of [3H]sulpiride is contrary to suggestions that sulpiride labels only those dopamine receptors that are not cyclase linked.

Animals↗
PubMed1980

Coronary artery spasm: use of ergonovine in diagnosis.

Ergonovine maleate was administered to 69 patients with chest pain but without significant coronary artery disease (less than 10% luminal diameter obstruction) to determine whether coronary artery spasm could be provoked. Coronary artery spasm was seen at angiography, or inferred from ECG or thallium myocardial perfusion scan changes. The test was positive in 16 patients: all five patients with documented variant angina (Group A); ten of the 19 patients with suspected variant angina (Group B); one of the 11 patients with exercise-induced chest pain (Group C); and none of the 34 patients with atypical chest pain (Group D). Patients with a positive test usually smoked, complained of recurrent nocturnal or early morning chest pain, showed ST changes during spontaneous chest pain and had minot degrees of fixed coronary obstruction (30--70%), when compared to those with a negative test. The only major side effect of the test was transient ventricular tachycardia which occurred in three patients and was reverted by sublingual and parenteral nitroglycerine.

Aged↗
PubMed1980

Coronary artery spasm.

Variant angina with ST elevation indicates transmural myocardial ischaemia and is due to spasm of a large epicardial coronary artery. Spasm occurs in arteries with varying degrees of fixed obstruction, giving rise to different clinical profiles of variant angina. However, coronary angiography is required to differentiate between those with minor coronary disease, and those with significant (greater than 70%) obstruction. In patients with minor coronary disease or normal arteries, beta-blockers are contraindicated, and treatment with calcium antagonist vasodilators should be commenced after documentation of spontaneous or ergonovine induced spasm. Patients with significant fixed coronary obstructions require bypass grafting if technically feasible. The role of coronary spasm is not confined to variant angina, as it causes angina at rest with ST depression, and may also cause myocardial infarction and sudden death.

Angina Pectoris↗
PubMed1980

Serial thallium-201 myocardial perfusion scanning in acute myocardial infarction.

Serial myocardial perfusion scanning was performed in 30 patients with acute myocardial infarction. Scanning was commenced less than six hours after onset of symptoms in 12 patients, 6-24 hr in eight and 24-120 hr in ten. All 30 patients showed thallium defects corresponding to the ECG site of infarction. When initial and four-hour scans were compared, constant defects were present in ten patients and changing defects in 20. Of the 169 segments with defects on the initial scan, 117 (69%) remained constant, 41 (24%) improved, and 11 (7%) deteriorated. More defects changed in the patients scanned earlier (less than 6 hr) than in the patients scanned later (more than 6 hr) (42% vs 23% P less than 0.025), and more defects changed in patients with subendocardial compared to transmural infarction (49% vs 26% P less than 0.025). During a mean follow-up period of 18 months, seven patients died, two developed left ventricular failure, seven had angina and 14 remained asymptomatic. The non-survivors had significantly larger thallium defects than the survivors (55 +/- 15% vs 37 +/- 14%, P less than 0.005). Serial change on thallium scanning was not related to the clinical course. Perfusion defects on serial thallium scanning are useful in detecting and localising early myocardial infarction and the size of defects is related to the subsequent clinical course. Changing perfusion defects on serial scanning suggesting peri-infarctional ischaemia are common, and make assessment of therapeutic interventions to limit infarct size difficult, but are not related to the clinical course.

Adult↗
PubMedDate not supplied

Delta and sigma sites of clonal NCB20 cells do not modulate calcium uptake.

Opiate alkaloids and peptides are reported to inhibit 45Ca2+ binding to synaptic plasma membranes and uptake into brain synaptosomes. We have examined the effects of a number of opiates on 45Ca2+ uptake in a clonal cell line NCB20 which expresses multiple opioid binding sites. The cells express voltage-dependent calcium channels that are blocked by verapamil and nifedipine. In contrast to brain, 45Ca2+ uptake in these cells, in normal or high potassium medium, is unaffected by opiates. This difference may be due to the particular receptor types; the delta and sigma sites of these cells do not inhibit 45Ca2+ uptake.

Animals↗
PubMedDate not supplied

A learning deficit related to age and beta-amyloid plaques in a mouse model of Alzheimer's disease.

Mice that overexpress the human mutant amyloid precursor protein (hAPP) show learning deficits, but the apparent lack of a relationship between these deficits and the progressive beta-amyloid plaque formation that the hAPP mice display is puzzling. In the water maze, hAPP mice are impaired before and after amyloid plaque deposition. Here we show, using a new water-maze training protocol, that PDAPP mice also exhibit a separate age-related deficit in learning a series of spatial locations. This impairment correlates with beta-amyloid plaque burden and is shown in both cross-sectional and longitudinal experimental designs. Cued navigation and object-recognition memory are normal. These findings indicate that A beta overexpression and/or A beta plaques are associated with disturbed cognitive function and, importantly, suggest that some but not all forms of learning and memory are suitable behavioural assays of the progressive cognitive deficits associated with Alzheimer's-disease-type pathologies.

Aging↗