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Biomedical subjects

T C Hamilton

Publications and source records attributed to T C Hamilton.

17 recordsLinked to original sources
PubMed1979

Ribonucleic acid in plasma from normal adults and multiple myeloma patients.

Reports of the presence of RNA in human plasma have been numerous, often suggesting that RNA in plasma is correlated with human disease. We critically examined the methods for determination of RNA in plasma. Lack of method specificity has caused previous workers to overestimate plasma RNA concentrations by more than 50-fold. To isolate RNA from plasma, we used both a phenol-chloroform extraction and a modified Schmidt-Thannhauser procedure. We show that RNA in plasma can be identified and quantified by alkaline hydrolysis of the plasma extract and subsequent separation of the resulting 2'- and 3'-mononucleotides by "high-performance" liquid chromatography. We could not detect RNA in plasma from either apparently healthy, normal adults or multiple myeloma patients, but found 1.1 mg/L in the plasma of a patient with Waldenström's macroglobulinemia. Our method is useful for the specific determination of RNA in plasma and will detect as little as 600 micrograms/L.

Chromatography, High Pressure Liquid↗
PubMed1978

Diminishing hypotensive effect of increasing doses of pindolol in DOCA/saline hypertensive rats.

In DOCA-saline hypertensive rats, pindolol (4, 20 or 50 mg/kg orally) produced a hypotensive effect which was inversely related to dose. Following adrenal demedullation, a hypotensive response to the highest dose of pindolol was unmasked and the magnitude of the responses to lower doses was increased. The results suggest that adrenal catecholamines moderate the hypotensive effects of high doses of pindolol.

Adrenalectomy↗
PubMed1977

Measurements of contraction latencies to mechanical and electrical stimulation of the protozoan, Spirostomum ambiguum.

Measurements made on contraction latencies in Spirostomun suggest that mechanical stimulation causes contractions to be initiated by the release of small amounts of calcium from a store tightly coupled to the contractile apparatus. Contraction to electrical stimulation appears to result from the gross electrophoretic mobilization of large amounts of calcium from a loosely coupled store. Contraction latencies to mechanical stimulation were three milliseconds and were independent of stimulus strength, previous stimulation, and contraction probability. For 0.5-millisecond biphasic electrical stimulation the contraction latencies varied widely. Latencies to initial contractions were dependent on stimulus strength: from 1.0 milliseconds for a stimulus that caused a 100% probability of contraction to 2.0 milliseconds for a stimulus that caused a 10% probability of contraction. Latencies of contraction to electrical stimulation were also dependent upon previous stimulation, lengthening to over 300 milliseconds after ten minutes of stimulation. Initial contraction latencies were not affected by previous stimulation to the other (electrical or mechanical) stimulus modality. Repeated electrical stimulation also reduced the animal's resting length and slowed the rate of post contraction re-extension, whereas mechanical stimulation did not have these effects.

Animals↗
PubMed1977

Electron microbeam analysis of calcium distribution in the ciliated protozoan, Spirostomum ambiguum.

Electron microprobe analyses of calcium distribution in the ciliated protozoan, Spirostomum ambiguum, indicated several calcium rich sites. One site was an endoplasmic distribution of calcium coincident with phosphorus which corroborates previous findings of hydroxyapatite deposits within Spirostomum. These apatite deposits were distributed throughout the endoplasm, but not within the nuclei or the contractile vacuole. Calcium was also detected within the cortical region. Cortical calcium was in greater concentration in the anterior portion of the organism and decreased towards the posterior end (region containing the contractile vacuole). Phosphorus and potassium were also detected as gradients from the anterior end, whereas magnesium was detected in the same density throughout the cortical region. Line scans of cortical regions suggested (1) distributions of calcium within mitochondria and/or vesicles, and (2) calcium associated with bundles of microfilaments.

Animals↗
PubMed1977

Studies on the cardiovascular effects of pindolol in DOCA/saline hypertensive rats.

1 A hypotensive response to orally administered pindolol in conscious normotensive and deoxycorticosterone acetate (DOCA)/saline hypertensive rats (DS-rats) is described. In DS-rats, pindolol (10-50 mug/kg) produced a dose-dependent fall in blood pressure and elevation of resting heart rate.2 The hypotensive response and tachycardia produced by oral pindolol (50 mug/kg) in DS-rats were prevented by propranolol (5 mg/kg), suggesting that pindolol's effects are mediated by beta-adrenoceptor stimulation.3 After mecamylamine (10 mg/kg), oral pindolol (50 mug/kg) produced a further fall in blood pressure in DS-rats, suggesting that its hypotensive effects are probably mediated in the peripheral vasculature.4 Pretreatment with oral pindolol (10 or 50 mug/kg) resulted in a reduction of neuronally-induced tachycardia in pithed DS-rats; neuronally-evoked pressor effects were also antagonized by pindolol (50 mug/kg, orally).5 Whereas pindolol, 50 mug/kg orally or intraperitoneally, produced a marked and progressive hypotensive response of rapid onset (20 min) in DS-rats the same dose intravenously produced a smaller response of delayed onset (80 minutes).6 In anaesthetized DS-rats, an equivalent degree of cardiac beta-adrenoceptor blockade was produced by pretreatment with pindolol, 50 mug/kg orally (2 h previously) or intravenously (1 h previously).7 After administration of pindolol, 2 mg/kg intravenously, to conscious DS-rats, the tachycardia produced by intravenous isoprenaline, 3 mug/kg, was almost abolished for the first 60 min of the study, whereas a hypotensive response to pindolol was delayed in onset (100 minutes).8 The hypotensive response and tachycardia produced by oral pindolol 50 mug/kg, in DS-rats were prevented by inhibition of metabolic enzyme activity by pretreatment with Proadifen (SKF 525-A), 80 mg/kg.9 The results suggest that pindolol's effects on blood pressure and heart rate in the conscious DS-rat are mediated by a metabolite(s) acting by stimulation of peripheral beta-adrenoceptors.

Administration, Oral↗
PubMed1977

Bufuralol, a new beta-adrenoceptor blocking agent in a series of benzofuran-2-ethanolamines. Part 2: pharmacology.

1-(7-Ethylbenzofuran-2-yl)-2-tert.-butylamino-1-hydroxyethane hydrochloride (bufuralol) is a non-selective beta-adrenoceptor blocking agent which closely resembles propranolol in its properties, including potency. Bufuralol is devoid of alpha-adrenoceptor blocking activity but possesses beta-adrenoceptor agonist activity. beta-Adrenoceptor blocking activity resides mainly in the (-)-isomer though membrane stabilising properties are associated with both optical isomers.

Adipose Tissue↗
PubMed1976

Hypotensive responses following oral adminstration of beta-adrenoceptor blocking drugs to the conscious cat.

On oral administration, the non-selective beta-adrenoceptor blocking drugs (+/-)-bufuralol, (-)-bufuralol, propanolol, oxprenolol, pindolol and alprenolol produced hypotensive responses in the conscious cat; (+)-bufuralol was without effect. The selective beta-adrenoceptor blocking drugs practolol and atenolol had no effect on blood pressure but tolamolol elicited a hypotensive response. All the drugs tested reduced the tachycardia due to intravenous isoprenaline in the conscious cat; however, not all doses of these drugs reduced blood pressure. (+)-Bufuralol was devoid to beta-adrenoceptive blocking activity. Only tolamolol reduced the pressor response to i.v. phenylephrine in the conscious cat, indicating that alpha-adrenoceptive blocking activity may contribute to its hypotensive action. The results suggest that beta-adrenoceptive blocking activity is necessary for the hypotensive responses of these drugs. However, for the different drugs, there was no correlation between peripheral beta-adrenoceptive blocking activity and hypotensive response.

Adrenergic alpha-Antagonists↗
PubMed1976

Prolonged effects of p-chlorophenylalanine on the blood pressure of conscious normotensive and DOCA/saline hypertensive rats.

1. In deoxycorticosterone acetate (DOCA) saline hypertensive rats a single dose of p-chlorophenylalanine methylester (PCPAME) (400 mg/kg i.p.) produced a significant fall in blood pressure (20-43 mmHg) which lasted for at least 8 days and was accompanied by a parallel depletion of brain stem 5-hydroxytryptamine (5-ht) but not of noradrenaline (NA). 2. In normotensive rats single doses of PCPAME (200 and 400 mg/kg i.p.) produced a significant hypotension (15-20 mmHg) after a latent period of 5 days. An initial pressor response (12 mmHg) was observed at the higher dose level only on day 3. 3. The hypotensive response to PCPAME (200 mg/kg i.p.) in normotensive rats was not modified by pretreatment with 5,6-dihydroxytryptamine (5,6-DHT; 50 mug i.c.v.) or 6-hydroxydopa (6-ohda; 3 X 250 mug intracerebroventricularly). 4. It is concluded that the hypotensive response to PCPAME in normotensive rats in independent of brain stem depletion of 5-HT and is probably not mediated by the formation of a false transmitter substance acting via central noradrenergic inhibitory pathways. The mechanism involved in the antihypertensive response to PCPAME in DOVA/saline hypertensive rats has yet to be defined.

Animals↗
PubMed1975

Influence of anti-hypertensive drug treatment on vascular reactivity in spontaneously hypertensive rats.

1. The effect of prolonged anti-hypertensive drug treatment on the blood pressure of conscious spontaneously hypertensive rats (SH-rats), and of age-matched normotensive Sprague-Dawley rats was determined during the development of hypertension in SH-rats and in the early stages of established hypertension. A comparison of the vascular reactivity to noradrenaline (NA) and 5-hydroxytryptamine (5-HT) was also made in isolated perfused mesenteric artery preparations from treated and control SH- and Sprague-Dawley rats. 2. Chronic treatment from age 4 to 16 weeks with hydrallazine alone, or a combination of hydrallazine/hydrochlorothiazide/reserpine, ad libitum in the drinking water, prevented the development of hypertension in SH-rats and also reduced the vascular reactivity to NA and 5-HT in isolated vessel preparations from treated compared to control rats. 3. Similar drug treatments started in early established hypertension reduced blood pressure in SH-rats over the 12 week treatment period (from age 8 to 20 weeks) without affecting vascular reactivity to NA and 5-HT in the isolated vessel preparation. 4. Drug treatments had little effect on blood pressure of age-matched Sprague-Dawley rats and no effect on vascular reactivity to NA and 5-HT in the isolated perfused mesenteric artery preparation from treated compared to control rats. 5. These results indicate that the development of increased vascular reactivity and of hypertension in SH-rats occurs simultaneously and, therefore, the vascular changes may be a consequence of the structural changes induced by the raised blood pressure. 6. In established hypertension, no regression of vascular changes was observed despite prolonged reduction of blood pressure. The role of an increased vascular reactivity in the maintenance of hypertension is therefore questionable.

Animals↗
PubMedDate not supplied

Evidence for the involvement of alpha-adrenoceptor blockade in the antihypertensive action of diazoxide in the renal hypertensive rat.

The effects of diazoxide on the blood pressure and heart rate of conscious renal hypertensive rats have been investigated. The antihypertensive action of diazoxide has been studied in relation to the effects of diazoxide pretreatment on pressor responses to stimulation of the complete sympathetic outflow and to injections of noradrenaline, phenylephrine, angiotensin and serotonin in pithed rats. In pithed preparations, pressor responses to sympathetic nerve stimulation, and to injected noradrenaline and phenylephrine were significantly reduced by diazoxide pretreatment, at a time corresponding to maximal reduction of blood pressure in conscious animals. At this time there was no significant reduction of pressor responses to injected angiotensin or serotonin. These findings suggest a contribution of alpha-adrenoceptor blockade to the antihypertensive activity of diazoxide.

Adrenergic alpha-Antagonists↗