Biomedical subjects

T W Wilson

Publications and source records attributed to T W Wilson.

At least 55 records · Page 3Linked to original sources

PubMed1994

A renal vasodilator effect of angiotensin II revealed by dual thromboxane inhibition.

Angiotensin II (AII) stimulates arachidonate release from renal endothelial and other cells. Arachidonate is then metabolized by cyclooxygenase to prostaglandin (PG) H2, then PGI2 and thromboxane A2 (TXA2). PGH2 and TXA2 activate the same receptor and should augment AII-mediated vasoconstriction, whereas PGI2 is a vasodilator. We had previously shown that inhibiting TXA2 synthesis with furegrelate (FRG) redirects PGH2 metabolism toward PGI2, causing renal vasodilation. Because TXA2 synthesis inhibition may be incomplete and unmetabolized PGH2 may cause vasoconstriction, we reasoned that adding a PGH2/TXA2 receptor antagonist (BMS 180,290, formerly SQ 29548 (SQ)) to furegrelate should cause further renal vasodilation in the presence of AII. Eight groups of 10 Sprague-Dawley rats received 120-min intravenous infusions of vehicle, FRG (2 mg.kg-1 plus 2 mg.kg-1.h-1), SQ (2 mg.kg-1 plus 2 mg.kg-1.h-1), FRG plus SQ, AII (10 ng.kg-1.min-1), AII plus FRG, AII plus SQ, or AII plus FRG plus SQ. Mean arterial pressure (MAP), p-[14C]aminohippurate clearance (CPAH), and [3H]insulin clearance were averaged for each rat for the final 90 min in three clearance periods. MAP did not change with any treatment. Estimating renal vascular resistance as MAP/CPAH confirmed a renal vasoconstrictor effect of this dose of AII: 58.1 +/- 6.3 vs. 47.3 +/- 6.8 (arbitrary units) with the vehicle (p < 0.05). FRG, SQ, or their combination did not affect renal vascular resistance, but adding FRG or SQ to AII prevented AII-mediated renal vasoconstriction. Adding both to AII caused net renal vasodilation to 24.8 +/- 2.6 (p < 0.05 vs. vehicle). Inulin clearance changed in the same direction in all groups, but the changes were less marked. We conclude that stimulation of renal arachidonate release by AII combined with TXA2 synthesis inhibition and receptor antagonism results in vasodilation. This renal effect could be due to increased and unopposed renal vasodilator PG (principally PGI2) action.

Angiotensin II↗

PubMed1994

The team approach.

Cardiovascular disease continues to be the major cause of death and illness in Canada. But the news is not all bad. The incidence can be reduced by minimizing one or more cardiovascular risk factors.

Cardiovascular Diseases↗

PubMed1994

Social functioning and overall mortality: prospective evidence from the Kuopio Ischemic Heart Disease Risk Factor Study.

We studied the associations between 11 scales of social functioning and risk of death over an average follow-up time of 71 months in 42- to 60-year-old men in the Kuopio Ischemic Heart Disease Risk Factor Study. In age-adjusted analyses, men were at increased risk of death if they reported few persons to whom they gave or received social support, nonparticipation in organizations, low quality of social relationships, a small number of friends, or not currently being married. Frequency of interaction, shyness, and use of emotional support when troubled were not associated with risk of death; the use of instrumental support when troubled was associated with increased risk. There was little evidence of confounding of these associations by the presence of 31 chronic or acute conditions, perceived health status, or six risk factors. Consistent associations were found in a healthy subgroup. These data add to the growing body of literature linking mortality risk with social functioning, especially in relation to organizational participation and quality of relationships.

Adult↗

PubMed1993

Association between plasma fibrinogen concentration and five socioeconomic indices in the Kuopio Ischemic Heart Disease Risk Factor Study.

The association between five socioeconomic indices (lifetime occupation, education, income, ownership of material possessions, and childhood socioeconomic status) and plasma fibrinogen levels was investigated in middle-aged Finnish men who were part of the Kuopio Ischemic Heart Disease Risk Factor Study. The Kuopio Ischemic Heart Disease Risk Factor Study is based on a representative age-stratified sample of 2,682 men aged 42, 48, 54, and 60 years. The data were collected between 1984 and 1989. The present analysis is restricted to the 2,011 men for whom information on fibrinogen and all covariates was available. The covariates were alcohol consumption, body mass index, physical fitness, smoking, coffee consumption, high density lipoprotein cholesterol, low density lipoprotein cholesterol, blood leukocyte count, and prevalent disease (at least one sign of ischemic heart disease, hypertension, diabetes, or previous stroke). An age-adjusted inverse association was found between levels of plasma fibrinogen and four of the five socioeconomic indices: current income, education, lifetime occupation status, and current material possessions. After adjustment for the covariates, the association persisted for education, current income, and lifetime occupation. Analysis of the joint effect of childhood and adult socioeconomic status indicated that those who were economically disadvantaged at both times had the highest fibrinogen levels, but the fibrinogen levels of those who were not poor as adults had no variation by childhood socioeconomic status.

Adult↗

PubMed1993

ETB receptors on aortic smooth muscle cells of spontaneously hypertensive rats.

The effect of the agonist sarafotoxin 6c (S6c), selective for endothelin (ET) receptor subtype B (ETB), on cytosolic free Ca2+ concentrations ([Ca2+]i) was determined by fura-2 methodology using aortic smooth muscle cells (ASMC) isolated from spontaneously hypertensive rats (SHR) and two normotensive strains, Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. The basal [Ca2+]i was significantly higher in the ASMC of SHR (139 +/- 8 nM) than WKY (107 +/- 7 nM) and SD (102 +/- 4 nM) rats. S6c produced concentration-dependent elevations in [Ca2+]i in the ASMC of WKY and SHR, whereas it did not evoke significant increases in the [Ca2+]i levels in the ASMC of SD rats. The peak [Ca2+]i levels observed with maximal concentrations of S6c (500 nM) was higher (P < 0.01) in the SHR (346 +/- 36 nM) than the WKY group (148 +/- 19 nM). The natural nonselective agonist, ET-1, evoked maximal [Ca2+]i in the ASMC of SHR, WKY, and SD rats of 635 +/- 43, 304 +/- 19, and 289 +/- 24 nM, respectively. Depletion of extracellular Ca2+ concentration led to the reduction of the peak [Ca2+]i response to ET-1 by 60 and 40% in the WKY and SHR cells, respectively, whereas the response to S6c remained unaffected. The ETA-selective antagonist, BQ-123 (1 microM), did not affect the [Ca2+]i response to S6c, whereas it attenuated the response to ET-1 by 90 and 70% in the WKY and SHR cells, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Thromboxane synthase inhibition enhances furosemide-induced renal vasodilation.

The effects of furegrelate (a thromboxane synthase inhibitor), indomethacin, and the combination on urine volume (V), para-aminohippurate clearance (CPAH), and mean arterial pressure (MAP) before and after intravenous furosemide were examined in Sprague-Dawley rats. Prior to furosemide, none of the treatments changed MAP, V, or CPAH. Furosemide increased urine volume from 16 +/- 7 to 148 +/- 25 microL.min-1. Concomitant administration of furegrelate or indomethacin did not affect furosemide-induced diuresis, but the combination of indomethacin, furegrelate, and furosemide caused increased diuresis (to 254 +/- 40 microliters.min-1, p < 0.05, compared with furosemide alone). Furosemide alone or with the other drugs had no effect on mean arterial pressure. CPAH was increased from 3.0 +/- 0.4 to 4.6 +/- 0.8 ml.min-1.100g-1 (p < 0.05, n = 6) by furosemide, and to an even greater extent (6.7 +/- 0.8, n = 6) after pretreatment with furegrelate. Pretreatment with indomethacin alone or in combination with furegrelate abolished the furosemide-induced CPAH increment. Urine excretion of the prostacyclin hydrolysis product 6-ketoprostaglandin F1 alpha was increased by furosemide in the presence of furegrelate. Given that the transient renal vasodilation with furosemide is due to prostanoid precursor release, these results are consistent with redirection of arachidonate metabolism toward vasodilator prostaglandins by furegrelate.

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Stratified initial values and change scores.

A common question that is encountered in many studies is relating a change in a variable to the variable's initial value. It is well known that regressing the change on the initial value creates a spurious association and misleads the unwary. One attempt to cope with this problem has been to stratify that data based on the initial value. We show that this approach does not solve the problem. Theoretical and simulation results for independent normal and independent exponential random variables are provided.

Statistics as Topic↗

PubMed1992

Burst testing of condoms. I. Basic features of the force-deformation curve of latex-rubber condoms.

Inflation of a rubber condom involves biaxial deformation of the material which can be modeled by the use of an appropriate strain-energy function. Force versus deformation data for uniaxial extension of strips of condoms were used to determine the parameters for Ogden's form of a strain-energy function. These parameters were then used to fit experimentally obtained burst test data to a stress-strain equation formulated for inflation of condoms in a burst test. Experimental data on inflation of condoms agree well with theoretical curves verifying the applicability of the biaxial stress-strain equation to the particular strain-energy function on which it is based.

Condoms↗

PubMed1992

Water sorption and mechanical properties of light-cured proprietary composite tooth restorative materials.

Seven light-cured proprietary composite restorative materials, P-50 (3M), P-10 (3M), P-30 (3M), FulFil (Caulk), Herculite (Kerr), Silux Plus (3M) and Silux (3M) were characterized in terms of water uptake at 37 degrees C. For several of the systems, elastic modulus and glass transition temperature were evaluated with a dynamic mechanical analyser (Autovibron DDV-II-C). Model systems such as bis-GMA (75%) + triethylene glycol dimethacrylate (25%), bis-GMA (30%) + triethylene glycol dimethacrylate (10%) + lithium aluminium silicate (60%), bis-GMA + triethylene glycol dimethacrylate (14%) + barium glass (silanated) (86%) and bis-GMA + triethylene glycol dimethacrylate (14%) + zinc glass (silanated) (86%) were also studied with reference to water sorption. It was concluded that the changes in elastic modulus tend to confirm the hypothesis that the matrix-filler interface contains water. Silux and Silux Plus accommodated the greatest amount of water at the interface. Silux Plus displayed a dramatic reduction in elastic modulus c. 0 degrees C, indicating possible melting of water clusters. It appeared that the only available hole for water clusters was at the matrix-filler interface.

Adsorption↗

PubMed1992

Diltiazem potentiates angiotensin II-mediated renal prostacyclin synthesis.

Diltiazem (DIL), a calcium antagonist, has variable effects on renal hemodynamics, and has been considered to act independently of renal prostaglandins (PGs). Angiotensin II (AII) constricts renal vasculature but also increases renal vasodilator PG synthesis. We examined interactions between AII and DIL on [14C]p-aminohippurate ([14C]PAH) clearance, mean arterial pressure (MAP), and urine 6-ketoprostaglandin F1 alpha excretion (U6k) in groups of seven to nine conscious Sprague-Dawley rats. We calculated the renal vascular resistance (RVR) as the ratio of MAP/[14C]PAH clearance. AII infusion (10 ng/kg/min i.v.) increased the RVR by 50-80% for at least 120 min. DIL (1 mg/kg plus 2 micrograms/kg/min) reversed this vasoconstriction but adding indomethacin to DIL prevented the reversal. DIL alone did not change the RVR at 30-60 min after starting an infusion but increased it by 22% at 90-120 min. Adding AII to the DIL infusion actually decreased the RVR and this decrease was abolished by indomethacin. DIL alone had no effect on U6k while AII increased it slightly (1.36 +/- 0.12 to 1.86 +/- 0.22 ng/30 min, n = 6, p less than 0.05), and adding DIL to AII increased it further (3.19 ng/30 min, n = 6, p less than 0.05). We conclude that DIL enhances AII-induced renal prostacyclin synthesis and that this is functionally relevant. This mechanism may explain the reported variability of the renal hemodynamic effects of DIL. Furthermore, DIL-enhanced renal vasodilator PG synthesis may help protect the kidney during vasoconstrictor stress.

6-Ketoprostaglandin F1 alpha↗

PubMed1992

Renal prostaglandin synthesis and angiotensin-converting enzyme inhibition.

Renal prostaglandins (PGs) help maintain renal blood flow and glomerular filtration rate when the kidney is exposed to a vasoconstrictor stress. In addition, they aid pressure natriuresis and blunt the antidiuretic effect of vasopressin. Angiotensin-converting enzyme (ACE) inhibitors could decrease renal PG synthesis by reducing angiotensin II (Ang II) formation or increase it by preventing kinin inactivation. Additionally, they could affect PG synthesis or catabolism directly. The effects of ACE inhibitors on blood pressure and renal hemodynamics appear to be largely independent of changes in renal PG synthesis. Similarly, there is no evidence that pressure natriuresis is modified by ACE inhibitors. A kinin induced increase in collecting duct PG synthesis may account for the water diuresis seen clinically with ACE inhibitors. A possible beneficial interaction between thromboxane synthesis inhibitors and ACE inhibitors may exist. Thromboxane synthetase inhibitors can reduce renal vascular resistance by redirecting PG endoperoxide synthesis toward prostacyclin. This effect may be offset by a prostaglandin-induced increase in renin release and Ang II formation. ACE inhibitors, by preventing Ang II synthesis, may increase the vasodilation due to thromboxane synthesis inhibition.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1992

Diuretic and non-diuretic actions of furosemide: effects of probenecid.

Furosemide causes not only natriuresis, but a rapid (5-10 min) increase in plasma renin activity. The latter has been attributed both to the release of eicosanoids from renal blood vessels and to changes in sodium delivery to the macula densa. Drugs like indomethacin abolish the renin increment and could potentially affect both mechanisms: they inhibit cyclooxygenase but could also compete with furosemide for transport into the tubular lumen, reducing furosemide concentration at its site of action. We studied the effects of probenecid, a weak acid without cyclooxygenase activity, on the responses to furosemide in 20 healthy young men. Each received placebo and low (1000 mg/d) or high (2000 mg/d) doses of probenecid for one week in double-blind, randomized trials, crossover fashion. One hour after the last dose, all participants were given furosemide 0.5 mg/kg intravenously. Probenecid reduced serum uric acid in a dose-dependent manner but did not change platelet thromboxane B2 production. Similarly, there was no change in urine excretion rates of thromboxane B2 or 6ketoprostaglandin F1 alpha, or in baseline or stimulated plasma renin activity. The total natriuresis in 4 h was also unchanged. By contrast, the sodium excretion rate in the first 30 min was reduced after both probenecid regimens while that of later periods was increased. These findings are consistent with the proposed effect of probenecid as reducing furosemide secretion in the proximal tubule, which reduces its concentration at the lumenal surface of the thick ascending limb of Henle's loop, but also prevents its excretion from the body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Effect of indomethacin on arachidonic acid metabolism in human leukocytes stimulated ex vivo.

We had previously shown that inhibition of cyclooxygenase in vitro by indomethacin can cause increased formation of products of the 5-lipoxygenase pathway of arachidonic acid metabolism in leukocytes. To determine if this effect also occurred in vivo, we studied leukocyte arachidonic acid metabolism in 12 volunteers before and after ingestion of 150 mg indomethacin daily for 3 days. Blood was collected before treatment and 2 hours, 2 days, and 5 days after the final dose of indomethacin. Serum thromboxane B2, a measure of platelet cyclooxygenase activity, was profoundly suppressed 2 hours after the final dose of indomethacin but had recovered to control values at 2 days. Mixed leukocyte suspensions and purified neutrophil suspensions were prepared and stimulated with calcium ionophore A23187 and the resultant 5-lipoxygenase metabolites were quantified by HPLC. Two hours after the final dose of indomethacin, the stimulated levels of 5-hydroxyeicosatetraenoic acid, leukotriene B4, and leukotriene C4 were significantly increased to 247% +/- 68%, 135% +/- 14%, and 149% +/- 23% of pretreatment values, respectively. Two days after the final dose of indomethacin, 5-hydroxyeicosatetraenoic acid levels were still significantly elevated. By 5 days all parameters had returned to baseline. Similar effects were not observed in purified neutrophil suspensions, probably because of the loss of indomethacin from the cells during the multiple washing procedures used in their preparation. This is in accord with the reversible nature of the inhibitory effect of indomethacin on cyclooxygenase. We conclude that indomethacin at a commonly used dose increases the ability of circulating leukocytes to produce 5-lipoxygenase products.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1991

Biohistory of slavery and blood pressure differences in blacks today. A hypothesis.

Genetic factors are known to play an important role in the variations in blood pressure levels. However, genetic factors that explain the higher average blood pressure levels of western hemisphere blacks when compared with African blacks have not been seriously considered. Because the genetic makeup of a population is largely determined by biological and ecological forces in the past, an examination of the biohistory of blacks, specifically the slavery era, was conducted. An overview of the salient findings of that investigation is included in this article. The published historical evidence on the transatlantic slave trade and New World slavery (from the 16th century to the 19th century) reveals that conditions existed for "natural selection," and therefore, genetic changes were virtually inevitable in the slave populations. During this period of history, mortality was extremely high, and fertility (or reproductive success) was so low among the survivors that most plantation societies in the western hemisphere depended on a constant importation of captives (over 12 million) from Africa for the viability of the plantation communities. Because the major causes of death were salt-depletive diseases such as diarrhea, fevers, and vomiting, it is argued that individuals with an enhanced genetic-based ability to conserve salt had a distinct survival advantage over others and were, therefore, more likely to bequeath their genotype to subsequent generations of Western hemisphere blacks. Thus, it is predicted that blacks in the Americas have a greater frequency of individuals with an enhanced genetic-based ability to conserve salt than African blacks.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People↗

PubMed1991

Systolic blood pressure levels in black populations in sub-Sahara Africa, the West Indies, and the United States: a meta-analysis.

Average systolic blood pressure levels from epidemiological studies conducted on black populations in sub-Sahara Africa were pooled and compared with pooled systolic blood pressure levels from black populations in the northern portion of the Western hemisphere (the West Indies and the United States). Studies published in English that listed systolic blood pressure means and standard deviations and sample sizes in 40-49-year-old men and women were included. Overall, systolic blood pressure levels were higher (p less than 0.05) in blacks from the northern Western hemisphere than in blacks from sub-Sahara Africa for both men (12 mm Hg higher) and women (13 mm Hg higher). The analysis was also conducted on regions within sub-Sahara Africa and in rural and urban subgroups. Systolic blood pressure was lower (p less than 0.05) in East Africa than in the other three regions within Africa for both sexes. Overall, urban blacks within Africa had higher systolic blood pressures (p less than 0.05) than rural blacks for both sexes. In the northern Western hemisphere, rural blacks had higher systolic blood pressures (p less than 0.05) than urban blacks for both sexes. Studies should be designed with standardized methods to unravel these intraracial differences in blood pressure levels.

Adult↗

PubMed1991

Lifestyle profiles of hypertensives.

Healthy lifestyles and quality of life are key elements in the health of individuals and the community as a whole. This study examines the relationship of specific lifestyle behaviours to blood pressure in subjects being treated for hypertension. Data were collected over a two-year period and analysis was completed in June, 1989. Discriminant analysis identified that, of the lifestyles selected, predictors of uncontrolled hypertension were a high calcium intake, a high perceived level of stress, and a 'normal' body mass index. Profiles of lifestyle behaviours identified by discriminant analysis found to be important to various age and sex groupings of the subjects are illustrated.

Adolescent↗

PubMed1991

Diltiazem increases renal prostacyclin.

We sought to determine whether the specific renal vasodilator effect of low dose diltiazem (D) was mediated by increased renal prostacyclin (PGI2) synthesis. Groups of 7-9 Sprague-Dawley rats were fitted with an indwelling transabdominal bladder cannula. Cannulae were placed in the jugular and femoral veins and the carotid artery and the rats allowed to recover for 24 h. Angiotensin II (AII) was infused intravenously at a rate (10 ng/kg/min) which increased mean arterial pressure (MAP) by 5-10%. After 30 min D(1 mg/kg and 2 micrograms/kg/min), D plus indomethacin (IND) (2 mg/kg and 33 micrograms/kg/min), IND plus vehicle or vehicle alone were added to AII. AII increased urinary 6-keto-prostaglandinF1 alpha (6-ketoPGF1 alpha) excretion from 1.36 +/- 0.12 to 1.86 +/- 0.20 ng/30 min (p less than 0.05) and D increased it further to 3.19 +/- 0.39 (p less than 0.05). Renal plasma flow (RPF) was estimated by 14C-PAH clearance (CPAH). Urinary excretion of 6-ketoPGF1 alpha was increased with AII indicating increased renal PGI2 synthesis. This increase in PGI2 was unable to prevent a reduction in RPF. D administration further increased the excretion of 6-ketoPGF1 alpha and reversed AII-induced renal vasoconstriction. IND augmented the AII response and prevented the effect of D, suggesting the renal vasodilator effect of D is, at least in part, PGI2-mediated. This mechanism may help maintain renal blood flow under conditions of vasoconstrictor stress.

6-Ketoprostaglandin F1 alpha↗

PubMed1991

Temporal contrast sensitivity loss in primary open-angle glaucoma and glaucoma suspects.

The need for more sensitive tests for the early detection of compromised visual function in glaucoma is established by anatomic and psychophysical evidence of damage occurring to optic nerve fibers in eyes with normal visual fields. The results are reported of temporal frequency testing on 51 glaucoma suspects without visual field loss in either eye, 52 glaucoma patients with visual field deficits in the tested eye, and 11 normal subjects. Modulation transfer functions were obtained using a sinusoidally flickering 5 degrees spatially uniform white field viewed with central fixation and plotted at six frequencies from 5-30 Hz. The results showed a frequency-specific sensitivity loss centered at 15 Hz and a nonfrequency-specific mean sensitivity loss, that was greater, on average, in glaucoma patients than in suspects. Sensitivity losses of both kinds were seen in most glaucoma patients, but only in a minority of glaucoma suspects. About 12% of suspects were indistinguishable from the lowest performing one third of these glaucoma patients. A smaller number of suspects appeared to form a second mode in the frequency distribution for temporal sensitivity at 15 and 25 Hz. In patients with glaucoma, age was found to be a significant factor associated with the magnitude of mean sensitivity loss. Age was not a significant factor contributing to sensitivity loss in individual suspect data as measured by regression analysis, but it contributed to a small and consistent sensitivity loss across frequency for group-averaged data in those older than 55 years of age.

Adult↗