PubMed Health⌕ Search

Biomedical subjects

T Bennett

Publications and source records attributed to T Bennett.

At least 37 records · Page 2Linked to original sources
PubMed2001

Regional haemodynamic responses to the cannabinoid agonist, WIN 55212-2, in conscious, normotensive rats, and in hypertensive, transgenic rats.

Regional haemodynamic responses to the cannabinoid agonist, WIN 55212-2 (5 - 250 microg kg(-1) i.v.) were assessed in conscious, normotensive, Hannover, Sprague-Dawley (HSD) rats, and in hypertensive, transgenic ((mRen-2)27) (abbreviated to TG) rats. In HSD rats, WIN 55212-2 caused pressor, and renal and mesenteric vasoconstrictor effects, with a hindquarters vasodilator effect occurring only at the highest dose. In TG rats, the effects of the cannabinoid agonist were qualitatively similar to those seen in HSD rats, except there was no hindquarters vasodilatation. In both strains of rat, in the presence of losartan, pentolinium and a vasopressin (V1-receptor) antagonist, the pressor and vasoconstrictor effects of WIN 55212-2 were abolished, but the hindquarters vasodilator response was enhanced (HSD rats) or was seen only in that circumstance (TG rats). Under these conditions, both strains of rat showed a modest fall in blood pressure, together with mesenteric vasodilatation. In additional experiments in normotensive SD rats from Charles River (CRSD), it was shown that, in the presence of the V1-receptor antagonist alone, or losartan alone, or the two antagonists together, the cardiovascular effects of WIN 55212-2 (50 or 150 microg kg(-1)) were not attenuated. Hence, the effects described above were likely due to pentolinium. There were no consistent differences between HSD and TG rats in their haemodynamic responses to methoxamine or noradrenaline, indicating the two strains were not likely to differ markedly in their responsiveness to any putative sympathetic activation induced by WIN 55212-2. Collectively, the results indicate that the predominant cardiovascular effects of WIN 55212-2 in conscious HSD and TG rats (i.e., pressor and vasoconstrictor actions) can be attributed largely to indirect, pentolinium-sensitive mechanisms, which appear to differ little in the normotensive and hypertensive state, at least in conscious animals. Under the conditions of our experiments, signs of cannabinoid-induced vasodilatation were modest.

Animals↗
PubMed2001

Haemodynamic effects of the bacterial quorum sensing signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone, in conscious, normal and endotoxaemic rats.

N-acylhomoserine lactones (AHLs) are small, diffusible signalling molecules, employed by Gram-negative bacteria to coordinate gene expression with cell population density. Recent in vitro findings indicate that AHLs may function as virulence determinants per se, through modification of cytokine production by eukaryotic cells, and by stimulating the relaxation of blood vessels. In the present study, we assessed the influence of AHLs on cardiovascular function in conscious rats, and draw attention to the ability of the N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL), a signal molecule produced by P. aeruginosa, to cause marked bradycardia. This bradycardic effect was blocked by atropine and atenolol, and did not occur in vitro. Furthermore, modification of the acyl side chain length resulted in the loss of activity, whereas removal of the homoserine lactone ring, did not. The bradycardic effect of 3-oxo-C12-HSL was also observed in endotoxaemic animals, albeit attenuated. In normal rats, 3-oxo-C12-HSL caused initial mesenteric and hindquarters vasoconstriction, but only slight, and delayed signs of vasodilatation in the renal and mesenteric vascular beds. Furthermore, administration of 3-oxo-C12-HSL (pre-treatment or 2 h post-treatment) together with LPS, did not modify the established regional haemodynamic effects of the LPS, 6 h after the onset of its infusion. Our observations do not provide any clear evidence for an ability of 3-oxo-C12-HSL to modify the haemodynamic responses to LPS infusion. However, they are not inconsistent with the hypothesis that some of the cardiovascular sequelae of bacterial infection may be modulated by an influence of bacterial quorum sensing signalling molecules on the host.

4-Butyrolactone↗
PubMed2001

Effects of the novel selective endothelin ET(A) receptor antagonist, SB 234551, on the cardiovascular responses to endotoxaemia in conscious rats.

1. In conscious, freely moving, male, Long Evans rats, regional haemodynamic responses to exogenous endothelin-1 (ET-1; 25, 50 and 250 pmol kg(-1) i.v.) were assessed in the presence of vehicle, or the selective ET(A)-receptor antagonist, SB 234551. On the following day, the effects of SB 234551 on the haemodynamic responses to lipopolysaccharide (LPS) infusion (150 microg kg(-1) h(-1), i.v.) were determined. 2. When SB 234551 was given i.v. by primed infusion at a dose of 0.3 mg kg(-1) bolus, 0.3 mg kg(-1) h(-1) infusion, it caused selective inhibition of the vasoconstrictor effects of exogenous endothelin-1, whereas at a dose of 1 mg kg(-1), 1 mg kg(-1) h(-1), SB 234551 also inhibited some of the vasodilator effects of endothelin-1. 3. Infusion of LPS, in the presence of vehicle, caused a short-lived (1 - 2 h) hypotension, tachycardia, and vasodilatation in renal, superior mesenteric and hindquarters vascular beds. Thereafter, blood pressure, heart rate and mesenteric vascular conductance returned to baseline values, but renal vasodilatation persisted, and there was vasoconstriction in the hindquarters. 4. In the presence of SB 234551 (0.3 mg kg(-1), 0.3 mg kg(-1) h(-1)), the early (1 - 2 h) cardiovascular responses to LPS infusion were unaffected, but the subsequent recovery of mean arterial blood pressure was impaired, due to developing vasodilatation in the mesenteric and, to a lesser extent, hindquarters, vascular beds. SB 234551 had no effect on the renal haemodynamic responses to LPS infusion. 5. The results confirm an important, regionally-selective, vasoconstrictor role for endogenous endothelin in this model of endotoxaemia.

Animals↗
PubMed2001

Continuous ambulatory monitoring of absolute right ventricular pressure and mixed venous oxygen saturation in patients with heart failure using an implantable haemodynamic monitor: results of a 1 year multicentre feasibility study.

BACKGROUND: Implantable sensors that monitor haemodynamics over time may be useful in patients with heart failure. This multicentre study assessed the feasibility of a system that has one sensor measuring absolute pressure and another measuring mixed venous oxygen saturation (SvO(2)). Both sensors were mounted on leads that were implanted in the right ventricle. METHODS: Twenty-one patients with heart failure (NYHA II-III) were included. Comparisons were made to right heart catheterizations at implant and at 2, 6 and 12 months thereafter. Patients underwent several haemodynamic provocations during the catheterizations. RESULTS: Overall, among functioning sensors, the IHM-1 values were highly correlated with reference values for all time points during all provocations, demonstrating high reproducibility and stability (r(2)=0.91, 0.79 and 0.78 for systolic, right ventricular diastolic and SvO(2), respectively). Although IHM-1 underestimated reference pressure values by 4.5 mmHg and SvO(2)by 1.6%, this difference was consistent across provocation and stable over 12 months of follow-up. Twelve of the 21 oxygen sensors failed to function and two pressure sensors had component failures. Preliminary analysis of long-term data revealed haemodynamic patterns that may be key indicators for therapeutic interventions. CONCLUSION: This multicentre feasibility study demonstrated the accuracy and stability of sensors implanted in the right ventricle. The IHM-1, using right ventricular pressures and SvO(2), with improved performance, might be useful in the study of pathophysiological mechanisms and treatment interventions in heart failure.

Adult↗
PubMed2001

Stress as a diagnostic challenge for postconcussive symptoms: sequelae of mild traumatic brain injury or physiological stress response.

There is considerable controversy regarding whether persistent postconcussive symptoms (PCS) are injury-specific, in a subgroup of individuals after mild traumatic brain injury (TBI). The following findings have contributed to this controversy: (1) The base rate of PCS in mild TBI is comparable to uninjured controls; and (2) The severity of PCS covary with daily stress levels (Gouvier, Cubic, Jones, Brantley, & Cutlip, 1992). We examined this relationship further by evaluating the effects of experimental conditions of stress or relaxation on individuals with TBI and uninjured control subjects, with low and high PCS endorsement. We evaluated psychophysiological parameters, neuropsychological performance, and changes in PCS and stress perception. In our study, subjects with TBI increased PCS after engaging in cognitively challenging tasks, and demonstrated significant autonomic changes in the stress condition. Symptomatic TBI subjects exposed to high stress had increases in PCS complaints, decreased speed of information processing, and subtle memory deficits. Our results suggest that PCS are injury-specific and that individuals with a history of TBI are susceptible to the effects of stress. Relaxation training including breathing retraining may be an effective means of decreasing PCS and cognitive complaints in subjects with mild TBI.

Adult↗
PubMed2001

Saccharomyces cerevisiae rad51 mutants are defective in DNA damage-associated sister chromatid exchanges but exhibit increased rates of homology-directed translocations.

Saccharomyces cerevisiae Rad51 is structurally similar to Escherichia coli RecA. We investigated the role of S. cerevisiae RAD51 in DNA damage-associated unequal sister chromatid exchanges (SCEs), translocations, and inversions. The frequency of these rearrangements was measured by monitoring mitotic recombination between two his3 fragments, his3-Delta5' and his3-Delta3'::HOcs, when positioned on different chromosomes or in tandem and oriented in direct or inverted orientation. Recombination was measured after cells were exposed to chemical agents and radiation and after HO endonuclease digestion at his3-Delta3'::HOcs. Wild-type and rad51 mutant strains showed no difference in the rate of spontaneous SCEs; however, the rate of spontaneous inversions was decreased threefold in the rad51 mutant. The rad51 null mutant was defective in DNA damage-associated SCE when cells were exposed to either radiation or chemical DNA-damaging agents or when HO endonuclease-induced double-strand breaks (DSBs) were directly targeted at his3-Delta3'::HOcs. The defect in DNA damage-associated SCEs in rad51 mutants correlated with an eightfold higher spontaneous level of directed translocations in diploid strains and with a higher level of radiation-associated translocations. We suggest that S. cerevisiae RAD51 facilitates genomic stability by reducing nonreciprocal translocations generated by RAD51-independent break-induced replication (BIR) mechanisms.

Chromosome Deletion↗
PubMed2001

Nitric oxide contributes to control of effusion in experimental otitis media.

OBJECTIVES/HYPOTHESIS: Nitric oxide (NO) is a small, short-lived free radical involved in cellular signaling and known to play a role in inflammation. It is generated on demand by the enzyme nitric oxide synthase (NOS) on arginine. We have previously found that mRNA encoding NOS is produced in the middle ear during otitis media. The role of NO was therefore explored in an experimental model of immune-mediated otitis media. STUDY DESIGN AND METHODS: Guinea pigs were systemically immunized and later challenged in the middle ear with the same antigen. One ear of each animal was challenged with antigen alone. In the opposite ear, antigen was combined with a potent inhibitor of NOS, N(G)-amino-L-arginine (L-NAA). After survival for 24, 48, or 72 hours, the middle ears were evaluated for otitis media. RESULTS: Inhibition of NOS resulted in significantly increased middle ear effusion at all three time periods. This increase was blocked by the addition of excess 1-arginine, which bypasses the inhibitory effects of L-NAA. The infiltration of cells into the middle ear lumen and the hyperplasia of the middle ear mucosa were unaffected by L-NAA administration. CONCLUSIONS: The results suggest that NO is involved in regulating the permeability of the middle ear vascular, the transudation of serum into the middle ear mucosa, and/or the movement of extracellular fluid across the middle ear mucosal epithelium.

Adjuvants, Immunologic↗
PubMed2001

Effect of creatine on performance of militarily relevant tasks and soldier health.

PURPOSE: Determine the short-term effects of creatine supplementation on performance of military tasks, thermoregulation, and health risks. METHODS: Male military personnel were randomly assigned to a creatine (CR; N = 8) or a placebo (CON; N = 8) supplementation group. Testing was conducted at baseline, after a 6-day load phase (20 g/d), and after 4 weeks of taking 6 g/d. Measurements included body composition, liver/kidney function tests, core body temperatures during a 10-mile march and 5-mile run, and performance on physical tasks. RESULTS: Serum and urine creatine increased significantly in the CR group. Body mass and number of pull-ups performed increased significantly in the CR group but not the CON group by week 4. No significant differences between the CR and CON groups were found for other performance measures, body composition, core body temperature, or other biochemical measures. CONCLUSION: Creatine supplementation increased body mass and pull-up performance but did not cause acute health problems. Creatine did not increase core temperature compared with placebo under the environmental conditions of the study, and it is unlikely that creatine will enhance the overall readiness or performance of soldiers.

Adult↗
PubMed2000

LINE L1 retrotransposable element is targeted during the initial stages of apoptotic DNA fragmentation.

Using a directional cloning strategy, DNA sequence information was obtained corresponding to the site of early radiation-induced apoptotic DNA fragmentation within the human lymphoblastoid cell line TK6. Data were obtained from 88 distinct clones comprising approximately 65 kbp of sequenced material. Analysis of all cloned material showed that sequences in the 10 bp immediately adjacent to the cleavage sites were enriched in short oligoT tracts. The proportion of repetitive DNA within the entire cloned material was found to be within the normal range. However the distribution of Alu and LINE repetitive DNA were biased to positions at or adjacent to the apoptotic cleavage site. In particular, a non-random distribution of five cleavage sites was found clustered within the second ORF of the LINE L1 that partially overlapped with two binding sites for the nuclear matrix-associated protein SATB1. Three other clones, containing alpha satellite elements, were also linked to a DNA matrix binding function. These data indicate that the site of chromatin loop formation at the nuclear matrix may be a specific target for early DNA fragmentation events during apoptosis.

Apoptosis↗
PubMed2000

Aggregation studies of humic acid using multiangle laser light scattering.

An aqueous phase study of the naturally occurring dissolved organic carbon humic acid (HA) is performed using multiangle laser light scattering (MALLS) to measure its RMS radius and average molecular weight. A Zimm plot using Berry Formulism and a second-order fit gave an average molar mass of 1.164 x 10(8) g/mol and an average RMS radius (Rz) of 436.0 +/- 36 nm at 25 degrees C.

Environmental Monitoring↗
PubMed2000

The effect of high intakes of casein and casein phosphopeptide on calcium absorption in the rat.

The effect of the level or source of dietary protein or protein-derived peptides on Ca absorption is not well understood. We determined, therefore, the influence of habitual dietary casein level, meal casein and meal casein phosphopeptide (CPP) on Ca absorption in the rat. True fractional Ca absorption was investigated in male 7-week-old rats, Wistar strain, in three separate studies using a faecal 47Sc: 47Ca ratio method. In studies A and C, rats (n 8 per group) were fed on a purified diet containing 200 g casein/kg for 2 weeks. Rats were then given a 47Ca-labelled meal (10 g) containing (per kg) either 0, 100, 200, or 300 g casein (study A) or 0, 100, 200, 350 or 500 g CPP (study C). In study B, rats (n 24 per group) were fed on a purified diet containing (per kg) either 200, 350 or 500 g casein for 2 weeks. Each group was then further randomized into three groups (n 8 per group) and given a 47Ca-labelled meal (10 g of the same diet) containing (per kg) either 200, 350 or 500 g casein. Ca absorption from a meal was unaffected by increasing meal casein concentration from 0 to 300 g/kg (study A), but was increased with a meal casein content of 500 g/kg (study B). Fractional Ca absorption decreased with increasing usual dietary casein intake in the range 200-500 g/kg (study B), suggesting intestinal adaptation. Ca absorption was unaffected by inclusion of 100 g CPP/kg in a single meal but was significantly (P < 0.001) reduced by 200, 350 and 500 g CPP/kg meal, with no evident dose-relationship. Thus, while Ca absorption was enhanced by high-casein meals, the mechanism remains unclear.

Animals↗
PubMed2000

Active immunization with angiotensin I peptide analogue vaccines selectively reduces the pressor effects of exogenous angiotensin I in conscious rats.

1. Male, Sprague-Dawley rats were actively immunized with novel angiotensin vaccines, and their pressor responses to exogenous angiotensin I (AI) and angiotensin II (AII) were assessed in vivo. Serum antibody titres were also measured. 2. The most effective vaccine consisted of an AI analogue conjugated with a tetanus toxoid carrier protein and adjuvanted with aluminium hydroxide. When this vaccine was injected on days 0, 21 and 42, pressor responses to AI on day 63 were significantly inhibited (maximum, 8.9 fold shift), but responses to AII were unaffected. The anti-angiotensin antibody titre was increased 32,100 fold, and, uniquely, these antibodies also cross-reacted with angiotensinogen. 3. These findings indicate that active immunization against AI may be a useful approach for treating cardiovascular disorders involving the renin-angiotensin system.

Algorithms↗
PubMed2000

Regional haemodynamic effects of recombinant murine or human leptin in conscious rats.

Regional haemodynamic responses to recombinant murine or human leptin were assessed in conscious, chronically-instrumented, male, Long-Evans rats (350 - 450 g). Human, but not murine, leptin caused a slight hindquarters vasoconstriction, but neither peptide had any effect on mean arterial blood pressure or heart rate. In the presence of the beta(2)-adrenoceptor antagonist, ICI 118551, a hindquarters vasoconstrictor response to human leptin was not seen, and there was a tachycardia, as there was to murine leptin. The nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, (L-NAME), did not influence the cardiovascular effects of murine or human leptin. The results indicate that the previously reported sympathoexcitatory effects of murine leptin in anaesthetized rats are not manifest as regional haemodynamic changes in conscious rats, and this is not due to beta(2)-adrenoceptor-mediated vasodilator mechanisms opposing any vasoconstrictor responses. Moreover, the ability of L-NAME to unmask a pressor effect of murine leptin in anaesthetized rats may not be apparent in the conscious state.

Adrenergic beta-Antagonists↗
PubMed2000

Cardiovascular effects of endothelin-1 and endothelin antagonists in conscious, hypertensive ((mRen-2)27) rats.

SB 209670 is a potent antagonist of the vasoconstrictor (ET(A)- and ET(B)-receptor-mediated) and vasodilator (ET(B)-receptor-mediated) effects of endothelin, whereas SB 234551 is relatively selective for the constrictor (ET(A)-receptor-mediated) effects. Since we had previously found SB 209670 exerted antihypertensive, vasodilator effects in conscious, heterozygous, transgenic ((mRen-2)27) (abbreviated to TG) rats, here we compared the two antagonists in that model, and assessed their chronic effects on responses to exogenous endothelin-1. We did this to test our global hypothesis, namely, that SB 209670, but not SB 234551, would cause inhibition of the depressor effects of exogenous endothelin-1 in vivo, and that this differential effect would be associated with a more marked antihypertensive action of SB 234551 in TG rats. SB 209670 and SB 234551 (infused for 50 h) exerted similar, sustained, antihypertensive effects in TG rats. The antihypertensive effects of the antagonists occurred at times when the pressor effects of exogenous endothelin-1 were not significantly inhibited. Furthermore, SB 234551 did not exert a greater antihypertensive effect than SB 209670 at a time (i.e., 2 - 4 h) when the depressor effects of endothelin-1 were abolished by the latter, but not by the former (although this differential action was lost after 24 h infusion). The results caused us to reject the hypothesis that selective antagonism of the vasoconstrictor effects of endothelin-1 would result in SB 234551 exerting a greater antihypertensive effect than SB 209670 in TG rats.

Anesthetics↗