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Biomedical subjects

S J Lewis

Publications and source records attributed to S J Lewis.

At least 181 records · Page 10Linked to original sources

Effects of the NMDA receptor antagonist MK-801 against amygdaloid-kindled seizures in the rat.

The effects of acute and subchronic administration of the noncompetitive NMDA receptor antagonist MK-801 on the duration and severity of amygdaloid-kindled seizures in rats were determined to evaluate its anticonvulsant activity. Both the highest acute (1000 micrograms/kg) and subchronic regimens (2 x 300 micrograms/kg, 7 days) produced significant reductions in the seizure stage and afterdischarge duration. Although ataxia may have affected the seizure stage, MK-801 attenuated the primary afterdischarge suggesting anticonvulsant effects in the fully amygdaloid-kindled rat. Since tolerance develops to the behavioral effects of MK-801, other noncompetitive NMDA antagonists related to MK-801 seem to warrant evaluation as anticonvulsants.

Amygdala↗

Acute intracerebroventricular injections of the mast cell degranulator compound 48/80 and behavior in rats.

The intracerebroventricular (ICV) injection of the mast cell degranulator Compound 48/80 (2.5-2.0 micrograms/kg) produced a marked behavioral syndrome in normotensive rats. The behaviors included head and body shakes, paw tremor, excessive grooming, unusual posture and gait, mild diarrhoea, piloerection, extreme agitation and irritability to touch, and a later phase of sedation. The highest doses (15 and 20 micrograms/kg) also produced catalepsy and episodes of "barrel rolling" (continuous rolling of 1-8 turns around the longitudinal axis). These behaviors were observed for approximately 15-30 min although the sedation and catalepsy were maintained for 90-120 min. A second ICV injection of the 10 micrograms/kg dose of Compound 48/80 given 2 hr after an initial injection of this dose, produced a much reduced response and the numbers of head and body shakes, and episodes of paw tremor and grooming were between 20-30% of those produced by the first injection. The reduced effect of the second injection indicates that the behavioral effects of Compound 48/80 may arise from the acute degranulation of mast cells rather than direct effects on neuronal populations or the cerebral vasculature.

Animals↗

Strain differences in central nervous system concentrations of cholecystokinin between normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats.

The regional brain and spinal cord concentrations of cholecystokinin-octapeptide (CCK-8) were measured in age-matched normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats. The relative order of distribution of CCK-8 in the WKY strain was hippocampus (20.5 +/- 1.3 pmol/g) greater than cortex greater than striatum = hypothalamus greater than midbrain = thalamus greater than spinal cord greater than medulla oblongata/pons (MO/P, 1.6 +/- 0.2 pmol/g) whereas in the SH strain this order was hippocampus (12.9 +/- 0.8 pmol/g) greater than cortex = striatum greater than hypothalamus greater than midbrain greater than thalamus = spinal cord greater than MO/P (1.4 +/- 0.2 pmol/g). The concentrations of CCK-8 in the cerebellum were at the level of assay sensitivity (0.5 pmol/g in both strains). In comparison to the WKY rats, the SH strain had significantly lower levels of CCK-8 in the hippocampus (-37%), cortex (-28%), spinal cord (-23%) and pituitary (-57%). The lowered levels of CCK-8 in the brain of the SH rat may be causally related to, or result from, the cardiovascular, behavioural or morphological abnormalities of this strain.

Age Factors↗

Factors influencing the detachment of a polymer-associated Acinetobacter sp. from stainless steel.

The role of an extracellular polymer secreted by an Acinetobacter sp. attached to stainless steel was investigated. Parameters expected to influence polymer conformation, viz. temperature, pH, ionic strength and the concentration of calcium and magnesium ions, were altered and the resulting detached bacteria enumerated. Increasing both the temperature and pH resulted in increased numbers of bacteria detached. The effects of increasing the concentration of sodium chloride up to 100 mM and magnesium or calcium chloride up to 30 mM were small and, although statistically significant, were considered unlikely to have had major influence on the association of the bacteria with the stainless steel surfaces. Treatments including ultraviolet irradiation of surface-associated bacteria always resulted in removal of greater numbers of bacteria when compared to treatments where irradiation was not employed. The results indicate that an adhesive extracellular acidic polysaccharide may mediate the attachment of the Acinetobacter sp. to stainless steel.

Acinetobacter↗

Serum glucose and insulin levels in normotensive (WKY) and spontaneously hypertensive (SH) rats during and after the cessation of continuous (10 day) clonidine infusion.

The concentrations of glucose were elevated whereas those of insulin were decreased in the sera of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats on day 10 of a continuous subcutaneous infusion of clonidine (10 micrograms kg-1 h-1 for 10 days). Fifteen to 18 h after cessation of infusion, the glucose levels of both strains had fallen to below those of the respective controls whereas the insulin levels remained suppressed. As such the hypoglycaemia may be related to the general increase in metabolic requirements associated with the post-infusion 'withdrawal syndrome'.

Animals↗

Cardiovascular effects of the N-methyl-D-aspartate receptor antagonist MK-801 in conscious rats.

Evidence from microinjection studies in anesthetized rats suggests that central excitatory amino acid pathways using N-methyl-D-aspartate receptors are involved in the regulation of the cardiovascular system. To test the hypothesis that these pathways are tonically involved in the maintenance of or the baroreceptor reflex regulation of cardiovascular function, we have examined the effects of intravenous injection of the centrally acting, noncompetitive N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), on the mean arterial pressure, heart rate, renal sympathetic nerve activity, and behavior of conscious, freely moving sham-operated and sinoaortic baroreceptor-denervated rats. Administration of MK-801 produced, within 5 minutes, dose-dependent elevations in mean arterial pressure, heart rate, and renal sympathetic nerve activity that were sustained for 0.5 to 2.5 hours. For an equivalent dose, MK-801 produced approximately twice the peak changes in mean arterial pressure and heart rate in the sinoaortic baroreceptor-denervated rats than in the sham-operated rats. Pretreatment results were as follows: 1) The ganglion blocker chlorisondamine markedly attenuated the hypertension and tachycardia in the sham-operated and sinoaortic baroreceptor-denervated rats, 2) pretreatment with the alpha 1-adrenergic receptor antagonist prazosin virtually abolished the hypertension, and 3) the beta 1-adrenergic receptor antagonist atenolol markedly reduced the tachycardia. MK-801 also produced stereotypic behaviors and ataxia in the sham-operated and sinoaortic baroreceptor-denervated rats; however, qualitatively and quantitatively similar changes in behavior were induced in the latter by doses approximately five time lower than required in sham operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of renal nerves in experimental hypertension: evaluation of neurogenic mechanisms.

To evaluate neurogenic mechanisms underlying variations in arterial pressure associated with removal of baroreflexes, renal sympathetic nerve activity (RSNA) was recorded in conscious unrestrained rats 1 day and 14 days following sinoaortic deafferentation (SAD) or sham operation. Fluctuations in RSNA and heart rate (HR) were correlated stastistically with moment to moment changes in pressure. One day and 14 days after SAD, the lability of mean arterial pressure (MAP) was increased, whereas the lability of RSNA and HR were reduced at 1 day and unchanged at 14 days. Arterial pressure and RSNA were negatively correlated in sham rats, however in rats with SAD negative correlations were virtually absent and positive correlations appeared only infrequently. These results indicate that SAD reduces variability of both RSNA and HR and that lability of arterial pressure appears to not be driven by variations in sympathetic discharge. To examine the central origins of RSNA in anesthetized rats we blocked neuronal transmission in two vasomotor regions of rostral medulla, rostral ventrolateral medulla (RVLM) and rostral ventromedial medulla (RVMM) using bilateral microinjections of lidocaine. Blockade of either or both RVLM and RVMM produced an equivalent marked reduction in arterial pressure but reduced RSNA to only 40% of control. Ganglionic blockade had little additional effect on arterial pressure but abolished the residual RSNA. These findings suggest that a substantial fraction of RSNA may be non-vasomotor in function and that this activity may originate from spinal sites or from supraspinal sites other than RVLM or RVMM.

Animals↗

Lasers in cardiovascular medicine.

The role of lasers in cardiovascular medicine and surgery is a rapidly evolving and uncertain field. Many alternative percutaneous techniques and technologies for removal of atherosclerotic plaque are under development. However, according to many clinicians, atherectomy devices that bore through occlusions with high speed burrs, shave them away with miniature knives, or micropulverize them with ultrasonic waves will be complements not substitutes to both lasers and balloons. Thus, it is unlikely that a cost-effective substitute for the laser is likely to come from developments in mechanical ablation systems. It is important to keep in mind that peripheral laser angioplasty is still considered of benefit to a small percentage of all candidates for peripheral percutaneous transluminal angioplasty, and that coronary laser angioplasty is strictly investigational. Although more devices may be approved in the next year, only two are available on the open market at publication, and both are approved only for peripheral angioplasty. With the rapid growth in the number of laser manufacturers entering the market, there are ample opportunities for large hospitals with active cardiology and cardiovascular surgery programs to become trial sites. However, the smaller hospital set on entering the market may want to consider only well-established, FDA approved technologies that are reasonably priced.

Angioplasty, Laser↗

The functional status of elderly people admitted to a local authority residential home.

One hundred and forty-one consecutive admissions to a large local authority residential home were studied to assess their functional level. Both panel (71) and emergency (70) admissions were assessed. Forty-seven per cent of the panel admissions came from hospital and 39% from home compared with 4% and 83% of the emergency admissions. Severe mental impairment was found in 22% panel admissions and 34% of emergencies. Dementia was the commonest underlying condition. Inability to cope at home was the most common reason for referral in both groups. The activities of daily living (ADL) were assessed where possible on admission and after two to four weeks. No statistically significant change was found in any aspect of ADL between the two assessments although 9% of the panel and 19% of the emergency group were assessed as being unacceptable for residential care in one function. Residents initially showed a high level of negative attitude to the concept of residential care but this lessened over the four weeks. This study has shown that although new residents are suitable on admission to residential care, they are marginally so and are likely to become more dependent. This has future implications for staff levels and training in residential homes.

Activities of Daily Living↗

Effects of continuous infusions (10 days) and cessation of infusions of clonidine and rilmenidine (S 3341) on cardiovascular and behavioral parameters of spontaneously hypertensive rats.

Clonidine is a centrally acting antihypertensive drug that acts in vivo at both alpha 1- and alpha 2-adrenoceptor sites, whereas rilmenidine (S 3341) is more selective for alpha 2 adrenoceptors. The present study compared the effects of continuous 10-day infusions of clonidine (5 micrograms/kg/hour) with those of rilmenidine (100 micrograms/kg/hour) on various cardiovascular and behavioral parameters in the spontaneously hypertensive rat. The changes in these parameters after cessation of the infusions were also compared. At these rates of infusion, clonidine and rilmenidine produced quantitatively similar reductions in mean arterial pressure (MAP), lability of MAP and cardiovascular responsiveness during normal behaviors such as eating and grooming. Neither drug infusion affected heart rate. The cessation of the clonidine infusion resulted in a "withdrawal" syndrome characterized by prominent rapid eye movement-sleep rebound, and cardiovascular and behavioral disturbances including an increased lability of MAP, exaggerated cardiovascular responses during normal behaviors, tachycardia, and an "opiate abstinence-like" syndrome including head and body shakes. Cessation of rilmenidine infusion resulted in somewhat similar cardiovascular and behavioral disturbances, but unlike clonidine there was a return to normal rapid eye movement sleep without rebound.

Adrenergic alpha-Agonists↗

Velten's mood induction technique: "real" change and the effects of personality and sex on affect state.

As an analogue approach to the study of depressed and elated mood formation, numerous investigators have attempted, with varying results, to induce mood in the laboratory by using variations of Velten's (1968) statements. Inconsistent results and theoretical doubts about situational demand influences have cast doubt on the efficacy of this technique. The present authors contend that "true" induction and the demand condition aspect of the technique both produce affect change. In addition, this study replicated Velten's original paradigm while it assessed the impact of personality traits, sex of subject, and different experimenters on mood inducibility. Ninety-five subjects completed pre-measures of self-esteem, locus of control, defense styles, and depression. Results show that the Velten technique appears to work independently of personality attributes in a college sample, although subject's sex and experimenter effects may well affect response to the induction.

Adult↗

Lack of involvement of endogenous mu-receptor opioids in the hypothermic effects of clonidine in normotensive and spontaneously hypertensive rats.

The effects of successive injections of the alpha-adrenoceptor agonist clonidine (25, 50 and 100 ug/kg given at hourly intervals) on the body temperature of normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats, previously treated for 48 hr with slow release emulsions (subcutaneous) containing either morphine (morphine SR, 100 mg/kg), naloxone (naloxone SR, 80 mg/kg) or no drug (vehicle SR), were examined. The successive injections of clonidine produced dose-dependent falls in body temperature which were quantitatively similar in the vehicle-treated WKY and spontaneously hypertensive rats. The hypothermic effects of clonidine in the morphine-dependent WKY and spontaneously hypertensive rats, and in the naloxone-treated WKY and spontaneously hypertensive rats, were not different to those of the respective vehicle-treated controls. These results suggest that endogenous mu-receptor opioid peptides do not have a major involvement in the hypothermic actions of clonidine, in either normotensive or spontaneously hypertensive rats.

Animals↗

Regional brain concentrations of cholecystokinin in the rat: the effects of kindled and non-kindled seizures.

In an attempt to understand the neurochemical basis of kindling, this study investigated the effects on brain cholecystokinin (CCK) of amygdaloid kindled and non-kindled seizures. Thirteen brain regions were examined in rats sacrificed either 24 hr or 3 weeks after the last kindled seizure, or 24 hr after a suprathreshold stimulation-induced (non-kindled) seizure; and in sham kindled rats. There were no significant differences in CCK immunoreactivity between any of these groups. These results do not confirm a previous report of an increase in CCK in the hippocampus following amygdaloid kindling in the rat.

Animals↗

A medium for the detection of yeasts using a conductimetric method.

A new medium is described for the detection of yeasts using a Malthus microbial growth analyser which measures conductivity. This medium is superior to previous media devised for use in the Malthus, and allows the detection of a wide range of yeasts including those important in food spoilage. The new medium was inferior to existing media used to detect yeasts in the Bactometer 32 instrument which measures impedance.

Colony Count, Microbial↗

Reduced glutamate binding in rat dorsal vagal complex after nodose ganglionectomy.

Quantitative receptor autoradiography with L-[3H]glutamate was employed to examine the distribution and properties of glutamate binding sites in the rat brain 14 days after excision of the right nodose ganglion. Slide-mounted coronal sections of the brain showed reduced L-[3H]glutamate binding in the nucleus tractus solitarius/dorsal motor nucleus of the vagus in the ipsilateral relative to the sham-operated side. Densitometric and saturation analyses of binding data indicated a significant reduction in the density of glutamate binding sites (57% decrease relative to sham), while there was a significant increase in receptor affinity (40% greater than sham). Binding was unaltered in the inferior olivary complex. Glutamate receptors are likely to exist on synaptic nerve terminals of vagal afferent fibres within the nucleus tractus solitarius and on vagal preganglionic neurones within the dorsal motor nucleus of the vagus and/or their dendritic processes within the nucleus tractus solitarius. Additionally, our receptor autoradiographic studies provide evidence for L-glutamate being a transmitter of vagal afferent neurones.

Animals↗