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Biomedical subjects

E MacDonald

Publications and source records attributed to E MacDonald.

At least 73 records · Page 4Linked to original sources
PubMed1992

Advanced glycosylation end products in the mesenteric artery.

We measured advanced glycosylation end products in the mesenteric artery of 37 patients (ages 29-82 years), 34 of whom were nondiabetic. Samples of arterial tissue were obtained during bowel resectioning. Advanced glycosylation end products were measured as collagen-linked fluorescence (excitation wavelength 370 nm, emission wavelength 440 nm) after collagenase digestion of tissue samples. Mean fluorescence of the arterial samples was 15 U/mg (range 5.3-27). Collagen fluorescence correlated with patients' age (r = 0.57; P less than 0.001). No difference in the collagen-linked fluorescence was observed between men and women (P = 0.63), hypertensive and normotensive patients (P = 0.44), smokers and nonsmokers (P = -0.52), and patients with and without symptomatic coronary heart disease (P = 0.7). This study demonstrates, for the first time, the relationship between collagen-linked fluorescence and patients' age in human arterial tissue ex vivo.

Adult↗
PubMed1992

Dexmedetomidine-induced ocular hypotension in rabbits with normal or elevated intraocular pressures.

This study covered the ocular hypotensive effects of the stereoisomers of the alpha 2-adrenoceptor agonist medetomidine. The dextro-isomer, dexmedetomidine, is known from pharmacologic experiments to be a specific, potent, and selective full agonist at alpha 2-adrenoceptors, whereas the levo-enantiomer seems to be almost inactive. Thus, the levo-isomer (0.5 mg/ml, 25 microliters) had no significant effect on intraocular pressure. After unilateral topical administration, dexmedetomidine (0.5 mg/ml, 25 microliters) lowered intraocular pressure bilaterally in normal rabbits and in rabbits with intraocular pressure elevated after laser irradiation of the pigmented trabecular band of the anterior chamber angle. In the treated (ipsilateral) eye of normal rabbits, a maximum decrease of 4.6 +/- 0.6 mmHg was observed at 2 hr post treatment. In the contralateral eye, the maximum decrease was 4.1 +/- 0.5 mmHg at 1 hr after treatment. In rabbits with laser-induced elevation of intraocular pressure, the maximum decrease in treated hypertensive eyes was 13.5 +/- 0.3 mmHg 1 hr after dexmedetomidine administration. These results indicate that the selective alpha 2-adrenoceptor agonist, dexmedetomidine, is a potent and effective drug for decreasing intraocular pressure in rabbits.

Administration, Topical↗
PubMed1991

The effect of medetomidine on GABA and benzodiazepine receptors in vivo: lack of anxiolytic but some evidence of possible stress-protective activity.

Medetomidine, a new selective alpha 2-adrenoceptor agonist, potentiated bicuculline seizures in mice. In vivo pretreatment with medetomidine in mouse cerebral cortex reduced dose-dependently (2.5-100 micrograms/kg) GABA-potentiated 3H-flunitrazepam binding. The affinity of 3H-muscimol was also reduced by medetomidine. This effect of medetomidine on GABA-potentiated benzodiazepine binding was reversed by pretreatment with atipamezole (1 mg/kg), a specific alpha 2-antagonist. In an elevated plus-maze model of anxiety medetomidine (0.5-10 micrograms/kg) was inactive both in rats and mice and did not antagonize the behavioural effects of an anxiogenic beta-carboline, DMCM. However, at lower doses medetomidine (10 but not 50 micrograms/kg) antagonized the swimming stress caused increase of central benzodiazepine binding sites (labeled with 3H-Ro 15-1788) in mouse cerebral cortex. The increase of peripheral benzodiazepine binding sites on brain and heart cryostat cut slices caused by stress was also antagonized by pretreatment with medetomidine. The behavioural and biochemical data obtained in this study are evidence that medetomidine does not have anxiolytic effect but may have, in lower doses, stress-protective activity.

Animals↗
PubMed1991

Comparison of the behavioral and neurochemical effects of the two optical enantiomers of medetomidine, a selective alpha-2-adrenoceptor agonist.

Medetomidine (MED) is a veterinary sedative whose mode of action is activation of alpha-2 adrenoceptors. Because the carbon atom which separates the two ring systems is methylated, there is a center of stereochemical asymmetry in the molecule. The resulting enantiomers, d-MED and l-MED have recently become available for study. The biological activity of MED, as is now demonstrated in rats in vivo, seems to reside almost exclusively in the d-MED form. Only at extremely high doses (e.g., 10 mg/kg) does l-MED exert any effects, interpreted as alpha-2 adrenoceptor antagonism. In contrast, doses of d-MED as low as 30 micrograms/kg cause sedation, hypothermia and induce neurochemical changes in norepinephrine and 5-hydroxytryptamine metabolism in brain characteristic of alpha-2-agonists (decreases in concentrations of biogenic amine metabolites, turnover and increases in concentration of parent amine). The most sensitive neurochemical indicator of the alpha-2-agonist action of d-MED was the concentration of unconjugated 3-methoxy-4-hydroxy-phenyethylene glycol in rat cerebral spinal fluid, doses of d-MED as low as 10 micrograms/kg caused a significant reduction in this norepinephrine metabolite. Simultaneous administration of the specific alpha-2 adrenoceptor antagonist, atipamezole (1 mg/kg), effectively inhibited the behavioral and most of the neurochemical actions of d-MED (100 micrograms/kg). It is concluded that the enantiomers of MED may be extremely useful in elucidating structure action relationships at alpha-2 adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1990

Determinants of functional health of older persons.

The study investigated relationships among demographics, self esteem, health locus of control, health promotion behaviors, perceived health and functional health ratings in 179 older men and women from 65 to 99 years. Canonical correlation and stepwise discriminant analyses demonstrated several meaningful and significant relationships suggesting that exercise and nutrition may be critical health promotion activities associated with better scores on five functional dimensions. The 85+ years age group differed from younger groups through having significantly higher reported exercise scores.

Activities of Daily Living↗
PubMed1990

Changes in rat brain monoamines, monoamine metabolites and histamine after a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Male Long-Evans rats were given 50 micrograms/kg 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intraperitoneally and after 1, 4, 28 or 76 hr, noradrenaline, dopamine, dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA), tryptophan and histamine were measured in the brain (dissected into ten parts) as well as in the pituitary gland. Several slight but significant changes were observed, e.g. in the hypothalamus where HVA and 5-HIAA were decreased after 4 hr, noradrenaline was decreased after 76 hr and histamine increased after 28 hr. Several late changes were also found, conspicuously tryptophan was increased in most brain areas after 76 hr and in some cases earlier; these changes may be due to starvation after hypophagia rather than TCDD directly. The results demonstrate that TCDD causes changes in brain neurotransmitter systems, but the changes are minor and it is not likely that aminergic systems are the key mediators in TCDD-induced hypophagia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Effects of 2,4-dichlorophenoxyacetic acid (2,4-D) on biogenic amines and their acidic metabolites in brain and cerebrospinal fluid of rats.

Effects of single subcutaneous doses of sodium 2,4-dichlorophenoxyacetate (2,4-D-Na) on biogenic amines and their acidic metabolites in rat brain and cerebrospinal fluid (CSF) were analyzed by high pressure liquid chromatography. After 200 mg/kg 2,4-D-Na, the cerebral concentration of 5-hydroxytryptamine (5-HT) was increased slightly and that of 5-hydroxyindoleacetic acid (5-HIAA) roughly 3-fold between 1 and 8 h after the administration. There was also a tendency towards slightly lowered dopamine (DA) levels. No statistically significant changes in brain concentrations of noradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) or tryptophan (TRY) were found. At the same time, however, the maximal increase in DOPAC, HVA and 5-HIAA concentrations in the CSF was 2.3-5.8-fold. The dependency of biogenic amines and metabolites on 2,4-D-Na dose was studied by injecting s.c. 0, 10, 30 and 100 mg/kg and sacrificing the rats at 2 h. In the brain, there was a dose-dependent increase in concentrations of 5-HIAA (at the two highest doses) and HVA (at the highest dose) while in the CSF those of all three acidic metabolites increased at the two highest doses. The 10 mg/kg dose had no effect. The results agree with the hypothesis that 2,4-D inhibits the organic acid transport out of the brain, which should then result in increased cerebral levels of acidic metabolites of biogenic amines, but it may also have effects on the activity of serotoninergic and dopaminergic neurones.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1989

Medetomidine--a novel alpha 2-adrenoceptor agonist: a review of its pharmacodynamic effects.

1. The pharmacodynamic effects of medetomidine, a novel alpha 2-adrenoceptor agonist, are reviewed. 2. In receptor binding experiments, and in isolated organ preparations medetomidine shows high specificity and selectivity to alpha 2-adrenoceptors. Its alpha 2/alpha 1 selectivity ratio is 1620 compared to 220 of clonidine. It is a highly potent full agonist at alpha 2-adrenoceptors, a fact that also distinguishes it from clonidine. 3. Medetomidine induces a dose-dependent decrease in the central release and turnover of norepinephrine (NE) measured as changes in metabolite concentrations or using pharmacological intervention techniques. 4. The selectivity, specificity and potency of medetomidine is further supported by various in vivo experiments showing dose-dependent hypotensive, bradycardic, sedative, anxiolytic mydriatic, hypothermic and analgesic effects. 5. The pharmacological, neurochemical and behavioral effects of medetomidine can be inhibited by prior, simultaneous or subsequent administration of selective and specific alpha 2-antagonists. 6. In humans medetomidine is well-tolerated and pharmacodynamic effects including e.g. dose-dependent decrease of vigilance, blood pressure, heart rate, salivary secretion and plasma NE are compatible with an agonistic action at alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1989

Aneurysmal subarachnoid hemorrhage.

To be able to understand and manage the devastating condition of subarachnoid hemorrhage due to ruptured aneurysm, the neuroscience practitioner needs to be thoroughly cognizant of its causes, symptoms, diagnosis and treatment. This article presents a descriptive review and current update of these factors. The high morbidity and mortality in survivors of initial subarachnoid hemorrhage is mainly due to development of complications of hydrocephalus, hypothalamic dysfunction, rebleeding and vasospasm. A thorough knowledge of their causes, symptoms, times of occurrence and treatment is vitally important. This article also discusses complications with emphasis upon studies being done and proposed new methods of therapy.

Humans↗
PubMed1989

An introduction to the pharmacology of alpha 2-adrenoceptors in the central nervous system.

alpha 2-Adrenoceptors mediate a variety of physiological functions in the central nervous system and in peripheral tissues; thus, the use of pharmacological agents either activating or blocking these receptors results in a mixture of responses from several organs and tissues. This may be utilized therapeutically in some situations. In anaesthesiology, alpha 2-adrenergic agonists are already widely used as veterinary sedative-analgesics, and it is now clear that they are also capable of potentiating the effects and reducing the required dosage of other drugs used in anaesthesia (barbiturates, volatile anaesthetics, narcotic analgesics). In addition, they attenuate sympatho-adrenal responses to noxious stimuli encountered during anaesthesia and surgery, providing improved hemodynamic, metabolic and hormonal stability. Recent results from molecular biology, biochemistry and pharmacology point to the existence of distinct alpha 2-adrenoceptor subtypes. The identification of such subpopulations of alpha 2-adrenoceptors may provide new opportunities for the development of subtype-selective pharmacological agents with more specific therapeutic actions.

Adrenergic alpha-Agonists↗
PubMed1989

Effects of acute administration of medetomidine on the behaviour, temperature and turnover rates of brain biogenic amines in rodents and reversal of these effects by atipamezole.

The effects of acute administration of medetomidine in rodents were examined. Low doses (2.5 micrograms/kg) were anxiolytic, higher doses (10-100 micrograms/kg) sedating, and above 100 micrograms/kg medetomidine treated rats lost their righting reflex and were hypothermic. These higher doses of medetomidine inhibited the release of noradrenaline (NA), dopamine and serotonin in the central nervous system, inhibition of NA release being the most sensitive to medetomidine. All the above effects could be antagonized by administration of suitable doses of the alpha 2-antagonist, atipamezole, indicating that the actions of medetomidine were mediated via activation of alpha 2-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1988

Behavioural and neurochemical effects of medetomidine, a novel veterinary sedative.

The effects of the novel veterinary sedative, medetomidine, were studied in rats. In addition to a dose-dependent sedation, which at high doses (greater than 100 micrograms/kg) included loss of the righting reflex and hypothermia, there was a concurrent decrease in the turnover rate of biogenic amines in the brain. Noradrenaline turnover was dose dependently decreased as judged by (i) the decrease in the brain concentration of its metabolite, MHPG-SO4, (ii) a decrease in the ability of alpha-methyl-p-tyrosine methyl ester to deplete brain noradrenaline stores and (iii) a dose-dependent decrease in the level of unconjugated MHPG in the CSF of freely moving rats. Brain dopamine turnover was also inhibited at higher doses as judged by the alpha-methyl-p-tyrosine method and by a decrease in the concentration of HVA in the rat brain 4 h after medetomidine. Serotonin turnover as estimated by the ratio of biogenic amine to its metabolite was also significantly depressed. These changes in brain biogenic amine turnover were inhibited by prior or simultaneous administration of alpha 2-adrenoceptor antagonists, either yohimbine or the more specific, novel alpha 2-antagonist, atipamezole.

Adrenergic alpha-Agonists↗
PubMed1988

Behavioural and neurochemical effects of antipamezole, a novel alpha 2-adrenoceptor antagonist.

The effects of antipamezole (MPV-1248), a novel selective and specific alpha 2-adrenoceptor antagonist, were studied on monoamine metabolism in rat brain and CSF. In addition, the ability of the drug to antagonize the behavioural and neurochemical effects of two alpha 2-adrenoceptor agonists, detomidine and medetomidine, was assessed. Atipamezole, 0.03-3.0 mg/kg, had no gross behavioral effects on the rats. Above 3 mg/kg, the rats showed increased vocalization and some hostility, rapid breathing and piloerection. The drug caused dose-dependent, rapid and relatively long-lasting increase in the central turnover of noradrenaline (NA) as reflected by increases in the levels of the major metabolites of NA in brain and CSF and an increase in the depleting effect of alpha-methyl-para-tyrosine on brain NA levels. An increase in the turnover of serotonin (5-HT) in brain was indicated by a decrease in the concentration of 5-HT and a corresponding increase in the level of its metabolite, 5-hydroxyindoleacetic acid. Atipamezole was able to antagonize the sedative, hypothermic and neurochemical effects of two potent alpha 2-agonists, detomidine and medetomidine. These results give support for the characterization of atipamezole as a potent antagonist at central alpha 2-adrenoceptors with a rapid onset of action.

Adrenergic alpha-Antagonists↗
PubMed1988

Early postnatal treatment with propranolol affects development of brain amines and behavior.

The present study examined the effects of early postnatal treatment with a beta-adrenoceptor antagonist propranolol (5 mg/kg IP daily) on concomitant and subsequent behavior and central aminergic transmission in rats. During propranolol exposure from the 7th to the 20th postnatal days sleep-wake recordings, carried out with the static charge sensitive bed (SCSB) method, showed a decrease in the percentage of active sleep and an increase in waking. When the animals were 1-3 months of age, the open field behavior was changed, immobility time in the Porsolt's swim test was lengthened, and voluntary alcohol consumption was increased in the propranolol-treated rats. Neither motor reactivity to auditory stimuli nor spontaneous alternation behavior was affected. At the age of 4 months concentrations of brain amines and their metabolites were measured from several brain regions. In the propranolol-treated rats the noradrenaline levels were increased in the limbic forebrain and cerebellum. The results suggest that in rats the exposure to propranolol during the rapid growth period of cerebral catecholamine systems, and the concomitant alterations in sleep are related to later changes in behavior and to increased noradrenaline content in the limbic forebrain and cerebellum.

Acoustic Stimulation↗
PubMed1988

Subchronic treatment with vanadate does not potentiate the toxicity of cardiac glycosides.

Since it has been claimed that vanadate is an endogenous regulator of Na/K-ATPase activity and that it potentiates the toxicity of cardiac glycosides, we were alarmed to discover that certain Finnish physicians were prescribing vanadate in combination with other trace minerals to elderly patients for many different chronic diseases (e.g., cancer, rheumatism). To study the interaction of vanadate and cardiac glycosides, we fed vanadate in the drinking water (25 micrograms/mL) to guinea pigs for 20 d, and studied either their sensitivity to the acute toxicity of the cardiac glycoside ouabain or whether the vanadate would influence the subacute toxicity of ouabain. Vanadate had no influence on the toxicity of ouabain either acute or subchronically administered, nor was there any sign of inhibition of Na/K-ATPase activity as measured by 86Rb-uptake into intact erythrocytes (RBCs), RBC content of sodium or potassium or Na/K-ATPase activity in RBC membranes prepared from the vanadate-treated guinea pigs. Vanadate had been absorbed in substantial quantities from the gastrointestinal tract, since serum, heart, liver, and especially kidney contained measurable amounts of vanadium in contrast to controls, but it is concluded that this vanadate is not in a biologically active form.

Animals↗