Search PubMed⌕ Search

Biomedical subjects

E MacDonald

Publications and source records attributed to E MacDonald.

At least 109 records · Page 6Linked to original sources
PubMed1984

Cardiovascular effects of copper in pithed rats.

The pithed rat preparation was used to study the effects of copper (as cupric chloride) on the release and re-uptake of noradrenaline from sympathetic nerves. At the highest concentration which could be tested without failure of the preparation, there was a slight prolongation in the duration of the tachycardia obtained by electrical stimulation of the cardioacceleratory nerves to the heart. However, the tachycardia obtained after intravenous injection of tyramine was also similarly prolonged from which it is concluded that the phenomenon is not related to inhibition of neuronal re-uptake but is more likely due to alterations in the metabolism of noradrenaline or in the factors governing its diffusion from the synapse. Copper itself caused a dose-dependent increase in blood pressure which was not due to release of noradrenaline from sympathetic neurones. In addition to its own vasoconstrictor effect, it inhibited the increase in blood pressure obtained after administration of phenylephrine, tyramine and vasopressin. Since the extent of the inhibition of all three compounds was similar, it is concluded that the effect is non-specific inhibition of blood vessel contractility. In the pithed rat preparation, as in the chick biventer preparation (Lin-Shiau & Fu 1980), the acute effects of copper seem to be more clearly seen on muscle with little evidence being available to support potent neurotoxicity.

Animals↗
PubMed1983

RBC membrane adenosine triphosphatase activities in patients with major affective disorders.

Red blood cell Na+, K+-, Mg2+-, and Ca2+-adenosine triphosphatase (ATPase) activities were studied longitudinally in eight patients with affective disorders and 12 healthy volunteers. The patients had a higher mean Ca2+-ATPase activity than the volunteers, and the fluctuations in all three ATPase activities were greater in the patients than in the volunteers. Even though the mean Ca2+-ATPase activity was higher during manias and euthymic periods than during depressions, mood and ATPase activities did not correlate with each other in all patients. Lithium carbonate treatment did not alter the ATPase activities, and the quantity of vanadium present in the membranes could not account for the variations in the enzyme activities observed. We suggest that either the RBCs of manic-depressive patients are very sensitive to fluctuations of a lipophilic ATPase activity--regulating factor present in plasma or the patients have at times high levels of such a factor. In some patients, the level of this hypothesized regulator may fluctuate in synchrony with mood changes.

Adenosine Triphosphatases↗
PubMed1981

Homovanillic acid and 5-hydroxyindoleacetic acid levels in cerebrospinal fluid of patients with senile dementia of Alzheimer type.

The possibility of disturbed dopamine and serotonin metabolism in senile dementia of Alzheimer type was studied. The basal concentrations of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in cerebrospinal fluid (CSF) were studied in 28 patients with senile dementia of Alzheimer type and in 13 controls of similar age with no neurological disease. The concentrations of HVA were significantly reduced in the dementia patients compared to the concentrations of the controls. The values of HVA were also significantly reduced in the most severely demented patients compared to the less severely demented ones. There was a slight but statistically significant decrease in the 5-HIAA levels in the dementia patients compared to the levels of the controls. The 5-HIAA levels were reduced in the most severely demented patients compared to the controls but not when compared with the less severely demented patients. It is concluded that in severe forms of senile dementia of Alzheimer type, there is a decrease in the levels of HVA and 5-HIAA in CSF which may reflect a decreased turnover of dopamine and serotonin. Patients diagnosed as senile dementia of Alzheimer type, but with less severe symptoms, had levels of HVA and 5-HIAA similar to controls.

Aged↗
PubMed1981

L-tryptophan-carbidopa trial in patients with long-standing progressive myoclonus epilepsy.

Eleven patients with long-standing progressive myoclonus epilepsy, PME, and age- and sex-matched epileptic controls received L-tryptophan (L-Trp) 100 mg/kg body weight combined with carbidopa in addition to their usual anticonvulsant regimen. During six weeks of the trial an improvement in activities of daily living and a decrease of action myoclonus was noted in the PME patients. The frequency of seizures compared with the past year decreased significantly in the PME patients, but not in the epileptic controls. Changes in the EEGs of the PME patients were scant, but a slight decrease was noted in myoclonic spikes. Both plasma Trp and platelet 5-HT increased significantly and at least as much as in epileptic controls. 5-HIAA and HVA concentrations in the CSF of the PME patients increased significantly during the trial. The results support previous findings concerning Trp treatment in PME, and longer trials with Trp + carbidopa could be of value in this disease.

Blood Platelets↗
PubMed1981

Pharmacological and toxicological properties of 4-hydroxypyrazole, a metabolite of pyrazole.

The effects of 4-hydroxypyrazole (4-HP), a principal metabolite of pyrazole, were studied in mice. The compound was toxic, much more so than pyrazole with an LD50 of 1.1 mmol/kg (92 mg/Kg) and doses greater than 1.5 mmol/kg (126 mg/kg) were almost invariably fatal. Toxicity seemed to be centered on the liver with microscopic evidence of centrolobular necrosis apparent. Mouse liver catalase was almost totally inhibited 1 hour after administration of 1 mmol/kg of 4-HP. Tryptophan pyrrolase was also inhibited 4-HP seemed to penetrate into the brain as judged by inhibition of brain catalase activity. A slight increase in brain serotonin concentration was found but 4-HP had no effect in the doses used (1.5 mmol/kg or 4 x 1.0 mmol/kg) in brain or heart noradrenaline. We conclude that the pyrazole-induced decrease in brain noradrenaline is not mediated via 4-HP. Furthermore, simultaneous treatment with methanol and pyrazole, which prevents the formation of 4-HP, did not prevent the decrease in brain noradrenaline levels. Since methanol prevented the pyrazole-induced decrease in brain catalase activity, we can also rule out the possibility that the decrease in brain noradrenaline is secondary to pyrazole-induced inhibition of brain catalase. It is concluded that though 4-HP is an active metabolite of pyrazole, causing, in particular, the hepatotoxicity of the parent molecule, it is not responsible for all the varied biological of pyrazole.

Animals↗
PubMed1981

Studies on the mechanism of action of the abortive effect of 6-hydroxydopamine in rats.

Administration of repeated large doses of 6-hydroxydopamine (6-OHDA)(100 mg/kg) to pregnant rats causes a 75% decrease in the litter size, which is accounted for a corresponding increase in the number of foetuses resorbed or stillborn. Guanethidine, which like 6-OHDA, causes a prolonged sympathectomy did not interfere with the course of the pregnancy nor did bethanidine which interferes with sympathetic transmission without causing ultrastructural damage. When 6-OHDA was given only prior to mating the abortive effect was no longer present, even though the concentration of noradrenaline in the peripheral sympathetic nerves was reduced for the entire duration of the pregnancy. The reported alpha-adrenoreceptor blocking effects of 6-OHDA are not exclusively responsible for the abortive effect, since injection of sympathectomised rats with phentolamine (10 mg/kg) had no abortive effect. There were normal concentrations of noradrenaline in the brains of pups born to mothers treated during pregnancy with 6-OHDA. Whether the same is true of those foetuses resorbed, remains unresolved. It seems likely that the abortive effect is not related to the depletion of noradrenaline but is due to other effects of 6-OHDA.

Abortifacient Agents↗
PubMed1980

Homovanillic acid and 5-hydroxyindoleacetic acid levels in cerebrospinal fluid of patients with progressive myoclonus epilepsy.

The possibility of disturbed dopamine and serotonin metabolism in the progressive myoclonus epilepsy (PME) occurring in Finland (a type of PME without Lafora bodies) was examined. Both basal concentrations of HVA and 5-HIAA in the CSF and their increase after oral probenecid administration were studied in 19 PME patients and in 19 age- and sex-matched control patients. The control patients had grand mal epilepsy but not myoclonus or ataxia. The basal value of HVA was significantly reduced and that of 5-HIAA was also slightly reduced in the PME patients as compared to the values of the epileptic controls or to those of 26 nonepileptic controls. The concentrations of HVA and 5-HIAA also seemed to correlate with the severity of the PME. The most severely affected patients had generally the lowest values. After oral probenecid this trend was also seen when the increases of HVA and 5-HIAA were expressed per microgram CSF probenecid, i.e. the mildly affected PME group showed higher increases in response to probenecid than the most severely affected PME group. The PME patients had higher probenecid levels in the CSF than the epileptic controls.

Adult↗
PubMed1980

Reappearance of Sporothrix schenckii lesions after administration of Solu-Medrol R to infected cats.

In 10 of 34 adult cats infected with Sporothrix schenckii, demonstrable lesions healed spontaneously in 31 to 88 days after inoculation of the organism. None of 5 untreated cats developed additional visible lesions during the period of observation, nor were they positive for S. schenckii by culture at necropsy. Five animals were treated with Solu-Medrol R to determine if the apparent clinical cure was also accompanied by a mycological cure. Lesions reappeared at, or near, the site of the original lesions in 3 of the 5 treated cats from 4 to 6 months after the initial lesions healed. Fungi were cultured both from the regional lymph node and from exudate of the skin lesions. Thus, it appears that viable S. schenckii may be sequestered in tissues for at least 6 months without showing clinical evidence of their presence. Moreover, apparently "healed" lesions may be reactivated and progress to typical demonstrable skin lesions following immuno-suppression.

Animals↗
PubMed1978

Role of nucleotides in tubulin polymerization: effect of guanosine 5'-methylene diphosphonate.

Incubation of purified rat brain tubulin with guanosine 5'-methylene diphosphonate [GMP(CH2)P] (1 mM), a GDP analog resistant to hydrolysis, results in the polymerization of 20-30% of the total tubulin present. Analogous incubations with GDP (1 mM) do not result in tubulin polymerization. Polymerization with GMP(CH2)P occurs in the presence of alkaline phosphatase (EC 3.1.3.1) under conditions that completely hydrolyze the likely phosphate donors (GTP, GDP, and GMP) as well as the potential product [GMP(CH2)PP] of the transphosphorylase activity present in purified tubulin preparations. Tubulin polymerization in vitro thus can occur in the absence of gamma-phosphate and phosphate bond hydrolysis at the exchangeable nucleotide-binding site of tubulin. Polymerization of tubulin by GMP(CH2)P is neither prevented nor reversed by concentrations of calcium (2 mM) that prevent microtubule assembly and disrupt already formed microtubules induced by GTP. However, tubulin polymerized with GMP(CH2)P is readily depolymerized by cold (4 degrees, 30 min). The possible involvement of GTP alpha-beta bond hydrolysis must be considered seriously as playing a role in the process of microtubule depolymerization.

Alkaline Phosphatase↗
PubMed1977

Role of nucleotides in tubulin polymerization: effect of guanylyl 5'-methylenediphosphonate.

Incubation of 48,000 X g rat brain supernatants for 30 min at 37 degrees with 1-2 mM guanylyl 5'-methylenediphosphonate [Gmp(CH2)pp] results in polymerization of 95-98% of the tubulin present. This is considerably more than the 50% polymerization that can be achieved with the natural nucleotide, GTP, under optimal conditions. Gmp(CH2)pp is also much more effective than GTP in inducing polymerization of purified tubulin. Assembly of microtubules with Gmp(CH2)pp occurs at tubulin concentrations one-third of those possible with GTP. Furthermore, with Gmp(CH2)pp, microtubule assembly does not require the high molecular weight basic proteins needed with GTP. Polymerization of tubulin by Gmp(CH2)pp is neither prevented nor reversed by concentrations of calcium (2 mM) that can either prevent microtubule assembly or disrupt already formed microtubules if the nucleotide used is GTP or guanylyl imidodiphosphate. When Ca2+ is added before or after microtubule assembly, electron microscopy of the Gmp(CH2)pp preparations reveals normal microtubules turning into twisted ribbons. Low temperature (4 degrees) can both prevent and disrupt the tubulin assembled Gmp(CH2)pp although disruption proceeds much more slowly when GTP is used.

Animals↗
PubMed1977

Evidence for inhibition of dopamine-beta-hydroxylase in vivo after sub-acute pyrazole treatment in rats.

Pyrazole, a widely used inhibitor of alcohol dehydrogenase, has been shown to cause a decrease of brain and heart noradrenaline (NA). An attempt to explain the mechanism of this effect is now described. L-DOPA (50-200 mg/kg, s.c.) was unable to restore brain or heart noradrenaline levels in pyrazole pre-treated rats. After monoamine oxidase inhibition with tranylcypromine or pargyline there was a slight increase in brain NA in these rats but no further increase was observed in response to L-DOPA (30 mg/kg). Brain dopamine levels were relatively higher in pyrazole pre-treated rats. This difference was particularly clear in the hypothalamus but not present at all in striatum. It was impossible to duplicate the above results using nialamide as the monoamine oxidase inhibitor. After depletion of monoamine stores by reserpine (2 x 2 mg/kg) or oxypertine (75 mg/kg) and treatment with tranylcypromine and L-DOPA it is possible to get an indication of the maximal rate of synthesis of NA. In pyrazole treated rats synthesis of NA in brain was 70% reduced and about 50% reduced in heart. Synthesis of dopamine from L-DOPA was unimpaired. Dopamine-beta-hydroxylase activity in the hypothalamus of rats treated for four days with pyrazole (100 mg/kg i.p.) was more than 40% reduced. This inhibition could not be obtained by addition of pyrazole to samples of purified dopamine-beta-hydroxylase. The results strongly suggest that the reason for the decrease in brain and peripheral NA seen after pyrazole administration in rats is due to inhibition of dopamine-beta-hydroxylase.

Animals↗
PubMed1977

Effects of pyrazole treatment of physical status and brain biogenic amines in rats.

The recovery of brain noradrenaline (NA) from a single dose of 100 mg/kg pyrazole was rapid, but after 500 mg/kg brain NA levels were still maximally reduced 3 days later and did not return to normal until 7 days after injection. The consumption of water followed a similar time course at this dose. Sub-acute experiments were carried out in two sets of animals: those with free access to food and water throughout the experiment and those which during the latter half of the experiment received a known, restricted quantity of food and fluid by gastric intubation. Diet restriction did not alter the pyrazole induced decrease in brain NA and potentiated the decrease observed in the heart. A significant increase in brain 5-hydroxyindoleacetic acid was observed with pyrazole 100 mg/kg in both diet schedules. In addition to the disturbances in food and water consumption, pyrazole also caused a decrease in locomotor activity which was only partly due to the starvation. Rectal temperature did not change. At the higher pyrazole dose in the rats fed by intubation there was incomplete emptying of the stomach. It is concluded that these many changes demonstrate the non-specificity of pyrazole and caution is advocated in its use combined with ethanol in research on experimental alcoholism.

Animals↗