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Biomedical subjects

E Heinonen

Publications and source records attributed to E Heinonen.

At least 91 records · Page 5Linked to original sources
PubMed1980

Uptake of radiocalcium by nerve endings isolated from rat brain: kinetic studies.

1 The uptake of radiocalcium by nerve-ending particles isolated from rat brain was studied in vitro by means of a rapid lanthanum quenching technique. 2 The observed uptake fits a theoretical three-compartment model with two separate uptake phases, a fast, initial phase followed by a late, slow phase. This holds true during control conditions as well as during high-potassium stimulation. 3 The uptake as a function of the external calcium concentration can be described in terms of Michaelis-Menten kinetics during high-potassium stimulation. Under control conditions the fit is clearly applicable but statistically not as good as during potassium stimulation. 4 The affinity for the uptake of calcium remains unchanged under control conditions while during high-potassium stimulation the affinity drastically decreases during the late, slow phase of uptake. 5 During high-potassium stimulation the maximal velocity of calcium uptake is twice that during control conditions. This holds true for both the fast and the slow phases of the uptake. 6 Mg2+ has an inhibitory effect on the uptake, the inhibition being more effective during high-potassium stimulation. Tetrodotoxin has a slight inhibitory effect additional to that extended by Mg2+ during the initial phase of uptake into high potassium stimulated synaptosomes.

Animals↗
PubMed1980

Uptake of radiocalcium by nerve endings isolated from rat brain: pharmacological studies.

1 The uptake of radiocalcium by nerve-ending particles isolated from the striatum of rat brain was studied using lanthanum as a quenching agent. 2 High potassium-induced calcium uptake occurred in two phases: an initial rapid phase and a late slow phase. Following preincubation with CaCl2 2.2 mmol/l for 1 h, dopamine at 1 to 2 x 10(-4) mol/l reduced the high potassium-induced calcium uptake which occurred during the initial rapid phase by 66 and 25% at 2 and 4 s of incubation, respectively, but had no effect on the late slow uptake phase. 3 Haloperidol at 1 x 10(-6) mol/l abolished the inhibitory effect of dopamine on the initial rapid phase of the high potassium-induced calcium uptake. Haloperidol per se had no effect on the calcium uptake. 4 Dibutyryl cyclic adenosine monophosphate at 2.5 x 10(-3) mol/l or prostaglandin E1 (PGE1) at 1 x 10(-5) mol/l had no effect on the initial rapid phase of the high potassium-induced calcium uptake by striatal synaptosomes. Neither of these agents affect calcium uptake by whole brain synaptosomes. 5 It appears that in the striatum, dopamine regulates the depolarization-induced influx of calcium in presynaptic nerve endings. This mechanism could constitute a feed-back inhibition for transmitter release in the striatum.

Animals↗
PubMed1980

Increased sister chromatid exchange frequencies in lymphocytes of nurses handling cytostatic drugs.

In oncology units, personnel handling chemotherapeutic drugs may occasionally be exposed to small amounts of genotoxic agents. This exposure was obviously the cause of the increased frequencies of sister chromatid exchange (SCE) observed in nurses in daily contact with cytostatics (N = 20, mean SCEs/cell +/- SE 9.4 +/- 0.3) as compared to a group of office workers (N = 10, mean SCEs/cell 8.1 +/- 0.3). The oncology nurses also had a higher SCE frequency than other hospital nurses (N = 10, mean SCEs/cell 8.7 +/- 0.2), but this difference was not statistically significant. The SCEs of patients under chemotherapy were about five times higher (mean SCEs/cell 36.8 +/- 0.6) than those of healthy subjects.

Antineoplastic Agents↗
PubMed1980

[The treatment of soft tissue sarcomas (author's transl)].

The treatment of soft tissue sarcomas gives poor results. Two thirds of the patients die of the disease. In retrospective studies the histological grading of the sarcomas has been shown to be the best prognostic sign. Combination of the effective treatment modalities: surgery, radiotherapy and chemotherapy in the primary phase of the treatment as well as the concentration of all the cases in selected care units is recommended.

Adult↗
PubMed1977

Studies on an adrenal antigen common to man and different animals.

Precipitating adrenal antibodies, originally described by Andrada et al., are often associated with patients suffering from the moniliasis-polyendocrinopathy syndrome. The syndrome may include contemporarily several organ-specific autoimmune diseases such as hypoparathyroidism. Addison's disease, thyroiditis, pernicious anaemia, gastritis and ovarian failure and often combined with moniliasis and alopecia. These antibodies seem to differ from those demonstrable by immunofluorescence (IFL) and complement fixation. This conclusion was made as the titres of immunofluorescence antibodies did not correlate with the presence or absence of precipitating antibodies (Krohn et al., Clin Immunol Immunopathol 3:59-68, 1974; Heinonen et al., Ann Clin Res 8:262-265 1976). In this study we describe the subcellular localization and distribution of the precipitable adrenal antigens within some animal species. We found two precipitable adrenal antigens; one of them, designated P-antigen (particulate), was found in precipitable form only in the mitochondrial fractions, and the other, designated S-antigen, could be found in all subcellular fractions of some animal species. Bovine and equine S-antigen could be fractionated on a Sephadex G-200 column, revealing also the soluble nature of the S-antigen. The human S-antigen seemed to differ from the animal S-antigen as in addition to one common antigenic determinant (Sc), the human S contained a second determinant (Sh) not present in the animals. There was no difference in the antigenic character of the P-antigen within different species, although this conclusion is mainly based on the absorption studies.

Adrenal Cortex↗
PubMed1976

Effect of prostaglandin E1 on neuromuscular transmission in the rat.

1 The effect of prostaglandin E1 on neuromuscular transmission in the phrenic nerve-diaphragm muscle preparation of the rat was studied with intra- and extracellular recording techniques. 2 Prostaglandin E1, in concentrations from 10 nM, induced intermittent failures in the generation of the end-plate potential in response to repeated indirect stimulation. 3 Failures appeared abruptly, the end-plate potential behaving in an all-or-nothing fashion. The effect occurred only at 36-38 degrees C when the nerve was stimulated at 30-80 Hz and was reversible upon washing with drug-free solution. 4 Since miniature end-plate potentials were not affected, such failures must be attributed to a presynaptic action of prostaglandin E1. 5 Extracellular recording suggested that prostaglandin E1 prevented the action potential from reaching the nerve terminal.

Animals↗
PubMed1976

Variety of determinants in an adrenal antigen common to man and some animals.

Precipitating adrenal antibodies are specifically associated with the moniliasis-polyendocrinopathy syndrome. This may include several simultaneous autoimmune disorders such as Addison's disease, hypoparathyroidism, thyroiditis, pernicious anaemia and ovarian failure often combined with moniliasis and alopecia. The antibodies react with two adrenal specific antigens present in man and in different animals. One of these antigens designated S-(soluble) antigen is present in all subcellular fractions and the other designated P-(particulate) antigen was found in precipitable form only in the mitochondrial fractions. Rabbits immunized with bovine adrenal homogenate and different subcellular fractions, produced three to four adrenal specific antibodies, which were qualitatively identical. The corresponding antigens were designed as S1-S4, one of which (S4) was strictly specific for bovine tissue. S1-, S2- and S3-antigens were identical in bovine and ovine adrenals, whereas a partial reaction of identity was found between ruminants and the S1- and S2-antigens of all other species tested. The S1- and S2-antigens seem to contain a variety of determinants, some common to all the species studied and some limited to certain species only. Of the four S-antigens only one (S1) in rabbits, was found to contain autoantigenic determinants. Comparative studies with sera from patients with the moniliasis-polyendocrinopathy syndrome indicate, that this molecule is the one with which human and rabbit antisera react.

Adrenal Glands↗
PubMed1976

Association of precipitating anti-adrenal anti-adrenal antibodies with moniliasis-polyendocrinopathy syndrome.

The association of precipitating anti-adrenal antibodies with different subgroups of idiopathic Addison's disease were studied. We had previously found these antibodies in patients with the moniliasis-polyendocrinopathy syndrome. Sera of 36 adult patients suffering from different froms of Addison's disease were examined for the presence of adrenal antibodies demonstrable either by immunofluorescence (IFL) or by gel diffusion. 3 of the 17 patients with tuberculous and 17 of 19 patients with idiopathic Addison's disease had IFL antibodies but only one had precipitating antibodies. There was one typical case of Schmidt's syndrome, and four additional cases with Addison's disease combined with diabetes or thyroiditis, who may later develop the syndrome. None of htese patients had precipitating anti-adrenal antibodies. The only patients with precipitating adrenal antibodies had the moniliasis-polyendocrinopathy syndrome. He was not typical as Addison' disease appeared unusually late and he did not have hypoparathyroidism. The presence of precipitating anti-adrenal antibodies in this patient, and the absence of these in other groups of Addison's disease, is further evidence for the association of precipitating antibodies with the moniliasis-polyendocrinopathy syndrome.

Addison Disease↗
PubMedDate not supplied

Prevention of ethanol-induced sympathetic overactivity and degeneration by dexmedetomidine.

The effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on rat sympathetic neurons were studied during a 12-day, heavy ethanol exposure. Adult male Wistar rats were given ethanol or isocaloric sucrose three times a day by intragastric intubation. Both acute (a single dose of 300 micrograms/kg p.o.) and chronic (100 micrograms/kg x 2 P.O. throughout the experiment) effects of dexmedetomidine were tested. The superior cervical ganglia (SCG) of the ethanol-exposed, non-dexmedetomidine-treated rats showed an abnormally high overall level of tyrosine hydroxylase immunoreactivity (TH-IR) and catecholamine histofluorescence. However, a subpopulation of neurons had apparently lost their catecholamine synthetic activity, as they exhibited no TH-IR or catecholamine fluorescence. The ethanol-exposed ganglia also showed structural alterations (e.g., decreased neuronal size and increased occurrence of vacuolated neurons). In the ethanol-exposed, chronically dexmedetomidine-treated group, by contrast, the SCG exhibited TH-IR and catecholamine fluorescence intensities comparable to those seen in the control ganglia. All the structural parameters studied, as well, were at the control level in the chronically dexmedetomidine-treated group. The single dose of dexmedetomidine offered only marginal protection against the ethanol-induced alterations. These results suggest that chronic dexmedetomidine treatment may prevent ethanol-induced overactivity and degeneration of catecholaminergic neurons.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Reduction of dosing frequency of carbamazepine with a slow-release preparation.

The occurrence of side effects and epileptic seizures and the pharmacokinetics of carbamazepine (CBZ) and carbamazepine-10,11-epoxide were studied using a slow-release CBZ preparation, Neurotol slow, and a conventional CBZ preparation, Tegretol. The study was an open, randomized cross-over trial, with a 2 week study period for each preparation. Tegretol was given 3 times and Neurotol slow twice a day. The earlier CBZ dose was kept unchanged. The initial sample consisted of 24 adult epileptic patients receiving CBZ treatment of whom 20 patients were evaluable. The fluctuation in serum CBZ concentrations did not differ significantly between the 2 treatment periods, even though the interdose interval of Neurotol slow was 4 h longer than that of Tegretol. The switch-over from conventional CBZ to the slow-release formulation did not seem to alter the efficacy and side effects of CBZ. By using Neurotol slow instead of a conventional CBZ preparation, Tegretol, it is evidently possible to reduce the dosing frequency from 3 times a day to twice daily administrations.

Adolescent↗
PubMedDate not supplied

Dexmedetomidine alleviates ethanol withdrawal symptoms in the rat.

The effect of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on ethanol withdrawal symptoms was studied in chronically ethanol-fed rats. After a 4-day ethanol intoxication period the rats were given s.c. injections of dexmedetomidine (3, 10, or 30 micrograms/kg) or saline (control group) at 10, 16, 22, and 39 h after the last dose of ethanol. The severity of ethanol withdrawal symptoms (rigidity, tremor, irritability, hypoactivity) was rated up to 58 h, blind to the treatments. The results showed that dexmedetomidine at doses 10 and 30 micrograms/kg significantly diminished the severity of the ethanol withdrawal reaction as measured by the sum score of the three most specific withdrawal signs (rigidity, tremor, and irritability). Dexmedetomidine at 10 micrograms/kg was the most effective dose, especially in the latter half of the withdrawal period (23-58 h after last dose of ethanol). The results suggest that dexmedetomidine in the treatment of ethanol withdrawal symptoms should be further studied.

Adrenergic alpha-Agonists↗
PubMedDate not supplied

Multiple-dose pharmacokinetics of selegiline and desmethylselegiline suggest saturable tissue binding.

The goal of this study was to examine the multiple-dose pharmacokinetics of selegiline and its metabolites desmethylselegiline, 1-methamphetamine, and 1-amphetamine after oral administration of selegiline HCl. Twelve healthy volunteers received 10 mg of selegiline HCl once daily for 8 days. The pharmacokinetic profiles of selegiline and the metabolites were examined from serum samples for 24 hours (i.e., the dosing interval, tau) on days 1, 4, and 8. The results indicated significant apparent accumulation of selegiline and desmethylselegiline during the 8-day period of selegiline administration. The AUC tau S of selegiline and desmethylselegiline were increased 2.7 fold (p < 0.001) and 1.5 fold (p < 0.001), respectively, from day 1 to day 8. However, the half-lives of selegiline (range, 1.5-3.5 h) and desmethylselegiline (range, 3.4-5.3 h) were found to be relatively short. Accordingly, the short half-lives of these compounds failed to predict the apparent accumulation. With both of the 1-amphetamine metabolites of selegiline, steady state was reached by day 4. We suggest that the most likely explanation for the apparent accumulation of selegiline and desmethylselegiline was the saturation of the MAO-B binding sites in tissues, although decreased first-pass metabolism of selegiline cannot be ruled out. The observed increase in selegiline and desmethylselegiline concentrations on multiple dosing is not likely to significantly increase the pharmacodynamic effect or adverse effects of selegiline compared with what has been found after a single 10-mg dose.

Administration, Oral↗