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Biomedical subjects

A Møller

Publications and source records attributed to A Møller.

At least 55 records · Page 3Linked to original sources
PubMed1995

Pharmacological profile and anti-ischemic properties of the Ca(2+)-channel blocker NS-638.

Included in the sequence of events leading to neuronal death in ischemic tissue following stroke is an excessive and toxic rise in the intracellular Ca(2+)-concentration, predominantly due to an influx of Ca2+ through nonselective cation-channels as well as Ca(2+)-channels. In the present study we have characterized the pharmacological profile and anti-ischemic effects of 2-amino-1-(4-chlorobenzyl)-5-trifluoromethylbenzimidazole (NS-638), a small nonpeptide molecule with Ca(2+)-channel blocking properties. NS-638 dose dependently inhibited K(+)-stimulated [45Ca2+]-uptake in chick cortical synaptosomes and 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA)-stimulated [3H]GABA-release from cultured cortical neurons with IC50 values of 2.3 and 4.3 microM, respectively. K(+)-stimulated intracellular Ca(2+)-elevation in cultured cerebellar granule cells was equipotently blocked with an IC50 value of 3.4 microM. At this concentration no effect on Ca(2+)-induced contractions in K(+)-depolarized guinea pig taenia coli was observed. The effect of NS-638 on neuronal Ca(2+)-channels was evaluated using whole cell patch clamp techniques. The compound reversibly blocked N- and L-type Ca(2+)-channels in cultured chick dorsal root ganglion cells in the concentration range of 1-30 microM. In the mouse middle cerebral artery occlusion (MCAO) model, NS-638 administered i.p. (50 mg kg-1) at 1 h and 6 h post-ischemia, and once a day for the next two days, resulted in a 48% reduction in total infarct volume. The compound did not show protection against ischemic neuronal damage in the gerbil model of bilateral carotid artery occlusion (BCAO). This data suggests, that neuronal Ca(2+)-channel blockers may have potential in ameliorating the pathological damage after focal ischemia.

Animals↗
PubMed1994

PCR typing of DNA fragments of the short tandem repeat (STR) system HUMTH01 in Danes and Greenland Eskimos.

DNA from the short tandem repeat (STR) system HUMTH01 was amplified by the polymerase chain reaction (PCR) and analyzed by vertical electrophoresis in polyacrylamide gels followed by silver staining. DNA samples from 100 unrelated Danes, 147 unrelated Greenland Eskimos, and 89 Danish mother/child pairs were analyzed. Significant differences were observed between the distribution of fragments ('alleles'), whereby allele number 7 was considerably more frequent in Eskimos (0.687) than in Danes (0.201). The distributions of HUMTH01 phenotypes were in Hardy-Weinberg equilibrium in both the Eskimo and Danish populations. In the 89 Danish mother/child pairs, the segregation of the HUMTH01 genotypes was in accordance with the genetic model of co-dominant inheritance and no mutations were found. In a blind trial, DNA samples from 40 unrelated Danes were investigated by one of us in Copenhagen, at the FBI Forensic Science Research and Training Center (FSRTC), Quantico, and at the Institut für Rechtsmedizin, Münster, Germany. Concordant HUMTH01 types were found in 39 out of 40 individuals. The allele which led to discrepant typing results was assigned type 9.3 in two laboratories and type 10 in one laboratory.

Alleles↗
PubMed1994

Relation of spatial learning of rats in the Morris water maze task to the number of viable CA1 neurons following four-vessel occlusion.

Male Wistar rats were tested in the Morris water maze task 1 week after 6, 9, or 12 min of transient global ischemia. The 9-min and 12-min ischemia groups were significantly impaired in the acquisition and the reversal experiment. A systematic counting of CA1 neurons in the whole hippocampal formation revealed a unilateral number of CA1 neurons of 286,000 in the sham group, of which 2/3 were located in the dorsal hippocampus. The ischemia groups showed a significant decline in the number of dorsal CA1 neurons, whereas only the 12-min ischemia group showed a significant but minor decline (10%-15%) in the number of ventral CA1 neurons. A correlation analysis showed that the escape distance declined with increasing number of viable CA1 neurons, but poor correlation coefficients were obtained. Thus, some of the ischemic rats with even very few viable CA1 neurons in the dorsal hippocampus were capable of performing this spatial learning task at sham-group level.

Animals↗
PubMed1994

Does neuronal damage of CA1 relate to spatial memory performance of rats subjected to transient forebrain ischemia?

The effect of ischemia-induced hippocampal neuronal damage on acquisition and performance in the Morris water maze task was investigated in male Wistar rats, subjected to 8 min of transient forebrain ischemia, induced by the 4-vessel occlusion (4-VO) method. After a morphological scoring of the neuronal damage within the CA1, CA2, and CA3 subfields of the anterior-dorsal part of hippocampus we found that rats with a total neuronal cell loss of the anterior-dorsal CA1 region showed memory performance impairments in the acquisition trials, in a probe trial, and in a reversal experiment. However, rats with only partial damage to the CA1 region did not exhibit significant impairments during the acquisition trials of the water maze test or in the probe trial and the reversal experiment. In conclusion, these results suggest that it is possible to relate the histological damage score of CA1 in the anterior-dorsal hippocampus to impaired memory performance in the present water maze setup.

Animals↗
PubMed1994

[Heart involvement in HIV infection].

Postmortal examinations have shown cardiac involvement in more than 50 percent of patients with AIDS. Echocardiographic studies have shown exudative pericarditis in 18-38 percent of patients with AIDS. The pericardial effusion is usually without haemodynamic consequence, but may be associated with cardiac tamponade. Dilation and hypokinesia of the left ventricle have been found in 30 per cent of patients with AIDS. The impairement of the left ventricular function is primarily seen in febrile, severely diseased AIDS patients, while ambulatory HIV-positive patients have a low prevalence of myocardial involvement. AIDS-patients should be examined by echocardiography in case shortness of breath and hypoxemia are out of proportion to the pulmonary findings.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Cardiac function in patients with human immunodeficiency virus infection and with no other active infections.

OBJECTIVE: to investigate cardiac function and prognostic significance of echocardiographic findings in patients with uncomplicated human immunodeficiency virus (HIV)-infection. PATIENTS AND METHODS: Doppler echocardiography was performed in 60 male patients with HIV-infection and no signs of other active infections, and in 36 age and sex matched normal control subjects. The survival time of the patients was assessed 36 months after the echocardiographic examination. RESULTS: None of the patients had significant pericardial effusions, intracardiac tumors, signs of valvular endocarditis or dilated cardiomyopathy. In none of the patients were the fractional shortening or the early and atrial mitral flow ration (E/A ratio) below the 95% confidence limit of the control group. The E/A ratio was slightly, but significantly, decreased in AIDS patients both as compared to asymptomatic HIV-infected patients and as compared to normal control subjects because of increased heart rated in the AIDS patients. Within the three-year observation period, 28 of the patients died from HIV-related disease. In the group of deceased patients, there was no significant correlation between blood pressure, heart rate, left ventricular diameters, fractional shortening, E/A ratio and the survival time. CONCLUSION: In a population of HIV-infected patients with no other active infections, cardiac abnormalities seen to be uncommon, and the echocardiographic fractional shortening and E/A ratio were not related to the survival time of such patients. Thus, our data does not evidence that HIV is a direct cardiac pathogen.

Acquired Immunodeficiency Syndrome↗
PubMed1993

[Cogan syndrome. Reversible perceptive hearing loss, non-syphilitic interstitial keratitis and aortic valve insufficiency].

Cogan's syndrome (CS) is a systemic disease of putative immunological origin. The syndrome comprises fluctuating and progressive sensorineural hearing loss and nonsyphilitic interstitial keratitis. Other manifestations are seen, aortic insufficiency in particular. A characteristic case of CS is described in which reversal of sensorineural hearing loss was achieved during oral corticosteroid therapy. In addition, aortic valve insufficiency was diagnosed, necessitating surgical valve replacement.

Aged↗
PubMed1993

Total numbers of various cell types in rat cerebellar cortex estimated using an unbiased stereological method.

A new and efficient stereological method for estimating the total number of the different cell types in rat cerebellar cortex is presented. The cells have been subdivided into the following categories: Purkinje cells, granule cells, Golgi cells, glial cells in the granular layer, Bergmann glial cells and neurons and glial cells in the molecular layer. The method has been used to estimate the total number of some of the cell types in rats exposed to orally administered toluene at doses of 200, 400 and 800 mg/kg/day for 12 weeks compared with a control group. No statistically significant differences were found between the exposed and non-exposed animals. The described method can be used in a number of both biological and experimental studies. With the use of new stereological methods it is possible to get precise estimates of total cell numbers in a much shorter time than earlier required. This makes it possible to improve the reliability of the final result by increasing the number of cases processed.

Animals↗
PubMed1993

Protective actions of human recombinant basic fibroblast growth factor on MPTP-lesioned nigrostriatal dopamine neurons after intraventricular infusion.

Basic fibroblast growth factor (bFGF, FGF-2) is a trophic factor for neurons and astrocytes and has recently been demonstrated in the vast majority of dopamine (DA) neurons of the ventral midbrain of the rat. Potential neuroprotective actions of FGF-2 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model have also been reported. The actions of the FGF-2 have now been further analyzed in a combined morphological and behavioural analysis in the MPTP model of the adult black mouse, using a continuous human recombinant FGF-2 (hrFGF-2) intraventricular (i.v.t.) administration in a heparin-containing (10 IU heparin/ml) mock cerebrospinal fluid (CSF) solution. Tyrosine hydroxylase (TH) immunocytochemistry in combination with computer assisted microdensitometry demonstrated a counteraction of the MPTP-induced disappearance of neostriatal TH-immunoreactive (ir) nerve terminals following the FGF-2 treatment. Unbiased estimates of the total number of nigral TH ir neurons, using stereological methods involving the optical disector (Olympus), showed that the MPTP-induced reduction in the number of nigral TH ir nerve cell bodies counterstained with cresyl violet (CV; by 56%) was partially counteracted by the FGF-2 treatment (by 26%). The behavioral analysis demonstrated an almost full recovery of the MPTP-induced reduction of the locomotor activity after FGF-2 treatment. This action was maintained also 1 week after cessation of treatment. The hrFGF-2 produced an astroglial reaction as determined in the lateral neostriatum and in the substantia nigra (SN) far from the site of the infusion, indicating that the growth factor may have reached these regions by diffusion to activate the astroglia. Immunocytochemistry revealed FGF-2 immunoreactivity (IR) in the nuclei of the astroglia cell population in the dorsomedial striatum and the microdensitometric and morphometric evaluation demonstrated an increase in the number, but not in the intensity, of these profiles on the cannulated side, suggesting the possibility that hrFGF-2 stimulates FGF-2 synthesis in astroglial cells with low endogenous FGF-2 IR. These results indicate that hrFGF-2, directly and/or indirectly via astroglia, upon i.v.t. infusion exerts trophic effects on the nigrostriatal DA system and may increase survival of nigrostriatal DA nerve cells exposed to the MPTP neurotoxin

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Chronic nicotine treatment counteracts nigral cell loss induced by a partial mesodiencephalic hemitransection: an analysis of the total number and mean volume of neurons and glia in substantia nigra of the male rat.

This study combines immunocytochemical and stereological methods for the first time to obtain unbiased estimates of the number of cells in the entire substantia nigra and their respective mean volume. Nicotine, delivered by subcutaneously implanted osmotic pumps (0.125 mg/kg/h, 14 days) to male Sprague-Dawley rats with a partial unilateral mesodiencephalic lesion, caused a significant counteraction of the lesion-induced reduction in total number of nigral tyrosine hydroxylase-like immunoreactive neurons counterstained with Cresyl Violet compared with saline treated control animals. The number of Nissl stained neurons without tyrosine hydroxylase-like immunoreactivity was not affected by the lesion nor by nicotine. The numbers of non-neuronal glial fibrillary acidic protein-like immunoreactive cells counterstained with Cresyl Violet and smaller cells seen after Cresyl Violet staining alone, possibly representing microglia, were increased by the lesion but not affected by nicotine. No nicotine-induced effects were found on the number of nigral cells located contralateral to the lesion. The lesion-induced reduction in the mean volume of the nigral cells showing tyrosine hydroxylase-like immunoreactivity, as determined with the stereological rotator method, was not affected by nicotine. These findings suggest that continuous nicotine infusion exerts protective effects on lesioned nigroneostriatal dopamine systems and that these protective effects are selective for the nigral dopamine neurons not affecting other populations of neurons or non-neuronal cells. This neuroprotective effect might lead to new therapeutic strategies in clinical neurodegenerative disorders such as Parkinson's Disease.

Animals↗
PubMed1992

Phenytoin-loading: pharmacokinetic comparison between an intravenous bolus injection and a diluted standard solution.

Phenytoin (PHT) is considered a first or second choice in the treatment of status epilepticus that is refractory to benzodiazepines. The use of an intravenous bolus injection of PHT is hazardous due to the risk of cardiac conduction disturbances, dose-dependent side effects in general, as well as the possibility of severe necrotic lesions in case of extravasation. We compared the number and intensity of side effects and serum level profiles of a highly concentrated, non-dilutable bolus (46 mg/ml) of PHT [Fenytoin, DAK] with a dilutable standard solution (1.5 mg/ml) [Phenhydan] administered intravenously in 500 ml saline. Six healthy volunteers received both regiments (9.1 mg/kg). The diluted solution showed a curvilinear saturation curve with a lower concentration maximum (C-max) than the concentrated solution. Lower toxicity of the diluted solution was indicated by a clinical rating of side effects. Based on a higher incidence and degree of side effects following administration of the more concentrated formulation of PHT, compared with the more diluted preparation, we recommend the use of the less concentrated formulation.

Adult↗
PubMed1992

Time- and temperature-dependent forebrain ischemic damage in Mongolian gerbils.

The influence of transient bilateral carotid artery occlusion time, core body temperature regulation and post-operative survival time was examined on delayed neuronal death in the hippocampal subregions of Mongolian gerbils. A simple and rapid histologically based scoring system was used. A carotid artery occlusion time of 5 min with stabile core body temperature at 37.5-38.0 degrees C and a post-operative survival time of 4 days was sufficient to induce a reproducible and almost total neuronal damage in the hippocampal subfields. Furthermore, the use of gerbils with ages varying from 50 to 100 days did not markedly influence the development of the neuronal damage although the variation in the severity of the damage seemed to decrease with age. The addition of a drop of room tempered (21-22 degrees C) isotonic water, to avoid adherence between the clips and the carotid artery, reduced neuronal damage in some animals.

Animals↗
PubMed1992

Mean volume of pigmented neurons in the substantia nigra in Parkinson's disease.

A new unbiased stereological estimator, the rotator, was used to estimate the mean volume of pigmented substantia nigra (SN) neurons in three Parkinson's disease (PD) brains and age-matched controls. Average pigmented neuron volume was 31,300 microns 3 (5200) in controls and 28900 microns 3 (120) in patients. Estimating the absolute size distribution, revealed that PD patients had approximately 80% less total SN pigmented volume than controls. Compared with biased methods, in addition to dramatic improvements in efficiency and accuracy, results obtained by the unbiased rotator suggest that primarily the largest pigmented neurons in SN are lost in PD.

Aged↗
PubMed1991

[Pneumocystitis carinii pneumonia in adult patients with AIDS].

Pneumocystis carinii pneumonia continues to be the commonest opportunistic infection seen in AIDS patients. Early diagnosis and treatment have caused the one-year survival in AIDS-patients with PCP to increase steadily. However, PCP is still the cause of death in 25% of the AIDS-patients. Secondary prophylaxis with pentamidine-isethionate inhalations has reduced the risk of PCP relapse considerably. The risk of PCP is markedly increased at CD4-cell counts below 200 mio/l. Therefore, inhalations of pentamidine twice monthly, as a primary prophylaxis against PCP, can be recommended in HIV-positive patients with CD4-cell counts below this level.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Irreversible effects in rats of toluene (inhalation) exposure for six months.

The irreversible CNS effects of six months' exposure to toluene (0, 500, and 1500 p.p.m.) in rats was studied applying a multi-disciplinary approach. After an exposure-free period, neurobehavioural, morphometric, pathological, and biochemical examinations were performed. No neurobehavioural or gross pathological changes were found. Morphometric measurements did not show loss of neurones. At 500 p.p.m. the mean nuclear volume and mean perikaryonal volume and the variation of the values of these parameters was increased in the exposed groups compared to the controls. Noradrenaline (NA), dopamine (DA), and 5-hydroxytryptamine (5-HT) levels were significantly changed in various brain regions. It is concluded that this investigation failed to reveal overt toluene-induced CNS-neurotoxicity, however, certain irreversible effects were found which further add to the accumulating evidence of the chronic CNS-neurotoxicity of toluene.

Administration, Inhalation↗
PubMed1991

The absolute number of nerve cells in substantia nigra in normal subjects and in patients with Parkinson's disease estimated with an unbiased stereological method.

Using an unbiased stereological technique, the total numbers of pigmented and non-pigmented neurons were estimated in the substantia nigra of seven patients with Parkinson's disease and seven control patients. Compared with the controls, in which the average total number of pigmented neurons was 550,000, the number of neurons was reduced by 66% in the patients. The average total number of non-pigmented neurons was 260,000 in controls and reduced by 24% in the patients. A significant correlation (r = 0.81) existed between the total numbers of pigmented and non-pigmented neurons in the controls, whereas a similar correlation (r = 0.72) in the patients fell just short of statistical significance. The stereological estimates made in this study are unbiased, in that they are independent of nerve cell size, section thickness and of dimensional changes in brain tissue induced by histological procedures. The stereological method is considerably more efficient than previous conventional methods.

Aged↗