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Biomedical subjects

M Borgers

Publications and source records attributed to M Borgers.

At least 19 recordsLinked to original sources
PubMed1992

Synaptic plasticity in rat hippocampus associated with learning.

Rats subjected to a one-way active avoidance task consisting of 3 daily training sessions, showed obvious shape changes in dendritic spines of the hippocampal supragranular molecular layer. Performance, expressed as the number of avoidances per 10 trials, significantly improved in the second and third session (P < 0.001). In trained animals, at the end of the third session, the amount of perforated concave synapses significantly increased as compared to untrained controls (P < 0.05). When compared with a group of sham-shocked rats, the increase was less pronounced. The length of the postsynaptic density in both, perforated and non-perforated synapses, significantly increased in comparison with untrained control and sham-shocked animals (perforated: P < 0.005; non-perforated: P < 0.05). The results are indicative for the existence of synaptic remodeling and turnover in rats subjected to one-way active avoidance training.

Animals↗
PubMed1992

Protection of human, rat, and guinea-pig atrial muscle by mioflazine, lidoflazine, and verapamil against the destructive effects of high concentrations of Ca2+.

In right atrial trabeculae from humans and in left atria from rat and guinea-pig hearts, the protective effects of mioflazine, lidoflazine, and verapamil against the accumulation of cellular calcium were investigated. Two consecutive, cumulative increases in the extracellular calcium concentration, [Ca2+]o (1-25 mmol/l), were induced, in between which the muscles were exposed for at least 30 minutes to solvent or drug. When using solvent in the 30-minute interval, the force of contraction was much lower during the second Ca2+ challenge, while the aftercontractions and the increase in passive tension at high [Ca2+]o tended to be larger. These signs of functional impairment were prevented by exposure to mioflazine or lidoflazine (3 mumol/l each) but not to verapamil (3 mumol/l). Muscles were fixed with glutaraldehyde at the end of the second Ca2+ challenge for morphological and cytochemical examination. After solvent treatment, more than half of the cells were severely damaged, showing cellular edema, contraction-band necrosis, mitochondrial swelling, and nuclear pyknosis; the sarcolemma was devoid of calcium deposits, damaged mitochondria contained either large deposits of calcium or flocculent densities, and in some cells, the cytoplasm was filled with calcium deposits. Following exposure to mioflazine and lidoflazine, but not to verapamil, the number of intact cells after the second Ca2+ challenge was not different from time-matched controls (80-90%). Furthermore, the shifts in cellular calcium distribution were prevented with mioflazine and lidoflazine, whereas verapamil was less effective. There were no species differences with respect to either morphological or contractile changes. In conclusion, exposure of atria to high [Ca2+]o induced similar ultrastructural and cytochemical changes as seen after ischemia-reperfusion induced damage. Indeed, under the mentioned conditions the sarcolemma lost its capacity to exclude Ca2+ after a challenge with high [Ca2+]o and allowed excessive Ca2+ entry. The pathway for this extra Ca2+ remains to be elucidated. L-type calcium channels are probably not involved, since verapamil cannot prevent the Ca2+ overload.

Animals↗
PubMed1992

Microwave-enhanced silver staining of degenerating neuronal processes.

A simple and rapid method for light and electron microscopic visualization of degenerating neuronal processes and axon terminals is described. Hundred-micrometer vibratome sections of perfusion-fixed rat brain were incubated briefly in a 5% silver nitrate solution in a conventional microwave oven. After a rinse in 1% acetic acid, the sections were silver enhanced. Differentiation and counterstaining was done respectively in ethanol 100% and cresyl violet. In the light microscope, degenerating neuronal processes appeared as black dots against a clear background. Areas of calcification were also positively stained. The presence of silver deposits in degenerating presynaptic terminals and dendrites was confirmed ultrastructurally.

Animals↗
PubMed1992

Species differences in adenosine metabolic sites in the heart.

5'-Nucleotidase and purine nucleoside phosphorylase, two key enzymes in nucleoside metabolism, have been localized electronmicroscopically in left ventricular myocardium of the human, dog, pig, rabbit, guinea pig and rat. Ectonucleotidase activity was present in all species at the plasma membrane of pericytes. Reactive endothelial cells in the microcirculatory bed were restricted to those covering resistance arterioles. Cardiomyocytes were reactive only in the rat. Purine nucleoside phosphorylase was localized uniformly in the vascular endothelium of all species. The strongest activity was seen in the pericytes of guinea pig, rat and dog. Pericytes of rabbit and pig were virtually unreactive, whereas a minority of cells in human samples were positive. Cardiomyocytes were unreactive in all species. These variations in the distribution pattern of adenosine metabolic sites may have definite consequences for disposal and recovery of adenylates and their breakdown products in ischaemia and for the effects to be expected from interference with nucleoside transport inhibition.

5'-Nucleotidase↗
PubMed1992

The course of vasospasm following subarachnoid haemorrhage in rats. A vertebrobasilar angiographic study.

The course of vasospasm following subarachnoid haemorrhage in rats was studied using vertebrobasilar angiography. Wistar and Sprague Dawley rats were compared with respect to vasospastic response after bleeding. A more pronounced vasospasm was found in Sprague Dawley rats. In order to avoid a possible toxic effect on the contrast medium, only one angiogram per animal was initially performed. However, a comparison with the results obtained in a separate series of non-challenged animals demonstrated a difficulty due to high variability in basilar artery size in the latter group. Therefore, vasospasm can be more readily shown if multiple angiograms are used in the same animal so that the vasospasm can be expressed as a percentage of the initial diameter of the basilar artery. It was found that multiple angiograms are well tolerated when non-ionic contrast media are used.

Animals↗
PubMed1992

Haemodynamic, intracranial pressure and electrocardiographic changes following subarachnoid haemorrhage in rats.

Experimental induction of subarachnoid haemorrhage in rats resulted in acute haemodynamic changes. Heart rate decreased concomitantly with a rise in arterial blood pressure. Intracranial pressure increased and consequently cerebral perfusion pressure dropped. These changes as well as the observed electrocardiographic (ECG) changes were comparable to those reported in patients. Apart from blood also saline, when introduced into the cisterna magna, was able to elicit such abnormalities. The haemodynamic and electrocardiographic changes, which result from subarachnoid haemorrhage, may even become aggravated, when repetitive injections of blood or saline are given into the cisterna magna and when cerebral angiography is performed prior to induction of the subarachnoid haemorrhage. Chronic intracranial pressure monitoring during the 48 hours following subarachnoid haemorrhage revealed no significant rise in pressure. A thorough control of the experimental conditions is thus of utmost importance in order to give a valid interpretation of the observed anomalies.

Animals↗
PubMed1992

Lysophosphatidylcholine-induced Ca(2+)-overload in isolated cardiomyocytes and effect of cytoprotective drugs.

It has been previously demonstrated that lysophosphatides accumulate rapidly in ischaemic tissue, and may play a key role in the genesis of ischaemia-reperfusion injury. The present study investigated the effects of exogenously added lysophosphatidylcholine (1-20 microM) on single isolated cardiomyocytes from adult rabbit hearts. Quiescent cells exposed to > or = 8 microM lysophosphatidylcholine dose-dependently displayed irreversible hypercontraction, whereas after 60 min at 3 microM lysophosphatidylcholine, most cells remained rod-shaped (87.2 +/- 2.0%, mean +/- S.E.M.). However, when combined with electrical field stimulation (1 Hz), exposure to 3 microM lysophosphatidylcholine resulted in irreversible hypercontracture of most cells after 60 min: only 27.5 +/- 7.5% of the cells remained rod-shaped. Contracture depended upon the presence of extracellular Ca2+, and coincided with a significant rise in the median intracellular free Ca2+ level from 72.2 to 352.1 nM (P = 0.0001), suggesting intracellular Ca(2+)-overload. Pretreatment with 10(-6) M flunarizine or R 56865 significantly reduced the fraction of damaged cells when exposed to 3 microM lysophosphatidylcholine and electrical stimulation: 78.3 +/- 12.2% and 56.3 +/- 13.1% respectively of the cells remained rod-shaped. No protection was observed when quiescent cells were exposed to 10 microM lysophosphatidylcholine. Cytochemical localization of Ca2+ showed that lysophosphatidylcholine induced a loss of sarcolemma-bound Ca2+ precipitate and an accumulation of Ca2+ clusters in mitochondria of damaged cells in a dose and time dependent way. These results suggest that lysophosphatidylcholine induces functional and structural damage (Ca(2+)-overload) in isolated cardiomyocytes and that this can be prevented by cytoprotective drugs.

Animals↗
PubMed1992

Developmental changes in tolerance to ischaemia in the rabbit heart: disparity between interpretations of structural, enzymatic and functional indices of injury.

The vulnerability of the heart to injury during ischaemia and reperfusion and its responsiveness to various protective and pharmacological interventions are age-dependent. Using three independent indices of tissue injury (cardiac structure, contractile function and creatine kinase leakage), we compared the response of adult (60-90 days old) and neonatal (7 days old) isolated perfused rabbit hearts to global ischaemia and reperfusion. Prior to ischaemia, heart rate was significantly higher in neonatal hearts, as were control values for coronary flow, aortic flow and cardiac output when expressed on a dry wt basis. In experiments in which adult and neonatal hearts (n = 8 per group) were subjected to 2 min of cardioplegia and 45 min of ischaemia, the post-ischaemic recovery of all indices of cardiac function (when expressed as a percentage of pre-ischaemic control) was significantly higher in neonatal than in adult hearts. Thus, cardiac output recovered to 82.9 +/- 3.6% in the neonate but to only 57.9 +/- 6.7% in the adult (P < 0.05). The functional evidence of a greater resistance to ischaemia in the neonate was, however, contradicted by the levels of creatine kinase leakage which tended to be greater in the neonatal than in the adult heart (32.0 +/- 4.7 vs 20.0 +/- 3.1 IU/15 min/g dry wt). Morphological studies indicated that injury was comparable (moderate-to-severe in degree) in both groups. To assess further the relationship between the three indices, additional experiments were undertaken in which the duration of ischaemia in the neonate was extended to 60 min so that the post-ischaemic recovery of function was reduced to a level similar to that seen in the adult after 45 min of ischaemia. Under these conditions cardiac output recovered to 55.6 +/- 4.8% in the neonatal heart (P = NS when compared with the adult) and creatine kinase leakage increased to 88.2 +/- 13.9 IU/15 min/g dry wt--a value over four times greater than that measured in adult hearts with a comparable degree of functional injury. Morphological examination of tissue obtained after 15 min of reperfusion revealed a remarkable recovery of structure in both age groups. In conclusion, in functional terms the neonatal heart was more resistant to ischaemia than the adult; enzymic leakage, however, indicated the opposite and structural assessment revealed no differences. Thus, in comparing injury during ischaemia and reperfusion between different age groups, it is clearly important to employ several independent indices.

Age Factors↗
PubMed1992

Effects of itraconazole on phagocytosis and killing of Candida glabrata by polymorphonuclear leucocytes from guinea pigs.

Itraconazole, a systemically active antifungal, was tested for its effects on microscopically assessed phagocytosis and killing of Candida glabrata 233 in vitro. Yeast cells were exposed to itraconazole in culture and guinea-pig peritoneal polymorphonuclear leucocytes were exposed to the drug injected intraperitoneally in vivo. At a concentration of 10(-7) M and with exposure times of 1 h, itraconazole pre-treatment of the leucocytes had no effect on the ability of PMNL to ingest or kill C. glabrata. However, pre-treatment of the growing C. glabrata cells under the same conditions significantly increased their vulnerability to both phagocytosis and intracellular killing. Longer exposures of the yeasts to itraconazole further increased their susceptibility to leucocyte phagocytosis, and it also rendered the cells vulnerable to killing merely by immersion in sodium deoxycholate solution. These findings indicate that short exposures of C. glabrata to low itraconazole concentrations damages the cells sublethally and renders them highly susceptible to leucocyte killing. Itraconazole had no direct effects on leucocyte function itself.

Animals↗
PubMed1979

Some observations on the phosphatase cytochemistry of the submandibular gland of cat.

The localization of reaction product arising from incubation with thiamine pyrophosphate at pH 7.2 and beta-glycerophosphate or nitrophenylphosphate at pH 5 has been examined in central and demilunar acinar cells, myoepithelial cells, and cells of the striated ducts. Thiamine pyrophosphate reaction product was seen in the inner saccules of the Golgi apparatuses of the different types of cell. beta-Glycerophosphate and nitrophenylphosphate reaction products were seen in lysosomes, and in GERL-like structures in all except the cells of the striated ducts, in which the reaction products were observed in the Golgi apparatus. In central cells, the latter two reactions products were also seen in secretory granules and the cytosol.

Animals↗
PubMed1979

Promotion of pseudomycelium formation of Candida albicans in culture: a morphological study of the effects of miconazole and ketoconazole.

The effects of miconazole and its new derivative ketoconazole on Candida albicans have been evaluated by light and electron microscopy. The growth characteristics and morphology of C. albicans in culture for various periods of time in a solution consisting of Eagle's minimum essential medium supplemented with amino acids and fetal calf serum are emphasized. This medium, normally used for culturing mammalian cells, promotes a rather fast growth of C. albicans and favours the development of pseudomycelium. The obvious interest in using such culture conditions for drug evaluation is the prevalence of pseudomycelium, which in vivo is the predominant pathological form of C. albicans. Suppression of pseudomycelium formation is found in the 10-9 to 10-7 M concentration range of the imidazoles. Growth retardation and the destruction of both yeast and pseudomycelial forms brought about by incubating the cells with 10-9 to 10-4 M of the drugs are reported. At low doses these changes include the alteration of cell division, an increase in cell volume and a progressive deterioration of subcellular organelles at the cell periphery. At higher doses the involvement of all other organelles is observed finally leading to complete cell necrosis.

Candida albicans↗
PubMed1978

Purine nucleoside phosphorylase in lymphocytes of various mammalian species.

The distribution of purine nucleoside phosphorylase has been assessed by light and electron microscopy in peripheral lymphocytes of man, the rabbit, rat, mouse, guinea-pig, pig and dog. The enzyme activity was detected in the cytosol of the majority of lymphocytes in all species. The amount of reaction product was high in the rabbit, man, guinea-pig and dog, mpderate in the rat and very low in the pig and mouse. Other blood cell types are reactive as well, although there is a variation between species. A possible relationship of purine nucleoside phosphorylase with particular subpopulations of lymphocytes is suggested.

Animals↗
PubMed1978

Alkaline phosphatase activity in human polymorphonuclear leukocytes.

Alkaline phosphatase has been localized ultracytochemically in PMN of man with normal and elevated levels of this enzyme. Contrary to guinea-pig PMN, no activity appears to be present in the specific granules. Instead, the plasma membrane and the membrane of the endocytic vacuoles show a strong staining. However, the demonstration of this activity depends on the preparatory procedure employed for PMN isolation. The use of dextran and Ficoll-Hypaque in the isolation procedure induces a marked increase in alkaline phosphatase staining of the PMN plasma membrane. Strongly increased activity at this site has been found in PMN from cancer patients. In most of them, additional staining has been observed in atypical vesicles and sometimes in the Golgi apparatus. These findings are discussed in the light of some previously reported controversial biochemical and cytochemical data on the distribution of alkaline phosphatase in human PMN.

Alkaline Phosphatase↗
PubMed1978

Oxatomide protects Trichinella spiralis infected mice from lethal anaphylaxis.

Infection with Trichinella spiralis in mice was accompanied by allergic sensitization as evidenced by anaphylactic death after intravenous injection of the antigen. Pre-treatment of the animals with oxatomide, a new orally active anti-allergic drug, resulted in significant protection of the animals; the lowest effective dose of the compound was 1.25 mg/kg orally. In contrast to cyproheptadine, oxatomide offered little protection against serotonin toxicity in mice. The present data suggest that, in this model of systemic hypersensitivity, the anti-anaphylactic effect of oxatomide can be attributed mainly to inhibition of release of allergic mediators.

Anaphylaxis↗
PubMed1978

Purine nucleoside phosphorylase in chronic lymphocytic leukemia (CLL).

Purine nucleoside phosphorylase (PNP), the enzyme schematically next to adenosine deaminase in the purine salvage pathway, has been demonstrated cytochemically in peripheral blood lymphocytes of healthy subjects and chronic lymphocytic leukemia (CLL) patients. The enzyme activity is confined to the cytosol. In healthy subjects the majority of lymphocytes are strongly reactive for PNP, whereas the rest are devoid of cytochemically demonstrable activity. The percentage of PNP-positive cells largely corresponds to the number of E rosette-forming cells and is inversely proportional to the number of Ig-bearing cells. In six of seven CLL patients studied only a minor percentage of the lymphocytes showed strong PNP activity, whereas the large majority (88%--98%) possessed trace activity. Such patients have a high number of Ig-bearing cells and a low number of E rosette-forming cells. A different pattern of markers was found in the lymphocytes of the seventh CLL patient: 66% were strongly reactive for PNP, an important number formed E rosettes, and a minor percentage were Ig bearing. These data indicate that PNP can be useful as a "nonmembrane" marker in the differentiation of the B and T cell origin in CLL and deserves to be studied in other lymphoproliferative disorders.

Histocytochemistry↗
PubMed1978

Scanning electron microscopic observations of Cysticercus fasciolaris (=Taenia taeniaeformis) after treatment of mice with mebendazole.

The time-related topographical changes in mature cysticerci of Taenia taeniaformis induced after medication of infected mice with 250 ppm of mebendazole are described. The changes included the gradual disappearance of microtriches and progressive degeneration of the tegment resulting in an irregular surface with grooves, holes, and craterlike structures. Host cells adhered to the altered areas and the number of these cells increased when more severe changes became apparent. Finally the necrotized cysticerci, which lost their tegument completely, were almost entirely covered with adhesive host cells. A difference in the time sequence of the reported changes occurred between the scolex, the pseudoproglottids, and the bladder. This difference in susceptibility towards the drug between the three parts of the parasite in relation to the morphology of their microtrichous covering is discussed.

Animals↗