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Biomedical subjects

M Bindoni

Publications and source records attributed to M Bindoni.

At least 19 recordsLinked to original sources
PubMed1997

Thymotrophic effect of ether lipid 1-O-octadecyl-2-O-methoxy-rac-glicero-3-phosphocholine in the mouse.

1-O-octadecyl-2-O-methoxy-rac-glicero-3-phosphocholine (ET-18-OCH3) is a synthetic derivate of 2-lysophosphatidyl-choline, endowed with some immunomodulatory and anticancer effects. In the present work we report that a chronic (1 microgram/g b.w. for 2 weeks) or acute single dose injection of ET-18-OCH3 produced a recovery of thymus weight and thymocytes cellularity in two different strains of mice, C57BL6 and Swiss mice, undergoing thymus age-dependent involution. This effect was significant when the thymus weight was reduced at 50% and it was without effect on thymus lacking age dependent involution, such as young mice. The ability of ET-18-OCH3 to produce thymus weight and thymocyte cellularity recovery was also demonstrated in adult mice showing hypotrophy of thymus induced by chronic corticosterone treatment, suggesting that this compound could be effective against thymus hypotrophy induced by external stimuli. This thymotrophic effect of ET-18-OCH3 was not dependent on direct action on thymocyte proliferation, but probably it was dependent on its action on thymic epithelial cells to produce hormone thymulin, which level was found significantly increased in the plasma. These results provide further immunomodulatory propriety of ET-18-OCH3 and open the possibility to use this compound to counteract thymus hypotrophy.

Aging↗
PubMed1996

Effects of ether lipid 1-O-octadecyl-2-methoxy-rac-glycero- 3-phosphocholine and its analogs PAF and CPAF on the release of nitric oxide in primary cultures of rat astrocytes.

Ether lipid 1-O-octadecyl-2-O-methoxy-rac-glicero-3-phosphocholine (ET-18-OCH3) is an immunomodulator with antineoplastic activity. Its analog compounds PAF and CPAF share some of its biological effects. In our experiments, even very small amounts of ET-18-OCH3 released a remarkable quantity of nitric oxide (NO) from rat astrocytes cultured in vitro. The NO biosynthesis was inhibited by pretreatment with the antagonist BN 50730. The effect of ET-18-OCH3 was greater than that of the LPS inducer. PAF did not produce NO, even at high doses, while the nonmetabolizable CPAF only induced a significant release of NO from 12 micrograms/ml onwards. These results demonstrate that ET-18-OCH3 is functionally active also in astrocyte cultures. Stimulation of NO biosynthesis is of a great value on account of its the known effect as a neurotransmitter, potentiator of immune defences and possible modulator of cerebral circulation.

Animals↗
PubMed1996

The effect of ether lipid 1-O-octadecyl-2-O-methoxy-rac-glycero-3-phosphocholine and its analogues platelet activating factor and carbamyl-platelet activating factor on the biosynthesis of interleukin-6 in human thymic epithelial cells cultivated in vitro.

The effect of ether lipid 1-O-Octadecyl-2-O-methoxy-rac-glycero-3-phosphocholine (ET-18-OCH3), platelet activating factor (PAF) and carbamyl activating factor (CPAF) on the release of IL-6 in human thymic epithelium cultivated in vitro was studied. ET-18-OCH3 significantly increased the release of IL-6, giving the greatest effect at the dose of 2 micrograms/ml. PAF had no effect. The non-metabolizable CPAF was less effective than ET-18-OCH3 and showed the greatest release of IL-6 at the dose of 1 microgram/ml. Ether lipid ET-18-OCH3 has a thymotrophic effect as has also been demonstrated by other results obtained in our previous work.

Azepines↗
PubMed1996

Change in neurotrophins and their receptor mRNAs in the rat forebrain after status epilepticus induced by pilocarpine.

We studied the effects of status epilepticus (SE) induced by lithium chloride/pilocarpine treatment on gene expression of neurotrophins of the nerve growth factor (NGF) family and of their high-affinity receptors of the tyrosine protein kinase (trk) family in the forebrain. Using in situ hybridization (ISH), we demonstrated an early (3 h after treatment) increase in brain-derived neurotrophic factor (BDNF) and trkB mRNA expression in the dentate gyrus, amygdala, and piriform cortex, as well as widespread increases in the cerebral cortex. NGF mRNA, but not the mRNA of its receptor trkA, was increased in the dentate gyrus. In contrast, 12 h after treatment, neurotrophin-3 (NT-3) decreased, and its receptor trkC mRNA increased. There was no change in NT-4 mRNA levels. All changes were blocked by pretreatment with scopolamine, a muscarinic antagonist. The noncompetitive N-methyl-D-aspartate (NMDA) antagonist ketamine blocked NGF, BDNF, and trkB mRNA increases in the hippocampus and cerebral cortex, but not in the amygdala and piriform cortex. In contrast, ketamine did not affect NT-3 and trkC changes. These results provide a complete description of changes in mRNA levels of neurotrophins and their receptors in the forebrain after SE and supply additional data supporting the view that neurotrophin gene expression is related to abnormal neuronal activity.

Animals↗
PubMed1995

Effects of ozone on some biological activities of cells in vitro.

The aim of this work was to study the in vitro effect of ozone on the 70 kDa family of inducible heat shock proteins (HSPs70). We also performed tests to investigate possible toxic effects of ozone at the different doses employed. In human haematic mononucleated cells ozone at doses up to 20 micrograms/ml had no toxic effects and induced biosynthesis of the HSPs70. Biosynthesis of these proteins was greater at 40 micrograms/ml. In murine macrophages testing with tetrazolium salt (MTT), neutral red, and 2-deoxy-D-[1-3H]glucose uptake and study of the cell morphology showed a remarkable resistance or no toxic effects at a dose of 100 micrograms/ml also. Melanoma B16 murine cells assayed with the MTT test demonstrated less resistance to the toxic effects of ozone than normal cells. These results provide indications relevant to the problems of ozone therapy.

Animals↗
PubMed1994

Neuroregulation of natural suppressor cell activity.

The neuronal control of murine natural suppressor (NS) cell activity was studied in mice following lesion of the arcuate nucleus of the hypothalamus performed by the postnatal treatment with monosodium glutamate (MSG). The suppressor activity was evaluated as the ability of spleen or bone marrow cells (suppressors) to suppress the mitogen-induced lymphocytes proliferation of allogeneic Balb/c spleen cells (indicators). The study was carried out on three different inbred strains of mice (C57BL/6, DBA/2 and CBA). The results demonstrated that, in all strains used, the treatment of mice (12 day-old) with MSG led to a marked reduction of natural suppressor cell activity. This reduction was observed in both spleen and bone marrow, the lymphoid organs in which the NS cell activity is usually present. A reduced NS activity was also present in the bone marrow of MSG-treated adult mice, suggesting a permanent alteration of NS cell activity. These results provide additional support on neuromodulation of immune system.

Animals↗
PubMed1993

Cytotoxic and cytostatic activity of copper(II) complexes. Importance of the speciation for the correct interpretation of the in vitro biological results.

The cytotoxicity of some copper(II) compounds against the mouse cancer cell line B16, murine L929, human KB cells, and fibroblasts was investigated. All the copper(II) systems tested were shown to have pronounced toxicity against transformed cells and a cytostatic effect against untransformed cells, i.e., human fibroblasts. A careful speciation of the actual in vitro conditions reveals that copper(II) is essentially present as mixed complexes formed with the amino acids of the culture medium, [Cu(glutamine)(histidine)] being the main species. It was found that the cytotoxic activity is related to the amount of copper(II) contained in the tested compounds.

Acetates↗
PubMed1993

Crossfostering and early development of natural killer cytotoxic activity in various inbred mouse strains.

In the present study using crossfostering among three inbred mouse strains (C57BL/6, DBA/2, and Balb/c) we compared the effects of lactation with milk of different compositions on the development of NK cells cytotoxic activity. The results show that the pups from C57BL/6 and DBA/2 mice exhibit a significant early increase of NK cells cytotoxic activity when fostered by Balb/c dams, in comparison to those fostered by natural mothers. The analysis of proteins, lactose, and lipids showed difference among the strains for all components. Strain effects for days of lactation were also observed. The naso-anal length and the body weight of young mice showed differences with the strain of fostering mothers. The results indicate that the characteristic of maternal milk composition interacts with the inbred genetic susceptibility of the pups to elicit the full expression of the level of NK activity.

Animals↗
PubMed1993

Platelet-activating factor and its methoxy-analogue ET-18-OCH3 stimulate immediate early gene expression in rat astroglial cultures.

In the present paper we analyzed c-fos and zif/268 expression in rat primary astroglial cell cultures after treatment with Platelet-activating Factor (PAF) and its 2-O-methyl-analogue, 1-O-octadecyl-2-O-methoxy-glycero-3-phosphocholine (ET-18-OCH3). Both compounds, at a dose (2 microM) that did not produce toxic effects on astroglial cells, induced a rapid and transient increase of c-fos and zif/268 mRNA level. Pretreatment of astroglial cells with the PAF antagonist BN50730 (5 microM) 10 min prior to the addition of alkyl-phospholipids almost completely prevented the activation of the immediate early genes. On the contrary triazolam, another PAF inhibitor, did not block PAF induced gene expression when added to the medium at 5 microM concentration. ET-18-OCH3 effect on gene expression is blocked by the same antagonist (BN50730) which is effective in inhibiting PAF effect on astrocytes, suggesting that both substances act through the same binding site. Results obtained support the view that astroglial cells are a cellular target for this lipid mediator, and, like macrophages, respond to its methoxy-analogue.

Animals↗
PubMed1993

Increased expression of trkB and trkC messenger RNAs in the rat forebrain after focal mechanical injury.

Tyrosine protein kinases trkA, trkB and trkC are signal transduction receptors for a family of neurotrophic factors known as the neurotrophins. Here we report on changes in the expression of messenger RNAs for trkA, trkB and trkC in the brain following an injury caused by insertion of a 30-gauge needle into adult rat hippocampus or neocortex. Quantitative in situ hybridization revealed no change in the level of trkA messenger RNAs in any brain region following this insult. In contrast, increased levels of trkB messenger RNA compared to untreated animals were seen in the granule cell layer of the dentate gyrus ipsilateral to the injury already 30 min after the injury. The increase reached maximal levels (four-fold) between 2 and 4 h, but returned to control levels 8 h after the injury. No change was seen in the contralateral dentate gyrus. The levels of trkC messenger RNA increased in the same brain regions as trkB messenger RNA, though with a delayed response, reaching a maximal increase of 3.3-fold 4 h after the injury. As for trkB messenger RNA, the level of trkC messenger RNA then tapered off and reached control levels 8 h after the injury. However, 4 h after the injury, a 1.7-fold increase of trkB and trkC messenger RNAs were seen in the ipsilateral piriform cortex. The increases of trkB and trkC messenger RNAs were confirmed using a nuclease protection assay. Increases of both trkB and trkC messenger RNAs were also seen in the piriform cortex, but not in the hippocampus, following needle insertion into the neocortex. Pretreatment of the animals with the non-competitive N-methyl-D-aspartate antagonist ketamine completely prevented the increases of trkB and trkC messenger RNAs, suggesting that the brain injury caused a release of glutamate with subsequent activation of N-methyl-D-aspartate receptors. In contrast, the anticonvulsive drug diazepam, the muscarinic antagonist atropine and the calcium-channel antagonist nimodipine had no effect on the increases of trkB and trkC messenger RNAs. Combined with previous data on the expression of neurotrophin messenger RNAs following similar injuries, our results support the hypothesis that increased levels of neurotrophins and their receptors could protect against neuronal damage following a brain insult.

Animals↗
PubMed1990

Effects of early destruction of the mouse arcuate nucleus by monosodium glutamate on age-dependent natural killer activity.

The present study has examined the effect on age-dependent natural killer (NK) cell cytotoxic (NKCC) activity after the destruction of the arcuate nucleus (AR) of the hypothalamus in newborn mice with the neurotoxin monosodium glutamate (MSG). The NKCC activity was determined at different ages from the 18th day to the 54th week. This treatment resulted in depressed NKCC activity and in disappearance of its age-dependent pattern. A high correlation between NKCC depression and decreased numbers of large granular lymphocytes was also noted in the MSG-treated mice. The conclusion is that normal development of NKCC activity requires the maturation of AR functions.

Aging↗
PubMed1990

Effect of cerebral hemisphere decortication on the cytotoxic activity of natural killer and natural cytotoxic lymphocytes in the mouse.

A comparison was made of the effects of left and right cerebral decortication on cytotoxic activity of natural killer and natural cytotoxic lymphocytes in the mouse. Natural killer cytotoxic activity was significantly reduced after right decortication, whereas left decortication led to a less pronounced, though still significant fall. The cytotoxic activity of natural cytotoxic cells, on the other hand, was significantly increased, particularly 15 days after left decortication. These findings mirror the results of previously published personal findings following electrothermocoagulation of the hypothalamus. The suggestion is made that the cortex and the hypothalamus form an integrated system for the control of certain aspects of natural immunity.

Analysis of Variance↗
PubMed1990

Hypothalamic control of the generation of mature natural killer lymphocytes in bone marrow and spleen of the mouse.

Following previous work showing that electrothermocoagulation of the median region of the hypothalamus (MH) caused a marked and permanent decrease in the cytotoxicity of natural killer (NK) cells and in the number of large granular lymphocytes, a study was made of the effect of such lesions on the generation of NK cells in the bone marrow (BM) and spleen of C57BL/6 mice. Fresh spleen and BM cells from MH-lesioned and sham-operated mice were cultured with 40 U of recombinant interleukin-2 (rIL-2). NK activity was significantly higher in BM of lesioned mice, whereas spleen NK activity was greater in the sham-operated controls. NK cells matured by culture with rIL-2 were characterized by assay with fluorescent monoclonal antibodies and found to display the typical NK phenotype. These results show that the number of NK precursors is greater in BM of MH-lesioned mice and that their migration into other organs is probably partially impeded. It can also be concluded that intactness of both BM and the hypothalamus is essential for the physiological generation of NK cells.

Animals↗
PubMed1989

Effect of trophic factors, released after hippocampal injury, on astroglial cell proliferation.

An increase in astrocyte mitogenic factors and in some specific astroglial enzymatic activities after neuronal injury has been observed. Our study is concerned with the effect of the intracerebral administration of ibotenic acid (IBO) into the rat hippocampus. IBO injection causes a selective degeneration of neurons while sparing afferent fibers. We observed a transient increase in glutamine synthetase activity, a well-known astroglial marker, reaching a peak at 9-15 days after injury in lesioned hippocampus. We investigated the presence of astrocyte mitogenic factors at various times after toxin injection. Crude extracts, prepared from lesioned hippocampi 4, 9, and 14 days after IBO injection, were tested for the ability to stimulate [methyl-3H]thymidine incorporation into rat astroglial cell cultures. Crude extracts prepared 9 and 14 days after IBO injection showed a higher mitogenic activity compared to extracts prepared 4 days after lesion. Mitogenic activity of injured brain extracts was suppressed by heat inactivation (100 degrees C for 10 min).

Animals↗
PubMed1988

Interleukin 2 modifies the bioelectric activity of some neurosecretory nuclei in the rat hypothalamus.

Introduction of 15-30 U of interleukin-2 (IL-2) into the 3rd ventricle of Wistar rats was followed by a marked and significant decrease in neuron discharge frequency in the ventromedial nucleus of hypothalamus and a marked increase in the supraoptic and paraventricular nuclei. The monoclonal antibody ART62 partly blocked these effects. The conventional anti-IL-2 receptor monoclonal antibody ART18 had only a non-significant influence on the effects of IL-2. Since the supraoptic and paraventricular nuclei secrete the antidiuretic hormone, their excitation may offer a partial explanation of the considerable water retention observed during IL-2 therapy against neoplasia.

Action Potentials↗
PubMed1987

Hypothalamic control of certain aspects of natural immunity in the mouse.

Electrothermocoagulation (ETC) of the individual nuclei of the median region of the hypothalamus (MH) in the C57BL/6 mouse leads to a significant reduction in the cytotoxic activity of natural killer cells (NK) and the number of large granular lymphocytes (LGL) compared with intact or sham-operated controls. This effect, however, is less than that observed after simultaneous destruction of all MH nuclei. By contrast, no significant change in NK activity was noted after ETC of the anterior (AH) or posterior (PH) regions. Diminution of NK activity due to nuclear MH destruction is not an outcome of the change in adenohypophysis secretion provoked by hypothalamic lesion. Natural cytotoxic activity was markedly increased after ETG located either in AH, or MH, or PH. These results indicate that NK- and NC-mediated immunity is governed by a control mechanism situated in the hypothalamus.

Animals↗
PubMed1986

Increased tumor cell multiplication after radiofrequency lesions in median hypothalamus in the mouse and rat.

A significant increase of cell multiplication in inoculated ascitic and solid tumors was demonstrated in both DBA/2 and C57BL/6 mice as well as in Wistar rats after radiofrequency lesions in the median hypothalamus (ventromedial and dorsomedial nuclei; part of arcuate nucleus). The following tests were performed: mitotic and metaphasic index, doubling time of tumor, incorporation of tritiated thymidine into DNA, cell cycle parameters and growth fraction. The increased rate of cell proliferation measured was predominantly due to the higher speed of DNA biosynthesis with a minor contribution by an increase of the growth fraction. In the animals with hypothalamic lesions we demonstrated a slight decrease in the secretory activity of the adenohypophysis. Because it is generally stated that failure of hypophysis function hinders cell multiplication in normal and neoplastic tissues, we think that heightened cell proliferation after hypothalamic lesions is due to suppression of an inhibitory mechanism located in the hypothalamus and which is independent of the hypophysis.

Animals↗