Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of lactacidosis was analyzed in vitro by employment of C 6 glioma cells and astrocytes from primary culture. The cells were suspended in an incubation chamber under continuous control of pH, temperature and pO2. Cell swelling and viability were quantified by flow cytometry using propidium iodide for staining of dead cells. After a control period, the pH of the suspension medium was titrated to levels between pH 6.8 down to 4.2 by addition of isotonic lactic acid. Acidification below pH 6.8 led to an immediate swelling of C 6 glioma cells as well as of astrocytes. The degree of cell swelling was related to the decrease in pH and the duration of exposure. For instance, lactacidosis of 60 min at pH 6.2 resulted in an increase of glial volume to 124.5 +/- 4.6%, while pH 4.2 in an increase to 190.9 +/- 8.4%. Cell viability remained unchanged down to pH 6.2. At pH 5.6 and below viability decreased in relation to the severity of acidosis. When sulfuric acid was used, the extent of cell swelling at pH 5.6 was only 50% of what was found by addition of lactic acid, whereas cell viability was not differently affected. The results demonstrate a specific efficacy of lactic acid to induce glial swelling, which might be due to a cellular accumulation of the compound.
 ...
PMID:Effects of lactacidosis on volume and viability of glial cells. 208 21

Effects of severe lactacidosis were analyzed in vitro by employment of C6 glioma cells and astrocytes from primary culture. The cells were suspended in a physiological medium, which was rendered acidotic by addition of lactic acid in rising concentrations. A pH range of 7.4-4.2 was studied under maintenance of isotonicity and a normal electrolyte concentration of the medium. Cell swelling was quantified by flow cytometry using an advanced Coulter system with hydrodynamic focusing. The method was also utilized for assessment of cell viability by exclusion of the fluorescent dye propidium iodide. The volume of C6 glioma cells was found to increase if the pH was titrated to pH 6.8 or below. From this level downward, the extent of cell swelling depended on the degree of acidosis and the duration of exposure. For example, lactacidosis of pH 6.2 for 60 min led to an increase in cell size to 124.5% of normal, while pH 5.0 or 4.2 led to a cell size of 151.1 or 190.9%, respectively. A comparative analysis of the acidosis-induced cell swelling was made by using sulfuric acid. Swelling of C6 glioma at a given pH was only half of what was found when using lactic acid. This indicates specific swelling-inducing properties of lactic acid, while cell viability was not differently affected by both acids. Of the C6 glioma cells, 89.1% were viable under control conditions at pH 7.4. The viability remained unchanged down to pH 6.2. At pH 5.6, viability remained normal for 30 min, but it decreased to 73.4% after 60 min. Further lowering of pH to 5.0 or 4.6 respectively, decreased the number of viable cells to 47.8 or 40.3%. At pH 4.2 only 21.1% of the cells were surviving 1 h of lactacidosis. Cell swelling from lactacidosis could be largely inhibited by replacement of Na+ and bicarbonate ions in the medium by choline chloride and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid buffer, suggesting an involvement of the Na+/H+ and Cl-/HCO3- antiporters in the swelling process. Omission of Na+ and bicarbonate was, however, associated with reduced viability of the glial cells in acidosis. The swelling response of astrocytes obtained from primary culture was similar to that of C6 glioma. Lactic acid was also more effective in inducing cell swelling than sulfuric acid at the same level of acidosis. In astrocytes, viability at, e.g., pH 5.6 appeared to be more affected by lactic than by sulfuric acid.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Effects of lactacidosis on glial cell volume and viability. 221 80

Swelling of glial and nerve cells is characteristic of brain damage in cerebral ischemia or trauma. The therapeutical efficiency of inhibition of Cl(-)-transport by a novel antagonist, the diuretic torasemide, on cytotoxic swelling of glial cells from lactacidosis, or glutamate was analyzed. Lactacidosis and the interstitial accumulation of glutamate are hallmarks of the pathophysiological alterations in ischemic or traumatic brain tissue. C6 glioma cells harvested from culture and suspended in a physiological medium were either exposed to pH 6.2, or 5.0 by lactic acid, or exposed to 1 mM glutamate at normal pH. Cell swelling and viability were quantified by flow cytometry. Lactacidosis of pH 6.2 led to an increase in cell volume to 117.9 +/- 0.7% within 60 min. Torasemide (1 mM) inhibited the swelling response by 50% (P < 0.01). Cell swelling at pH 5.0, although more severe, was again attenuated by torasemide (P < 0.01). No effect was seen on the decrease in cell viability at this level of acidosis. Addition of glutamate led to a steady increase in cell volume which, contrary to cell swelling from lactacidosis, was not inhibited by torasemide. Inhibition of cell swelling from acidosis by this diuretic may be attributed to blocking of Cl-/HCO3- exchange mechanisms activated by acidosis. The lack of effect by torasemide in glial cell swelling from glutamate indicates operation of a different mechanism inducing cell swelling, for example cellular accumulation of the amino acid together with Na+ and water.
 ...
PMID:Swelling of glial cells in lactacidosis and by glutamate: significance of Cl(-)-transport. 768 80

Lactacidosis occurring in cerebral ischemia or trauma is a major mechanism of cytotoxic brain edema and brain damage. Respective effects of lactacidosis were currently analyzed in vitro by employment of the murine neuronal cell line, Neuro-2A, in order to obtain a better understanding of specific mechanisms underlying cell swelling and cell death in comparison with glial cells. The cells were suspended in a physiological medium in the presence of lactic acid at increasing concentrations. Levels of acidosis reaching from pH 6.8-5.6 were obtained while other parameters, such as osmolarity and electrolyte concentrations, were maintained in the physiological range. Assessment of cell swelling and cell viability using exclusion of propidium iodide was made by flow cytometry with employment of an advanced Coulter system. Swelling of Neuro-2A cells commenced once the pH in the medium was lowered to 6.8 or below. From this level downward, cell swelling was a function of the severity of acidosis and duration of exposure. For example, lactacidosis of pH 6.8 or 5.6 lasting 90 min led to an increase in cell volume to 109.5% or 159.6% of normal, respectively. Viability of the neuronal cells was 85% under control conditions. It remained in this range down to pH 6.2. At pH 5.6, however, cell viability decreased in a time-dependent fashion. At 90 min, only 48.9% of the neuronal cells were viable at pH 5.6. The swelling response and impairment of viability of the neuronal cells was compared with that of C6 glioma cells.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Swelling and death of neuronal cells by lactic acid. 824 14

The mechanism of cellular swelling induced by extra-cellular lactic acidosis and the effect of diuretics were studied using neuroblastoma-glioma hybrid (NG108-15) cells. The cells were incubated in one of three lactate concentrations (0, 15, or 30 mM), each of which was randomized to one of three pH groups (7.4, 6.2, or 5.0). Analysis of the swelling was measured using a Coulter counter technique. Cellular swelling was most prominent at pH 6.2 at all lactate levels. Cellular swelling was noted to be pH dependent but not lactate dependent. The addition of 1 mM amiloride completely blocked cellular swelling, suggesting that the main mechanism of neuronal cellular swelling induced by extracellular lactic acidosis was the activation of Na+/H+ exchange. Second, three dissimilar diuretic drugs were used for cellular swelling: amiloride (Na+/H+ exchange inhibitor), mannitol (osmotic diuretic), and bumetanide (loop diuretic). Amiloride and mannitol were found effective in reducing the lactic acidosis-induced cellular swelling. Furthermore, the combination of these drugs had additive effects. However, bumetanide was not effective. The results indicate that the direct inhibition of Na+/H+ exchange and/or removal of water from the cell by mannitol was effective against cellular swelling induced by the activation of Na+/H+ exchange in NG108-15 cells.
 ...
PMID:Mechanism of cellular swelling induced by extracellular lactic acidosis in neuroblastoma-glioma hybrid (NG108-15) cells. 889 76

The therapeutical efficacy of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate), an isomer of the intracellular messenger IP3, was analyzed on cytotoxic swelling and damage of glial cells in vitro from lactacidosis or glutamate. C6 glioma cells suspended in a physiological medium were either exposed to pH 5.0 by administration of lactic acid, or to 1 mM glutamate. Cell swelling and viability were quantified by flow cytometry. Lactacidosis of pH 5.0 led to an increase in cell volume to 139.7 +/- 1.3% within 20 min whereas alpha-trinositol was reducing the swelling response by approximately 25% (P < 0.01). In addition, at pH 5.0 the fraction of viable cells was lowered from 94.3 +/- 0.2% (control) to only 53.8 +/- 3.1% after 60 min. Alpha-trinositol was found to protect also cell viability; at 60 min of lactacidosis 70.2 +/- 1.6% of the cells still were viable (P < 0.01). The addition of glutamate (1 mM) to the cell suspension led to a steady increase in cell size, reaching 110% of control at 120 min, irrespectively of whether alpha-trinositol was added or not.
 ...
PMID:Swelling and damage of glial cells by lactacidosis and glutamate: effect of alpha-trinositol. 935 18

Tissue acidosis occurring in cerebral ischemia and traumatic brain injury is a mediator of cytotoxic brain edema. In vitro, extracellular lactacidosis induces swelling of glial cells in a dose dependent manner. pH-regulatory membrane transporters and channels have been identified which are involved in the increase of the glial cell volume. Underlying mechanisms of their activation are poorly understood, however. We have, therefore, addressed the question, whether and how Ca(2+)-ions play a role in acidosis-induced glial swelling and intracellular acidification. For that purpose C6 glioma cells were suspended and the pH in the medium was lowered from 7.4 (baseline) to 6.2 by isotonic lactic acid. Cell volume and intracellular pH (pHi) were assessed by flow cytometry. In the presence of Ca(2+)-ions the cell volume reached a maximum of 125.1% from acidosis. In experiments using a calcium-free suspension medium, cell swelling from acidosis was inhibited by 74%. Additional buffering of intracellular calcium (Ca2+i) had no further inhibitory effect on acidosis-induced cell swelling, while buffering of Ca2+i by BAPTA-AM alone did not affect the glial volume increase secondary to administration of lactic acid. pHi which was decreasing from acidosis was not affected by the experimental modifications of the Ca(2+)-concentration in the medium or cytosol. The present data indicate that lactacidosis-induced glial swelling depends on the presence of extracellular Ca(2+)-ions, while release of Ca(2+)-ions from intracellular stores does not seem to be involved.
 ...
PMID:Role of calcium ions in acidosis-induced glial swelling. 941 4

The therapeutic efficacy of alpha-trinositol (D-myo-inositol-1,2,6-trisphosphate), an isomer of the intracellular messenger IP3, was analyzed for cytotoxic swelling and damage of glial cells in vitro from lactacidosis or glutamate. Lactacidosis and the interstitial accumulation of glutamate are prominent sequelae in ischemic or traumatic brain tissue. C6 glioma cells harvested from culture and suspended in a physiological medium were either exposed to pH 5.0 by administration of lactic acid, or to 1 mM glutamate at normal pH. Cell swelling and viability were quantified by blood flow cytometry. Addition of alpha-trinositol (3 mM) under control conditions at pH 7.4 resulted in transient cell shrinking to 96.5 +/- 1.3% of control within 3 min (p < 0.05). Lactacidosis of pH 5.0 led to an increase in cell volume to 139.7 +/- 1.3% within 20 min, whereas alpha-trinositol reduced the swelling response by approximately 25% (p < 0.01). In addition, cell viability was severely affected at pH 5.0 amounting to only 53.8 +/- 3.1% after 60 min. alpha-Trinositol was found to markedly improve cell viability; at 60 min 70.2 +/- 1.6% of the cells were still viable (p < 0.01). Addition of glutamate (1 mM) led to a steady increase in cell size, reaching 110% of control after 120 min, irrespective of wether alpha-trinositol was present or not. The attenuation of cell swelling may be attributed to an interference with pH-regulatory mechanisms, such as the Na+/H(+)-antiporter, while protection of cell viability might be caused be effects of alpha-trinositol on Ca(2+)-overload. On the other hand, the increase in cell volume by glutamate associated with its intracellular uptake was not influenced by alpha-trinositol.
 ...
PMID:Effect of alpha-trinositol on swelling and damage of glial cells by lactacidosis and glutamate. 941 15

A major factor in secondary brain injury following cerebral trauma is accumulation of lactic acid resulting in glial swelling. Further, evidence obtained in this context demonstrates activation of protein kinase C (PKC) under these circumstances. Glial swelling from acidosis is attributable to activation of the Na+/H(+)-exchanger, mediating influx of Na(+)-ions in exchange for the extrusion of H+ ions. The antiporter is activated following phosphorylation by PKC. The current study was made to elucidate the role of PKC activation in acidosis-induced glial swelling. For that purpose, suspended C6 glioma cells were used to examine changes of the cell volume and intracellular pH (pHi). Acidosis was induced by administration of isotonic lactic acid. Stimulation of PKC by the phorbol-ester PMA was significantly enhancing glial swelling from severe acidosis (pH 6.2), whereas the decrease of pHi was somewhat attenuated. On the other side, inhibition of PKC by staurosporine did not affect cell swelling nor the decrease of pHi from acidosis. The results indicate that activation of PKC in cerebral trauma or ischemia may enhance glial swelling from lactacidosis.
 ...
PMID:Role of protein kinase C in acidosis induced glial swelling--current understanding. 941 29

The effect of mild (32 degrees C) and moderate (27 degrees C) hypothermia was analyzed on the cell volume and intracellular pH (pHi) of C6 glioma cells at normal pH and during lactacidosis at pH 6.2 in vitro. The cells were suspended in an incubation chamber under continuous control of pH, PO2 and temperature. Cell swelling was quantified by an advanced Coulter-system. pHi was measured by flow cytometry using the fluorescent dye bis-carboxyethyl carboxyfluorescein (BCECF). Following a control period at 37 degrees C, the ambient temperature was decreased to 32 degrees C for 30 min, and subsequently to 27 degrees C for another 30 min. Hypothermia alone led to an immediate and significant cell volume increase of 107.3 +/- 0.4% (mean +/- SEM) of control after 30 min at 32 degrees C, and further swelling to 110.5 +/- 0.9% after 30 min at 27 degrees C. Yet, hypothermia (27 degrees C) afforded partial protection against the acidosis-induced cell swelling at pH 6.2, which was reaching to 120.4 +/- 0.9% in the normothermic control group after 60 min, while only to 111.3 +/- 0.9% at 27 degrees C. Hypothermia, however, was associated with a more pronounced decrease of the pHi during acidosis (6.3 +/- 0.04) as compared to that of the normothermic control falling then to 6.5 +/- 0.03. The results demonstrate that mild and moderate hypothermia induce glial cell swelling, but simultaneously inhibit cell swelling from acidosis. The protection against cell swelling, however, has its price as indicated by the enhancement of the intracellular acidification.
 ...
PMID:Effect of mild and moderate hypothermia on the acidosis-induced swelling of glial cells. 941 41


1 2 Next >>