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R Dana

Publications and source records attributed to R Dana.

At least 19 recordsLinked to original sources
PubMed2004

Morphofunctional changes in neurons in the temporal cortex of the brain in relation to spatial memory in bulbectomized mice after treatment with mineral ascorbates.

The effects of an antioxidant mixture of mineral ascorbates (MA) on the state of neurons in the temporal area of the cortex and the behavior of mice subjected to bulbectomy (BE) were studied; these mice, as demonstrated previously, are characterized by deficiency of spatial memory and the development of a neurodegenerative process in brain structures showing pathological changes in Alzheimer's disease. One month after BE, there were abnormalities in the cytoarchitectonics of the temporal area of the cortex, with loss of clarity of the boundaries between its layers because of dystrophy of pyramidal neurons and foci of loss of these cells. There were sharp increases in the numbers of neurons showing pyknosis, karyolysis, and vacuolysis on the background of decreases in neuronal density. Three weeks of treatment by addition of MA to the diet prevented the degradation of spatial memory in mice after BE and protected neurons in the temporal area of the cortex from degenerative changes. These results provide evidence for the possibility of prophylaxis of neurodestructive changes of the Alzheimer's type.

Animals↗
PubMed2003

[Morpho-functional changes of neurons in temporal cortex in comparison with spatial memory in bulbectomized mice after treatment with minerals and ascorbates].

The effect of antioxidant mixture of mineralascorbates (MA) on the status of neurons of brain temporal cortex and behavior of mice after olfactory bulbectomy (BE) was studied, as it was previously shown by us that these animals were characterized by a deficit of spatial memory and development of neurodegenerative process in brain structures, which are affected by Alzheimer disease. Disorganization of cytoarchitectonics of temporal cortex with the deletion of its layers as a result of dystrophy of pyramidal neurons and foci of their complete disappearance were shown 1 month after BE. The increased number of neurons with the phenomena of karyopyknosis, karyolysis and vacuolysis was observed with a concomitant reduction in neuronal density. Addition of MA to the diet for three weeks prevented the development of deterioration of spatial memory in mice after BE and protected the neurons of brain temporal cortex from the degenerative changes. The results obtained suggest the possibility of realization of prophylaxis aimed at the prevention of the development of Alzheimer-type neurodestructive processes.

Animals↗
PubMed2000

Elevated cytosolic phospholipase A(2) expression and activity in human neutrophils during sepsis.

Sepsis is defined as the systemic inflammatory response to infection. Phospholipase A(2) (PLA(2)) plays an important role in inflammation processes by initiating the production of inflammatory mediators. The role of cytosolic PLA (cPLA(2)) has not yet been identified in inflammatory and infectious disease clinical settings. The aim of the present research was to determine whether cPLA(2) activity has a role during sepsis. Since neutrophil activation has been documented during sepsis, these cells were chosen as a model to evaluate the function of cPLA(2) in this clinical setting. cPLA(2 )was studied at 3 levels: activity, protein expression, and messenger RNA (mRNA). Neutrophils from 32 septic patients with and without bacteremia were examined. cPLA(2) activity was measured using labeled phosphatidyl choline vesicles as a substrate, and total PLA(2) was determined by the release of labeled arachidonic acid from prelabeled cells. A significant increase in cPLA(2) activity, protein expression, and total PLA(2) activity in neutrophils was detected during sepsis. mRNA levels, detected by reverse transcriptase-polymerase chain reaction, were significantly higher during sepsis, indicating that the increase in the amount of cPLA(2) is regulated on the mRNA level. The significant elevation of cPLA(2) activity and expression in neutrophils during sepsis suggests that this enzyme plays a major role in neutrophil function in this clinical setting. (Blood. 2000;95:660-665)

Adult↗
PubMed2000

Cytosolic phospholipase A2 is required for the activation of the NADPH oxidase associated H+ channel in phagocyte-like cells.

The NADPH oxidase producing-superoxide is the major mechanism by which phagocytes kill invading pathogens. The human myeloid cell line PLB-985 was transfected to express p85 cytosolic phospholipase A2 (cPLA2) antisense mRNA and stable clones were selected which lack detectable cPLA2. cPLA2-deficient PLB-985 cells differentiate similarly to control PLB-985 cells in response to retinoic acid, DMSO or 1,25 dihydroxyvitamin D3 indicating that cPLA2 is not involved in the differentiation process. Despite the normal synthesis of NADPH oxidase subunits during differentiation of cPLA2-deficient PLB-985 cells, these cells fail to activate NADPH oxidase in response to a variety of soluble and particulate stimuli, but addition of exogenous arachidonic acid (AA) fully restores oxidase activity. This establishes an essential requirement of cPLA2 generated AA for activation of phagocyte NADPH oxidase. In order to elucidate the mechanism by which cPLA2 regulates the oxidase, the role of cPLA2 in NADPH oxidase associated H+ channel was studied. Activation of differentiated PLB cells resulted in a Zn+2 sensitive alkalization, indicating H+ channel activity. In contrast, differentiated PLB-D cells failed to activate the H+ channel, but addition of exogenous AA fully restored this activity, indicating an essential and specific physiological requirement of cPLA2-generated AA for activation of the H+ channel. The presence of the H+ channel inhibitor, Zn+2, caused significant inhibition of NADPH oxidase activity, suggesting a role of the NADPH oxidase associated H+ channel in regulating oxidase activity.

Arachidonic Acid↗
PubMed1998

Essential requirement of cytosolic phospholipase A2 for activation of the phagocyte NADPH oxidase.

Arachidonic acid (AA) can trigger activation of the phagocyte NADPH oxidase in a cell-free assay. However, a role for AA in activation of the oxidase in intact cells has not been established, nor has the AA generating enzyme critical to this process been identified. The human myeloid cell line PLB-985 was transfected to express p85 cytosolic phospholipase A2 (cPLA2) antisense mRNA and stable clones were selected that lack detectable cPLA2. cPLA2-deficient PLB-985 cells differentiate similarly to control PLB-985 cells in response to retinoic acid or 1,25-dihydroxyvitamin D3, indicating that cPLA2 is not involved in the differentiation process. Neither cPLA2 nor stimulated [3H]AA release were detectable in differentiated cPLA2-deficient PLB-985 cells, demonstrating that cPLA2 is the major type of PLA2 activated in phagocytic-like cells. Despite the normal synthesis of NADPH oxidase subunits during differentiation of cPLA2-deficient PLB-985 cells, these cells fail to activate NADPH oxidase in response to a variety of soluble and particulate stimuli, but the addition of exogenous AA fully restores oxidase activity. This establishes an essential requirement of cPLA2-generated AA for activation of phagocyte NADPH oxidase.

Biological Transport↗
PubMed1998

Granular cell ameloblastoma of jaw. A report of rare case and brief review of literature.

Ameloblastoma is an epithelial odontogenic tumour of the jaw and exhibits diverse microscopic patterns which occurs either singly or in combination with other patterns. The rare granular cell variant is seen in combination usually with follicular or plexiform subtypes. The reported case reveals the microscopic patterns characteristic of granular cell variant only, which is uncommon. The tumour was excised and no recurrence has been observed after nineteen months of surgery.

Adult↗
PubMed1997

Cytosolic phospholipase A2 and its mode of activation in human neutrophils by opsonized zymosan. Correlation between 42/44 kDa mitogen-activated protein kinase, cytosolic phospholipase A2 and NADPH oxidase.

The role of cytosolic phospholipase A2 (cPLA2) and its mode of activation by opsonized zymosan (OZ) was studied in human neutrophils in comparison with activation by PMA. The activation of cPLA2 by 1 mg/ml OZ or 50 ng/ml PMA is evidenced by its translocation to the membrane fractions on stimulation. This translocation is consistent with dithiothreitol (DTT)-resistant phospholipase A2 (PLA2) activity detected in the membranes of activated cells. Neutrophils stimulated by either OZ or PMA exhibited an immediate stimulation of extracellular-signal-regulated kinases (ERKs). The inhibition of ERKs, DTT-resistant PLA2 and NADPH oxidase activities by the MAP kinase kinase inhibitor PD-98059 indicates that ERKs mediate the activation of cPLA2 and NADPH oxidase stimulated by either OZ or PMA. The protein kinase C (PKC) inhibitor GF-109203X inhibited epidermal growth factor receptor peptide kinase activity, the release of [3H]arachidonic acid, DTT-resistant PLA2 activity and superoxide generation induced by PMA, but did not inhibit any of these activities induced by OZ. PKC activity was similarly inhibited by GF-109203X in membrane fractions separated from neutrophils stimulated by either PMA or OZ. In the presence of the tyrosine kinase inhibit orgenistein, ERKs, PLA2 and NADPH oxidase activities were inhibited in cells stimulated by OZ, whereas they were hardly affected in cells stimulated by PMA. The results suggest that the activation of cPLA2 by PMA or OZ is mediated by ERKs. Whereas PMA stimulates ERKs activity through a PKC-dependent pathway, signal transduction stimulated by OZ involves tyrosine kinase activity leading to activation of ERKs via a PKC-independent pathway.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1996

Comparison of oral and intravenous hydration and diuretic, choice for protecting cisplatin induced nephrotoxicity.

Efficacy of oral hydration was compared with that of traditional intravenous hydration along with comparison of furasemide with mannitol in 65 patients of solid tumours undergoing Cisplatin based anterior chemotherapy. Incidence of reversible uremia was found to be equivalent in the series. Our results suggest superiority of oral hydration and furosemide diuresis owing to cost efficiency and patient comfort.

Administration, Oral↗
PubMed1994

The requirement of p47 phosphorylation for activation of NADPH oxidase by opsonized zymosan in human neutrophils.

Protein kinase C (PKC) inhibitors, staurosporine or 1,5-isoquinolinesulfonyl)-2-methylpiperazine (H7), inhibited NADPH oxidase activity and phosphorylation of 47 kDa protein (p47) in PMA-stimulated neutrophils in a dose-dependent manner. These PKC inhibitors, at the same doses, did not affect oxidase activity and caused only partial inhibition of p47 phosphorylation in OZ-stimulated neutrophils. There was residual (20%) phosphorylated p47 in the membranes of OZ-stimulated cells in the presence of PKC inhibitors, at concentrations which caused total inhibition of oxidase activity and p47 phosphorylation in PMA-stimulated neutrophils. In the presence of ionomycin, which increased intracellular calcium ion concentrations, staurosporine was less effective in inhibiting both superoxide generation and p47 phosphorylation stimulated by PMA, similar to its effect in OZ-stimulated cells. The results indicate that some phosphorylation of p47 always accompanied oxidase activation induced by PMA or OZ, though the degree of phosphorylation of membrane-bound p47 does not directly correlate with rates of superoxide production.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

The requirement for phospholipase A2 for activation of the assembled NADPH oxidase in human neutrophils.

Phospholipase A2 (PLA2) inhibitors suppressed simultaneously, in a dose-dependent manner, the activation of NADPH oxidase and the release of 3H-labelled arachidonic acid ([3H]AA) stimulated by either phorbol 12-myristate 13-acetate (PMA) or opsonized zymosan (OZ) in human neutrophils. In spite of total inhibition of superoxide production in the presence of the PLA2 inhibitors, 10 microM bromophenacyl bromide (BPB) or 20 microM quinacrine, a maximal phosphorylation of p47 and translocation of p47 and p67 to the neutrophil membranes induced by PMA or OZ was observed. Addition of 10 microM free AA, which by itself did not stimulate superoxide generation, restored oxidase activity in neutrophils treated with PLA2 inhibitors. These findings indicate that phosphorylation and translocation of the cytosolic factors to the membranes are not sufficient for generating superoxide; a functional PLA2 is also needed to stimulate the oxidase activity. The inhibition of PLA2 activity did not prevent the phosphorylation of p47, suggesting that the location of PLA2 is downstream of and does not activate protein kinase C.

Acetophenones↗
PubMed1992

Decreased G-CSF and IL-3 production and gene expression from mononuclear cells of newborn infants.

Newborns are predisposed to neutropenia and thrombocytopenia during bacterial sepsis. The presence of peripheral cytopenias during overwhelming infection may be secondary to decreased hematopoietic growth factor production during states of increased demand. We therefore examined circulating levels of granulocyte-colony stimulating factor (G-CSF) and IL-3, production of G-CSF and IL-3 from unstimulated and stimulated mononuclear cells (MNC), expression of G-CSF and IL-3 genes during unstimulated and stimulated conditions, and equilibrium and binding of G-CSF receptors on mature effector peripheral blood cells of adults and neonates. Serum from cord and adult peripheral blood contained negligible amounts of both G-CSF (less than or equal to 50 pg/mL) and IL-3 (less than or equal to 5 pg/mL). Constitutive supernatant levels of G-CSF and IL-3 from cord and adult unstimulated MNC were also undetectable. However, there was a significant difference in G-CSF and IL-3 production from stimulated cord and adult MNC. Supernatants from stimulated adult MNC had significantly more G-CSF (p less than 0.007) and IL-3 (p less than 0.02). Additionally, Northern blot hybridization and densitometry of autoradiographs demonstrated significantly more G-CSF and IL-3 mRNA transcripts from adult than from cord MNC. Lastly, affinity, binding, and number of G-CSF receptors on cord and adult peripheral effector cells were equal. These data suggest that, during states of increased demand, cord MNC produce less G-CSF and IL-3 than do adult MNC and have an associated reduction in their respective mRNA transcripts. These findings may have implications in the pathogenesis of neonatal cytopenias during states of increased demand, such as sepsis.

Adult↗
PubMed1991

Influence of calcium channel blockers on polymorphonuclear and monocyte bactericidal and fungicidal activity.

The effect of calcium channel blocking agents on the killing activity of human peritoneal polymorphonuclears (PMN) and monocytes was studied. The organisms used were Escherichia coli, Staphylococcus aureus and Candida albicans. The pharmacological concentration of verapamil (5 microM), nifedipine (10 microM) and diltiazem (10 microM) caused a similar inhibition of killing activity in both PMN and monocytes. The calcium channel blockers significantly reduced the in vitro killing of E. coli, S. aureus and C. albicans by PMN to about 47%, 30% and 20% respectively, compared with 81 +/- 6%, 65 +/- 5% and 40 +/- 4% in the controls. The killing of these organisms by monocytes was 60 +/- 6%, 42 +/- 7% and 35 +/- 5% respectively, as compared with 30%, 20% and 17% in the presence of these drugs. The bactericidal activity of the phagocytic cells from patients under treatment with calcium channel blockers was not affected and was found to be within the normal range, indicating that calcium channel blockers do not cause an irreversible impairment in PMN and monocyte killing activity. However, their potential inhibition of phagocytic cell activity should be taken into consideration during treatment.

Adult↗
PubMed1988

Human growth hormone releasing factor infusion effects on plasma growth hormone in affective disorder patients and normal controls.

In a preliminary, prospective pilot study, five patients with major depressive disorder and eleven age and sex matched normal controls received intravenous human growth hormone releasing factor (hGRF) (1 microgram/kg in 5 cc of normal saline infused over five minutes) and placebo. Thirty minutes after insertion of the catheter, blood was sampled every 15 minutes for thirty minutes prior to and for 2 hours subsequent to intravenous infusion of hGRF or placebo. hGRF but not placebo caused significant elevations of plasma growth hormone levels in all subjects. Of interest, the depressed patients had a significantly attenuated rise in plasma growth hormone concentrations when compared with the normal controls. These results must be considered preliminary awaiting replication with a larger subject population.

Adult↗
PubMed1986

Activating and 'anxiogenic' effects of corticotropin releasing factor are not inhibited by blockade of the pituitary-adrenal system with dexamethasone.

Central administration of corticotropin releasing factor (CRF) in rats produces pituitary-adrenal activation and a variety of "anxiogenic-like" effects. The present study was designed to explore the contribution of the peripheral pituitary-adrenocortical axis in mediating these CRF responses. Intraventricularly administered CRF produced suppression of responding in the conflict test and a marked locomotor activation. Neither behavioral effect was altered by the prior administration of dexamethasone in a dose that blocked pituitary-adrenal activation to CRF. These results support the hypothesis that behavioral effects of CRF are mediated by its action at central sites and not via an action on the pituitary-adrenocortical system.

Animals↗
PubMed1986

Enhanced elevation of corticosterone following arecoline administration to rats selectively bred for increased cholinergic function.

Serum corticosterone levels were determined following administration of the cholinergic agonist arecoline (4 mg/kg) to rats selectively bred for differences in cholinergic function. The Flinders Sensitive Line (FSL) of rats exhibited both greater suppression of behavioural activity and enhanced elevation fo serum corticosterone than the Flinders Resistant Line of rats. These enhanced responses to arecoline in the FSL rats parallel those reported in depressed humans, suggesting that these rats may provide a new animal model of affective disorders.

Animals↗
PubMed1986

Neuroendocrine responses in psychiatric and pain patients with major depression.

Basal and postdexamethasone concentrations of cortisol and prolactin were studied in three groups of male patients: chronic pain patients with no psychiatric diagnosis (n = 12), chronic pain patients with coexisting major depression by Research Diagnostic Criteria (RDC) (n = 24), and pain-free psychiatric patients meeting RDC criteria for major depression (n = 28). Basal cortisol concentrations were significantly higher in pain-major depression and psychiatric-major depression patients compared to pain patients without psychiatric illness. The frequency of cortisol nonsuppression after dexamethasone was significantly greater in pain patients with major depression (41.7%) compared to pain patients without psychiatric disorder (8.3%), and was comparable to that of psychiatric patients (21.4%). Prolactin concentrations, but not cortisol levels, were significantly correlated with observer-rated severity of depression in pain patients. These findings suggest that cortisol and prolactin abnormalities in chronic pain may be related to psychiatric disorder rather than to pain per se, at least in male patients, and may indicate a role for cholinergic mechanisms in the interface of pain and depression.

Adult↗
PubMed1985

[Drug metabolism in the septic liver: conclusions about the pharmacokinetics of chloramphenicol].

In nine patients in anaerobic septic shock, five of them with hepatic injury compatible with sepsis liver failure, hematic chloramphenicol concentration was determined at 5 minutes, 1, 2, 3 and 6 hours after intravenous administration of the first of three daily dose (50 mg/k/day); in the hepatic failure group the procedure was repeated with the next dose, previous attempt of haemodynamic compensation with two hours dopamine (3-10 mcg/k/min.) infusion. Starting from experimental data computation adjustment of time-concentration curve and lineal regression with a p = 0.0001 adjustment was done, determining half live (HL), distribution volume (DV), constant of elimination (K) and clearance (CL). In septic shock without hepatic injury patient group, there was noticed a uniform behavior in time-concentration graphic, withdrawn from chloramphenicol bone-marrow depression levels and pharmacokinetics parameters quite near the normal ones, with a reasonable extension of (DV). When attempting hepatic injury patient group, though an individual variability, drug concentration reach bone marrow depression levels and there was a significant lowering of Cl (p = 0.001) and a reasonable one of DV. Dopamine haemodynamic compensation attempt results in an increase of chloramphenicol hematic concentration in the sepsis liver group and the pharmacokinetics levels bear new deterioration. Practical meaning of the methodology used in drug handling in severe hepatic failure is stressed, to allow mathematic valuation of different pathogenic compounds. Though each patient should be individually evaluated, in septic shock without liver injury chloramphenicol dosification should not been any changes but in presence of sepsis liver doses should be diminished to half and administration interval extended to 11.5 hours.

Chloramphenicol↗