Biomedical subjects

B Pardo

Publications and source records attributed to B Pardo.

At least 19 recordsLinked to original sources

PubMed2005

Randomized phase II trial of carboplatin versus paclitaxel and carboplatin in platinum-sensitive recurrent advanced ovarian carcinoma: a GEICO (Grupo Espanol de Investigacion en Cancer de Ovario) study.

BACKGROUND: The aim of this study was to determine whether the response rate for the paclitaxel-carboplatin combination is superior to carboplatin alone in the treatment of patients with platinum-sensitive recurrent ovarian carcinoma. PATIENTS AND METHODS: Patients with recurrent ovarian carcinoma, 6 months after treatment with a platinum-based regimen and with no more than two previous chemotherapy lines, were randomized to receive carboplatin area under the curve (AUC) 5 (arm A) or paclitaxel 175 mg/m(2) + carboplatin AUC 5 (arm B). The primary end point was objective response, following a 'pick up the winner' design. Secondary end points included time to progression (TTP), overall survival, tolerability and quality of life (QoL). RESULTS: Eighty-one patients were randomized and included in the intention-to-treat analysis. The response rate in arm B was 75.6% [26.8% complete response (CR) + 48.8% partial response (PR)] [95% confidence interval (CI) 59.7% to 87.6%] and 50% in arm A (20% CR + 30% PR) (95% CI 33.8% to 66.2%). No significant differences were observed in grade 3-4 hematological toxicity. Conversely, mucositis, myalgia/arthralgia and peripheral neurophaty were more frequent in arm B. Median TTP was 49.1 weeks in arm B (95% CI 36.9-61.3) and 33.7 weeks in arm A (95% CI 25.8-41.5). No significant differences were found in the QoL analysis. CONCLUSIONS: Paclitaxel-carboplatin combination is a tolerable regimen with a higher response rate than carboplatin monotherapy in platinum-sensitive recurrent ovarian carcinoma.

Adult↗

PubMed2002

Parametric and resonant transition radiation in periodic stratified structures.

We consider the problem of electromagnetic emission when an electrically charged particle crosses a periodically stratified structure following an arbitrary linear trajectory. A theory generalizing a recently developed method [Phys. Rev. E 63, 016613 (2001)] is presented in the framework of the classical theory of electromagnetism in continuous media. It allows one to account for both the so-called parametric radiation and the resonant transition radiation. We implement our model to interpret the experiments performed by Kaplin et al. [Appl. Phys. Lett. 76, 3647 (2000)] in the x-ray domain with a stack of 300 W/B(4)C bilayers irradiated by 500 MeV electrons.

Journal Article↗

PubMed2001

Citrin and aralar1 are Ca(2+)-stimulated aspartate/glutamate transporters in mitochondria.

The mitochondrial aspartate/glutamate carrier catalyzes an important step in both the urea cycle and the aspartate/malate NADH shuttle. Citrin and aralar1 are homologous proteins belonging to the mitochondrial carrier family with EF-hand Ca(2+)-binding motifs in their N-terminal domains. Both proteins and their C-terminal domains were overexpressed in Escherichia coli, reconstituted into liposomes and shown to catalyze the electrogenic exchange of aspartate for glutamate and a H(+). Overexpression of the carriers in transfected human cells increased the activity of the malate/aspartate NADH shuttle. These results demonstrate that citrin and aralar1 are isoforms of the hitherto unidentified aspartate/glutamate carrier and explain why mutations in citrin cause type II citrullinemia in humans. The activity of citrin and aralar1 as aspartate/glutamate exchangers was stimulated by Ca(2+) on the external side of the inner mitochondrial membrane, where the Ca(2+)-binding domains of these proteins are localized. These results show that the aspartate/glutamate carrier is regulated by Ca(2+) through a mechanism independent of Ca(2+) entry into mitochondria, and suggest a novel mechanism of Ca(2+) regulation of the aspartate/malate shuttle.

Amino Acid Transport Systems, Acidic↗

PubMed2001

Fungal infections in patients with solid tumors treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation.

The incidence and risk factors for fungal infection were assessed in 291 patients who had solid tumors and were undergoing autologous peripheral blood stem cell transplantation. The first 162 patients received prophylactic itraconazole, and 129 patients received nystatin. Empiric amphotericin B was given at day 7 of febrile neutropenia. Fungal infections developed in 52 patients: 47 (16%) were superficial and 6 (2%) were systemic. Itraconazole prophylaxis and only a few days of febrile neutropenia were independently associated with a decrease in the incidence of superficial infections. Only two patients required empiric amphotericin B. Systemic antifungal prophylaxis does not seem to be justified for patients with solid tumors and autologous peripheral blood stem cell transplantation. Empiric amphotericin B may be safely started at day 7 of febrile neutropenia.

Adolescent↗

PubMed2001

[Changes in dietary habits and selected cardiovascular risk factors of the Warsaw population over the 5-year observation period (1993-97/98)].

The aim of the study was to characterise changes in dietary habits and cardiovascular risk factors of the Warsaw cohort population over a 5-year observation period. Two Warsaw population samples (249 men and 259 women), aged 35-64, were surveyed in 1993 and resurveyed in years 1997/98. Over a five-year observation period, daily dietary cholesterol decreased from 363 mg to 319 mg in men and from 263 mg to 232 mg in women, the percentage of energy from fat decreased from 38.8% to 34.7% in men and from 37.1% to 31.2% in women, the percentage of energy from saturated fatty acids from 13.6% to 11.7% and from 12.9% to 10.5% respectively. These changes resulted in a significant reduction in atherogenicity of the average diet as expressed by Keys score. Intakes of vitamins B1 and B2, calcium, magnesium and iron was consistently below Recommended Dietary Allowances (RDA) for the Polish population. Participants of both genders consumed significantly greater amounts of total bread (35%), milk (50%) and butcher meat products (22%). In the same time increase of HDL-cholesterol level (average of 2.0 mg/dl in men and 3.1 mg/dl in women) and decrease of LDL-cholesterol by 5 mg/dl in men was noted.

Adult↗

PubMed2000

Classical theory of resonant transition radiation in multilayer structures.

A rigorous classical electromagnetic theory of the transition radiation in finite and infinite multilayer structures is presented. It makes the standard results of thin-film optics, such as the matrix formalism, accountable; it allows thus an exact treatment of the propagation of the waves induced by the electron. This method is applied to the particular case of the periodic structures to treat the resonant transition radiation (RTR). It is noted that the present theory gives, in the hard x-ray domain, results previously published. The reason for this approach is to make the numerical calculations rigorous and easy. The numerical results of our theory are compared to experimental RTR data obtained recently by Yamada et al. [Phys. Rev. A 59, 3673 (1999)] with a nickel-carbon multilayer structure.

Journal Article↗

PubMed2000

Differentiation of rat striatal embryonic stem cells in vitro: monolayer culture vs. three-dimensional coculture with differentiated brain cells.

Several groups have demonstrated the existence of self-renewing stem cells in embryonic and adult mouse brain. In vitro, these cells proliferate in response to epidermal growth factor, forming clusters of nestin-positive cells that may be dissociated and subcultured repetitively. Here we show that, in stem cell clusters derived from rat embryonic striatum, cell proliferation decreased with increasing number of passages and in response to elevated concentrations of potassium (30 mM KCl). In monolayer culture, the appearance of microtubule-associated protein type-5-immunoreactive (MAP-5(+)) cells (presumptive neurons) in response to basic fibroblast growth factor (bFGF) was reduced at low cell density and with increasing number of passages. In the presence of bFGF, elevated potassium caused a more differentiated neuronal phenotype, characterized by an increased proportion of MAP-5(+) cells, extensive neuritic branching, and higher specific activity of glutamic acid decarboxylase. Dissociated stem cells were able to invade cultured brain cell aggregates containing different proportions of neurons and glial cells, whereas they required the presence of a considerable proportion of glial cells in the host cultures to become neurofilament H-positive. The latter observation supports the view that astrocyte-derived factors influence early differentiation of the neuronal cell lineage.

Animals↗

PubMed2000

Weight gain and its correlates in Poland between 1983 and 1993.

BACKGROUND: Weight gain and its unfavorable consequences on coronary heart disease (CHD) risk have been observed worldwide. Determinants of weight gain were studied in a Polish cohort of 1042 men and women age 35-64 at baseline. Participants were randomly selected from an urban population in Warsaw and a rural population in Tarnobrzeg Province surveyed by investigators in Krakow. The surveys, part of the Pol-MONICA project, were conducted in 1983-1984, 1987-1988, and 1992-1993. The purpose of this report is to gain insight into the dynamics of weight gain in this population that could be helpful in identifying high-risk groups for intervention, and to determine if economic changes that took place shortly after the second survey had any impact on weight gain. METHODS: Weight, height and demographic characteristics were measured at each visit according to Pol-MONICA standard protocol. Body mass index (BMI) was calculated as kg/m2. Years of schooling, 7-day alcohol history and smoking history were self-reported. RESULTS: Sixty percent of the cohort gained some weight, averaging 0.3-0.7kg/y. Weight gain was highest in younger rural women, in urban men and in rural women with low education. In multiple linear regression, low education was related to a 1.29 kg greater weight gain (P<0.01), ex-smoking status was related to a 2.54 kg greater weight gain (P<0.001), and younger age was related to a 1.14 kg greater weight gain (P<0.001). CONCLUSION: Our results indicate a need to target intervention programs at young low SES adults. Developing effective means of reaching these vulnerable groups is a critical research goal.

Adult↗

PubMed1999

High sensitivity of immature GABAergic neurons to blockers of voltage-gated calcium channels.

The involvement of voltage-gated calcium channels in the survival of immature CNS neurons was studied in aggregating brain cell cultures by examining cell type-specific effects of various channel blockers. Nifedipine (10 microM), a specific blocker of L-type calcium channels, caused a pronounced and irreversible decrease of glutamic acid decarboxylase activity, whereas the activity of choline acetyltransferase was significantly less affected. Flunarizine (1-10 microM, a relatively unspecific ion channel blocker) elicited similar effects, that were attenuated by NMDA. The glia-specific marker enzymes, glutamine synthetase and 2',3'-cyclic nucleotide 3'-phosphohydrolase, were affected only after treatment with high concentrations of nifedipine (50 microM) or NiCl2 (100 microM, shown to block T-type calcium channels). Nifedipine (50 microM), NiCl2 (100 microM), and flunarizine (5 microM) also caused a significant increase in the soluble nucleosome concentration, indicating increased apoptotic cell death. This effect was prevented by cycloheximide (1 microM). Furthermore, the combined treatment with calcicludine (10 nM, blocking L-type calcium channels) and funnel-web spider toxin-3.3 (100 nM, blocking T-type channels) also caused a significant increase in free nucleosomes as well as a decrease in glutamic acid decarboxylase activity. In contrast, cell viability was not affected by peptide blockers specific for N-, P-, and/or Q-type calcium channels. Highly differentiated cultures showed diminished susceptibility to nifedipine and flunarizine. The present data suggest that the survival of immature neurons, and particularly that of immature GABAergic neurons, requires the sustained entry of Ca2+ through voltage-gated calcium channels.

Acetylcholine↗

PubMed1999

Selective neurodegeneration induced in rotation-mediated aggregate cell cultures by a transient switch to stationary culture conditions: a potential model to study ischemia-related pathogenic mechanisms.

Aggregating brain cell cultures at an advanced maturational stage (20-21 days in vitro) were subjected for 1-3 h to anaerobic (hypoxic) and/or stationary (ischemic) conditions. After restoration of the normal culture conditions, cell loss was estimated by measuring the release of lactate dehydrogenase as well as the irreversible decrease of cell type-specific enzyme activities, total protein and DNA content. Ischemia for 2 h induced significant neuronal cell death. Hypoxia combined with ischemia affected both neuronal and glial cells to different degrees (GABAergic neurons>cholinergic neurons>astrocytes). Hypoxic and ischemic conditions greatly stimulated the uptake of 2-deoxy-D-glucose, indicating increased glucose consumption. Furthermore, glucose restriction (5.5 mM instead of 25 mM) dramatically increased the susceptibility of neuronal and glial cells to hypoxic and ischemic conditions. Glucose media concentrations below 2 mM caused selective neuronal cell death in otherwise normal culture conditions. GABAergic neurons showed a particularly high sensitivity to glucose restriction, hypoxia, and ischemia. The pattern of ischemia-induced changes in vitro showed many similarities to in vivo findings, suggesting that aggregating brain cell cultures provide a useful in vitro model to study pathogenic mechanisms related to brain ischemia.

Animals↗

PubMed1999

Separate neuronal and glial Na+,K+-ATPase isoforms regulate glucose utilization in response to membrane depolarization and elevated extracellular potassium.

The role of cell type-specific Na+,K+-ATPase isozymes in function-related glucose metabolism was studied using differentiated rat brain cell aggregate cultures. In mixed neuron-glia cultures, glucose utilization, determined by measuring the rate of radiolabeled 2-deoxyglucose accumulation, was markedly stimulated by the voltage-dependent sodium channel agonist veratridine (0.75 micromol/L), as well as by glutamate (100 micromol/L) and the ionotropic glutamate receptor agonist N-methyl-D-aspartate (NMDA) (10 micromol/L). Significant stimulation also was elicited by elevated extracellular potassium (12 mmol/L KCl), which was even more pronounced at 30 mmol/L KCl. In neuron-enriched cultures, a similar stimulation of glucose utilization was obtained with veratridine, specific ionotropic glutamate receptor agonists, and 30 mmol/L but not 12 mmol/L KCl. The effects of veratridine, glutamate, and NMDA were blocked by specific antagonists (tetrodotoxin, CNQX, or MK801, respectively). Low concentrations of ouabain (10(-6) mol/L) prevented stimulation by the depolarizing agents but reduced only partially the response to 12 mmol/L KCl. Together with previous data showing cell type-specific expression of Na+,K+-ATPase subunit isoforms in these cultures, the current results support the view that distinct isoforms of Na+,K+-ATPase regulate glucose utilization in neurons in response to membrane depolarization, and in glial cells in response to elevated extracellular potassium.

Animals↗

PubMed1999

Xuv resonant transition radiations from periodic stratified media.

General formulation of the xuv intensity emitted when relativistic electrons cross through any periodic stratified medium is presented in the framework of electromagnetism in continuous media. Application is made to the resonant transition radiation emitted in the geometries of both normal and oblique incidence. In the first case, agreement is found between our calculated results and published values. Intensity emitted by a periodic multilayer stack used in the Bragg conditions is determined and the practical interest of a such a radiation source is discussed.

Journal Article↗

PubMed1998

Muscimol-induced death of GABAergic neurons in rat brain aggregating cell cultures.

During brain development, spontaneous neuronal activity has been shown to play a crucial role in the maturation of neuronal circuitries. Activity-related signals may cause selective neuronal cell death and/or rearrangement of neuronal connectivity. To study the effects of sustained inhibitory activity on developing inhibitory (GABAergic) neurons, three-dimensional primary cell cultures of fetal rat telencephalon were used. In relatively immature cultures, muscimol (10 microns), a GABAA receptor agonist, induced a transient increase in apoptotic cell death, as evidenced by a cycloheximide-sensitive increase of free nucleosomes and an increased frequency of DNA double strand breaks (TUNEL labeling). Furthermore, muscimol caused an irreversible reduction of glutamic acid decarboxylase activity, indicating a loss of GABAergic neurons. The muscimol-induced death of GABAergic neurons was attenuated by the GABAA receptor blockers bicuculline (100 microns) and picrotoxin (100 microns), by depolarizing potassium concentrations (30 mM KCl) and by the L-type calcium channel activator BAY K8644 (2 microns). As compared to the cholinergic marker (choline acetyltransferase activity), glutamic acid decarboxylase activity was significantly more affected by various agents known to inhibit neuronal activity, including tetrodotoxin (1 micron), flunarizine (5 microns), MK 801 (50 microns) and propofol (40 microns). The present results suggest that the survival of a subpopulation of immature GABAergic neurons is dependent on sustained neuronal activity and that these neurons may undergo apoptotic cell death in response to GABAA autoreceptor activation.

Animals↗

PubMed1997

Neuronal-enriched cultures from embryonic rat ventral mesencephalon for pharmacological studies of dopamine neurons.

The method described herein provides a convenient and rapid procedure to obtain enriched neuronal cultures containing reproducible numbers of dopamine (DA) cells. These cultures allow experimental paradigms designed to study the effect of drugs on DA neurons without astroglial mediation. Neuronal-enriched cultures are prepared from the mesencephalon of rat embryos at the 14th day of gestation (E14). At that moment, DA cells of the developing substantia nigra are located ventrally at the level of the mesencephalic flexure. Because the neurons of the pars compacta are mostly born between E12 and E15, E14 corresponds to an optimal stage for obtaining a high survival of DA cells. A defined medium (EF12) allows the maturation of DA neurons and reduces drastically the number of astrocytes. After 7 days in vitro (DIV) in EF12, the cultures contain 2-5% astrocytes (GFAP+ cells) and DA neurons represent 0.5-2% of the cells, as assessed by immunostaining to tyrosine hydroxylase (TH). The function of DA neurons is assessed by [3H]DA uptake and of those non-DA neurons by the high affinity [3H]GABA uptake. Cell survival is assessed by Trypan blue dye exclusion.

Animals↗

PubMed1995

Toxic effects of L-DOPA on mesencephalic cell cultures: protection with antioxidants.

The toxicity of L-3,4-dihydroxyphenylalanine (L-DOPA) was studied in neuronal cultures from rat mesencephalon. The survival and function of DA neurons were assessed by the number of tyrosine hydroxylase-positive (TH+) cells and 3H-DA uptake and those non-DA neurons by the exclusion of Trypan blue and the high-affinity 3H-GABA uptake. L-DOPA was toxic for both DA and non-DA neurons. DA neurons were more severely affected than non-DA neurons after short periods of treatment and with exposure to a low dose of L-DOPA (25 vs. 100 microM) and less selectively affected after 1 or 2 days of treatment. After incubation with L-DOPA, a disruption of the neuritic network and an overall deterioration were observed, more evident for TH+ cells in the whole culture. Auto-oxidation to quinones is responsible in part for L-DOPA toxicity in non-DA neurons since the levels of quinones correlated well with the severity of cell death in the cultures. The damage of DA neurons took place before the rising of quinones, suggesting that quinones are not essential in L-DOPA toxicity for DA neurons. Antioxidants, such as ascorbic acid and sodium metabisulfite, completely prevented L-DOPA-induced quinone formation as well as the death of non-DA neurons. In contrast, they could only partially prevent the damage produced by L-DOPA in DA neurons. Mazindol, a selective inhibitor of DA uptake, protected TH+ cells from L-DOPA.

Animals↗

PubMed1995

L-dopa inhibits complex IV of the electron transport chain in catecholamine-rich human neuroblastoma NB69 cells.

L-3,4-Dihydroxyphenylalanine (L-dopa) is toxic for human neuroblastoma cells NB69 and its toxicity is related to several mechanisms including quinone formation and enhanced production of free radicals related to the metabolism of dopamine via monoamine oxidase type B. We studied the effect of L-DOPA on activities of enzyme complexes in the electron transport chain (ETC) in homogenate preparations from the human neuroblastoma cell line NB69. As a preliminary step we compared the activity of ETC in cellular homogenates with that of purified mitochondria from NB69 cells and rat brain. Specific activities for complex I, complex II-III, and complex IV in NB69 cells were, respectively, 65, 96, and 32% of those in brain mitochondria. Complex I activity was inhibited in a dose-dependent way by 1-methyl-4-phenylpyridinium ion with an EC50 of approximately 150 microM. Treatment with 0.25 mM L-dopa for 5 days reduces complex IV activity to 74% of control values but does not change either complex I or citrate synthase. Ascorbic acid (1 mM), which protects NB69 cells from L-dopa-induced neurotoxicity, increases complex IV activity to 133% of the control and does not change other ETC complexes. Ascorbic acid also reverses L-dopa-induced reduction of complex IV activity in NB69 cells. This observation might indicate that the protection observed with ascorbic acid is related to complex IV activation. In vitro incubation with L-dopa (0.125-4 mM) for 2 min produced a dose-dependent reduction of complex IV without change in complex I and II-III activities.

1-Methyl-4-phenylpyridinium↗

PubMed1995

Effects of calcium antagonists on the dopamine system.

Calcium channel antagonists are drugs currently used in the treatment of neurological and cardiovascular disorders and occasionally produce parkinsonism and movement disorders as a side effect. We investigated the effects of calcium channel antagonists on the pharmacology of dopamine systems in vivo and in vitro. Flunarizine, cinnarizine, and diltiazem reduce the viability of dopamine-rich human neuroblastoma cells in vitro. These compounds plus verapamil, nifedipine, and nicardipine reduce 3H-spiperone binding to bovine striatal membranes, 3H-dopamine uptake, K(+)-induced 3H-dopamine release, and apomorphine-induced rotation, but not amphetamine-induced rotation, in 6-OH-dopamine-lesioned rats. Therefore, all calcium channel antagonists tested reduce dopamine neurotransmission in vitro and in vivo, whereas the evidence of toxicity for dopamine cells in vitro is restricted to flunarizine, cinnarizine, and diltiazem. The clinical relevance of these toxic effects may depend on several factors, including age, penetration across the blood-brain barrier, and types of calcium channels present in the different neuronal subtypes. On the other hand, the finding of dopamine-regulating properties not associated to neurotoxic effects in the dihydropyridines and verapamil provides new putative therapeutics tools for the treatment of neurologic disorders associated with dopamine hyperactivity.

Animals↗

PubMed1995

[Evaluation of dietary changes during a 10 year observation period of the local Pol-MONICA population in Warsaw with regard to risk of cardiovascular diseases].

In the frame of the Warsaw Pol-MONICA Project three population screenings were performed in randomly selected 35-64 year men and women in 1984 (2571 participants), in 1988 (1397) and 1993 (1485). Twenty-four-hour dietary recalls were used for assessment of nutritional value of daily food ration and food products consumption. Statistical analyses was performed by linear regression method (SAS REG procedure). Substantial changes in food consumption pattern were noted during 10 years, particularly in the last 4 years. In 1993 participants of both sexes consumed significantly less cereals, butter, eggs (trend p < 0.01) and more fats of vegetable origin (trend p < 0.01). This changes reflected in nutritional values of daily food ration from 1984 to 1993: dietary cholesterol decreased from 630 mg to 433 mg in men and from 447 to 284 in women, percent of energy from saturated fatty acids decreased from 15.7% to 14.7% in men and from 15.9% to 13.9% in women, percent of energy from polyunsaturated fatty acids increased from 4.1% to 5.4% and from 4.3% to 5.5% respectively. Above mentioned changes resulted in a significant reduction of atherogenicity level of diet as expressed by Keys score. A period covered by the study was a period of economical changes in Poland associated with an introduction of a free food-market. Changes in food consumption and nutrient intake reflect the mixture of industry, mass communication patterns, and commercial advertising.

Adult↗