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Biomedical subjects

B Rolland

Publications and source records attributed to B Rolland.

At least 19 recordsLinked to original sources

Radiological consequences of the extreme flooding on the lower course of the Rhone valley (December 2003, south east France).

In early December 2003 unusual weather conditions led to major flooding of the lower Rhone valley. When it floods, the Rhone carries large masses of solid matter in suspension, which potentially includes associated artificial (anthropogenic) radioactive contaminants from soil drainage in the catchment area and from re-uptake of sedimentary matter that has been contaminated with low-level radioactive liquid effluents from almost twenty nuclear facilities situated along the Rhone valley. A sampling campaign was carried out to investigate the level and spread of both sediment mass and associated radioactive contamination across the flooded areas. An attempt was made to assess the radiological consequences of such an extreme event on contamination of the food chain. Our results show that almost 700,000 tons of sediment was transported onto the floodplain, of which 80% were coarse and fine sands. These materials transferred 6660 MBq of 137Cs, 93 MBq of (239+240)Pu, 13 MBq of 238Pu and 204 MBq of 60Co over a surface area of 60 km2. More than 90% of deposited sediments are concentrated in a 10 km2 area of agricultural soils, and we estimated that 18% were plowed into the soil. Nevertheless, the level of activity measured in the vegetable crops and milk was not significantly different from the level measured in similar samples from regions that were not affected by the December 2003 floods.

Animals↗

[Hemodynamic instability and long-term lithium therapy].

Lithium is known to be responsible for many adverse events on the cardiovascular system. Among these events, it was experimentally noted that lithium could block the action of catecholamines on myocardium. The authors report the case of a patient under lithium therapy developing a myocardial infarction secondarily complicated of a severe cardiac failure. The inotropic support essential to balance hemodynamic could be raised only after lithium's stop. This example could be a clinical translation of the experimental effect previously observed.

Aged↗

Comparison of the efficacy and safety of valaciclovir and acyclovir for the treatment of herpes zoster ophthalmicus.

OBJECTIVE: To compare the efficacy and safety of valaciclovir and acyclovir in immunocompetent patients with herpes zoster ophthalmicus. DESIGN: A multicenter, randomized, double-masked study. PARTICIPANTS: One hundred ten immunocompetent patients with herpes zoster ophthalmicus diagnosed within 72 hours of skin eruption were treated; 56 were allocated to the valaciclovir group and 54 to the acyclovir group. METHODS: Patients randomized to the valaciclovir group received two 500-mg tablets of valaciclovir three times daily and one tablet of placebo twice daily. Patients in the acyclovir group received one 800-mg tablet of acyclovir five times daily and one tablet of placebo three times daily for 7 days. MAIN OUTCOME MEASURES: Main outcome measures included the frequency, severity, and duration of ocular complications, patient reports of zoster-associated pain, and the outcome of skin lesions. Tolerance was also assessed on the incidence and types of adverse effects and changes in laboratory parameters. The analysis was mainly descriptive and performed on an intent-to-treat basis. RESULTS: Ocular complications of herpes zoster ophthalmicus were similar in the valaciclovir and acyclovir treatment groups. The main complications were conjunctivitis (54% and 52%, respectively), superficial keratitis (39% and 48%, respectively for punctate keratitis; 11% in each group for dendritic keratitis), stromal keratitis (13% in each group), and uveitis (13% and 17%, respectively). The long-term outcomes of these ocular complications were favorable and similar in both treatment groups. Pain duration and severity and outcome of skin lesions were similar between groups. Most patients reported prodromal pain. After 1 month, 25% of patients in the valaciclovir group and 31% in the acyclovir group still reported pain. The percentage of patients experiencing postherpetic neuralgia decreased during follow-up. The tolerance to acyclovir and valaciclovir was comparable and considered good. The most frequent adverse events were vomiting and edema of the eyelids or face (3%-5%). Three serious adverse events not linked to the study drugs occurred. CONCLUSIONS: Valaciclovir is as effective as acyclovir in preventing ocular complications of herpes zoster ophthalmicus, including conjunctivitis, superficial and stromal keratitis, and pain. Tolerability of the two drugs is similar, but the dosing schedule of valaciclovir is simpler.

Acyclovir↗

Detection of the peripheral nervous system (PNS)-type glial fibrillary acidic protein (GFAP) and its mRNA in human lymphocytes.

Glial fibrillary acidic protein (GFAP), an astroglial marker, has been detected in the peripheral nervous system (PNS) in a shorter version and its mRNA in a longer form (beta-type) than the brain alpha-type. To determine the characteristics of the GFAP gene expression in nonneural cells, we have investigated its in vivo transcription and translation products in human lymphocytes. Using RT-PCR, we demonstrate that the GFAP gene is transcribed in these cells. Most or all of the mRNA resulting from this transcription was longer than the brain-type at its 5' end and thus may correspond to the beta-type. In addition, immunoblotting of lymphocyte extracts with a monoclonal antibody revealed a 41 KDa fragment instead of the 50 KDa expected from brain GFAP. These results suggest that GFAP expression in lymphocytes is preferentially of the PNS beta-type giving rise to longer mRNA and shorter protein. However, compared to two other astroglial mRNAs (S-100beta and aldolase C) which were synthesized in significant amounts in lymphocytes, GFAP mRNA was detected in minute amounts representing 0.03% of the brain level. This low expression may subserve a special role in lymphocytes since it is translated.

Antibodies, Monoclonal↗

High-volume, zero-balanced hemofiltration to reduce delayed inflammatory response to cardiopulmonary bypass in children.

BACKGROUND: In previous studies, researchers suggested a beneficial role of hemofiltration performed during cardiopulmonary bypass in children. This study was performed to assess both clinical effects and inflammatory mediator removal by high-volume, zero-fluid balance ultrafiltration during rewarming (Z-BUF). METHODS: Twenty children undergoing cardiac surgery were assigned randomly to Z-BUF or a control group. Plasma C3a, interleukin (IL)-1, IL-6, IL-8, IL-10, tumor necrosis factor, myeloperoxidase, and leukocyte count were measured before (T1) and after (T2) hemofiltration and 24 h later (T3). The intensive care unit staff was blinded to the patient's group. Postoperative alveolar-arterial oxygen gradient, time to extubation, body temperature, and postoperative blood loss were monitored. RESULTS: Ultrafiltration rate was 4,972 (3,183-6,218) mL/m2 (median [minimum-maximum]) in the Z-BUF group, where significant reductions were observed in postoperative blood loss, time to extubation (10.8[9-18] vs. 28.2 [15-58] h) and postoperative alveolar-arterial oxygen gradient (320 [180-418] vs. 551 [485-611] mmHg at T3). In the Z-BUF group, significant removal of tumor necrosis factor, IL-10, myeloperoxidase, and C3a were observed at T2. Interleukin 1, IL-6, IL-8, and myeloperoxidase were decreased at T3, suggesting earlier removal of factor(s) that may trigger their release. CONCLUSIONS: These results suggest that hemofiltration exerts some beneficial clinical effects that are not due to water removal. The role of the early removal of factors triggering the inflammatory response, rather than a direct removal of cytokines, deserves further investigation.

Anesthetics↗

Glutamine synthetase gene expression in a glioblastoma cell-line of clonal origin: regulation by dexamethasone and dibutyryl cyclic AMP.

We investigated the expression of glutamine synthetase (GS), an enzyme involved in astroglial metabolism and marker of astroglial functional maturity, in a glioblastoma cell-line (GL-15) of clonal origin. In spite of their phenotypic immaturity, evidenced in a mosaic fashion by a poor glial fibrillary acidic protein (GFAP) expression, the level of GS-mRNA is high in GL15 cells and the considerable amount of GS biological activity can be further induced and stabilized by glucocorticoids. A correlation between the induction by dexamethasone of the GS-mRNA level and the GS biological activity suggests a transcriptional regulation of GS expression by the aforesaid hormone. Under this hormonal action, changes in cell morphology occur and they are correlated with an overexpression of the GFAP, a marker of astroglial differentiation. On the contrary, dibutyryl cyclic AMP (dbc AMP) down-regulates the GS-mRNA expression and decreases GS activity. These results suggest that GL-15 cells have a common glucocorticoid dependent mechanism able to induce GS and GFAP as well as morphological changes. However in these cells AMPc responsive elements are involved in the negative modulation of the GS expression, contrary to what occurs in normal astroglial cells.

Astrocytes↗

Long-term astroglial reaction to serotonergic fiber degeneration.

Glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS) expression were analysed by Western and Northern blotting in the hippocampus, the frontal and occipital cortex, and the cerebellum of the adult rat, as a manifestation of the astroglial reaction, 2 and 3 months after 5,7-dihydroxytryptamine injection into the lateral ventricule. 5HT injury stimulated GFAP and GS expression in a temporally and regionally specific fashion. At 2 months postlesion, the GFAP-mRNA and GFAP levels appeared enhanced but returned to control levels at 3 months. The GFAP-mRNA and GS-mRNA levels increased in the frontal cortex at 3 months. Such a delayed astroglial reactivity might implicate astrocytes in neurodegenerative disorders.

5,7-Dihydroxytryptamine↗

Thyroid hormones influence the astroglial plasticity: changes in the expression of glial fibrillary acidic protein (GFAP) and of its encoding message.

Normal development of the brain requires the presence of thyroid hormones. To progress in the understanding of the contribution of astrocytes to brain pathophysiology we investigated the effect of T3, on the astroglial plasticity through the expression of two astroglial proteins: the Glial fibrillary acidic protein (GFAP) and the glutamine synthetase (GS). Western and northern blots were performed using astroglial primary cultures initiated from neocortex and cerebellum of new-born mice. Treatment with T3 caused a decrease of GFAP and of its encoding message level in both areas, suggesting a transcriptional regulation of its expression, whereas it had no apparent effect on GS expression. This reduction in GFAP expression was developmentally regulated; it was significant in proliferating but not in more mature astrocytes. T3 effect on astrocytes was higher in the cerebellum compared to the neocortex, suggesting the presence of astroglial subpopulations differing by their sensitivity to T3. The astroglial specific response to T3, corresponds to a precise, targetted and regulated adaptation of the cell. Factors of the microenvironment may modulate this specific astroglial response in vivo.

Animals↗

DBcAMP effect on the expression of GFAP and of its encoding mRNA in astroglial primary cultures.

Short term and chronic dBcAMP effects on the expression of glial fibrillary acidic protein (GFAP) in astroglial primary cultures are investigated. Short (48 h) and long (more than 7 days) treatments with the cAMP derivative induce both cell shape changes and an increase in GFAP immunolabelling. Such effects are only associated with an increase in GFAP and in GFAP-mRNA levels in the long term treatment. These results suggest that the short term effect of dBcAMP induces post-translational modifications of the protein whereas the long term effect is associated with an increase in GFAP mRNA transcription and/or stability.

Animals↗

GFAP turnover during astroglial proliferation and differentiation.

The expression and turnover of the glial fibrillary acidic protein (GFAP) were studied in astroglial primary cultures during postnatal proliferation and maturation. 1. Immunocytochemical studies demonstrated that in immature proliferating astrocytes. GFAP was expressed as a filamentous organized crown around the nucleus whereas in the maturating cells, a GFAP labelled network began to radiate throughout the cytoplasm and GFAP was highly expressed in the astroglial processes. 2. GFAP turnover was studied at 3 periods of culture. The decay of radioactivity from prelabelled GFAP was followed from day 4-12 (immature stage), 11-19 (maturing stage) and 21-29 (morphologically differentiated stage). GFAP displayed a biphasic decay kinetic at each considered period. Two pools of GFAP distinctly appeared. The first one was a fast decaying pool with a half life of 16-18 h and of 5-6 days for the stable one. The unstable pool decreased from 70% to 30% of the total incorporated radioactivity from the proliferating stage to the most mature stage, whereas the stable pool increased proportionally.

Animals↗

Glutamine synthetase modulation in astrocyte cultures of different mouse brain areas.

Astroglial cells from mouse cerebral hemispheres, cerebellum, olfactory bulbs, and medulla oblongata were grown in the presence of either hormones (hydrocortisone, insulin) or cell second messengers (dBcAMP, dBcGMP). Glutamine synthetase (GS) specific activity, GS protein level, and GS translation were investigated under the effect of these factors. Hydrocortisone produced a simultaneous increase in GS translation, GS level, and activity. This increase was observed in the astrocytes cultured from the four brain areas but at a variable magnitude depending on the area. The hydrocortisone effect appeared at the transcriptional level. Inversely, insulin decreased both the GS activity and the in vitro translated GS. This effect was seen only in the olfactory bulbs and the medulla. DBcAMP increased the GS biological activity only in the cerebral hemisphere cultures. It raised, however, the level of translated GS and GS protein in astrocytes from all the areas, suggesting a post-translational effect for intracellular cAMP. DBcGMP only affected GS in the astrocytes from cerebral hemispheres and the medulla modulating either the GS transcription or the messenger RNA stability. These results suggest specific regulation for GS expression, depending on the brain area from which the cells were dissociated or on the astroglial cell population present in these cultures affecting either the transcription, the mRNA stability, or the biological activity of the protein.

Animals↗

Glutamine synthetase: a marker of an astroglial subpopulation in primary cultures of defined brain areas.

Primary cultures from various areas of newborn mouse brain were developed and characterized. Enriched astroglial cultures of the cerebral hemispheres, cerebellum, medulla oblongata and olfactory bulbs contained about 80-90% glial fibrillary acidic protein (GFA) immunolabelled cells. These cultures were composed of a majority of flat, 'protoplasmic-like' cells. The aim of this culture model was used: (1) to study glutamine synthetase (GS) activity during in vitro astroglial development; (2) to consider the hydrocortisone effect on GS activity during both growth and maturation periods, and (3) to determine the development of GS immunoreactivity in the cells and eventual GFA and GS expression in these cells. We observed that GS increased during brain maturation in vivo and in vitro, and that addition of hydrocortisone (1 microM, 48 h) to the culture medium induced varying GS activity depending on the developmental stage and the area. In the four areas studied, the number and intensity of GS-immunolabelled cells reached an optimum between 18 and 30 days in vitro. Only about 50-70% of the cell population was GS positive. Double-labelling experiments showed that three groups of cells coexist whatever the considered area. Two expressed both GFA and GS proteins, the last marker at either a low or a high level, and the third was devoid of GS immunoreactivity. Regional differences in GS-specific activity, GS inducibility and GS immunoreactivity exist in the astroglial population, but the factors responsible for these variations are not yet known.

Animals↗

Absence of correlations between glutamine-synthetase activity and dysmyelination-associated modifications of astroglia in the brain of murine mutants.

Glutamine Synthetase (GS) activity was investigated in cerebellum (ce), cerebral cortex (cc), olfactory bulb (ob), and medulla oblongata (mo) of murine dysmyelinating mutants for correlations with modifications of astroglia associated with genetic dysmyelination. One of these mutants, jimpy, develops a strong gliosis throughout the CNS. The other three mutants: shiverer, mld, and quaking, exhibit various astrocytic responses to dysmyelination, but reduced gliosis if any. Comparison between CNS areas in control animals showed a higher GS activity in the olfactory bulb than in the cerebral cortex, medulla, and cerebellum. The developmental patterns of GS activity were similar in mutants and in controls in all four areas investigated. Data on Jimpy suggest that GS activity is not associated with reactive astrocytes.

Animals↗

Further characterization of [3H] flunitrazepam binding sites on cultured mouse astroglia.

Astroglial cells in primary cultures bind [3H]flunitrazepam with a high affinity on a single type of site and on a number of binding sites which increased during astroglial growth and differentiation. These binding sites show a particular pharmacological spectrum characterized by an inhibition of high affinity by RO-5-4864 (4'-chlorodiazepam), an anticonvulsant of the benzodiazepine family and by an inhibition of binding of lower affinities by diazepam clonazepam and clobazam. RO-5-4864 and clonazepam compete for the same binding site in astroglia. The heat stability and the hormonal modulation by thyroxine are similar for astroglia and neuronal-cells. Benzodiazepines modulate the astroglial 5-HT receptor. Such an effect could be a possible physiological response to benzodiazepines for astroglial cells in primary cultures.

Animals↗

Microtubule-associated proteins and in vitro astrocyte differentiation.

Primary cultures of mouse brain astrocytes have been used to identify the microtubule-associated proteins (MAPs) present in this cell type at different stages of in vitro differentiation. The MAPs of the astrocyte have been identified by polyacrylamide gel electrophoresis and immunological detection. Two antisera were raised against two brain MAPs, tau and MAP-2. These antisera were also used to label the microtubular network in the intact astrocytes at different stages of the culture. The mature astrocyte contains a variety of MAP-like proteins. Anti-MAP-2 serum detected several proteins of high molecular weight (380,000, 260,000, 205,000 and 165,000 mol wt) and one microheterogeneous peak of 83,000 mol wt. Anti-tau also detected high molecular weight components (380,000 to approximately 200,000 mol wt) but not the 165,000-mol-wt peak; in addition two microheterogeneous peaks of 83,000 and 62,000 mol wt were detected by the anti-tau serum. The 62,000-mol-wt peak was therefore detected only by the anti-tau serum whereas the 83,000-mol-wt component cross-reacted with both antisera. At early stages of the culture the immature cell contained about two times less immunoreactive material than at mature stages. Qualitative changes of the high molecular weight components were also observed. In the intact cell both antisera revealed a dense fibrous network. At early stages of the culture the astroblasts were stained by the antisera but the reaction was very diffuse in the cytoplasm; few fibrous cells were intensively stained. Morphological differentiation, which began after serum deprivation and which was accelerated by forskolin (a drug that induces cyclic AMP accumulation), led to high labeling of both the cell body and the cellular processes. In the presence of colchicine the staining regressed, the processes shortened, and the cell returned to a less-apparently differentiated state.

Animals↗