Search PubMed⌕ Search

Biomedical subjects

N Bertrand

Publications and source records attributed to N Bertrand.

At least 37 records · Page 2Linked to original sources
PubMed1999

Preischemic blood glucose supply to the brain modulates HSP(72) synthesis and neuronal damage in gerbils.

Preischemic hyperglycemia is known to aggravate brain damage caused by transient forebrain ischemia. Because heat shock proteins (HSPs) 72 have been proposed to play a protective role against ischemic neuronal injury, we studied the HSP(72) mRNA expression and protein synthesis in gerbils subjected to 10 min bilateral carotid occlusion under normoglycemic, hyperglycemic and fasting conditions. HSP(72) mRNA expression and HSP(72) synthesis were studied using in situ hybridization and immunostaining, respectively. After 8 h of blood recirculation, HSP(72) mRNAs were expressed in all the hippocampal subfields of the three different groups, with higher expression in the hyperglycemic gerbils. After 48 h of reperfusion, HSP(72) mRNAs had almost completely disappeared in the hyper- and normoglycemic groups, and were more strongly expressed in the CA(1) neurons of the fasted group. At this time, fasted gerbils exhibited intense HSP(72) immunoreactivity in the CA(1), whereas an absence of immunoreactivity was observed in that area in the other groups. Finally, ischemia was also associated with marked astrocytic activation, as evidenced by GFAP immunostaining. Overall results indicate that preischemic differences in blood glucose supply to the brain are related to HSP(72) mRNA expression (in terms of duration) and to HSP(72) protein induction (in terms of intensity) in the vulnerable CA(1) neurons of the hippocampus. Ability of CA(1) neurons to synthesize HSP(72) proteins was associated with higher neuronal survival in the fasted group after 48 h of reflow, suggesting a protective role of HSP(72), even though evaluation of neuronal damage at 7 days indicated that neuronal death was mainly delayed in the time.

Animals↗
PubMed1999

Regulation of hemopexin synthesis in degenerating and regenerating rat sciatic nerve.

In injured peripheral nerves, hemopexin mRNA is expressed by fibroblasts, Schwann cells, and invading blood macrophages, and the protein accumulates in the extracellular matrix. This and its absence of regulation in injured central optic nerve suggest that hemopexin could play a positive role in peripheral nerve repair. Here, we studied the regulation of hemopexin expression in degenerating and regenerating nerves. After a sciatic nerve injury, both the synthesis of hemopexin and the level of its mRNA increase sharply during the first 2 days, leading to an accumulation of hemopexin in the nerve. Afterward, hemopexin expression decreases progressively in regenerating nerves. In permanently degenerated nerves, it is again transiently increased and then strongly decreased, whereas hemopexin from blood origin is accumulating. As part of the elucidation of the complex regulation of hemopexin expression in injured nerves, we demonstrate that interleukin-6 increases hemopexin synthesis in intact nerves, whereas adult rat serum, but not purified hemopexin, inhibits it in degenerated nerves. Hemopexin, known as acute-phase protein, is therefore one of the molecules rapidly and specifically up-regulated in injured peripheral nerves. More generally, our findings suggest that the acute phase could be not only a systemic liver-specific response but also a reaction of injured tissues themselves.

Age Factors↗
PubMed1999

[Changing indications and histological and biological results of radical prostatectomy].

OBJECTIVES: To compare: 1) the incidence of positive resection margins after radical prostatectomy, 2) the incidence of secondary elevation of PSA, in two groups of patients operated before and after May 1994. METHODS: We collected and compared preoperative (PSA, Gleason score on biopsies, positive apical biopsies) and postoperative variables (number and site of positive margins, secondary elevation of PSA) in two historical cohorts of 115 and 67 patients undergoing retropubic radical prostatectomy. RESULTS: We currently operate on tumours characterized by lower PSA values with a smaller proportion of positive apical biopsies. Inversely, the proportion of high Gleason scores appears to be greater, although the difference is not statistically significant. The decreased incidence of positive resection margins and PSA failure rate compared to our initial series reflects the improvement of the oncological results. The respective place of improvement of techniques and changing indications has yet to be defined. CONCLUSION: This study demonstrates the changing operative indications and histological and laboratory results over time. The documented improvement of oncological results is partly related to the progress in surgical indications.

Biopsy↗
PubMed1999

[Vascular microsurgery in the treatment of vasculogenic erectile dysfunction: clinical experience apropos of 115 operations performed according to 2 different surgical techniques].

OBJECTIVES: The treatment of vascular erectile insufficiency may require surgery because of the high failure rate of intracavernous injections. Implantation of penile prostheses is a last resort which can be avoided in certain selected patients in whom vascular surgery can be proposed. However, the modalities and results of this type of treatment remain controversial. We therefore evaluated the results of two different techniques. MATERIAL AND METHODS: From 1st January, 1985 to 31st December, 1995, 114 patients were operated for impotence due to pure veno-cavernous incompetence in 23 cases (20%), associated with arterial disease in 38 cases (46%) or purely arterial insufficiency in 39 cases (34%). The mean age was 47.5 +/- 11 years (range: 20 to 74). These patients had suffered from erectile insufficiency for an average of 33.3 +/- 3 years. Pharmacological erection tests achieved rigid erection in only 6 cases. Two surgical techniques were used: end-to-end bypass graft between the epigastric artery and the dorsal artery of the penis (DAP) in 44 cases and arterialisation of the deep dorsal vein of the penis (DVP) in 71 cases. RESULTS: Overall, there were 54 good results (48%), defined by return of normal erections allowing satisfactory sexual intercourse without any complementary treatment, 15 improvements (14%) and 45 failures (38%) with a mean follow-up of 18 months (range: 3 to 120). These results were equivalent in the case of pure veno-cavernous incompetence (65%) of good results) or associated arterial disease (52%) of good results), but poorer results (31% of good results) were obtained in the case of pure arterial disease. The results were not statistically influenced by age or the presence of graft in all 3 types of erectile insufficiency, arterial, veno-cavernous or mixed. However, this difference was only statistically significant for pure veno-cavernous incompetence. The morbidity of arterialisation of the DVP was marked by high-flow syndrome in 21% of cases (n = 15), requiring surgical revision in 77% of cases (n = 11). Interestingly, 85% of good results on erectile function were obtained in this subgroup. CONCLUSION: The results obtained in this series of vascular erectile impotence, regardless of the aetiology of erectile insufficiency, are in favour of the better efficacy of arterialisation of the DVP compared to arterial bypass graft. The biological mechanisms underlying this better result need to be elucidated.

Adult↗
PubMed1998

Vascular endothelial growth factor is up-regulated in vitro and in vivo by androgens.

Evidence from pathophysiological studies support the concept that embryonic development, tumor progression, and hormonally-regulated tissue masses such as adult prostate and corpus luteum are angiogenesis-dependent. We examined if the prostatic expression of vascular endothelial growth factor (VEGF), the major regulator of normal and pathological angiogenesis, was regulated by testosterone. Northern blot of VEGF messenger ribonucleic acid (mRNA) extracted from a human immortalized epithelial prostatic cell line (PNT1) showed that dihydrotestosterone (DHT) up-regulated VEGF mRNA at a level comparable to that observed upon exposure to growth factors. Polymerase chain reaction of reverse transcribed mRNA demonstrated that the ratio of the two splice variants encoding the 121 and 165 isoforms of VEGF were not affected by DHT. VEGF biological activity, measured in the conditioned medium by radio receptor assay, was increased by DHT. Injection of testosterone in adult rats induced a transient increase of the ventral lobe weight and the specific activity of prostatic VEGF, leading to a 7-fold increase in the prostate content of VEGF.

Androgens↗
PubMed1998

Changes in expression and localization of hemopexin and its transcripts in injured nervous system: a comparison of central and peripheral tissues.

The recent demonstration of hemopexin synthesis in the adult rat sciatic nerve and its accumulation after injury has raised the question of the possible role of this acute phase protein during the process of nerve repair. To gain insight into its function, we have compared the distribution of both hemopexin and its messenger RNA in the peripheral and the central nervous systems. We find that hemopexin is present in all types of peripheral nerves and ganglia, confined to the extracellular matrix and basement membranes of the endoneurium, blood vessels and connective tissues. After injury, hemopexin messenger RNA is overexpressed by Schwann cells, fibroblasts and invading macrophages. The content in hemopexin protein increases in all nerves studied, without changes in localization. Therefore, hemopexin does not appear to be associated with the fate of myelin or with the regeneration of a particular type of nerve fibre. In the central nervous system, hemopexin messenger RNA cannot be detected and the protein is only found in basement membranes of the vascular system (capillaries, meninges and choroid plexus). Furthermore, hemopexin and its messenger RNA remain absent from the distal part of the injured optic nerves. Our results further support the idea that hemopexin plays specific roles during nerve repair, and that it may be associated with the endoneurial extracellular matrix.

Animals↗
PubMed1998

The rpfA gene of Xanthomonas campestris pathovar campestris, which is involved in the regulation of pathogenicity factor production, encodes an aconitase.

Xanthomonas campestris pv campestris (Xcc) is a plant pathogenic bacterium that controls the production of pathogenicity factors in part by a cluster of genes designated rpf (regulation of pathogenicity factors). Sequence analysis of one of these genes (rpfA) revealed an open reading frame with amino acid sequence similarity to aconitases from other bacteria. Aconitase activity was lower in cellular extracts of an rpfA::Tn5 mutant than in those from the wild type. A zymogram of aconitase activity after native gel electrophoresis showed the presence of two distinct aconitases in Xcc; the major aconitase was absent in the rpfA::Tn5 mutant. This mutant also had reduced levels of extracellular enzymes and extracellular polysaccharide (EPS). Supplying rpfA in trans to the rpfA::Tn5 mutant restored both the major aconitase activity and the synthesis of these pathogenicity factors. The transcription of the genes for two extracellular enzymes (prtA, encoding a serine protease, and engXCA, encoding endoglucanase) was reduced in the rpfA mutant background. Because some eukaryotic aconitases are also involved in iron regulation, we explored a possible connection between rpfA and iron metabolism. Intracellular iron levels in the mutants were lower than in the wild type as assessed by sensitivity to the iron-activated antibiotic, streptonigrin. Wild-type bacteria grown in iron-deficient conditions had a similar sensitivity to streptonigrin as the aconitase mutant. Overall, these results suggest that a prokaryotic aconitase can also act as a regulator of gene expression and that the regulation is possibly related to changes in intracellular iron levels.

Aconitate Hydratase↗
PubMed1997

Cell release of bioactive fibroblast growth factor 2 by exon 6-encoded sequence of vascular endothelial growth factor.

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor which is synthesized and secreted by many differentiated cells in response to various stimuli including hypoxia and growth factor exposure. Alternative splicing of vascular endothelial growth factor mRNA results in three distinct molecular forms: V189 and V165 or V121 which lack the exons 6 or 6 and 7, respectively. To clarify the functions of the 24-amino acid insertion, the biological activity of V165 was compared with that exerted by purified recombinant V189 and a synthetic peptide designed on the sequence encoded by exon 6 (Ex6P). V189 and Ex6P, but not V165, induced cell proliferation on corneal endothelial cells cultured in vitro. These effects were due to the release of fibroblast growth factor 2 (FGF2) stored in the extracellular matrix but not to direct interactions with FGF receptors since V189 was inefficient on heparan sulfate-deficient cells expressing constitutively FGF-R1. Moreover corneas incubated ex vivo with Ex6P solubilized 10-fold more FGF2 than a isocationic peptide containing a scrambled sequence. Ex6P elicited an angiogenic response in a corneal pocket assay which was totally inhibited by addition of anti-FGF2 IgG. Moreover the angiogenic response to V189, but not to V165, was inhibited by FGF2 immunoneutralization. These findings demonstrate that the presence of the exon 6-encoded sequence confers VEGF with the ability to exert its biological effects through FGF2 signaling pathways.

Amino Acid Sequence↗
PubMed1997

[Surgical treatments of erectile impotence].

Impotence affects 10 to 15% of the male population. Organic factors are recognized in 80% of cases. Intracavernosal injections of vasoactive agents (Virag) have provided advances in the physiopathologic understanding of impotence and provide new ways of treating this incapacity. However this option is inaffective in most organic cases: arteriogenic, venogenic or disorders of smooth cavernous muscle. Vasoactive injections for many reasons are abandoned in about 40% of the cases. Two kinds of surgical management can be performed: microrevascularization in order to restore the arterial penile flow or to reduce penile venous flow during erection; implantation of penile prosthesis when other therapeutic possibilities are exhausted. Arterialization of the deep dorsal vein (DDV) appears to be the best procedure in arteriogenic and principally venous impotence. Erectile function in theses case is restored in 60% of our patients. Two types of prostheses can be implanted: semi-rigid with an axial permanent rigidity and inflatable or hydraulic devices with a flaccid aspect after intercourse. These prostheses are technically successful in 75 to 90% of cases, but partner satisfaction does not match surgical success rates.

Arteriovenous Shunt, Surgical↗
PubMed1997

Microrevascularisation of the penis in vascular impotence.

PURPOSE: We evaluated the results of microvascular penile revascularization in impotent men and carefully selected those whose vasculogenic impotence was defined as arteriogenic impotence, veno-cavernous leakage or mixed vasculogenic impotence. MATERIALS AND METHODS: Over a period of 11 y, 114 patients were treated for vasculogenic impotence with two surgical procedures: Michal II arterial bypass (44 patients) and modified Furlow-Fisher technique of deep dorsal vein arterialization (DDVA) (70 patients). Initial evaluation included history, physical and neurological examination, hormonal level determination, pharmacological erection test, Rigiscan, duplex ultrasonography, selective pudendal arteriograpy, dynamic cavernosometry and cavernosography. The patients were followed up for a mean period of 17 months and the results were clinically evaluated. RESULTS: The results at the end of one month were considered as good in 69.5% and improved in 12.2% and failed in 18.3%. Follow-up results are good in 47.8%, improved in 14.6% and failed in 37.4%. The best success rate was obtained with patients with pure venogenic impotence treated with DDVA, whereas the worst was observed in patients with pure arteriogenic impotence treated with the Michal II procedure. DDVA seems to provide better results than arterial bypass regardless of the etiology of impotence. CONCLUSIONS: Penile microvascular revascularization is not the best cure for all impotent men but appears to have a place in the treatment for selected patients with vasculogenic impotence. Further studies will be necessary to define parameters able to permit a better understanding and selection of candidates. DDVA is the most effective procedure to treat surgically vasculogenic impotence although the hemodynamic and biologic consequences of this operation are unknown.

Adult↗
PubMed1997

Vascular endothelial growth factor confers a growth advantage in vitro and in vivo to stromal cells cultured from neonatal hemangiomas.

Neonatal hemangioma is a common benign proliferation of unorganized structures containing stromal and capillary endothelial cells. We tested the hypothesis that such cell proliferation might result from the release by stromal cells of endothelial cell mitogens. Stromal cells cultured from biopsies of surgically removed life-threatening hemangiomas released an endothelial cell mitogen in vitro that was indistinguishable from vascular endothelial growth factor (VEGF) based on independent criteria such as affinity chromatography for heparin or anti-VEGF IgG and radioreceptor assay. A functional product of the KDR gene encoding a cognate VEGF receptor was also expressed by these stromal cells. Transient transfection with antisense oligonucleotides targeted on the translation initiation codon of KDR abolished its tyrosine phosphorylation and mitogenic response of neonatal hemangioma cells to VEGF, confirming the existence of an autocrine loop of proliferation. When grafted in nude mice, these stromal cells elicited an angiogenic response that was blocked by neutralizing anti-VEGF IgG. These results might provide a clue to the importance of stromal cells in the pathogeny of neonatal hemangiomas.

Animals↗
PubMed1996

Cerebral ischemia in young and adult gerbils: effects on cholinergic metabolism.

The effect of transient cerebral ischemia on cholinergic metabolism was investigated in adult and young gerbils subjected to bilateral carotid artery occlusion (15 min) alone or with release. Ischemia decreased brain acetylcholine (ACh) and increased choline (Ch) levels, affecting the young to a lesser degree than the adult gerbils. Blood recirculation induced a rapid early restoration of brain ACh levels in young animals, whereas a tremendous rebound of ACh was observed in the adults. After 2 h of reflow, Ch levels normalized in the adult brain, whereas a decreased choline level was seen in the young brain. This is the first study demonstrating an age-dependent susceptibility of cholinergic neurotransmission to cerebral ischemia.

Acetylcholine↗
PubMed1996

[Modulation of the tumoral progression by anti-idiotypic antibodies of angiogenesis factors].

We took advantage of the anti-idiotypic strategy to design circulating probes mimicking the biological effects of VEGF (vascular endothelial growth factor) or FGF2 (fibroblast growth factor 2). The activation of the VEGF receptor KDR/flk-1 induced endothelial cell proliferation but not their migration, whereas that of the FGF receptor FGF-R1 gave opposite results. The long lasting delivery of KDR/flk-1 agonists, but not that of FGF-R1, in nude mice grafted with tumor fragments enhanced the tumor volume. Microscopic examination showed an increase in both the vascularization and the proliferation of cancer cells. In contrast, no difference in cell proliferation was observed within normal tissues.

Adenocarcinoma↗
PubMed1995

Involvement of cAMP in the regulation of high affinity choline uptake by rat brain synaptosomes.

The role of cAMP in the regulation of the high affinity choline uptake (HACU) was investigated in resting and KCl-stimulated rat brain synaptosomes. The data indicate that the permeable cAMP analogue, monobutyryl-8-bromo cAMP, increased dose-dependently the HACU in resting synaptosomes. Treatments of resting synaptosomes by oxotremorine, quinacrine, and promethazine resulted in a reduced cAMP formation with a concomitant decrease of HACU. The reduction of HACU could be completely counteracted by the monobutyryl-8-bromo cAMP following oxotremorine treatment and was only partially inhibited in quinacrine and promethazine treated resting synaptosomes. KCl stimulation resulted in a significant increase in cAMP formation and HACU by the synaptosomes. The different profile of data obtained following the previous pharmacological treatments in KCl-stimulated synaptosomes suggests that both cAMP and phospholipase A2 pathways may act synergistically to coordinate the neuronal choline incorporation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1994

Arachidonic acid release and permeability changes induced by endothelins in human cerebromicrovascular endothelium.

The vasoactive peptide endothelin-1 (ET-1) dose-dependently increased release of 51Cr from human cerebromicrovascular endothelial cells (HBEC), without affecting cell viability as assessed by lactate dehydrogenase release. ET-1 also induced transient accumulation of inositol triphosphate (IP3) and release of [3H] arachidonic acid (AA) from HBEC. The ET-1-induced 51Cr release, formation of IP3, and AA release from HBEC were competitively inhibited by selective ETA subtype receptor antagonist BQ-123. ET-1-stimulated 51Cr- and AA release from HBEC were potentiated by proteinkinase C (PKC) activator phorbol-myristate ester, and abolished by H7, an inhibitor of PKC. Dexamethasone, indomethacin, acetylsalicylic acid, imidazole, as well as the inhibitor of protein kinase A, H8, had no effect on 51Cr release. The results suggest that ETA-receptor mediated activation of PKC and increase in the HBEC 'permeability' for low molecular weight molecules in response to excessive release of endothelins from either HBEC or surrounding tissues during pathologic conditions may contribute to the formation of cerebral edema.

Arachidonic Acid↗
PubMed1994

The relationship between cerebral ischemic edema and monoamines: revisited.

The association of changes in the metabolic pathway of monoamines (dopamine and 5-hydroxytryptamine) with mitochondrial enzymatic systems which are involved in the production and removal of free radicals formed during dopamine metabolism and formation of edema was investigated in bilateral brain ischemia in gerbils. The results suggest that the involvement of DA-derived free radicals in brain edema is unlikely in early reflow, because disbalance between H2O2-producing reactions of DA-metabolism, and mitochondrial antioxidative capacity does not occur prior to 1 hour reflow after 15 min bilateral ischemia in gerbils. However, the findings of this study reinforce the participation of 5-HT in the formation of ischemic brain edema.

Animals↗
PubMed1994

Time course of decline of radiolabeled acetylcholine formed following intracerebroventricular administration of tritiated choline: effects of oxotremorine and scopolamine.

Rats were injected intracerebroventricularly with 5 microCi of [methyl-3H]choline. The time course of decline of the radiolabeled acetylcholine (ACh) formed was estimated in the ipsilateral cerebral cortex and striatum. The [3H]ACh levels declined biphasically from the cerebral tissue. The initial decline proceeded rapidly, after which labeled ACh declined more slowly. Scopolamine (1 mg/kg, i.v.) caused a significant increase in the rate of [3H]ACh disappearance, which can be interpreted as an enhancement of ACh release. By contrast, oxotremorine (0.8 mg/kg, i.v.) markedly reduced the [3H]ACh disappearance. The results show that drug-induced changes in cholinergic neuronal activities can be estimated from the disappearance of radioactive ACh after labeling the endogenous transmitter through intracerebroventricular administration of labeled choline.

Acetylcholine↗