Jacques-Philippe Moulinoux

Centre Hospitalier Universitaire de Rennes, Roazhon, Brittany, France

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Publications (22)63.97 Total impact

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    Bernard Cipolla, Jean-Yves Bansard, J. Pierre Ecalard, Jacques-Philippe Moulinoux
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    ABSTRACT: Background Polyamine (PA) dietary deprivation may be of clinical interest in castration-resistant prostate cancer (CRPC). Purpose We assessed tolerance and side effects of PA-free oral nutritional supplement (ONS) combined with partial intermittent intestinal decontamination (PIID) in a Phase I trial. Methods Ten volunteers of mean age 68 ± 12 years and with symptomatic, metastatic CRPC were enrolled. PA-free ONS was given as the only food source three times daily during the first 2 weeks; twice daily with one PA-reduced meal for 3 weeks; and then once daily with two PA-reduced meals for 7 weeks. Oral neomycin was administered at 0.75 g/day as PIID every other week. Toxicity, performance, and pain status were rated on World Health Organization and European Organisation for Research and Treatment of Cancer scales. Prostate-specific antigen, blood counts, ionograms, and hepatic transaminases were regularly assessed. Bone and computed tomography scans were performed at weeks 0, 5 and 12. Results One patient disliked the taste and stopped on Day 4. Nine patients experienced transient Grade I diarrhea. Performance status and pain score were significantly improved in five patients and maintained in three patients. No significant differences in body weight, hemoglobin, serum proteins, and ionograms were noted. Four patients had 20–40% prostate-specific antigen baseline decline during the first 5 weeks of the trial. Five patients had bone and computed tomography scan stabilization. Conclusion This PA-free ONS was safe and well tolerated with PIDD. It seemed to benefit quality of life and control pain. The effects were dose dependent, with maximum improvement observed during the first 5 weeks when PA depletion was maximal.
    Biomedicine 09/2013; 3(3):114–119.
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    Bernard G Cipolla, René Havouis, Jacques-Philippe Moulinoux
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    ABSTRACT: Background Reducing polyamine uptake by selecting low polyamine-containing foodstuffs and reducing bacterial gut production can improve performance status and pain control in hormone refractory prostate cancer (HRPC) patients. Long term PRD observance and tolerance were assessed. Cancer specific survival was studied in function of PRD and time of PRD initiation.Methods Twenty-six volunteers, age: 68 ± 10 years with metastatic HRPC accepted a polyamine reduced diet and partial gut decontamination with oral neomycin or nifuroxazide (750 mg daily, one week out of two). Time from HRPC to PRD initiation was 10 ± 8 months. WHO performance status, EORTC pain scale, body weight, blood counts and serum proteins were regularly assessed. Sixteen other HRPC patients eating a normal diet served as “controls”.ResultsMean diet observance is 25 ± 24 months. Tolerance is good. WHO performance status and EORTC pain scales were significantly improved respectively at 3 months (0.5 ± 0.7 vs 0.7 ± 0.9: p = 0.03) and 6 months (0.5 ± 0.8 vs 1 ± 1.3, p = 0.02) compared to initial values. Median cancer specific survival times after HRPC and PRD initiation are respectively 36 and 21 months. Eleven PRD patients started the diet before a 9 months cut-off period (after HRPC) and 15 patients after. Median cancer specific survival times for these two groups of patients are respectively 44 and 34 months, p = 0.014. Median cancer specific survival times (after HRPC) for PRD patients compared to controls are 36 vs 17 months (p = 0.004).Conclusions Polyamine-reduced diet is well observed and tolerated. It seems to improve and/or maintain quality of life for HRPC patients. Early PRD initiation in HRPC is promising and may impact favorably cancer specific survival. These results open a rationale for PRD in HRPC management and warrant further investigation.
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    ABSTRACT: Oxaliplatin is an anticancer drug used for the treatment of advanced colorectal cancer, but it can also cause painful peripheral neuropathies. The pathophysiology of these neuropathies has not been yet fully elucidated, but may involve spinal N-methyl-D-aspartate (NMDA) receptors, particularly the NR2B subunit. As polyamines are positive modulators of NMDA-NR2B receptors and mainly originate from dietary intake, the modulation of polyamines intake could represent an interesting way to prevent/modulate neuropathic pain symptoms by opposing glutamate neurotransmission. The effect of a polyamine deficient diet was investigated in an animal model of oxaliplatin-induced acute pain hypersensitivity using behavioral tests (mechanical and cold hypersensitivity). The involvement of spinal glutamate neurotransmission was monitored by using a proton nuclear magnetic resonance spectroscopy based metabolomic approach and by assessing the expression and phosphorylation of the NR2B subunit of the NMDA receptor. A 7-day polyamine deficient diet totally prevented oxaliplatin-induced acute cold hypersensitivity and mechanical allodynia. Oxaliplatin-induced pain hypersensitivity was not associated with an increase in NR2B subunit expression or phosphorylation, but with an increase of glutamate level in the spinal dorsal horn which was completely prevented by a polyamine deficient diet. As a validation that the oxaliplatin-induced hypersensitivity could be due to an increased activity of the spinal glutamate system, an intrathecal administration of the specific NR2B antagonist, ifenprodil, totally reversed oxaliplatin-induced mechanical and cold hypersensitivity. A polyamine deficient diet could represent a promising and valuable nutritional therapy to prevent oxaliplatin-induced acute pain hypersensitivity.
    PLoS ONE 01/2013; 8(10):e77828. · 3.53 Impact Factor
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    Bernard G Cipolla, René Havouis, Jacques-Philippe Moulinoux
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    ABSTRACT: Reducing polyamine uptake by selecting low polyamine-containing foodstuffs and reducing bacterial gut production can improve performance status and pain control in hormone refractory prostate cancer (HRPC) patients. Long term PRD observance and tolerance were assessed. Cancer specific survival was studied in function of PRD and time of PRD initiation. Twenty-six volunteers, age: 68+/-10 years with metastatic HRPC accepted a polyamine reduced diet and partial gut decontamination with oral neomycin or nifuroxazide (750 mg daily, one week out of two). Time from HRPC to PRD initiation was 10+/-8 months. WHO performance status, EORTC pain scale, body weight, blood counts and serum proteins were regularly assessed. Sixteen other HRPC patients eating a normal diet served as "controls". Mean diet observance is 25+/-24 months. Tolerance is good. WHO performance status and EORTC pain scales were significantly improved respectively at 3 months (0.5+/-0.7 vs 0.7+/-0.9: p=0.03) and 6 months (0.5+/-0.8 vs 1+/-1.3, p=0.02) compared to initial values. Median cancer specific survival times after HRPC and PRD initiation are respectively 36 and 21 months. Eleven PRD patients started the diet before a 9 months cut-off period (after HRPC) and 15 patients after. Median cancer specific survival times for these two groups of patients are respectively 44 and 34 months, p=0.014. Median cancer specific survival times (after HRPC) for PRD patients compared to controls are 36 vs 17 months (p=0.004). Polyamine-reduced diet is well observed and tolerated. It seems to improve and/or maintain quality of life for HRPC patients. Early PRD initiation in HRPC is promising and may impact favorably cancer specific survival. These results open a rationale for PRD in HRPC management and warrant further investigation.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 05/2010; 64(5):363-8. · 2.24 Impact Factor
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 01/2010; 33(9).
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    ABSTRACT: There is a compelling body of evidence that N-methyl-d-aspartate receptors (NMDA-R) play a critical role in the development and maintenance of pain hypersensitivity. However, long-term treatments with NMDA-R antagonists are limited by unacceptable side effects. Since polyamines modulate the functioning of NMDA-R and mainly originate from normal dietary intake and bacterial metabolism in the gut, we developed a nutritional therapy based on dietary polyamine deficiency. Here, we reported that a polyamine deficient diet (PD diet) for 7 days prevented the enhancement of tyrosine phosphorylation of the spinal NR2B subunit-containing NMDA-R associated with inflammation in rats. Based on these data, we studied the ability of PD diet to prevent long-lasting pain hypersensitivity associated with tissue injury on one hind paw by evaluating long-lasting changes in both mechanical nociceptive threshold and weight bearing. A PD diet strongly reduced long-lasting hyperalgesia induced by inflammation or incision, especially in fentanyl-treated rats. Moreover a PD diet also prevented the exaggerated hyperalgesia induced by a second inflammation performed 7 days after the first one. A PD diet also opposed paradoxical hyperalgesia induced by non-nociceptive environmental stress in rats with pain and opioid experiences. A PD diet reversed pain hypersensitivity associated with monoarthritis or neuropathy and restored the analgesic effect of morphine. Since PD diet was devoid of any noticeable side effects, this nutritional therapy could be part of an effective and safe strategy for pre-emptive analgesia and for reducing the transition from acute to chronic pain and its outcomes in various pain syndromes.
    Pain 08/2008; 137(1):125-37. · 5.64 Impact Factor
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    ABSTRACT: The present study aimed to examine the effects of an acute administration of the mu-opioid receptor fentanyl on affect as assessed by place-conditioning procedure in rats. We determined the affective properties of fentanyl not only immediately following its administration, but also 24h later. Experiments were performed using the dose of fentanyl (240 gamma/kg; four injections of 60 gamma/(ml kg) every 15 min, subcutaneously) for which secondary hyperalgesia has been previously described. Our results show that the acute administration of fentanyl display biphasic affective properties, with early rewarding and 24-h delayed aversive components. The 24-h delayed aversive effects of fentanyl were not observed in animals submitted to a polyamine-deficient diet, suggesting an NMDA-dependent mechanism.
    Behavioural Brain Research 07/2008; 190(1):119-23. · 3.33 Impact Factor
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    Frédérique Pédrono, Bernard Saïag, Jacques-Philippe Moulinoux, Alain B Legrand
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    ABSTRACT: 1-O-alkylglycerols (alkyl-Gro) are natural etherlipids with multiple biological activities. We previously demonstrated that alkyl-Gro reduce endothelial permeability. Here we showed that alkyl-Gro reduced the basic Fibroblast Growth Factor (bFGF)-stimulated endothelial cell proliferation in a concentration-dependent manner. The effects of 0.5 and 5 ng/ml bFGF on growth were completely suppressed after 72 h-treatment by 50 microM alkyl-Gro. Since bFGF greatly increased (+56%+/-15) the production of 1-O-alkyl-2-acyl-sn-glycerophosphate in alkyl-Gro-treated endothelial cells, our data suggest that the observed effects of alkyl-Gro could be mediated through PLD activation. Inhibition of bFGF-stimulated endothelial proliferation could support anti-angiogenic activity of alkyl-Gro.
    Cancer Letters 07/2007; 251(2):317-22. · 5.02 Impact Factor
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    ABSTRACT: Polyamines are thought to be involved in the regulation of numerous metabolic and electrophysiological processes in the nervous system. In this study we evaluated the effect of a synthetic polyamine-deficient diet on pain in a carrageenan (Car)-induced inflammatory rat model. Inflammation was induced with a unilateral subcutaneous injection of Car in a plantar hindpaw in rats fed without (control group) or with (deficiency group) a polyamine-deficient diet. Ipsilateral and contralateral hyperalgesia was evaluated using the Randall-Sellito pressure test. Heart rate changes were also recorded under general anesthesia. Then, the effects of a bupivacaine sciatic nerve block and subcutaneous injection of naloxone or ketamine were evaluated for Car-induced hyperalgesia. Data were analyzed using analysis of variance followed by unpaired Student's t-test (significance P < 0.05). Before Car injection, no significant difference was observed in response to mechanical stimuli between the control and the deficiency groups (n = 114 in pooled data). Car injection induced significant ipsilateral and contralateral hyperalgesia in the control groups, whereas a significant analgesic effect appeared in the deficient groups on both the ipsilateral and contralateral hindpaws. This analgesic effect was confirmed by the electrocardiogram recording that showed a significant increase in heart rate in the control group after Car injection compared with the deficiency group that showed a decrease in heart rate under general anesthesia. Bupivacaine sciatic nerve block had no significant effect on hypoalgesia phenomena induced by polyamine deficiency. Naloxone administration had no effect in the control group but reversed the analgesic effect in the deficiency group. Ketamine administration induced a significant analgesic effect in the control group and partly reversed the analgesic effect in the deficiency group. In conclusion, a synthetic polyamine-deficient diet had a significant general analgesic effect on Car-induced mechanical hyperalgesia. The mechanism of analgesic action remains to be elucidated.
    Anesthesia and analgesia 06/2006; 102(6):1781-8. · 3.08 Impact Factor
  • Analytical Biochemistry 07/2005; 341(2):385-7. · 2.58 Impact Factor
  • François Gaboriau, Michel Vaultier, Jacques-Philippe Moulinoux, Jean-Guy Delcros
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    ABSTRACT: Structural analogues of natural polyamines, which contain a -Si(CH3)2 group in the central carbon chain, have previously been found to be cytotoxic to various tumor cell lines in vitro and to inhibit tumor cell growth in experimentally grafted animals. In the present study, the antioxidative properties of dimethylsilane polyamine analogues were analyzed in comparison with the natural polyamines. Reactivities of these various polyamines against superoxide anions (generated from the hypoxanthine/xanthine oxidase reaction) and peroxyl radicals (produced from the thermal decomposition of water-soluble 2,2'-azo-bis-[2-amidinopropane] hydrochloride) were investigated. The dimethysilane analogues, and more particularly the hexamine derivative, exhibited the highest scavenging efficiency towards these two reactive oxygen species (ROS). Furthermore, analysis of their ability to prevent hydroxyl radical formation and to trap this ROS showed that the efficiency of the hexamine as a metal chelator and hydroxyl radical scavenger is similar to that of spermine. The higher antioxidant efficiency of the dimethylsilane polyamine analogues with respect to spermidine, together with their ability to displace this polyamine, essential for the promotion of cell growth, from its cellular anionic binding sites that are particularly prone to oxidation, could be biologically relevant and contribute to their in vivo cytotoxic effect and anti-tumor activity. Further experiments will be necessary to demonstrate clearly the relationship between their antioxidant properties and their antiproliferative effects.
    Redox report: communications in free radical research 02/2005; 10(1):9-18. · 1.51 Impact Factor
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    ABSTRACT: Renal cell carcinoma (RCC) is known to display a wide variation in biological behavior and clinical outcome. Although usual bioclinical prognostic parameters (eg, nuclear grade, tumor stage) are to a certain extent useful in predicting the outcome of RCC after radical nephrectomy, they now appear to be insufficient. The polyamines (spermidine, spermine, and putrescine) are ubiquitous polycations that are essential for cell proliferation. To support their excessive proliferation, cancer cells have high rates of polyamine metabolism. Indeed, malignant cells typically have higher polyamine levels than their normal counterparts. Before this report, antipolyamine antibodies that are potentially valuable tools for the in situ observation of polyamines had not been exploited in clinical conditions. In the present study, tumor tissues obtained from radical nephrectomy performed for RCC (n = 73) were immunostained with the anti-spermine monoclonal antibody Spm8-2, and the immunoreactivity was evaluated as a prognostic tool. RCC cells displayed various reactivity to the antibody Spm8-2 that translated into a heterogeneous cytoplasmic staining. The prognostic value of the labeling index (LI) on clinical outcome was correlated with the usual clinicopathologic parameters, and the cell proliferation rate was evaluated using Ki-67 labeling. Multiple correspondence analysis and ascending hierarchical classification were performed to determine significant prognostic factors. Univariate statistical survival analysis demonstrated that tumor size (P < .001), nuclear grade (P < .01), necrosis (P < .007), tumor stage (P < .004), metastasis (P < .001), Ki-67 LI (P < .0003), and Spm8-2 immunoreactivity (P < .0001) were predictors of tumor-related death. A positive correlation was found between Ki-67 LI and Spm8-2 immunoreactivity (r' = .53). Multivariate analysis revealed that only Ki-67 LI and Spm8-2 immunoreactivity were significant independent factors in patients with metastases (P < .04 and <.001, respectively) and in patients without metastases (P < .006 and <.001, respectively). Moreover, 100% of the patients with Spm8-2 immunoreactivity <10% were alive at the end of the follow-up. In terms of predictive values, Spm8-2 immunoreactivity had the highest predictive values (sensitivity, 89; specificity, 75; risk ratio, 11) of all clinicopathologic parameters. This study demonstrates that the anti-spermine monoclonal antibody Spm8-2 may be used at the time of radical nephrectomy as a reliable prognostic marker for defining RCC patients at high risk for progression.
    Human Pathlogy 11/2004; 35(10):1279-84. · 2.84 Impact Factor
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    ABSTRACT: Polyamines are ubiquitous molecules, which, like iron, are essential for cell growth. All eukaryotic cells are equipped with a specific polyamine transport system (PTS). Polyamines have primary and secondary amino groups which chelate bivalent metal cations such as Fe and Cu. In the present study, we investigated the potential contribution of naturally occurring polyamines and their active transport system to iron uptake. In presence of subtoxic Fe(III) (10microM), treatment of CHO cells with spermine, and to a lesser extent with spermidine (10-100microM), resulted in a marked cytotoxic effect. This cytotoxicity was prevented by the addition of an iron-chelator, deferioxamine, and was not observed in CHO-MG cells, a mutant cell line devoid of polyamine transport activity. Experiments using 14C-polyamines and 55Fe(III) revealed that these toxic effects were related to polyamine-modulation of iron uptake, and were dependent on the presence of the active PTS. These results demonstrated active uptake of polyamine-iron complexes via the PTS. The number of amino groups affected the efficacy of the studied natural polyamines to transport iron via the PTS. Spermine, a tetramine, was more efficient than the triamine spermidine. Co-transport of iron by the diamine putrescine was not observed. These results demonstrate that the cell polyamine transport system is a potential cell entry pathway for iron. The studied polyamines, spermine and spermidine, may be components of the pool of transferrin-independent iron-chelating vectors, which have recently attracted the attention of many investigators.
    Biochemical Pharmacology 06/2004; 67(9):1629-37. · 4.58 Impact Factor
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    ABSTRACT: Alkylglycerols are natural etherlipids abundant in shark liver oil (SLO) in a diacylated form. SLO is known to have antitumor properties and was recently described as an inhibitor of tumor neovascularization. However, most studies did not discriminate between the respective activities of alkylglycerols and of fatty acids, which both have potent biological properties. In this work, a mouse model was used to investigate the antitumor effects of SLO and of alkylglycerols purified from the same source, both administered orally. We demonstrated that either pure alkylglycerols or SLO reduced the tumor growth in a similar manner, suggesting that alkylglycerols were involved in this effect. In alkylglycerol-treated mice, metastasis dissemination was reduced by 64 +/- 8%, whereas SLO effect was 30 +/- 9% below control. Purified alkylglycerols also decreased significantly plasmalogen content in tumors, whereas SLO had no such effect. Finally, we demonstrated that a 5-day treatment with alkylglycerols curtailed the presence in tumors of von Willebrand factor, a marker of endothelial cells. This result suggested an anti-angiogenic effect of alkylglycerols. In summary, alkylglycerols were shown to decrease the growth, vascularization, and dissemination of Lewis lung carcinoma tumors in mice. These findings suggest that the antitumor activity of SLO is likely mediated by the presence of alkylglycerols.
    Nutrition and Cancer 02/2004; 48(1):64-9. · 2.70 Impact Factor
  • François Gaboriau, René Havouis, Jacques-Philippe Moulinoux, Jean-Guy Delcros
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    ABSTRACT: Determination of polyamine pools is still a step impossible to circumvent in studies aimed at determining the pathophysiological role of natural polyamines. In addition, polyamine measurement in biological fluids and tissues may have clinical relevance, especially in cancer patients. Among the wide panel of analytical methods developed for the quantification of polyamines, high-performance liquid chromatographic (HPLC) separation of polyamines after derivatization with dansyl chloride remains the most commonly used method. In this work, we show that atmospheric pressure chemical ionization-mass spectrometry (MS) can be used to detect and quantify biologically relevant polyamines after dansylation, without chromatographic separation. Positive-ion mass spectra for each dansylated polyamine were generated after optimization by flow injection analysis (FIA). FIA coupled with MS detection by selected ion monitoring greatly increased the sensitivity of the polyamine detection. The method is linear over a wide range of polyamine concentrations and allows detection of quantities as low as 5 fmol. The FIA/MS method is about 50-fold more sensitive than the conventional HPLC/fluorimetry procedure. A good correlation (r>0.98) between these two methods was observed. The FIA/MS method notably reduces the time of analysis per sample to 1.5 min and turns out to be rapid, efficient, cost saving, reproducible, and sufficiently simple to allow its routine application.
    Analytical Biochemistry 07/2003; 318(2):212-20. · 2.58 Impact Factor
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    ABSTRACT: We studied the inhibition of peroxidation by local anesthetics in an inflammatory animal model. Inflammatory lipid peroxidation was assessed by the thiobarbituric assay in plasma from rats injected or not injected with carrageenan (Carra) and killed 1, 2, 4, 6, 12, and 24 h thereafter. Thiobarbituric acid reactive substances (TBARS) values in inflammatory animals were maximal 6 h after Carra administration. This result, in accordance with the evolution of paw edema width during time, supports that TBARS reflect the intensity of inflammation. Local anesthetics (bupivacaine, lidocaine, ropivacaine, or bupivacaine-loaded microspheres) or amitriptyline were injected in clinically relevant concentrations as a sciatic nerve block or intraperitoneally in inflamed animals. Ropivacaine did not exhibit any protective effect on Carra-induced lipid peroxidation in rats. With all the other drugs administered as a sciatic nerve block, the maximal TBARS increase was not observed at 6 h. Our conclusion is that bupivacaine (plain or encapsulated), lidocaine, and amitriptyline in clinically relevant concentrations administered via the sciatic nerve showed antioxidant properties toward lipid peroxidation induced by Carra inflammation. Intraperitoneal injection of those drugs gave the same effect as nerve block; this result suggests that their mechanism of action is not strictly limited to the nerve. IMPLICATIONS. We investigated the antioxidant effects of local anesthetics and amitriptyline in an inflammatory rat model. Amitriptyline exhibits antioxidant properties per se, whereas lidocaine and bupivacaine (plain or encapsulated) seem to inhibit the peroxidation process. This may have future application in limiting toxic oxygen metabolite production during the inflammatory process.
    Anesthesia & Analgesia 11/2002; 95(4):992-6, table of contents. · 3.30 Impact Factor
  • Gwenaëlle Desury, Jacques-Philippe Moulinoux, Jean-Guy Delcros
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    ABSTRACT: Polyamines are essential for rapidly dividing cells such as enterocytes and tumour cells. In both cells, polyamine pools are maintained by biosynthetic pathways along with active uptake systems. Because of their strategic position, enterocytes play an important role in the trafficking of luminal polyamines. The aim of this study was to determine whether the high polyamine demanding MAT-LyLu prostatic tumour alter the absorption and metabolism of putrescine in the small intestine tissue of rats. In vivo, after intragastric intubation of [14C]-putrescine, both the uptake of putrescine and its metabolic conversion into non-polyamine metabolites were enhanced in the small intestine of tumour-bearing rats. The presence of the tumour also altered the biodistribution of the radioactivity with a striking increased level of radioactivity in the plasma, which was probably the consequence of a higher net flux of putrescine from the lumen to the blood. Ex vivo studies using everted small intestine segments supported this hypothesis. The stimulation of putrescine uptake and metabolism in enterocytes of tumour-bearing animals may be an adaptation to compensate for the energy deficit caused by the competition with the tumour for nutrients and worsened by the tumour-associated cachexy.
    International Journal of Oncology 10/2002; 21(3):569-76. · 2.66 Impact Factor
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    ABSTRACT: Polyamine vectors are attractive for tumor targeting. We envisaged (Z)-1,4-diamino-2-butene (Z-DAB), an unsaturated analogue of putrescine as vector of (10)B, (18)F and (131)I for boron neutron capture therapy (BNCT), and tumor imaging by positron emission tomography or scintigraphy respectively. In the present work, the synthesis and characterization of new derivatives of Z-DAB were reported. Z-DAB was actively transported in cells via the polyamine transport system and converted into the spermidine analogue.(E)-2-iodo-1,4-diamino-2-butene (E-I-DAB) was not taken up by the polyamine transport system and may not be suitable for tumor imaging. In contrast, (Z)-2-[4-(5,5-dimethyl-dioxaborinan-2-yl)phenyl]methyl-1,4-diamino-2-butene (Z-4-Bbz-DAB) was a substrate of the transport system and allowed significant boron accumulation in 3LL cells. Its potential in BNCT will be evaluated.
    Bioorganic & Medicinal Chemistry 10/2002; 10(9):2863-71. · 2.90 Impact Factor
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    ABSTRACT: Structural analogues of the natural polyamines which contain a Si(CH3)2 group in the central carbon chain have previously been found to be cytostatic to various tumor cell lines and to inhibit tumor cell growth in experimentally-grafted animals. We show that membrane damages induced by hexamine in chinese ovary cells are the earliest cytotoxic events. We report the interaction of natural and dimethylsilane polyamines with membrane models. These polyamines protect the red blood cell membrane from hypotonic-induced cell lysis. In the case of dimethylsilane derivatives and to a lesser extent for putrescine, this stabilizing effect is followed, for longer times, by the progressive lysis of cell membranes, suggesting a biphasic interaction of polyamines with membrane components. The Langmuir's monolayer method shows that the first step of the electrostatic interaction of spermine with negatively charged phospholipids, egg phosphatidic acid (EPA), is characterised by a decrease of the mean molecular area of phospholipid. Over longer times, an increase of the mean molecular area is observed for all polyamines suggesting the insertion of their hydrocarbon chains into the monolayers. Probably as a consequence of their higher hydrophobicity, the maximal increase is obtained with dimethylsilane derivatives.
    Colloids and surfaces B: Biointerfaces 01/2002; · 4.28 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the effect of different durations of local anesthetic neural blockade on hyperalgesia after carrageenan infiltration in a rat model. Inflammation was obtained by injection of carrageenan in the righ hind paw. Hyperalgesia was determined by measuring the threshold of response to increasing mechanical stimuli on the contralateral and on the ipsilateral paw. The development of edema was measured. After identification of the sciatic nerve by nerve stimulation, blockade was performed either one hour before or after carrageenan infiltration. Animals were randomly assigned into three groups: without sciatic nerve block (control group; n = 20), block with bupivacaine (B) and block with bupivacaine-loaded microspheres (B-Ms) injection before or after carrageenan infiltration (n = 10 for each group). Carrageenan infiltration in the control group induced a severe ipsilateral and contralateral hyperalgesia. After blockade with B (duration = 2 +/- 0.5 hr) hyperalgesia was present and delayed only by the duration of the local anesthetic effect. A longer duration of block achieved with B-Ms (duration greater than five hours), was associated with the absence of development of both ipsilateral and contralateral hyperalgesia. No preemptive effect was recorded. B-Ms as a drug delivery system prolongs the duration of neural blockade and avoids hyperalgesia phenomena in this rat model of inflammation.
    Canadian Journal of Anaesthesia 01/2002; 49(7):690-3. · 2.13 Impact Factor

Publication Stats

198 Citations
63.97 Total Impact Points

Institutions

  • 2002–2013
    • Centre Hospitalier Universitaire de Rennes
      Roazhon, Brittany, France
  • 2010
    • Centre Hospitalier Privé Saint-Grégoire
      Sant-Gregor, Brittany, France
  • 2002–2010
    • Université de Rennes 2
      Roazhon, Brittany, France
  • 2003–2008
    • Université de Rennes 1
      • Faculté de Médecine
      Roazhon, Brittany, France