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Biomedical subjects

P Poindron

Publications and source records attributed to P Poindron.

At least 55 records · Page 3Linked to original sources
PubMed1996

Cytotoxicity of peritoneal murine macrophages against encapsulated pancreatic rat islets: in vivo and in vitro studies.

The aim of this work was to study in vivo and in vitro the involvement of macrophages and interleukin-1beta (IL-1beta) in the necrosis of encapsulated islets during xenograft and to evaluate the immunoprotective efficiency of the AN69 membrane. In vivo, 6 days after implantation, 65% of the membrane surface of the devices containing the islets was colonized with macrophages compared with only 5% of the surface of the empty control devices. The morphological aspect of implanted islets was altered and their insulin release decreased significantly compared with freshly isolated ones (265 +/- 50 vs. 507 +/- 81 microU/mL). In vitro, the insulin release of encapsulated islets cultured for 2 days decreased to 32 and 28%, respectively, in the presence of IL-1beta and macrophages. The addition of anti-IL-1beta antibody to the co-culture of macrophages and islets did not modify this loss of functional activity. Furthermore, IL-1beta passed through the AN69 membrane. In conclusion, macrophages are involved in damaging encapsulated pancreatic islets and are probably partly responsible for islet transplantation failure.

Animals↗
PubMed1996

Enhancement of mouse sciatic nerve regeneration by the long chain fatty alcohol, N-Hexacosanol.

The purpose of the present study was to determine the effects of n-hexacosanol (hexa) on nerve regeneration. Hexa, a long chain fatty alcohol has been shown to possess neurotrophic properties on cultured neurons and to attenuate the degeneration of cholinergic neurons after injury. The effects of daily intraperitoneal injections of hexa (1 mg/kg) on regeneration of nerve fibers were studied in mice following a sciatic nerve crush. Measurement of axonal regeneration using the pinch test 7 days postlesion showed a 40% increase of the regeneration rate of sensory fibers in hexa-treated mice compared to controls (1.67 +/- 0.15 mm/day and 1.09 +/- 0.03 mm/day, respectively). The recovery of neuromuscular function was significantly improved, as shown by quantitative electromyography and and sensorimotor tests. Clinical signs of recovery evaluation with toe spreading reflex appeared earlier in hexa group than in control animals. Electrophysiological recordings were performed each 3 days during 34 days following nerve injury. Higher values of the compound muscle action potential (CMAP) were obtained in hexa-treated animals that correspond to an improved regeneration. Moreover, hexa induced a significantly faster regeneration rate (hexa: 2.87 +/- 0.15 mV/day; control: 2.00 +/- 0.06 mV/day), as measured by the slope of CMAP increase (44% enhancement). A morphometric analysis performed 7 days following crush showed an increased number of regenerating fibers, as well as increased diameter and thickness of the myelin in hexa-treated mice. Thus, hexa increased the regeneration of both sensory and motor axons in lesioned nerve, leading to an improved functional recovery.

Animals↗
PubMed1996

Electromyographical and motor performance studies in the pmn mouse model of neurodegenerative disease.

The mouse autosomal recessive mutation progressive motor neuronopathy (pmn) results in early onset motor neuron disease with rapidly progressive hindlimb paralysis, severe muscular wasting, and death at around 6 weeks of age. This mutant provides opportunities for testing novel therapeutic strategies, including the administration of trophic factors, to prevent the degeneration of diseased neurons. The construction of a strain expressing the pmn and the Extra-toe (Xt) phenotypes allows the detection, and therefore the treatment, of affected progeny before the onset of the clinical weakness. Electromyography is the most appropriate technique for a longitudinal study in which a given individual is examined repeatedly. We present the results of an electrophysiological and behavioral exploration of the pmn disease and show that electromyography is a powerful tool for following the course of the disease and evaluating potential therapies relevant to motor neuron diseases.

Action Potentials↗
PubMed1996

Mucosal inflammatory cytokine production by intestinal biopsies in patients with ulcerative colitis and Crohn's disease.

Chronic inflammation in inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis) may be attributed partly to increased secretion of inflammatory cytokines. The aim of this study was to investigate simultaneously the spontaneous release patterns of tumor necrosis factor-alpha (TNF-alpha), interleukin-1-beta (IL-1 beta), and interleukin-6 (IL-6) by organ cultures of inflamed mucosa from IBD patients. Organ cultures of involved IBD mucosa spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6 compared to normal mucosa. The patterns of cytokine release between Crohn's disease and ulcerative colitis organ cultures were not significantly different. Increased inflammatory cytokine production by lamina propria mononuclear cells (LPMCs) and mucosa treated with EDTA suggests that these cytokines originate mainly from LPMCs. These results confirm the role of inflammatory cytokines in IBD and shed a new light on the role of TNF-alpha in IBD.

Adult↗
PubMed1996

Neurotrophins increase motoneurons' ability to innervate skeletal muscle fibers in rat spinal cord--human muscle cocultures.

Neurotrophins, nerve growth factor (NGF), neurotrophin-3 (NT-3), neurotrophin-5 (NT-5) and brain-derived neurotrophic factor (BDNF), were studied in vitro in a coculture model of human skeletal muscle myotubes and rat embryo spinal cord explants, which enables the different steps of functional innervation to be followed, including neurite outgrowth, synapse formation and induction of contractile activity. We found that NT-3, NT-5, BDNF, but not NGF simultaneously induced a significant increase in the number and length of neurites emerging from spinal cord explants, the number of endplates per muscle fiber, and the area of innervated muscle fibers around each spinal cord explant. These results suggest that neurotrophins NT-3, NT-5 and BDNF enhance spinal cord motoneurons potential of innervation.

Animals↗
PubMed1996

Increased production of tumour necrosis factor-alpha interleukin-1 beta, and interleukin-6 by morphologically normal intestinal biopsies from patients with Crohn's disease.

BACKGROUND: Increasing evidence points to a important role for inflammatory cytokines for the pathogenesis of Crohn's disease. AIM: To compare the secretion rate of tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) by morphologically normal and inflamed intestinal mucosa from patients with Crohn's disease. RESULTS: Organ cultures of intestinal biopsy specimens taken from areas of affected mucosa from patients with Crohn's disease spontaneously produced increased amounts of TNF-alpha, IL-1 beta, and IL-6 compared with controls but also biopsy specimens taken in macroscopically and microscopically unaffected areas in the same patients. Concentrations of IL-1 beta and IL-6 measured in the supernatant fluid of biopsy cultures were positively correlated with the degree of tissue involvement measured by both endoscopic and histological grading. By contrast, TNF-alpha concentrations were not correlated to endoscopic and histological grading. CONCLUSIONS: These consistently raised TNF-alpha, IL-1 beta and IL-6 secretions by normal appearing mucosa from patients with Crohn's disease provide evidence for a sustained immune stimulation in Crohn's disease even in the absence of patent inflammation. The results shed a new light on the role of inflammatory cytokines in the onset of intestinal tissue damage in Crohn's disease and suggest that the range of intestinal lesions in Crohn's disease may be wider than suspected on the basis of regular endoscopic and histological examinations.

Adult↗
PubMed1996

In situ activation of mouse alveolar macrophages by aerosolized liposomal IFN-gamma and muramyl tripeptide.

Interferon-gamma (IFN-gamma) was entrapped with an efficiency of 30-40% in muramyl tripeptide-containing liposomes by a freeze-thawing procedure. A microcytotoxicity assay was developed to measure the tumoricidal activity of mouse alveolar macrophages (AM) against tumoral target cells with a colorimetric viability test. Free IFN-gamma and liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) were found to be only slightly effective to activate in vitro AM, whereas encapsulation of both INF-gamma and MTP-PE within the same liposomes produced higher activation of AM. Aerosolized IFN-gamma and liposomal immunomodulators enhanced antitumor properties of AM recovered in mice 24 h postinhalation. Whereas free IFN-gamma also induced a substantial activation of peritoneal macrophages, liposomal encapsulation significantly reduced the systemic activity of inhaled immunomodulators. This approach provides a useful model for the compartmentalized organ-specific activation of AM in mice.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1996

Mycophenolic acid suppresses protein N-linked glycosylation in human monocytes and their adhesion to endothelial cells and to some substrates.

Mycophenolic acid (MPA) is the active part of the corresponding morpholinoethyl ester pro-drug Mycophenolate Mofetil. MPA, an inhibitor of IMP dehydrogenase, depletes GTP and thereby suppresses transfer of mannose and fucose to proteins. Treatment of human monocytes with a clinically attainable concentration of MPA (10 microM) decreases their attachment to endothelial cells and to laminin, but not to type I collagen or fibronectin. Our results not only elucidate a major role of mannose/fucose residues in homing of monocytes on activated endothelium but also explain in part the beneficial effects of MPA in rheumatoid arthritis and organ graft rejection.

Antigens, Surface↗
PubMed1995

Constitutive muscular abnormalities in culture in spinal muscular atrophy.

To explore the cause of spinal muscular atrophy (SMA), we used an in-vitro model of nerve-muscle co-cultures in which motoneurons were normal and satellite cells were obtained from SMA patients. In co-cultures initiated with satellite cells from type I and type II SMA patients only, we observed degeneration of the innervated fibres after 1-3 weeks of nerve-muscle co-culture. This process involved vacuolisation, disorganisation, and death of the innervated muscle fibres. This observation points to a muscular implication in the severe forms of SMAs.

Culture Techniques↗
PubMed1995

Antioxidant lazaroids enhance differentiation of C2 skeletal muscle cells.

We have examined the incidence of new antioxidant compounds, so-called lazaroids, on the morphological and biochemical aspects of differentiation of C2 mouse skeletal muscle cells. We show that three lazaroids (U-74006F, U-74389F and U-83836E) enhance fusion of myogenic cells when added at the day of fusion. A parallel increase in nicotinic acetylcholine receptor expression and skeletal muscle alpha-actin content was observed. This promoting effect of lazaroids on myogenesis could be related to inhibition of free radical-mediated muscle damage. Therefore, one could expect that lazaroids might be useful in the treatment of degenerating muscle diseases such as Duchenne muscular dystrophy.

Actins↗
PubMed1995

Myasthenia gravis: comparative autoantibody assays using human muscle, TE671, and glucocorticoid-treated TE671 cells as sources of antigen.

The use of acetylcholine receptors (AChR) from the readily available TE671 cell line as a practical alternative to human muscle for monitoring the anti-AChR antibody assay in sera of Myasthenia gravis patients has been recently proposed. Most of the TE671 culture protocols include the use of glucocorticoids. Glucocorticoids were shown to upregulate the acetylcholine receptor expression in TE671 cells. To confirm the advantage of using AChR from TE671 cells (AChRTE) and to validate the use of AChR from glucocorticoid-treated cells (AChRGT) in AChR antibody measurement, the three different antigens (muscle AChR (AChRMU), AChRTE, and AChRGT) were compared for radioimmunoprecipitation assay. We found that, despite a slight underestimation of the antibody titers using AChRTE and AChRGT compared to AChRMU, and considering the rare cases of AChRMU antibody titer category permutations, the correlations between the values were satisfactory.

Adolescent↗
PubMed1995

Involvement of the main but not the accessory olfactory system in maternal behavior of primiparous and multiparous ewes.

The respective roles of the main and accessory olfactory systems in the development of maternal behavior and selective suckling were investigated in parturient primiparous and multiparous ewes. Vomeronasal nerve section before parturition did not disturb either maternal behavior or maternal selectivity at suckling. By contrast, anosmia induced by zinc sulphate infusion had significant effects on the onset of maternal behavior in primiparous ewes. The onset of licking and of suckling were delayed and licking times and maternal bleats were reduced. Such disturbances were not observed in multiparous anosmic ewes, indicating that experience can compensate for the loss of olfactory information. On the other hand, anosmia prevented selective care regardless of maternal experience. Our results underline the importance of the main olfactory system for the development of adequate maternal behavior in sheep.

Animals↗
PubMed1995

Naltrexone delays the onset of maternal behavior in primiparous parturient ewes.

Previous studies indicate that morphine facilitates the induction of maternal behavior in nonpregnant multiparous ewes but has no effect in nulliparous females. Naltrexone (NAL) has the opposite effect. The aim of the present experiment was to investigate whether this also applied at parturition in ewes lambing for the first time. We studied the behavior of parturient ewes that received either saline (n = 9) or 50 mg (n = 7) or 150 mg (n = 8) of naltrexone, intravenously, at the first signs of lambing. either dose of naltrexone was found to reduce significantly the duration of maternal licking of the neonate and the emission of low-pitched bleats during the first 30 min following parturition (p < 0.005). The proportion of mothers failing to display an immediate onset of maternal care (in < 5 min) was also significantly higher in NAL-treated ewes (six of 15 vs. none of nine; p = 0.05). On the other hand, there was no indication that NAL affected the establishment of selectivity or that it facilitated the manifestation of postpartum estrus. Our results therefore tend to confirm that opiates have a role in the facilitation of maternal behavior at parturition in the ewe.

Animals↗
PubMed1995

Modulation by prednisolone of calcium handling in skeletal muscle cells.

1. Increased calcium (Ca2+) influx has been incriminated as a potential pathological mechanism in the chronic skeletal muscle degeneration exhibited by Duchenne muscular dystrophy (DMD) patients. We have studied the influence of the glucocorticoid alpha-methylprednisolone (PDN), the only drug known to have a beneficial effect on the degenerative course of DMD, on Ca2+ handling in the C2 skeletal muscle cell line. 2. PDN, when added 3 days (when myoblasts start to fuse into myotubes) after cell seeding, led to a 2 to 4 fold decrease in cellular Ca2+ uptake. This decrease was independent of the extracellular Ca2+ concentration applied to cells. The effect took at least 24 h in order to become established (PDN of 10(-5) M) and took longer for lower PDN concentrations (EC50 of ca. 10(-6) M at day 5, 10(-6.5) M at day 7 and 10(-7.5) M at day 9 in culture). 3. Cellular calcium accumulation was also decreased in PDN-treated myotubes exposed to 45Ca(2+)-containing medium for 1 to 6 days. 4. No effect of PDN was seen on 45Ca2+ efflux; a decrease in the amount of 45Ca2+ released was observed due to the reduction of cellular 45Ca2+ loading. 5. PDN treatment led to an approximately 2 fold decrease in basal cytosolic Ca2+ concentration. 6. Three antioxidant drugs (lazaroids), previously shown to enhance in vitro skeletal muscle cell differentiation to the same extent as PDN, induced a similar decrease in Ca2+ influx. 7. Our results suggest that long-term incubation of C2 cells with PDN leads to a decrease of the size of the cellular Ca2+ pools and to reduced resting cytosolic Ca2+ levels. Part of the beneficial effect of PDN in DMD patients could be attributed to a reduction of Ca2+ influx and of the size of Ca2+ pools in dystrophic muscle fibres.

Animals↗
PubMed1994

Flow cytometry distinction between adherent and phagocytized yeast particles.

Our laboratory recently developed a light microscopy staining technique that provides a mean to distinguish between yeast that are simply bound to the surface of macrophages and yeast that have actually been phagocytized by macrophages (7). We adapted this technique by using fluorescent probes in order to test phagocytic activity by flow cytometry. Thus we are able to distinguish unambiguously extracellular from intracellular yeast during phagocytosis with the fast rate of flow cytometry (approximately 200 cells/s). The fluorescence quenching induced by a 1% tannic acid solution (w/v) can be applied to any FITC-labeled, heat-killed yeast cell or bacteria. The yeast cells already engulfed in the macrophage remain with their native fluorescence (internal and external pH equilibrated by 50 microM monensin 30 min/4 degrees C) protected from the action of tannic acid, a nonmembrane permeable molecule. The results presented here validate this new technique. An application is presented showing the inhibition of endocytosis by cytochalasin-B.

Animals↗
PubMed1994

A new method for studying the binding and ingestion of zymosan particles by macrophages.

One of the major problems encountered during quantitative studies of phagocytosis is the discrimination without ambiguity between intracellular and extracellular particles. This difficulty is especially acute when zymosan particles are used because of their poor affinity for dyes. We show in this paper that zymosan particles may be stained by a mixture of a basic dye and tannic acid in water (or in an isotonic non saline solution). Crystal violet is one of the most suitable dyes and by combining this staining step with May-Grünwald Giemsa staining, it was possible to observe two populations of macrophage-associated particles. One comprises blue violet particles (BVP), and the second consists of particles with a purple-stained core (PPC). Treating macrophages in culture with various concentrations of cytochalasin B decreases the number of PPC and increases the number of BVP, in a dose dependant manner. Moreover, treatment with alpha-mannan or laminarin decreases the number of cell-associated particles, especially that of PPC. From these observations we concludes that BVP are extracellularly located and PPC are ingested.

Animals↗
PubMed1994

Lazaroids enhance skeletal myogenesis in primary cultures of dystrophin-deficient mdx mice.

Growing evidence suggests a role for free radicals in the degeneration of dystrophin-deficient muscle (as observed in Duchenne muscular dystrophy). We therefore decided to test the action of the lazaroid antioxidant compounds on primary skeletal muscle cell cultures derived from an animal model of Duchenne muscular dystrophy, the mdx mouse. Both vitamin E-derived U-83836E and glucocorticoid-derived U-74389F enhanced myogenesis of dystrophin-deficient cultures as determined by the number of myotubes, the amount of nicotinic acetylcholine receptor, skeletal muscle alpha-actin levels and myosin light chain. U-83836E enhanced myogenesis of control congenic C57BL/10 mouse-derived muscle cultures whereas U-74389F had no detectable effect. This enhanced myogenesis was in most respects similar to the one triggered by alpha-methylprednisolone which is the only drug known to be beneficial in Duchenne muscular dystrophy.

Animals↗