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Biomedical subjects

P Breton

Publications and source records attributed to P Breton.

At least 19 recordsLinked to original sources

Cross-polarization/magic-angle-spinning nuclear magnetic resonance in selectively 13C-labeled synthetic eumelanins.

We report a solid-state NMR study of synthetic eumelanins prepared by oxidation of 5,6-dihydroxyindole (DHI) selectively 13C-labeled at positions 2 or 3 of the indole ring. The 13C-1H couplings have been used to quantify the carbons by selecting the non-protonated and protonated carbon resonances. By comparing the data of non-labeled melanin to that obtained using [2-(13)C]- and [3-(13)C]-enriched DHI, it was possible to clearly demonstrate the high chemical reactivity of position 2 and, to a lesser extent, position 3 of the DHI unit. These two sites together are responsible for three-quarters of the proton loss during polymerization. The cross-polarization/magic-angle-spinning spectra likewise point to a partial oxidation of positions 2 and 3 to the carboxyl and carbonyl oxidation states during the formation of melanin. Furthermore, it is shown that 13C-13C dipolar interactions in [2-(13)C]-enriched DHI melanins can be observed using radiofrequency-driven dipolar recoupling (RFDR) 2D experiments. An upper limit of about 4 A for the distance between the C-2 carbons is deduced from the RFDR experiments. This result is in agreement with the basic arrangement of the different atoms expected in the DHI melanins.

Carbon Isotopes

Chronic, low-level exposure to the cholinesterase inhibitor DFP. I. Time course of neurochemical changes in the rat pontomesencephalic tegmentum.

Rats were repeatedly administered with a low dose of diisopropylfluorosphosphate (DFP; 0.2 mg/kg/day, SC, for 9 or 21 days), an irreversible cholinesterase (ChE) inhibitor. Control rats received a daily injection of oil vehicle. Neurochemical changes occurring in the pontomesencephalic tegmentum (PMT), a brain stem region critically involved in behavioral state control, were evaluated at various times of treatment and after DFP withdrawal. First, enzyme assay revealed a profile of ChE inhibition in the whole PMT which looked like that observed in the striatum; both the inhibition and recovery proceeded more slowly than they did in the plasma. Second, quantitative histochemistry indicated that ChE activity in the mesopontine cholinergic nuclei and the pontine reticular formation progressively decreased across the first days of DFP exposure, to reach an asymptotic level of inhibition after 6 days (74-82% inhibition). The inhibition was less pronounced in the locus coeruleus (49%). Third, [3H]QNB autoradiography showed that muscarinic receptor density was unchanged in any of the PMT areas selected. These results are discussed regarding the question of regional variation in susceptibility to anti-ChE agents. To what extent behavioral state alterations occur concomitantly with ChE activity changes is assessed in the companion article.

Animals

Molecular mechanisms of the adsorption of a model protein (human serum albumin) on poly(methylidene malonate 2.1.2) nanoparticles.

PURPOSE: To understand the molecular mechanisms involved in protein-methylidene malonate 2.1.2 polymer interactions. METHODS: To assess the importance of electrostatic forces in polymer-protein interactions use was made of HSA and its derivatives, which were anionized by succinylation and aconitylation. Surface plasmon resonance measurements, using the three HSA molecules as immobilized ligands and polymer nanoparticles as analytes in the liquid phase, allowed the determination of initial kinetic constants and affinity constants at equilibrium at two different temperatures. RESULTS: Saturation of binding for the three proteins occurred at approximately 900 protein molecules/nanoparticle. The apparent affinity decreased with increasing electronegativity of the proteins. Surface plasmon resonance measurement of proteins, covalently linked to the chip matrix, showed a high affinity for the nanoparticles (K(A) approximately 10(10) M(-1) and confirmed the moderate decrease of affinity with increasing electronegativity of the modified albumins. Measurements at 25 and 37 degrees C showed no significant increase in the albumin-nanoparticle interactions. Dissociation of the proteins from the nanoparticles could only be realized with chaotropic salt solutions. CONCLUSIONS: These results suggest the molecular forces initiating the protein-nanoparticle interactions are mainly of electrostatic nature followed by stabilization by hydrophobic forces. The high affinity confirms the nanoparticles as excellent carriers for protein delivery.

Aconitic Acid

Swainsonine protects both murine and human haematopoietic systems from chemotherapeutic toxicity.

The haematopoietic system is sensitive to cytotoxic damage and is often the site of dose-limiting toxicity. We previously reported that swainsonine, an inhibitor of protein glycosylation, reduced the bone marrow toxicity resulting from a single dose of anticancer drugs in otherwise healthy mice. However, more important questions are (1) can swainsonine protect tumour-bearing mice without interfering with the anti-tumour effects of the drugs, and (2) can swainsonine stimulate haematopoietic activity of human, as well as murine, bone marrow. We demonstrate here that swainsonine protects C57BL/6 mice bearing melanoma-derived tumours from cyclophosphamide-induced toxicity without interfering with the drug's ability to inhibit tumour growth. Similar results were obtained in vivo with 3'-azido-3'-deoxythymidine (AZT), a myelosuppressive agent often used in therapy for acquired immune deficiency syndrome. Swainsonine increased both total bone marrow cellularity and the number of circulating white blood cells in mice treated with doses of AZT that typically lead to severe myelosuppression. Swainsonine also increased the number of erythroid and myeloid colony forming cells (CFCs) in short-term cultures of murine bone marrow, restoring the number of progenitor cells to the control level in the presence of AZT doses that reduced CFCs by 80%. With respect to the sensitivity of human haematopoietic cells to swainsonine, we show that swainsonine protected human myeloid progenitor cells from AZT toxicity in vitro. These results suggest that swainsonine may be useful as an adjuvant in several types of human chemotherapy.

Adjuvants, Immunologic

Chronic n-3 polyunsaturated fatty acid diet-deficiency acts on dopamine metabolism in the rat frontal cortex: a microdialysis study.

The effects of alpha-linolenic acid diet deficiency on rat dopaminergic metabolism were investigated in the frontal cortex of male 2-3 month-old rats using the microdialysis method. Increased basal levels of dopamine metabolites were observed in the frontal cortex of awake deficient rats, without modification of dopamine levels. Moreover, using KCl perfusion which releases newly synthesized dopamine, no difference was observed in anaesthetized deficient rats versus control rats. In addition, a decrease in dopamine release was observed in anaesthetized deficient rats versus control rats after tyramine stimulation, which is known to induce release of dopamine from vesicular stores. A working model is proposed which suggests that a chronic n-3 polyunsaturated fatty acids (PUFA) deficiency may lead to modifications in the internalization of dopamine in the storage pool in the frontal cortex.

Analysis of Variance

Pharmacological profile of CEB-1957 and atropine toward brain muscarinic receptors and comparative study of their efficacy against sarin poisoning.

This study consists of two parts, first to compare the pharmacological profile of atropine and CEB-1957 substance toward muscarinic receptor subtypes. In various rat brain structures, binding properties were determined by competition experiments of [3H]pirenzepine, [3H]AF-DX 384, and [3H]4-DAMP in quantitative autoradiography of M1, M2, and M3 muscarinic receptor subtypes, respectively. Competition curves have shown that atropine presents similar nanomolar inhibition constants toward each subtype, while CEB-1957 has distinct affinities (Ki from 0.26 to 73 nM) with the following range order: M3 > or = M2 > M1. The second part is to compare atropine and CEB-1957 (in combination with pralidoxime) for their ability to protect against the lethality induced by 2 x LD50 of the acetylcholinesterase inhibitor sarin. CEB-1957 reduced the mortality at doses 10 times lower than atropine. Finally, from these results, it is proposed that a selective blockade of M2 and M3 receptor subtypes could play a pivotal role in the protective effect against sarin poisoning.

Animals

Brain neurotoxicity of Penitrem A: electrophysiological, behavioral and histopathological study.

The neurotoxicity of Penitrem A (PA) in rats was assessed against neurophysiological, behavioral and histopathological parameters. Animals were acutely given intracerebroventricular (22-45 mg) or intraperitoneal injections (0.5-1.5 mg/kg) of PA. A typical trembling syndrome associated with PA was always noted. Depending on the dose administered, animals may convulse and eventually die (1-1.5 mg/kg). PA-induced transient alterations of the EEG involving an increase in the frequency and voltage of electrical activity recorded from the cerebral cortex. Hippocampal activity was not modified and some pathologic activities may be recorded at the thalamus. Generally these EEG alterations disappeared at d 3 after the injection and the animals progressively recovered. However in the most severe cases, neuromotor disturbances were maintained at d 7 (rotarod test). Coronal sections of the brain at the striatal, thalamic, hippocampal and pons levels mainly revealed that PA was able to induce dose related injuries in the cerebellum with massive degeneration of Purkinje cells and a significant vacuolization within the molecular layer. The neurotoxic mechanism remains unclear. Action of the mycotoxin on the cerebello-thalamo-cortical tract is discussed.

Animals

[An experimental study of a new bidirectional distraction appliance].

The goals of mandibular distraction are to restore a normal length but also a normal shape to the hypoplastic mandible. These two goals are related to the elongation vector which is itself related to the location of the cortictomy and of the device. Other factors influence this elongation vector. So it is impossible to precisely predict the elongation vector. With the monodirectional distraction device no modification can be made during the distraction time. With a bidirectional distraction device offering the possibility to modulate the angulation between the two elongation rods it is possible to adjust the elongation vector during distraction. Precise distraction gap modeling is possible. This is particularly important to correct anterior open-bite. This device was tested on animals (pigs).

Animals

[Congenital infiltrating lipomatosis of the face. Presentation of a new clinical case].

A new case of this rarely described pathology is reported. It concerns a benign infiltrating lipomatosis, strictly located to the face. However, dento-musculo-squelettal structures are constantly involved, usually located to a hemiface. A young female patient has been followed up from her birth. Surgical procedures are reported. Diagnostic and therapeutic difficulties of this rare clinicopathologic entity are discussed.

Adipocytes

[Maxillofacial fractures. Surgical and prosthetic procedures].

A patient presented complex fractures of the face and skull with leg trauma after a traffic accident. Maxillofacial repair used sophisticated procedures: bone grafts, muscle flaps and multiple osteotomies. After reconstructing the mid face and the mandibular repair, bone implants were used to stabilize the maxillary prosthesis. The psychological and functions problems raised in this case are discussed considering the occupational and social outcome.

Bone Transplantation

[Secondary rhinoplasty for unilateral cleft lip and palate. Review of the literature and 50 clinical cases].

The nasal sequelae of unilateral cleft lip and palate are almost always present: more or less severe deformities, essentially consisting of nostril deformity and deviated septum. After an anatomical study of nasal deformities and the consequences of the primary procedures of cheiloplasty or cheilorhinoplasty, the authors review all of the most satisfactory technical aspects of secondary proposed in the literature. Five clinical cases illustrate the therapeutic strategy and the results.

Adult

[Unusual lung mycosis: Penicillium++ marneffei infection].

We report an uncommon radiographic finding which led to the diagnosis of Penicillium marneffei pulmonary mycosis in an HIV positive woman. The patient who lived in France had travelled several times to her native country. Thailand, prior to the development of fever, weight loss, skin lesions with a macular aspect around the umbilicus. The chest x-ray demonstrated non-excavated round opacities. Penicillium marneffei was isolated from alveolar lavage fluid and blood samples. This rare fungus is usually found in immunodepressed subjects, especially HIV+ patients (CD4 < 50) should be suspected in subjects who have travelled to endemic zones (Southeast Asia). Penicillium marneffei is considered as a criteria for AIDS. P. marneffei is the only dimorphic member of the Penicillium genus and has a particular affinity for the reticuloendothelial system. Clinical manifestations vary, usually with skin lesions. Mycology diagnosis is usually made on blood samples as well as alveolar lavage or pleural fluids. Antifungals (amphotericin B. itraconazole, ketoconazole) are generally effective but the risk of relapse underlines the importance of secondary prophylaxis in immunodepressed subjects.

Female

[Esthetic reconstruction of the superior hemilip using the Abbé technique modified by Burget. Apropos of 5 cases].

When a patient must undergo resection of part of the upper lip for the treatment of a cancer or following a traumatic defect of the upper hemilip, the surgeon is faced with the problem of reconstruction of a lip whose appearance and function must be as close as possible to the normal lip. The limits of the normal lip must be restored: the symmetry, equilibrium of the lips and position of the commissures must be maintained. The upper lip esthetic unit can be divided into subunits, as described by Burget and Menick. If a large part of a subunit is removed, replacement of the entire subunit rather than simple reconstruction of the defect often gives a better esthetic result (Burget). The best tissue for esthetic reconstruction of a full thickness defect of the upper lip is the lower lip. We apply Burget's principles to raise an Abbé flap, which is transferred in two stages. This approach is illustrated by 5 patients operated by this technique. Finally, this technique is compared to other techniques allowing reconstruction of the upper hemilip.

Adult

[Rare pulmonary mycoses in patients with hematologic diseases].

Patients with hematology disease in post-chemotherapy medullary aplasia are susceptible to life-threatening bronchopulmonary mycoses, especially aspergillosis. Other less common pulmonary mycoses are also observed. We report 4 cases due to Penicillium purpurogenum, Acromonium strictum and Scedosporium apiospermum (n = 2) infections. These unusual fungi appear to be emerging as pathogens in this population. They have common ubiquitous, opportunistic and low pathogenicity characteristics in immunocompetent subjects. The major risk factor is neutropenia. Isolating one of these fungi in an immunodepressed patient modifies management protocols since certain unusual fungi such as Scedosporium are resistant to amphotericin B.

Acremonium

[Late results of the surgical treatment of temporomandibular joint ankylosis in children].

Long-term outcome after surgical treatment of temporomandibular joint ankylosis is not always satisfactory in children. Interposition of a temporalis muscle flap is insufficient to ensure good functional results if the surgical procedure is not followed by careful active and passive physiotherapy. The results can be evaluated only after the child has grown.

Ankylosis