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Biomedical subjects

J Fontaine

Publications and source records attributed to J Fontaine.

At least 19 recordsLinked to original sources

Effects of anthracene on development of an arbuscular mycorrhizal fungus and contribution of the symbiotic association to pollutant dissipation.

The influence of anthracene, a low molecular weight polycyclic aromatic hydrocarbon (PAH), on chicory root colonization by Glomus intraradices and the effect of the root colonization on PAH degradation were investigated in vitro. The fungus presented a reduced development of extraradical mycelium and a decrease in sporulation, root colonization, and spore germination when exposed to anthracene. Mycorrhization improved the growth of the roots in the medium supplemented containing 140 mg l(-1) anthracene, suggesting a positive contribution of G. intraradices to the PAH tolerance of roots. Anthracene disappearance from the culture medium was quantified; results suggested that nonmycorrhizal chicory roots growing in vitro were able to contribute to anthracene dissipation, and in addition, that mycorrhization significantly enhanced anthracene dissipation. These monoxenic experiments demonstrated a positive contribution of the symbiotic association to anthracene dissipation in the absence of other microorganisms. In addition to anthracene dissipation, intracellular accumulation of anthracene was detected in lipid bodies of plant cells and fungal hyphae, indicating intracellular storage capacity of the pollutant by the roots and the mycorrhizal fungus.

Anthracenes↗

The efficacy of an antiseptic and microbial anti-adhesive ear cleanser in dogs with otitis externa.

A new antimicrobial ear cleanser was evaluated for the treatment of bacterial and yeast ear infection in dogs. Forty-five dogs with erythemato-ceruminous or purulent otitis externa were randomly allocated to two treatment groups: reference ear cleanser (Epiotic, Virbac) or test ear cleanser (Epiotic Advanced, Virbac). Ear cleansing was performed twice daily for 2 weeks, and no other treatment was allowed. By week 2, clinical (exudate quantity, erythema, stenosis, excoriation, and odor) and discomfort (pain, ear scratching, and head shaking) scores were significantly decreased (P < .0001 for all) and no microbial overgrowth could be detected in 25 (64.1%) and 32 (68.1%) ears treated with Epiotic and Epiotic Advanced, respectively. The new pH-balanced, propylene glycol-free test ear cleanser, which incorporates microbial adhesin-blocking carbohydrates, proved as effective as the reference acidic formula.

Administration, Topical↗

BMP-4 inhibits follicle-stimulating hormone secretion in ewe pituitary.

Activins and inhibins, members of the transforming growth factor-beta family are able to stimulate and inhibit, respectively, FSH synthesis and release. Other members of this superfamily, the bone morphogenetic proteins (BMPs), may also affect FSH synthesis in the mouse. The aim of this work was to determine whether BMPs are expressed in the ovine pituitary and whether they play a role in the regulation of FSH release. The mRNAs encoding BMP-2, BMP-4, BMP-7 and the oocyte-derived growth factor, growth differentiation factor (GDF)-9 were detected in the pituitaries of cyclic ewes by reverse-transcriptase PCR, as well as the mRNAs encoding the BMP type I receptors, BMPR-IA (activin-receptor-like kinase (ALK)-3) and BMPR-IB (ALK-6), and type II receptors (BMPR-II). Immunolabeling of pituitary sections revealed the presence of BMPR-IA (ALK-3) and BMPR-II in gonadotrope cells. To investigate the potential effects of BMPs on FSH secretion, ewe pituitary cell cultures were treated with BMP-4 (10(-11) M to 10(-9) M) for 48 h. Interestingly, FSH release was decreased in a dose-dependent manner. At 10(-9) M BMP-4 both FSH concentration and FSHbeta mRNA expression were reduced by 40% of control values. In contrast, there was no inhibitory effect on either LH or LHbeta mRNA expression. A similar result was found with BMP-6. BMP-4 triggered the phosphorylation of Smad1, suggesting that the effect of BMP-4 on FSH secretion is due to the activation of the BMPs signaling pathway. Furthermore, BMP-4 blocked the stimulatory effect of activin on both FSH release and FSHbeta mRNA and amplified the suppression of FSH release and FSHbeta mRNA levels induced by 17beta-estradiol. These results indicate that a functional BMP system operates within the sheep pituitary, at least in vitro, to decrease FSH release and to modulate the effect of activin.

Animals↗

Cytotoxic constituents from Plumbago zeylanica.

The bioassay-guided fractionation of the dichloromethane extract of aerial parts of Plumbago zeylanica led to the isolation of beta-sitosterol, beta-sitosteryl-3beta-glucopyranoside, beta-sitosteryl-3beta-glucopyranoside-6'-O-palmitate (1), lupenone, lupeol acetate, plumbagin and trilinolein. Compound 1 showed cytotoxic activity against MCF7 and Bowes cancer cell lines (IC50 113 microM and 152 microM, respectively), beta-sitosterol inhibited Bowes cell growth (IC50 36.5 microM) and plumbagin was cytotoxic against MCF7 and Bowes cells (IC50 1.28 microM and 1.39 microM, respectively).

Antineoplastic Agents, Phytogenic↗

Activin and inhibin receptor gene expression in the ewe pituitary throughout the oestrous cycle.

In mammals, activin and inhibin are important regulators of FSH secretion. Previous studies have demonstrated that primary ovine pituitary cells express different activin receptor subtypes: activin receptor-like (ALK)2, ALK4, activin type II receptor A (ActRIIA), ActRIIB and Smad proteins in vitro. Here, we have carried out physiological studies to investigate the pattern of mRNA expression of the activin receptor subunits in the ewe pituitary throughout the oestrous cycle. The oestrous cycles of ewes were synchronized with progestagen sponges. The animals were killed 36 h (before the preovulatory surge, n=4), 48 h (during the preovulatory surge, n=4), 72 h (during the second surge of FSH, n=6) and 192 h (during the luteal phase, n=4) after sponge removal. Using Northern blots, we have shown that the levels of ALK2, ALK4 and ActRIIB mRNA were significantly higher before the preovulatory surge and during the secondary surge of FSH as compared with both during the preovulatory surge and the luteal phase, whereas the level of the ActRIIA mRNA was similar throughout the oestrous cycle. Using Western blots we have also demonstrated that the level of phospho-Smad2 did not vary during the reproductive cycle. Inhibin binding protein (InhBP/p120) and the transforming growth factor-beta type III receptor, betaglycan, have been identified as putative inhibin co-receptors. In this study, we cloned a fragment of both InhBP/p120 and betaglycan cDNAs in the ewe and showed by Northern blot that pituitary betaglycan and InhBP/p120 mRNA levels did not fluctuate across the oestrous cycle nor did they correlate with serum FSH levels.

Activin Receptors↗

[National survey of dermatologists].

OBJECTIVE: The purpose of this survey was to ascertain current management practices of French dermatologists treating immunocompetent patients with cutaneomucosal herpes (ocular herpes excluded) as a prelude to the French consensus conference on this topic. METHOD: A random sample of French dermatologists were invited to respond to a telephone interview: 928 dermatologists were contacted. RESULTS: The 216 dermatologists who responded to the telephone interview provided care for five persons per month (pregnancy excluded) who consulted for orofacial or genital herpes. Nearly half of the dermatologists stated they do not talk about herpes spontaneously with their patients. When a suspect lesion is seen for the first time, 48 p. 100 of the dermatologists order one or two complementary exams. Their advice on prevention between partners basically concerns use of preservatives. Therapeutic attitudes vary depending on the type of herpes or the number of recurrences per year: 84 p. 100 of the dermatologists prescribe a specific antiviral treatment for patients with solar herpes. Virological proof of infection is not acquired in 84 p. 100 of the cases before initiating a long-term treatment for recurrence. The most widely used agents are valaciclovir 500 and aciclovir 200. CONCLUSION: This survey demonstrates a certain degree of divergence from the recommendations of the consensus conference. The participation rate appears to be satisfactory, but herpes serology is ordered too often and antiviral agents are not used in compliance with current guidelines. This survey will be redone after diffusion of the guidelines in order to evaluate their impact.

Acyclovir↗

[National survey of gynecologists-obstetricians and general practitioners].

OBJECTIVE: The purpose of this survey was to ascertain current practices of French gynecologists-obstetricians (GO) and general practitioners (GP) treating immunocompetent patients with cutaneomucosal herpes (ocular lesions excluded) as a prelude to the French consensus conference on this topic. METHODS: A random sample of French GOs and GPs were invited to respond to a telephone interview: 330 GOs and 331 GPs were contacted. RESULTS: Response rate was 24 p. 100 among the GOs who could be contacted (49 responses) and 14 p. 100 among the GPs (45 responses). More than half the GPs cared for 1 to 5 cases of orofacial or genital herpes monthly. When a suspect lesion is seen for the first time, 51 p. 100 of the GOs order one or two tests to achieve virology proof: 65 p. 100 order herpes serology and 47 p. 100 PCR. For the GPs, 56 p. 100 do not order a complementary exam. Advice on prevention between partners basically concerns use of preservatives. The therapeutic attitude varies depending on the type of herpes and the number of recurrences per year. The most widely used agent is valaciclovir. A specific antiviral agent is prescribed for non-ocular herpes by 92 p. 100 of the GOs and 98 p. 100 of the GPs. Virological proof of herpes infection is not obtained by 65 p. 100 of the GOs and 78 p. 100 of the GPs before initiating long-term treatment for recurrence. Genital herpes during pregnancy appears to be rare; 57 p. 100 of the GOs had less than one case over the last five years. Only 33 p. 100 of them discuss herpes spontaneously with their consultants. When a suspect genital lesion is observed during pregnancy, 82 p. 100 seek virological proof. When there is a risk of neonatal herpes, the type of delivery depends on the type of herpes infection and the date of occurrence during the pregnancy. Cesarean section is performed systematically by 63 p. 100 of the GOs when there is a primary herpes infection after 34 weeks gestation. Most practitioners did not respond concerning their attitude for exams and surveillance for the infant. DISCUSSION: The number of responding practitioners was too small in this study to provide a representative sample. This study will be renewed with a larger sample of GOs in order to obtain reliable data. For general practitioners, there is a need for education concerning management of cutaneomucosal herpes which should be provided at the same time as the consensus conference guidelines are distributed.

Acyclovir↗

Original 2-alkylamino-6-halogenoquinazolin-4(3H)-ones and K(ATP) channel activity.

A series of 6-substituted 2-alkylaminoquinazolin-4(3H)-ones structurally related to 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides were synthesized and tested as putative K(ATP) channel openers on isolated pancreatic endocrine tissue as well as on isolated vascular, intestinal, and uterine smooth muscle. Most of the 6-halogeno-2-alkylaminoquinazolin-4(3H)-ones were found to inhibit insulin release from pancreatic B-cells and to exhibit vasorelaxant properties. In contrast to their pyridothiadiazine dioxide isosteres previously described as more active on the endocrine than on the smooth muscle tissue, quinazolinones cannot be considered as tissue selective compounds. Biological investigations, including measurements of (86)Rb, (45)Ca efflux from pancreatic islet cells and measurements of vasodilator potency in rat aortic rings exposed to 30 or 80 mM KCl in the presence or the absence of glibenclamide, were carried out with 6-chloro- and 6-iodo-3-isopropylaminoquinazolin-4(3H)-ones. Such experiments showed that, depending on the tissue, these new compounds did not always express the pharmacological profile of pure K(ATP) channel openers. Analyzed by X-ray crystallography, one example of quinazolinones appeared to adopt a double conformation. This only suggests a partial analogy between the 2-alkylaminoquinazolin-4(3H)-ones and the 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxides. In conclusion, the newly synthesized quinazolinones interfere with insulin secretion and smooth muscle contractile activity. Most of the compounds lack tissue selectivity, and further investigations are required to fully elucidate their mechanism(s) of action.

Adenosine Triphosphate↗

Role of the parasite-derived prostaglandin D2 in the inhibition of epidermal Langerhans cell migration during schistosomiasis infection.

Epidermal Langerhans cells (LCs) play a key role in immune defense mechanisms and in numerous immunological disorders. In this report, we show that percutaneous infection of C57BL/6 mice with the helminth parasite Schistosoma mansoni leads to the activation of LCs but, surprisingly, to their retention in the epidermis. Moreover, using an experimental model of LC migration induced by tumor necrosis factor (TNF)-alpha, we show that parasites transiently impair the departure of LCs from the epidermis and their subsequent accumulation as dendritic cells in the draining lymph nodes. The inhibitory effect is mediated by soluble lipophilic factors released by the parasites and not by host-derived antiinflammatory cytokines, such as interleukin-10. We find that prostaglandin (PG)D2, but not the other major eicosanoids produced by the parasites, specifically impedes the TNF-alpha-triggered migration of LCs through the adenylate cyclase-coupled PGD2 receptor (DP receptor). Moreover, the potent DP receptor antagonist BW A868C restores LC migration in infected mice. Finally, in a model of contact allergen-induced LC migration, we show that activation of the DP receptor not only inhibits LC emigration but also dramatically reduces the contact hypersensitivity responses after challenge. Taken together, we propose that the inhibition of LC migration could represent an additional stratagem for the schistosomes to escape the host immune system and that PGD2 may play a key role in the control of cutaneous immune responses.

Animals↗

Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells.

Peroxisome proliferator-activated receptor gamma (PPARgamma ), a member of the nuclear receptor superfamily, has recently been described as a modulator of macrophage functions and as an inhibitor of T cell proliferation. Here, we investigated the role of PPARgamma in dendritic cells (DC), the most potent antigen-presenting cells. We showed that PPARgamma is highly expressed in immature human monocyte-derived DC (MDDC) and that it may affect the immunostimulatory function of MDDC stimulated with lipopolysaccharide (LPS) or via CD40 ligand (CD40L). We found that the synthetic PPARgamma agonist rosiglitazone (as well as pioglitazone and troglitazone) significantly increases on LPS- and CD40L-activated MDDC, the surface expression of CD36 (by 184% and 104%, respectively) and CD86 (by 54% and 48%), whereas it reduces the synthesis of CD80 (by 42% and 42%). Moreover, activation of PPARgamma resulted in a dramatic decreased secretion of the Th1-promoting factor IL-12 in LPS- and CD40L-stimulated cells (by 47% and 62%), while the production of IL-1beta, TNF-alpha, IL-6 and IL-10 was unaffected. Finally, PPARgamma ligands down-modulate the synthesis of IFN-gamma -inducible protein-10 (recently termed as CXCL10) and RANTES (CCL5), both chemokines involved in the recruitment of Th1 lymphocytes (by 49% and 30%), but not the levels of the Th2 cell-attracting chemokines,macrophage-derived chemokine (CCL22) and thymus and activation regulated chemokine (CCL17), in mature MDDC. Taken together, our data suggest that activation of PPARgamma in human DC may have an impact in the orientation of primary and secondary immune responses by favoring type 2 responses.

Chemokine CCL4↗

Schistosoma mansoni induces the synthesis of IL-6 in pulmonary microvascular endothelial cells: role of IL-6 in the control of lung eosinophilia during infection.

The nature of the interactions between the intravascular parasite Schistosoma mansoni and the host pulmonary vasculature is critical in determining the outcome of infection. In this report, we show that lung schistosomula selectively induce the synthesis of IL-6 mRNA and protein in cultured human and mouse lung microvascular endothelial cells (EC) and that parasite excretory/secretory lipophilic compounds, particularly prostaglandin E(2), are responsible for this effect. In vivo, a striking increase of IL-6 expression is observed in the pulmonary microvasculature of S. mansoni-infected C57BL/6 mice suggesting that, in vivo, parasites also induce the synthesis of IL-6 in lung EC. In infected mice, IL-6 deficiency results in an accelerated mobilization of eosinophils into the lung tissue and in a dramatic increased number of recruited leukocytes, particularly eosinophils, in the airway. This effect is associated with an enhanced production of eotaxin (CCL11) and IL-5 in the lungs of IL-6 knockout (KO) animals. Finally, compared to wild-type mice, we detect a dramatic increased level of parasite mortality in the lungs of IL-6 KO mice. Taken together, we suggest that parasite larvae activate EC to produce IL-6 to escape the inflammatory reaction that develops in the lungs of infected hosts. Finally, we show that the parasite-induced IL-6 synthesis is mediated by a protein kinase A-dependent pathway that principally targets the cAMP-response element and the nuclear factor-kappaB sites from the -256/+20 region of the IL-6 promoter.

Animals↗

Effects of antiinflammatory triterpenes isolated from Leptadenia hastata latex on keratinocyte proliferation.

Several triterpenes isolated from Leptadenia hastata latex were tested for their anti-inflammatory activity. Lupeol (1), its acetate (2) and palmitate (3) esters were found to be the main antiinflammatory constituents in the croton oil-induced ear oedema test. Furthermore, lupeol hemisuccinate (4), synthesized from lupeol, exhibited a higher activity than lupeol in the test. These results prove that the triterpenes play a pivotal role in the topical antiinflammatory effect of this latex. In addition, an in vitro model of human skin keratinocytes (epidermal explants) cultured at an air-liquid interface on a de-epidermized human dermis (DED) was used to investigate the effects of lupeol esters on skin repair in vitro. Compared with the control, compounds 2 and 3 improved keratinocyte proliferation at a concentration of 5 microM in the culture medium; however, they remained less active than compounds 1 and 4. In contrast to compound 1, all the lupeol esters (2-4), and particularly compound 4, induced a good differentiation of keratinocytes with a well-formed stratum corneum without parakeratosis. These results substantiate the topical use of Leptadenia hastata latex in traditional medicine and showed that both antiinflammatory activity and the effect on keratinocyte proliferation of compound 1 could be improved by its hemisuccinylation; on the contrary, esterification by acetylation or palmitoylation decreased these activities.

Adult↗

Sterol biosynthesis by the arbuscular mycorrhizal fungus Glomus intraradices.

Ri-T-DNA-transformed carrot roots were used for investigating sterol metabolism by the arbuscular mycorrhizal (AM) fungus Glomus intraradices under three distinct experimental conditions: (i) a symbiotic stage (fungus still attached to the host roots); (ii) a detached stage (fungus physically separated from the roots); and (iii) a germinating stage (germinating spores). In all three stages, G. intraradices was found to contain a mixture of 24-alkylated sterols, with 24-methyl and 24-ethyl cholesterol as the main compounds, but no ergosterol, the predominant sterol in most fungi. Feeding experiments with [1-14C]sodium acetate were performed to check the ability of the fungus to synthesize sterols. Whatever the experimental conditions, G. intraradices was able to actively take up exogenous acetate and to incorporate it into sterols and their precursors. Our data provide first evidence for de novo sterol synthesis by an AM fungus.

Cholesterol Esters↗

[Lipid metabolism of the endomycorrhizal fungus: Glomus intraradices].

The use of monoxenic cultures of the obligately biotrophic vesicular arbuscular fungus Glomus intraradices now permits investigation of the lipid metabolism of this organism. In bicompartmental culture plates, sporulating extraradical hyphae can be obtained, totally free of roots, and then provided with 14C-acetate as lipid precursor. Three experimental stages were studied: i) stage A, symbiotic stage corresponding to the fungus still attached to the host plant roots, ii) stage B, consisting of the fungus detached from the host roots, iii) stage C, germinating spores. In each case, the fungus proved to be able to synthesise its own lipids: 1,2- and 1,3-diacylglycerols, triacylglycerols, phospholipids, sterols and free fatty acids, de novo. Lipid metabolism varied with the experimental conditions. Phospholipid synthesis was intensive in germinating spores. Thus the obligately biotrophic status of this fungus cannot be explained by a deficiency in synthesis of these various lipid classes.

Acetates↗

Near-infrared reflectance spectroscopy enables the fast and accurate prediction of the essential amino acid contents in soy, rapeseed meal, sunflower meal, peas, fishmeal, meat meal products, and poultry meal.

Near-infrared reflectance spectroscopy (NIRS) calibrations were developed to enable the accurate and fast prediction of the total contents of methionine, cystine, lysine, threonine, tryptophan, and other essential amino acids, protein, and moisture in the most important protein-rich feed ingredients. More than 1000 samples of global origin collected over four years were analyzed on amino acids following the official methods of the United States and the European Union. Detailed data and graphics are given to characterize the obtained calibration equations. NIRS was validated with independent samples for soy and meat meal products and compared to the amino acid predictions using linear crude protein regressions. With a few exceptions, validation showed that 85-98% of the amino acid variance in the samples could be explained using NIRS. NIRS predictions compared to reference results agree excellently, with relative mean deviations below 5%. Especially for meat and poultry meals, NIRS can predict amino acids much better than crude protein regressions. By enabling the amino acid analysis of many samples to be completed in a short time, NIRS can improve the accuracy of feed formulation and thus the quality and production costs of mixed feeds.

Amino Acids, Essential↗

Peroxisome proliferator-activated receptor gamma activators inhibit interleukin-12 production in murine dendritic cells.

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily. They are divided into three subtypes (alpha, beta or delta, and gamma) and are involved in lipid and glucose homeostasis and in the control of inflammation. In this study, we analyzed the expression of PPARs in murine dendritic cells (DCs), the most potent antigen presenting cells. We find that immature as well as mature spleen-derived DCs express PPARgamma, but not PPARalpha, mRNA and protein. We also show that the PPARgamma activator rosiglitazone does not interfere with the maturation of DCs in vitro nor modifies their ability to activate naive T lymphocytes in vivo. Finally, we present evidence that PPARgamma activators down-modulate the CD40-induced secretion of interleukin-12, a potent Th1-driving factor. These data suggest a possible role for PPARgamma in the regulation of immune responses.

Animals↗