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Biomedical subjects

F Bureau

Publications and source records attributed to F Bureau.

At least 37 records · Page 2Linked to original sources

NF-kappaB activation in response to toxical and therapeutical agents: role in inflammation and cancer treatment.

The NF-kappaB transcription factor is ubiquitously expressed and controls the expression of a large number of genes. Experimental data clearly indicate that NF-kappaB is a major regulator of the inflammatory reaction by controlling the expression of pro-inflammatory molecules in response to cytokines, oxidative stress and infectious agents. We demonstrated that NF-kappaB activation by IL-1beta follows three distinct cell-specific pathways. Moreover, our studies indicated that in one model of inflammatory diseases, horse recurrent airway obstruction (RAO), the extent of NF-kappaB basal activity correlates with pulmonary dysfunction. Another role of NF-kappaB activity protects cancer cells against apoptosis and could participate in the resistance to cancer treatment. However, we did not observe any increased cytotoxicity after treatment with anticancer drugs or TNF-alpha of cells expressing a NF-kappaB inhibitor. Therefore, we can conclude that the inhibition of apoptosis by NF-kappaB is likely to be cell type and stimulus-dependent. Further studies are required to determine whether NF-kappaB could be a target for anticancer treatments.

Animals↗

Mechanisms of persistent NF-kappa B activity in the bronchi of an animal model of asthma.

In most cells trans-activating NF-kappaB induces many inflammatory proteins as well as its own inhibitor, IkappaB-alpha, thus assuring a transient response upon stimulation. However, NF-kappaB-dependent inflammatory gene expression is persistent in asthmatic bronchi, even after allergen eviction. In the present report we used bronchial brushing samples (BBSs) from heaves-affected horses (a spontaneous model of asthma) to elucidate the mechanisms by which NF-kappaB activity is maintained in asthmatic airways. NF-kappaB activity was high in granulocytic and nongranulocytic BBS cells. However, NF-kappaB activity highly correlated to granulocyte percentage and was only abrogated after granulocytic death in cultured BBSs. Before granulocytic death, NF-kappaB activity was suppressed by simultaneous addition of neutralizing anti-IL-1beta and anti-TNF-alpha Abs to the medium of cultured BBSs. Surprisingly, IkappaB-beta, whose expression is not regulated by NF-kappaB, unlike IkappaB-alpha, was the most prominent NF-kappaB inhibitor found in BBSs. The amounts of IkappaB-beta were low in BBSs obtained from diseased horses, but drastically increased after addition of the neutralizing anti-IL-1beta and anti-TNF-alpha Abs. These results indicate that sustained NF-kappaB activation in asthmatic bronchi is driven by granulocytes and is mediated by IL-1beta and TNF-alpha. Moreover, an imbalance between high levels of IL-1beta- and TNF-alpha-mediated IkappaB-beta degradation and low levels of IkappaB-beta synthesis is likely to be the mechanism preventing NF-kappaB deactivation in asthmatic airways before granulocytic death.

Airway Obstruction↗

A multipotential beta -1,6-N-acetylglucosaminyl-transferase is encoded by bovine herpesvirus type 4.

The beta-1,6-N-acetylglucosaminyltransferase (beta1,6GnT) gene family encodes enzymes playing crucial roles in glycan synthesis. Important changes in beta1,6GnT expression are observed during development, oncogenesis, and immunodeficiency. The most characterized beta1,6GnTs in this gene family are the human (h) C2GnT-L and h-IGnT, which have core 2 [Galbeta1-->3(GlcNAcbeta1-->6)GalNAc] and I branching [GlcNAcbeta1-->3(GlcNAcbeta1-->6)Gal] activities, respectively. Recently, h-C2GnT-M was shown to be unique in forming core 2, core 4 [GlcNAcbeta1-->3(GlcNAcbeta1-->6)GalNAc], and I structures. To date, the beta1,6GnT gene family has been characterized only in mammals. Here, we describe that bovine herpesvirus type 4 (BHV-4) encodes a beta1,6GnT expressed during viral replication and exhibiting all of the core 2, core 4, and I branching activities. Sequencing of the BHV-4 genome revealed an ORF, hereafter called BORFF3-4, encoding a protein (pBORFF3-4) exhibiting 81.1%, 50.7%, and 36.6% amino acid identity with h-C2GnT-M, h-C2GnT-L, and h-IGnT, respectively. Reverse transcriptase-PCR analysis revealed that BORFF3-4 is expressed during BHV-4 replication. Expression of BORFF3-4 in Chinese hamster ovary cells directed the expression of core 2 branched oligosaccharides and I antigenic structures on the cell surface. Moreover, a soluble form of pBORFF3-4 had core 4 branching activity in addition to core 2 and I branching activities. Finally, infection of a C2GnT-negative cell line with BHV-4 induced expression of core 2 branched oligosaccharides. This study extends the beta1,6GnT gene family to a viral gene and provides a model to study the biological functions of a beta1,6GnT in the context of viral infection.

Amino Acid Sequence↗

The effect of cysteine and 2,4-dinitrophenol on heme and nonheme absorption in a rat intestinal model.

Previous studies have showed that purified heme iron forms insoluble polymers that are poorly absorbed. The presence of peptides and of amino acids maintaining heme iron in a soluble form could improve its bioavailability. The digestive uptake and transfer of a concentrated hydrolysate of heme peptides (HPH) and of iron gluconate (Gluc) at 100 µM were compared in vitro in a Ussing chamber. The effects of an enhancing amino acid (L-cysteine) on the uptake and transfer of both forms were assessed. An inhibitor of the oxidative phosphorylation (2,4-dinitrophenol; DNP) was used to differentiate the active and passive mechanisms of the absorption. The mucosal uptake (%Tot) and enterocyte transfer (%S) of the two sources of iron did not differ. DNP significantly reduced %Tot and %S of both forms. Cysteine significantly enhanced %Tot and %S of HPH and Gluc, partly corrected the inhibition exerted by DNP on %Tot of HPH and %S of both forms, and fully restored %Tot of Gluc. In presence of peptides produced by globin hydrolysis, the absorption of hemoglobin iron was efficient; it was mostly energy dependent and, therefore, should have occurred by a regulated transcellular pathway. Cysteine enhanced the passive uptake of iron and the passive processes involved in the enterocyte transfer of the common pool made of both sources (heme and nonheme) of iron. These results showed that heme iron can be purified and concentrated without impairing its digestive absorption, provided it remains in presence of peptides or amino acids.

Journal Article↗

Zinc and iron status and growth in healthy infants.

OBJECTIVE: To elucidate the relationships between growth and zinc and iron status in normal infants. STUDY DESIGN: Growth of normal infants (less than 3 y old: n = 66) was prospectively assessed with a mean delay of 24+/-6 weeks between measurements; subjects were free from illness and presented with a normal growth. Growth was compared to serum zinc (s-zinc), IGF-1 and iron status. SETTING: Teaching hospital of Caen. RESULTS: No relation was found between linear or weight growth and s-zinc; when taking into account the effect of age, linear growth was significantly associated with ferritin (P<0.001); weight gain was significantly correlated with IGF-1 (P = 0.034) and ferritin (P = 0.008). No relationship was found between s-zinc and iron status. CONCLUSIONS: In normal infants iron status, more than serum zinc, seems to be correlated with growth.

Child, Preschool↗

Mechanics of the respiratory system in healthy newborn calves using impulse oscillometry.

Arterial blood gases, acid-base balance and respiratory function tests using impulse oscillometry (IOS) were performed on 40 clinically healthy newborn calves during the first 24 hours of life to evaluate their respiratory adaptation to extrauterine life. Gas exchange efficiency of the lung was significantly improved with time and was accompanied by the correction of the mixed acidosis observed at birth and by significant changes in respiratory mechanics. Major changes were detected within the first 6 hours. The significant decrease in resistance (R) and the increase in reactance (X) with time, demonstrate the improvement in respiratory mechanics of both upper and lower airways, and reflect the increase in lung volume, the improved lung tissue elasticity and/or distribution of the ventilation. Respiratory mechanical, arterial blood gases and acid-base balance data provided in this study describe a successful respiratory adaptation to extrauterine life in healthy newborn calves.

Acid-Base Equilibrium↗

Evaluation of accuracy of pulse oximetry in newborn calves.

In human medicine, pulse oximetry is widely used to measure non-invasively and accurately the percentage of oxygen saturation of arterial haemoglobin (SpO(2)). Recently, pulse oximetry has been used in calves, but its accuracy has not been evaluated in newborn calves. The purpose of this study was to evaluate the accuracy of a pulse oximeter in newborn calves by comparing SpO(2) with arterial oxyhaemoglobin saturation (SaO(2)) obtained by use of a blood gas analyser. Fifty-five newborn calves were investigated from birth to 20 days old. Pulse oximetry readings and arterial blood samples were performed 5, 15, 30, 45, 60 min, 2, 3, 6, 12, 24 h and 1 and 3 weeks after birth. The transmission-type sensors of the pulse oximeter were fixed at the recommended site in the bovine species (at the base of the calf tail, where the skin had been shaved and was not pigmented) and arterial blood samples were withdrawn from the subclavian artery and analysed for SaO(2). Five-hundred paired data of SaO(2) and mean SpO(2)(mSpO(2)) were collected. Linear regression of the pooled data indicated a highly significant correlation of mSpO(2) with SaO(2) (r = 0.87;P< 0.001; mSpO(2) = 15.8 + 0.84 SaO(2)). The overall data bias value was positive (+2.1%), which indicated that the pulse oximeter tended to overestimate the SaO(2). The bias value for each SaO(2) category tended to become higher for lower ranges of SaO(2). Precision was also lower when SaO(2) values were low. The lower the SaO(2) value, the higher the positive bias (overestimation) and the lower the precision. These results suggest that pulse oximetry provides a relatively accurate non-invasive, immediate and portable method to monitor SaO(2) and to evaluate objectively the pulmonary function effectiveness in newborn calves during their adaptation to extra-uterine life.

Aging↗

Validation and prognostic value of plasma lactate measurement in bovine respiratory disease.

The purpose of this study was to evaluate the accuracy of a portable blood lactate analyser for bovine blood and to study the relevance of plasma lactate concentration in the prognosis of bovine pulmonary disorders. Measurements with the portable analyser were highly correlated (R = 0.94, P<0.0001) with the measurements of the reference method but significantly different (P<0.0001). The portable apparatus slightly overestimated plasma lactate concentration compared to the reference method (bias = + 0.412). Plasma lactate measurements on 109 calves suffering from acute bronchopneumonia showed increasing lactate concentrations with severity of the disease. A plasma lactate concentration higher than 3.6 mmol/L or 4 mmol/L, measured with the reference method and the portable analyser respectively, appeared to be a reliable prognostic indicator for mortality within 24 h. Consequently, this measurement could be very helpful to decrease economic losses in cases of bovine respiratory disease, by avoiding unnecessary treatment costs on cattle with poor prognosis.

Animals↗

Correlation between nuclear factor-kappaB activity in bronchial brushing samples and lung dysfunction in an animal model of asthma.

Asthma is a chronic inflammatory disease of the airways, in which many inflammatory genes are overexpressed. Transcription factor, nuclear factor-kappaB (NF-kappaB), which is thought to control the transcriptional initiation of inflammatory genes, has been poorly investigated in asthma. In the present report, bronchial cells (BCs), recovered by bronchial brushing in healthy and heaves-affected horses (i.e., an animal model of asthma), were assessed for NF-kappaB activity. Small amounts of active NF-kappaB were present in BCs of healthy horses, whereas high levels of NF-kappaB activity was found during crisis (i.e., acute airway obstruction) in all heaves-affected horses. Three weeks after the crisis, the level of NF-kappaB activity found in BCs of heaves-affected horses was highly correlated (p < 0.01) to the degree of residual lung dysfunction. Unexpectedly, active NF- kappaB complexes found in BCs of heaves-affected horses were mainly p65 homodimers, rather than classic p65-p50 heterodimers. At last, intercellular adhesion molecule-1 (ICAM-1) expression paralleled p65 homodimers activity in these cells. These results demonstrate that the kinetics of NF-kappaB activity is strongly related to the course of the disease and confirm the relevance of NF-kappaB as a putative target in asthma therapy. Moreover, uncommon p65 homodimers could transactivate, in BCs, a subset of genes, such as ICAM-1, characteristic of chronic airway inflammation.

Animals↗

Influence of the extent of haemoglobin hydrolysis on the digestive absorption of haem iron in the rat. An in vitro study.

This study was designed to assess the haem-peptide interactions which occur during progressive haemoglobin hydrolysis by digestive enzymes and their relationship with haem iron digestive absorption. The behaviour of different haemoglobin hydrolysates was studied using the Ussing chamber model. Hydrolysates were produced from enzyme digestion of bovine haemoglobin at pH 3 by pepsin and at pH 10 by subtilisin. Samples with increasing degrees of hydrolysis (0-15 %) were studied. Biochemical assays (pyridine haemochromogen method and UV absorption spectra) were used to follow haem solubility and haem-peptide interactions in samples. Increasing the hydrolysis level of haemoglobin was associated with an enhanced iron uptake; the highest uptake rate was reached between 8 and 11 % of globin hydrolysis, whichever enzyme was used. The mechanisms rendering iron soluble and available differ between the two enzymes. The comparison between biochemical and absorption data suggests that the formation of soluble peptide-haem complexes was not sufficient to enhance haem iron absorption, since globin-bound iron is poorly absorbed; an efficient absorption occurred only when haem was loosely bound to low molecular weight peptides.

Animals↗

Long-term effects of iron:zinc interactions on growth in rats.

The influence of iron (Fe) on the bioavailability and functional status of zinc (Zn) was studied in young rats using metabolic balances and tissue dosages, which were compared to growth. Diets supplied adequate intakes of Fe (45 and 300 mg/kg diet) and Zn (14 and 45 mg/kg) for 2 mo. Two metabolic balance determinations were performed that were correlated for Zn and Fe during the first and the last weeks of the study. A significant effect of Fe supply, but not of Zn was displayed on Fe absorption; both Fe and Zn diet concentrations had a significant influence on Zn absorption. Fe and Zn organ contents were significantly correlated with the amount absorbed during the two metabolic balances. There was a positive correlation between liver and muscle Fe and Fe absorption, and Fe absorption and muscle Zn, as well as a negative one with liver Zn; a positive correlation was displayed between Zn absorption and Zn organ content. No correlation was found between Zn absorption and Fe tissue content. Growth was correlated with Zn, but not with Fe absorption during both balances. A positive correlation was displayed between growth and Zn liver content, and a negative one with Fe liver content. Care must be taken to give growing subjects balanced diets or supplementation, since the negative interactions between these trace elements are likely to persist as long as the diet is given.

Animals↗

Mechanisms of absorption of caseinophosphopeptide bound iron.

Binding iron (Fe) to the 1-25 caseinophosphopeptide obtained from enzyme hydrolysis of beta casein (beta CPP) improves Fe bioavailability in the rat. To assess the mechanisms involved in its absorption, a perfused, vascularized duodenal rat loop model was used in controls and in Fe-deficient (bleeding of 25% blood volume) rats. Inhibitors of oxidative phosphorylation [2-4 dinitrophenol (DNP)] and/or of endocytosis [phenylarsine oxide (PAO)] were added to the perfusion solution containing 50 microM Fe as beta CPP bound Fe (Fe-beta CPP) or gluconate (Fe Gluc). Fe-beta CPP enhanced Fe uptake, reduced mucosal storage, and improved net absorption both in controls and in deficient animals. DNP reduced uptake, mucosal storage, and net absorption by the same percentage in Fe-beta CPP and Fe Gluc perfused rats in both control and Fe-deficient animals. PAO decreased uptake, mucosal storage, and net absorption of Fe-beta CPP but not of Fe Gluc. At the end of the experiment Fe serum levels were increased only in Fe Gluc animals. These results confirm the improved bioavailability of beta CPP bound Fe. They suggest that at least part of its absorption can occur by a different pathway than usual Fe salts. Fe-beta CPP can be taken up by endocytosis and absorbed bound to amino acids or peptides.

Journal Article↗

Maximal ventilation assessment in healthy calves.

In order to define a reliable method for estimating maximal ventilation in cattle, 12 healthy calves underwent a rebreathing trial and injections of increasing doses of lobeline, a respiratory analeptic. The effects of these tests on the main ventilatory parameters (tidal volume, VT; respiratory frequency, fRand minute volume,.VE) recorded during the 15 s of maximal response were studied and compared. The sharp rise in.VE(4.8 times higher than the resting value) observed during the rebreathing trial was mainly due to an increase in VT. This rise in ventilation was the highest ever reported in calves. Lobeline dose-dependently enhanced ventilation up to a threshold dose of 0.25 mg/kg, which always produced a maximal response. This maximal response (3.7 times higher than the resting value), reflecting both an increase in fR and VT, was reproducible at an interval of 12 h and was highly correlated with that observed during the rebreathing trial (R = 0.98, P< 0.001). These results suggest that: (1) rebreathing trial is a reliable method to induce and measure maximal ventilation in calves; and (2) lobeline administration (0.25 mg/kg) is a reliable means of accurately estimating this variable. Lobeline administration, unlike the rebreathing trial, is safe and easy to standardize, and the test therefore seems to be the preferred way of studying maximal ventilation in calves.

Animals↗

Spirometric variables recorded after lobeline administration in healthy Friesian and Belgian white and blue calves: normal values and effects of somatic growth.

The purposes of the present study were: (1) to develop original equations to predict spirometric variables (SV) in healthy Friesian and Belgian White and Blue (BWB) calves < 1 year of age; and (2) to determine the effects of somatic growth on SV. Sixty-seven Friesian and 500 BWB calves were investigated. For each calf, the following SV were calculated: (1) the average minute volume derived using all the ventilatory cycles recorded during the 15 s of maximal ventilatory changes induced by lobeline administration (0.25 mg/kg, i.v.) (15-s LMV); (2) the maximal tidal volume, the maximal peak expiratory flow and the maximal peak inspiratory flow recorded from single breaths after lobeline administration (MVTL, MPEFLand MPIFL, respectively); (3) the ventilatory reserve (VRL= 15-s LMV - VEr; VEr= minute volume at rest). Mass specific (s) values were also calculated. All SV changed linearly with somatic growth in both Friesian and BWB calves. Since the rise in SV was more related to body weight than the age of calves, equations for reference values of SV always had body weight as the only independent variable. In the youngest calves, s SV were lower in the BWB breed. In the oldest calves (i.e. 1 year of age), s MPEFLand s MPIFLremained small in BWB calves whereas s MVTL, s 15-s LMV and s VRLwere almost equal in both breeds. These results could be related to the lower resistance to respiratory disorders in BWB calves < 1 year of age than in Friesian calves < 1 year of age.

Age Factors↗

Relationship between bone mineralization and aluminium in the healthy infant.

OBJECTIVE: This prospective study was designed to assess the relationship between variations of serum Aluminium levels and bone mineralization, which is one of its target tissues, in healthy premature (PT) and fullterm (FT) infants. STUDY DESIGN: Lumbar spine bone mineral density (BMD) and content (BMC) studied by dual energy X-ray absorptiometry were compared to serum aluminium (S-Al), Ca (S-Ca), P (S-P), osteocalcin, alkaline phosphatase activity (S-AP), and 25 OH Vitamin D (25 OH D) by simple and multiple regressions in healthy PT (n = 44) following their hospital discharge and FT (n = 82). PT (gestational age at birth (mean +/- 1 s.d.) 32 +/- 2 weeks) and FT were 43 +/- 39 and 36 +/- 32 weeks old respectively. RESULTS: In PT multiple stepwise regression analysis including gestational age at birth, postconceptional age and postnatal age displayed only a significant correlation between BMD or BMC and postnatal age and a negative one with S-Al. In FT correlations were found between BMD or BMC and age and S-Ca. CONCLUSIONS: In PT, variations in blood Al are associated with developmental delays. Care should be taken to lessen Al levels, even in healthy PT babies.

Aging↗

Potentiation of cisplatin and carboplatin cytotoxicity by amphotericin B in different human ovarian carcinoma and malignant peritoneal mesothelioma cells.

An in vitro study of the combined cytotoxicity of either cisplatin (CDDP) or carboplatin and amphotericin B (AmB) was undertaken on a set of different ovarian carcinoma (IGROVI, IGROVI-C10, OAW42) and peritoneal malignant mesothelioma (CFB-CARP1) cell lines and ascitic cells freshly obtained from ovarian cancer patients so as to investigate the possibility of overcoming their resistance to platinum compounds. Growth-inhibition curves obtained 6 days after a 2-h period of exposure to the drugs showed that AmB at 5-10 mg/l allowed a 5- to 10-fold decrease in the 50% growth-inhibitory concentrations (IC50) of CDDP and carboplatin on either sensitive or resistant cells. Intracellular platinum assays with IGROVI cells showed that AmB acted by increasing dramatically the platinum uptake at a proportion that accounted for the increase in cytotoxicity. In the subline IGROVI-C10, a 10-fold resistant subline of IGROVI, AmB at 10 mg/l allowed recovery to the level of sensitivity seen in the parental cell line in the absence of AmB but not to the level observed in the presence of AmB. Acquisition of resistance mechanisms that are independent of the regulation of platinum uptake might be involved in this cell line. Thus, AmB might act by increasing the intracellular concentration of platinum without modifying the resistance mechanism involved downstream. However, in our models an increase in the intracellular level of platinum was always sufficient for the recovery of chemosensitivity in vitro. We also show that the phosphodiesterase inhibiting methylxanthines act synergistically with AmB. The latter drugs are weakly toxic and could also attenuate the nephrotoxicity of AmB.

Adenocarcinoma↗

Relationships between iron and zinc metabolism: predictive value of digestive absorption on tissue storage.

The responses of animals to intake of a trace element could vary if it is ingested with a single test meal or due to chronic intake. The metabolic relationships between zinc (Zn) and iron (Fe) were assessed in the young animal by comparing their digestive absorption studied at the beginning of the study with their tissue storage after two months of being fed on experimental diet. Diets supplied adequate intakes of Fe (45 and 300mg/kg diet) and Zn (14 and 45 mg/kg). A significant effect of Fe supply (p < 0.0001) but not of Zn was displayed on Fe absorption; both Fe and Zn diet concentrations influenced Zn absorption (p < 0.01, p < 0.0001). Fe and Zn organ contents significantly correlated with the amount absorbed during the metabolic balance (p < 0.0001). There was a positive correlation between liver, bone, and muscle Fe and Fe absorption (mg/d)(p < 0.0001), and Fe absorption and bone and muscle Zn (p < 0.04) and a negative one with liver Zn (p < 0.0001); a positive correlation was displayed between Zn absorption (mg/d) and Zn organ content (p < 0.0001). There was no correlation between Zn absorption and Fe tissue content (p > 0.05). This study suggests that interactions occur at every step of Fe and Zn metabolism; Fe is more efficient in altering Zn storage than the reverse. The organism seems to be unable to diminish the consequences of an unbalanced diet and digestive absorption. Care must be taken to give the young growing balanced diets.

Analysis of Variance↗