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T Chinet

Publications and source records attributed to T Chinet.

At least 19 recordsLinked to original sources
PubMed2006

[Is the severity of occupational asthma related to the molecular weight of the allergen?].

INTRODUCTION: The aim of the study was to compare the characteristics of occupational asthma (OA) resulting from sensitisation to allergens of high (HMW) or low (LMW) molecular weight. METHODS: All new cases of allergic OA seen in an occupational health department between January 2001 and March 2004 were included. The patients underwent a standardised assessment including a questionnaire, skin tests, spirometry and measurement of non-specific bronchial reactivity. They were divided into 2 groups depending on the molecular weight of the causal agent (groups HMW and LMW). RESULTS: 77 patients were included, 30 in the HMW group and 47 in the LMW group. No significant difference in severity at the time of diagnosis was found between the two groups (symptoms, spirometry, PD20 methacholine) but the time between the first symptoms and diagnosis was longer in the HMW group (7.1 +/- 7.8 years against 3.2 +/- 4.1 years, p = 0.01). Atopy was more common in the HMW group (57% vs. 27%, p = 0.01). CONCLUSION: The severity of OA at the time of diagnosis does not appear to be influenced by the molecular weight of the causal agent.

Adult↗
PubMed2005

Abnormal ion content, hydration and granule expansion of the secretory granules from cystic fibrosis airway glandular cells.

The absence or decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) induces increased Na(+) absorption and hyperabsorption of the airway surface liquid (ASL) resulting in a dehydrated and hyperviscous ASL. Although the implication of abnormal airway submucosal gland function has been suggested, the ion and water content in the Cystic Fibrosis (CF) glandular secretory granules, before exocytosis, is unknown. We analyzed, in non-CF and CF human airway glandular cell lines (MM-39 and KM4, respectively), the ion content in the secretory granules by electron probe X-ray microanalysis and the water content by quantitative dark field imaging on freeze-dried cryosections. We demonstrated that the ion content (Na(+), Mg(2+), P, S and Cl(-)) is significantly higher and the water content significantly lower in secretory granules from the CF cell line compared to the non-CF cell line. Using videomicroscopy, we observed that the secretory granule expansion was deficient in CF glandular cells. Transfection of CF cells with CFTR cDNA or inhibition of non-CF cells with CFTR(inh)-172, respectively restored or decreased the water content and granule expansion, in parallel with changes in ion content. We hypothesize that the decreased water and increased ion content in glandular secretory granules may contribute to the dehydration and increased viscosity of the ASL in CF.

Cell Line, Transformed↗
PubMed2002

[The role of endothelin in the physiology and pathophysiology of airways].

Following its discovery in 1988 endothelin initially attracted attention in the cardiovascular field. It is only more recently that the involvement of this peptide, and its role in the physiology and pathophysiology of the airways, has been established. Endothelin receptors have been demonstrated in the majority of cells in the airways from the main bronchi to the alveoli, where endothelin exerts endocrine and paracrine effects on the fine regulation of bronchial muscular tone, the process of cell proliferation and repair, alveolar and bronchial secretion as well as microvascular permeability. The intra and extracellular pathways of the mechanisms of action of endothelin are currently under investigation. Furthermore, it has been shown in the last ten years that endothelin is also, in certain circumstances, a powerful inflammatory mediator. The implication of endothelin in pathological processes such as asthma, chronic airflow obstruction, bronchiectasis, some broncho-pulmonary cancers, ideopathic pulmonary fibrosis, and ARDS is currently suspected if not proven. This opens up the possibility of new therapies. The object of this revue is to summarise the current knowledge of the role played by endothelin in the physiology and pathophysiology of the airways and respiratory system.

Endothelins↗
PubMed2000

[Changes in metered dose inhaler propellants].

The understanding of the damaging effect of chlorofluorocarbons (CFCs) on the stratospheric ozone has led to international agreements calling for the total phase-out of CFC production. The banning of CFCs in pressurized metered dose inhalers used in airways disorders has been postponed on a temporary basis until replacement propellants have been identified. Hydrofluoroalkanes HFA-134a and HFA-227 have been shown to have no ozone damaging potential and to be safe. However, HFAs cannot simply be substituted for CFCs in inhalers of identical design. Their use has required changes in many aspects of the drug formulation, inhaler design and manufacture. This, in turn, has provided at least to some pharmaceutical companies an opportunity to assess and enhance the performances of new inhalers. The new products are neither technically nor pharmacologically identical to their CFC-based counterparts. Some of them have now completed clinical trials and the transition has already started: by the end of 1998, 2 short acting beta-agonist HFA-based inhalers and a corticosteroid HFA-based inhaler have reached the marketplace in France.

Adrenal Cortex Hormones↗
PubMed2000

[Diagnosis of cystic fibrosis in adults].

Cystic fibrosis is a genetic recessive disorder caused by mutations in the gene that encodes the CFTR protein. The diagnosis of cystic fibrosis is usually established in early childhood but it is now being made in an increasing number of adults. Many of them present with mild or atypical cystic fibrosis clinical features, mostly lung disease. In addition, some adults with congenital bilateral absence of vas deferens or idiopathic chronic pancreatitis may be assigned a diagnosis of cystic fibrosis. The diagnosis of cystic fibrosis in adults should be based on the presence of one or more characteristic clinical features, a history of cystic fibrosis in a sibling, plus evidence of defective CFTR function as documented by elevated sweat chloride concentrations or abnormal ion transport across the nasal epithelium, or identification of mutations on both CFTR genes.

Adolescent↗
PubMed2000

[Massive hemoptysis during sarcoidosis].

Hemoptysis is a rare but often severe event in sarcoidosis. It usually occurs in patients with advanced, fibrotic lung disease. We herein report the case of a 36-year old female patient with type II pulmonary sarcoidosis who presented with abundant hemoptysis very early during the course of her disease. Two attempts to embolize bronchial arteries remained unsuccessful and surgery was eventually required to stop the bleeding. Clinical, microbiological, radiological and pathological data indicate that haemoptysis was caused by systemic hypervascularization around sarcoidosis granuloma.

Adult↗
PubMed1999

Regulation of electrogenic anion secretion in normal and cystic fibrosis gallbladder mucosa.

Fluid and ion transport across biliary epithelium contributes to bile flow. Alterations of this function may explain hepatobiliary complications in cystic fibrosis (CF). We investigated electrogenic anion transport across intact non-CF and CF human gallbladder mucosa in Ussing-type chambers. In non-CF tissues, baseline transmural potential difference (PD), short-circuit current (Isc), and resistance (R) were -2.2 +/- 0.3 mV (lumen negative), 40.7 +/- 7.8 microA/cm2, and 66.5 +/- 9.6 Omega. cm2, respectively (n = 14). The addition of forskolin (10(-5) mol/L) to the apical and basolateral baths and that of adenosine 5'-triphosphate (ATP) (10(-4) mol/L) to the apical bath induced significant increases in Isc by 8.0 +/- 1.4 and 10.3 +/- 1.8 microA/cm2, respectively. Depletion of bathing solutions in Cl- and HCO3- significantly reduced baseline Isc and the forskolin- and ATP-induced increases in Isc. Anion secretion was stimulated by extracellular ATP via P2Y2 purinoceptors, as indicated by the effects of different nucleotides on Isc and on 36Cl efflux in cultured gallbladder epithelial cells. This effect was mediated by cytosolic calcium increase and Ca2+/calmodulin-dependent protein kinase II, as ascertained by using inhibitors. In CF preparations, basal PD and Isc were lower than in non-CF, and the response to forskolin was abolished, whereas the response to ATP was enhanced (P <.05 for all). We conclude that electrogenic anion secretion occurs in human gallbladder mucosa under basal state and is stimulated by an adenosine 3',5'-cyclic monophosphate (cAMP)-dependent pathway mediated by cystic fibrosis transmembrane conductance regulator (CFTR), and by exogenous ATP via a CFTR-independent pathway that is up-regulated in CF and involves P2Y2 purinoceptors and a calcium-dependent pathway.

Adenosine Triphosphate↗
PubMed1999

[Physiopathology of cystic fibrosis lung disease].

Cystic fibrosis is a common genetic disorder caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Although the link between the mutations of the CFTR gene and the progressive lung disease is not completely understood, noteworthy advances have been made in the understanding of the mechanisms underlying lung injury in CF. The pathophysiologic cascade starts with CFTR dysfunction resulting from mutations of the CFTR gene, and leading to abnormal ion and water transport across airway epithelia. Abnormal airway surface liquid may in turn lead to impairment of mucociliary clearance, airway mucosal anti-microbial defenses, chronic bacterial infection and inflammation. Each of these steps has been elucidated in more detail in the recent years. This is of relevance from a therapeutic viewpoint. New therapeutic interventions include gene therapy, agents that may circumvent the defect in intracellular processing of mutated CFTR, agents that may modulate defects in epithelial ion transport, and anti-inflammatory agents.

Anti-Inflammatory Agents↗
PubMed1999

[Bronchial and pulmonary vaso-occlusions].

The technique of vaso-occlusion (or embolisation) consists in occluding one or several vessels which are causing haemoptysis. Either of the pulmonary circulations (systemic bronchial or pulmonary) may be the cause and sometimes both are. In systemic pulmonary hypervascularization the pathological issues are affected by high pressure vascularisation at the expense of functional vascularisation and are the source of frequent episodes of bleeding. Bronchial and systemic vaso-occlusion has proven efficacy and safety on condition that strict rules are respected to avoid complications; the detection of potentially dangerous arteries (spinal, coronary and visceral) and a choice of material for embolisation which is adapted to the therapeutic strategy and the clinical and angiographic presentation. The indications for the procedure are dictated by severe or recurrent haemoptysis. Vaso-occlusion of pulmonary arteries which is a rarer indication dominated by conditions such as arteriovenous malformation (MAVP). The technique is adapted to the number, to the size and to the diffusion of MAVP which is characterised precisely by computed tomography. Vaso-occlusion is the treatment of first choice for MAVP only leaving failures of vaso-occlusion to surgery and certain pedicular forms have a very short afferent of large calibre.

Arteriovenous Malformations↗
PubMed1998

Endothelin-1 is synthesized and inhibits cyclic adenosine monophosphate- dependent anion secretion by an autocrine/paracrine mechanism in gallbladder epithelial cells.

Ion and fluid transport across the biliary epithelium contributes to bile secretion. Since endothelin (ET)-1 affects ion transport activities and is released by human gallbladder- derived biliary epithelial cells in primary culture, we examined the expression of ET peptides and ET receptors and the influence of ET-1 on ion transport in this epithelium ex vivo. In freshly isolated gallbladder epithelial cells, preproET-1, -2, and -3 mRNAs were detected by reverse transcription PCR and ET-1 isopeptide was identified by chromatography. The cells also displayed ET receptor mRNAs and high-affinity binding sites for ET-1, mostly of the ETB type. Electrogenic anion secretion across intact gallbladder mucosa was stimulated by forskolin, secretin, and exogenous ATP, as assessed by short-circuit current (Isc) increases in Ussing-type chambers. ET-1 inhibited forskolin- and secretin-induced changes in Isc, without affecting baseline Isc or ATP-induced changes. Accordingly, ET-1 significantly reduced the accumulation of intracellular cAMP elicited by forskolin and secretin in the epithelial cells, and this effect was abolished by pertussis toxin. This is the first evidence that ET-1 is synthesized and inhibits, via a Gi protein-coupled receptor, cAMP-dependent anion secretion in human gallbladder epithelium, indicating a role in the control of bile secretion by an autocrine/paracrine mechanism.

Anions↗
PubMed1998

Bioelectric properties of human cystic fibrosis and non-cystic fibrosis fetal tracheal xenografts in SCID mice.

We measured, the bioelectric properties of 14 cystic fibrosis (CF) and 33 non-CF human fetal tracheal xenografts in severe combined immunodeficiency (SCID) mice. All xenografts exhibited a mature airway-type epithelium irrespective of their gestational age, duration of engraftment, and genotype. The in vivo potential difference and the in vitro baseline short-circuit current (Isc) were significantly higher in non-CF than in CF xenografts. In non-CF xenografts, sequential addition of amiloride, forskolin, and ATP resulted in a 39.4% decrease, a 24.1% increase, and a 43.6% increase in Isc, respectively. In CF xenografts, forskolin had no significant effect on Isc, whereas amiloride- and ATP-induced changes in Isc were proportionally higher than in non-CF xenografts (-60.0 and +68.8%, respectively). These results indicate that the bioelectric properties of non-CF xenografts are similar to those of postnatal airways and that CF xenografts exhibit lower baseline electrogenic activity than non-CF xenografts but similar regulation of ion transport processes to postnatal CF airways. This model of mature human fetal tracheal mucosa may help gain insight into early CF airway pathogenesis.

Animals↗
PubMed1997

Induction of a cAMP-stimulated chloride secretion in regenerating poorly differentiated airway epithelial cells by adenovirus-mediated CFTR gene transfer.

In cystic fibrosis (CF), the airway epithelium is in the process of injury and regeneration. In the context of the CF gene therapy, we previously reported that regenerating poorly differentiated (PD) cells of human airway epithelium represent preferential cell targets for recombinant adenoviral gene vectors. To define whether PD non-CF and CF epithelial cells possess a functional cystic fibrosis transmembrane conductance regulator protein (CFTR) chloride channel, we analyzed the CFTR expression and the regulation of chloride secretion under cyclic (c)AMP stimulation in these regenerating PD epithelial cells of non-CF and CF airway tissue. Moreover, we studied the effects of CFTR gene transfer mediated by a replication-defective adenovirus containing the wild-type CFTR gene (AdCFTR) on CFTR expression and on cAMP-stimulated chloride secretion. Distribution of the CFTR protein was evaluated in regenerating PD airway cells by light fluorescence microscopy and scanning laser confocal microscopy. The cAMP-mediated regulation of cell membrane chloride secretion was investigated using the whole-cell patch clamp and SPQ (6-methoxy-N-[3-sulfopropyl]quinolinium) techniques. Compared with the absence of CFTR expression and cAMP-regulated chloride secretion in nontransduced regenerating PD cells of either non-CF or CF origin, transduction with AdCFTR induces a CFTR expression and a cAMP-regulated stimulation of the cell membrane chloride secretion in the regenerating PD cells. These results suggest that, out of the context of CF, remodeled and poorly differentiated airway epithelium may present abnormalities in ion transport. Moreover, our data suggest that, in the context of CF gene therapy, adenoviral vectors can be efficient in correcting, at least partially, the chloride secretion defect in the remodeled CF airway epithelium.

Adenoviridae↗
PubMed1997

Extracellular ATP stimulates K+ secretion across cultured human airway epithelium.

Extracellular ATP applied to the luminal side of human airway epithelium (HAE) activates an apical membrane Cl- conductance and transepithelial Cl- secretion. However, in some HAE preparations, we have found that luminal ATP induces a change in short-circuit current (Isc), consistent with K+ secretion. Using intracellular microelectrodes and radioisotopic flux studies, we investigated whether extracellular ATP regulates transepithelial K+ secretion in primary HAE cultures. In physiological Ringer solution, HAE had a negligible electrochemical driving force for Cl- secretion (DFCl), and luminal ATP induced a change in Isc opposite in polarity to Cl- secretion. Intracellular microelectrode measurements indicated that the "reversed" Isc was associated with activation of a hyperpolarizing (K+) conductance in the apical membrane. Radioisotope studies of HAE pretreated with amiloride to induce a favorable DFCl revealed that luminal ATP stimulates a small 42K secretory flux concurrently with Cl- secretion. In ion-substituted Ringer solution, luminal ATP stimulated both the outward (K+) current and the inward (Cl-) current with approximately equal potency (approximately 10(-6) M). We conclude that luminal ATP activates an apical membrane K+ conductance and transepithelial K+ secretion across HAE.

Adenosine Triphosphate↗
PubMed1997

Ambulatory inhalation therapy in obstructive lung diseases.

The inhalation route is widely used for the treatment of obstructive lung diseases, because administered drugs have a high therapeutic index as they reach their target directly; this requires that they be of adequate size to penetrate the conducting airways, i.e. 2-5 microns. Pressurized inhalers were the first reliable metered-dose devices available, and are still the most frequently used. However, metered-dose inhaler (MDI) suspensions will have to be reformulated: they contain chlorofluorocarbons (CFCs), whose production has to be stopped within a few years, as they affect the stratosphere. Another limitation of MDI usage is paradoxical bronchospasm; this phenomenon, however, occurs in a low number of patients and is rarely clinically relevant. The main cause of concern with MDIs is their misuse by more than 50% of patients, which leads to a reduced lung deposition and clinical efficacy. Therefore, other inhalation devices have been developed: spacers, dry-powder inhalers (DPIs), and breath-actuated MDIs have been shown to increase lung deposition of drugs in poor coordinators. However, all have limitations which may have varying consequences on clinical efficacy: cumbersome dimensions of spacers, effect of inspiratory flow rate and humidity on lung deposition of dry powders, need for reformulation with CFC-free gases for breath-actuated pressurized inhalers. Reformulation of MDI aerosols is a complex procedure, which may not be feasible for all drugs. The new products need extensive toxicological and clinical testing, as some of their characteristics may differ from those of their predecessors.

Aerosols↗
PubMed1997

[Effects of leukotrienes on bronchial secretions].

Leukotrienes have multiple effects on the bronchi (inflammation, bronchoconstriction, increased vascular permeability...). They are also directly involved in regulating the composition of bronchial secretions. In vitro studies in animals and in man have demonstrated that sulphidopeptide leukotrienes stimulate active secretion of chloride by airway epithelial cells, an effect that should favor hydration of bronchial secretions. In addition, sulphidopeptide leukotrienes are powerful stimulants for mucin glycoprotein secretion. This effect is limited, at least in vitro, by inhibitors of the lipoxygenase pathway. These results underline the need for clinical studies to better define the role of leukotrienes in bronchial hypersecretion and to evaluate the effect of anti-leukotriene agents.

Animals↗