Biomedical subjects

C Bertrand

Publications and source records attributed to C Bertrand.

At least 109 records · Page 6Linked to original sources

PubMed1993

Role of neurogenic inflammation in antigen-induced vascular extravasation in guinea pig trachea.

Conflicting results have been reported about the role of sensory nerves in the allergen-induced plasma extravasation in sensitized guinea pigs using capsaicin desensitization. To investigate the role of tachykinins released from sensory nerves in the anaphylactic reaction in guinea pigs in vivo, we used a selective inhibitor of neutral endopeptidase, phosphoramidon, and a selective neurokinin (NK)-1 receptor antagonist, CP-96,345. Male Hartley guinea pigs were sensitized to OVA by two i.p. injections (70 mg) at 1-wk intervals. Two wk later, the animals were anesthetized and OVA was administered for 2 min by aerosol through a tracheal cannula. Plasma extravasation was assessed by the photometric measurement of the extravasated Evans blue after formamide extraction. Administration of aerosolized OVA to sensitized guinea pigs increased dye extravasation in the trachea in a dose-dependent manner, an effect that was demonstrable 5 min after exposure to allergen and that reached a maximum 10 min after exposure. At 5 min after OVA (5%), phosphoramidon (2.5 mg/kg, i.v.) did not increase the amount of dye in the trachea significantly and CP-96,345 (4 mg/kg) did not decrease the extravasated dye. At 10 min after OVA, allergen-induced plasma extravasation was potentiated by phosphoramidon by 56%, and was inhibited by CP-96,345 (4 mg/kg) by 42%. In the presence of phosphoramidon, CP-96,345 reduced the OVA-evoked plasma extravasation at 10 min in a dose-related manner (0.1-4 mg/kg). CP-96,345 (4 mg/kg) did not affect plasma extravasation induced by platelet-activating factor (100 nmol/kg, i.v.). These results suggest that tachykinin release from sensory nerves after allergen challenge to airways in sensitized guinea pigs is not responsible for the early increase in plasma extravasation, but, tachykinin release appears to play an important role in the subsequent extravasation.

Animals↗

PubMed1993

Very long chain acyl-CoA dehydrogenase deficiency: identification of a new inborn error of mitochondrial fatty acid oxidation in fibroblasts.

A patient highly suspected of long chain fatty acid oxidation defect was investigated for membrane-bound palmitoyl-CoA dehydrogenation in a membrane extract from skin fibroblasts, using 1% sodium cholate as detergent. The profoundly decreased activity observed is consistent with a deficiency of the newly identified mitochondrial 'very long chain acyl-CoA dehydrogenase'.

Acyl-CoA Dehydrogenase, Long-Chain↗

PubMed1993

An epithelial-dependent contracting factor induced by calcium influx in guinea-pig trachea.

The effects of epithelium removal were studied on the contraction induced by Ca2+ in K(+)-depolarizing solution, and by the calcium ionophore A 23187 in guinea-pig isolated tracheal strips. Epithelium removal reduced the maximal response to Ca2+ in K(+)-depolarizing solution and caused a significant shift to the right of the Ca2+ concentration-response curves. The contraction induced by the calcium ionophore A 23187 (10(-6) M) was also markedly reduced by epithelium removal. These results suggest the occurrence of an epithelium-derived contracting factor. The effects of hexamethonium, atropine, spantide and thiorphan showed that acetylcholine and neurokinins play a minor role in the Ca(2+)-induced contraction. The epithelium-dependent potentiation of the calcium- and of the A 23187-induced contractions was inhibited by an antibody selective for rat calcitonin gene-related peptide (rCGRP alpha). Therefore, CGRP-like immunoreactive material may be part of the epithelium-dependent contracting factor of guinea-pig trachea. Comparison of concentration-response curves for rCGRP alpha in epithelium-free and in intact guinea-pig tracheal strips suggests that an epithelium-dependent contracting factor may be mobilized by CGRP.

Acetylcholine↗

PubMed1993

Identification of cis-acting elements involved in the regulation of the pathogenesis-related gene STH-2 in potato.

We have characterized a genomic clone containing the potato pathogenesis-related genes STH-2 and STH-21. The two genes are found 4 kb apart on the same chromosome and their sequences are highly similar. They present the same transcriptional orientation and are both interrupted by a single intron. A chimaeric gene consisting of 1015 bp of 5'-flanking sequence and part of the first exon of STH-2 fused to the bacterial beta-glucuronidase gene was highly-expressed in tubers of transgenic potato plants after wounding and elicitor treatments. The levels of activity observed in these transgenic plants parallel those observed for the accumulation of STH-2 mRNAs under similar conditions. This indicates that cis-acting elements necessary for the proper activation of the gene are present within 1 kb of 5'-flanking sequences. Functional analysis of 5' deletions of the STH-2/GUS constructs by transient expression in leaf protoplasts revealed the presence of an upstream regulatory sequence between -135 and -52 which contains a TGAC motif, and a possible negative regulatory region between -52 and -28. A factor present in nuclear extracts of wounded potato tubers was found to bind specifically to nucleotides located between -135 to -105, suggesting that this region contains important cis-regulatory elements.

Amino Acid Sequence↗

PubMed1993

Transgenic potato plants overexpressing the pathogenesis-related STH-2 gene show unaltered susceptibility to Phytophthora infestans and potato virus X.

The STH-2 gene is rapidly activated in potato leaves and tubers following elicitation or infection by Phytophthora infestans. However, its biochemical function remains unknown. In order to ascertain if STH-2 protein is directly involved in the defense of potato against pathogens, the STH-2 coding sequence under the control of the CaMV 35S promoter was introduced into potato plants. Transgenic plants expressing the STH-2 gene were analyzed for an altered pattern of susceptibility to a compatible race of P. infestans and to potato virus X. Results indicate that constitutive expression of the STH-2 gene did not reduce susceptibility of potato to these pathogens.

Cloning, Molecular↗

PubMed1993

Morphometry of human epidermis in vivo by real-time confocal microscopy.

Real-time confocal microscopy has brought substantial improvements to the imaging of the human skin in vivo. On early images, the stratum corneum could be distinguished from the living epidermis and the circulatory network of the superficial dermis. We have adapted the Tandem Scanning Microscope to obtain images of the living skin, showing thinner structures such as the stratum lucidum and the dermo-epidermal junction, both of which are essential markers for micron-order measurements of the thickness of the stratum corneum and living epidermis. The measurements were corrected for the differences in the refractive index of the various cutaneous layers, and the undulation of the dermo-epidermal junction. Furthermore, nucleus size and number could be assessed from horizontal optical sections. To illustrate the sensitivity of the thickness measurements, changes in the thickness of the epidermis were recorded during and after stripping of the horny layers. This non-invasive methodology is a very promising tool for morphometric studies of the living human skin at the cellular level.

Epidermal Cells↗

PubMed1993

Carnitine palmitoyl transferase I deficiency presenting as a Reye-like syndrome without hypoglycaemia.

An apparently healthy girl aged 2 years 9 months developed a coma with hepatomegaly within 24 h after an influenza-like infection. Plasma glucose and urinary organic acid profile were normal but plasma and urinary carnitine concentrations were increased. Despite symptomatic therapy, she died 11 days later. Oxidation of [1-14C] palmitic acid in the patient's fibroblasts was severely decreased (13% of controls). Further investigations revealed a deficiency of carnitine palmitoyl transferase I (CPT I) in the patient's fibroblasts (15% of controls) whereas CPT II activity was normal. Only four patients with CPT I deficiency have been reported so far. The subtle clinical and biochemical presentation of this disorder, which may account for the small number of cases diagnosed, is discussed.

Carnitine↗

PubMed1993

Tachykinins contract the circular muscle of the human esophageal body in vitro via NK2 receptors.

BACKGROUND: The action of tachykinins in the circular muscle of the human esophageal body is not known. The present study aimed to determine the response to tachykinins and the receptor type mediating this response. METHODS: Specimen were obtained from organ donors or patients undergoing esophagectomy for cancer, and isometric tension in response to tachykinins was measured. RESULTS: Substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) evoked a concentration-dependent contraction with the following order of potency: NKA > NKB > SP. The neutral endopeptidase inhibitor, phosphoramidon, increased only the response to SP. [beta Ala8]NKA(4-10), a selective agonist of the NK2 receptor, produced a concentration-dependent contraction, whereas [Sar9,Met(O2)11]SP and [MePhe7]NKB, selective agonists of NK1 and NK3 receptors, respectively, had no effect. Contraction evoked by NKA was inhibited by the nonpeptide NK2 antagonist SR 48968 but not by the nonpeptide NK1 receptor antagonist CP-96,345, tetrodotoxin, or atropine. SR 48968 did not affect the response to carbachol. CONCLUSIONS: Tachykinins contract the circular muscle of human esophageal body by activation of NK2 receptors without involvement of neural mechanisms. Response to SP is modulated by a phosphoramidon-sensitive enzymatic activity.

Adolescent↗

PubMed1993

Umbilical and placental vessels: modifications of their mechanical properties in preeclampsia.

OBJECTIVES: Our objective in this study was to assess the basic mechanical properties of umbilical and chorionic vessels of placentas delivered after both normal and preeclamptic pregnancies. STUDY DESIGN: Placentas were selected when the parturient women were admitted to the delivery room. Normal pregnancy (n = 17) was characterized by delivery at term (38 to 40 weeks) after uncomplicated pregnancy without any medication. Preeclamptic pregnancy (n = 7) was characterized by delivery after 28 weeks of pregnancy (28 to 39 weeks) after sustained hypertension and proteinuria. Arteries and veins from the umbilical cord and chorionic plate were prepared in rings for in vitro study in tissue baths. Passive and active (on stimulation by potassium chloride or serotonin) mechanical properties of these vessels were studied. RESULTS: In vessels from normal pregnancy, responsiveness, but not sensitivity, was increased with increasing passive tension on vessels until optimal tension was reached. The passive stretch-tension curve was shifted downward in umbilical veins and upward in umbilical arteries and chorionic veins obtained from preeclamptic mothers in comparison with normal parturient women. In the absence of passive tension, contractions in response to potassium chloride were produced in all umbilical veins and some chorionic veins from preeclampsia but not from normal pregnancy. Developed wall tension curves in chorionic vessels from preeclampsia were shifted upward. In umbilical veins and arteries and in chorionic veins, the optimal passive tension was lower in tissues from preeclampsia than in tissues from normal pregnancy. CONCLUSION: Our results indicate that both passive and active mechanical properties of umbilical vessels are modified after pregnancy complicated by preeclampsia.

Arteries↗

PubMed1993

Epithelial factors: modulation of the airway smooth muscle tone.

The airway epithelium is composed of a heterogeneous population of cells. This epithelial layer is not only a physical barrier but also a target responding to a variety of inflammatory mediators. These cells can respond by releasing contracting and relaxing factors to modulate airway responsiveness. They can also metabolize some of the inflammatory mediators. Epithelial damage is a consistent feature of some respiratory conditions, but whether or not such damage contributes to airway disease is for the moment unknown. This review summarizes the literature on the known and proposed roles of the epithelium in the modulation of the airway smooth muscle tone.

Animals↗

PubMed1993

Ruthenium red, but not capsazepine reduces plasma extravasation by cigarette smoke in rat airways.

1. Cigarette smoke increases vascular permeability in rat airways by activating release of tachykinin from capsaicin-sensitive sensory nerves. However, the mechanism by which cigarette smoke induces secretion of sensory neuropeptides is unknown. Here we hypothesized that cigarette smoke activates sensory nerve endings via a mechanism similar to that of capsaicin. 2. We studied the effects of ruthenium red, an inorganic dye which blocks the cation influx promoted by capsaicin and of the capsaicin antagonist capsazepine on the increase in vascular permeability produced by cigarette smoke, capsaicin, hypertonic saline and substance P in the trachea of pentobarbitone anaesthetized rats. We also investigated the ability of cigarette smoke to desensitize sensory nerve fibres. 3. Ruthenium red (10 mM) by aerosol blocked the increase in vascular permeability induced by capsaicin (0.5 microM) and reduced the response to cigarette smoke (5 puffs) but did not affect responses evoked by hypertonic saline (7.2%) or by substance P (10 microM) (all given by aerosol). Aerosols of capsazepine (0.1 mM) prevented extravasation by capsaicin, but did not inhibit response to cigarette smoke, hypertonic saline or substance P. Finally, pre-exposure to a high dose of cigarette smoke (10 puffs) prevented the extravasation caused by cigarette smoke (5 puffs) itself and by intravenous capsaicin (150 micrograms kg-1), but not that by intravenous substance P (10 nmol kg-1). 4. The present results show that cigarette smoke: (a) increases vascular permeability in the rat airways by a mechanism that is not antagonized by capsazepine, and is partially sensitive to rutheniun red; (b)produces desensitization of capsaicin-sensitive sensory nerves. We propose that chemical(s) contained in or agent(s) produced by cigarette smoke in the airways share partially a common pathway with capsaicin to activate peptide release from capsaicin-sensitive sensory nerves, but do not bind to the putative 'capsaicin receptor'.

Aerosols↗

PubMed1993

Characterization of tachykinin receptors in ferret trachea by peptide agonists and nonpeptide antagonists.

The tachykinin receptors mediating mucus secretion and smooth muscle contraction were studied in the ferret trachea in vitro. Substance P (SP) and the selective agonist for NK1 receptor ([Sar9,Met(O2)11]SP), but not selective agonists for NK2 ([Ala5,beta-Ala8]neurokinin A-(4-10)) and NK3 ([MePhe7]neurokinin B) receptors, induced secretion of macromolecules in a concentration-dependent fashion. The nonpeptide NK1 receptor antagonist, CP-96,345, but not the nonpeptide NK2 receptor antagonist, SR-48968, inhibited SP-induced secretion. Both neurokinin A (NKA) and [Ala5,beta-Ala8]NKA-(4-10), but not NK1 and NK3 selective agonists, evoked a concentration-dependent smooth muscle contraction. SR-48968, but not CP-96,345, inhibited in a concentration-dependent manner the response to NKA. CP-96,345 and SR-48968 did not affect the concentration-dependent increase in macromolecule secretion or smooth muscle contraction by carbachol. These findings indicate that NK1 receptors mediate secretion of macromolecules and NK2 receptors mediate smooth muscle contraction, in response to tachykinins in the ferret trachea in vitro.

Animals↗

PubMed1993

Involvement of neurogenic inflammation in antigen-induced bronchoconstriction in guinea pigs.

The role of tachykinins released from sensory nerves in bronchoconstriction induced by antigen was studied in sensitized guinea pigs anesthetized with pentobarbital sodium and pretreated with atropine. The combination of NK2 (SR-48968) and NK1 (CP-96,345) tachykinin-receptor antagonists abolished the increase in total pulmonary resistance (RL) evoked by intravenous capsaicin but did not affect the response evoked by intravenous histamine. A small dose of aerosolized ovalbumin (OVA, 0.1%) produced a small increase in RL that was further increased and markedly prolonged by the neutral endopeptidase (NEP) inhibitor phosphoramidon; this bronchoconstrictor effect of OVA was markedly reduced by the NK2-receptor antagonist and was abolished by the combination of the NK1 and NK2-receptor antagonists together. When a larger dose of OVA (0.5%) was used, a maximal bronchoconstrictor response was obtained. Phosphoramidon did not potentiate this response significantly. The combination of NK1- and NK2-receptor antagonists blunted the response at 5 min only slightly but markedly attenuated the later (10-20 min) response. These results show that tachykinins released from sensory nerves play a significant role in antigen-induced bronchoconstriction in guinea pigs. This effect is exaggerated when the normal modulation of neuropeptides by NEP is inhibited and is mediated predominantly by NK2-receptor activation, with a smaller contribution by NK1 receptors.

Aerosols↗

PubMed1993

Role of peptidases and NK1 receptors in vascular extravasation induced by bradykinin in rat nasal mucosa.

We used Evans blue dye to assess the effects of bradykinin on vascular extravasation in nasal mucosa of pathogen-free F344 rats. There was a dose-dependent increase in Evans blue extravasation when bradykinin was delivered by topical instillation in the nose (doses, 25-100 nmol). Only the highest intravenous doses (2 and 5 mumol/kg) of bradykinin caused increased extravasation. When bradykinin was delivered by either route, its effect on extravasation was exaggerated by pharmacological inhibition of the enzymes neutral endopeptidase (NEP) and kininase II [angiotensin-converting enzyme (ACE)]. When bradykinin was instilled locally, the effect of NEP inhibition was predominant; when bradykinin was injected intravenously, the effect of ACE inhibition was predominant. The mechanism of extravasation also varied with the mode of bradykinin delivery: when bradykinin was instilled locally in the nose, the selective neurokinin 1 (NK1) receptor antagonist CP-96,345 markedly inhibited the response, whereas it had no effect on Evans blue extravasation when bradykinin was injected intravenously. We conclude that bradykinin causes dose-related increases in Evans blue dye extravasation in the nose and that these effects are exaggerated when NEP and ACE are inhibited. Topically instilled bradykinin causes vascular extravasation to a large extent via NK1 receptor stimulation, thus suggesting a major role for tachykinins released from sensory nerve endings.

Animals↗

PubMed1993

Capsaicin increases airflow resistance in guinea pigs in vivo by activating both NK2 and NK1 tachykinin receptors.

The role of NK1 tachykinin receptors in the increase in total pulmonary resistance (RL) produced by release of endogenous tachykinins was investigated in anesthetized guinea pigs pretreated intravenously with atropine (1 mumol/kg) by using the novel nonpeptide antagonists of NK1 (CP-96,345) and NK2 (SR 48968) tachykinin receptors. SR 48968 (0.3 mumol/kg) and CP-96,345 (2 mumol/kg) given intravenously completely blocked the response to the selective NK2 receptor agonist [beta Ala8]neurokinin A(4-10) and NK1 receptor agonist [Sar9,Met(O2)11]substance P, respectively. The response to neurokinin A was reduced dose-dependently, but not abolished, by SR 48968, and it was completely prevented by a combination of SR 48968 and CP-96,345. The response to capsaicin was reduced, but not blocked, by SR 48968, and it was completely abolished by the combination of the two antagonists. The combination of SR 48968 and CP-96,345 did not affect the increase in RL evoked by histamine. Thus, NK1, as well as NK2, receptor activation contributes to the noncholinergic increase in RL evoked by capsaicin and ascribed to release of endogenous tachykinins from sensory nerves.

Airway Resistance↗

PubMed1993

Neurogenic vasodilation in the rat nasal mucosa involves neurokinin1 tachykinin receptors.

We studied the role of different tachykinin receptors in mediating neurogenic vasodilation in the nasal mucosa of anesthetized pathogen-free rats. Three successive determinations of blood flow were made by injecting radionuclide-labeled microspheres suspended in 70% dextrose into the left ventricle. A selective agonist of the tachykinin NK1 receptor increased nasal blood flow, but neurokinin NK2- and NK3-selective agonists were without effect. The natural agonist of NK1 receptors, substance P (1 microgram/kg), increased nasal blood flow, an effect that was abolished by the selective NK1 receptor antagonist (+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine (CP-99,994). Capsaicin (25 micrograms/kg), a drug that releases tachykinins from sensory nerves, increased nasal blood flow, and this effect was significantly reduced by CP-99,994. We conclude that a significant component of neurogenic vasodilation in rat nasal mucosa is due to the stimulation of NK1 tachykinin receptors.

Animals↗

PubMed1993

A new NK1 receptor antagonist (CP-99,994) prevents the increase in tracheal vascular permeability produced by hypertonic saline.

The increase in tracheal vascular permeability evoked by hypertonic saline depends on capsaicin-sensitive sensory nerves, which contain substance P and other neuropeptides. The present study was performed to determine whether a novel, nonpeptide, selective antagonist of the NK1 tachykinin receptor CP-99,994, [(+)-(2S-3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine], can prevent the effect of substance P, capsaicin and hypertonic saline on tracheal vascular permeability. CP-99,994 was also tested against a nonpeptide inflammatory mediator, platelet-activating factor (PAF), to assess the selectivity of its action. Anesthetized F-344 rats were injected with either substance P (5 micrograms/kg i.v.), capsaicin (100 micrograms/kg i.v.) or PAF (10 micrograms/kg i.v.), or were exposed to ultrasonically nebulized 3.6% NaCl. In each group, some of the rats were pretreated with CP-99,994 (1 to 4 mg/kg i.v.), and some with its vehicle (0.9% NaCl). Groups of rats injected with substance P or exposed to hypertonic saline were pretreated with the (2R, 3R)-enantiomer CP-100,263, [(-)-(2R-3R)-3-(2-methoxybenzylamino)-2-phenylpiperidine] (2 or 4 mg/kg i.v.). The magnitude of the increase in tracheal vascular permeability was measured by quantifying the extravasation of Evans blue dye. CP-99,994 prevented the increase in tracheal vascular permeability produced by inhalation of hypertonic saline, by substance P and by capsaicin, but did not prevent the effect of PAF. CP-100,263 did not affect substance P- and hypertonic saline-induced increase in vascular permeability. These results indicate that the NK1 receptor antagonist CP-99,994 produces stereoselective inhibition of neurogenic plasma extravasation evoked by inhalation of hypertonic saline.

Animals↗

PubMed1993

[Multiple acyl-CoA dehydrogenase deficiency. Report of 2 siblings].

The authors report on two siblings with a multiple acyl-CoA dehydrogenase deficiency. The first child died from a Reye's syndrome when he was 9 month-old. The diagnosis was made in the neonatal period in his brother. Early treatment with glucose and carnitine should prevent acute attacks.

Acyl-CoA Dehydrogenases↗