Constituents of Pilocarpus trachylophus.
Four flavonoids, two terpenoids and a mixture of three polyprenols have been isolated from the leaves of Pilocarpus trachylophus.
Flavonoids↗
Biomedical subjects
C Bertrand
Publications and source records attributed to C Bertrand.
MRI prior computation and parallel tempering algorithm: a probabilistic resolution of the MEG/EEG inverse problem.
Since the MEG inverse problem is ill-posed and admits many possible solutions, it is not possible to give it a single "true" answer. Therefore, we propose here to use a specific probabilistic algorithm to map the full probability distribution of the MEG sources with Markov Chain Monte Carlo methods. Using a Bayesian approach, the probability of the MEG solutions is expressed as the product of the likelihood by the prior probability. To compute the prior and constrain the MEG inverse problem resolution, MRI data are also acquired and automatically processed to determine the brain position and volume. We then use Parallel Tempering algorithm to estimate the full posterior probability and determine the likely solutions of the inverse problem. We illustrate the method with results obtained from the analysis of somatosensory data. This illustrates both the MRI processing for the prior computation, and how the knowledge of the full posterior probability distribution can be used to estimate the position of the sources, as well as their likely extension.
Adult↗
IL-5 deficiency abolishes aspects of airway remodelling in a murine model of lung inflammation.
BACKGROUND AND OBJECTIVES: Lung remodelling is a recognized feature of chronic asthma. In the present study, we have used IL-5-deficient mice to evaluate the role of this cytokine and eosinophilic inflammation in the initial stages of the structural changes occurring in the lung after antigen challenge. METHODS: Ovalbumin-sensitized wild type and IL-5-deficient mice were daily challenged for 5 consecutive days and killed 3 or 7 days after the last challenge to study the inflammatory and remodelling events, respectively. RESULTS: Wild type mice challenged with ovalbumin exhibited an accumulation of eosinophils in the bronchoalveolar lavage (BAL) fluid, associated with a production of BAL cellular fibronectin. Histological analysis also revealed an antigen-specific increase in epithelial and alveolar cell proliferation together with an increase in mucus producing epithelial cells. Eosinophilic infiltration and the associated lung remodelling were totally abrogated in IL-5-deficient mice. In wild type mice, treated intranasally with 1 microg of murine IL-5 for 5 consecutive days, no BAL eosinophilia and structural changes of the lungs could be observed. CONCLUSION: Our results demonstrate that eosinophil accumulation, but not IL-5 alone, plays a central role in the initial stages of the lung remodelling process and suggests that therapies directed at inhibiting eosinophilic inflammation may be beneficial in treating chronic asthma.
Animals↗
A probabilistic solution to the MEG inverse problem via MCMC methods: the reversible jump and parallel tempering algorithms.
We investigated the usefulness of probabilistic Markov chain Monte Carlo (MCMC) methods for solving the magnetoencephalography (MEG) inverse problem, by using an algorithm composed of the combination of two MCMC samplers: Reversible Jump (RJ) and Parallel Tempering (PT). The MEG inverse problem was formulated in a probabilistic Bayesian approach, and we describe how the RJ and PT algorithms are fitted to our application. This approach offers better resolution of the MEG inverse problem even when the number of source dipoles is unknown (RJ), and significant reduction of the probability of erroneous convergence to local modes (PT). First estimates of the accuracy and resolution of our composite algorithm are given from results of simulation studies obtained with an unknown number of sources, and with white and neuromagnetic noise. In contrast to other approaches, MCMC methods do not just give an estimation of a "single best" solution, but they provide confidence interval for the source localization, probability distribution for the number of fitted dipoles, and estimation of other almost equally likely solutions.
Algorithms↗
Inducible nitric oxide synthase inhibitors suppress airway inflammation in mice through down-regulation of chemokine expression.
Growing evidence demonstrates that inducible NO synthase (iNOS) is induced in the airways of asthmatic patients. However, the precise role of NO in the lung inflammation is unknown. This study investigated the effect of both selective and nonselective iNOS inhibitors in an allergen-driven murine lung inflammation model. OVA challenge resulted in an accumulation of eosinophils and neutrophils in the airways. Expression of iNOS immunostaining in lung sections together with an increase in calcium-independent NOS activity in lung homogenates was also observed after OVA challenge. Treatment with iNOS inhibitors from the day of challenge to the day of sacrifice resulted in an inhibition of the inflammatory cell influx together with a down-regulation of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1 production. In contrast, eosinophilic and neutrophilic inhibition was not observed with treatment during the sensitization. Both treatments induced an increased production of Th2-type cytokines (IL-4 and IL-5) with a concomitant decrease in production of Th1-type cytokine (IFN-gamma). In vitro exposure of primary cultures of murine lung fibroblasts to a NO donor, hydroxylamine, induced a dose-dependent release of macrophage inflammatory protein-2 and monocyte chemoattractant protein-1. Our results suggest that lung inflammation after allergen challenge in mice is partially dependent on NO produced mainly by iNOS. NO appears to increase lung chemokine expression and, thereby, to facilitate influx of inflammatory cells into the airways.
Administration, Intranasal↗
N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide: an orally active neurokinin NK1/NK2 antagonist.
The stereoselective synthesis of N-[(R,R)-(E)-1-(4-chloro-benzyl)-3-(2-oxo-azepan-3-ylcarbamoyl+ ++)-allyl]-N-methyl-3,5-bis-trifluoromethyl-benzamide (4) and its NK1 and NK2 receptor binding properties are reported. In addition the potent inhibitory effects in vivo on sar9-SP- and beta-Ala-NKA-induced airway bronchoconstriction in guinea pigs are demonstrated.
Administration, Oral↗
FGF-2 isoforms of 18 and 22.5 kDa differentially modulate t-PA and PAI-1 expressions on the pancreatic carcinoma cells AR4-2J: consequences on cell spreading and invasion.
Pancreatic tumors overexpress FGF-2 and t-PA, but the implication of the growth factor in t-PA synthesis and t-PA-dependent tumor invasion remains unknown. FGF-2 is present in different isoforms: The 18 kDa FGF-2 is secreted, while the 22.5 kDa one is nuclearized and exerts intracrine regulations bypassing cell-surface FGF receptors. Rat pancreatic carcinoma AR4-2J cells producing either the 18 or the 22.5 kDa FGF-2 after transfection with FGF-2 cDNAs have been used to analyze the role of FGF-2 in t-PA expression and t-PA-related cell spreading. The 22.5 kDa FGF-2 reduced t-PA and PAI-1 synthesis 2-fold. Addition of recombinant 18 kDa FGF-2 (rFGF-2) to cell cultures resulted in increased t-PA and decreased PAI-1 expression. By contrast, rFGF-2 did not significantly modify t-PA synthesis in cells producing the 22.5 kDa FGF-2. Cell spreading was t-PA-dependent. Furthermore, cells producing the 22.5 kDa FGF-2 migrated less than control cells and cells producing the 18 kDa FGF-2. Overall, our data show that secretory FGF-2 is involved in t-PA synthesis by pancreatic cancer cells and facilitates cell spreading. The 22.5 kDa FGF-2 exerts opposite effects by decreasing t-PA expression in basal conditions and during rFGF-2 stimulation. Since the expression of the 22.5 kDa FGF-2 is under specific controls, its up-regulation might have the potential to reduce spreading of pancreatic cancer cells.
Animals↗
PLA2 phosphorylation and cyclooxygenase-2 induction, through p38 MAP kinase pathway, is involved in the IL-1beta-induced bradykinin B2 receptor gene transcription.
We hypothesized that inflammatory mediators such as interleukin-1beta (IL-1beta) might be responsible for the hyperreactivity to bradykinin observed in asthmatic patients. We reported previously that IL-1beta induced a prostanoid-dependent increase in the density of bradykinin B2 receptors in cultured human bronchial smooth muscle cells. Our experiments demonstrate that the rapid prostaglandin E2 (PGE2) synthesis induced by IL-1beta is abolished by cycloheximide, suggesting the involvement of protein synthesis. The formation of PGE2 is preceded by the phosphorylation of cPLA2 and the expression of cyclooxygenase-2 (Cox-2). The inhibition of p38 MAP kinase inhibited PGE2 synthesis, cPLA2 phosphorylation and abolished Cox-2 expression. The inhibition of Cox-2 expression correlated with a decrease of bradykinin B2 receptor expression. These data demonstrate that the activation of p38 MAP kinase elicited by IL-1beta leads to the phosphorylation of cPLA2 and Cox-2 overexpression, allowing rapid synthesis of PGE2 as a prerequisite for bradykinin B2 gene expression in human bronchial smooth muscle cells which could explain the hyperresponsiveness of asthmatic patients to bradykinin.
Bronchi↗
Comorbidity of post-traumatic stress disorder and chronic pain: implications for clinical and forensic assessment.
A summary of the current state of science is presented with reference to post-traumatic stress disorder (PTSD) and pain. Historical development of the diagnosis, current nosology, epidemiology, pathophysiology, and controversies are discussed. Issues of evaluation are reviewed, with specific reference to forensic assessment. Treatment outcome studies are briefly reviewed, with a review of currently accepted treatment interventions, including pharmacologic and behavioral modalities. An emphasis is placed on an integrated treatment plan in which chronic pain and PTSD both are present.
Chronic Disease↗
[Assessment of quality of life after antireflux surgery].
AIM OF THE STUDY: To assess the quality of life (QoL) of patients operated for gastroesophageal reflux disease (GERD). PATIENTS AND METHODS: This prospective study included 82 consecutive patients submitted to antireflux surgery between October 1998 and January 1999. A new questionnaire was used to assess their QoL: the Gastrointestinal Quality of Life Index (GIQLI) that includes 36 items concerning 5 dimensions: symptoms, vitality, emotions, social relations and medical treatment. The series consisted of 44 men and 38 women with a mean age of 47 years (range: 18-78). QoL was assessed before and 6 months after surgery; the follow-up rate was 94% (77/82). The pre- and postoperative GIQLI scores of the study group and the GIQLY score of a control group of 110 healthy patients were compared. RESULTS: Before surgery, the GIQLI score (90 +/- 23) was greatly impaired compared to the score (123 +/- 13) observed in the control group (p < 0.001). After surgery, the GIQLI score (110 +/- 23) increased significantly (p < 0.001), but remained statistically lower than the score of the control group (p < 0.001). The postoperative score recorded in the symptoms dimension was lower than the control group score: 55 +/- 11 versus 66 +/- 6 (p < 0.001), while no significant difference was observed in the other 4 dimensions. Univariate statistical analysis revealed that the postoperative GIQLI score (y) was correlated with the preoperative GIQLI score (x) according to the formula: y = 0.43 x + 71 (p < 0.001) and the sex of the patients, as the postoperative GIQLI score was higher in male patients (115 +/- 19) than in female patients (103 +/- 23) (p < 0.02). CONCLUSION: The QoL of the patients was greatly improved after antireflux surgery, but remained lower than that of a control group of healthy subjects. Better patient selection should improve the results. In our series, male patients or patients with a high preoperative GIQLI score were the best candidates for antireflux surgery.
Adolescent↗
Role of nitric oxide and septide-insensitive NK(1) receptors in bronchoconstriction induced by aerosolised neurokinin A in guinea-pigs.
The tachykinin, neurokinin A (NKA), contracts guinea-pig airways both in vitro and in vivo, preferentially activating smooth muscle NK(2) receptors, although smooth muscle NK(1) receptors may also contribute. In vitro evidence suggests that NKA activates epithelial NK(1) receptors, inducing the release of nitric oxide (NO) and subsequent smooth muscle relaxation. A number of selective NK(1) receptor agonists have been reported to activate both smooth muscle and epithelial NK(1) receptors, however septide appears only to activate smooth muscle NK(1) receptors. The aim of the present study was to investigate whether NKA-induced bronchoconstriction in guinea-pigs in vivo may be limited by NO release via NK(1) receptor activation, and whether selective NK(1) receptor agonists may activate this mechanism differently. Aerosolized NKA caused an increase in total pulmonary resistance (RL) that was markedly reduced by the NK(2) receptor antagonist, SR 48968, and abolished by the combination of SR 48968 and the NK(1) receptor antagonist, CP-99, 994. The increase in RL evoked by NKA was potentiated by pretreatment with the NO synthase (NOs) inhibitor, L-NAME, but not by the inactive enantiomer D-NAME. Potentiation by L-NAME of NKA-induced increase in RL was reversed by L-Arginine, but not by D-Arginine. Pretreatment with L-NAME did not affect the increase in RL induced by the selective NK(2) receptor agonist, [beta-Ala(8)]NKA(4-10), and by the selective NK(1) receptor agonist, septide, whereas it markedly potentiated the increase in RL caused by a different NK(1) selective agonist, [Sar(9),Met(O(2))(11)]SP. Dose-response curves showed that septide was a more potent bronchoconstrictor than [Sar(9),Met(O(2))(11)]SP to cause bronchoconstriction. Pretreatment with the NK(1) receptor antagonist, CP-96,994, abolished the ability of L-NAME to increase bronchoconstriction to aerosolized NKA. Bronchoconstriction to aerosolized NKA was increased by L-NAME, after pretreatment with the NK(3) receptor antagonist, SR 142801. The present study shows that in vivo bronchoconstriction in response to the aerosolized naturally occurring tachykinin, NKA, is limited by its own ability to release relaxant NO via NK(1) receptor activation. This receptor is apparently insensitive to septide, thus justifying, at least in part, the high potency of septide to cause bronchoconstriction in guinea-pigs.
Aerosols↗
Time course of inflammatory and remodeling events in a murine model of asthma: effect of steroid treatment.
The kinetics of airway inflammation and remodeling processes following ovalbumin aerosol challenge in sensitized BALB/c mice was studied. Mice were exposed to either single or five ovalbumin challenges over 5 days. In both protocols, time-dependent increases in bronchoalveolar lavage (BAL) cellular fibronectin, neutrophils and eosinophils were observed. The kinetics of these events were similar in both protocols; however, the magnitude of the response was much greater following repeated challenges. BAL protein levels and lymphocyte numbers were increased only following repeated challenges, whereas interleukin (IL)-5 and IL-4 were increased in both protocols. Histological analysis revealed a time-dependent increase in epithelial cell proliferation and in mucus-producing epithelial cells. Proliferation of alveolar cells was observed only following repeated challenges. Airway hyperreactivity was observed in both protocols but was much greater following repeated challenges. Pretreatment with dexamethasone fully inhibited the inflammatory response and airway hyperreactivity but only partially inhibited the remodeling process. These data suggest that glucocorticoids, although potent anti-inflammatory agents, may not be potent in reducing the lung remodeling process associated with asthma.
Animals↗
Presence and bronchomotor activity of protease-activated receptor-2 in guinea pig airways.
The protease activated receptor-2 (PAR-2) belongs to a family of G-protein-coupled receptors that are activated by proteolysis. Trypsin cleaves PAR-2, exposing an N-terminal tethered ligand (SLIGRL) that activates the receptor. Messenger RNA (mRNA) for PAR-2 was found in guinea pig airway tissue by reverse transcription-polymerase chain reaction, and PAR-2 was found by immunohistochemistry in airway epithelial and smooth-muscle cells. In anesthetized guinea pigs, trypsin and SLIGRL-NH(2) (given intratracheally or intravenously) caused a bronchoconstriction that was inhibited by the combination of tachykinin-NK(1) and -NK(2) receptor antagonists and was potentiated by inhibition of nitric oxide synthase (NOS). Trypsin and SLIGRL-NH(2) relaxed isolated trachea and main bronchi, and contracted intrapulmonary bronchi. Relaxation of main bronchi was abolished or reversed to contraction by removal of epithelium, administration of indomethacin, and NOS inhibition. PAR-1, PAR-3, and PAR-4 were not involved in the bronchomotor action of either trypsin or SLIGRL-NH(2), because ligands of these receptors were inactive either in vitro or in vivo, and because thrombin (a PAR-1 and PAR-3 agonist) did not show cross-desensitization with PAR-2 agonists in vivo. Thus, we have localized PAR-2 to the guinea-pig airways, and have shown that activation of PAR-2 causes multiple motor effects in these airways, including in vivo bronchoconstriction, which is in part mediated by a neural mechanism.
Airway Resistance↗
Re: Management of Parkinson's disease: a review of current and new therapies. Tilak Mendis, Oksana Suchowersky, Anthony Lang, Serge Gauthier. Can J Neurol Sci 1999;26:89-103.
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Globus Pallidus↗
Anti-apoptotic activity of p53 maps to the COOH-terminal domain and is retained in a highly oncogenic natural mutant.
The tumour suppressor p53 plays a complex role in the regulation of apoptosis. High levels of wild type p53 potentiate the apoptotic response, while physiological range, low levels of the protein have an anti-apoptotic activity in serum starved immortalized fibroblasts. Here we report that primary fibroblast-like cells that show normal growth control are also efficiently protected from apoptosis by the endogenous p53 activity. The capacity to inhibit apoptosis is not restricted to the wild type protein: the R-->H175 p53 mutant fully retains the anti-apoptotic activity of the wild type p53, providing a possible explanation for its high oncogenicity. Using a series of point and deletion mutants of p53 under the control of tetracycline-regulated promoter we show that certain mutants, like the wild type, protect cells at low levels but lead to apoptosis when overexpressed. This latter effect is lost upon deletion of a proline-rich domain in the NH2 part of the protein. The anti-apoptotic activity can be mapped to the extreme carboxy-terminal part of the protein and is therefore independent of other well characterized p53 activities. Our results add a new level of complexity to the network of interactions mediated by p53 in normal physiology and pathology.
Animals↗
Functional anatomy of the avian centrifugal visual system.
Although first described over a century ago, the centrifugal visual system (CVS) projecting to the retina still remains somewhat of an enigma with regard to its functional role in visually-guided behavior. The highly developed avian CVS has been the most extensively investigated and the anatomical organization of its two component centrifugal structures, the n. isthmo-opticus (NIO) and ectopic neurons (EN), including its afferent brainstem projections is reviewed. The results of double-labeling studies combining axonal tracing techniques and immunohistofluorescence have demonstrated GABA immunoreactivity (-ir) of interneurons within the neuropilar zone of the NIO, choline acetyltransferase (ChAT)-ir and nitric oxide synthase (NOS)-ir in the centrifugal cells of the NIO and EN as well as in the afferent projection neurons of layers 9/10 of the optic tectum. The data are discussed in terms of neurochemical and excitatory/inhibitory mechanisms within the different components of the avian CVS in relation to hypotheses which have implicated this system in visual attention and ground-feeding behavior.
Animals↗
Severe exacerbation of systemic lupus erythematosus after hepatitis B vaccination and importance of pneumococcal vaccination in patients with autosplenectomy: comment on the article by Battafarano et al.
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Bacterial Vaccines↗
Reactivities to serotonin and histamine in umbilical and placental vessels during the third trimester after normotensive pregnancies and pregnancies complicated by preeclampsia.
OBJECTIVE: The aim of the study was to evaluate responses of umbilical and placental arteries and veins to serotonin and histamine after normotensive pregnancies and pregnancies complicated by preeclampsia. STUDY DESIGN: Each pair of placentas from a normotensive woman and a woman with preeclampsia was matched for gestational age. Rings of these vessels were prepared and mounted in tissue baths under their respective optimal passive tension. Cumulative concentration-response curves to serotonin and histamine were measured. RESULTS: Responses to serotonin were decreased in umbilical vessels from the preeclampsia group with respect to the normotensive group. This is reflected by reduced maximum responses and sensitivity (negative logarithm of the 50% effective concentration) to serotonin. Maximum response to serotonin was significantly decreased in placental vein rings from the preeclampsia group. We recorded a decreased maximal response to histamine in placental vein rings from pregnancies complicated by preeclampsia with respect to those from normal pregnancies. Among normotensive women there was a significant positive linear relationship between neonatal weight and sensitivity to serotonin in umbilical and placental veins. This relationship was totally absent in preeclampsia. Sensitivity to histamine was linearly related to neonatal weight in umbilical vessels of the pooled results of both experimental groups. CONCLUSION: The vasoconstrictive effects of serotonin, but not those of histamine, are decreased in umbilical and placental vessels after preeclampsia. Sensitivities to serotonin and histamine change in umbilicoplacental vessels during the third trimester. Altered reactivity to serotonin may play a significant role in the reduction of umbilicoplacental blood flow in preeclampsia.
Dose-Response Relationship, Drug↗