Abstract Background Asthma and chronic obstructive pulmonary disease are characterized by inappropriate constriction of the airway smooth muscle. In this context, the physiological response of the ...human airways to selective relaxant agonists like PGE 2 is highly relevant. The aim of this study was thus to characterize the PGE 2 receptor subtypes (EP 2 or EP 4 ) involved in the relaxation of human bronchial preparations. Methods Human bronchial preparations cut as rings were mounted in organ baths for isometric recording of tension and a pharmacological study was performed using selective EP 2 or EP 4 ligands. Results In the presence of a thromboxane TP receptor antagonist and indomethacin, PGE 2 induced the relaxation of human bronchi (Emax = 86 ± 04% of papaverine response; pEC 50 value = 7.06 ± 0.13; n = 6). This bronchodilation was significantly blocked by a selective EP 4 receptor antagonist (GW627368X, 1 and 10 μmol/L) with a pK B value of 6.38 ± 0.19 ( n = 5). In addition, the selective EP 4 receptor agonists (ONO-AE1-329; L-902688), but not the selective EP 2 receptor agonist (ONO-AE1-259), induced potent relaxation of bronchial preparations pre-contracted with histamine or anti-IgE. Conclusion PGE 2 and EP 4 agonists induced potent relaxations of human bronchial preparations via EP 4 receptor. These observations suggest that EP 4 receptor agonists could constitute therapeutic agents to treat the increased airway resistance in asthma.
TEMPRANO was a multicentre, open-label trial in which human immunodeficiency virus (HIV) infected adults with high CD4 counts were randomised into early or deferred antiretroviral therapy (ART) arms ...with or without 6-month isoniazid preventive therapy (IPT) in a setting where the World Health Organization (WHO) recommends IPT in HIV-infected patients. Despite the WHO recommendation, IPT coverage remains low due to fear of the presence of undiagnosed active TB before prescribing IPT, and the related risk of drug resistance.
To report the frequency of undiagnosed TB in patients enrolled for IPT and describe the results of a 1-month buffer period to avoid prescribing IPT for active TB cases.
Patients were screened using a clinical algorithm and chest X-ray at Day 0 and started on isoniazid at Month 1 if no sign/symptom suggestive of TB appeared between Day 0 and Month 1.
Of 1030 patients randomised into IPT arms. 10% never started IPT at Month 1. Of these, 23 had active TB, including 16 with prevalent TB. Among the 927 patients who started IPT, 6 had active TB, including 1 with prevalent TB. Only 1 patient with active TB received IPT due to the 1-month buffer period between Day 0 and IPT initiation.
In this study, 1.6% of adults considered free of active TB based on clinical screening at pre-inclusion actually had active TB.
Avec 2,9 % de sa population infectée par le VIH, la Côte d’Ivoire fait partie des pays d’Afrique de l’Ouest les plus touchés par l’épidémie à VIH. On estime que seules 63 % des personnes infectées ...par le VIH connaissent leur statut. Une enquête transversale, par téléphone, a été réalisée auprès d’un échantillon représentatif de 3 867 personnes afin de décrire les pratiques et les facteurs associés à la réalisation récente (≤ 1 an) d’un dépistage du VIH en Côte d’Ivoire. Les données collectées concernaient le dernier test réalisé ainsi que les caractéristiques sociodémographiques, comportements sexuels, accès à l’information, perceptions, capacités, autonomies ainsi que l’environnement social et géographique des participants. Des modèles de régression logistique ont été réalisés afin d’identifier les facteurs associés à la réalisation récente d’un test du VIH (≤ 1 an). Le manque d’information est l’un des principaux freins au dépistage (seuls 60 % des individus connaissent un lieu où réaliser un test). Chez les hommes, malgré la gratuité du dépistage, une faible condition économique semble être un frein à la réalisation d’un test. L’environnement social, notamment l’influence des pairs, semble aussi avoir un effet sur le recours au dépistage chez les hommes. Chez les femmes, le dépistage est associé à leurs perceptions d’exposition au VIH. L’offre de dépistage actuelle en Côte d’Ivoire nécessite de repenser la communication autour du test ainsi que d’identifier des incitatifs économiques ou sociaux permettant de lever les freins au dépistage.
Human leukocyte antigen‐G (HLA‐G), a nonclassical HLA class I protein, promotes immune tolerance of solid‐organ allografts, yet its role in lung transplantation (LTx) is unknown. We examined the ...expression of HLA‐G in lung allografts through immunohistochemistry by a cross‐sectional study of 64 LTx recipients, classified into four groups (stable patients, acute rejection AR, bronchiolitis obliterans syndrome BOS and symptomatic viral shedders). A marked expression of HLA‐G in bronchial epithelial cells (BEC) was frequently observed in stable recipients (n = 18/35 51%), but not in patients with AR (n = 14) or with BOS (n = 8). HLA‐G was also expressed by 4 of 7 symptomatic viral shedders. In addition, HLA‐G‐positive patients from the stable group (n = 35) experienced lower incidence of resistant AR and/or BOS during long‐term follow‐up, as compared with their HLA‐G‐negative counterparts. Finally, in vitro data showed that interferon‐γ, a cytokine present in lung allograft microenvironment, upregulated HLA‐G mRNA and protein expression in primary cultured human BEC. We conclude that HLA‐G expression in the bronchial epithelium of lung allograft is elevated in some LTx recipients in association with their functional stability, suggesting a potential role of HLA‐G as a tolerance marker.
HLA‐G expression in the bronchial epithelium of lung allograft is elevated in some LTx recipients in association with their functional stability.
Cortinarius spp. poisoning is characterized by a delayed acute renal failure. The main features of this severe poisoning are still poorly known and often overlooked. The aim of this literature review ...is a better description of Cortinarius spp. poisoning.
The main medical databases were searched: Abstracts of Mycology, Current Contents, Medline, Pascal, Micromedex Poisindex, Toxicology abstracts, Toxline. All case reports that included a description of the clinical features of Cortinarius spp. poisoning were studied.
245 cases were collected and 90 cases could be analyzed in details. Gastrointestinal disorders are the main symptoms of the prerenal phase of the poisoning. They appear a few days after the ingestion of the mushrooms (median 3 days). The renal phase is delayed (median 8.5 days). Moderate and transient hepatic abnormalities have been reported. A severe hepatic failure can be ruled out. Muscular lesions are highly questionable. Treatment is supportive. No specific treatment can be recommended. Acute renal failure progressed towards chronic renal failure in half of the cases; intermittent hemodialysis or kidney transplantations were necessary in 70% of those cases.
Cortinarius spp. poisoning is severe. Ingestion of Cortinarius species must be systematically suspected whenever tubulo-interstitial nephritis is diagnosed, especially as mushrooms may have been ingested 1-2 weeks before.