Blocking α2δ-1 Subunit Reduces Bladder Hypersensitivity and Inflammation in a Cystitis Mouse Model by Decreasing NF-kB Pathway Activation

Bladder pain is frequently associated with bladder inflammation, as in conditions like interstitial cystitis (IC), for which current analgesic therapies have limited efficacy. The antinociceptive effect of alpha-2-delta (α2δ) ligands on inflammation-associated visceral pain like that experienced in cystitis has been poorly investigated. To investigate the effect of pregabalin (PGB), an α2δ ligand, we evaluated its impact on mechanical hyperalgesia in a mouse model of cystitis induced by cyclophosphamide (CYP). We further studied its effect on inflammation and NF-kB pathway activation. Acute cystitis was induced by intraperitoneal injection of 150 mg kg-1 of CYP in C57Bl/6J male mice. PGB was subcutaneously injected (30 mg kg-1) 3 h after CYP injection. The effect of PGB on CYP-induced mechanical referred hyperalgesia (abdominal Von Frey test), inflammation (organ weight, cytokine production, α2δ subunit level, NF-kB pathway activation) were assessed 1 h after its injection. In parallel, its effect on cytokine production, α2δ subunit level and NF-kB pathway activation was assessed in vitro on peritoneal exudate cells (PECs) stimulated with LPS. PGB treatment decreased mechanical referred hyperalgesia. Interestingly, it had an anti-inflammatory effect in the cystitis model by reducing pro-inflammatory cytokine production. PGB also inhibited NF-kB pathway activation in the cystitis model and in macrophages stimulated with LPS, in which it blocked the increase in intracellular calcium. This study shows the efficacy of PGB in hypersensitivity and inflammation associated with cystitis. It is therefore of great interest in assessing the benefit of α2δ ligands in patients suffering from cystitis

Socializing One Health: an innovative strategy to investigate social and behavioral risks of emerging viral threats

In an effort to strengthen global capacity to prevent, detect, and control infectious diseases in animals and people, the United States Agency for International Development’s (USAID) Emerging Pandemic Threats (EPT) PREDICT project funded development of regional, national, and local One Health capacities for early disease detection, rapid response, disease control, and risk reduction. From the outset, the EPT approach was inclusive of social science research methods designed to understand the contexts and behaviors of communities living and working at human-animal-environment interfaces considered high-risk for virus emergence. Using qualitative and quantitative approaches, PREDICT behavioral research aimed to identify and assess a range of socio-cultural behaviors that could be influential in zoonotic disease emergence, amplification, and transmission. This broad approach to behavioral risk characterization enabled us to identify and characterize human activities that could be linked to the transmission dynamics of new and emerging viruses. This paper provides a discussion of implementation of a social science approach within a zoonotic surveillance framework. We conducted in-depth ethnographic interviews and focus groups to better understand the individual- and community-level knowledge, attitudes, and practices that potentially put participants at risk for zoonotic disease transmission from the animals they live and work with, across 6 interface domains. When we asked highly-exposed individuals (ie. bushmeat hunters, wildlife or guano farmers) about the risk they perceived in their occupational activities, most did not perceive it to be risky, whether because it was normalized by years (or generations) of doing such an activity, or due to lack of information about potential risks. Integrating the social sciences allows investigations of the specific human activities that are hypothesized to drive disease emergence, amplification, and transmission, in order to better substantiate behavioral disease drivers, along with the social dimensions of infection and transmission dynamics. Understanding these dynamics is critical to achieving health security--the protection from threats to health-- which requires investments in both collective and individual health security. Involving behavioral sciences into zoonotic disease surveillance allowed us to push toward fuller community integration and engagement and toward dialogue and implementation of recommendations for disease prevention and improved health security

Etudes de la liberation du GP87 (secretogranine II) par les cellules hypophysaires de rat in vitro

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 82811 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Closed-loop control of nervous response

International audienc

Quantitative determination of the gonadotrope polypeptide (GP87) contained in and release by gonadotrope cells using a specific anti-rat GP87

A polyclonel antibody has been reised against the gonadotrope polypeptide (GP87), a secretogranin II form released by rat gonadotrope cells under LHRH stimulation. GP87 was previously isolated through bidirectional polyacrylamide gel electrophoresis followed by electrotransfer onto nitrocellulose membrane. Using this antibody, it could be shown by immunoelectron microscopy that GP87 was localised in the secretory granules of several restricted cell types. A specific quantitative immunoassay was then devised to determine the cell content of GP87 or its release into culture medium. This assay involved an SDS-polyacrylamide gel electrophoresis of proteins followed by western blotting with anti-GP87 and densitometry of the nitrocellulose membrane. Combining this assay with preliminary separation of cell populations by centrifugal elutriation, it was demonstrated that GP87 is highly concentrated in gonadotropes. Moreover, the LHRH-stimulated minute-to-minute release of GP87 by rat pituitary cell aggregates in perifusion xas shown to be closely correlated to that of LH especially in its biphasic pattern. This anti-rat GP87 thus appears highly suitable to analyse the intracel1ular compartmentation ofsecretogranin II/GP87 and putative modification processes preceding or following LHRH-induced exocytosis

Quantitative determination of the gonadotrope polypeptide (GP87) contained in and release by gonadotrope cells using a specific anti-rat GP87

A polyclonel antibody has been reised against the gonadotrope polypeptide (GP87), a secretogranin II form released by rat gonadotrope cells under LHRH stimulation. GP87 was previously isolated through bidirectional polyacrylamide gel electrophoresis followed by electrotransfer onto nitrocellulose membrane. Using this antibody, it could be shown by immunoelectron microscopy that GP87 was localised in the secretory granules of several restricted cell types. A specific quantitative immunoassay was then devised to determine the cell content of GP87 or its release into culture medium. This assay involved an SDS-polyacrylamide gel electrophoresis of proteins followed by western blotting with anti-GP87 and densitometry of the nitrocellulose membrane. Combining this assay with preliminary separation of cell populations by centrifugal elutriation, it was demonstrated that GP87 is highly concentrated in gonadotropes. Moreover, the LHRH-stimulated minute-to-minute release of GP87 by rat pituitary cell aggregates in perifusion xas shown to be closely correlated to that of LH especially in its biphasic pattern. This anti-rat GP87 thus appears highly suitable to analyse the intracel1ular compartmentation ofsecretogranin II/GP87 and putative modification processes preceding or following LHRH-induced exocytosis

Quantitative determination of the gonadotrope polypeptide (GP87) contained in and release by gonadotrope cells using a specific anti-rat GP87

A polyclonel antibody has been reised against the gonadotrope polypeptide (GP87), a secretogranin II form released by rat gonadotrope cells under LHRH stimulation. GP87 was previously isolated through bidirectional polyacrylamide gel electrophoresis followed by electrotransfer onto nitrocellulose membrane. Using this antibody, it could be shown by immunoelectron microscopy that GP87 was localised in the secretory granules of several restricted cell types. A specific quantitative immunoassay was then devised to determine the cell content of GP87 or its release into culture medium. This assay involved an SDS-polyacrylamide gel electrophoresis of proteins followed by western blotting with anti-GP87 and densitometry of the nitrocellulose membrane. Combining this assay with preliminary separation of cell populations by centrifugal elutriation, it was demonstrated that GP87 is highly concentrated in gonadotropes. Moreover, the LHRH-stimulated minute-to-minute release of GP87 by rat pituitary cell aggregates in perifusion xas shown to be closely correlated to that of LH especially in its biphasic pattern. This anti-rat GP87 thus appears highly suitable to analyse the intracel1ular compartmentation ofsecretogranin II/GP87 and putative modification processes preceding or following LHRH-induced exocytosis

Quantitative determination of the gonadotrope polypeptide (GP87) contained in and release by gonadotrope cells using a specific anti-rat GP87

A polyclonel antibody has been reised against the gonadotrope polypeptide (GP87), a secretogranin II form released by rat gonadotrope cells under LHRH stimulation. GP87 was previously isolated through bidirectional polyacrylamide gel electrophoresis followed by electrotransfer onto nitrocellulose membrane. Using this antibody, it could be shown by immunoelectron microscopy that GP87 was localised in the secretory granules of several restricted cell types. A specific quantitative immunoassay was then devised to determine the cell content of GP87 or its release into culture medium. This assay involved an SDS-polyacrylamide gel electrophoresis of proteins followed by western blotting with anti-GP87 and densitometry of the nitrocellulose membrane. Combining this assay with preliminary separation of cell populations by centrifugal elutriation, it was demonstrated that GP87 is highly concentrated in gonadotropes. Moreover, the LHRH-stimulated minute-to-minute release of GP87 by rat pituitary cell aggregates in perifusion xas shown to be closely correlated to that of LH especially in its biphasic pattern. This anti-rat GP87 thus appears highly suitable to analyse the intracel1ular compartmentation of secretogranin II/GP87 and putative modification processes preceding or following LHRH-induced exocytosis

Activated caspases in thawed epididymal and testicular spermatozoa of patients with congenital bilateral absence of the vas deferens and intracytoplasmic sperm injection outcome

International audienc

Vitrification of human ovarian tissue: a practical and relevant alternative to slow freezing.

International audienceCryopreservation of ovarian tissue can be used to preserve the fertility of patients who are about to receive treatment(s) that could compromise their future ovarian function. Here we evaluate the effectiveness of a vitrification protocol by carrying out a systematic comparison with a conventional slow-freezing method on human ovarian tissue