Chronic Stress in Early Development and Effects on Traumatic Brain Injury Outcome.

In recent years, significant advances have been made in the study of mild traumatic brain injury (mTBI). Complete recovery from mTBI normally requires days to weeks, yet a subset of the population suffers from symptoms for weeks to months after injury. The risk factors for these prolonged symptoms have not yet been fully understood.

Improvement in edema and cognitive recovery after moderate traumatic brain injury with the neurosteroid prodrug NTS-104.

Neuroactive steroids reduce mortality, decrease edema, and improve functional outcomes in preclinical and clinical traumatic brain injury (TBI) studies. In this study, we tested the efficacy of two related novel neuroactive steroids, NTS-104 and NTS-105, in a rat model of TBI. NTS-104 is a water-soluble prodrug of NTS-105, a partial progesterone receptor agonist.

P2RY1/ALK3-Expressing Cells within the Adult Human Exocrine Pancreas Are BMP-7 Expandable and Exhibit Progenitor-like Characteristics.

Treatment of human pancreatic non-endocrine tissue with Bone Morphogenetic Protein 7 (BMP-7) leads to the formation of glucose-responsive β-like cells. Here, we show that BMP-7 acts on extrainsular cells expressing PDX1 and the BMP receptor activin-like kinase 3 (ALK3/BMPR1A). In vitro lineage tracing indicates that ALK3 cell populations are multipotent.

A novel PDE1A coupled to M2AChR at plasma membranes from bovine tracheal smooth muscle.

Muscarinic antagonists, via muscarinic receptors increase the cAMP/cGMP levels at bovine tracheal smooth muscle (BTSM) through the inhibition of phosphodiesterases (PDEs), displaying a similar behavior of vinpocetine (a specific-PDE1 inhibitor). The presence of PDE1 hydrolyzing both cyclic nucleotides in BTSM strips was revealed. Moreover, a vinpocetine and muscarinic antagonists inhibited PDE1 located at plasma membranes (PM) fractions from BTSM showing such inhibition, an M(2)AChR pharmacological profile.

M2 Muscarinic acetylcholine receptor modulates rat airway smooth muscle cell proliferation.

Airways chronic inflammatory conditions in asthma and COPD are characterized by tissue remodeling, being smooth muscle hyperplasia, the most important feature. Non-neuronal and neuronal Acetylcholine acting on muscarinic receptors (MAChRs) has been postulated as determinant of tissue remodeling in asthma and COPD by promoting proliferation and phenotypic changes of airway smooth muscle cells (ASMC). The objective was to evaluate proliferative responses to muscarinic agonist as carbamylcholine (Cch) and to identify the MAchR subtype involved.

Soluble guanylyl cyclase is reduced in airway smooth muscle cells from a murine model of allergic asthma.

Airway remodeling plays an important role in the development of airway hyperresponsiveness in asthma. Muscarinic agonists such as carbamylcholine increased cyclic GMP (cGMP) levels in bovine tracheal smooth muscle strips, via stimulation of NO-sensitive soluble guanylylcyclase (NO-sGC), which is an enzyme highly expressed in the lungs. cGMP production, by activation of a NO-sGC, may contribute to airway smooth muscle relaxation.

Muscarinic agonists acting through M2 acetylcholine receptors stimulate the migration of an NO-sensitive guanylyl cyclase to the plasma membrane of bovine tracheal smooth muscle.

Muscarinic agonists acting on bovine tracheal smooth muscle (BTSM) induce two separate cGMP signals, one at 20 sec associated with NO-sensitive-soluble-guanylyl-cyclase (NO-sGC) and another at 60 sec, linked to natriuretic-peptide-GC. The 20-sec-cGMP novel cascade starts with mAChRs, via unknown components, activates an NO-sGC. To unravel this cascade, in crude membranes isolated from intact BTSM strips exposed to muscarinic agonists, we detected GC activities increments at 20 sec and 60 sec.