The Future of CMC Regulatory Submissions: Streamlining Activities Using Structured Content and Data Management.

Recent advancements in data engineering, data science, and secure cloud storage can transform the current state of global Chemistry, Manufacturing, and Controls (CMC) regulatory activities to automated online digital processes. Modernizing regulatory activities will facilitate simultaneous global submissions and concurrent collaborative reviews, significantly reducing global licensing timelines and variability in globally registered product details. This article describes advancements made within the pharmaceutical industry from theoretical concepts to utilization of structured content and data in CMC submissions.

MdmX inhibits Smad transactivation.

Mdm2 overexpression confers a growth promoting activity upon cells primarily by downregulating the p53 tumor suppressor protein. Nevertheless, Mdm2 deregulation has also been implicated in inhibiting TGF-beta growth repression in a p53 independent manner. Our goal in this study was to examine whether overexpression of Mdm2 or MdmX, a Mdm2-related protein, could affect Smad-induced transactivation.

Bacterial endotoxin induces fos immunoreactivity in primary afferent neurons of the vagus nerve.

Subdiaphragmatic vagotomy inhibits brain-mediated illness responses to peripherally administered bacterial endotoxin, including fever, hyperalgesia, sickness behavior, and activation of the hypothalamic-pituitary-adrenal axis. However, direct evidence implicating vagal afferents specifically in conveying information about peripheral immune activation to the brain is still lacking. This study assessed whether (1) endotoxin induces the expression of the functional activation marker Fos in the vagal sensory ganglia, and (2) vagotomy abrogates endotoxin-induced Fos expression in these ganglia.

Thermogenic and corticosterone responses to intravenous cytokines (IL-1beta and TNF-alpha) are attenuated by subdiaphragmatic vagotomy.

The brain orchestrates changes in behavior and physiology as a consequence of peripheral immune activation and infection. These changes require that the brain receives signals from the periphery that an immunological challenge has occurred. Previous research has established that cytokines play a role in signalling the brain.

Neurocircuitry of conditioned inhibition of analgesia: effects of amygdala, dorsal raphe, ventral medullary, and spinal cord lesions on antianalgesia in the rat.

Pain inhibition (analgesia) is produced by learned danger signals and inhibited by learned safety signals (antianalgesia). Conditioned analgesia is mediated by brain-to-spinal pathways releasing spinal endogenous opiates. Spinal morphine mimics learned danger signals in producing analgesia, which is inhibited by antianalgesia.