Realising the therapeutic potential of neuroactive steroid modulators of the GABA_A receptor

In the 1980s particular endogenous metabolites of progesterone and of deoxycorticosterone were revealed to be potent, efficacious, positive allosteric modulators (PAMs) of the GABAA receptor (GABAAR). These reports were followed by the discovery that such steroids may be synthesised not only in peripheral endocrine glands, but locally in the central nervous system (CNS), to potentially act as paracrine, or autocrine "neurosteroid" messengers, thereby fine tuning neuronal inhibition. These discoveries triggered enthusiasm to elucidate the physiological role of such neurosteroids and explore whether their levels may be perturbed in particular psychiatric and neurological disorders. In preclinical studies the GABAAR-active steroids were shown to exhibit anxiolytic, anticonvulsant, analgesic and sedative properties and at relatively high doses to induce a state of general anaesthesia. Collectively, these findings encouraged efforts to investigate the therapeutic potential of neurosteroids and related synthetic analogues. However, following over 30 years of investigation, realising their possible medical potential has proved challenging. The recent FDA approval for the natural neurosteroid allopregnanolone (brexanolone) to treat postpartum depression (PPD) should trigger renewed enthusiasm for neurosteroid research. Here we focus on the influence of neuroactive steroids on GABA-ergic signalling and on the challenges faced in developing such steroids as anaesthetics, sedatives, analgesics, anticonvulsants, antidepressants and as treatments for neurodegenerative disorders

Alien Registration- Foster, Delia J. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/23187/thumbnail.jp

Alien Registration- Foster, Delia J. (Portland, Cumberland County)

https://digitalmaine.com/alien_docs/23187/thumbnail.jp

Food safety: Reducing and managing food scares

A series of high-profile food-related scares around the globe has drawn attention to the issue of food safety and other health risks associated with agriculture. Because the scope of the problem is different at different levels of economic development, we need nuanced policy options to promote safer food production systems worldwide

Variational derivation of two-component Camassa-Holm shallow water system

By a variational approach in the Lagrangian formalism, we derive the nonlinear integrable two-component Camassa-Holm system (1). We show that the two-component Camassa-Holm system (1) with the plus sign arises as an approximation to the Euler equations of hydrodynamics for propagation of irrotational shallow water waves over a flat bed. The Lagrangian used in the variational derivation is not a metric.Comment: to appear in Appl. Ana

Livestock epidemic

The Handbook provides a comprehensive statement and reference point for hazard and disaster research, policy making, and practice in an international and multi-disciplinary context. It offers critical reviews and appraisals of current state of the art and future development of conceptual, theoretical and practical approaches as well as empirical knowledge and available tools. Organised into five inter-related sections, this Handbook contains sixty-five contributions from leading scholars. Section One situates hazards and disasters in their broad political, cultural, economic, and environmental context. Section Two contains treatments of potentially damaging natural events/phenomena organized by major earth system. Section Three critically reviews progress in responding to disasters including warning, relief and recovery. Section Four addresses mitigation of potential loss and prevention of disasters under two sub-headings: governance, advocacy and self-help, and communication and participation. Section Five ends with a concluding chapter by the editors