Lab-Scale Permeability Enhancement by Chemical Treatment in Fractured Granite (Cornubian Batholith) for the United Downs Deep Geothermal Power Project, Cornwall (UK)

A hydrothermal doublet system was drilled in a fault-related granitic reservoir in Cornwall. It targets the Porthtowan Fault Zone (PTF), which transects the Carnmenellis granite, one of the onshore plutons of the Cornubian Batholith in SW England. At 5058 m depth (TVD, 5275 m MD) up to 190 °C were reached in the dedicated production well. The injection well is aligned vertically above the production well and reaches a depth of 2393 m MD. As part of the design process for potential chemical stimulation of the open-hole sections of the hydrothermal doublet, lab-scale acidification experiments were performed on outcrop analogue samples from the Cornubian Batholith, which include mineralised veins. The experimental setup comprised autoclave experiments on sample powder and plugs, and core flooding tests on sample plugs to investigate to what degree the permeability of natural and artificial (saw-cut) fractures can be enhanced. All samples were petrologically and petrophysically analysed before and after the acidification experiments to track all changes resulting from the acidification. Based on the comparison of the mineralogical composition of the OAS samples with the drill cuttings from the production well, the results can be transferred to the hydrothermally altered zones around the faults and fractures of the PTF. Core Flooding Tests and Autoclave Experiments result in permeability enhancement factors of 4 to >20 and 0.1 to 40, respectively. Mineral reprecipitation can be avoided in the stimulated samples by sufficient post-flushing.

Role of the Cholinergic Anti-Inflammatory Reflex in Central Nervous System Diseases

In several central nervous system diseases, it has been reported that inflammation may be related to the etiologic process, therefore, therapeutic strategies are being implemented to control inflammation. As the nervous system and the immune system maintain close bidirectional communication in physiological and pathological conditions, the modulation of inflammation through the cholinergic anti-inflammatory reflex has been proposed. In this review, we summarized the evidence supporting chemical stimulation with cholinergic agonists and vagus nerve stimulation as therapeutic strategies in the treatment of various central nervous system pathologies, and their effect on inflammation.

EFFECTS OF NEW PIPERIDINE DERIVATIVES WITH SUBSTITUTIONS IN THE 1ST AND 4TH POSITIONS IN NALOXONE SENSITIVE ANALGESY

Background. Despite the wide arsenal of painkillers, pain relief is an urgent interdisciplinary problem that requires a search for new solutions. Purpose of the study. To establish the role of opioid receptors in the mechanism of the analgesic action of the piperidine derivatives AGV-22 and AGV-23. Material and methods. The studies were carried out on 96 white mice of both sexes weighing 30-40 g. The analgesic effect of the compounds was tested on models of thermal and chemical irritation with preliminary administration of the opioid receptor antagonist naloxone. Results. The pain reactions of mice with models of thermal and chemical stimulation in the AGV-22 / AGV-23 + naloxone and AGV-22 / AGV-23 groups were comparable. Conclusions. The mechanism of the analgesic action of the piperidine derivatives AGV-22 and AGV-23 is not associated with the activation of opioid receptors.

Novel chemical stimulation for geothermal reservoirs by chelating agent driven selective mineral dissolution in fractured rocks

Improving geothermal systems through hydraulic stimulation to create highly permeable fractured rocks can induce seismicity. Therefore, the technique must be applied at a moderate intensity; this has led to concerns of insufficient permeability enhancement. Adding chemical stimulation can mitigate these issues, but traditional methods using strong mineral acids have challenges in terms of achieving mineral dissolution over long distances and highly variable fluid chemistry. Here, we demonstrate a novel chemical stimulation method for improving the permeability of rock fractures using a chelating agent that substantially enhances the dissolution rate of specific minerals to create voids that are sustained under crustal stress without the challenges associated with the traditional methods. Applying this agent to fractured granite samples under confining stress at 200 °C in conjunction with 20 wt% aqueous solutions of sodium salts of environmentally friendly chelating agents (N-(2-hydroxyethyl)ethylenediamine-N, N′, N′-triacetic acid and N, N-bis(carboxymethyl)-l-glutamic acid) at pH 4 was assessed. A significant permeability enhancement of up to approximately sixfold was observed within 2 h, primarily due to the formation of voids based on the selective dissolution of biotite. These results demonstrate a new approach for chemical stimulation.

Chemical Stimulation of Rodent and Human Cortical Synaptosomes: Implications in Neurodegeneration

Synaptic plasticity events, including long-term potentiation (LTP), are often regarded as correlates of brain functions of memory and cognition. One of the central players in these plasticity-related phenomena is the α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR). Increased levels of AMPARs on postsynaptic membranes thus constitute a biochemical measure of LTP. Isolated synaptic terminals (synaptosomes) are an excellent ex vivo tool to monitor synaptic physiology in healthy and diseased brains, particularly in human research. We herein describe three protocols for chemically-induced LTP (cLTP) in synaptosomes from both rodent and human brain tissues. Two of these chemical stimulation protocols are described for the first time in synaptosomes. A pharmacological block of synaptosomal actin dynamics confirmed the efficiency of the cLTP protocols. Furthermore, the study prototypically evaluated the deficiency of cLTP in cortical synaptosomes obtained from human cases of early-onset Alzheimer’s disease (EOAD) and frontotemporal lobar degeneration (FLTD), as well as an animal model that mimics FLTD.

Visualization of trigeminal ganglion sensory neuronal signaling regulated by Cdk5

The mechanisms underlying facial and oral pain are still incompletely understood, posing major therapeutic challenges. Cyclin-dependent kinase 5 (Cdk5) is a key neuronal kinase involved in pain signaling. However, the regulatory roles of Cdk5 in orofacial pain signaling and the possibility of therapeutic intervention at the level of mouse trigeminal ganglion primary neurons remain elusive. In this study, we used optimized intravital imaging to directly compare trigeminal neuronal activities after mechanical, thermal, and chemical stimulation. We then tested whether facial inflammatory pain in mice could be alleviated by the Cdk5 inhibitor peptide TFP5. We demonstrated regulation of total Ca2+ intensities by Cdk5 activity using transgenic and knockout mouse models. In mice with orofacial inflammation, application of TFP5 specifically decreased total Ca2+ intensities in response to noxious stimuli. It also alleviated inflammation-induced allodynia by inhibiting activation of trigeminal peripheral sensory neurons. Cdk5 inhibitors may provide promising non-opioid candidates for pain treatment.