Latest Insights into the In Vivo Studies in Murine Regarding the Role of TRP Channels in Wound Healing-A Review.

Wound healing involves physical, chemical and immunological processes. Transient receptor potential (TRP) and other ion channels are implicated in epidermal re-epithelization. Ion movement across ion channels can induce transmembrane potential that leads to transepithelial potential (TEP) changes. TEP is present in epidermis surrounding the lesion decreases and induces an endogenous direct current generating an epithelial electric field (EF) that could be implicated in wound re-epithelialization. TRP channels are involved in the activation of immune cells during mainly the inflammatory phase of wound healing. The aim of the study was to review the mechanisms of ion channel involvement in wound healing in in vivo experiments in murine (mice, rats) and how can this process be influenced. This review used the latest results published in scientific journals over the last year and this year to date (1 January 2023-31 December 3000) in order to include the in-press articles. Some types of TRP channels, such as TRPV1, TRPV3 and TRPA1, are expressed in immune cells and can be activated by inflammatory mediators. The most beneficial effects in wound healing are produced using agonists of TRPV1, TRPV4 and TRPA1 channels or by inhibiting with antagonists, antisense oligonucleotides or knocking down TRPV3 and TRPM8 channels.

Anti-Psoriasis Effect of Diclofenac and Celecoxib Using the Tail Model for Psoriasis.

Non-steroidal anti-inflammatory drugs (NSAIDs) showed effects in some hyperproliferative dermatologic pathologies. The aim of the study is the assessment of anti-psoriasis effect of diclofenac and celecoxib using a mice tail model. The topical application of substances on the proximal mice tails was performed for two weeks. The effects on the epidermal granular layer and mean epidermal thickness (excluding the stratum corneum) were evaluated using hematoxylin-eosin staining. Orthokeratosis degree and percentual drug activity were calculated. A positive control group treated with tretinoin and two negative controls (white soft paraffin and untreated mice) were used. Orthokeratosis degree significantly increased in all the NSAIDs groups (celecoxib 1%, 2% and diclofenac 1%, 2%) and in the tretinoin 0.05% group, versus negative controls. Celecoxib 1% and 2%, tretinoin 0.05% and white soft paraffin significantly increased mean epidermal thickness, versus untreated mice. The values obtained in the case of celecoxib 2% ointment regarding the orthokeratosis degree and percentual drug activity are providing premises for further investigations regarding this effect and the mechanisms of action involved. Celecoxib 2% had the greatest percentual drug activity and is a promising substance for the anti-psoriasis topical treatment. Along with the COX-2 inhibition, celecoxib might have an anti-psoriasis effect by other independent mechanisms.

Topological Defect Engineering and PT Symmetry in Non-Hermitian Electrical Circuits.

We employ electric circuit networks to study topological states of matter in non-Hermitian systems enriched by parity-time symmetry PT and chiral symmetry anti-PT (APT). The topological structure manifests itself in the complex admittance bands which yields excellent measurability and signal to noise ratio. We analyze the impact of PT-symmetric gain and loss on localized edge and defect states in a non-Hermitian Su-Schrieffer-Heeger (SSH) circuit. We realize all three symmetry phases of the system, including the APT-symmetric regime that occurs at large gain and loss. We measure the admittance spectrum and eigenstates for arbitrary boundary conditions, which allows us to resolve not only topological edge states, but also a novel PT-symmetric Z_{2} invariant of the bulk. We discover the distinct properties of topological edge states and defect states in the phase diagram. In the regime that is not PT symmetric, the topological defect state disappears and only reemerges when APT symmetry is reached, while the topological edge states always prevail and only experience a shift in eigenvalue. Our findings unveil a future route for topological defect engineering and tuning in non-Hermitian systems of arbitrary dimension.

A Systematic Review of Clinical Studies on the Effect of Psychoactive Cannabinoids in Psychiatric Conditions in Alzheimer Dementia.

BACKGROUND: The systematic reviews and meta-analyses performed until now did not provide the adequate picture of actual knowledge in the field of neuropsychiatric symptoms treatment using psychotropic cannabinoids in patients with Alzheimer disease (AD). THE STUDY QUESTION: Which is the level of evidence, from quantitative and qualitative point of view, concerning the efficacy and safety of the treatment with psychotropic cannabinoids of neuropsychiatric symptoms in AD? STUDY DESIGN: PubMed, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar Data, and Clinicaltrials.gov were searched for randomized clinical trials with cannabinoids in Alzheimer dementia agitation and aggression. MEASURES AND OUTCOMES: The rationale, the objectives, and the methods used for searching the trials have been established according to PRISMA Criteria 2009. RESULTS: The total number of patients in the 9 publications evaluated in this study, which included data from 6 clinical trials, was 422 patients-treatments, where treatment was a psychoactive cannabinoid or placebo, some of them obtained by multiplying selected patients with the number of cannabinoid treatments in the crossover studies. There are multiple sources of bias in the analyzed studies; 2 elements have prevented conclusive results. One element was polypragmazia, a major role being played by the use of psychotropic drugs other than cannabinoids, in an effort to reduce agitation and aggressive behavior. The second one was the large number of concomitant symptoms, for example, pain (commonly causing anxiety and agitation). CONCLUSIONS: No clear conclusion can be drawn on the effectiveness of psychoactive cannabinoids in the treatment of psychiatric manifestations, in particular agitation and aggression, in AD. In the future, large randomized controlled trial with adequate designs, without crossover and for longer duration, adapted to cannabinoid pharmacokinetics, is required to establish the real efficacy and safety of these drugs in aggressive and/or agitated patients with AD.

Antidepressant effect of the interaction of fluoxetine with granisetron.

Selective serotonin reuptake inhibitors (SSRIs) may produce digestive side effects such as nausea and vomiting, diarrhoea and decreased appetite. These side effects are determined by the increase in serotonin availability at 5-HT3 receptors. Granisetron, a serotonin 5-HT3 receptor antagonist, is expected to antagonize the digestive adverse effects of serotonin reuptake inhibitors, but the question is to what extent granisetron influences the antidepressant effect of these substances. The aim of this study was to determine the dose of fluoxetine that has an antidepressant effect in the Porsolt test, and the interaction between fluoxetine and granisetron with respect to the antidepressant effect in this test. In experiment 1, fluoxetine was antidepressant only at 20 mg/kg body weight (bw). In experiment 2, granisetron 1 mg/kg bw had a statistically significant antidepressant effect vs. control. Fluoxetine 20 mg/kg bw associated with a small dose of granisetron (0.1 mg/kg bw) produced a significant antidepressant effect vs. control. This shows that low doses of granisetron associated to fluoxetine might produce a significant antidepressant effect, suggesting a potentiation between these two drugs used in sub-effective antidepressant doses. In conclusion, in our experimental conditions, we can assume that granisetron in low doses could be used to combat intestinal transit disorders produced by SSRI antidepressants. These low doses are preferred, because they increase the antidepressant effect of these SSRIs.

Topological Phases without Crystalline Counterparts.

We construct a two-dimensional higher-order topological phase protected by a quasicrystalline eightfold rotation symmetry. Our tight-binding model describes a superconductor on the Ammann-Beenker tiling hosting localized Majorana zero modes at the corners of an octagonal sample. In order to analyze this model, we introduce Hamiltonians generated by a local rule, and use this concept to identify the bulk topological properties. We find a Z_{2} bulk topological invariant protecting the corner modes. Our work establishes that there exist topological phases protected by symmetries impossible in a crystal.

Visualization of an axion insulating state at the transition between 2 chiral quantum anomalous Hall states.

Quantum-relativistic materials often host electronic phenomena with exotic spatial distributions. In particular, quantum anomalous Hall (QAH) insulators feature topological boundary currents whose chirality is determined by the magnetization orientation. However, understanding the microscopic nature of edge vs. bulk currents has remained a challenge due to the emergence of multidomain states at the phase transitions. Here we use microwave impedance microscopy (MIM) to directly image chiral edge currents and phase transitions in a magnetic topological insulator. Our images reveal a dramatic change in the edge state structure and an unexpected microwave response at the topological phase transition between the Chern number [Formula: see text] and [Formula: see text] states, consistent with the emergence of an insulating [Formula: see text] state. The magnetic transition width is independent of film thickness, but the transition pattern is distinct in differently initiated field sweeps. This behavior suggests that the [Formula: see text] state has 2 surface states with Hall conductivities of [Formula: see text] but with opposite signs.

The histaminergic control of the iridal vascular tone in rats and its influencing by topical administration of olopatadine and ranitidine.

Objective. We evaluated the histamine's role in regulating the iris vasomotricity in rats, using as a research tool topical olopatadine, a selective H1 blocker, which is indicated for the treatment of allergic conjunctivitis and ranitidine, a selective H2 blocker mainly used for the treatment of peptic ulcer disease. Methods. Two groups of six Wistar rats anesthetized with ketamine 200 mg/kg body weight were used. They received distilled water in conjunctival instillations, initially and after 5 minutes, olopatadine 2.5 mmol/ l for the first group, respectively ranitidine 2.5 mmol/ l for the second group. The changes of the iris arteriolar and venular diameters were recorded. Results. Both olopatadine and ranitidine produced statistically significant iridal arteriolar vasoconstriction and ranitidine determined statistically significant venuloconstriction, while distilled water did not produce any statistically significant effect. Conclusions. There is a vasodilator histaminergic tone exerted through the histaminergic H1 and H2 receptors in the iris arterioles and, respectively, through the H2 receptors in the iridal venules. Olopatadine, a topical H1 antagonist used in the treatment of ocular allergies, may interfere with the humoral regulation of the iris arteriolar tone. Ranitidine, an H2 antagonist, decreased the diameter of the iris arterioles and venules, when administered topically in rats.

Partial Lattice Defects in Higher-Order Topological Insulators.

Nonzero weak topological indices are thought to be a necessary condition to bind a single helical mode to lattice dislocations. In this work we show that higher-order topological insulators (HOTIs) can, in fact, host a single helical mode along screw or edge dislocations (including step edges) in the absence of weak topological indices. When this occurs, the helical mode is necessarily bound to a dislocation characterized by a fractional Burgers vector, macroscopically detected by the existence of a stacking fault. The robustness of a helical mode on a partial defect is demonstrated by an adiabatic transformation that restores translation symmetry in the stacking fault. We present two examples of HOTIs, one intrinsic and one extrinsic, that show helical modes at partial dislocations. Since partial defects and stacking faults are commonplace in bulk crystals, the existence of such helical modes can measurably affect the expected conductivity in these materials.

Observation of Electron Coherence and Fabry-Perot Standing Waves at a Graphene Edge.

Electron surface states in solids are typically confined to the outermost atomic layers and, due to surface disorder, have negligible impact on electronic transport. Here, we demonstrate a very different behavior for surface states in graphene. We probe the wavelike character of these states by Fabry-Perot (FP) interferometry and find that, in contrast to theoretical predictions, these states can propagate ballistically over micron-scale distances. This is achieved by embedding a graphene resonator formed by gate-defined p-n junctions within a graphene superconductor-normal-superconductor structure. By combining superconducting Aharanov-Bohm interferometry with Fourier methods, we visualize spatially resolved current flow and image FP resonances due to p-n-p cavity modes. The coherence of the standing-wave edge states is revealed by observing a new family of FP resonances, which coexist with the bulk resonances. The edge resonances have periodicity distinct from that of the bulk states manifest in a repeated spatial redistribution of current on and off the FP resonances. This behavior is accompanied by a modulation of the multiple Andreev reflection amplitude on-and-off resonance, indicating that electrons propagate ballistically in a fully coherent fashion. These results, which were not anticipated by theory, provide a practical route to developing electron analog of optical FP resonators at the graphene edge.

Topical administration of Metamizole and its implications on vascular reactivity in Wistar rats- Experimental research.

Aim: The aim of this paper was to describe the possible implications of topical (ocular) administration of Metamizole on vascular reactivity of the iris in Wistar rats. No other study regarding its topical use was found. Methods: Male adult Wistar rats were anaesthetized with Ketamine 100 mg /kg body weight - injected intraperitoneally - while maintaining spontaneous respiration and the blink reflex. After selecting the area of interest (long posterior ciliary artery - LPCA), manual adjustments of the image magnitude, clarity, and brightness were made, and the experiment began. The image recording lasted 10 minutes. Results: Metamizole induced a slight vasoconstriction that started with the initial moment for all the doses used. After the topical administration of Metamizole, we did not observe an increase of the vascular diameter of LPCA in a dose dependent manner. The saline solution used as a negative control did not modify the vessel diameter. Conclusions: Metamizole (dipyrone) is a non-opioid drug, which is commonly used in human and veterinary medicine. It is the most popular first-line analgesic in various populations. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug. The high analgesic efficacy of metamizole, as well as its spasmolytic effect, makes it a very important pharmaceutical agent that could be used in the therapy of various eye disorders in humans and in animals. Abbreviations: COX = Cyclooxygenase; LPCA = Long Posterior Ciliary Artery; PRP = panretinal photocoagulation; PDR = proliferative diabetic retinopathy; Sec = second(s); VSPR = very severe non proliferative diabetic retinopathy.

Coexisting edge states and gapless bulk in topological states of matter.

We consider two-dimensional systems in which edge states coexist with a gapless bulk. Such systems may be constructed, for example, by coupling a gapped two-dimensional state of matter that carries edge states to a gapless two-dimensional system in which the spectrum is composed of a number of Dirac cones. We find that, in the absence of disorder, the edge states could be protected even when the two systems are coupled, due to momentum and energy conservation. We distinguish between weak and strong edge states by the level of their mixing with the bulk. In the presence of disorder, the edge states may be stabilized when the bulk is localized or destabilized when the bulk is metallic. We analyze the conditions under which these two cases occur. Finally, we propose a concrete physical realization for one of our models based on bilayer Hg(Cd)Te quantum wells.

Recent data on cannabinoids and their pharmacological implications in neuropathic pain.

Natural cannabinoids have been used for centuries for their psychotropic properties, but their possible therapeutic implications in analgesia have been recently documented. The present review intended to make an analysis of the neuroanatomy and physiology of the cannabinoid system (receptors, functions, agents acting on these receptors) and of its implications in neuropathic pain. There were also described the complex phenomena implicated in the generation and maintenance of neuropathic pain, by high lightening the implications of endogenous cannabinoids in this complex of painful conditions. The pharmacological analgesia test proves of cannabinoid implication in neuropathic pain was sustained by many studies presented in this paper. Therapeutic approaches using natural and synthetic cannabinoid receptor agonists were reviewed. Therapeutic perspectives in neuropathic pain might involve the development of new agents that influence the cannabinoid system. Thus, peripheral acting cannabinoid 1 receptors agonists, selective cannabinoid 2 receptor agonists and also modulators of endocannabinoids metabolism might be a way to success in the treatment of this complex entity called neuropathic pain.