Receptors and channels possibly mediating the effects of phytocannabinoids on seizures and epilepsy

Epilepsy contributes to approximately 1% of the global disease burden. By affecting especially young children as well as older persons of all social and racial variety, epilepsy is a present disorder worldwide. Currently, only 65% of epileptic patients can be successfully treated with antiepileptic drugs. For this reason, alternative medicine receives more attention. Cannabis has been cultivated for over 6000 years to treat pain and insomnia and used since the 19th century to suppress epileptic seizures. The two best described phytocannabinoids, (−)-trans-Δ9- tetrahydrocannabinol (THC) and cannabidiol (CBD) are claimed to have positive effects on different neurological as well as neurodegenerative diseases, including epilepsy. There are different cannabinoids which act through different types of receptors and channels, including the cannabinoid receptor 1 and 2 (CB1, CB2), G protein-coupled receptor 55 (GPR55) and 18 (GPR18), opioid receptor μ and δ, transient receptor potential vanilloid type 1 (TRPV1) and 2 (TRPV2), type A γ-aminobutyric acid receptor (GABAAR) and voltage-gated sodium channels (VGSC). The mechanisms and importance of the interaction between phytocannabinoids and their different sites of action regarding epileptic seizures and their clinical value are described in this review

Cannabinoid profiling of hemp seed oil by liquid chromatography coupled to high-resolution mass spectrometry

Hemp seed oil is well known for its nutraceutical, cosmetic and pharmaceutical properties due to a perfectly balanced content of omega 3 and omega 6 polyunsaturated fatty acids. Its importance for human health is reflected by the success on the market of organic goods in recent years. However, it is of utmost importance to consider that its healthy properties are strictly related to its chemical composition, which varies depending not only on the manufacturing method, but also on the hemp variety employed. In the present work, we analyzed the chemical profile of ten commercially available organic hemp seed oils. Their cannabinoid profile was evaluated by a liquid chromatography method coupled to high-resolution mass spectrometry. Besides tetrahydrocannabinol and cannabidiol, other 30 cannabinoids were identified for the first time in hemp seed oil. The results obtained were processed according to an untargeted metabolomics approach. The multivariate statistical analysis showed highly significant differences in the chemical composition and, in particular, in the cannabinoid content of the hemp oils under investigation

Antiseizure effects of cannabidiol leading to increased peroxisome proliferator-activated receptor gamma levels in the hippocampal CA3 subfield of epileptic rats

We evaluated the effects of cannabidiol (CBD) on seizures and peroxisome proliferator activated receptor gamma (PPAR) levels in an animal model of temporal lobe epilepsy (TLE). Adult male Sprague-Dawley rats were continuously monitored by video-electrocorticography up to 10 weeks after an intraperitoneal kainic acid (15 mg/kg) injection. Sixty-seven days after the induction of status epilepticus and the appearance of spontaneous recurrent seizures in all rats, CBD was dissolved in medium-chain triglyceride (MCT) oil and administered subcutaneously at 120 mg/kg (n = 10) or 12 mg/kg (n = 10), twice a day for three days. Similarly, the vehicle was administered to ten epileptic rats. Brain levels of PPAR immunoreactivity were compared to those of six healthy controls. CBD at 120 mg/kg abolished the seizures in 50% of rats (p = 0.033 vs. pretreatment, Fisher’s exact test) and reduced total seizure duration (p < 0.05, Tukey Test) and occurrence (p < 0.05). PPAR levels increased with CBD in the hippocampal CA1 subfield and subiculum (p < 0.05 vs. controls, Holm–Šidák test), but only the highest dose increased the immunoreactivity in the hippocampal CA3 subfield (p < 0.001), perirhinal cortex, and amygdala (p < 0.05). Overall, these results suggest that the antiseizure effects of CBD are associated with upregulation of PPAR in the hippocampal CA3 region

Accuracy improvement in the TDR-based localization of water leaks

A time domain reflectometry (TDR)-based system for the localization of water leaks has been recently developed by the authors. This system, which employs wire-like sensing elements to be installed along the underground pipes, has proven immune to the limitations that affect the traditional, acoustic leak-detection systems.Starting from the positive results obtained thus far, in this work, an improvement of this TDR-based system is proposed. More specifically, the possibility of employing a low-cost, water-absorbing sponge to be placed around the sensing element for enhancing the accuracy in the localization of the leak is addressed.To this purpose, laboratory experiments were carried out mimicking a water leakage condition, and two sensing elements (one embedded in a sponge and one without sponge) were comparatively used to identify the position of the leak through TDR measurements. Results showed that, thanks to the water retention capability of the sponge (which maintains the leaked water more localized), the sensing element embedded in the sponge leads to a higher accuracy in the evaluation of the position of the leak. Keywords: Leak localization, TDR, Time domain reflectometry, Water leaks, Underground water pipe

Reflectometric System for Continuous and Automated Monitoring of Irrigation in Agriculture

In this work, a time domain reflectometry (TDR)-based system for continuous and diffused monitoring of soil water content in agriculture is presented. The proposed TDR-based system employs elongate sensing elements (SEs). In practical application, each wire-like SE is buried along the cultivation row to be monitored, and through a single TDR measurement it is possible to retrieve the water content profile of the cultivation along the length of the SE. By connecting the TDR-based monitoring system to the irrigation machines, it would be possible to automatically start/stop irrigation based on the actual water requirement of the cultivations, thus favoring precision agriculture and enhancing irrigation efficiency. To demonstrate the feasibility of the proposed monitoring solution, a dedicated hardware+software platform was developed and the TDR-based system was experimented in open-field cultivations

Microwave reflectometric systems and monitoring apparatus for diffused-sensing applications

Most sensing networks rely on punctual/local sensors; they thus lack the ability to spatially resolve the quantity to be monitored (e.g. a temperature or humidity profile) without relying on the deployment of numerous inline sensors. Currently, most quasi-distributed or distributed sensing technologies rely on the use of optical fibre systems. However, these are generally expensive, which limits their large-scale adoption. Recently, elongated sensing elements have been successfully used with time-domain reflectometry (TDR) to implement diffused monitoring solutions. The advantage of TDR is that it is a relatively low-cost technology, with adequate measurement accuracy and the potential to be customised to suit the specific needs of different application contexts in the 4.0 era. Based on these considerations, this paper addresses the design, implementation and experimental validation of a novel generation of elongated sensing element networks, which can be permanently installed in the systems that need to be monitored and used for obtaining the diffused profile of the quantity to be monitored. Three applications are considered as case studies: monitoring the irrigation process in agriculture, leak detection in underground pipes and the monitoring of building structures

Combined Punctual and Diffused Monitoring of Concrete Structures Based on Dielectric Measurements

This work presents a microwave reflectometry-based system for monitoring large concretestructures (during the curing process and also while the structure is in use), through the combineduse of punctual and diffused sensing elements. In particular, the adoption of punctual probes ona reference concrete specimen allows the development of an innovative and accurate calibrationprocedure, useful to obtain the value of the water content on a larger structure made of the samematerial. Additionally, a wire-like diffused sensing element can be permanently embedded inbuildings and used to monitor the structure along the entire length of the sensing element. Theadopted diffused sensing element can be used not only to detect dielectric variation during the curingprocess, but also throughout the service life of the structure. The combined use of punctual anddiffused sensing elements represents an important innovation from a procedural point of view, ableto provide detailed and quantitative information on the health status of the structure both duringand after construction

On the use of a reliable low-cost set-up for characterization measurements of antennas

In this paper, a low-cost time domain-based approach to antenna characterization is presented. The goal is to prove that time domain-based antenna measurements, after appropriate processing, represent an accurate and more practicable alternative to the universally accepted (yet highly expensive) antenna measurements in anechoic chamber, and provide information just as complete. Measurements on two commercial antennas are carried out in the time domain (in a non-controlled environment) and in the frequency domain (in an anechoic chamber): experimental data obtained from the two approaches are compared in terms of Return Loss. Results show that reliable results can be extracted from time domain data, and that a good insight into the antenna characteristics can be obtained even without using highly expensive facilities

Quality Traits of "Cannabidiol Oils": Cannabinoids Content, Terpene Fingerprint and Oxidation Stability of European Commercially Available Preparations

Cannabidiol (CBD)-based oil preparations are becoming extremely popular, as CBD has been shown to have beneficial effects on human health. CBD-based oil preparations are not unambiguously regulated under the European legislation, as CBD is not considered as a controlled substance. This means that companies can produce and distribute CBD products derived from non-psychoactive hemp varieties, providing an easy access to this extremely advantageous cannabinoid. This leaves consumers with no legal quality guarantees. The objective of this project was to assess the quality of 14 CBD oils commercially available in European countries. An in-depth chemical profiling of cannabinoids, terpenes and oxidation products was conducted by means of GC-MS and HPLC-Q-Exactive-Orbitrap-MS in order to improve knowledge regarding the characteristics of CBD oils. Nine out of the 14 samples studied had concentrations that differed notably from the declared amount, while the remaining five preserved CBD within optimal limits. Our results highlighted a wide variability in cannabinoids profile that justifies the need for strict and standardized regulations. In addition, the terpenes fingerprint may serve as an indicator of the quality of hemp varieties, while the lipid oxidation products profile could contribute in evaluation of the stability of the oil used as milieu for CBD rich extracts

Molecular modeling studies, synthesis, configurational stability and biological activity of 8-chloro-2,3,5,6-tetrahydro-3,6-dimethyl-pyrrolo[1,2,3-de]-1,2,4-benzothiadiazine 1,1-dioxide

The potential therapeutic benefit of compounds able to activate AMPA receptors (AMPArs) has led to a search for new AMPAr positive modulators. Among them, 8-chloro-2,3,5,6-tetrahydro-3,6-dimethyl-pyrrolo[1,2,3-de]-1,2,4-benzothiadiazine 1,1-dioxide (1) has attracted particular attention, because it is one of the most active benzothiadiazine\u2013derived positive modulators of the AMPA receptor. It possesses two stereogenic centers, C3 and C6, thus it can exist as four stereoisomers. In this work, preliminary in silico studies suggested that 1 interacts stereoselectively with AMPArs. Single stereoisomers of 1 were prepared in order to evaluate their biological activity. However, studies regarding the configurational stability of the investigated compounds suggested a rapid epimerization at C3 in aqueous solvents, and we can expect the same reaction in vivo. Thus, electrophysiological experiments were performed on the two epimeric mixtures, (3 17,6R)- and (3 17,6S)- 8-chloro-2,3,5,6-tetrahydro-3,6-dimethyl-pyrrolo[1,2,3-de]-1,2,4-benzothiadiazine 1,1-dioxide, in order to evaluate their activities as positive allosteric modulators of AMPArs. The obtained data suggest that the (3 17,6S) epimeric mixture is the most active in positively modulating AMPArs, confirming in silico results