Cannabinol and cannabidiol exert opposing effects on rat feeding patterns

Rationale: Increased food consumption following Δ9- tetrahydrocannabinol-induced cannabinoid type 1 receptor agonism is well documented. However, possible non-Δ9- tetrahydrocannabinol phytocannabinoid-induced feeding effects have yet to be fully investigated. Therefore, we have assessed the effects of the individual phytocannabinoids, cannabigerol, cannabidiol and cannabinol, upon feeding behaviors. Methods: Adult male rats were treated (p.o.) with cannabigerol, cannabidiol, cannabinol or cannabinol plus the CB1R antagonist, SR141716A. Prior to treatment, rats were satiated and food intake recorded following drug administration. Data were analyzed for hourly intake and meal microstructure. Results: Cannabinol induced a CB1R-mediated increase in appetitive behaviors via significant reductions in the latency to feed and increases in consummatory behaviors via increases in meal 1 size and duration. Cannabinol also significantly increased the intake during hour 1 and total chow consumed during the test. Conversely, cannabidiol significantly reduced total chow consumption over the test period. Cannabigerol administration induced no changes to feeding behavior. Conclusion: This is the first time cannabinol has been shown to increase feeding. Therefore, cannabinol could, in the future, provide an alternative to the currently used and psychotropic Δ9-tetrahydrocannabinol-based medicines since cannabinol is currently considered to be non-psychotropic. Furthermore, cannabidiol reduced food intake in line with some existing reports, supporting the need for further mechanistic and behavioral work examining possible anti-obesity effects of cannabidiol

Defining key structural determinants for the pro-osteogenic activity of flavonoids

Epidemiological studies suggest that fruits and vegetables may play a role in promoting bone growth and preventing age-related bone loss, attributable, at least in part, to phytochemicals such as flavonoids stimulating osteoblastogenesis. Through systematically screening the effect of flavonoids on the osteogenic differentiation of human mesenchymal stem cells in vitro, and correlating activity with chemical structure using comparative molecular field analysis, we have successfully identified important structural features which relate to their activity, as well as reliably predicting the activity of compounds with unknown activity. Contour maps emphasised the importance of electronegativity, steric bulk, and a 2-C-3-C double bond at the flavonoid C-ring, as well as overall electropositivity and reduced steric bulk at the flavonoid B-ring. These results support a role for certain flavonoids in promoting osteogenic differentiation, thus their potential for preventing skeletal deterioration, as well as providing a foundation for the lead optimisation of novel bone anabolics

Time of arrival as a diagnostic for far-field high explosive blast waves

The ability to accurately determine blast loading parameters will enable more fundamental studies on the sources of blast parameter variability and their influence on the magnitude and form of the loading itself. This will ultimately lead to a better fundamental understanding of blast wave behaviour, and will result in more efficient and effective protective systems and enhanced resilience of critical infrastructure. This article presents a study on time of arrival as a diagnostic for far-field high explosive blasts, and makes use of the results from a large number of historic tests and newly performed experiments where the propagating shock front was filmed using a high-speed video (HSV) camera. A new method for optical shock tracking of far-field blast tests is developed and validated, and full-field arrival time results are compared against those determined from the historic data recorded using traditional pressure gauges. Arrival time variability is shown to be considerably lower than peak pressure and peak specific impulse, and is shown to decrease exponentially with increasing scaled distance. Further, the method presented in this article using HSV cameras to determine arrival time yields further reductions in variability. Finally, it is demonstrated that the method can be used to accurately determine far-field TNT equivalence of high explosives

Measurements of reflected overpressure in the extreme near field

Blast protection design requires a detailed knowledge of the loading imparted on a structure by a particular blast threat. This includes an understanding of the mechanisms involved in the rapid energy release that leads to fireball expansion and air shock development. In the far field (Z > 2 m/kg1/3) reliable semi-empirical methods exist for both the positive and negative phases of the blast wave. In the far field the explosion is sufficiently far away that only the propagating air shock interacts with the structure, while in the near field the fireball is still driving the air shock and can itself interact with the structure. There is currently a lack of reliable experimental data in this near field region, as the incredibly high pressures and temperatures pose particular experimental challenges. This is particularly the case in the extreme near field (Z < 0.5 m/kg1/3), where semi-empirical and physics-based predictions can vary by an order of magnitude. This paper presents the design of an experimental facility capable of recording spatially resolved reflected pressures in the extreme near field. The Mechanisms and Characterisation of Explosions (MaCE) facility is an evolution of the Characterisation of Blast Loading (CoBL) facility used for buried blasts, but with key near fieldspecific adaptations. An array of Hopkinson pressure bars embedded in a stiff target plate is used to make pressure measurements over a 100 mm radius instrumented area. Maraging steel pressure bars and specially designed strain gauges are used to increase the measurement capacity from 600 MPa to 1800 MPa, and 33 pressure bars in a radial grid are used to improve the spatial resolution from 25 mm to 12.5 mm. In addition, the pressure bar diameter is reduced from 10 mm to 4 mm, which greatly reduces stress wave dispersion, increasing the effective bandwidth. This enables the observation of high-frequency features in the pressure measurements, which is vital for validating the near-field transient effects predicted by numerical modelling and developing effective blast mitigation methods

Temporally and spatially resolved reflected overpressure measurements in the extreme near field

The design of blast-resistant structures and protective systems requires a firm understanding of the loadings imparted to structures by blast waves. While empirical methods can reliably predict these loadings in the far field, there is currently a lack of understanding on the pressures experienced in the very near field, where physics-based numerical modelling and semi-empirical fast-running engineering model predictions can vary by an order of magnitude. In this paper, we present the design of an experimental facility capable of providing definitive spatially and temporally resolved reflected pressure data in the extreme near field (Z<0.5 m/kg1/3 ). The Mechanisms and Characterisation of Explosions (MaCE) facility is a specific near-field evolution of the existing Characterisation of Blast Loading (CoBL) facility, which uses an array of Hopkinson pressure bars embedded in a stiff target plate. Maraging steel pressure bars and specially designed strain gauges are used to increase the measurement capacity from 600 MPa to 1800 MPa, and 33 pressure bars in a radial grid are used to improve the spatial resolution from 25 mm to 12.5 mm over the 100 mm radius measurement area. In addition, the pressure bar diameter is reduced from 10 mm to 4 mm, which greatly reduces stress wave dispersion, increasing the effective bandwidth. This enables the observation of high-frequency features in the pressure measurements, which is vital for validating the near-field transient effects predicted by numerical modelling and developing effective blast mitigation methods

MicroBlast - a benchmarking study of gramme-scale explosive trials

Explosions are a pressing and pervading threat in the modern world. The extensive damage caused by recent large scale urban explosions such as Tianjin (2015) and Beirut (2020) has highlighted a key gap in our knowledge. That is, we still do not yet understand, nor can we reliably and rapidly predict, blast loading in complex cityscape environments. Accordingly, determination of consequences related to risk, structural damage, and casualty numbers, is severely limited. Current experimental approaches do not have the sophistication nor fidelity required to accurately measure blast loading in urban environments, and there is a significant and growing disparity in the complexity with which numerical models and experimental work can operate. Because of this, key insights gained from detailed modelling studies have not been validated, and we do not yet fully understand how blast waves propagate and interact with multiple obstacles. This paper presents the development of a series of experimental studies aimed at addressing this shortfall. The ultimate objective of this work is to develop the MicroBlast facility: an ultra small-scale testing apparatus for rapid, high-rate, high-resolution, multi-parameter measurements of blast loading in complex environments. Here, we present results from preliminary trials aimed at establishing the reliability and repeatability of small-scale explosive testing, in increasingly complex layouts. The results are directly compared to commensurate larger-scale test data to confirm scalability of gramme-scale detonations

Making sense of being at 'high risk' of coronary heart disease within primary prevention

types: Journal ArticleCurrent National Health Service policy advocates screening to identify individuals at 'high risk' of cardio-vascular disease (CHD) in primary care. This article utilizes the work of Radley to explore how 'high risk' of CHD patients make sense of their new risk status. Results are presented here from a nested qualitative study within a quantitative randomized trial of a CHD risk intervention in primary care. 'Discovery' interviews were conducted with 'high risk' participants (n = 38, mean age = 55) two weeks after intervention and thematically analysed. In response to perceived threat, many participants sought to both 'minimize' and 'normalize' their risk status. They also reported intentions to act, particularly concerning dietary change and exercise, although less so for smoking amongst the lower socio-economic status participants. Such perceptions and intentions were contextualized within the life-course of later middle-age, so that both being at risk, and being treated for risk, were normalized as part of growing older. Social position, such as gender and SES, was also implicated. CHD risk interventions should be context-sensitive to the life-course and social position of those who find themselves at 'high risk' of CHD in later middle-age

Recent development and research at the University of Sheffield blast lab in Buxton, UK

The Blast and Impact Dynamics Lab in Buxton, UK has recently undergone a significant refurbishment due to investment by the University of Sheffield and funding from the Engineering & Physical Sciences Research Council (EPSRC) through a Strategic Equipment Grant. This has complimented development in measurement techniques funded through standard EPSRC grants and commercial blast testing undertaken by Blastech Ltd. a spin out company of the University of Sheffield

Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats

Rationale The appetite-stimulating properties of cannabis are well documented and have been predominantly attributed to the hyperphagic activity of the psychoactive phytocannabinoid, ∆9-tetrahydrocannabinol (∆9-THC). However, we have previously shown that a cannabis extract devoid of ∆9-THC still stimulates appetite, indicating that other phytocannabinoids also elicit hyperphagia. One possible candidate is the non-psychoactive phytocannabinoid cannabigerol (CBG), which has affinity for several molecular targets with known involvement in the regulation of feeding behaviour. Objectives The objective of the study was to assess the effects of CBG on food intake and feeding pattern microstructure. Methods Male Lister hooded rats were administered CBG (30–120 mg/kg, per ora (p.o.)) or placebo and assessed in open field, static beam and grip strength tests to determine a neuromotor tolerability profile for this cannabinoid. Subsequently, CBG (at 30–240 mg/kg, p.o.) or placebo was administered to a further group of pre-satiated rats, and hourly intake and meal pattern data were recorded over 2 h. Results CBG produced no adverse effects on any parameter in the neuromotor tolerability test battery. In the feeding assay, 120–240 mg/kg CBG more than doubled total food intake and increased the number of meals consumed, and at 240 mg/kg reduced latency to feed. However, the sizes or durations of individual meals were not significantly increased. Conclusions Here, we demonstrate for the first time that CBG elicits hyperphagia, by reducing latency to feed and increasing meal frequency, without producing negative neuromotor side effects. Investigation of the therapeutic potential of CBG for conditions such as cachexia and other disorders of eating and body weight regulation is thus warranted