Receptor mechanism and antiemetic activity of structurally-diverse cannabinoids against radiation-induced emesis in the least shrew

Xenobiotic cannabinoid CB1/CB2-receptor agonists appear to possess broad-spectrum antiemetic activity since they prevent vomiting produced by a variety of emetic stimuli including the chemotherapeutic agent cisplatin, serotonin 5-HT3-receptor agonists, dopamine D2/D3-receptor agonists and morphine, via the stimulation of CB1-receptors. The purpose of this study was to evaluate whether structurally-diverse cannabinoids [Delta9-THC, (delta-9-tetrahydrocannabinol); (Delta8-THC, delta-8-tetrahydrocannabinol); WIN55,212-2, (R (+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)), methyl] pyrolol [1,2,3-de]-1,4 benzoxazinyl]-(1-naphthalenyl) methenone mesylate); and CP55,940, ((-)-3-[2-hydroxy-4-(1,1-dimethylheptyl]-4-[3-hydroxypropyl] cyclohexane-1-ol)), can prevent radiation-induced emesis. Exposure to total body radiation (0, 5, 7.5 and 10 Gy) caused robust emesis in the least shrew (Cryptotis parva) in a dose-dependent manner (ED50=5.99 (5.77-6.23) Gy) and all animals vomited at the highest tested dose of radiation. In addition, the radiation exposure reduced locomotor behaviors to a significant but mild degree in a non-dose-dependent fashion up to one hour post-treatment. Radiation-induced emesis (10 Gy) was blocked in a dose-dependent manner by the CB1/CB2-receptor agonists with the following ID50 potency order: CP55,940 (0.11 (0.09-0.12) mg/kg)>WIN55,212,2 (3.65 (3.15-4.23) mg/kg)=Delta8-THC (4.36 (3.05-6.22) mg/kg)>Delta9-THC (6.76 (5.22-8.75) mg/kg). Although the greater antiemetic potency and efficacy of Delta8-THC relative to its isomer Delta9-THC is unusual as the latter cannabinoid possesses higher affinity and potency for cannabinoid receptors in functional assays, the current data support the results of a clinical study in children suggestive of complete protection from emesis by Delta8-THC. This effect has not been clinically observed for Delta9-THC in cancer patients receiving chemo- or radiation-therapy. Cannabinoids prevented the induced emesis via the stimulation of cannabinoid CB1-receptors because the CB1 (SR141716A)--and not the CB2 (SR144528)--receptor antagonist reversed both the observed reduction in emesis frequency and shrew emesis protection afforded by either Delta9-THC or CP55,940 against radiation-induced emesis. These findings further suggest that the least shrew can be utilized as a versatile and inexpensive small animal model to rapidly screen the efficacy of investigational antiemetics for the prevention of radiation-induced emesis.     

Proton Spectroscopy in Patients With Post-Traumatic Headache Attributed to Mild Head Injury

Background.— Post traumatic headaches (PTH) following mild head injury (MHI) impose important diagnostic challenges to clinicians, and are often the scope of litigation.
Objective.— To investigate whether spectroscopy magnetic resonance imaging (MRS) demonstrates markers of PTH following MHI.
Methods.— We imaged individuals with PTH following MHI (n = 17), as well as controls (n = 12), using Proton MRS (1-HS MRI). We estimated the metabolic ratios of N-acetylaspartate (NAA) and choline (Cho), relative to creatine (Cr). Compared with controls, individuals with PTH following MHI had reduced values of NAA in the right (1.64 ppm vs 2.05 ppm, P  = .012) and left anterior regions of the frontal lobe white matter (1.52 ppm vs 2.10 ppm; P  = .024); anterior (1.52 ppm vs 1.78 ppm; P  = .0155) and posterior medial region of the frontal lobes (1.6 ppm vs 2.07 ppm; P  = .0045), and medial region of parietal lobes (1.76 ppm vs 2.23 ppm; P  = .0065). Contrasted to controls, Cho measures were statistically increased in the posterior region of the white matter of the right side fontal lobe (1.18 ppm vs 0.99 ppm; P  = .0095), anterior medial region of the frontal lobe (1.20 ppm; vs 1.07 ppm; P  = .0265), and medial region of the parietal lobes (0.92 ppm vs 0.65 ppm; P  = .0005).
Conclusions.— Proton MRS may be useful as an imaging marker for PTH following mild injury. Future studies should contrast PTH following mild vs severe trauma, as well as PTH with other forms of headache, to clarify if the findings are specific of the disease, may be correlated with disease severity, or if they are unspecific headache markers.     

Development of an Index for the Inspection of Aedes aegypti Breeding Sites in Brazil: Multi-criteria Analysis

BackgroundAedes aegypti is a vector for the transmission of diseases such as dengue fever, chikungunya, Zika fever, and yellow fever. In 2016, over 1 million cases of these diseases were reported in Brazil, which is an alarming public health issue. One of the ways of controlling this disease is by inspecting and neutralizing the places where A. aegypti lays its eggs. The Ministry of Planning, Development, and Administration of Brazil maintains the inspection statistics.ObjectiveWe propose a multi-criteria analysis to create an index for A. aegypti inspections reported through the Ministry of Planning, Development, and Administration system of Brazil.MethodsBased on the repository from urban cleaning services combined with data on inspections conducted by government agencies in several Brazilian cities and municipalities, we selected and combined metrics, which we further ranked using the analytic hierarchy process methodology. We also developed risk maps based on the analytic hierarchy process ranking of the A. aegypti breeding sites.ResultsBased on our analysis and the available data, the priority for inspections should consider the number of sick people (weight 0.350), medical evaluations (weight 0.239), inspections (weight 0.201), mosquito breeding sites (weight 0.126), and days of absence from work (weight 0.096).ConclusionsThe proposed index could aid public health practitioners in preventing the appearance of new A. aegypti breeding sites. This information technology application can help solve such public health challenges.     

Primary and post-chemoradiotherapy staging using MRI in rectal cancer: the role of diffusion imaging in the assessment of perirectal infiltration

Abdominal Radiology - To analyze changes in MRI diagnostic accuracy in main rectal tumor (T) evaluation resulting from the use of diffusion-weighted imaging (DWI), according to the degree of...     

Cigarette smoking and lung cancer--relative risk estimates for the major histological types from a pooled analysis of case-control studies

Lung cancer is mainly caused by smoking, but the quantitative relations between smoking and histologic subtypes of lung cancer remain inconclusive. By using one of the largest lung cancer datasets ever assembled, we explored the impact of smoking on risks of the major cell types of lung cancer. This pooled analysis included 13,169 cases and 16,010 controls from Europe and Canada. Studies with population controls comprised 66.5% of the subjects. Adenocarcinoma (AdCa) was the most prevalent subtype in never smokers and in women. Squamous cell carcinoma (SqCC) predominated in male smokers. Age-adjusted odds ratios (ORs) were estimated with logistic regression. ORs were elevated for all metrics of exposure to cigarette smoke and were higher for SqCC and small cell lung cancer (SCLC) than for AdCa. Current male smokers with an average daily dose of >30 cigarettes had ORs of 103.5 (95% confidence interval (CI): 74.8-143.2) for SqCC, 111.3 (95% CI: 69.8-177.5) for SCLC and 21.9 (95% CI: 16.6-29.0) for AdCa. In women, the corresponding ORs were 62.7 (95% CI: 31.5-124.6), 108.6 (95% CI: 50.7-232.8) and 16.8 (95% CI: 9.2-30.6), respectively. Although ORs started to decline soon after quitting, they did not fully return to the baseline risk of never smokers even 35 years after cessation. The major result that smoking exerted a steeper risk gradient on SqCC and SCLC than on AdCa is in line with previous population data and biological understanding of lung cancer development.