Protective Effects of Cannabis sativa on chemotherapy-induced nausea in a rat: Involvement of CB1 receptors

Cyclophosphamide is an anticancer and immunosuppressive agent used in the treatment of various malignancies but causing gastrointestinal distress. Cannabis sativa and its derivatives have been used for the treatment of human gastrointestinal disorders. A purpose of this study was to investigate the effect of C. sativa on nausea induced by cyclophosphamide in rats. The rats were divided into four groups (eight animals per group): Group 1: Normal control (saline i.p.). Group 2: Rats received cyclophosphamide (200 mg/kg i.p.) 3 consecutive days. Group 3 and 4: Rats received cyclophosphamide (200 mg/kg i.p.) across Days 1–7, and C. sativa (20 and 40 mg/kg s.c.) was administered on cyclophosphamide days 4–7. We examined intake of kaolin, normal food and changes in body weight, as an indicator of the emetic stimulus. Oxidative stress markers, antioxidant enzymes status, serotonin (5-HT), dopamine, noradrenaline and CB1R levels were evaluated in the intestinal homogenate. Moreover, histopathological study was performed. Results showed that C. sativa ameliorates cyclophosphamide-induced emesis by increasing in body weight and normal diet intake with a decrease in kaolin diet intake after 7 days. Moreover, C. sativa significantly decreases (serotonin) 5-HT, dopamine and noradrenaline, as well as decreasing oxidative stress and inflammation. Administration of C. sativa significantly increased the expression of CB1R in intestinal homogenate. Treatment with C. sativa also improved the histological feature of an intestinal tissue. These results suggested that C. sativa possess antiemetic, antioxidant and anti-inflammatory effects in chemotherapy-induced nausea in rats by activating CB1R.     

Influence of chrysin on D-galactose induced-aging in mice: Up regulation of AMP kinase/liver kinase B1/peroxisome proliferator-activated receptor-γ coactivator 1-α signaling pathway

Adenosine monophosphate kinase/liver kinase B1/peroxisome proliferator-activated receptor-γ coactivator 1-α (AMPK/LKB1/PGC1α) pathway has a vital role in regulating age-related diseases. It controls neurogenesis, cell proliferation, axon outgrowth, and cellular energy homeostasis. AMPK pathway also regulates mitochondrial synthesis. The current study evaluated the effect of chrysin on D-galactose (D-gal) induced-aging, neuron degeneration, mitochondrial dysfunction, oxidative stress, and neuroinflammation in mice. The mice were allocated randomly into four groups (10 each group): Group 1: normal control group, Group 2: D-gal group, Groups 3 and 4: chrysin (125 and 250 mg/kg, respectively). Groups 2–4 were injected with D-gal (200 mg/kg/day; s.c) for 8 weeks to induce aging. Groups 3 and 4 were orally gavaged every day concurrent with D-gal. At the end of experiment, behavioral, brain biochemical and histopathological changes were monitored. Chrysin administration elevated discrimination ratio in object recognition, Y Maze percentage alternation, locomotor activity and brain contents of AMPK, LKB1, PGC1α, NAD (P)H quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), nerve growth factor (NGF) (neurotrophin-3; NT-3), and seretonin as well as reduced brain contents of tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), advanced glycation end products (AGEs) and glial fibrillary acidic protein (GFAP) compared to D-gal-treated mice. Chrysin also alleviated cerebral cortex and white matter neurons degeneration. Chrysin protects against neurodegeneration, improves mitochondrial autophagy and biogenesis as well as activates antioxidant genes expression. In addition, chrysin ameliorates neuroinflammation and stimulates the release of NGF and serotonin neurotransmitter. So, chrysin has a neuroprotective effect in D-gal induced-aging in mice.     

Thermal inactivation of Alkhumra hemorrhagic fever virus

The physico-chemical and biological characteristics of Alkhumra hemorrhagic fever virus (AHFV) are not yet known. The present study describes the thermal stability of this virus at different temperatures for different periods. The kinetics of thermal inactivation were studied, linear regressions were plotted, the Arrhenius equation was applied, and the activation energy was calculated accordingly. Titers of the residual virus were determined in median tissue culture infective dose (TCID₅₀), and the rate of destruction of infectivity at various temperatures was determined. Infectivity of AHFV was completely lost upon heating for 3 minutes at 60 °C and for 30 min at 56 °C. However, the virus could maintain 33.2 % of its titer after heating for 60 min at 45 °C and 32 % of its titer after heating for 60 min at 50 °C. In conclusion, AHFV is thermo-labile, and its inactivation follows first-order kinetics.     

Infections with cardiopulmonary and intestinal helminths and sarcoptic mange in red foxes from two different localities in Denmark

Monitoring parasitic infections in the red fox is essential for obtaining baseline knowledge on the spread of diseases of veterinary and medical importance. In this study, screening for cardiopulmonary and intestinal helminths and sarcoptic mange (Sarcoptes scabiei) was done on 118 foxes originating from two distinct localities in Denmark, (Copenhagen) greater area and southern Jutland. Fifteen parasite species were recorded in 116 foxes (98.3%), nine parasitic species are of zoonotic potential. Parasite diversity was greater in foxes of Copenhagen in terms of overall parasite species richness and species richness of all helminth groups individually: trematodes; cestodes; and nematodes. Six parasite species were recovered from foxes of Copenhagen, but not from foxes of Southern Jutland: Echinochasmus perfoliatus; Echinostoma sp.; Pseudamphistomum truncatum; Dipylidium caninum; Angiostrongylus vasorum; and Sarcoptes scabiei, but Toxascaris leonina was only recorded in foxes of southern Jutland. A high prevalence and abundance of A. vasorum in foxes of Copenhagen was observed. The prevalence of four nematode species; Eucoleus (Capillaria) aerophilus, Uncinaria stenocephala, Toxocara canis, and Crenosoma vulpis, in foxes of both localities were comparable and ranging from 22.9% to 89%. The prevalence of Mesocestoides sp. was significantly higher in foxes of Copenhagen. Taenia spp. were detected using morphological and molecular analysis, which revealed the dominance of T. polyacantha in foxes of both localities. Infections with sarcoptic mange were evident only among foxes of Copenhagen (44.9%), which significantly affected the average weight of the infected animals. Further remarks on the zoonotic and veterinary implications of the parasites recovered are given.     

Normative MDCT Cross-Sectional Data Estimation of Superior Vena Cava and Innominate Vein in Growing Children Using Age as a Predictor

This retrospective study aimed to determine the superior vena cava (SVC) and left innominate vein (INV) normative cross-sectional area in children noninvasively using age as a predictor and also to compare the correlation of the area measured with the diameter on multidetector computed tomography (MDCT). Analysis of the SVC-INV cross-sectional area was performed for 73 consecutive patients. The cross-sectional area of the SVC-INV was manually estimated. A regression analysis was performed for the cross-sectional area and age separately, and regression equations were compared. One-way analysis of variance (ANOVA) was performed to evaluate significant differences in the area means according to age groups. Regression analysis showed that age can be a predictor for the area of the SVC (50.6 mm² + 1.01 × age), te INV (48.3 mm² + 0.93 × age), and the left SVC-INV junction (47.2 mm² + 0.92 × age), with respective R ² values of 93, 88 and 94 %. The comparative evaluation of the cross-sectional area and the diameter measurement of SVC showed that the cross-sectional area was more closely associated with the increasing age of the cohort (R ² of 68 vs. 61 %) than the measured diameter. For a cohort of patients without congenital or acquired heart disease, MDCT can be used as a complementary test for a normative cross-sectional normogram area database of SVC-INV using age as a predictor.     

Synthesis of new oxadiazol-phthalazinone derivatives with anti-proliferative activity; molecular docking,pro-apoptotic,and enzyme inhibition profile

Background and aim: The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives. Methods: The synthetic reactions were carried out under both conventional and ultrasonic irradiation conditions. The anti-proliferative activity of the newly synthesized compounds against two human epithelial cell lines; liver (HepG2) and breast (MCF-7) in addition to normal fibroblasts (WI-38) was investigated. In addition to molecular docking studies, the possible mechanism(s) of action were also explored. Results: In general, an improvement in synthetic rates and yields was observed when reactions were carried out under sonication compared with classical conditions. The structures of the products were established based on analytical and spectral data. Derivatives 2e and 7d, in addition to compound 1, had significant and selective anti-proliferative activity against liver and breast cancer cell lines without harming normal fibroblasts. These derivatives arrested the cell cycle progression and/or induced apoptosis. This has been manifested by the elevation in the expression of p53 and caspase 3, down-regulation of cdk1, and a reduction in the concentrations of MAPK and Topo II at submicromolar concentrations. The latter results confirmed the molecular docking study. Conclusions: Compound 1 had the best profile on the gene and protein levels (arresting cell cycle and inducing apoptosis). The ability of compounds 1 and 2e to inhibit both MAPK and Topo II nominates these derivatives as potential candidates for further anticancer and antitumor studies.

The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives.     

Half Metallic Ferromagnetism and Transport Properties of Zinc Chalcogenides ZnX2Se4 (X = Ti,V, Cr) for Spintronic Applications

In ferromagnetic semiconductors, the coupling of magnetic ordering with semiconductor character accelerates the quantum computing. The structural stability, Curie temperature (T_c), spin polarization, half magnetic ferromagnetism and transport properties of ZnX₂Se₄ (X = Ti, V, Cr) chalcogenides for spintronic and thermoelectric applications are studied here by density functional theory (DFT). The highest value of T_c is perceived for ZnCr₂Se₄. The band structures in both spin channels confirmed half metallic ferromagnetic behavior, which is approved by integer magnetic moments (2, 3, 4) μ_B of Ti, V and Cr based spinels. The HM behavior is further measured by computing crystal field energy ΔE _crystal, exchange energies Δ _x(d), Δ _x (pd) and exchange constants (N_o α and N_o β ). The thermoelectric properties are addressed in terms of electrical conductivity, thermal conductivity, Seebeck coefficient and power factor in within a temperature range 0–400 K. The positive Seebeck coefficient shows p-type character and the PF is highest for ZnTi2Se4 (1.2 × 10¹¹ W/mK²) among studied compounds.     

Fabrication of Lead Free Borate Glasses Modified by Bismuth Oxide for Gamma Ray Protection Applications

In the present work, bismuth borate glass samples with the composition of (99-x) B₂O₃ + 1Cr₂O₃ + (x) Bi₂O₃ (x = 0, 5, 10, 15, 20, and 25 wt %) were prepared using the melt quenching technique. The mass attenuation coefficient (MAC) of the prepared glass samples was measured through a narrow beam technique using a NaI(Tl) scintillation detector. Four point sources were used (²⁴¹Am, ¹³³Ba, ¹⁵²Eu, and ¹³⁷Cs) to measure the MAC for the prepared glasses. The experimental data were compared with the theoretical results obtained from the XCOM, and it was shown that for all samples at all tested energies, the relative deviation between the samples is less than 3%. This finding signifies that the experimental data can adequately be used to evaluate the shielding ability of the glasses. The MAC of the sample with x = 25 wt % was compared with different lead borate glasses and the results indicated that the present sample has high attenuation which is very close to commercial lead borate glasses. We determined the transmission factor (TF), and found that it is small at low energies and increases as the energy increases. The addition of Bi₂O₃ leads to reduction in the TF values, which improves the shielding performance of the glass system. The half value layer (HVL) of the BCrBi-10 sample was 0.400 cm at 0.595 MeV, 1.619 cm at 0.2447 MeV, and 4.946 cm at 1.4080 MeV. Meanwhile, the HVL of the BCrBi-20 sample is equal to 0.171 and 4.334 cm at 0.0595 and 1.4080 MeV, respectively. The HVL data emphasize that higher energy photons tend to penetrate through the glasses with greater ease than lower energy photons. Furthermore, the fast neutron removable cross section (FNRC) was determined for the present samples and compared with lead borate glass and concrete, and the results showed a remarkable superiority of the bismuth borate glass samples.     

Seizure semiology in temporal lobe vs. temporal plus epilepsy using intracranial EEG monitoring

Objectives:To utilize our tertiary center’s experience with Temporal lobe epilepsy (TLE) and Temporal plus epilepsy (TPE) cases and determine whether a correlation exists between ictal semiology signs, their localization/lateralization value after intracranial electroencephalography (EEG) monitoring, and surgical outcomes.Methods:A retrospective study was conducted among epilepsy patients who underwent resective surgery for TLE or TPE after intracranial EEG monitoring between January 2008 and December 2018 at King Faisal Specialist Hospital in Riyadh, Saudi Arabia. Data were retrieved for 464 patients; 181 had intracranial electrode monitoring.Results:Forty-eight patients with a mean age of 27 years (SD=8.4) were included; 15 patients had TPE. Auras were frequently reported, emotional auras, in the form of fear (35%). The localization/lateralization value of aura was statistically significant for TPE patients, including visual hallucinations and vertigo, lateralized to the left and right temporo-occipital, respectively (p=0.009 and <0.001). Early-onset ictal manual automatism, oral automatism, late-onset dystonic posture, and late head-turning were significant for TLE without significant lateralization value. The ictal onset zone’s localization was significant between the scalp and intracranial EEG findings in mesial TLE patients. The probability of seizure freedom (Engel class I) was 74%, 60%, and 67% at 2-year follow-up for mesial, lateral TLE, and TPE, respectively.Conclusion:Our results are consistent with previous studies and confirm the importance of ictal semiology signs in TLE and TPE. The addition of intracranial EEG monitoring in these cases helped improve the surgical outcomes.

Epilepsy is one of the most common neurological disorders, affecting approximately 70 million people globally.¹ Thirty percent of these patients have drug-resistant epilepsy,² and most cases referred for epilepsy surgery involve temporal lobe epilepsy (TLE).³ However, after standard temporal lobectomy, around 40% of these patients will experience recurrent seizures.⁴ A variety of explanations have been proposed for these surgical failures, including incomplete removal of the epileptogenic zone, additional contralateral focus (bilateral TLE), dual pathology (mesial and neocortical), and extended epileptogenic focus to the neighboring structures, including extratemporal or temporal plus epilepsy (TPE).⁵The TPE is defined as focal epilepsy with a complex epileptogenic network involving the temporal lobe and the surrounding areas, such as the orbitofrontal cortex, insula, operculum, and temporo-parieto-occipital junction.⁶ A thorough presurgical evaluation is required to delineate the epileptogenic zone for successful resective surgery. In phase I assessment, scalp video electroencephalography (EEG) monitoring, brain magnetic resonance imaging (MRI), and neuropsychological evaluation are needed. Further non-invasive investigations can be included if the initial results are discordant. To reach a well-demarcated epileptogenic focus requires intracranial monitoring, including the subdural grid, strips, and depth, which is known as phase II assessment.⁷ Seizure semiology is the first step in a presurgical evaluation, and ictal semiology and scalp-EEG results play a valuable role in distinguishing TLE from TPE.⁸ Patients with TLE are more likely to experience abdominal auras, ictal gestural automatism, and post-ictal amnesia. However, TPE patients are more likely to experience gustatory hallucinations, rotatory vertigo, auditory illusions, contralateral eye and head versions, piloerection, and ipsilateral tonic posturing. Similar findings were highlighted in a review of TPE cases.4 Furthermore, laryngeal and throat constriction and the atypical distribution of somatosensory symptoms at seizure onset have been found.4Although some studies have found a correlation between seizure semiology and intracranial EEG monitoring in TLE (mesial vs. lateral) vs. TPE, none evaluated lateralization values. This study aims to utilize our tertiary center’s experience with TLE and TPE cases and determine whether a correlation exists between ictal semiology signs, their localization/lateralization value after intracranial electroencephalography (EEG) monitoring and surgical outcomes. We also highlight the process of phase I presurgical assessment (including ictal/interictal scalp EEG, MRI, positron emission tomography [PET], and neuropsychology) in our center.