11. Exploring the safety of cannabidiol (CBD) : a comprehensive in vitro evaluation of the genotoxic and mutagenic potential of a CBD isolate and extract from Cannabis sativa LAlja Štern, Matjaž Novak, Katja Kološa, Jurij Trontelj, Sonja Žabkar, Tjaša Šentjurc, Metka Filipič, Bojana Žegura, 2024, original scientific article Abstract: Cannabidiol (CBD), a naturally occurring cyclic terpenoid found in Cannabis sativa L., is renowned for its diverse
pharmacological benefits. Marketed as a remedy for various health issues, CBD products are utilized by patients
as a supplementary therapy or post-treatment failure, as well as by healthy individuals seeking promised advantages. Despite its widespread use, information regarding potential adverse effects, especially genotoxic
properties, is limited. The present study is focused on the mutagenic and genotoxic activity of a CBD isolate
(99.4 % CBD content) and CBD-rich Cannabis sativa L extract (63.6 % CBD content) in vitro. Both CBD samples
were non-mutagenic, as determined by the AMES test (OECD 471) but exhibited cytotoxicity for HepG2 cells
(~IC50 (4 h) 26 µg/ml, ~IC50 (24 h) 6–8 µg/ml, MTT assay). Noncytotoxic concentrations induced upregulation of
genes encoding metabolic enzymes involved in CBD metabolism, and CBD oxidative as well as glucuronide
metabolites were found in cell culture media, demonstrating the ability of HepG2 cells to metabolize CBD. In this
study, the CBD samples were found non-genotoxic. No DNA damage was observed with the comet assay, and no
influence on genomic instability was observed with the cytokinesis block micronucleus and the γH2AX and p-H3
assays. Furthermore, no changes in the expression of genes involved in genotoxic stress response were detected in
the toxicogenomic analysis, after 4 and 24 h of exposure. Our comprehensive study contributes valuable insights
into CBD’s safety profile, paving the way for further exploration of CBD’s therapeutic applications and potential
adverse effects.
Keywords: cannabidiol, CBD, metabolism, cytotoxicity, genotoxicity, mutagenicity
Published in DiRROS: 09.07.2024; Views: 195; Downloads: 181
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12. Health-related quality of life in Slovenian patients with colorectal cancer : a single tertiary care center studyJan Grosek, Jerica Novak, Katja Kitek, Alta Bajrić, Ana Majdič, Jurij Aleš Košir, Aleš Tomažič, 2019, original scientific article Keywords: health-related quality of life, colorectal cancer, colorectal surgery, Slovenia
Published in DiRROS: 05.07.2024; Views: 201; Downloads: 97
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13. High burden of clonal mast cell disorders and hereditary ▫$α-tryptasemia$▫ in patients who need Hymenoptera venom immunotherapyPeter Korošec, Gunter Sturm, Jonathan J. Lyons, Tinkara Pirc Marolt, Manca Svetina, Mitja Košnik, Mihaela Zidarn, Mark Kačar, Nina Frelih, Nika Lalek, Ajda Demšar Luzar, Samo Zver, Matevž Škerget, Ewa Czarnobilska, Wojciech Dyga, Sanja Popović-Grle, Miroslav Samaržija, Lisa Arzt-Gradwohl, Urban Čerpes, Grzegorz Porebski, Branko Pevec, Eva Schadelbauer, Peter Kopač, Julij Šelb, Matija Rijavec, 2024, original scientific article Abstract: Background
In patients who require venom immunotherapy (VIT), there is a need to identify underlying mast cell (MC) disorders since these may affect the risk and severity of future sting reactions and the long-term effectiveness of VIT.
Methods
1319 individuals with Hymenoptera venom allergy (HVA) who needed VIT from referral centers in Slovenia, Austria, Croatia, and Poland underwent examination for KIT p.D816V in peripheral blood leukocytes (PBL) using a highly sensitive PCR test and tryptase genotyping by digital droplet PCR. We also included 183 control individuals with large local reactions (LLRs) to Hymenoptera stings and with asymptomatic sensitization to Hymenoptera venoms.
Results
285 of 1319 individuals recommended for VIT (21.6%) were positive for KIT p.D816V in PBL, preferably those who present with severe reaction (33.9% [n = 207 of 610] with Ring-Messmer grade 3–4 vs. 11% [n = 78 of 709] with Grade 1–2; p < .0001), whereas only 1.3% (n = 2 of 152) of controls with LLR and none with asymptomatic sensitization (n = 31) had KIT p.D816V. KIT p.D816V allelic burden was higher in those with severe reaction (median 0.018% [n = 207] in Grade 3–4 vs. 0.001% [n = 78] in Grade 1–2; p < .0001), and the majority had normal baseline serum tryptase levels (69% [n = 196 of 285]). All KIT p.D816V-positive individuals (n = 41) who underwent bone marrow (BM) biopsy were found to have underlying clonal diseases, principally BM mastocytosis. HαT was also associated with severe HVA and symptoms (p < .01), and remarkably, 31.0% (n = 31 of 100) were found to have concomitant KIT p.D816V. Concomitant HαT and KIT p.D816V showed an additive effect, and having both was associated with the highest risk for severe HVA, even higher than having either HαT or KIT p.D816V alone (OR = 3.8; p < .01).
Conclusions
By employing prospective universal tryptase genotyping and examination for KIT p.D816V in PBL in large HVA populations, we have demonstrated a high burden of clonal MC disorders and HαT in patients who require VIT.
Keywords: anaphylaxis, hereditary α-tryptasemia, hypersensitivity, immunotherapy, mast cell, mastocytosis, venom
Published in DiRROS: 17.06.2024; Views: 328; Downloads: 226
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14. A novel mutation in the FOXC2 gene : a heterozygous insertion of adenosine (c.867insA) in a family with lymphoedema of lower limbs without distichiasisTanja Planinšek Ručigaj, Matija Rijavec, Jovan Miljković, Julij Šelb, Peter Korošec, 2017, original scientific article Keywords: primary lymphedema, FOXC2 mutation, distichiasis, lower limbs lymphedema
Published in DiRROS: 31.05.2024; Views: 290; Downloads: 154
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16. Incidental uptake of 18F-fluorocholine (FCH) in the head or in the neck of patients with prostate cancerMarina Hodolič, Jurij Fettich, 2014, original scientific article Abstract: Background. Positron emission tomography-computed tomography (PET/CT) with 18F-fluorocholine (FCH) is routinely performed in patients with prostate cancer. In this clinical context, foci of FCH uptake in the head or in the neck were considered as incidentalomas, except for those suggestive of multiple bone metastases. Case reports. In 8 patients the incidental focus corresponded to a benign tumour. The standard of truth was histologyin two cases, correlative imaging with MRI in four cases, 99mTc-SestaMIBI scintigraphy, ultrasonography and biochemistry in one case and biochemistry including PTH assay in one case. The final diagnosis of benign tumoursconsisted in 3 pituitary adenomas, 2 meningiomas, 2 hyperfunctioning parathyroid glands and 1 thyroid adenoma. Malignancy was proven histologically in 2 other patients: 1 papillary carcinoma of the thyroid and 1 cerebellar metastasis.Conclusions. To the best of our knowledge, FCH uptake by pituitary adenomas or hyperfunctioning parathyroidglands has never been described previously. We thus discuss whether there might be a future indication for FCH PET/CT when one such tumour is already known or suspected: to detect a residual or recurrent pituitary adenoma aftersurgery, to guide surgery or radiotherapy of a meningioma or to localise a hyperfunctioning parathyroid gland. Inthese potential indications, comparative studies with reference PET tracers or with 99mTc-sestaMIBI in case of hyperparathyroidism could be undertaken.
Keywords: FCH, PET/CT, incidentaloma, meningioma, pituitary adenoma, hyperparathyroidism, thyroid adenoma
Published in DiRROS: 10.04.2024; Views: 438; Downloads: 111
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17. Consequence of the introduction of routine FCH PET/CT imaging for patients with prostate cancer : a dual centre surveyMarina Hodolič, Laure Michaud, V. Huchet, S. Balogova, V. Nataf, K. Kerrou, M. Vereb, Jurij Fettich, Jean-Noël Talbot, 2014, original scientific article Abstract: Background. Fluorocholine(18F) (FCH) was introduced at the beginning of April 2010 in France, Slovenia and three other EU member states for the localisation of bone metastases of prostate cancer with PET. The aim of the study was to compare the evolution of diagnostic imaging in patients with prostate cancer using a new radiopharmaceutical FCH, observed in France and in Slovenia, and to quantify the consequence of the results of new imaging modality on the detection rate of abnormal metastases and recurrences of prostate cancer.Patients and methods. In two centres (France/Slovenia), a survey of the number of nuclear medicine examinations in patients with prostate cancer was performed, covering 5 quarters of the year since the introduction of FCH. For each examination, the clinical and biological circumstances were recorded, as well as the detection of bone or soft tissue foci.Results. Six hundred and eighty-eight nuclear medicine examinations were performed impatients with prostate cancer. Nuclear medicine examinations were performed for therapy monitoring and follow-up in 23% of cases. The number of FCH PET/CT grew rapidly between the 1st and 5th period of the observation (+220%), while the number of bone scintigraphies (BS) and fluoride(18F) PET/CTs decreased (-42% and -23% respectively). Fluorodeoxyglucose(18F) (FDG) PET/CT remained limited to few cases of castrate-resistant or metastatic prostate cancer in Paris. The proportion of negative results was significantly lower with FCH PET/CT (14%) than with BS (49%) or fluoride(18F) PET/CT (54%). For bone metastases, the detection rate was similar, but FCH PET/CT was performed on average at lower prostate-specific antigen (PSA) levels and was less frequently doubtful (4% vs. 28% for BS). FCH PET/CT also showed foci in prostatic bed (53% of cases) or in soft tissue (35% of cases).Conclusions. A rapid development of FCH PET/CT was observed in both centres and led to a higher detection rate of prostate cancer lesions.
Keywords: prostate cancer, PET/CT, fluorocholine (FCH), fluoride(18F), bone scintigraphy, indication of imaging, prostata, rak (medicina), slikovna diagnostika
Published in DiRROS: 04.04.2024; Views: 750; Downloads: 555
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18. The Sierpiński product of graphsJurij Kovič, Tomaž Pisanski, Sara Sabrina Zemljič, Arjana Žitnik, 2023, original scientific article Abstract: In this paper we introduce a product-like operation that generalizes the construction of the generalized Sierpiński graphs. Let $G$, $H$ be graphs and let $f: V(G) \to V(H)$ be a function. Then the Sierpiński product of graphs $G$ and $H$ with respect to $f$, denoted by $G\otimes_f H$, is defined as the graph on the vertex set $V(G) \times V(H)$, consisting of $|V(G)|$ copies of $H$; for every edge $\{g, g'\}$ of $G$ there is an edge between copies $gH$ and $g'H$ of form $\{(g, f(g'), (g', f(g))\}$. Some basic properties of the Sierpiński product are presented. In particular, we show that the graph $G\otimes_f H$ is connected if and only if both graphs $G$ and $H$ are connected and we present some conditions that $G, \, H$ must fulfill for $G\otimes_f H$ to be planar. As for symmetry properties, we show which automorphisms of $G$ and $H$ extend to automorphisms of $G\otimes_f H$. In several cases we can also describe the whole automorphism group of the graph $G\otimes_f H$. Finally, we show how to extend the Sierpiński product to multiple factors in a natural way. By applying this operation $n$ times to the same graph we obtain an alternative approach to the well-known $n$-th generalized Sierpiński graph.
Keywords: Sierpiński graphs, graph products, connectivity, planarity, symmetry
Published in DiRROS: 19.03.2024; Views: 520; Downloads: 384
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19. An experimental study of liquid micro-jets produced with a gas dynamic virtual nozzle under the influence of an electric fieldBor Zupan, Gisel Esperanza Peña-Murillo, Rizwan Zahoor, Jurij Gregorc, Božidar Šarler, Juraj Knoška, Alfonso M. Gañán-Calvo, Henry N. Chapman, Saša Bajt, 2023, original scientific article Abstract: The results of an experimental study of micro-jets produced with a gas dynamic virtual nozzle (GDVN) under the influence of an electric field are provided and discussed for the first time. The experimental study is performed with a 50% volume mixture of water and ethanol, and nitrogen focusing gas. The liquid sample and gas Reynolds numbers range from 0.09–5.4 and 0–190, respectively. The external electrode was positioned 400–500 μm downstream of the nozzle tip and an effect of electric potential between the electrode and the sample liquid from 0–7 kV was investigated. The jetting parametric space is examined as a function of operating gas and liquid flow rates, outlet chamber pressure, and an external electric field. The experimentally observed jet diameter, length and velocity ranged from 1–25 μm, 50–500 μm and 0.5–10 m/s, respectively. The jetting shape snapshots were processed automatically using purposely developed computer vision software. The velocity of the jet was calculated from the measured jet diameter and the sample flow rate. It is found that micro-jets accelerate in the direction of the applied electric field in the downstream direction at a constant acceleration as opposed to the standard GDVNs. New jetting modes were observed, where either the focusing gas or the electric forces dominate, encouraging further theoretical and numerical studies towards optimized system design. The study shows the potential to unlock a new generation of low background sample delivery for serial diffraction measurements of weakly scattering objects.
Keywords: micro jet, electric field, experimental study, flow focusing, Taylor cone, gas dynamic virtual nozzles
Published in DiRROS: 07.02.2024; Views: 583; Downloads: 219
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