Non-Aromatic Naphthalane: A Future Remedy For Oral Mucosal Lesions

Svrha je ovoga rada prikazati podatke dobivene iz nekoliko eksperimentata koje su proveli autori u vezi sa sastavom posebne frakcije Hrvatske nafte, nazvane “NeAromatskim - Visoko Steranskim (NAVS) naftalanom, te njezinim izraženim protutupalnim djelovanjem i djelovanjem na kontrolu stanične proliferacije. NAVS je dobiven iz nafte vrlo bogate steranima, koja se desetljećima uspješno upotrebljava u liječenju psorijaze (Naftalan, Ivanić Grad, Hrvatska). Proizvodi se gotovo potpunim uklanjanjem policikličkih aromata (od kojih su neki kancerogeni), čime se dobiva potpuno bezbojno ulje ugodnoga mirisa. Prigodom postupka dearomatizaije sterani su održani i čak koncentrirani, kako je i dokazano plinskom kromatografijom i vezanim sustavom plinske kromatografije i spektrometrije masa. Ti su geogeni sterani molekularnom strukturom srodni bioaktivnim spojevima, npr. kortikosteroidima i vitaminu D. Zbog tih strukturnih sličnosti, moguće je objasniti dobru učinkovitost u liječenju psorijaze NAVS-om, u čemu su rezultati obećavajući. Tijekom liječenja NAVS-om nije bilo nikakvih promjena hematoloških niti biokemijskih nalaza. In vitro studije dokazuju izraženu dozno-ovisnu inhibiciju proliferacije stanica planocelularnoga karcinoma SCC VII, ali ne i inhibiciju nemalignih fibroblasta L929, pokazujući time selektivnost u kontroli staničnoga rasta. In vivo rezultati pokazuju znatno usporavanje rasta malignoga tumora. Uzrok tome, osim u samoj kontroli proliferacije tumorskih stanica, autori također vide i u sprječavanju neoangiogeneze (poput onom vitamina D), koje još treba dokazati imunohitokemijskim studijama. Planiraju se dodatna istraživanja i razvija se animalni model oralnog planocelularnoga karcinoma u svrhu budućeg uvođenja NAVS-a u liječenje različitih bolesti oralne sluznice budući da je NAVS i učinkovit i vrlo upotrebljiv zbog superiornih organoleptičnih svojstava.The purpose of this lecture is to summarize data obtained from several experiments conducted by authors, regarding the composition of special Croatian petrol fraction reffered to as “Non Aromatic- Very rich in Steranes” (NAVS) naphthalane, as well as its potent-inflammatory and cellular growth controlling effect. NAVS is derived from ordinary brown naphthalane, particulaly rich in steranes, that has been famous for decades in the treatment of psoriasis vulgaris (Naftalan, Ivanić Grad, Croatia). NAVS was prepared by removing virtually all of its original polycyclic aromatic content (some of them are carcinogenic), which resulted in completely colourless transparent oil with a pleasant scent. Steranes were preserved and concentrated during the de-aromatisation process, as was proven by means of GC and GC-MS. These geogenic steranes have molecular skeletons analogous to bioactive compounds, such as corticosteroids and vitamin D. Due to these structure similarities, we can explain the beneficial affects in treating psoriatic patients with NAVS, which yielded promising results. NAVS treatment did not affect either haematological or biochemical findings. Further studies established In vitro dose dependant inhibition of planocellular carcinoma (SCC VII) cell proliferation, withhout interfering with nonmalignant fibroblast (L929) cells, thus showing selectivity in cell proliferation control. In vivo results showed marked delay in tumour growth. A rationale for that, besides cell proliferation control, authors see also in the antineoangiogenetic activity of NAVS (similar to vitamin D), wich is yet to bi proved through immunohistochemical studies. Future studies are planned and oral planocellular carsinoma animal models are being developed in order to introduce NAVS in the treatment of different conditions of oral mucosa, because the preparation is not only effective, but also highly applicable in oral tissues, due to its superior organoleptic properties

International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients with Psoriasis

Importance: A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. Objective: To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Design, Setting, and Participants: Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). Main Outcomes and Measures: In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Results: Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. Conclusions and Relevance: In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.