Nove spoznaje o fiziološkim i farmakološkim mehanizmima zaštite sluznice želuca

master's thesis

• Title (english): New insights in the physiological and pharmacological mechanisms of gastric mucosa protection
• Author: Ivan Maria Smoday
• Mentor: Predrag Sikirić (mentor)
• Committee member: Marko Sever (predsjednik povjerenstva)
• Committee member: Marija Bakula (član povjerenstva)
• Committee member: Predrag Sikirić (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pharmacology); Zagreb
• Defense date and country: 2023-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract

Zaštita sluznice želuca još uvijek je relevantno istraživačko pitanje. Značajnost zaštite sluznice želuca polazi iz temeljnih principa teorije stresa. Dva temeljna pristupa u istraživanju su smanjivanje agresivnih čimbenika koji djeluju na sluznicu, poput povišenja pH i eradikacija Hp, te poticanje endogenih zaštitnih mehanizama poput NO, PG, SH i angiogenih faktora rasta. Periferni i centralni mehanizmi djeluju u sinergiji da bi organizam cjelovito održao integritet želučane sluznice. Nove spoznaje ukazuju da je mepiramin učinkovit u zaštiti od iritirajućih agensa kada je primjenjen centralno. Uništavanjem izvora endogenih projekcija dopaminskih neurona moždanog debla prema amigdali pogoršavaju se stresne lezije. Nadalje, zašitita sluznice želuca od ishemijsko reperfuzijske ozljede i prekondicioniranje ovisno je o glukokortikoidima. S obzirom na sve veću rezistenciju bakterija, nove terapijske opcije za Hp su nužne. BQT donosi sve više rezultata učinkovite terapijske opcije. Hspp, često nerazmotreni od strane kliničara, pokazali su ovisnost o pH, gdje je viši pH smanjio njihovu vijabilnost. PD-MSC pokazala je ogroman potencijal u rješavanju problema kroničnog atrofičnog gastritisa. Adenokarcinomi želuca bi se u budućnosti mogli liječiti u jednostavnim oblicima s izocijanatima izolirano ili u kombinaciji sa cisplatinom. Također ivermektin je pokazao potencijal liječenja adenokarcinoma preko WNT/B-cateninskog molekularnog puta. NSAIL-i, u kombinaciji s “plinovitim” medijatorima citoprotekcije, mogli bi uistinu održati funkcionalnost NSAIL-a uz smanjivanje njihovih komplikacija. Na kraju, pentadekapeptid BPC 157 opetovano pokazuje u kliničkim i pretkliničkim studijama djelotvornost u bolestima razne etiopatogeneze, što ide u prilog teoriji da je probavni sustav ipak jedan od temeljnih integratora reakcije protiv ugroze homeostaze.

Abstract (english)

Protection of the gastric mucosa is still a relevant research question. The importance of protecting the stomach mucosa is based on the basic principles of stress theory. The two basic research approaches are the reduction of aggressive factors that act on the mucous membrane, such as an increase in pH and the eradication of Hp, and the stimulation of endogenous protective mechanisms, such as NO, PG, SH, CO and angiogenic growth factors. Peripheral and central mechanisms work in synergy for the organism to maintain the integrity of the gastric mucosa. New insights indicate that mepyramine is effective in protecting against irritating agents when administered centrally. By destroying the source of endogenous projections of brainstem dopamine neurons to the amygdala, stress lesions are exacerbated. Furthermore, protecting the gastric mucosa from ischemia-reperfusion injury and preconditioning is dependent on glucocorticoids. New therapeutic options for Hp are necessary today as increasing bacterial resistance develops. BQT is bringing more and more results as an effective therapeutic option. Hspp, often overlooked by clinicians, have shown pH dependence, where higher pH decreased their viability. PD-MSC has shown great potential in solving the problem of chronic atrophic gastritis. In the future, gastric adenocarcinomas could be treated with isocyanates alone or in combination with other chemotherapeutics. Also, ivermectin has shown the potential to treat adenocarcinoma via the WNT/B-catenin molecular pathway. NSAIDs in combination with "gaseous" mediators of cytoprotection could truly maintain the functionality of NSAIDs while reducing their complications. Pentadecapeptide BPC 157 repeatedly shows in clinical and preclinical studies its effectiveness in diseases of various etiopathogenesis, which supports the theory that the digestive system is one of the fundamental integrators of the reaction against threats to homeostasis.

• Keywords: citoprotekcija; želudac; vagus
• Keywords (english): cytoprotection; stomach; vagus
• Language: croatian
• URN:NBN: urn:nbn:hr:105:038251
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2023-10-31 09:22:57