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Male Mune Codicil From the 18th Century – a Glimpse Into the Past of Everyday-Life at the Opatija Karst
No full textU bogatoj ostavini povjesničara i svećenika dr. sc. Maksa Peloze čuva se nadopuna oporuke (kodicil) Jurja Samse (izv. Giorgio Samsa) iz sela Male Mune. Ta je razredba posljednje volje oporučitelja zapisana pred svjedocima 1754. godine rukom lokalnoga dušobrižnika. Osim što daje uvid u prošlost nasljednopravnih odnosa, ona predstavlja višestruko vrijedan izvor za istraživanje novovjekovne prošlosti na području Opatijskoga krasa kojemu selo Male Mune pripada, osobito uzimajući u obzir rijetkost takvoga arhivskoga gradiva.
Polazeći od sadržajne analize kodicila, autori donose pregled teritorijalno-crkvene pripadnosti sela Male Mune sredinom 18. stoljeća te predstavljaju u kodicilu zabilježene antroponime i mikrotoponime koji svoje postojanje svjedoče i danas.In the rich legacy of historian and priest Makso Peloza, PhD, the supplement to the will of George Samsa (originally: Giorgio Samsa) from the village of Male Mune is preserved. This statement of the testator’s last will was written down by a local priest in 1754 in front of witnesses. In addition to providing an insight into the past of inheritance relations, it is a multifaceted valuable resource for researching the history of daily life in the area of the Opatija Karst to which the village of Male Mune belongs, especially given the rarity of such archival material.
Starting with the content analysis of the will, the authors will provide an overview of the territorial and church affiliation of the village of Male Mune in the mid-18th century. The authors will also present the anthroponyms and microtoponyms recorded in the will, which continue to exist even today
CONNECTION BETWEEN HEPATITIS C VIRUS INFECTION AND MALADAPTIVE PERSONALITY FUNCTIONING IN OPIOID-DEPENDENT PATIENTS IN OPIOID SUBSTITUTION TREATMENT
No full textCilj istraživanja: Cilj istraživanja bio je analizirati povezanost infekcije hepatitis C virusom
(HCV) i neprilagođenog funkcioniranja ličnosti u ovisnika o opioidima na opioidnom
supstitucijskom liječenju.
Ispitanici i metode: Provedeno je presječno istraživanje. U istraživanje su uključene odrasle
osobe ovisne o opioidima koje su najmanje tri mjeseca bile na opioidnom supstitucijskom
liječenju u jednom od pet centara u Bosni i Hercegovini, a ne pate od velikih psihijatrijskih
bolesti (shizofrenija, depresija, bipolarni poremećaj). Ispitivanu skupinu činili su pacijenti na
opioidnom supstitucijskom liječenju koji su pozitivni na HCV, a kontrolnu skupinu, usklađenu
po dobi i spolu, pacijenti na supstitucijskom liječenju koji nisu pozitivni na HCV. Stupanj
prilagođenosti funkcioniranja ličnosti sudionika u istraživanju mjeren je upitnikom simptoma
poremećaja ličnosti (engl. Severity Indices of Personality Problems) (SIPP-118).
Rezultati: U istraživanju je sudjelovalo ukupno 206 pacijenata, od kojih je bilo 19 (9,2 %) žena
i 187 (90,8 %) muškaraca. Medijan starosti pacijenata iznosio je 29,0 godina, uz interkvartilni
raspon od 10 godina. Ukupno 112 (54,4 %) pacijenata bilo je HCV-pozitivno, a 94 (45,6 %)
HCV-negativno. Čimbenici značajno povezani s infekcijom HCV-om jesu: domena relacijskog
kapaciteta, omjer izgleda (OR) = 1,20 (95 % CI 1,07 – 1,36, p = 0,003), domena integracije
identiteta – stavka samopoštovanja, OR = 0,95 (95 % CI 0,91 – 0,99, p = 0,012), domena
relacijskog kapaciteta – stavka trajnog odnosa, OR = 0,88 (95 % CI 0,80 – 0,97, p = 0,008),
domena društvene usklađenosti – stavka suradnje, OR = 0,93 (95 % CI 0,89 – 0,98, p = 0,005),
trajanje liječenja, OR = 1,08 (95 % CI 1,02 – 1,14, p = 0.013) i bilo koja vrsta poremećaja
ličnosti, OR = 2,17 (95 % CI 1,16 – 4,05, p = 0,015).
Zaključak: Ovisnici o opioidima na opioidnom supstitucijskom liječenju imali su veći rizik od
infekcije HCV-om ako je njihova ličnost bila disfunkcionalna, posebno u aspektima
samopoštovanja, uspostavljanja trajnih odnosa, suradnje i tolerancije frustracije. Bilo koja vrsta
poremećaja ličnosti, nesuradnja u procesu liječenja, nestabilno mjesto stanovanja, život bez
djece, nezaposlenost i zloporaba više vrsta tvari pojačavaju negativne učinke neprilagođenog
funkcioniranja ličnosti.Objectives: The aim of this research was to analyze the association between HCV infection
and maladaptive personality functioning in opioid addicts receiving opioid substitution
treatment.
Subjects and methods: The study was designed as a cross-sectional study. The participants of
the study were adult opioid addicts who had been receiving opioid substitution treatment for at least
three months in one of the five centers in Bosnia and Herzegovina and who did not have major
psychiatric disorders (schizophrenia, depression, bipolar disorder). The case group consisted of
patients in opioid substitution treatment who were positive for hepatitis C virus (HCV), and the
control group, matched in age and sex, consisted of patients in substitution treatment who were
not HCV-positive. The level of adjustment of personality functioning of the study participants
was measured using the Severity Indices of Personality Problems (SIPP-118).
Results: A total of 206 patients participated in the study, of whom 19 (9.2%) were women and
187 (90.8%) were men. The median age of the patients was 29.0 years, with an interquartile
range of 10 years. A total of 112 (54,4%) patients were HCV-positive, and 94 (45,6%) were
HCV-negative. Factors that were significantly associated with HCV infection were: relational
capacity domain, odds ratio (OR) = 1,20 (95% CI 1,07 – 1,36, p = 0,003), identity integration
domain – self-esteem item, OR = 0,95 (95% CI 0,91 – 0,99, p = 0,012), relational capacity
domain –lasting relationship item, OR = 0,88 (95% CI 0,80 – 0,97, p = 0,008), social harmony
domain – cooperation item, OR = 0,93 (95% CI 0,89 – 0,98, p = 0,005), duration of treatment,
OR = 1,08 (95% CI 1,02 – 1,14, p = 0.013), and any type of personality disorder, OR = 2,17
(95% CI 1,16 – 4,05, p = 0,015).
Conclusion: Opioid addicts in substitution treatment have a higher risk of HCV infection if
their personality is dysfunctional, especially in the aspects of self-esteem, establishing lasting
relationships, cooperation, and frustration tolerance. Any type of personality disorder, lack of
cooperation in the treatment process, housing instability, life without children, unemployment,
and polysubstance abuse increase the negative effects of maladaptive personality functioning
IMMUNE ROLE OF PrPC PROTEIN DURING VIRAL INFECTION
No full textCilj istraživanja: Stanični prionski protein, PrP, mali je glikoprotein na površini stanica
poznat prvenstveno po svojoj ključnoj ulozi u patogenezi neurodegenerativnih poremećaja
poznatih kao prionske bolesti. Sve veći broj istraživanja ukazuje na ulogu proteina PrP u
moduliranju imunosnog sustava, posebno u utišavanju imunosnog odgovora u tkivima poput
mozga, gdje izražena upala može prouzročiti značajna oštećenja. PrP nije samo prisutan na
površini imunosnih stanica, već se može vezati na njih i modulirati njihovu funkciju, što
ukazuje na njegovo prepoznavanje od strane imunosnih receptora. U slučaju prirođene
infekcije citomegalovirusom (CMV-om), pojačana aktivacija imunosnog odgovora može
uzrokovati ozbiljna neurološka oštećenja. Stoga je glavni cilj ovog istraživanja odrediti
imunosnu funkciju proteina PrP u modelu prirođene infekcije mišjim CMV-om (MCMV-om).
Materijali i metode: Za istraživanje utjecaja infekcije MCMV-om na biologiju proteina PrP,
primijenili smo protočnu citometriju, konfokalnu mikroskopiju i metodu imunoblota za analizu
razine PrP-a u inficiranim stanicama te identificirali mehanizam odstranjivanja proteina PrP iz
stanica inficiranih MCMV-om korištenjem inhibitora i detekcije proteina PrP. U modelu
prirođene infekcije MCMV-om kod novookoćenih miševa divljeg tipa i miševa kojima
nedostaje PrP, uklanjanjem populacije limfocita identificirali smo stanice odgovorne za utjecaj
PrP-a na tijek infekcije. Karakterizirali smo te stanice fenotipski i funkcionalno protočnom
citometrijom i sekvenciranjem RNK na razini jedne stanice. Za analizu ispoljavanja topivih
imunosnih medijatora u uzorcima tkiva nakon prirođene infekcije MCMV-om, proveli smo
multipleks analizu citokina i kemokina. Također smo proveli funkcionalne testove proizvodnje
proupalnih citokina kako bismo istražili utjecaj slobodnog proteina PrP na efektorsku funkciju
imunosnih stanica te istražili utjecaj prisustva proteina PrP na ishod imunopatologije mozga.
Rezultati: CMV utječe na ispoljavanje proteina PrP, prvenstveno potičući njegov pojačan
izražaj, pri čemu ujedno dolazi do odcjepljivanja sa stanične membrane pod utjecajem proteaze
ADAM10 i uklanjanja PrP-a iz stanica. Slobodni protein PrP se veže na limfocite CD8 T kod
novookoćenih miševa inficiranih MCMV-om, smanjujući njihovu sposobnost proizvodnje
proupalnih citokina. U miševa kojima nedostaje protein PrP, limfociti CD8 T pokazuju
povećanu aktivnost, uključujući veći broj virus-specifičnih stanica, povećanu citotoksičnost i
izlučivanje citokina. Ovi miševi su pokazali poboljšanu sposobnost uklanjanja virusa bez
izazivanja povećane imunopatologije.
Zaključak: Protein PrP modulira imunosni odgovor tijekom prirođene infekcije CMV-om,
umanjujući aktivnost imunosnih stanica CD8 T i posljedično uklanjanja virusa.Objectives: The cellular prion protein, PrP, is a small glycoprotein on the cell surface primarily
known for its critical role in the pathogenesis of neurodegenerative prion diseases. An
increasing body of research points to the role of PrP in modulating the immune system,
particularly in dampening immune responses in tissues such as the brain, where severe
inflammation can cause significant damage. PrP is not only present on the surface of immune
cells but also binds to them and modulates their function, implying its recognition by immune
receptors. In the case of congenital cytomegalovirus (CMV) infection, enhanced activation of
the immune response can lead to serious neurological damage. Therefore, the main goal of this
research is to determine the immune function of PrP protein in a model of congenital infection
with murine CMV (MCMV).
Materials and methods: To investigate the impact of MCMV infection on the biology of the
PrP protein, we used flow cytometry, confocal microscopy and immunoblot to analyze the
levels of PrP in infected cells and identified the mechanism of PrP protein cleavage by detecting
PrP in MCMV infected cells treated by inhibitors. In a model of MCMV congenital infection
in newborn wild-type mice and mice lacking PrP, by depleting the lymphocyte population, we
identified the cells responsible for the influence of PrP on the course of the infection. We
characterized these cells phenotypically and functionally by flow cytometry and single cell
RNA sequencing. To analyze the expression of soluble immune mediators in tissue samples
after congenital MCMV infection, we used a multiplex assay of cytokines and chemokines. We
also conducted functional assay of pro-inflammatory cytokine production to investigate the
influence of cleaved PrP protein on the effector function of immune cells and investigated the
influence of the PrP protein on the outcome of brain immunopathology.
Results: CMV affects the expression of the PrP protein primarily by promoting its increased
expression, while simultaneously causing its removal from the cell membrane through cleavage
by the ADAM10 protease. Cleaved PrP protein binds to CD8 T lymphocytes in neonatal mice
infected with MCMV, reducing their ability to produce pro-inflammatory cytokines. In mice
lacking the PrP protein, CD8 T lymphocytes show increased activity, including a higher
number of virus-specific cells, increased cytotoxicity, and cytokine secretion. These mice
showed an improved ability to clear the virus without causing excessive immunopathology.
Conclusion: The protein PrP modulates the immune response during congenital CMV
infection, reducing the activity of CD8 T immune cells and consequently clearing the virus
Six Decades of the Journal Medicina Fluminensis: A Constant Guide of Medical Thought from the City That Flows
No full text-
The Applied Genomics Development Strategy by the Croatian Academy of Sciences and Arts paves the way for the future development of applied genomics in Croatia
No full textDifferences in segmental fat accumulation patterns by sex and ethnicity: An international approach
No full textExcess fat on the body impacts obesity-related co-morbidity risk; however, the location of fat stores affects the severity of these risks. The purpose of this study was to examine segmental fat accumulation patterns by sex and ethnicity using international datasets. An amalgamated and cross-calibrated dataset of dual x-ray absorptiometry (DXA)-measured variables compiled segmental mass for bone mineral content (BMC), lean mass (LM), and fat mass (FM) for each participant; percentage of segment fat (PSF) was calculated as PSFsegment = (FMsegment/(BMCsegment + LMsegment + FMsegment)) × 100. A total of 30 587 adults (N = 16 490 females) from 13 datasets were included. A regression model was used to examine differences in regional fat mass and PSF. All populations followed the same segmental fat mass accumulation in the ascending order with statistical significance (arms < legs < trunk), except for Hispanic/Latinx males (arms < [legs = trunk]). Relative fat accumulation patterns differed between those with greater PSF in the appendages (Arab, Mexican, Asian, Black, American Caucasian, European Caucasian, and Australasian Caucasian females; Black males) and those with greater PSF in the trunk (Mexican, Asian, American Caucasian, European Caucasian, and Australasian Caucasian males). Greater absolute and relative fat accumulation in the trunk could place males of most ethnicities in this study at a higher risk of visceral fat deposition and associated co-morbidities
The necessity of ethics in the midwifery profession: from the construction of the identity of the profession to the determination of everyday midwifery practice
No full textEtika je jedan od odredbenih čimbenika svake profesije pa tako i primaljska etika za primaljstvo. Primalje se u svojoj svakodnevnoj praksi suočavaju s brojnim etičkim pitanjima. Njihov odnos prema trudnici, majci i djetetu, babinjači te ginekološkoj pacijentici vrlo je kompleksan i ona mora posjedovati vještine i znanje za etičko djelovanje. Pristup bioetičkim pitanjima danas je multidisciplinaran, a posebna pozornost u perinatalnoj medicini, ginekologiji i porodništvu nije prepuštena samo zdravstvenim djelatnicima, nego je u nju uključena klijentica/pacijentica i njena obitelj, uz značajnu pozornost na pravima fetusa. Stoga se u radu pokazuje da osim neophodnosti primaljske etike u konstrukciji primaljstva kao zaokružene profesije, etika je primalji temelj za uspostavu adekvatnog odnosa prema klijentici/pacijentici i njenoj obitelji u svakodnevnoj primaljskoj praksi i pružanju adekvatne zdravstvene skrbi.Ethics is one of the defining factors of every profession, including midwifery. Midwives face numerous ethical issues in their daily practice. Their relationship towards pregnant women, mothers and children, midwives and gynecological patients is very complex and they must have the skills and knowledge to act ethically. The approach to bioethical issues today is multidisciplinary, and special attention in perinatal medicine, gynecology and obstetrics is not left only to health professionals, but includes the client/patient and her family, with significant attention to the rights of the fetus. Therefore, the paper shows that in addition to the necessity of midwifery ethics in the construction of midwifery as a well-rounded profession, midwifery ethics is the basis for establishing an adequate relationship with the client/patient and her family in everyday midwifery practice and providing adequate health care
SALIVARY BIOMARKERS AND THE QUALITY OF LIFE IN PATIENTS WITH ORAL MANIFESTATIONS OF INFLAMMATORY BOWEL DISEASE : doctoral thesis
No full textCiljevi:. Utvrditi povezanost oralnih očitovanja upalnih bolesti crijeva (UBC) s vrstom bolesti,
aktivnosti bolesti, vrstom terapije, upalnim markerima iz krvi i stolice, koncentracijama
laktoferina i neopterina u slini te kvalitetom života povezanom s oralnim zdravljem. Utvrditi
prevalenciju specifičnih i nespecifičnih oralnih promjena, prevalenciju oportunističkih oralnih
infekcija u bolesnika na biološkoj terapiji, utjecaj oralnog zdravlja na kvalitetu života i
koncentraciju salivarnih laktoferina i neopterina u UBC ispitanika.
Ispitanici i metode: U istraživanje je uključen 71 UBC i 71 zdravi kontrolni ispitanik. Ispunili
su anamnestički upitnik, upitnik samoprocjene oralnih simptoma i znakova i upitnik
samoprocjene utjecaja oralnog zdravlja na kvalitetu života. Napravljeni su oralno klinički
pregled, obrisak oralne sluznice radi mikrobiološke analize i test lučenja nestimulirane sline.
Uzorak sline je korišten za imunoenzimsku analizu koncentracije laktoferina i neopterina.
Rezultati: S oralnim očitovanjima se prezentiralo 73,2 % UBC i 22,5 % kontrolnih ispitanika
(p=<0,001). Viša prevalencija atrofičnog glositisa (p=0,001), bijelo obloženog jezika (p=0,01),
protetskog palatitisa (p=0,006), kandidijaze (p=0,003) i hiposalivacije (p=0,000) je zabilježena
u UBC ispitanika u odnosu na kontrolne ispitanike. Dva UBC ispitanika su imala specifična
očitovanja. UBC ispitanici na anti-TNFα i anti-integrin α4β7 terapiji su imali višu prevalenciju
kandidijaze (p=0,016) u odnosu na kontrolne ispitanike. Nije bilo značajne razlike u
samoprocjeni utjecaja oralnog zdravlja na kvalitetu života između UBC i kontrolnih ispitanika
(p=0,125). Ispitanici s oralnim očitovanjem su imali veći utjecaj oralnog zdravlja na kvalitetu
života. UBC ispitanici s i bez oralnih očitovanja su imali višu koncentraciju laktoferina u slini
u ng/ml (p=0,020) u odnosu na kontrolne ispitanike, ali nije zabilježena značajna razlika u
koncentraciji salivarnog neopterina (p=0,969). Pronađena je povezanost hiposalivacije s
koncentracijom laktoferina u slini u ng/ml (p<0,01, r=0,377) i Mayo score indeksom (p<0,05,
r=0,248), atrofičnog glositisa s koncentracijom neopterina u slini u ng/ml (p<0,01, r=0,392) i
utjecajem oralnog zdravlja na kvalitetu života (p<0,001, r=0,393) te eksfolijativnog glositisa s
C-reaktivnim proteinom (p<0,01, r=0,453).
Zaključak: UBC bolesnici imaju učestalije oralne promjene u odnosu na zdrave osobe.
Uključenje specijalista oralne medicine u liječenje UBC bolesnika bi doprinijelo ranom
prepoznavanju, dijagnostici i liječenju oralnih promjena sa svrhom poboljšanja oralnog zdravlja
i njegovog utjecaja na kvalitetu života.Objectives: To determine the correlation between oral manifestations (OM) of inflammatory
bowel disease (IBD) and disease type, disease activity, type of therapy, blood and faecal
inflammation markers, salivary lactoferrin and neopterin concentrations and oral health-related
quality of life. To define the prevalence of specific and non-specific OM, the prevalence of oral
opportunistic infections in subjects receiving biologic therapy, the impact of oral health on the
quality of life and concentrations of salivary lactoferrin and neopterin in IBD subjects.
Patients and methods: 71 IBD and 71 healthy control subjects were included in the study. All
subjects completed the patients’ history questionnaire, a self-assessment questionnaire on oral
symptoms and signs, and a self-assessment oral health impact questionnaire. Oral examination,
oral swab test and non-stimulated salivary flow rate were conducted. Saliva samples were used
for immunoenzyme analysis of lactoferrin and neopterin concentrations.
Results: 73.2% of IBD and 22.5% of control subjects have presented with OM (p=<0,001).
IBD subjects had a higher prevalence of atrophic glossitis (p=0.001), coated tongue (p=0.01),
denture palatitis (p=0.006), candidiasis (p=0.003) and hyposalivation (p=0,000) compared to
control subjects, while 2 IBD subjects presented with specific manifestations. IBD subjects on
anti-TNFα and anti-integrin α4β7 therapy had a higher prevalence of candidiasis (p=0.016)
compared to control subjects. No significant difference was found in self-assessment of oral
health impact on the quality of life between groups (p=0.125). Subjects with OM had higher
oral health-related quality of life impact. IBD subjects with and without OM had higher
concentrations of salivary lactoferrin (ng/ml) compared to control subjects (p=0.020), but no
significant difference was found in salivary neopterin concentrations between groups
(p=0.969). Hyposalivation was correlated with salivary lactoferrin concentration (p<0.01,
r=0.377) and Mayo score index (p<0.05, r=0.248), atrophic glossitis was correlated with
salivary neopterin concentration (p<0.01, r=0.392) and oral health-related quality of life
(p<0.001, r=0.393), while exfoliating glossitis was in correlation with C-reactive protein
(p<0.01, r=0.453).
Conclusion: IBD patients have more OM than healthy subjects. The involvement of an oral
medicine specialist in treating IBD patients could contribute to early recognition, diagnostics,
and treatment of OM for oral health improvement and its impact on quality of lif
Effective Strategies and a Ten-Point Plan for Cardio-Kidney-Metabolic Health in Croatia: An Expert Opinion
No full textCardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, including in Croatia. Since most patients have multiple disorders and diseases caused largely by the same risk factors, and as it is essential to approach each patient as a person with all disorders, today, we are talking about a new paradigm—cardio-renal-metabolic (CKM) syndrome and cardio-renal-metabolic health, which necessarily includes brain health. Elevated systolic blood pressure, LDL cholesterol, smoking, obesity, diabetes, impaired renal function or chronic kidney disease, which all stem from insufficient physical activity, an unhealthy diet with excessive intake of table salt, and air pollution, are the leading causes of overall morbidity and mortality from CKM diseases, especially mortality from CVD. Experts from various fields key to CKM health have written this document with the aim of integrating it as part of the national plan for the prevention of chronic non-communicable diseases with a focus on CVD, which should become mandatory and be based on the existing guidelines of professional societies
THE ROLE OF RELATIVE HYPOGLYCEMIA CAUSED BY VIRAL INFECTION IN PROMOTING INNATE ANTIVIRAL IMMUNE RESPONSE
No full textCiljevi: Tijekom bolesti patogeni izazivaju niz promjena u sistemskom metabolizmu i ponašanju koji
zajednički nazivamo ponašanje povezano s bolešću (eng. sickness behaviour). Jedan od sustava
obuhvaćenih ovim promjenama je i endokrini sustav koji kontrolira energetsku homeostazu
organizma. Primijetio sam da jaka virusna infekcija miševa, za razliku od normalne infekcije, izaziva
pad u razini glukoze u krvi koji sam nazvao relativna hipoglikemija (RHG). Cilj istraživanja bilo je
utvrditi kako i zašto nastaje RHG. Htio sam razjasniti kojim mehanizmom pri jakoj infekciji nastaje
pad u razini glukoze i radi li se o djelovanju virusa ili odgovoru organizma na infekciju. Također, htio
sam odrediti izaziva li RHG promjene u progresiji infekcije i kojim mehanizmom se to ostvaruje.
Materijali i metode: Za proučavanje učinaka različitih razina glukoze na progresiju virusne infekcije
in vitro koristio sam metode uzgoja primarnih i imortaliziranih staničnih kultura i infekcije in vitro. Za
praćenje tijeka infekcije koristio sam test virusnih čistina ili sam koristio viruse koji izražavaju
fluorescentni protein i pratio ih koristeći protočnu citometriju i konfokalnu mikroskopiju. Za
proučavanje utjecaja niske razine glukoze na napredak infekcije koristio sam stanične medije s
različitim koncentracijama glukoze ili medije u koje su bili dodani različiti metaboliti koji sudjeluju u
energetskom metabolizmu. Za određivanje razine različitih markera i molekula koristio sam niz
metoda, od kolorimetrijskih testova, ELISA-e do Western blota.
Za praćenje učinaka infekcije in vivo koristio sam različite genetski modificirane miševe.
Miševi su bili inficirani različitim virusima (MCMV, LCMV, gripa tip A) u različitim dozama, a
potom sam mjerio razinu šećera u krvi ili provodio druge metaboličke testove. Za određivanje količine
virusa u tkivima koristio sam qPCR i metodu virusnih čistina. Za određivanje količine glikogena u
jetri koristio sam kolorimetrijsku analizu i priredio i obojao histološke preparate jetre.
Rezultati: Pokazao sam da jaka infekcija virusom izaziva pad u razini glukoze u krvi, i da takva, niska
razina glukoze tijekom virusne infekcije ima protektivan učinak. Jaka infekcija potiče
hiperinzulinemiju putem aktivacije limfocita T i zajedničkog djelovanja citokina IFN i IL-1 To
rezultira smanjenom razgradnjom glikogena u jetri što na kraju dovodi do relativne hipoglikemije (RHG). Niska razina glukoze potiče pojačano lučenje interferona tipa I zbog smanjene proizvodnje
laktata u stanicama koji inhibira ovaj signalni put.
Zaključak: Jaka virusna infekcija izaziva pad u razini šećera u krvi (RHG) zbog privremene
hiperinzulinemije uzrokovane aktivacijom imunosnog sustava i lučenjem IFN i IL-1. RHG potiče
odgovor putem interferona tipa I što ima zaštitno antivirusno djelovanje. Ovo otkriće pruža novi uvid
u interakciju imunosnog i endokrinog sustava te daje na važnosti promjenama u energetskom
metabolizmu organizma tijekom infekcije. S obzirom na sve veći udio populacije koja boluje od
(pre)dijabetesa, odnosno ima probleme s održavanjem normalne razine glukoze u krvi i pojačanoj
sklonosti infekcijama u toj grupi, ovo istraživanje može biti od pomoći pri bolničkom tretmanu
pacijenata tijekom jakih virusnih infekcija.Goals: During disease pathogens cause a series of changes in systemic metabolism and behaviour
which we call sickness behaviour. One of the systems impacted by these changes is the endocrine
system that controls energy homeostasis. I have noticed that strong viral infection, but not normal
level of infection, causes a drop in blood glucose levels that I have termed relative hypoglycaemia
(RHG). The goal of this research was to determine how and why RHG appears. I wanted to elucidate
the mechanisms by which strong infection causes a drop in glucose levels, and whether that is the
result of virus or our systemic response to infection. Furthermore, I wanted to determine whether RHG
has an impact on the progression of infection and by which mechanisms and pathways.
Materials and methods: To study the effects of the different glucose levels on the progression of
viral infection in vitro I have used the methods of cell culture using primary and immortalized cell
lines and infection in vitro. To monitor the progress of infection I have used plaque assay or viruses
that express fluorescent protein which enabled me to visualize infected cells using flow cytometry or
confocal microscopy. To study the effects of low glucose levels on infection rate I have used cell
media with varying levels of glucose or those with added key metabolites which take parti n energy
metabolism of the cell. To determine the levels of various biomarkers and molecules I have used
various methods including colorimetric assays, ELISA, and Western blot.
To track the infection in vitro I have used an array of genetically modified mice. They were infected
with different viruses (MCMV, LCMV, influenza, etc.) in varying concentrations, then I was tracking
their fasting blood glucose levels or other metabolites. To determine the viral load in tissues I have
used qPCR or plaque assay. To determine the level of liver glycogen I have used colorimetric assay
and histology slides of the liver.
Results: I have shown that strong viral infection causes a drop in blood glucose levels, and that lower
blood glucose levels during viral infection have a protective effect. Strong infection induces
hyperinsulinemia via its effect on T cells and production of cytokines IFN and IL-1. This results
in a decreased glycogen utilization in liver which leads to relative hypoglycemia (RHG). Low glucose levels then lead to an increase in type I interferon production via changes in cell lactate production
which affects signaling pathways that promote the secretion of type I interferons.
Conclusions: Strong viral infection causes a drop in blood glucose levels (RHG) due to temporary
hyperinsulinemia caused by immune system activation and secretion of IFN and IL-1. RHG
promotes immune response via type I interferons and that has a protective antiviral effect. This
discovery offers a new insight in the interactions between immune and endocrine system, giving
weight to changes in energy metabolism during infection. Considering that an increasing part of global
population suffers from (pre)diabetes which causes aberrations in blood glucose level management
and the increase in infections persistence in that group, this research can help with medicinal practices
in regard to treatment during strong viral infections