17 research outputs found
Puzzling functions of HSV-1 miRNAs in productive and latent infection
Herpes simplex virus (HSV) is a widespread human pathogen able to cause a broad spectrum of diseases of varying severity. HSV-1, and closely related virus HSV-2, employ a number of functions to evade host defense mechanisms and tailor the cellular environment during their complex life cycle comprised of productive and life-long latent infection. Once the latency is established, the virus can periodically reactivate in response to different stimuli and cause recurrent disease. Despite being one of the most intensively studied viruses, many biological aspects involved in the control of the lytic-latent switch and regulation of viral and host gene expression remained unclear. Discovery of the HSV-encoded miRNAs, a class of small regulatory RNAs, led to the hypothesis that they could have a central role in the establishment and maintenance of latency. HSV-1 and HSV-2 encode many miRNAs, differentially expressed during both phases of infection. The functions of HSV-encoded miRNAs have been experimentally addressed by several laboratories; however, the exact roles remain inconclusive. In this review, we will discuss the function of HSV-encoded miRNAs described to date, in terms of their viral and host targets, and the potential significance of such regulation for viral infection.</p
Surgical Scientific Publication and the 1991ā1995 War in Croatia
The aim of this study was to evaluate surgical scientific publication in relation to the 1991ā1995 war in Croatia,
based on the articles indexed in Medline database that were published in 1980ā2005 period. The number of articles was
extracted from PubMed and analysed with trend analysis, which is preferred analytic approach over calculation of crude
publication rates. The results indicate sporadic pre-war output, which was almost completely reduced by the onset of war.
During wartime, a significant increasing trend in the number of published surgical articles that were related to warfare
was detected (p=0.003). During the post-war period a gradual shift towards surgical articles that were not related to
warfare was detected, also marked by the significant increasing trend (p=0.027). Both trends were significantly steeper
than the overall Croatian biomedical output, suggesting that surgical scientific articles were being published more dynamically
than in other biomedical areas in Croatia. The results suggest that war in Croatia has had a strong modifying
effect on the surgical scientific output
HepatotoksiÄni potencijal smeÅ”e toluena, stirena i etanola: in silico toksikogenomiÄka analiza
Organic solvents are still widely used in various industries and considered the most
common chemicals associated with liver injury in workers. For research into the
relationships between these chemicals and genes, interactions among chemicals, molecular
pathways and biological processes, a significant place in toxicity testing has been taken by in
silico methodologies. This study aims to provide evidence for the involvement of a selected
mixture of organic solvents (toluene, styrene, ethanol) in liver disease development and
show the potential of in silico toxicogenomic data-mining in determining possible
mechanisms of mixture toxicity. The Comparative Toxicogenomics Database (CTD),
GeneMania and ToppGene Suite were used for data-mining. The results showed that there
were 17 genes connected with liver injury common for all the tested solvents. Co-expression
(61.73%) was the most prominent interaction between the genes, while physical
interactions were present at 14.56%, co-localization at 12.54% and interactions predicted by
the server at 6.62%. Gene ontology analysis revealed biological processes affected by the
investigated mixture (reactive oxygen species metabolic and biosynthetic process, response
to oxidative stress, and response to organic cyclic compound). Oxidative stress response,
antioxidant and oxidoreductase activity, vitamin B12 metabolism were noted as the key
molecular pathways contributing to liver disease development. Our results emphasize the
role of oxidative stress as one of the mechanisms of organic solvents' mixture toxicity and
provide new insights into molecular mechanisms involved in hepatotoxicity.Organski rastvaraÄi se joÅ” uvek Å”iroko koriste u raznim industrijama i smatraju se
najÄeÅ”Äim hemikalijama povezanim sa oÅ”teÄenjem jetre kod radnika. Za istraživanje odnosa
izmeÄu ovih hemikalija i gena, interakcija meÄu hemikalijama, molekularnih puteva i
bioloÅ”kih procesa, znaÄajno mjesto pripada i in silico metodologijama. Cilj ove studije je da
pruži dokaze za povezanost odabrane smeÅ”e organskih rastvaraÄa (toluen, stiren, etanol) u
razvoju bolesti jetre, i da pokaže potencijal in silico toksikogenomiÄke analize podataka u
odreÄivanju moguÄih mehanizama toksiÄnosti smjeÅ”e. Za prikupljanje podataka koriÅ”teni su
Comparative Toxicogenomics Database (CTD), GeneMania i ToppGene Suite. Rezultati ove
analize su pokazali da postoji 17 gena povezanih s oÅ”teÄenjem jetre zajedniÄkih za sva tri
navedena rastvaraÄa. Koekspresija (61,73%) bila je najistaknutija interakcija izmeÄu gena,
dok su fiziÄke interakcije bile prisutne sa 14,56%, kolokalizacije sa 12,54%, a interakcije
predviÄene od strane servera sa 6,62%. Analiza ontologije gena izdvojila je bioloÅ”ke procese
na koje utiÄe ispitivana smeÅ”a (metaboliÄki i biosintetski proces reaktivnih kiseonikovih
vrsta, odgovor na oksidativni stres i odgovor na organska cikliÄna jedinjenja). Odgovor na
oksidativni stres, aktivnost antioksidanata i oksidoreduktaze, i metabolizam vitamina B12 su
navedeni kao kljuÄni molekularni putevi koji dobrinose razvoju bolesti jetre. Rezultati ovog
rada naglaÅ”avaju ulogu oksidativnog stresa kao jednog od mehanizama toksiÄnosti smeÅ”e
organskih rastvaraÄa i daju novi uvid u molekularne mehanizme ukljuÄene u
hepatotoksiÄnost.VIII Kongres farmaceuta Srbije sa meÄunarodnim uÄeÅ”Äem, 12-15.10.2022. Beogra
Human Papillomaviruses-Associated Cancers: An Update of Current Knowledge
Human papillomaviruses (HPVs), which are small, double-stranded, circular DNA viruses infecting human epithelial cells, are associated with various benign and malignant lesions of mucosa and skin. Intensive research on the oncogenic potential of HPVs started in the 1970s and spread across Europe, including Croatia, and worldwide. Nowadays, the causative role of a subset of oncogenic or high-risk (HR) HPV types, led by HPV-16 and HPV-18, of different anogenital and head and neck cancers is well accepted. Two major viral oncoproteins, E6 and E7, are directly involved in the development of HPV-related malignancies by targeting synergistically various cellular pathways involved in the regulation of cell cycle control, apoptosis, and cell polarity control networks as well as host immune response. This review is aimed at describing the key elements in HPV-related carcinogenesis and the advances in cancer prevention with reference to past and ongoing research in Croati
PARP14 and PARP9/DTX3L regulate interferon-induced ADP-ribosylation
PARP-catalysed ADP-ribosylation (ADPr) is important in regulating various cellular pathways. Until recently, PARP-dependent mono-ADP-ribosylation has been poorly understood due to the lack of sensitive detection methods. Here, we utilised an improved antibody to detect mono-ADP-ribosylation. We visualised endogenous interferon (IFN)-induced ADP-ribosylation and show that PARP14 is a major enzyme responsible for this modification. Fittingly, this signalling is reversed by the macrodomain from SARS-CoV-2 (Mac1), providing a possible mechanism by which Mac1 counteracts the activity of antiviral PARPs. Our data also elucidate a major role of PARP9 and its binding partner, the E3 ubiquitin ligase DTX3L, in regulating PARP14 activity through protein-protein interactions and by the hydrolytic activity of PARP9 macrodomain 1. Finally, we also present the first visualisation of ADPr-dependent ubiquitylation in the IFN response. These approaches should further advance our understanding of IFN-induced ADPr and ubiquitin signalling processes and could shed light on how different pathogens avoid such defence pathways
PoveÄani oksidacijski stres u obuÄarskih radnika izloženih mjeÅ”avini niskih razina hlapljivih organskih spojeva
This study aimed to assess the redox status and trace metal levels in 49 shoe industry workers (11 men and 38 women) occupationally exposed to a mixture of volatile organic compounds (VOCs), which includes aliphatic hydrocarbons, aromatic hydrocarbons, ketones, esters, ethers, and carboxylic acids. All measured VOCs were below the permitted occupational exposure limits. The control group included 50 unexposed participants (25 men and 25 women). The following plasma parameters were analysed: superoxide anion (O2ā¢-), advanced oxidation protein products (AOPP), total oxidative status (TOS), prooxidant-antioxidant balance (PAB), oxidative stress index (OSI), superoxide dismutase (SOD) and paraoxonase-1 (PON1) enzyme activity, total SH group content (SHG), and total antioxidant status (TAS). Trace metal levels (copper, zinc, iron, magnesium, and manganese) were analysed in whole blood. All oxidative stress and antioxidative defence parameters were higher in the exposed workers than controls, except for PON1 activity. Higher Fe, Mg, and Zn, and lower Cu were observed in the exposed vs control men, while the exposed women had higher Fe and lower Mg, Zn, and Cu than their controls. Our findings confirm that combined exposure to a mixture of VOCs, even at permitted levels, may result in additive or synergistic adverse health effects and related disorders. This raises concern about current risk assessments, which mainly rely on the effects of individual chemicals, and calls for risk assessment approaches that can explain combined exposure to multiple chemicals.Cilj istraživanja bio je procijeniti redoks status i koncentracije metala u tragovima kod 49 radnika (11 muÅ”karaca i 38 žena) zaposlenih u
industriji obuÄe, izloženih mjeÅ”avini hlapljivih organskih spojeva (engl. volatile organic compounds, krat. VOC) koju su Äinili alifatski i aromatiÄni
ugljikovodici, ketoni, esteri, eteri i karboksilne kiseline. Sve izmjerene razine VOC bile su ispod dozvoljenih granica profesionalne izloženosti.
U kontrolnoj je skupini bilo 50 neizloženih ispitanika (25 muÅ”karaca i 25 žena). U plazmi obuÄarskih radnika analizirani su sljedeÄi parametri:
superoksid anion radikal (O2
ā¢-
), uznapredovali produkti oksidacije proteina (AOPP), totalni oksidacijski status (TOS), prooksidacijsko-
antioksidacijski balans (PAB), indeks oksidacijskoga stresa (OSI), aktivnost superoksid-dismutaze (SOD), aktivnost enzima paraoksonaze-1
(PON1), ukupni sadržaj sulfhidrilnih grupa (SHG) i totalni antioksidacijski status (TAS). Koncentracije metala u tragovima (bakar, cink,
željezo, magnezij i mangan) analizirane su u punoj krvi. U usporedbi s kontrolnom skupinom, svi parametri oksidacijskoga stresa i
antioksidacijske obrane u izloženih radnika bili su poviÅ”eni, osim aktivnosti PON1. PoveÄana koncentracija Fe, Mg i Zn te smanjena
koncentracija Cu uoÄene su u izloženih muÅ”karaca u usporedbi s kontrolnima, a u žena je primijeÄena poviÅ”ena koncentracija Fe, a niža
koncentracija Mg, Zn i Cu u odnosu na kontrolnu skupinu. NaÅ”i nalazi potvrÄuju da kombinirano izlaganje mjeÅ”avini VOC, Äak i pri
dozvoljenim koncentracijama, može dovesti do aditivnih ili sinergistiÄkih Å”tetnih uÄinaka na zdravlje i popratnih poremeÄaja. Trenutna
procjena rizika, koja se uglavnom oslanja na uÄinke pojedinaÄnih kemikalija, izaziva zabrinutost i upuÄuje na potrebu za novim pristupima
koji Äe objasniti kombiniranu izloženost veÄem broju kemikalija
Roles of ADAR1 protein in herpes simplex virus 1 replication
Infekcija virusom herpes simpleksa 1 (HSV-1) uzrokuje nekoliko bolesti, u rasponu od kožnih, oralnih i genitalnih infekcija do fatalnog encefalitisa (1). UnatoÄ napretku protuvirusnih terapija koje su znaÄajno smanjile morbiditet i mortalitet HSV-a kod imunokompromitiranih osoba, i dalje je od velikog interesa pobliže razumijevanje elemenata koji pridonose virulenciji HSV-1. Iz tog razloga postoji velika potreba za detaljnom analizom, razliÄitih faktora domaÄina koje virus koristi za promicanje infekcije kao i faktora obrane koji djeluju protivno HSV-1 infekciji (2). Jedan od potencijalnih faktora koji utjeÄe na HSV-1 virulenciju je adenozin deaminaza koja djeluje na RNA (ADAR1). Njegova funkcija A-u-I ureÄivanja dvolanÄanih RNA nedavno je prepoznata kao kljuÄan proces u oznaÄavanju dsRNA kao vlastite, prevenirajuÄi tako aktivaciju uroÄenog imunoloÅ”kog odgovora te djelujuÄi na razvoj i ishod imunoloÅ”ki posredovanih bolesti i infekcija. Prethodna istraživanja pokazala su da, ovisno o specifiÄnim interakcijama virusa i domaÄina, ADAR1 može djelovati protuvirusno, ali i provirusno. Do danas, njegova uloga u HSV-1 infekciji nije istražena, stoga je cilj ovog rada bio odrediti utjecaj ADAR1 enzima na replikaciju HSV-1. U svrhu ostvarenja tog cilja koriÅ”tene se stanice s utiÅ”anom ekspresijom ADAR1 te stanice negativne kontrole, kod kojih je praÄena razina faktora uroÄenog imunoloÅ”kog odgovora i virusnih proteina. Dobiveni rezultati ukazuju na protuvirusni uÄinak ADAR1 tijekom rane faze HSV-1 infekcije s obzirom da se njegovim utiÅ”avanjem znaÄajno poveÄala razina neposredno ranih virusnih proteina te faktora ureÄenog imunoloÅ”kog odgovora eIf-2Ī±, Äija aktivnost potiÄe ekspresiju virusnih gena. S druge strane, utiÅ”avanje ekspresije ADAR1 nije dovelo do znaÄajne promjene u replikaciji virusa izmeÄu ispitivanih stanica, stoga je pretpostavljeno da njegova protuvirusna aktivnost nema dovoljno snažan uÄinak koji bi uzrokovao veÄi poremeÄaj u replikaciji HSV-1. ZakljuÄno, rezultati ovog rada potvrÄuju ulogu ADAR1 tijekom HSV-1 infekcije te ukazuju na ADAR1 kao potencijalnu metu za pojaÄavanje protuvirusnog imunoloÅ”kog odgovora.Herpes simplex virus type-1 (HSV-1) infection can cause several diseases, ranging from cutaneous, oral and genital infections to fatal encephalitis (1). Despite advances in antiviral therapies that have significantly reduced HSV morbidity and mortality, a closer understanding of the elements contributing to HSV-1 virulence remains of great interest. For this reason, there is a great need for a detailed analysis of the host factors that the virus uses to promote infection as well as defense factors that act against HSV-1 infection (2). One of the potential factors affecting HSV-1 virulence is ADAR1. A-to-I editing by ADAR1 has recently been recognized as a key process in marking dsRNA as self, thus preventing activation of the innate immune response and affecting the development and outcome of immune-mediated diseases and infections. Previous research has shown that depending on different virus-host combinations, ADAR1 can have both antiviral and proviral effects. To date, its role in HSV-1 infection has not been evaluated, therefore the aim of this study was to investigate the role of ADAR1 in HSV-1 infection. To achieve this goal, cells with downregulated ADAR1 expression and negative control cells were used to examine the level of innate immune factors and viral proteins. The obtained results indicate the antiviral effect of ADAR1 during the early phase of HSV-1 infection since its downregulation significantly increased the level of immediate-early viral proteins and translation initiation factor eIf-2Ī±, which promotes the expression of viral genes. On the other hand, we did not observe a difference in virus replication when ADAR1 was downregulated, therefore this data suggests that its antiviral activity is not strong enough to cause HSV-1 replication defect. In summary, the results of this study confirm the role of ADAR1 during HSV-1 infection and pointing towards ADAR1 as a potential target to boost antiviral immune response
Roles of ADAR1 protein in herpes simplex virus 1 replication
Infekcija virusom herpes simpleksa 1 (HSV-1) uzrokuje nekoliko bolesti, u rasponu od kožnih, oralnih i genitalnih infekcija do fatalnog encefalitisa (1). UnatoÄ napretku protuvirusnih terapija koje su znaÄajno smanjile morbiditet i mortalitet HSV-a kod imunokompromitiranih osoba, i dalje je od velikog interesa pobliže razumijevanje elemenata koji pridonose virulenciji HSV-1. Iz tog razloga postoji velika potreba za detaljnom analizom, razliÄitih faktora domaÄina koje virus koristi za promicanje infekcije kao i faktora obrane koji djeluju protivno HSV-1 infekciji (2). Jedan od potencijalnih faktora koji utjeÄe na HSV-1 virulenciju je adenozin deaminaza koja djeluje na RNA (ADAR1). Njegova funkcija A-u-I ureÄivanja dvolanÄanih RNA nedavno je prepoznata kao kljuÄan proces u oznaÄavanju dsRNA kao vlastite, prevenirajuÄi tako aktivaciju uroÄenog imunoloÅ”kog odgovora te djelujuÄi na razvoj i ishod imunoloÅ”ki posredovanih bolesti i infekcija. Prethodna istraživanja pokazala su da, ovisno o specifiÄnim interakcijama virusa i domaÄina, ADAR1 može djelovati protuvirusno, ali i provirusno. Do danas, njegova uloga u HSV-1 infekciji nije istražena, stoga je cilj ovog rada bio odrediti utjecaj ADAR1 enzima na replikaciju HSV-1. U svrhu ostvarenja tog cilja koriÅ”tene se stanice s utiÅ”anom ekspresijom ADAR1 te stanice negativne kontrole, kod kojih je praÄena razina faktora uroÄenog imunoloÅ”kog odgovora i virusnih proteina. Dobiveni rezultati ukazuju na protuvirusni uÄinak ADAR1 tijekom rane faze HSV-1 infekcije s obzirom da se njegovim utiÅ”avanjem znaÄajno poveÄala razina neposredno ranih virusnih proteina te faktora ureÄenog imunoloÅ”kog odgovora eIf-2Ī±, Äija aktivnost potiÄe ekspresiju virusnih gena. S druge strane, utiÅ”avanje ekspresije ADAR1 nije dovelo do znaÄajne promjene u replikaciji virusa izmeÄu ispitivanih stanica, stoga je pretpostavljeno da njegova protuvirusna aktivnost nema dovoljno snažan uÄinak koji bi uzrokovao veÄi poremeÄaj u replikaciji HSV-1. ZakljuÄno, rezultati ovog rada potvrÄuju ulogu ADAR1 tijekom HSV-1 infekcije te ukazuju na ADAR1 kao potencijalnu metu za pojaÄavanje protuvirusnog imunoloÅ”kog odgovora.Herpes simplex virus type-1 (HSV-1) infection can cause several diseases, ranging from cutaneous, oral and genital infections to fatal encephalitis (1). Despite advances in antiviral therapies that have significantly reduced HSV morbidity and mortality, a closer understanding of the elements contributing to HSV-1 virulence remains of great interest. For this reason, there is a great need for a detailed analysis of the host factors that the virus uses to promote infection as well as defense factors that act against HSV-1 infection (2). One of the potential factors affecting HSV-1 virulence is ADAR1. A-to-I editing by ADAR1 has recently been recognized as a key process in marking dsRNA as self, thus preventing activation of the innate immune response and affecting the development and outcome of immune-mediated diseases and infections. Previous research has shown that depending on different virus-host combinations, ADAR1 can have both antiviral and proviral effects. To date, its role in HSV-1 infection has not been evaluated, therefore the aim of this study was to investigate the role of ADAR1 in HSV-1 infection. To achieve this goal, cells with downregulated ADAR1 expression and negative control cells were used to examine the level of innate immune factors and viral proteins. The obtained results indicate the antiviral effect of ADAR1 during the early phase of HSV-1 infection since its downregulation significantly increased the level of immediate-early viral proteins and translation initiation factor eIf-2Ī±, which promotes the expression of viral genes. On the other hand, we did not observe a difference in virus replication when ADAR1 was downregulated, therefore this data suggests that its antiviral activity is not strong enough to cause HSV-1 replication defect. In summary, the results of this study confirm the role of ADAR1 during HSV-1 infection and pointing towards ADAR1 as a potential target to boost antiviral immune response
Roles of ADAR1 protein in herpes simplex virus 1 replication
Infekcija virusom herpes simpleksa 1 (HSV-1) uzrokuje nekoliko bolesti, u rasponu od kožnih, oralnih i genitalnih infekcija do fatalnog encefalitisa (1). UnatoÄ napretku protuvirusnih terapija koje su znaÄajno smanjile morbiditet i mortalitet HSV-a kod imunokompromitiranih osoba, i dalje je od velikog interesa pobliže razumijevanje elemenata koji pridonose virulenciji HSV-1. Iz tog razloga postoji velika potreba za detaljnom analizom, razliÄitih faktora domaÄina koje virus koristi za promicanje infekcije kao i faktora obrane koji djeluju protivno HSV-1 infekciji (2). Jedan od potencijalnih faktora koji utjeÄe na HSV-1 virulenciju je adenozin deaminaza koja djeluje na RNA (ADAR1). Njegova funkcija A-u-I ureÄivanja dvolanÄanih RNA nedavno je prepoznata kao kljuÄan proces u oznaÄavanju dsRNA kao vlastite, prevenirajuÄi tako aktivaciju uroÄenog imunoloÅ”kog odgovora te djelujuÄi na razvoj i ishod imunoloÅ”ki posredovanih bolesti i infekcija. Prethodna istraživanja pokazala su da, ovisno o specifiÄnim interakcijama virusa i domaÄina, ADAR1 može djelovati protuvirusno, ali i provirusno. Do danas, njegova uloga u HSV-1 infekciji nije istražena, stoga je cilj ovog rada bio odrediti utjecaj ADAR1 enzima na replikaciju HSV-1. U svrhu ostvarenja tog cilja koriÅ”tene se stanice s utiÅ”anom ekspresijom ADAR1 te stanice negativne kontrole, kod kojih je praÄena razina faktora uroÄenog imunoloÅ”kog odgovora i virusnih proteina. Dobiveni rezultati ukazuju na protuvirusni uÄinak ADAR1 tijekom rane faze HSV-1 infekcije s obzirom da se njegovim utiÅ”avanjem znaÄajno poveÄala razina neposredno ranih virusnih proteina te faktora ureÄenog imunoloÅ”kog odgovora eIf-2Ī±, Äija aktivnost potiÄe ekspresiju virusnih gena. S druge strane, utiÅ”avanje ekspresije ADAR1 nije dovelo do znaÄajne promjene u replikaciji virusa izmeÄu ispitivanih stanica, stoga je pretpostavljeno da njegova protuvirusna aktivnost nema dovoljno snažan uÄinak koji bi uzrokovao veÄi poremeÄaj u replikaciji HSV-1. ZakljuÄno, rezultati ovog rada potvrÄuju ulogu ADAR1 tijekom HSV-1 infekcije te ukazuju na ADAR1 kao potencijalnu metu za pojaÄavanje protuvirusnog imunoloÅ”kog odgovora.Herpes simplex virus type-1 (HSV-1) infection can cause several diseases, ranging from cutaneous, oral and genital infections to fatal encephalitis (1). Despite advances in antiviral therapies that have significantly reduced HSV morbidity and mortality, a closer understanding of the elements contributing to HSV-1 virulence remains of great interest. For this reason, there is a great need for a detailed analysis of the host factors that the virus uses to promote infection as well as defense factors that act against HSV-1 infection (2). One of the potential factors affecting HSV-1 virulence is ADAR1. A-to-I editing by ADAR1 has recently been recognized as a key process in marking dsRNA as self, thus preventing activation of the innate immune response and affecting the development and outcome of immune-mediated diseases and infections. Previous research has shown that depending on different virus-host combinations, ADAR1 can have both antiviral and proviral effects. To date, its role in HSV-1 infection has not been evaluated, therefore the aim of this study was to investigate the role of ADAR1 in HSV-1 infection. To achieve this goal, cells with downregulated ADAR1 expression and negative control cells were used to examine the level of innate immune factors and viral proteins. The obtained results indicate the antiviral effect of ADAR1 during the early phase of HSV-1 infection since its downregulation significantly increased the level of immediate-early viral proteins and translation initiation factor eIf-2Ī±, which promotes the expression of viral genes. On the other hand, we did not observe a difference in virus replication when ADAR1 was downregulated, therefore this data suggests that its antiviral activity is not strong enough to cause HSV-1 replication defect. In summary, the results of this study confirm the role of ADAR1 during HSV-1 infection and pointing towards ADAR1 as a potential target to boost antiviral immune response
INFANTILNA FORMA POMPEOVE BOLESTI
Pompeova bolest je rijetko autozomno recesivno nasljedno metaboliÄko oboljenjeuzrokovano nedostatkom enzima kisele alfa glukozidaze usljed mutacije GAA gena.KarakteriÅ”e se nakupljanjem glikogena u lizozomima svih Äelija, posebno Äelija miÅ”iÄa,jetre, srca i mozga. Simptomi bolesti mogu se javiti u razlicĢitoj dobi i mogu biti razliÄitetežine, Å”to najviÅ”e zavisi od prirode mutacije i rezidualne enzimske aktivnosti. Najteži jeinfantilni oblik kod koga rano nastaju kardiomegalija, hepatomegalija, hipotonija i miÅ”iÄnaslabosti, i kod koga do smrtnog ishoda dolazi u toku prve godine života. Od 2006.godine dostupno je i odobreno lijeÄenje Pompeove bolesti enzimskom supstitucionomterapijom. UspjeÅ”nost ovog vida lijeÄenja najviÅ”e zavisi od stadija bolesti u vrijeme zapoÄinjalijeÄenja, genotipa i CRIM statusa. VeÄinom pacijenti sa CRIM negativnim statusomimaju loÅ” odgovor na lijeÄenje, viÅ”e komplikacija i samim tim loÅ”iju prognozu.U ovom radu smo prikazali prvi sluÄaj infantilne forme Pompeove bolesti koju smolijeÄili enzimskom supstitucionom terapijom u naÅ”oj zdravstvenoj ustanovi. Pompeovabolest se kod ovog pacijenta prvo manifestovala hipertrofiÄnom kardiomiopatijom iimala je brzu progresiju sa razvojem hepatomegalije, teÅ”ke hipotonije, miÅ”iÄne slabostii konaÄno srÄane i respiratorne slabosti. Enzimsku supstitucionu terapijou pacijent jepoÄeo da prima u dobi od 3 mjeseca. Odgovor na terapiju je bio loÅ” i pacijent je umrou dobi od 6 mjeseci.Smatramo da bi prepoznavanje ove bolesti u ranijoj dobi i zapoÄinjanje lijeÄenja prijerazvoja kliniÄkih simptoma vjerojatno dalo bolji rezultat lijeÄenja i produžilo životnivijek oboljelih od Pompeove bolesti