Congenital Cytomegalovirus Infection

Infekcija citomegalovirusom (CMV) najučestalija je prirođena virusna infekcija u ljudi i glavni je uzrok oštećenja mozga u perinatalnom razdoblju. Zbog nastanka encefalitisa i razvojnih oštećenja, kao posljedicu ima trajne neurološke poremećaje. Infekcija humanim citomegalovirusom (HCMV) kod većine osoba s normalnom funkcijom imunološkog sustava ne izaziva klinički manifesnu bolest. Zbog toga je infekcija HCMV-om u trudnoći često neprepoznata, što predstavlja dodatan rizik za razvoj kongenitalne infekcije HCMV-om. Uz to što virus ima direktan citopatski učinak na neurone tijekom razvoja, samo prisustvo virusa u moždanom parenhimu dovodi do aktivacije upalnih stanica domaćina i niza patohistoloških lezija koje odgovaraju nastanku encefalitisa. Zbog toga bi daljnja istraživanja trebala biti usmjerena na razvoj sigurnog i učinkovitog cjepiva i lijekova koji će smanjiti rizik infekcije majki, a u slučaju prijelaza virusa s majke na dijete imati mogućnost spriječiti razvoj kongenitalne infekcije CMV-om.Cytomegalovirus (CMV) infection is the most common congenital viral infection in humans and the major cause of wide-spread encephalitis and developmental abnormalities of the newborn brain which can lead to several neurological consequences. Infection with the human CMV (HCMV) in patients with normal immune function does not cause a clinically manifest disease. As the HCMV infection in pregnancy is often unrecognized, it represents an additional risk for development of congenital HCMV infection. Beside the direct cytopathic effect of CMV on neurons during neurogenesis, the presence of the virus in brain parenchyme leads to the activation of host inflammatory response and development of pathohistological lesions. Therefore, further studies should be focused on development of safe and effective vaccines and drugs that will reduce the risk of maternal infection and in case of virus transfer from mother to child have the ability to prevent the development of congenital CMV infection

Congenital Cytomegalovirus Infection

Infekcija citomegalovirusom (CMV) najučestalija je prirođena virusna infekcija u ljudi i glavni je uzrok oštećenja mozga u perinatalnom razdoblju. Zbog nastanka encefalitisa i razvojnih oštećenja, kao posljedicu ima trajne neurološke poremećaje. Infekcija humanim citomegalovirusom (HCMV) kod većine osoba s normalnom funkcijom imunološkog sustava ne izaziva klinički manifesnu bolest. Zbog toga je infekcija HCMV-om u trudnoći često neprepoznata, što predstavlja dodatan rizik za razvoj kongenitalne infekcije HCMV-om. Uz to što virus ima direktan citopatski učinak na neurone tijekom razvoja, samo prisustvo virusa u moždanom parenhimu dovodi do aktivacije upalnih stanica domaćina i niza patohistoloških lezija koje odgovaraju nastanku encefalitisa. Zbog toga bi daljnja istraživanja trebala biti usmjerena na razvoj sigurnog i učinkovitog cjepiva i lijekova koji će smanjiti rizik infekcije majki, a u slučaju prijelaza virusa s majke na dijete imati mogućnost spriječiti razvoj kongenitalne infekcije CMV-om.Cytomegalovirus (CMV) infection is the most common congenital viral infection in humans and the major cause of wide-spread encephalitis and developmental abnormalities of the newborn brain which can lead to several neurological consequences. Infection with the human CMV (HCMV) in patients with normal immune function does not cause a clinically manifest disease. As the HCMV infection in pregnancy is often unrecognized, it represents an additional risk for development of congenital HCMV infection. Beside the direct cytopathic effect of CMV on neurons during neurogenesis, the presence of the virus in brain parenchyme leads to the activation of host inflammatory response and development of pathohistological lesions. Therefore, further studies should be focused on development of safe and effective vaccines and drugs that will reduce the risk of maternal infection and in case of virus transfer from mother to child have the ability to prevent the development of congenital CMV infection

Altered development of the brain after focal herpesvirus infection of the central nervous system

Human cytomegalovirus infection of the developing central nervous system (CNS) is a major cause of neurological damage in newborn infants and children. To investigate the pathogenesis of this human infection, we developed a mouse model of infection in the developing CNS. Intraperitoneal inoculation of newborn animals with murine cytomegalovirus resulted in virus replication in the liver followed by virus spread to the brain. Virus infection of the CNS was associated with the induction of inflammatory responses, including the induction of a large number of interferon-stimulated genes and histological evidence of focal encephalitis with recruitment of mononuclear cells to foci containing virus-infected cells. The morphogenesis of the cerebellum was delayed in infected animals. The defects in cerebellar development in infected animals were generalized and, although correlated temporally with virus replication and CNS inflammation, spatially unrelated to foci of virus-infected cells. Specific defects included decreased granular neuron proliferation and migration, expression of differentiation markers, and activation of neurotrophin receptors. These findings suggested that in the developing CNS, focal virus infection and induction of inflammatory responses in resident and infiltrating mononuclear cells resulted in delayed cerebellar morphogenesis

Diabetes mellitus and DPP IV/CD26 Inhibitors

Šećerna bolest ili dijabetes (lat. diabetes mellitus) metabolička je bolest kronične naravi, karakterizirana perzistentnom hiperglikemijom te poremećajima u metabolizmu ugljikohidrata, masti i proteina. Bolest se dijeli na dijabetes tipa 1 i 2, gestacijski dijabetes te ostale, manje zastupljene oblike. Zbog velikog rasta incidencije i prevalencije bolesti, riječ je o značajnom javno-zdravstvenom problemu te jednom od deset vodećih uzroka smrtnosti u svijetu. Dipeptidil-peptidaza IV, odnosno molekula CD26 (DPP IV/CD26, EC 3.4.14.5), ubikvitaran je multifunkcionalan transmembranski i solubilni glikoprotein te serinska peptidaza, prepoznat kao krucijalan čimbenik u održavanju homeostaze glukoze u krvi, prije svega zbog mogućnosti razgradnje inkretina. Znanstvena i klinička ispitivanja ukazala su na visok terapijski potencijal inhibitora enzimske aktivnosti DPP IV/CD26 kod oboljelih od dijabetesa. Ovaj se pregledni rad fokusira na različite aspekte dijabetesa tipa 1 i 2 te novije mogućnosti terapije ovih oboljenja, s posebnim osvrtom na inhibitore DPP IV/CD26 kao efikasne terapijske opcije.Diabetes (lat. Diabetes mellitus) is a chronic metabolic disease characterized by persistent hyperglycaemia and carbohydrate, fat and protein metabolism disorders. Diabetes could be classified as type 1 or 2, gestational diabetes, and other, less common forms. Due to a prominent increase in the incidence and prevalence of the disease, it represents a significant public-health problem, being between the ten leading causes of mortality in the world. Dipeptidyl peptidase IV, or molecule CD26 (DPP IV / CD26, EC 3.4.14.5), is an ubiquitous multifunctional transmembrane and soluble glycoprotein and serine peptidase, recognized as a crucial factor in maintaining glucose homeostasis, primarily due to the ability to hydrolize incretins. Scientific and clinical studies have shown a high therapeutic potential of DPP IV/CD26 inhibitors in diabetic patients. This review focuses on various aspects of type 1 and 2 diabetes and newer treatment approaches for these diseases, with a special focus on DPP IV/CD26 inhibitors as effective therapeutic options

Wound healing process and dipeptidyl peptidase IV

Cijeljenje rane dinamičan je proces koji se odvija u više međuovisnih faza koje uključuju reguliranu interakciju među različitim vrstama stanica, izvanstaničnog matriksa, proteaza i njihovih supstrata. Rastući znanstveni dokazi naglašavaju važnost proteaza u regulaciji ključnih procesa cijeljenja rane. Dipeptidil-peptidaza IV (DPP IV/CD26, EC 3.4.14.5), glavni je član obitelji DPP IV proteina. Riječ je o ubikvitarnom multifunkcionalnom transmembranskom glikoproteinu koji je prisutan i u topljivom obliku, a djeluje kao proteolitička i kostimulacijska molekula te vezni protein. Izražena je na površini različitih vrsta stanica, uključujući epitelne, endotelne stanice i limfocite. Pokazano je da ima značajnu ulogu u različitim fiziološkim i patološkim procesima. DPP IV/CD26 je u velikoj mjeri istraživana zbog svoje sposobnosti održavanja homeostaze glukoze. Štoviše, budući na utvrđene pozitivne učinke inhibicije DPP IV/CD26 u cijeljenju kroničnih dijabetičkih ulkusa, kao i uključenosti u drugim patološkim procesima, ova je molekula od rastućeg znanstvenog interesa u cilju razjašnjavanja mehanizama njezinog djelovanja. Poznato je da DPP IV/CD26 sudjeluje u regulaciji stanične adhezije, migracije i apoptoze stanica kao i angiogenezi te razgradnji ekstracelularnog matriksa, ključnim procesima u cijeljenju rana. Prethodne studije pokazale su da DPP IV/CD26 ima posebno važnu ulogu u regeneraciji kože, gdje je utvrđeno da može posredovati upalne procese i utjecati na epitelizaciju ranjenog tkiva. Stoga je cilj ovog preglednog rada sažeti ključna otkrića u procesima cijeljenja rana te prikazati nove spoznaje o ulozi DPP IV/CD26 u procesima regeneracije tkiva.Wound healing is a dynamic process occurring in multiple interdependent stages that include a regulated interaction between different cell types, extracellular matrix, proteases and their substrates. Increasing scientific evidence emphasizes the importance of proteases playing crucial roles in the regulation of processes of wound healing. Dipeptidyl peptidase IV (DPP IV/CD26, EC 3.4.14.5), the main member of the DPP IV family of proteins, is a ubiquitous multifunctional transmembrane as well as soluble glycoprotein, acting as a proteolytic and costimulation molecule, and binding protein. It is expressed on the surface different cell types, including epithelial, endothelial cells and lymphocytes. It has been shown to play a significant role in different physiological as well as pathological processes. DPP IV/ CD26 was largely investigated given its ability to maintain glucose homeostasis. Moreover, since positive effects of DPP IV/CD26 inhibition in healing of chronic diabetic foot ulcers as well as other pathologies have been shown, growing efforts are made in order to elucidate its mechanisms of action. It is known that DPP IV/CD26 is involved in the regulation of cell adhesion, migration, apoptosis, angiogenesis and extracellular matrix degradation, which are all key processes in wound healing. Previous studies indicated that DPP IV/CD26 plays a particularly relevant role in skin regeneration where it was found to mediate inflammatory processes and influence epithelialization of wounds. Therefore, the aim of this review was to summarize crucial findings regarding wound healing as well as new insights about the involvement of DPP IV/CD26 in tissue regeneration

Relevance of DPP IV/CD26 among the Gut-brain Axis during Experimental Colitis

Inflammatory bowel diseases (IBD) represent a group of chronic conditions of the gastrointestinal tract of unknown etiology. Latest knowledge accentuates the bidirectional connection between the central and enteric nervous systems. An important role of peptidases has been proposed in maintaining the homeostasis in the gut. One of them is dipeptidil-peptidase IV (DPP IV/CD26), a multifunctional glycoprotein found in both soluble and membrane-bound form in living organisms. In order to evaluate the relevance of DPP IV/CD26 among the gut-brain axis, a TNBS (Crohn-like) model of colitis has been induced in CD26 deficient and wild type mice. Results of this study showed that CD26 deficient mice show specificity in histological damage compared to wild type mice. A decreased DPP IV/CD26 activity was found in serum, colon and brain in wild type mice with colitis, while CD26 protein expression was increased in colon of those mice. DPP IV/CD26-like activity was decreased only in colon of CD26 deficient mice. Changes occurring during inflammatory processes in colon reflected on investigated parameters in brain. Therefore, our results indicate the importance of the gut-brain axis in the pathogenesis of IBD. (doi: 10.5562/cca1813

Diabetes, Dipeptidyl Peptidase iv and Wound Healing: from Basic Science to Therapeutic Possibilities

Hyperglycemia, often accompanied with various complications such as chronic ulcers, represents a major socio-economic health problem. Dipeptidyl peptidase IV or CD26 molecule (DPP IV/CD26), is an omnipresent transmembrane protein with significant involvements in different physiological and pathological processes. It has been recognized as a therapeutic option in the treatment of hyperglycemia, especially in patients suffering from type 2 diabetes, given its capability to regulate the biological activity of incretins, which are major regulators of glucose homeostasis. Furthermore, DPP IV/CD26 has been indicated to be involved in the regulation of inflammatory processes as well as cell proliferation and angiogenesis. New scientific evidence shows that inhibition of DPP IV/CD26 leads to a more efficacious healing of chronic ulcers in diabetic patients as well as in mice models of wounded tissue restoration. However, the role of DPP IV/CD26 in the process of wound healing in hyperglycemia is not entirely known. Our aim was to summarize most important findings on the involvement of DPP IV/CD26 in the regulation of glycemia as well as tissue regeneration and reparation. This work reviews basic biochemical

Wound Healing Process, Diabetes and Implications of Dipeptidyl Peptidase IV (DPP IV/CD26

Dipeptidyl Peptidase IV or molecule CD26 (DPP IV/CD26) is a multifunctional protein, identified as a therapeutic target for type 2 diabetes, due to its ability to degrade incretins, insulin secretagogues. Delayed wound healing is a significant complication in diabetic patients that represents a major socio-economic health problem. It has been proposed that DPP IV/CD26 inhibition accelerates healing of chronic diabetic ulcers in those patients, through the induction of a histological pattern consistent with enhanced angiogenesis. Studies on mice models of diabetesdisturbed wound healing also suggested that the inhibition of DPP IV enzymatic activity may improve tissue regeneration processes. However, further research is needed to elucidate the role of DPP IV/CD26 in diabetic wound healing. The objective of this work was to discuss recent findings on the implications of DPP IV/CD26 in tissue regeneration and reparation in diabetic environmen

Clinical Relevance of CD-68 Positive Cells in Normal Buccal Mucosa in Patients with Inflammatory Bowel Disease

The aim of this study was to investigate the presence of microaggregates of macrophages (CD- 68 positive cells) in macroscopically normal buccal mucosa in patients with inflammatory bowel disease (IBD). Fifty two patients with clinically and pathohistologically diagnosed IBD, thirty patients with Crohn’s disease (CD), twenty two patients with ulcerative colitis (UC), and twenty five controls, matched for sex and age, were involved. The occurrence of CD-68 positive cells microaggregates was more frequent in CD patients comparing with UC patients (P = 0.0093), and the controls (P = 0.0001) respectively. There was no statistically significant difference in occurrence of CD-68 positive microaggregates in patients with positive microbiological findings (P = 0.8258). The results suggest that microaggregates of macrophages are more frequently present in apparently normal buccal mucosa in patients with CD than in patients with UC independently of microbiological findings. Therefore, it could be a potential marker for differentiating patients with Crohn’s disease from UC patients, when standard tools failed. (doi: 10.5562/cca1779