Endovascular treatment of intracranial aneurysms

Intrakranijske aneurizme su abnormalna proširenja intrakranijskih krvnih žila koje nalazimo u 2-5% populacije. Dijelimo ih s obzirom na veličinu, smještaj i oblik. Najteža klinička prezentacija je ruptura aneurizme sa subarahnoidalnim krvarenjem, koje ima visoku smrtnost. Sprječavanje rupture nerupturirane i ponovnog krvarenja rupturirane aneurizme je jedino moguće isključivanjem aneurizme iz krvotoka. Donedavno je to bilo moguće samo kirurškim postavljanjem kopče na vrat aneurizme. U posljednjih dvadesetak godina razvilo se endovaskularno liječenje kao alternativa neurokirurgiji. Prototip endovaskularnog liječenja je embolizacija aneurizme zavojnicama, kojima se postiže stvaranje tromba unutar aneurizmatske vreće. Istraživanja su pokazala bolje rezultate i kliničke ishode nakon endovaskularnog nego nakon kirurškog liječenja, uz manje komplikacija. Međutim i dalje je ostalo pitanje trajnosti okluzije nakon embolizacije. Kako bi se riješio problem rekanalizacije, a i kako bi se liječile složenije i veće aneurizme, razvile su se pomoćne metode kao što su embolizacija zavojnicama uz pomoć balona, embolizacija uz ugradnju potpornice, embolizacija preusmjeravanjem protoka i druge. Svaka od tehnika ima prednosti i nedostatke, stoga ju treba odabrati individualno u skladu s karakteristikama pacijenta, aneurizme i sposobnostima operatera.Intracranial aneurysms are abnormal dilations of intracranial vessels which affect 2-5% of the population. They can be divided into several categories according to their size, morphology and anatomic location. The most severe clinical presentation is rupture with subarachnoid haemorrhage. Prevention of rupture of unruptured and rebleeding of ruptured aneurysms can only be achieved by excluding the aneurysm from the bloodstream. Until recently, surgical clipping was the only treatment option. In the last twenty years, endovascular techniques have been developed as an alternative to surgery. Coiling of an aneurysm, the standard of endovascular treatment, leads to thrombus formation within the aneurysm sac. Studies have shown better results and clinical outcome comparing endovascular to surgical treatment, associated with less complications. However, the question of durability of occlusion after coiling remains. To address the problem of aneurysm recurrence, as well as to treat more complex and larger aneurysms, adjunct techniques have been developed. They include balloon-assisted coiling, stent-assisted coiling, flow diversion and other. Each technique provides a different advantage and should be chosen individually, according to patient and aneurysm characteristics, and operator skill

Endovascular treatment of intracranial aneurysms

Intrakranijske aneurizme su abnormalna proširenja intrakranijskih krvnih žila koje nalazimo u 2-5% populacije. Dijelimo ih s obzirom na veličinu, smještaj i oblik. Najteža klinička prezentacija je ruptura aneurizme sa subarahnoidalnim krvarenjem, koje ima visoku smrtnost. Sprječavanje rupture nerupturirane i ponovnog krvarenja rupturirane aneurizme je jedino moguće isključivanjem aneurizme iz krvotoka. Donedavno je to bilo moguće samo kirurškim postavljanjem kopče na vrat aneurizme. U posljednjih dvadesetak godina razvilo se endovaskularno liječenje kao alternativa neurokirurgiji. Prototip endovaskularnog liječenja je embolizacija aneurizme zavojnicama, kojima se postiže stvaranje tromba unutar aneurizmatske vreće. Istraživanja su pokazala bolje rezultate i kliničke ishode nakon endovaskularnog nego nakon kirurškog liječenja, uz manje komplikacija. Međutim i dalje je ostalo pitanje trajnosti okluzije nakon embolizacije. Kako bi se riješio problem rekanalizacije, a i kako bi se liječile složenije i veće aneurizme, razvile su se pomoćne metode kao što su embolizacija zavojnicama uz pomoć balona, embolizacija uz ugradnju potpornice, embolizacija preusmjeravanjem protoka i druge. Svaka od tehnika ima prednosti i nedostatke, stoga ju treba odabrati individualno u skladu s karakteristikama pacijenta, aneurizme i sposobnostima operatera.Intracranial aneurysms are abnormal dilations of intracranial vessels which affect 2-5% of the population. They can be divided into several categories according to their size, morphology and anatomic location. The most severe clinical presentation is rupture with subarachnoid haemorrhage. Prevention of rupture of unruptured and rebleeding of ruptured aneurysms can only be achieved by excluding the aneurysm from the bloodstream. Until recently, surgical clipping was the only treatment option. In the last twenty years, endovascular techniques have been developed as an alternative to surgery. Coiling of an aneurysm, the standard of endovascular treatment, leads to thrombus formation within the aneurysm sac. Studies have shown better results and clinical outcome comparing endovascular to surgical treatment, associated with less complications. However, the question of durability of occlusion after coiling remains. To address the problem of aneurysm recurrence, as well as to treat more complex and larger aneurysms, adjunct techniques have been developed. They include balloon-assisted coiling, stent-assisted coiling, flow diversion and other. Each technique provides a different advantage and should be chosen individually, according to patient and aneurysm characteristics, and operator skill

Povezanost proteina nm23 i ketapsina D sa kliničkim i patološkim značajkama oralnog karcinoma pločastih stanica

The most important prognostic factor in oral squamous cell carcinoma (OSCC) is the presence of metastases in regional lymph nodes. Study group comprised of 107 patients with OSCC and control group comprised of 77 specimens of unchanged oral mucosa. The purpose of this study was to determine the immunohistochemical expression of cathepsin D and nm23 protein in OSCC and to compare it to the other clinical and histological features and to the occurrence of regional metastases, in order to assess their prognostic value. In contrast to normal epithelium a diff use expression of cathepsin D and nm23 protein in OSCC has been found. By comparing the expression of cathepsin D and nm23 protein in tumor cells and in tumor stroma and the type of reaction to the pT, the degree of diff erentiation, mode of invasion and tumor stroma the following has been found: a signifi cant connection between nm23 protein in tumor cells with the degree of diff erentiation, nm23 protein with the characteristics of the tumor stroma and mode of invasion and cathepsin D with the degree of tumor diff erentiation. The results of this research highlight the important role of tumor stroma in metastatic potential of OSCC.Svrha ovog istraživanja bila je imunohistokemijski utvrditi izraženost proteina nm23 i katepsina D u oralnim pločastim karcinomima, usporediti ju s patohistološkim nalazima, pojavom područnih presadnica i procijeniti njihovu vrijednost u prognozi bolesti. Ispitivano je 107 tkivnih uzoraka bolesne i 77 zdrave ustne sluznice. Uočena je pojačana difuzna izraženost proteina nm23 i katepsina D u bolesnom tkivu. Usporedbom proteina nm23 i katepsina D u tumorskim stanicama i tumorskoj stromi, te tipa reakcije s pT, stupnjem diferencijacije, načinom invazije i izraženošću tumorske strome, nađena je znakovita povezanost izraženosti proteina nm23 u tumorskim stanicama sa stupnjem diferencijacije, proteina nm23s izraženošću tumorske strome i načinom invazije, te katepsina D sa stupnjem diferencijacije tumora. Najvažniji prognostički pokazatelj u oralnim pločastim karcinomima su metastaze u područnim limfnim čvorovima. Rezultati istraživanja pokazuju važnost tumorske strome za metastatski potencijal ostnog ustnog pločastog karcinoma

Povezanost proteina nm23 i ketapsina D sa kliničkim i patološkim značajkama oralnog karcinoma pločastih stanica

The most important prognostic factor in oral squamous cell carcinoma (OSCC) is the presence of metastases in regional lymph nodes. Study group comprised of 107 patients with OSCC and control group comprised of 77 specimens of unchanged oral mucosa. The purpose of this study was to determine the immunohistochemical expression of cathepsin D and nm23 protein in OSCC and to compare it to the other clinical and histological features and to the occurrence of regional metastases, in order to assess their prognostic value. In contrast to normal epithelium a diff use expression of cathepsin D and nm23 protein in OSCC has been found. By comparing the expression of cathepsin D and nm23 protein in tumor cells and in tumor stroma and the type of reaction to the pT, the degree of diff erentiation, mode of invasion and tumor stroma the following has been found: a signifi cant connection between nm23 protein in tumor cells with the degree of diff erentiation, nm23 protein with the characteristics of the tumor stroma and mode of invasion and cathepsin D with the degree of tumor diff erentiation. The results of this research highlight the important role of tumor stroma in metastatic potential of OSCC.Svrha ovog istraživanja bila je imunohistokemijski utvrditi izraženost proteina nm23 i katepsina D u oralnim pločastim karcinomima, usporediti ju s patohistološkim nalazima, pojavom područnih presadnica i procijeniti njihovu vrijednost u prognozi bolesti. Ispitivano je 107 tkivnih uzoraka bolesne i 77 zdrave ustne sluznice. Uočena je pojačana difuzna izraženost proteina nm23 i katepsina D u bolesnom tkivu. Usporedbom proteina nm23 i katepsina D u tumorskim stanicama i tumorskoj stromi, te tipa reakcije s pT, stupnjem diferencijacije, načinom invazije i izraženošću tumorske strome, nađena je znakovita povezanost izraženosti proteina nm23 u tumorskim stanicama sa stupnjem diferencijacije, proteina nm23s izraženošću tumorske strome i načinom invazije, te katepsina D sa stupnjem diferencijacije tumora. Najvažniji prognostički pokazatelj u oralnim pločastim karcinomima su metastaze u područnim limfnim čvorovima. Rezultati istraživanja pokazuju važnost tumorske strome za metastatski potencijal ostnog ustnog pločastog karcinoma

Značaj rutinskih krvnih pretraga u bolesnika s karcinomima glave i vrata

More research suggest that parts of complete blood count might indicate disease-free and overall survival in patients with various cancers and therefore also in patients with head and neck cancer. Therefore, the aim of this paper was to review current knowledge upon signifi cance of complete blood count in head and neck cancers. PubMed was searched in the last 10 years in order to fi nd out references upon this topic and 19 articles were included. Leukocytosis and thrombocytosis negatively correlate with treatment outcome in patients with head and neck cancers, however not in all studies. High preoperative values of neutrophil and lymphocyte ratio suggest poorer disease outcome, i.e. shorter disease free period and overall survival in patients with head and neck cancer. It seems that published data provide an additional practical guidelines for evaluation of disease course in patients with head and neck cancer.Sve vise je istraživanja koja pokazuju kako elementi kompletne krvne slike mogu ukazati na period bez bolesti i ukupno preživljenje u bolesnika s raznim karcinomima. PubMed pregledom nađeno je 19 radova objavljenih zadnjih 10 godina o rutinskim laboratorijskim pretragama i karcinomima glave i vrata. Leukocitoza i trombocitoza su negativno povezane s ishodom liječenja u većini slučajeva bolesnika s orofaringealnim karcinomom, iako ne u svim istraživanjima. Visoke prijeoperacijske vrijednosti odnosa neutrofi la i limfocita ukazuju na lošiji ishod bolesti odnosno na kraći period bez bolesti i na lošije ukupno preživljenje u bolesnika s karcinomima glave i vrata. Čini se kako rezultati istraživanja omogućuju dodatne praktične vodiče u prognostici tijeka bolesti u bolesnika koji boluju od karcinoma glave i vrata

Inhibition of Notch Signaling Stimulates Osteoclastogenesis From the Common Trilineage Progenitor Under Inflammatory Conditions

Osteoclasts, macrophages and dendritic cells (DCs) can be derived from a common trilineage myeloid progenitor of hematopoietic origin. Progenitor commitment is susceptible to regulation through Notch signaling. Our aim was to determine the effects of Notch modulation on trilineage progenitor commitment and functional properties of differentiated cells under inflammatory conditions. We used the conditional inducible CX3CR1CreERT2 mouse strain to achieve overexpression of the Notch 1 intracellular domain (NICD1) or to inhibit Notch signaling via deletion of the transcription factor RBP-J in a bone marrow population, used as a source of the trilineage progenitor (CD45+Ly6G-CD3-B220-NK1.1- CD11b-/loCD115+). Cre-recombinase, under the control of the CX3CR1 promoter, expressed in the monocyte/macrophage lineage, was induced in vitro by 4-hydroxytamoxifen. Differentiation of osteoclasts was induced by M-CSF/RANKL ; macrophages by M-CSF ; DCs by IL-4/GM-CSF, and inflammation by LPS. Functionally, DCs were tested for the ability to process and present antigen, macrophages to phagocytose E. coli particles, and osteoclasts to resorb bone and express tartrate- resistant acid phosphatase (TRAP). We found that Notch 1 signal activation suppressed osteoclast formation, whereas disruption of the Notch canonical pathway enhanced osteoclastogenesis, resulting in a higher number and size of osteoclasts. RANK protein and Ctsk gene expression were upregulated in osteoclastogenic cultures from RBP-J+ mice, with the opposing results in NICD1+ mice. Notch modulation did not affect the number of in vitro differentiated macrophages and DCs. However, RBP-J deletion stimulated Il12b and Cd86 expression in macrophages and DCs, respectively. Functional assays under inflammatory conditions confirmed that Notch silencing amplifies TRAP expression by osteoclasts, whereas the enhanced phagocytosis by macrophages was observed in both NICD1+ and RBP-J+ strains. Finally, antigen presentation by LPS-stimulated DCs was significantly downregulated with NICD1 overexpression. This experimental setting allowed us to define a cell-autonomous response to Notch signaling at the trilineage progenitor stage. Although Notch signaling modulation affected the activity of all three lineages, the major effect was observed in osteoclasts, resulting in enhanced differentiation and function with inhibition of canonical Notch signaling. Our results indicate that Notch signaling participates as the negative regulator of osteoclast activity during inflammation, which may be relevant in immune and bone diseases

Association of increased osmotic fragility of red blood cells with common systemic inflammatory diseases in dogs

Red blood cell osmotic fragility (RBCOF) refers to susceptibility to hemolysis in vivo and in vitro. An increase in mean cellular hemoglobin concentration (MCHC) also reflects in vivo and in vitro hemolysis. Common inflammatory infectious diseases in dogs are often characterized by an increase in MCHC; however, it is not known if there is a concomitant increase in RBCOF. The objective of this study was to determine RBCOF in dogs with babesiosis, dirofilariosis, parvovirosis, pyometra, and canine distemper and to investigate whether RBCOF correlates with routine hematologic and biochemical parameters and lipoprotein fractions. The diagnosis of canine infectious disease was made and complete blood count, serum biochemical profiles, and lipoprotein electrophoresis were determined according to current institutional protocols. RBCOF of healthy control (n=8) and infected dogs (n=73) was measured with a phosphate-buffered saline dilution test, and mean corpuscular fragility (MCF) was calculated. MCF was increased in dirofilariosis, pyometra, and distemper; MCHC was increased in all infected groups; HDL was decreased in babesiosis, pyometra, and distemper compared with healthy controls. However, no correlation was found between these parameters. On the other hand, hematological and biochemical parameters, that are highly predictive of specific infections, correlated with MCF: ALP for babesiosis (r=0.415, P=0.035), urea (r=-0.488, P=0.034) for dirofilariosis, and leukocyte count (r=-0.820, P=0.046) for pyometra. Although elevated MCHC levels in all samples from infected dogs indicate hemolysis, RBCOF was elevated only in dirofilariosis, pyometra, and canine distemper, leading to the conclusion that these apparently related phenomena are controlled by different mechanisms

Notch signaling pathway of osteoclast progenitors in rheumatoid arthritis mouse model

Lokalni i sustavni gubitak kosti u reumatoidnom artritisu posljedica je pojačane aktivnosti osteoklasta. Cilj ovog rada bio je istražiti učinke modulacije signalnog puta Notch na diferencijaciju osteoklastnih progenitora (OCP) i razgradnju kosti u mišjem modelu artritisa potaknutog kolagenom. OCP mišje koštane srži (CD45+Ly6G−CD3−B220−NK1.1− CD11b−/loCD115+) i slezene (CD45+Ly6G−CD3−B220−NK1.1−CD11b+CD115+) podrijetla su mijeloidne loze, izražavaju kemokinski receptor CX3CR1 i njihov je udio povećan u artritisu. OCP izražavaju sva četiri receptora signalnog puta Notch, a u artritisu povećan je udio OCP koji izražavaju receptore Notch 2 i 3. Poticanje OCP ligandima signalnog puta Notch JAG1 i DLL1 dovodi do inhibicije osteoklastogeneze. Obrada neutralizacijskim protutijelima na receptore Notch 1 i 2 pojačala je osteoklastogenezu in vitro, a obrada miševa s artritisom in vivo dovela je do povećanja udjela OCP. Koristeći transgenični mišji soj s utišanim signalnim putem Notch u OCP (CX3CR1CreERT2/RBP-J) uočili smo pojačanu osteoklastogenezu, a u mišjem soju s aktiviranom signalizacijom putem receptora Notch 1 u OCP (CX3CR1CreERT2/NICD1) uočili smo smanjenu osteoklastogenezu. U artritičnih miševa s utišanim signalnim putem Notch u OCP potvrdili smo pojačanu diferencijaciju osteoklastnih progenitora i pojačanu koštanu razgradnju koja dovodi do smanjenog volumena mineralizirane kosti. Naši rezultati potvrđuju inhibicijsku ulogu signalnog puta Notch u diferencijaciji osteoklastnih progenitora u artritisu.Periarticular and systemic bone loss in rheumatoid arthritis is mediated by increased osteoclast activity. We aimed to determine the effects of Notch signaling modulation on osteoclast progenitor (OCP) differentiation and arthritis-induced bone resorption in murine collagen-induced arthritis. Murine bone marrow and splenic OCPs, identified as CD45+Ly6G−CD3−B220−NK1.1−CD11b−/loCD115+ and CD45+Ly6G−CD3−B220−NK1.1− CD11b+CD115+ cells, respectively, derived from the myeloid lineage are specifically increased in arthritis and express the chemokine receptor CX3CR1. OCPs express all four Notch receptors and are susceptible to regulation through Notch signaling. In arthritis, we observed an increase in the frequency of OCPs expressing Notch 2 and 3. Stimulation with Notch ligand JAG1 and DLL1 results in inhibition of osteoclast differentiation, and treatment with neutralizing antibodies targeting Notch 1 and 2 results in increased osteoclastogenesis in vitro and increased frequency of OCPs in mice treated in vivo. We used transgenic mice with Notch signaling inhibition (CX3CR1CreERT2/RBP-J) or Notch 1 overexpression (CX3CR1CreERT2/NICD1) in OCPs and observed stimulated osteoclastogenesis with Notch deletion and reduced osteoclastogenesis with Notch 1 signal activation. Arthritic mice with inhibition of Notch signaling in OCPs had increased osteoclast differentiation and reduced talar bone volume. Our results confirm an inhibitory role of Notch signaling in osteoclast differentiation during arthritis

Notch signaling pathway of osteoclast progenitors in rheumatoid arthritis mouse model

Lokalni i sustavni gubitak kosti u reumatoidnom artritisu posljedica je pojačane aktivnosti osteoklasta. Cilj ovog rada bio je istražiti učinke modulacije signalnog puta Notch na diferencijaciju osteoklastnih progenitora (OCP) i razgradnju kosti u mišjem modelu artritisa potaknutog kolagenom. OCP mišje koštane srži (CD45+Ly6G−CD3−B220−NK1.1− CD11b−/loCD115+) i slezene (CD45+Ly6G−CD3−B220−NK1.1−CD11b+CD115+) podrijetla su mijeloidne loze, izražavaju kemokinski receptor CX3CR1 i njihov je udio povećan u artritisu. OCP izražavaju sva četiri receptora signalnog puta Notch, a u artritisu povećan je udio OCP koji izražavaju receptore Notch 2 i 3. Poticanje OCP ligandima signalnog puta Notch JAG1 i DLL1 dovodi do inhibicije osteoklastogeneze. Obrada neutralizacijskim protutijelima na receptore Notch 1 i 2 pojačala je osteoklastogenezu in vitro, a obrada miševa s artritisom in vivo dovela je do povećanja udjela OCP. Koristeći transgenični mišji soj s utišanim signalnim putem Notch u OCP (CX3CR1CreERT2/RBP-J) uočili smo pojačanu osteoklastogenezu, a u mišjem soju s aktiviranom signalizacijom putem receptora Notch 1 u OCP (CX3CR1CreERT2/NICD1) uočili smo smanjenu osteoklastogenezu. U artritičnih miševa s utišanim signalnim putem Notch u OCP potvrdili smo pojačanu diferencijaciju osteoklastnih progenitora i pojačanu koštanu razgradnju koja dovodi do smanjenog volumena mineralizirane kosti. Naši rezultati potvrđuju inhibicijsku ulogu signalnog puta Notch u diferencijaciji osteoklastnih progenitora u artritisu.Periarticular and systemic bone loss in rheumatoid arthritis is mediated by increased osteoclast activity. We aimed to determine the effects of Notch signaling modulation on osteoclast progenitor (OCP) differentiation and arthritis-induced bone resorption in murine collagen-induced arthritis. Murine bone marrow and splenic OCPs, identified as CD45+Ly6G−CD3−B220−NK1.1−CD11b−/loCD115+ and CD45+Ly6G−CD3−B220−NK1.1− CD11b+CD115+ cells, respectively, derived from the myeloid lineage are specifically increased in arthritis and express the chemokine receptor CX3CR1. OCPs express all four Notch receptors and are susceptible to regulation through Notch signaling. In arthritis, we observed an increase in the frequency of OCPs expressing Notch 2 and 3. Stimulation with Notch ligand JAG1 and DLL1 results in inhibition of osteoclast differentiation, and treatment with neutralizing antibodies targeting Notch 1 and 2 results in increased osteoclastogenesis in vitro and increased frequency of OCPs in mice treated in vivo. We used transgenic mice with Notch signaling inhibition (CX3CR1CreERT2/RBP-J) or Notch 1 overexpression (CX3CR1CreERT2/NICD1) in OCPs and observed stimulated osteoclastogenesis with Notch deletion and reduced osteoclastogenesis with Notch 1 signal activation. Arthritic mice with inhibition of Notch signaling in OCPs had increased osteoclast differentiation and reduced talar bone volume. Our results confirm an inhibitory role of Notch signaling in osteoclast differentiation during arthritis

Endovascular treatment of intracranial aneurysms

Intrakranijske aneurizme su abnormalna proširenja intrakranijskih krvnih žila koje nalazimo u 2-5% populacije. Dijelimo ih s obzirom na veličinu, smještaj i oblik. Najteža klinička prezentacija je ruptura aneurizme sa subarahnoidalnim krvarenjem, koje ima visoku smrtnost. Sprječavanje rupture nerupturirane i ponovnog krvarenja rupturirane aneurizme je jedino moguće isključivanjem aneurizme iz krvotoka. Donedavno je to bilo moguće samo kirurškim postavljanjem kopče na vrat aneurizme. U posljednjih dvadesetak godina razvilo se endovaskularno liječenje kao alternativa neurokirurgiji. Prototip endovaskularnog liječenja je embolizacija aneurizme zavojnicama, kojima se postiže stvaranje tromba unutar aneurizmatske vreće. Istraživanja su pokazala bolje rezultate i kliničke ishode nakon endovaskularnog nego nakon kirurškog liječenja, uz manje komplikacija. Međutim i dalje je ostalo pitanje trajnosti okluzije nakon embolizacije. Kako bi se riješio problem rekanalizacije, a i kako bi se liječile složenije i veće aneurizme, razvile su se pomoćne metode kao što su embolizacija zavojnicama uz pomoć balona, embolizacija uz ugradnju potpornice, embolizacija preusmjeravanjem protoka i druge. Svaka od tehnika ima prednosti i nedostatke, stoga ju treba odabrati individualno u skladu s karakteristikama pacijenta, aneurizme i sposobnostima operatera.Intracranial aneurysms are abnormal dilations of intracranial vessels which affect 2-5% of the population. They can be divided into several categories according to their size, morphology and anatomic location. The most severe clinical presentation is rupture with subarachnoid haemorrhage. Prevention of rupture of unruptured and rebleeding of ruptured aneurysms can only be achieved by excluding the aneurysm from the bloodstream. Until recently, surgical clipping was the only treatment option. In the last twenty years, endovascular techniques have been developed as an alternative to surgery. Coiling of an aneurysm, the standard of endovascular treatment, leads to thrombus formation within the aneurysm sac. Studies have shown better results and clinical outcome comparing endovascular to surgical treatment, associated with less complications. However, the question of durability of occlusion after coiling remains. To address the problem of aneurysm recurrence, as well as to treat more complex and larger aneurysms, adjunct techniques have been developed. They include balloon-assisted coiling, stent-assisted coiling, flow diversion and other. Each technique provides a different advantage and should be chosen individually, according to patient and aneurysm characteristics, and operator skill