Tetrahydrophthalazine Derivative »Sodium Nucleinate« Exert its Anti-Inflammatory Effects through Inhibition of Oxidative Burst in Human Monocytes

We described the use of a new chemical substance Sodium nucleinate (SN) as an immunomodulatory substance exhibiting antiinflammatory properties. Sodium nucleinate (SN) registrated in Russian Federation as Tamerit®, is 2-amino- -1,2,3,4-tetrahydrophthalazine-1,4-dione sodium salt dihydrate, derivative of well known chemical substance luminol. To comprehend the mechanisms of SN immunomodulatory activity, we examined the SN modulation of the oxidative burst responses of whole blood human monocytes and polimorphonuclear cells (PMC) stimulated with phorbol 12-myristate 13-acetate (PMA) or E. coli suspension in vitro. SN did not inhibit the proportion of neutrophils and monocytes phagocytosing E. coli. Oxidative burst responses of monocytes stimulated with PMA were strongly inhibited at SN concentration ranging from 10–500 mg/ml, less efficient inhibitor was SN in E. coli stimulated monocytes (inhibition range was from 50–500 mg/ml SN). SN inhibited PMC oxidative burst only in range 100–500 mg/ml SN. In conclusion, we found SN as an efficient inhibitor of oxidative burst in monocytes. Since ROS generation in monocytes/macrophages has been found to be important for LPS-driven production of several proinflammatory cytokines, SN may exsert its antiinflammatory effects through monocyte/macrophage oxidative burst inhibition

The Appereance of Pars Planitis in Multiple Sclerosis

The aim of the study was to investigate the clinical association of multiple sclerosis and pars planitis (or intermediate uveitis), as well as to determine the incidence of pars planitis in multiple sclerosis patients. During the period of one year authors examined 42 patients with multiple sclerosis divided into two groups. First group consisted of 23 patients with history of optic neuritis and the second group consisted of 19 patients who have never had optic neuritis. The mean age of patients in the first group was 31.7±5.1 years and in the second group 29.1±8.1 years. Pars planitis was found in 12 patients with multiple sclerosis. Age, sex and degree of neurological disability had no influence on the appearance of pars planitis. Although optic neuritis is considered to be the most common ocular manifestation of multiple sclerosis, the significant number of patients with multiple sclerosis has pars planitis

History of Endemic Goiter in Croatia: From Severe Iodine Deficiency to Iodine Sufficiency

At the time after the Second World War, endemic goiter was present in most parts of Croatia with a prevalence of more than 50% and presence of cretinism. In the village of Rude near Zagreb, goiter was detected in 85% of school children with 2.3% of cretins in the village population. In 1953 the first regulation on obligatory salt iodination, requiring 10 mg of potassium iodide (KI) per kg of salt was established in former Yugoslavia. A three-fold reduction of goiter prevalence, together with disappearance of cretinism was recorded ten years later. In 1992, the National Committee for Eradication of Goiter was founded. The survey performed during 1991–1993 exhibited prevalence of goiter among school children between 8% and 35% and urinary iodine excretion under 10 _g/dL in most of the children from continental parts of the country. The new obligatory regulation, requiring 25 mg of KI/kg of salt, was proposed by the National Comittee and finally established in 1996. In 2002 thyroid volumes and medians of urinary iodine excretion were normal according to the ICCIDD criteria. Overall median of urinary iodine excretion for schoolchildren in Croatia was 14 ug/dL. Croatia crossed a path from severe iodine deficiency detected in the 1950’, to the period of mild to moderate iodine deficiency during the 1990’, and finally, nowadays, iodine sufficiency has been achieve

Application of OWL ontologies in technical systems

U skladu s današnjim ubrzanim razvojem tehnologija, u računarstvu i informatici sve se više spominje pojam „ontologije“. U području računarstva pojam „ontologije“ predstavlja dokument koji sadrži iskaze o međusobnim odnosima određenih pojmova od kojih se nekih sustav sastoji. Područja primjene i istraživanja ontologije su područja poput inženjerstva znanja, obrade prirodnog jezika, informacijskih sustava i tako dalje. Ontologije su kao grane metafizike usmjerene na identificiranje stvari koje postoje u općenitim terminima, a intenzivno se koristi u području semantičkog weba koji predstavlja proširenje trenutnog weba. Povećanjem veza i različitih međudjelovanja računala, stvaranje ontologija je postajalo sve važnije, a ontološki jezici sve potrebniji jer su njihovi zapisi razumljivi svim računalima. Ontološki jezici pružaju različite sadržaje, a jedan od novijih standardnih jezika za ontologije je OWL (Ontology Web Language). OWL ontološki jezik se razvio kao jezik za predstavljanje znanja zahvaljujući mogućnosti izvođenja činjenica koje nisu eksplicitno navedene. Budući da se društveni napredak danas sve više svodi na razvoj računalnih i informacijskih sustava, OWL ontologija stječe sve veći potencijal primjene u tehničkim sustavima, posebno vezanim uz područje robotike.In line with today's global development of technology, computing and information technology, the term "ontology" is increasingly mentioned. In the field of computing, the term "ontology" is a document that contains statements about the relationships between certain concepts that some systems contain. Fields of application and research on ontology are areas such as engineering, natural language processing, information systems and so on. Ontologies are metaphysical branches focused on identifying things that exist in general terms. They are intensively used in the field of semantic web, which is the extension of the current web. The development of ontology creation became more powerful, thanks to increasing connections and different computer interactions, and ontological languages more necessary because their records are understandable to all computers. Ontologies languages provide different contents, and one of the new standard languages for ontology is OWL (Ontology Web Language). OWL Ontology Language has developed as a language for the presentation of knowledge thanks to the possibilities of performing facts that are not explicitly mentioned. Since social progress increasingly leads to the development of computer and information systems, OWL ontology gains increasing potential in technical systems, particularly in the field of robotics

Supklinička hipotireoza

The term ‘subclinical hypothyroidism’ describes the state of slightly elevated serum TSH and normal serum free T4 and T3 levels, usually without any other clinical findings characteristic of hypothyroidism. The state is quite common in the elderly, especially in women. Subclinical hypothyroidism is most commonly an early stage of overt hypothyroidism. Progression to overt hypothyroidism ranges from 5 to 20 percent per year in patients with slightly elevated serum TSH and high thyroid antibody levels. Patients with subclinical hypothyroidism may have increased levels of are total and HDL cholesterol, which are less pronounced than in overt disease but predispose these patients to the development of severe cardiac disease. For this reason, it is necessary to consider levothyroxine therapy in some of these patients, in order to improve their quality of life and to prevent development of full-blown disease with all its sequels. Because subclinical hypothyroidism is common in the elderly (4% - 8% of people older than 60), it is necessary to establish a screening policy based on serum TSH level measurement.Pojam ‘supklinička hipotireoza’ opisuje stanje blago povišene razine TSH uz uredne referentne vrijednosti FT4 i FT3 u serumu, obično bez drugih kliničkih nalaza znakovitih za hipotireozu. Ovo je stanje često u starijoj životnoj dobi, osobito kod žena. Supklinička hipotireoza je najčešće rani stadij manifestne hipotireoze. Oko 5% do 20% bolesnika s blago povišenim TSHi visokom koncentracijom tiroidnih protutijela prijeđe u hipotireozu kroz godinu dana. Bolesnici sa supkliničkom hipotireozom mogu imati povišene vrijednosti ukupnog i HDL kolesterola, koje su manje izražene nego u manifestnoj hipotireozi, ali povećavaju rizik za nastanak teške bolesti srca. Zbog navedenih činjenica neophodno je neke od ovih bolesnika liječiti tiroksinom radi poboljšanja kvalitete života i sprječavanja razvoja uznapredovale bolesti sa svim mogućim posljedicama. Zbog visoke supkliničke hipotireoze u starijoj životnoj dobi (4% • 8% osoba starijih od 60 godina) neophodno je uvesti metodu probiranja koja se temelji na mjerenju serumske vrijednosti TSH

A Tetrahydrophthalazine Derivative »Sodium Nucleinate« Exerts a Potent Suppressive Effect upon LPS-Stimulated Mononuclear Cells in vitro and in vivo

We described the use of a new chemical substance Sodium nucleinate (SN) as an immunomodulatory substance exhibiting antiinflammatory properties. Sodium nucleinate (SN) registrated in Russian Federation as Tamerit®, is 2-amino- 1,2,3,4-tetrahydrophthalazine-1,4-dione sodium salt dihydrate, derivative of well known chemical substance luminol. To comprehend the mechanisms of SN immunomodulatory activity, we examined the SN modulation of the innate inflammatory cytokine response of human PBMC stimulated with LPS in vitro. Furthermore, we studied the immunomodulatory effects of SN in mice challenged with E. coli LPS in vivo to investigate a possible novel approach to therapy of excessive inflammation that interfere with the response to endotoxin and inflammatory mediators. Our results demonstrated that SN is an efficient inhibitor of sepsis development in mice model of LPS-induced sepsis. The changes induced by SN include decreased mice plasma inflammatory cytokine production. Simmilary we demonstrated a decreased TNF-a, IFN-g and IL-6 response in human LPS-stimulated PBMNCs. SN was therefore shown to be a promising inhibitor of multiple inflammatory cytokine secretion

Palatal and Dental Arch Morphology in Down Syndrome

The analysis of palatal vault morphology and maxillary dental arch shape was carried out in the sample of 42 Down syndrome (DS) patients with trisomy 21. The data were compared to those of healthy controls from the same population matched for age and sex. Palatal morphology and upper dental arch shape were studied on hard plaster casts of the patients and controls. No sexual dimorphism in palatal and dental arch shape was observed in DS and controls. Normal palatal shape was more frequent in controls than in DS subjects (52.38% vs. 28.57%; p < 0.05). DS patients displayed significantly higher frequency of shelf-like or »stair palate« (38.1%) than controls (11.9%) (p < 0.02). The younger age group (3–14 year) showed much higher frequency of »stair palate « than controls (26.19% vs. 2.38%; c2 = 9.72; p = 0.003). The older group of DS patients did not show increased frequency of such shape of the palatal vault. There was no significant difference in dental arch shape between DS patients and controls. High frequency of shelf-like palate in DS subjects is decreasing by age. The obtained results indicate that palatal vault morphology is subjected to the age related changes. These changes can be attributed to the growth of caraniofacial structures and increased tonus of tongue and other orofacial muscles

Medularni karcinom štitnjače - pregled značajki i novosti u sustavnom liječenju

Medullary thyroid carcinoma (MTC) is a rare malignancy that originates from parafollicular (C cells) of the thyroid and accounts for 2-4% of all thyroid malignancies. MTC may be sporadic or inherited, the latter as part of the MEN 2 syndromes. Germline mutations in the RET proto-oncogene (REarranged during Transfection) are driver mutations in hereditary MTC, whereas somatic RET mutations and, less frequently, RAS mutations, have been described in tumor tissues of sporadic MTC. Genetic screening for germline mutations in RET proto-oncogene identifies gene carriers of germline mutations. That enables primary prevention (the avoidance of disease onset by total prophylactic thyroidectomy), or at least secondary prevention (early detection) of the disease. Radical surgery with complete tumor resection is still pivotal in attaining cure for MTC. Despite recent advances, the treatment of advanced, metastatic, and progressive MTC remains challenging. Metastatic MTC can have an indolent clinical course; therefore, it is necessary to assess which patient to cure and when to initiate the treatment. Multidisciplinary boards of various specialists involved in the diagnostics and therapy of the patients with MTC in highly specialized centers with a high volume of patients provide optimal patient management. Multikinase inhibitors (MKI) vandetanib and cabozantinib were approved for the treatment of progressive or symptomatic metastatic/unresectable MTC. Although these treatments have been shown to improve progression-free survival (PFS) with higher overall response rates (ORR) compared with placebo, no MKI has been shown to increase the overall survival (OS) yet, except in the subgroup of patients with RETM918T-mutations on cabozantinib therapy. As these drugs are nonselective, significant off-target toxicities may occur. Recently, next-generation small-molecule tyrosine kinase inhibitors (TKIs) have been developed. These highly selective RET-inhibitors are specifically designed for highly potent and selective targeting of oncogenic RET alterations, making them promising drugs for the treatment of advanced MTC. The selective RET-inhibitor selpercatinib has been very recently registered for the treatment of RET-mutated thyroid cancer.Medularni karcinomi štitnjače (MKŠ) rijetke su zloćudne bolesti podrijetla parafolikularnih (C-stanica) štitnjače i čine oko 2-4% svih zloćudnih tumora štitnjače. MKŠ može biti sporadičan ili nasljedan, potonji kao dio MEN 2 sindroma. N asljedne mutacije protoonkogena RET (od engl. REarranged during Transfection) pokretačke su mutacije kod nasljednih MKŠ, dok su somatske RET mutacije, ili, rjeđe, RAS mutacije, opisane u tumorskom tkivu kod sporadičnih MKŠ. Genetski probir na nasljedne mutacije protoonkogena RET identificira nosioce nasljednih genetskih mutacija. To omogućuje primarnu (sprječavanje razvoja bolesti provođenjem profilaktičke totalne tireoidektomije) ili barem sekundarnu prevenciju bolesti (rano otkrivanje MKŠ-a). Radikalna operacija s kompletnom resekcijom tumora još je uvijek ključna u postizanju izlječenja kod MKŠ. Naime, unatoč nedavnim dostignućima, liječenje uznapredovalog, metastatskog i progresivnog MKŠ-a i dalje predstavlja izazov. Metastatski MKŠ može biti indolentnog kliničkog tijeka, stoga je potrebno procijeniti kojeg bolesnika liječiti i kada liječenje započeti. Multidisciplinarni timovi različitih specijalista uključenih u dijagnostiku i liječenje bolesnika s MKŠ-om u visoko specijaliziranim centrima s velikim brojem bolesnika omogućuju njihovo optimalno zbrinjavanje. Multikinazni inhibitori (MKI) vandetanib i kabozantinib, odobreni su za liječenje progresivnog ili simptomatskog metastatskog/ neresektabilnog MKŠ. Premda je ovo liječenje pokazalo dobit u preživljenju bez progresije bolesti (PFS, od engl. Progression Free Survival) uz veću ukupnu stopu odgovora (ORR, od engl. Overall Response Rate) naspram placeba, MKI nisu polučili dobit u ukupnom preživljenju (OS, od engl. Overall Survival), osim kod podskupine bolesnika s RETM918T-mutacijama na terapiji kabozantinibom. Multikinazni inhibitori su neselektivni, stoga je moguća značajna toksičnost terapije. Nedavno su razvijene nove generacije tirozin-kinaznih inhibitora (TKI). Ovi visoko selektivni RET-inhibitori specifično su dizajnirani za visoko učinkovito i selektivno ciljanje onkogenih RET alteracija, što ih čini obećavajućim lijekovima u liječenju uznapredovalog MKŠ. Selektivni RET-inhibitor selperkatinib vrlo je nedavno registriran za liječenje RET-mutiranih karcinoma štitnjače

Sub-inner limiting membrane haemorrhage successfully treated with pars plana vitrectomy – case report

Preretinal haemorrhages typically occur at the boundary between the posterior hyaloid and inner limiting membrane (ILM). Sub-ILM haemorrhages have been observed in various clinical contexts and are likely to cause significant visual impairment due to their tendency to occur in the macular region