Miastenična kriza kao nuspojava liječenja metimazolom: Prikaz slučaja

Myasthenia gravis and Graves’ disease are two autoimmune diseases with a similar mechanism, both having circulating organ autoantibodies and cell specific autoantibodies. It is not unusual for these diseases to occur together. There is a large body of data proving that antithyroid drugs such as methimazole and propylthiouracil have an immunomodulatory effect in addition to their thyrosuppressant action. This case report describes a 34-year-old woman hospitalized for just diagnosed myasthenic crisis (Osserman IV). She had a prior history of hyperthyroidism and treatment with methimazole was initiated. However, improvement in thyroid disease led to the burst of myasthenia. The phenomenon described as worsening of one disease while improving the other, the so-called ‘see-saw’ relationship, occurred in this case. The question is whether antithyroid drugs improve hyperthyroidism while unveiling or worsening myasthenia. Is the ‘see-saw’ relationship actually a therapeutic side effect of antithyroid drug? The proposed mechanism of methimazole action is intracellular: it lowers the level of proliferating cell nuclear antigen (PCNA). PCNA pro¬motes selective apoptosis in some T lymphocyte clones. In this way, CD4+CD25+ regulatory T cells might ‘skip’ immune self-tolerance and autoantibodies against acetylcholine receptor may occur. Do antithyroid drugs actually create an immune ‘thymic surrounding’?Miastenija gravis i Gravesova bolest su dvije autoimune bolestI sa sličnim mehanizmom nastanka, u objema se nalaze cirkulirajuća antitijela te stanično specifična autoantitijela. Pojava navedenih bolesti zajedno nije neuobičajena. Postoji mnogo podataka koji pokazuju da antitireoidni lijekovi kao što su metimazol i propiltiouracil uz tireosupresivno djelovanje imaju i imunomodulacijski učinak. Opisuje se slučaj 34-godišnje bolesnice koja je hospitalizirana zbog prvi puta dijagnosticirane miastenije sa slikom miastenične krize (Osserman IV.). U njenoj ranijoj povijesti bolesti navodila se hipertireoza, zbog čega je započeto liječenje metimazolom. Međutim, uz poboljšanje bolesti štitnjače došlo je do pojave miastenije. Fenomen “klackalice”, tj. see-saw relationship, je pojava opisana kao poboljšanje jedne bolesti za vrijeme pogoršanja druge. Pitanje je poboljšavaju li antitireoidni lijekovi hipertireozu, u isto vrijeme razotkrivajući ili pogoršavajući miasteniju?. Jeli fenomen “klackalice” zapravo nuspojava tireostatika? Pretpostavljeni učinak metimazola je unutarstanični: on snižava razinu nuklearnog antigena stanične proliferacije (PCNA). PCNA potiče selektivnu apoptozu u nekim klonovima T limfocita. Na taj bi način CD4+CD25+ regulatorni T limfociti mogli ‘zaobići’ imunu toleranciju prema vlastitom tkivu te dovesti do pojave autoantitijela protiv acetilkolinskog receptora. Stvaraju li zapravo doista antitireoidni lijekovi okruženje slično onome u timusu

The Structure of Thorium(IV) Dititanium(IV) Oxide, ThTi206

The crystal structure of a modification of ThTbOG, obtained from the melt at 1100 °C, has been analysed by X-ray diffraction and refined to the R value of 0.051. The crystals are monoclinic with a= 1.0799(7), b = 0.8570(6), c = 0.5192(3) nm and p = 115.29(3)0 , space group C2/c, Z = 4, F(OOO) = 728. The structure is based on a near-hexagonal close-packing of the oxygen atoms, with the thorium and titanium atoms in »octahedral sites«. The coordination polyhedron of Th is a distorted square antiprism with Th-0 distances from 0.232 to 0.265 nm, that of Ti a distorted octahedron with Ti-0 distances from 0.187 to 0.201 nm like those characteristic for Ti02 polymorphs. The Ti coordination polyhedra form layers parallel_to the (100) which are connected by zig-zag chains of the Th coordination polyhedra which run in the [001] direction. The relations to another ThTi20 6 polymorph structure1 (isomorphous with brannerite) have been examined

CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES

Uvod: Hrvatsko društvo za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora izradilo je 2011. godine prve nacionalne smjernice o prehrani, edukaciji i samokontroli te farmakološkom liječenju šećerne bolesti tipa 2. Sukladno povećanom broju dostupnih lijekova te novim spoznajama o učinkovitosti i sigurnosti primjene već uključenih lijekova, pokazala se potreba za obnovom postojećih smjernica za farmakološko liječenje šećerne bolesti tipa 2 u Republici ­Hrvatskoj. Sudionici: Kao koautori Smjernica navedeni su svi članovi Hrvatskog društva za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora, kao i ostalih uključenih stručnih društava, koji su svojim komentarima i prijedlozima pridonijeli izradi Smjernica. Dokazi: Ove su Smjernice utemeljene na dokazima, prema sustavu GRADE (engl. Grading of Recommendations, Assessment, Development and Evaluation) koji uz razinu dokaza opisuje i snagu preporuke. Zaključci: Individualan pristup temeljen na fiziološkim principima regulacije glikemije nuždan je u liječenju osoba sa šećernom bolesti. Ciljeve liječenja i odabir medikamentne terapije treba prilagoditi oboljeloj osobi, uzimajući u obzir životnu dob, trajanje bolesti, očekivano trajanje života, rizik od hipoglikemije, komorbiditete, razvijene vaskularne i ostale komplikacije, kao i ostale čimbenike. Zbog svega navedenoga od nacionalnog je interesa imati praktične, racionalne i provedive smjernice za farmakološko liječenje šećerne bolesti tipa 2.Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of ­diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the ­pharmacotherapy of type 2 diabetes in the Republic of Croatia. Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes’ patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglycemia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes

Hrvatske smjernice za farmakološko liječenje šećerne bolesti tipa 2 [Croatian guidelines for the pharmacotherapy of type 2 diabetes]

Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the pharmacotherapy of type 2 diabetes in the Republic of Croatia. Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes' patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglyce- mia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes

Technical characteristics of tankers

Tankeri su brodovi za prijevoz tekućeg tereta unutar sustava skladištenja zvanih tankovi. Dizajn i izgradnja tankera dugotrajan je proces sastavljen od brojnih izazova. Uvid u konstrukciju tankera ukazuje na znatnu složenost sustava kojim se omogućuje siguran rad tankera. Brodske konstrukcije tako rastavljamo na veći broj manjih podsustava kako bi se lakše proučile značajne karakteristike tankera. Tankeri su danas prisutni na svim morima, njihova uporaba poprima i različite tipove, stoga je potrebno osigurati što veću efikasnost kod izrade. Brojni su vanjski čimbenici koji negativno utječu na plovidbu tankera. Međunarodno su postavljene norme i kriteriji po kojima se treba voditi pri konstrukciji tankera, kako bi se spriječio nastanak nesreće i nepoželjnih posljedica. U radu su navedena neke od bitnih odredbi tih normi i kriterija. Osim toga navedeni su i pojedini dijelovi, podsustavi, koji sačinjavaju složeni sustav tankera, te su dane najbitnije informacije o njima samima. Kao primjer obrađen je najveći izrađen tanker Seawise Giant.Tankers are ships used for liquid cargo transport inside of specialized storage spaces called tanks. A design and production of tankers is a long-lasting process made up of many obstacles. Insight into the construction of the tanker shows huge system complexity which enable tanker’s safe running. Therefore, ship’s constructions are separated on variety of smaller sub-systems, in order to explain different tanker’s characteristics more easily. Nowadays, they are present throughout all the parts of the world, their usage acquires variety of forms, hence it is necessary to maximize the efficiency of these systems throughout the production. Plenty of external factors, negatively affect the ship’s voyage. International rules and criteria have been set to follow up on when developing tankers, in order to prevent accidents and undesirable consequences. In the thesis, different sub-systems, parts, of which the complex tanker’s system is consisted off, are being cited, as well as the most important information about those sub-systems. Thesis ends with an example of tanker Seawise Giant, internationally recognized as the largest tanker ever produced

Empagliflozin in women with type 2 diabetes and cardiovascular disease – an analysis of EMPA-REG OUTCOME®

Aims/hypothesis The global epidemic of type 2 diabetes affects women and men equally ; however, the relative impact on the cardiovascular (CV) system appears greater for women than men when compared with peers without diabetes. Furthermore, women are often under-represented in CV outcome trials, resulting in less certainty about the impact of CV prevention therapies across the sexes. The EMPA-REG OUTCOME (R) trial, which included 28.5% women, found that empagliflozin, given in addition to standard of care, reduced the risk of CV death by 38%, heart failure (HF) hospitalisation by 35% and a composite endpoint for incident or worsening nephropathy by 39%. Here we report a secondary analysis of the trial to determine the relative effects of empagliflozin in women vs men. Methods The population studied were individuals with type 2 diabetes (HbA(1c) 53-86 mmol/mol [7- 10%] and eGFR >30 ml min(-1) [1.73 m](-2)), with established atherosclerotic CV disease. Individuals were randomised to receive empagliflozin 10 mg or 25 mg, or placebo once daily in addition to standard of care, and followed. The trial continued until (3)691 individuals had experienced an adjudicated event included in the primary outcome. All CV outcome events, including HF hospitalisations and deaths were prospectively adjudicated by blinded clinical events committees. Results At baseline, the demographic profile of the 2004 women (age +/- standard deviation 63.6 +/- 8.8 years) compared with the 5016 men (age 63.0 +/- 8.6 years) in the trial was largely similar, with the exception that LDL-cholesterol was numerically higher in women (2.5 +/- 1.0 vs 2.1 +/- 0.9 mmol/l), consistent with lower rates of lipid- lowering therapies (75.4% vs 83.2%). Women were also less likely to have smoked (31.5% vs 69.9%). The annualised incidence rate for women in the placebo group was numerically lower than in men for CV death (1.58% vs 2.19%), numerically higher for HF hospitalisation (1.75% vs 1.33%) and similar for renal events (7.22% vs 7.75%). We did not detect any effect modification by sex within the statistical power restrictions of the analysis for CV death, HF hospitalisation and incident or worsening nephropathy (interaction p values 0.32, 0.20 and 0.85, respectively). Compared with placebo, empagliflozin increased the rates of genital infections in both women (2.5% vs 10.0%) and men (1.5% vs 2.6%). Conclusions/interpretation CV death, HF hospitalisation and incident or worsening nephropathy rate reductions induced by empagliflozin were not different between women and men

CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES

Uvod: Hrvatsko društvo za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora izradilo je 2011. godine prve nacionalne smjernice o prehrani, edukaciji i samokontroli te farmakološkom liječenju šećerne bolesti tipa 2. Sukladno povećanom broju dostupnih lijekova te novim spoznajama o učinkovitosti i sigurnosti primjene već uključenih lijekova, pokazala se potreba za obnovom postojećih smjernica za farmakološko liječenje šećerne bolesti tipa 2 u Republici ­Hrvatskoj. Sudionici: Kao koautori Smjernica navedeni su svi članovi Hrvatskog društva za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora, kao i ostalih uključenih stručnih društava, koji su svojim komentarima i prijedlozima pridonijeli izradi Smjernica. Dokazi: Ove su Smjernice utemeljene na dokazima, prema sustavu GRADE (engl. Grading of Recommendations, Assessment, Development and Evaluation) koji uz razinu dokaza opisuje i snagu preporuke. Zaključci: Individualan pristup temeljen na fiziološkim principima regulacije glikemije nuždan je u liječenju osoba sa šećernom bolesti. Ciljeve liječenja i odabir medikamentne terapije treba prilagoditi oboljeloj osobi, uzimajući u obzir životnu dob, trajanje bolesti, očekivano trajanje života, rizik od hipoglikemije, komorbiditete, razvijene vaskularne i ostale komplikacije, kao i ostale čimbenike. Zbog svega navedenoga od nacionalnog je interesa imati praktične, racionalne i provedive smjernice za farmakološko liječenje šećerne bolesti tipa 2.Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of ­diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the ­pharmacotherapy of type 2 diabetes in the Republic of Croatia. Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes’ patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglycemia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes

CROATIAN GUIDELINES FOR THE PHARMACOTHERAPY OF TYPE 2 DIABETES

Uvod: Hrvatsko društvo za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora izradilo je 2011. godine prve nacionalne smjernice o prehrani, edukaciji i samokontroli te farmakološkom liječenju šećerne bolesti tipa 2. Sukladno povećanom broju dostupnih lijekova te novim spoznajama o učinkovitosti i sigurnosti primjene već uključenih lijekova, pokazala se potreba za obnovom postojećih smjernica za farmakološko liječenje šećerne bolesti tipa 2 u Republici ­Hrvatskoj. Sudionici: Kao koautori Smjernica navedeni su svi članovi Hrvatskog društva za dijabetes i bolesti metabolizma Hrvatskoga liječničkog zbora, kao i ostalih uključenih stručnih društava, koji su svojim komentarima i prijedlozima pridonijeli izradi Smjernica. Dokazi: Ove su Smjernice utemeljene na dokazima, prema sustavu GRADE (engl. Grading of Recommendations, Assessment, Development and Evaluation) koji uz razinu dokaza opisuje i snagu preporuke. Zaključci: Individualan pristup temeljen na fiziološkim principima regulacije glikemije nuždan je u liječenju osoba sa šećernom bolesti. Ciljeve liječenja i odabir medikamentne terapije treba prilagoditi oboljeloj osobi, uzimajući u obzir životnu dob, trajanje bolesti, očekivano trajanje života, rizik od hipoglikemije, komorbiditete, razvijene vaskularne i ostale komplikacije, kao i ostale čimbenike. Zbog svega navedenoga od nacionalnog je interesa imati praktične, racionalne i provedive smjernice za farmakološko liječenje šećerne bolesti tipa 2.Introduction: The Croatian Association for Diabetes and Metabolic Disorders of the Croatian Medical Association has issued in 2011 the first national guidelines for the nutrition, education, self-control, and pharmacotherapy of ­diabetes type 2. According to the increased number of available medicines and new evidence related to the effectiveness and safety of medicines already involved in the therapy there was a need for update of the existing guidelines for the ­pharmacotherapy of type 2 diabetes in the Republic of Croatia. Participants: as co-authors of the Guidelines there are listed all members of the Croatian Association for Diabetes and Metabolic Diseases, as well as other representatives of professional societies within the Croatian Medical Association, who have contributed with comments and suggestions to the development of the Guidelines. Evidence: These guidelines are evidence-based, according to the GRADE system (eng. Grading of Recommendations, Assessment, Development and Evaluation), which describes the level of evidence and strength of recommendations. Conclusions: An individual patient approach based on physiological principles in blood glucose control is essential for diabetes’ patients management. Glycemic targets and selection of the pharmacological agents should be tailored to the patient, taking into account the age, duration of disease, life expectancy, risk of hypoglycemia, comorbidities, developed vascular and other complications as well as other factors. Because of all this, is of national interest to have a practical, rational and applicable guidelines for the pharmacotherapy of type 2 diabetes