Feroptoza: regulirana stanična smrt

Ferroptosis is a recently identified form of regulated cell death that differs from other known forms of cell death morphologically, biochemically, and genetically. The main properties of ferroptosis are free redox-active iron and consequent iron-dependent peroxidation of polyunsaturated fatty acids in cell membrane phospholipids, which results in the accumulation of lipid-based reactive oxygen species due to loss of glutathione peroxidase 4 activity. Ferroptosis has increasingly been associated with neurodegenerative diseases, carcinogenesis, stroke, intracerebral haemorrhage, traumatic brain injury, and ischemia-reperfusion injury. It has also shown a significant therapeutic potential in the treatment of cancer and other diseases. This review summarises current knowledge about and the mechanisms that regulate ferroptosis.Feroptoza je nedavno identificirani oblik regulirane stanične smrti koji se od ostalih poznatih oblika stanične smrti razlikuje morfološki, biokemijski i genetski. Glavna svojstva feroptoze uključuju slobodno redoks aktivno željezo i posljedičnu, o željezu ovisnu, peroksidaciju polinezasićenih masnih kiselina u fosfolipidima staničnih membrana te gubitak aktivnosti glutation peroksidaze 4, što rezultira akumulacijom lipidnih, reaktivnih kisikovih spojeva. Feroptoza se sve više povezuje s raznim bolestima kao što su neurodegenerativne bolesti, karcinom, moždani udar, intracerebralna krvarenja, traumatične ozljede mozga i ishemijsko-reperfuzijska ozljeda. Također je pokazan značajan terapijski potencijal u liječenju raka i drugih bolesti. Ovaj pregled sažima trenutačne spoznaje i mehanizme koji reguliraju feroptozu

Istine i kontroverze o selenu

Selenium is a trace element, essential in small amounts, but can be toxic in larger amounts. Levels in the body are mainly dependent on the amount of selenium in the diet, which is a function of the selenium content of the soil. Humans and animals require selenium for normal function of more than about 30 known selenoproteins, of which approximately 15 have been purified to allow characterisation of their biological functions. The selenoproteins are comprised of four glutathione peroxidases, three iodothyronine deiodinases, three thioredoxin reductases, selenoprotein P, selenoprotein W and selenophosphate synthetase. Selenium is essential for normal functioning of the immune system and thyroid gland, making selenium an essential element for normal development, growth, metabolism, and defense of the body. Supportive function of selenium in health and disease (male infertility, viral infections, including HIV, cancer, cardiovascular and autoimmune diseases) is documented in great number of clinical examinations. A great number of studies confirm that selenium supplementation play a preventive and therapeutical role in different diseases. Definitive evidence regarding the preventive and therapeutical role of selenium as well as the exact mechanism of its action should be investigated in further studies. Investigations in Croatia indicate a possibility of inadequate selenium status of people in the area.Selen je mikroelement neophodan organizmu u malim količinama, a toksičan u većim količinama. Količina selena u hrani ovisi o količini selena u tlu. Ljudi i životinje trebaju ga za normalno funkcioniranje brojnih procesa. Selen je sastavni dio više od tridesetak poznatih selenoproteina, od kojih su za petnaestak dobro poznata biološka svojstva, primjerice četiri glutation peroksidaze, tri jodtironin dejodinaze, tri tioredoksin reduktaze, selenoprotein P, selenoprotein W i selenofosfat sintetaza. Selen je nužan za normalno funkcioniranje obrambenog sustava i za funkcioniranje tireoidne žlijezde, što znači da je selen esencijalan za normalan razvoj, rast, metabolizam i obranu organizma. Brojna su klinička ispitivanja potvrdila da selen potpomaže u zdravlju i bolesti (muška neplodnost, virusne infekcije, uključujući HIV, karcinom, kardiovaskularne bolesti, autoimune bolesti). Brojne su studije pokazale da suplementacija selena može imati i preventivnu i terapijsku ulogu kod različitih bolesti, ali za konačnu potvrdu kao i točan mehanizam njegova djelovanja nužna su daljnja istraživanja. Istraživanja u Hrvatskoj ukazuju na smanjenu količinu selena u tlu i moguć nedostatan unos selena u ljudski ogranizam

Istine i kontroverze o selenu

Selenium is a trace element, essential in small amounts, but can be toxic in larger amounts. Levels in the body are mainly dependent on the amount of selenium in the diet, which is a function of the selenium content of the soil. Humans and animals require selenium for normal function of more than about 30 known selenoproteins, of which approximately 15 have been purified to allow characterisation of their biological functions. The selenoproteins are comprised of four glutathione peroxidases, three iodothyronine deiodinases, three thioredoxin reductases, selenoprotein P, selenoprotein W and selenophosphate synthetase. Selenium is essential for normal functioning of the immune system and thyroid gland, making selenium an essential element for normal development, growth, metabolism, and defense of the body. Supportive function of selenium in health and disease (male infertility, viral infections, including HIV, cancer, cardiovascular and autoimmune diseases) is documented in great number of clinical examinations. A great number of studies confirm that selenium supplementation play a preventive and therapeutical role in different diseases. Definitive evidence regarding the preventive and therapeutical role of selenium as well as the exact mechanism of its action should be investigated in further studies. Investigations in Croatia indicate a possibility of inadequate selenium status of people in the area.Selen je mikroelement neophodan organizmu u malim količinama, a toksičan u većim količinama. Količina selena u hrani ovisi o količini selena u tlu. Ljudi i životinje trebaju ga za normalno funkcioniranje brojnih procesa. Selen je sastavni dio više od tridesetak poznatih selenoproteina, od kojih su za petnaestak dobro poznata biološka svojstva, primjerice četiri glutation peroksidaze, tri jodtironin dejodinaze, tri tioredoksin reduktaze, selenoprotein P, selenoprotein W i selenofosfat sintetaza. Selen je nužan za normalno funkcioniranje obrambenog sustava i za funkcioniranje tireoidne žlijezde, što znači da je selen esencijalan za normalan razvoj, rast, metabolizam i obranu organizma. Brojna su klinička ispitivanja potvrdila da selen potpomaže u zdravlju i bolesti (muška neplodnost, virusne infekcije, uključujući HIV, karcinom, kardiovaskularne bolesti, autoimune bolesti). Brojne su studije pokazale da suplementacija selena može imati i preventivnu i terapijsku ulogu kod različitih bolesti, ali za konačnu potvrdu kao i točan mehanizam njegova djelovanja nužna su daljnja istraživanja. Istraživanja u Hrvatskoj ukazuju na smanjenu količinu selena u tlu i moguć nedostatan unos selena u ljudski ogranizam

Ferroptosis - a link between iron biology, aging and COVID-19?

Severe form of COVID-19 is more common in the elderly and although it may include a variety of extrapulmonary manifestations, respiratory dysfunction is primarily present, which includes iron dy- shomeostasis. The aging process is characterized by a chronic pro-inflammatory condition of a milder type, and COVID-19 by strong acute inflammation, both resulting in changes in iron metabolism. A new, iron-dependent form of programmed cell death, ferroptosis, is associated with iron dyshomeosta- sis. The main features of ferroptosis include intracellular iron overload, inhibition of the cellular GSH / GPX4 system, and accumulation of lipid reactive compounds. Clinical manifestations of COVID-19 and changes during aging include GSH depletion, GPX4 inactivation, changes in iron metabolism markers as well as markers of enhanced lipid peroxidation. There is therefore a possibility that SARS- CoV-2 may cause feroptotic death of lung cells but also cells of other organs. This review considers the molecular mechanisms of ferroptosis, their relationship to the aging process and the pathogenesis of COVID-19, and the consideration of ferroptosis as a factor linking aging and the pathogenesis of COVID-19

Ferroptosis - a link between iron biology, aging and COVID-19?

Severe form of COVID-19 is more common in the elderly and although it may include a variety of extrapulmonary manifestations, respiratory dysfunction is primarily present, which includes iron dy- shomeostasis. The aging process is characterized by a chronic pro-inflammatory condition of a milder type, and COVID-19 by strong acute inflammation, both resulting in changes in iron metabolism. A new, iron-dependent form of programmed cell death, ferroptosis, is associated with iron dyshomeosta- sis. The main features of ferroptosis include intracellular iron overload, inhibition of the cellular GSH / GPX4 system, and accumulation of lipid reactive compounds. Clinical manifestations of COVID-19 and changes during aging include GSH depletion, GPX4 inactivation, changes in iron metabolism markers as well as markers of enhanced lipid peroxidation. There is therefore a possibility that SARS- CoV-2 may cause feroptotic death of lung cells but also cells of other organs. This review considers the molecular mechanisms of ferroptosis, their relationship to the aging process and the pathogenesis of COVID-19, and the consideration of ferroptosis as a factor linking aging and the pathogenesis of COVID-19

Interferences in quantitative immunochemical methods

Antitijelo koje se u imunokemijskim metodama koristi kao reagens otkriva ciljni analit (antigen). Iako je nekovalentna veza između analita i komplementarnog antitijela specifična, moguće su lažno pozitivne ili negativne interferencije. Neke su interferencije slične interferencijama kod kemijskih analiza, a neke su svojstvene samo imunokemijskim analizama. Na interferencije u imunokemijskim metodama treba pomisliti ako se dobije neprihvatljiv rezultat, ako postoji nelinearnost prilikom razrjeđivanja, ako nema podudarnosti s ostalim nalazima, odnosno kliničkim podacima, ako se različitim imunokemijskim metodama dobiju značajno različiti rezultati određivanja istog analita. U ovom će radu biti opisane neke od mogućih interferencija: 1) križna reaktivnost s endogenim i egzogenim supstancama koje nemaju strukturu antitijela; 2) križna reaktivnost s endogenim i egzogenim supstancama koje imaju strukturu antitijela; 3) prozonski učinak -hook efekt; i 4) utjecaj matriksa. Poznavanjem i prepoznavanjem interferencija u imunokemijskim analizama mogu se izbjeći moguće neželjene posljedice: pogreške u dijagnozi, liječenju i praćenju uspješnosti liječenja, nepotrebna dodatna laboratorijska istraživanja, nepotrebna terapija.In the immunoassays, an antibody used as a reagent, detects an analyte (antigen) of interest. Although the noncovalent bound between analyte and complementary antibody is specific, false-positive and false-negative interferences are possible. Some interferences are similar to those in chemical analyses and some are typical only for immunoassays. One should suspect interferences in following cases: upon receiving an unacceptable result, if there is non-linearity during dilution, if there is no agreement with other test results or clinical data, if different immunoassays in determination of the same analyte provide significantly different results. This paper reviews some of the possible interferences: 1) cross-reactivity with endogenous and exogenous non antibody-structured substances; 2) cross-reactivity with endogenous and exogenous antibody-structure substances; 3) the hook effect; and 4) the matrix effect. By knowing and recognizing interferences in immunoassays, one can avoid possible undesired consequences: diagnostic errors, treatment and monitoring of its efficacy, unnecessary additional laboratory testing, unnecessary therapy

Suvremena laboratorijska dijagnostika alergije

The requests for laboratory diagnosis of allergic diseases refer to a battery of tests that should provide the following: 1) determine the type of allergic reaction by detecting humoral (total IgE) and cellular (eosinophilic and basophilic granulocyte count, eosinophil cationic protein) mediators of allergic reaction; 2) identify triggers of allergic reaction (specific IgE to particular causative allergens, tests for basophilic granulocyte ex vivo activation, leukotrienes, CD63, histamine); 3) assess the clinical course of allergic reaction (tryptase for immediate reaction, eosinophil cationic protein for delayed reaction); 4) enable specific immunotherapy monitoring (total and specific IgE, specific IgG4 and IgG1, IgG4/IgG1 ratio, proallergic and proinflammatory cytokines); and 5) estimate diagnostic efficiency of determination of particular humoral or cellular mediators of allergic reaction (i.e., sensitivity, specificity, positive and negative predictive value). Althouh laboratory investigations are a useful tool in the diagnosis and management of allergic diseases many problems remain unsolved. Those problems can be grouped into three categories: preanalytical (specimen collection), analytical and post-analytical (interpretation, follow-up, retesting) phases of laboratory testing.Zahtjevi laboratorijske dijagnostike alergijskih bolesti odnose se na odabir analiza koje bi trebale: 1. odrediti vrstu alergijske reakcije otkrivanjem humoralnih (ukupni IgE) i staničnih (broj eozinofilnih odnosno bazofilnih granulocita, eozinofilni kationski protein); 2. otkriti pokretače alergijske reakcije (specifični IgE na pojedinačne uzročne alergene, testovi ex vivo aktivacije bazofilnih granulocita – leukotrijeni, CD63, histamin); 3. procijeniti klinički tijek reakcije (triptaza za ranu reakciju, eozinofilni kationski protein za kasnu reakciju); 4. omogućiti praćenje uspješnosti specifične imunoterapije (ukupni i specifični IgE, specifični IgG4 i IgG1, omjer IgG4/IgG1, proalergijski i proupalni citokini); 5. odrediti dijagnostičku djelotvornost određivanja pojedinih humoralnih ili staničnih posrednika alergijske reakcije (osjetljivost, specifičnost, pozitivna i negativna, predvidljiva vrijednost). Iako su laboratorijska istraživanja korisna u dijagnozi i liječenju alergijskih bolesti, brojni problemi još su neriješeni. Ti se problemi mogu svrstati u tri glavne kategorije: preanalitička (uzorkovanje), analitička i poslijeanalitička (tumačenje, praćenje, ponavljno testiranje) faza laboratorijskog određivanja