Uloga genskih polimorfizama u metabolizmu vitamina D i multiploj sklerozi

Multiple sclerosis (MS) is a complex inflammatory disease of the central nervous system (CNS) resulting in neurological impairment and disability. There is evidence that adequate vitamin D levels may lower the risk of MS development. The aetiology of MS is complex and involves both genetic and environmental factors. In fact, not one but several genes are believed to lead to the disease. As for environmental factors, one of the most important risk factors is vitamin D deficiency, which, in turn, is closely related to gene polymorphisms that play a role in vitamin D metabolism and regulation. However, information about these gene polymorphisms is quite contradictory. The aim of this review is to discuss the association between some of the vitamin D-related gene variants and MS.Multipla skleroza složena je upalna bolest središnjeg živčanog sustava koja dovodi do neuroloških poremećaja i invalidnosti. Prema nekim istraživanjima, rizik od multiple skleroze manji je u osoba s dovoljnim razinama vitamina D. Etiologija bolesti je složena i obuhvaća nasljedne i okolišne čimbenike. Štoviše, vjeruje se da je više gena odgovorno za nastanak bolesti, a od okolišnih se čimbenika najviše izdvaja nedostatak vitamina D, što je opet povezano s genskim polimorfizmima koji su važni za regulaciju njegova metabolizma u tijelu. Dosadašnja saznanja o tim polimorfizmima i njihovoj ulozi, međutim, prilično su oprečna. Stoga je namjera ovoga preglednog članka raspraviti o mogućoj povezanosti između pojedinih varijanti gena za metabolizam vitamina D i nastanka multiple skleroze

Primjena kometnog testa u procjeni oštećenja DNA nastalih zbog ishemijskoreperfuzijskih ozljeda u bolesnika podvrgnutih kirurškim zahvatima na koronarnim žilama

Ischaemia-reperfusion (I/R) injury is responsible for a number of conditions such as coronary bypass and myocardial infarction, and deaths. Oxygen-free radicals formed during I/R have been proposed as the leading causes of tissue injury, and they play an important role in I/R injury. I/R induces oxidative DNA damage (such as purinic and pyrimidinic base lesions). Comet assay is a suitable and sensitive method for early detection of low-level DNA damage. We used modified alkaline comet assay in peripheral blood lymphocytes and evaluated I/R-induced DNA damage in patients undergoing coronary artery bypass graft (CABG) operation (in vivo model for I/R). No statistically significant difference in DNA damage levels was found before surgery, after anaesthesia, ischemia, reperfusion, and surgery. However, blood lactate levels (assessed in parallel with the comet assay) increased after I/R and did not return to the baseline level. Our findings showed that I/R injury did not induce DNA damage, but increased the lactate levels. This finding suggests that there might be reversible and uncommon necrosis that did not refl ect on overall DNA base damage. Further studies are needed using this approach.Ishemijsko-reperfuzijska (I/R) ozljeda čest je uzročnik pobola i smrtnosti u slučajevima kao što su ugradnja koronarnih premosnica, infarkt miokarda i sl. Slobodni kisikovi radikali koji nastaju tijekom procesa ishemije i reperfuzije smatraju se jednim od glavnih uzročnika oštećenja tkiva i imaju važnu ulogu u I/R ozljedama. I/R ozljede izazivaju oksidativna oštećenja u DNA (primjerice oštećenja purinskih i pirimidinskih baza). Kometni test osjetljiva je metoda koja omogućuje utvrđivanje niskih razina primarnih oštećenja u molekuli DNA. U ovom smo istraživanju primjenom kometnog testa na bijelim krvnim stanicama procjenjivali razine oštećenja u DNA nastale zbog I/R ozljeda u bolesnika podvrgnutih ugradnji premosnice koronarne arterije (in vivo model za I/R). Rezultati istraživanja upućuju na to da nema značajnih razlika u razinama oštećenja DNA izmjerenim u uzorcima krvi uzimanima prije kirurškog zahvata, nakon anestezije te tijekom ishemije, reperfuzije i zahvata. Međutim, uočeno je da su nakon I/R ozljede porasle razine laktata u serumu koje se više nisu vratile na početne vrijednosti. Takve vrijednosti laktata u serumu upućuju na to da tijekom I/R nastupa neobična i reverzibilna nekroza koja se, međutim, ne odražava na stupanj oštećenja DNA. Za objašnjenje ovih zapažanja potrebna su daljnja istraživanja

Hepatotoksičnost povezana sa statinima

Treatment with statins is known all over the world. They are generally considered safe at therapeutic doses. Nevertheless, clinical trials are not enough to assess their scarce adverse effects such as idiosyncratic drug induced liver injury (DILI). Due to some conditions, such as concomitant usage (drug-drug interaction using an identical metabolising enzyme) and genetic polymorphisms, there is an increasing concern about their safety. Hepatotoxicity and rhabdomyolysis have begun to appear in published studies. Most of investigations have focused on both these adverse effects and mechanisms of drug induced toxicity. The present review has attempted to compile almost all of the existing studies on the hepatotoxicity of statins but not rhabdomyolysis. The aim of our study is to provide an overview of the studies on the statin-associated hepatotoxicity and to discuss the published studies. The researchers are of the opinion that the research on this topic is incomplete but extremely necessary.Terapija statinima opće je prihvaćena diljem svijeta i njihove se terapijske doze općenito smatraju sigurnima. Ipak, klinička ispitivanja nisu dostatna kako bi se procijenile rijetke nuspojave primjene statina, poput idiosinkratske lijekom izazvane ozljede jetara (drug induced liver injury – DILI). Zbog nekih stanja poput istodobne uporabe određenih lijekova (interakcija dvaju lijekova koji imaju isti metabolizirajući enzim) i genskih polimorfizama, javlja se određena zabrinutost u vezi s njihovom sigurnom primjenom. U brojnim se studijama kao nuspojave primjene statina navode hepatotoksičnost i rabdomioliza. Većina istraživanja usredotočena je na nuspojave i mehanizme lijekom izazvane toksičnosti. U ovom se preglednom radu nastoje sažeti gotovo sve postojeće studije o hepatotoksičnosti statina, ali ne i o rabdomiolizi. Cilj je ponuditi pregled istraživanja hepatotoksičnosti koja je povezana s uporabom statina te razraditi objavljene rezultate tih istraživanja. Istraživači su mišljenja da je istraživanje ovoga problema nepotpuno ali prijeko potrebno

Povezanost OGG1 Ser326Cys polimorfizma i razina 8-OHdG u mokraći sa sklonosti obolijevanju od karcinoma pluća: rezultati ispitivanja na bolesnicima i kontrolnoj populaciji u Turskoj

High incidence and poor prognosis of lung cancer make it a major health problem worldwide. Although smoking is a major cause of lung cancer, only some smokers develop lung cancer, which suggests that there is a genetic predisposition in some individuals. 8-OHG is an important oxidative base lesion and may elevate due to cancer and smoking. It is repaired by 8-hydroxyguanine DNA glycosylase 1 (OGG1), which has several polymorphisms. Although the Ser326Cys polymorphism is consistently associated with a range of cancers, findings about this polymorphism and lung cancer risk are contradictory. To date, no study has examined this association in the Turkish population. We conducted a case-control study to investigate the association between OGG1 Ser326Cys polymorphism and the risk of lung cancer using PCR-RFLP. We also evaluated gene-smoking interaction and excretion of urinary 8-OHdG. Our results suggest that the OGG1 Ser326Cys polymorphism is not a genetic risk factor for lung cancer, and that the heterozygous genotype is associated with a significantly reduced risk for lung cancer. The levels of 8-OHdG did not correlate with the polymorphism and smoking. Larger association studies are needed to validate our findings, and mechanistic studies are needed to elucidate the underlying molecular mechanisms of this association.Karcinom pluća velik je javnozdravstveni problem u čitavom svijetu zbog svoje visoke učestalosti i loše prognoze. Premda je navika pušenja jedan od glavnih uzročnika karcinoma pluća, od ove bolesti oboli samo dio populacije pušača, što govori u prilog postojanju genetske predispozicije za njezin nastanak. 8-OHG je oksidativno oštećenje baze u molekuli DNA čija se učestalost može povećati zbog zloćudnih tumora i pušenja. U popravku tog oštećenja sudjeluje enzim 8-hidroksigvanin DNA-glikozilaza (OGG1) za koji je dokazano postojanje polimorfizma. Iako se polimorfizam Ser326Cys često dovodi u vezu s različitim vrstama zloćudnih bolesti, dosadašnji su rezultati o vezi izme|u polimorfizma tog enzima i rizika od pojave karcinoma pluća kontradiktorni. Do danas na turskoj populaciji nisu provedena istraživanja koja bi dala jasne odgovore o toj povezanosti. Ovo je istraživanje usporedo provedeno u bolesnika i u zdravoj populaciji primjenom metode PCR-RFLP s ciljem utvrđivanja moguće povezanosti polimorfizma OGG1 Ser326Cys i rizika od karcinoma pluća. Nadalje, istražena je interakcija gena i navike pušenja te ekskrecija 8-OHdG u mokraći. Dobiveni rezultati pokazuju da polimorfizam OGG1 Ser326Cys nije genetski čimbenik rizika od pojave karcinoma pluća, a pokazalo se da je heterozigotni genotip povezan sa značajno nižim rizikom od karcinoma pluća. Razine 8-OHdG izmjerene u mokraći nisu bile u korelaciji ni s polimorfizmom ni s navikom pušenja. Zaključujemo da su za vrednovanje dobivenih rezultata potrebna istra`ivanja na još većem broju ispitanika te mehanistička istraživanja koja bi mogla razjasniti molekularne mehanizme koji su u pozadini ove povezanosti

Povezanost genskoga polimorfizma OPRM1 A118G s ovisnosti u turskoj populaciji

Susceptibility to addiction has a complex genetic basis that includes genes associated with the action and metabolism of drugs of abuse. One important gene in that respect is OPRM1, which codes for the μ-opioid receptor and has an important role in mediating the rewarding effects of addiction substances. The aim of our study was to assess the prevalence of the OPRM1 A118G polymorphism (rs1799971) in Turkish population and to investigate its association with opioid and other substance addiction. In addition, we examined the association of rs1799971 in addicted patients who were also diagnosed with psychiatric disorders. The study included 103 patients addicted to opioids, cocaine, ecstasy, alcohol, lysergic acid diethylamide (LSD), cannabis, and sedative/hypnotic substances and 83 healthy volunteers with similar demographic features as controls. rs1799971 polymorphisms were identified with the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). The genotype frequencies were significantly higher in the addicted patients than controls (32.0 % vs 16.9 %, respectively; p=0.027). The prevalence of the G allele was 16.1 % in the addicted group and 8.4 % in the control group (p=0.031). Our study confirmed the association between the rs1799971(G) allele frequency and opioid and other substance addiction, but not with psychiatric disorders.Sklonost ovisnosti ima svoju složenu gensku pozadinu, koja obuhvaća gene povezane s djelovanjem i metabolizmom opojnih tvari i droga. U tom je smislu jedan od istaknutih gena OPRM1, koji kodira μ-opioidni receptor te ima važnu ulogu u nagradnom djelovanju tvari koje stvaraju ovisnost. Cilj je ovoga istraživanja bio utvrditi prevalenciju OPRM1 A118G polimorfizma (rs1799971) u turskoj populaciji te njegovu povezanost s ovisnosti o opijatima i drugim drogama. Usto smo istražili povezanost rs1799971 u ovisnika s dijagnozom psihijatrijskih poremećaja. Istraživanje je obuhvatilo 103 ovisnika o opioidima, kokainu, ekstaziju, alkoholu, lizergidu (LSD-u), kanabisu i o sedativima/hipnoticima, odnosno 83 zdrava dobrovoljca sličnih demografskih karakteristika koji su poslužili kao kontrolna skupina. Polimorfizmi rs1799971 utvrđeni su pomoću metode lančane reakcije polimerazom s obzirom na dužinu restrikcijskoga fragmenta (PCR-RFLP). Učestalost ciljanoga genotipa bila je značajno viša u ovisnika nego u kontrolnih ispitanika (32,0 % odnosno 16,9 %; p=0,027), a učestalost G alela iznosila je 16,1 % u ovisnika, odnosno 8,4 % u kontrolnoj skupini (p=0,031). Time je naše istraživanje potvrdilo povezanost između učestalosti rs1799971(G) alela i ovisnosti o opioidima i drugim opojnim tvarima, ali ne i povezanost s psihijatrijskim poremećajima

The effect of anxiety and depression scores of couples who underwent assisted reproductive techniques on the pregnancy outcomes.

Objective: The aim of this study was to determine the effect of anxiety and depression scores of couples who underwent Assisted Reproductive Techniques (ART) on pregnancy outcomes. Method: This study was conducted as a prospective and comparative study with 217 couples. The study data was collected by using a semi-structured questionnaire and the Turkish version of the State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). The questionnaire, STAI and BDI were applied to couples who initiated ART treatment. Couples\u2019 state anxiety scores were re-evaluated after embryo transfer (ET). Results: A significant relationship was found between the depression score of women and pregnancy outcome (p < 0.05). It was determined that anxiety scores for both men and women were higher before the ART procedure, but their anxiety scores decreased after ET (p < 0.05). Spouses of women with a negative pregnancy outcome had higher trait and state anxiety mean scores (p > 0.05) and lower depression scores (p <0.05) than spouses of women with a positive pregnancy outcome. Conclusion: Study results indicated that the anxiety and depression scores of couples who had achieved a positive pregnancy result were lower than for couples with a negative result. The results of this study will contribute to the health professionals especially to the nurses who spend the most time with couples in providing consulting services and supporting psychological status of couples during ART process in Turkey

Povezanost između polimorfizama XRCC1 ARG399GLN i P53 ARG72PRO s rizikom od raka želuca i debeloga crijeva u turskoj populaciji

Gastric cancer is one of the most common cancers of the gastrointestinal system, and its overall fi ve-year survival rate is still 15 % to 20 %, as it can mostly be diagnosed at an advanced stage. On the other hand, although colorectal cancer has a rather good prognosis, mortality is one half that of the incidence. As carcinogenesis is believed to involve reactive radicals that cause DNA adduct formation, impaired repair activity, and weakened tumour suppression, it would help to understand the role of the polymorphisms of nucleotide excision repair enzyme XRCC1 and of tumour suppressor gene p53 in gastric and colorectal cancers. Our study included 94 gastric cancer patients, 96 colorectal cancer patients, and 108 cancer-free individuals as control with the aim to see if there was an association between XRCC1 Arg399Gln and p53 Arg72Pro polymorphisms and cancer susceptibility. DNA was extracted from peripheral blood cells and genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism. Polymorphism p53 Arg72Pro was not associated with either gastric or colorectal carcinoma, while XRCC1 Arg399Gln was not associated with the increased risk of colorectal cancer. However, XRCC1 homozygous Gln allele at codon 399 was associated with 2.54 times higher risk of gastric cancer.Rak želuca najčešći je oblik karcinoma probavnoga sustava, a ukupno mu je preživljenje i dalje 15 % do 20 %, budući da se većinom dijagnosticira u poodmakloj fazi razvoja. S druge pak strane, premda rak debeloga crijeva ima prilično dobru prognozu, smrtnost je i dalje 50 %. Vjeruje se da je nastanak karcinoma povezan s reaktivnim radikalima koji uzrokuju stvaranje DNA-adukata, onemogućavaju popravak DNA te slabe supresiju tumora. Stoga bi bilo korisno razumjeti ulogu polimorfi zama gena za enzim XRCC1 koji sudjeluje u popravku isjecanjem nukleotida i tumor-supresorskoga gena p53 u nastanku raka želuca i debeloga crijeva. Naše je ispitivanje obuhvatilo 94 bolesnika s rakom želuca, 96 bolesnika s rakom debeloga crijeva te 108 kontrolnhih ispitanika (koji nisu oboljeli od bilo kojeg oblika raka) s ciljem da se utvrdi povezanost između polimorfi zama XRCC1 Arg399Gln i p53 Arg72Pro i sklonosti nastanku raka. DNA je dobiven iz stanica periferne krvi, a genotip utvrđen s pomoću metode lančane reakcije polimerazom - polimorfi zma restrikcijskih fragmenata na osnovi dužine (PCRRLFP). Polimorfi zam p53 Arg72Pro nije se pokazao povezanim s povećanim rizikom od raka želuca ili debeloga crijeva niti je XRCC1 Arg399Gln bio povezan s povećanim rizikom od raka debeloga crijeva, ali je zato rizik od raka želuca u homozigotnih nositelja ovoga polimorfi zma bio 2,54 puta veći

Utjecaj desflurana i sevoflurana na razine oksidativnog stresa u tkivima štakora

General anaesthetics are often used in patients who are under oxidative stress due to a critical illness or surgical trauma. Some anaesthetics may worsen oxidative stress and some may act as antioxidants. The aim of this study was to evaluate liver, brain, kidney, and lung tissue oxidative stress in rats exposed to desflurane and sevoflurane and in unexposed rats. The animals were divided in three groups: control (received only air); sevoflurane (8 %), and desflurane (4 %). After four hours of exposure, we evaluated the levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Cu, and Zn. Exposure to either of the anaesthetics significantly increased lung MDA levels compared to control (Mann-Whitney U test; P<0.05), probably because it is the tissue directly exposed to anaesthetic gases. Oxidative stress and antioxidant activity in other tissues varied between the desflurane and sevoflurane groups. Our results suggest that anaesthesiologist should not only be aware of the oxidative or antioxidative potential of anaesthetics they use, but should also base their choices on organs which are the most affected by their oxidative actionkisikovih radikala tako i zbog smanjene aktivnosti obrambenih sustava koji se mogu oduprijeti njihovu djelovanju. Stoga su saznanja o antioksidativnom kapacitetu anestetika koji se primjenjuju prije nekoga kirurškog zahvata vrlo važna i od velikog su kliničkog značenja. Sevofl uran i desfl uran su inhalacijski anestetici koji se učestalo rabe u svrhu uvođenja bolesnika u anesteziju. Cilj ovog istraživanja bio je utvrditi razine oksidativnog stresa u različitim tkivima štakora i usporediti razlike u odgovoru tkiva na izlaganje navedenim anesteticima. U tu svrhu razine oksidativnog stresa izmjerili smo u jetri, mozgu, bubrezima i plućima štakora podijeljenih u tri eksperimentalne skupine. Kontrolna skupina udisala je samo zrak, dok su druge dvije skupine izložene 8 %-tnomu sevofl uranu te 4 %-tnomu desfl uranu tijekom 4 h. Nakon završetka obrade životinje su žrtvovane i uzimani su im uzorci tkiva za biokemijske analize. Mjerena je razina malondialdehida (MDA), aktivnst enzima superoksid dismutaze (SOD) i glutation peroksidaze (GSH-Px) te razine bakra i cinka. Izloženost anesteticima izazvala je oksidativni stres u plućima, na što upućuje značajno povišena razina MDA (Mann-Whitney U-test P<0.05) izmjerena u plućnom tkivu štakora obiju izloženih skupina u odnosu na kontrolu. Plućno je tkivo u odnosu na ostala tkiva podložnije štetnim utjecajima reaktivnih kisikovih radikala vjerojatno stoga što je ono prvo izloženo plinovitim anesteticima nakon njihova ulaska u organizam. Razine oksidativnog stresa i antioksidativne aktivnosti koje smo izmjerili u ostalim tkivima bile su različite te su ovisile o primijenjenom anestetiku. Na osnovi dobivenih rezultata možemo zaključiti da bi se zbog različitog odgovora tkiva izbor anestetika trebao provoditi na individualnoj osnovi

Genotoxicity of Anesthetics Evaluated In Vivo (Animals)

The anesthesia has been improved all over the years. However, it can have impact on health, in both patients and animals anesthetized, as well as professionals exposed to inhaled anesthetics. There is continuing effort to understand the possible effects of anesthetics at molecular levels. Knowing the effects of anesthetic agents on genetic material could be a valuable basic support to better understand the possible mechanisms of these agents. Thus, the purpose of this review is to provide an overview on the genotoxic potential, evaluated in animal models, of many anesthetics that have already been used and those currently used in anesthesia