Komparativna analiza homeostaze kalcijuma u uslovima fiziološke i medikamentne hiperprolaktinemije : eksperimentalna studija

Na osnovu rezultata ovog eksperimenta, može se zaključiti da je genska ekspresija prolaktinskih receptora, u ciljnim organima homeostaze kalcijuma, značajno različita u fiziološkoj i medikamentnoj hiperprolaktinemiji. U fiziološkoj hiperprolaktinemiji potvrđena je signifikantno viša ekspresija PRLR u duodenumu, što je u saglasnosti sa rezultatima dosadašnjih istraživanja. Istovremeno je, po prvi put, u uslovima fiziološke hiperprolaktinemije, verifikovana signifikantno niža ekspresija PRLR u bubregu i pršljenovima. U medikamentnoj hiperprolaktinemiji, istraživanja u domenu genske ekspresije PRLR do sada nisu sprovedena. Rezultati ovog eksperimenta, po prvi put, otkrivaju značajno sniženu ekspresiju PRLR u duodenumu, a povišenu u bubregu i pršljenovima. Ovako različita genska ekspresija PRLR, u target organima metabolizma kalcijuma, u uslovima fiziološke i medikamentne hiperprolaktinemije, objašnjava rezličite mehanizme homeostaze kalcijuma. U stanju fiziološke hiperprolaktinemije, viša ekspresija PRLR u duodenumu dovodi do povećane intestinalne apsorpcije kalcijuma, a snižena ekspresija PRLR u pršljenovima sprečava resorpciju kalcijuma iz skeletnog sistema. U medikamentnoj hiperprolaktinemiji, niska ekspresija PRLR u duodenumu praćena je smanjenom apsorpcijom kalcijuma, povišena ekspresija PRLR u bubregu rezultuje povišenom kalcijumurezom, a viša ekspresija PRLR u pršljenovima dovešće do povećane koštane resorpcije kalcijuma. Kao posledica različite homeostaze kalcijuma, promene koje trpi koštani sistem u fiziološkoj hiperprolaktinemiji, su blage i reverzibilne, dok se medikamentna hiperprolaktinemija može smatrati značajnim faktorom rizika za gubitak koštane mineralne gustine. Na osnovu postavljenih hipoteza i rezultata ovog eksperimentalnog rada mogu se izvesti sledeći zaključci: I. U stanju fiziološke hiperprolaktinemije verifikovana je značajno viša ekspresija PRLR u duodenumu, što omogućuje povećanu intestinalnu apsorpciju kalcijuma. Značajno niža ekspresija PRLR u pršljenovima ostavlja manje prostora za resorpivno dejstvo PRL i time štiti skeletni sistem od gubitka kalcijuma. II. U medikamentnoj hiperprolaktinemiji dolazi do nishodne regulacije ekspresije PRLR u duodenumu, čime se gubi značajna uloga prolaktina u apsorpciji kalcijuma iz intestinuma. Tražeći drugi izvor kalcijuma, koji bi nadomestio smanjenu intestinalnu apsorpciju, prolaktin se okreće koštanom sistemu, odakle ubrzano crpi kalcijum zahvaljujući ushodnoj regulaciji PRLR u pršljenovima. III. Blagovremeno uključivanje suplementne terapije kalcijumom i vitaminom D, dovodi do značajno više ekspresije PRLR u duodenumu pacova sa prolongiranom hiperprolaktinemijom, čime se može oporaviti intestinalna apsorpcija kalcijum

Bone turnover markers in medicamentous and physiological hyperprolactinemia in female rats

Background/Aim. There is a lack of data on the effects of prolactin on calcium metabolism and bone turnover in hyperprolactinemia of various origins. The aim of this study was to compare the influence of medicamentous and physiological hyperprolactinemia on bone turnover in female rats. Methods. Experimental animals (18 weeks old, Wistar female rats) were divided as follows: the group P - 9 rats, 3 weeks pregnant; the group M3-10 rats that were intramuscularly administrated sulpirid (10 mg/kg) twice daily for 3 weeks, the group M6 - 10 rats that were intramuscularly administrated with sulpirid (10 mg/kg) twice daily for 6 weeks, and age matched nulliparous rats as the control group: 10 rats, 18-week-old (C1) and 7 rats, 24 weeks old (C2). Laboratory investigations included serum ionized calcium and phosphorus, urinary calcium and phosphorous excretion, osteocalcin and serum procollagen type 1 N-terminal propeptide (P1NP). Results. Experimental animals in the group P compared to the control group, displayed lower mean serum ionized calcium (0.5 ± 0.2 vs 1.12 ± 0.04 mmol/L; p < 0.001); higher mean serum phosphorus (2.42 ± 0.46 vs 2.05 ± 0.2 mmol/L; p < 0.05); increased urinary calcium (3.90 ± 0.46 vs 3.05 ± 0.58; p < 0.01) and significantly increased P1NP (489,22 ± 46,77 vs 361.9 ± 53,01 pg/mL; p < 0.001). Experimental animals in the group M3 had significantly decreased P1NP, compared to the control group. Prolongated medicamentous hyperprolactinemia (the group M6) induced increased serum ionized calcium (1.21 ± 0.03 vs 1.15 ± 0.02 mmol/L; p < 0.001); decreased serum phosphorus (1.70 ± 0.13 vs 1.89 ± 0.32 mmol/L; p < 0.001); decreased osteocalcin and P1NP. Conclusions. Physiological hyperprolactinemia does not have such harmful effect on bone metabolism as medicamentous hyperprolactinemia. Chronic medicamentous hyperprolactinemia produces lower serum levels of bone formation markers. Assessment of bone turnover markers in prolongated medicamentous hyperprolactinemia provides an opportunity for earlier diagnosis of bone metabolism disturbances and should be considered as mandatory

METABOLIC PARAMETERS IN TYPE 2 DIABETIC PATIENTS WITH POSITIVE CANDIDA CULTURES

The gut microbiota plays an important role in host metabolism, immunity, digestibility and even behaviour. Candida spec. is common resident of the gastrointestinal tract and integral part of the microbiota. The aim of the study was to evaluate if positive Candida cultures in the stool influence metabolic parameters in type 2DM patients. 46 patients with type 2 DM and oral antidiabetic treatment, were divided into a study group (S=18 patients with positive Candida sp. cultures in stool) and the control group (C= remaining 28 patients). Besides medical history and clinical examination, all patients were tested for coproculture, fasting glycaemia (FPG), HbA1C, total cholesterol (CL) triglycerides (TG), high- density lipoproteins (HDL) and low- density lipoproteins (LDL). Study group patients had a significantly higher BMI (31.41 ± 5.29 vs. 25.18 ± 3.58; p<0.001); HbA1C (9.8 % ± 1.74 vs 6.9% ± 1.89; p<0.05) as well as FPG (10.87 ± 1.35 vs 7.47 ± 1.03; p<0.01), compared to the control group. Even though the study group patients had higher TG, CL, LDL and HDL, compared to the control group, there was no statistical significance verified. Uncontrolled glucoregulation is one of the host condition which favours candida colonization and subsequent infection. This may be related to the decrease in commensal bacteria, probably as the result of yeast-bacterial competition. On the other hand, we have to keep in mindthat a significantly increased number of Candida colonies can affect the rate of digestion and absorption of carbohydrates and consequently increase the level of glycaemia in patients with diabetes

Genetic prediction of hemophilia a by int18/BclI RFLP analysis

Hemofilija A je X vezana bolest, koja se javlja sa učestalošću od 1 do 2 na 10000 muškaraca. Ona predstavlja najčešći koagulacioni poremećaj i izazvana je mutacijama u genu koji kodira osmi faktor koagulacije (FVIII). Nakon kloniranja gena za FVIII okarakterisan je veliki broj mutacija koje dovode do hemofilije A, što otežava direktnu DNK dijagnostiku ove bolesti. Indirektna DNK dijagnostika primenom polimorfizama u dužini restrikcionih fragmenata DNK (RFLPs) predstavlja alternativni pristup. Cilj ovog rada je bio da se utvrdi informativnost porodica u kojima se javlja hemofilija A za prenatalnu dijagnostiku u narednim trudnoćama. Korišćenjem reakcije lančanog umnožavanja DNK (PCR), analizirano je 67 uzoraka DNK članova, 24 porodice, u kojima se javlja hemofilija A. Umnožavan je polimorfan region u intronu 18, gena za VIII faktor koagulacije i obrađivan restrikcionim enzimom BclI. Utvrđeno je da je 12 porodica (50%) informativno za 18/BclI RFLP. Urađena je i jedna prenatalna dijagnoza, kod žene u prvom trimestru trudnoće, i pri tom je kod fetusa muškoga pola detektovan isti obrazac restrikcionih fragmenata kao kod obolelog od hemofilije. S obzirom da je indirektna DNK dijagnostika brz i ekonomski isplativ metod, ona predstavlja dijagnostičku strategiju izbora u većini porodica u kojima je indikovana genetička dijagnostika hemofilije A.Hemophilia A, an X linked genetic disease, is the most common coagulation disorder with an incidence of about 1-2 in 10 000 males. It is caused by mutations in the factor VIII coagulation gene. After cloning of the factor VIII gene, almost all types of mutations causing hemophilia A were characterized. The wide spectrum of different mutations in the factor VIII gene made direct DNA diagnosis of the disease not the method of choice. Indirect DNA diagnosis, using restriction fragment length polymorphisms (RFLPs) offers an alternative. The aim of our study was to provide carrier and prenatal diagnostics for affected families using the indirect approach. The genomic DNA of 67 members of 24 hemophilia A families were analyzed by polymerase chain reaction (PCR) amplification of the BclI polymorphic region at intron 18 of the factor VIII gene. Twelve families were informative for int18/BclI RFLP (50%). One prenatal diagnosis of hemophilia A was performed in the first trimester of gravidity, and the fetus was found to be a male affected by hemophilia A. Indirect DNA testing is straightforward, rapid and inexpensive to perform. Thus, in many families requiring genetic diagnosis of hemophilia A, as well as genetic counseling, the use of intragenic polymorphism analysis represents the diagnostic strategy of choice

Impact of acquired and genetic factors on thrombophilic phenotype in FV Leiden mutation carriers

FV Leiden mutacija je veoma značajan genetički faktor rizika za pojavu venskog tromboembolizma (VTE). U okviru ove studije analizirana je klinička slika i uticaj stečenih i genetičkih faktora rizika u grupi od 100 bolesnika, nosilaca FV Leiden mutacije (95 heterozigota i 5 homozigota). Devedeset jedan bolesnik je imao VTE, sa trombozom dubokih vena donjih ekstremiteta kao najčešćom manifestacijom. Kod 68,6% žena bio je prisutan neki od stečenih faktora rizika, dok je to bio slučaj kod 28,6% muškaraca. Mutacija FII G20210A je detektovana kod 9,5%, MTHFR 677TT kod 8,4%, a obe mutacije su bile prisutne u 2,1% heterozigotnih nosilaca FV Leiden mutacije. Rezultati ove studije ukazuju na značaj poznavanja udruženih faktora rizika kod pacijenata koji su nosioci FV Leiden mutacije.FV Leiden mutation is an important genetic risk factor for venous thromboembolsm (VTE). In this study we have analyzed clinical manifestation and the impact of other genetic and acquired risk factors in 100 patients (95 heterozygous and 5 homozygous) carriers of FV Leiden mutation. Among these patients, 91 experienced VTE, with down limb deep vein thrombosis as the most frequent manifestation. An acquired risk factor was present in 68.6% of women, whereas this was the case in 28.6% of men. FIIG20210A was present in 9.5%, MTHFR 677TT in 8.4% and both mutations in 2.1% of the heterozygous FV Leiden carriers. Our results suggest that knowledge of coexisting factors predisposing to VTE is very important for FV Leiden mutation carriers and may contribute to the prevention of VTE episodes

FV Leiden, FII G20210A and MTHFR C677T mutations in patients with lower or upper limb deep vein thrombosis

Tromboze dubokih vena (TDV) su multifaktorijalno oboljenje koje se javlja sa učestalošću 1/1000 stanovnika godišnje. Mutacije FV Leiden, FII G20210A i MTHFR C677T predstavljaju genetske faktore za nastanak venskih tromboza. Cilj ove studije je da se utvrdi učestalost FV Leiden, FII G20210A i MTHFR C677T mutacija kod bolesnika sa TDV gornjih ili donjih ekstremiteta. Studija je obuhvatila 119 bolesnika podeljenih u dve grupe. Grupa bolesnika sa TDV donjih ekstremiteta brojila je 77, a grupa sa TDV gornjih ekstremiteta 42 bolesnika. Prisustvo FV Leiden, FII G20210A i MTHFR C677T mutacija dokazivano je umnožavanjem odgovarajućeg fragmenta gena pomoću lančane reakcije umnožavanja polimerazom i digestijom dobijenih fragmenata restrikcionim enzimima (PCR-RFLP).Učestalost FV Leiden mutacije, u grupi bolesnika sa TDV donjih ekstremiteta, iznosila je 26,0% u heterozigotnom obliku i 1,3% u homozigotnom obliku. U grupi bolesnika sa TDV gornjih ekstremiteta, učestalost heterozigotnih nosilaca iznosila je 7,2%. Mutacija FII G20210A bila je prisutna kod 15,6% ispitanika u grupi bolesnika sa TDV donjih ekstremiteta u heterozigotnom obliku, dok je u grupi sa TDV gornjih ekstremiteta ova mutacija bila zastupljena sa 7,2% u heterozigotnom i 2,3% u homozigotnom obliku. Učestalost MTHFR C677T mutacije kod bolesnika sa TDV donjih ekstremiteta iznosila je 42,8% u heterozigotnom obliku i 13% u homozigotnom obliku, a kod TDV gornjih ekstremiteta 52,4% u heterozigotnom obliku i 9,5% u homozigotnom obliku.Mutacije FV Leiden i FII G20210A predstavljaju značajne faktore rizika za nastanak TDV donjih ekstremiteta. Kod TDV gornjih ekstremiteta ove mutacije su manje zastupljene i potrebno je sprovesti dalja istraživanja koja obuhvataju veći broj bolesnika. MTHFR C677T mutacija je manje značajan faktor rizika i treba ga razmatrati samo u slučajevima kada se pojavljuje u kombinaciji sa drugim faktorima rizika.Deep vein thrombosis (DVT) is a multifactorial disease that occurs with frequency of 1/1000 per year. The FV Leiden, FII G20210A and MTHFR C677T mutations represent genetic factors for the occurrence of vein thrombosis. The goal of this study was to determine the frequency of these mutations in patients with DVT of upper and lower limbs. The study encompassed 119 patients divided in two groups. The group of patients with the lower limbs thrombosis included 77 patients, while the upper limbs thrombosis group included 42 patients. The presence of FV Leiden, FII G20210A and MTHFR C677T mutations was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. In patients with DVT of lower limbs, the frequency of FV Leiden mutation was 26,0% in heterozygous form and 1,3% in homozygous form. In the group of patients with DVT of upper limbs, the frequency of heterozygous carriers was 7.2%. In patients with DVT of lower limbs, FII G20210A mutation occurred in heterozygous form in 15.6% subjects, and in the group with DVT of upper limbs the frequency was 7.2% in heterozygous and 2.3% in homozygous form. The frequency of MTHFR C677T mutation in patients with lower limbs DVT was 42.8% in heterozygous form and 13% in homozygous form, while in the group of patients with upper limbs DVT, the frequency was 52.4% in heterozygous form and 9.5% in homozygous form. The FV Leiden and FII G20210A mutations represent significant risk factors for the occurrence of DVT of lower limbs. These mutations are less frequent in DVT of upper limbs and more extensive further studies are needed to determine their potential role. The MTHFR C677T mutation represents less significant risk factor for lower limb DVT and should be taken into account only in cases when it occurs in combination with other risk factors

Type and Location of Venous Thromboembolism in Carriers of Factor V Leiden or Prothrombin G20210A Mutation Versus Patients With No Mutation

Factor V Leiden (FVLeiden) and prothrombin G20210A are the most common genetic causes of thrombophilia and established risk factors for different clinical manifestations of venous thromboembolism (VTE). This study investigated whether the clinical manifestation of VTE, the extension of deep vein thrombosis (DVT) and the presence of transient risk factors at the time of the first VTE, differed among patients with mutations (97 with FVLeiden; 33 with prothrombin G20210A) and in 109 patients without thrombophilia. Isolated pulmonary embolism (PE) was less prevalent in patients with FVLeiden (6%) and no thrombophilia (6%) than in those with prothrombin G20210A (15%). No difference was found in the incidence of distal DVT. Regarding the extension of proximal DVT, the lowest incidence for isolated popliteal vein and the highest for iliofemoral vein were observed in patients with prothrombin G20210A. No difference was observed between groups of patients with or without thrombophilia by unprovoked VTE. The pregnancy/puerperium was the most prevalent risk factor in carriers of prothrombin G20210A. Among FVLeiden carriers, the most prevalent risk factor was surgery, and in patients without thrombophilia, it was trauma (P lt .05). Thrombosis of the upper limb was more frequent in a group without thrombophilia than in patients with mutations (P lt .01). Transverse sinus venous thrombosis was present only in patients with prothrombin G20210A. Carriers of prothrombin G20210A have an increased risk of developing isolated PE and more severe clinical manifestations than those with FVLeiden or without thrombophilia

The improvement of ferroelectric properties of BiFeO3 ceramics by doping with La3+ and Eu3+

Bismuth ferrite is a unique multiferroic material that has a ferroelectric and antiferromagnetic order at room temperature. The rhombohedrally (R3c) distorted BiFeO3 perovskite structure is a result of relative cation displacement along [111] axis of the cubic perovskite structure and relative rotation of two oxygen octahedra in opposite directions around [111] axis [1]. The partial substitution of Bi3+ with rare-earth ions can affect the magnitude of lattice distortion and thus the value of electric polarization. The presence of undesirable secondary phases (Bi2Fe4O9 and Bi25FeO39) and structural point defects (oxygen and bismuth vacancies) in pure BiFeO3 lead to a high leakage current, which deteriorates its ferroelectric properties. Doping with rare-earth elements with large ionic radii is found to reduce the number of the structural defects and thus improve ferroelectric properties [2]. The influence of partial substitution of Bi3+ with La3+ and/or Eu3+ on ferroelectric properties of BiFeO3 ceramics was investigated. The Bi1-(x+y)LaxEuyFeO3 (x = 0, 0.025 0.05, 0.10; y = 0, 0.025, 0.05, 0.10) powders were synthesized by hydro-evaporation method, uniaxially pressed at 9 t/cm2 and sintered at 835 °C for 3 h. All the ceramic samples showed a rhombohedral structure, without presence of the secondary phases. Their morphology indicated the complete sintering under the given conditions. The grain size and grain shapes differed more depending on the dopant type and amount. The introduction of La3+ and/or Eu3+ at the site of Bi3+ led to such distortions within the rhombohedral lattice that resulted in much greater remnant electric polarization (Pr) in comparison with the undoped sample. The Bi1-(x+y)LaxEuyFeO3 ceramic samples with x+y = 0.10 showed approximately quadratic polarization vs. electric field P(E) hysteresis curves as well as significantly high values of pure ferroelectric polarization Pr, in large electric fields (100 – 140) kV/cm. The leakage currents of La3+/Eu3+-doped samples are mostly reduced, especially those doped only with Eu3+

Fenotyp typu &#8222;talia hipertriglicerydemiczna&#8220; i zespół metaboliczny określany na podstawie różnych kryteriów oraz zależności między tymi zaburzeniami a kontrolą stężeń lipidów i glikemii u chorych na cukrzycę typu 2

Background: Metabolic syndrome (MetS) describes clustering of obesity, dyslipidemia, hyperglycemia and hypertension and increases risk for cardiovascular disease and type 2 diabetes. The &#8216;hypertriglyceridemic waist&#8217; phenotype (HTGW) represents a simple approach to identifying individuals with increased risk. The aim of the study was to determine the prevalence of HTGW and MetS in type 2 diabetic patients, and to examine their relation to lipids and blood glucose control. Material and methods: 300 type 2 diabetic patients were analysed, and their history of diabetes, anthropometric measures, measurements of blood pressure (BP), lipids and glycemic control parameters were taken. Results: In type 2 diabetic patients, the prevalence of MetS was 71.0% by the AHA/NHLBI definition and 75.33% by the IDF definition. The prevalence was 62.58% and 66.45% in men, and 80% and 84.83% in women by the same definitions, respectively. There were 41.33% of patients with HTGW (42.76% among women and 40% among men). There were statistically significant differences of age, fasting plasma glucose (FPG) and postprandial glucose (PPG) in women with and without MetS according to both definitions, and of total and LDL cholesterol with and without MetS according to AHA/NHLBI (but not IDF). In men, there were statistically significant differences of total cholesterol and of HbA1c with and without MetS according to AHA/NHLBI (but not IDF). Women with HTGW had higher levels of total and LDL cholesterol, systolic and diastolic BP. Men with HTGW had higher levels of total cholesterol, diastolic BP, HbA1c, FPG and PPG. Conclusions: Determining MetS or HTGW helps identify those with increased cardiovascular risk. (Pol J Endocrinol 2011; 62 (4): 316&#8211;323)Wstęp: Zespół metaboliczny (MetS) obejmujący otyłość, dyslipidemię, hiperglikemię i nadciśnienie tętnicze zwiększa ryzyko chorób sercowo-naczyniowych i cukrzycy typu 2. Określanie fenotypu &#8222;talii hipertriglicemicznej&#8221; (HTGW) jest prostą metodą identyfikowania chorych z grupy wysokiego ryzyka. Celem badania było ustalenie częstości HTGW i MetS u chorych na cukrzycę typu 2 oraz ocena zależności miedzy tymi zaburzeniami a kontrolą stężeń lipidów i glikemii. Materiał i metody: Do badania włączono 300 chorych na cukrzycę typu 2 i przeanalizowano dane dotyczące przebiegu cukrzycy, parametrów antropometrycznych, wartości ciśnienia tętniczego, stężeń lipidów i kontroli glikemii. Wyniki: U chorych na cukrzycę typu 2 kryteria MetS według definicji AHA/NHLBI spełniało71,0%, a kryteria IDF &#8212; 75,33%; odsetek chorych z MetS wynosił wśród mężczyzn odpowiednio 62,58% i 66,45%, a wśród kobiet 80% i 84,83%. U 41,33% chorych stwierdzono cechy HTGW, 42,76% tej grupy stanowiły kobiety, a 40% mężczyźni. U kobiet wykazano istotne statystycznie różnice w zakresie wieku, glikemii na czczo (FPG) i glikemii poposiłkowej (PPG) między grupami z MetS i bez niego, rozpoznanym na podstawie obu definicji, natomiast w zakresie stężenia cholesterolu całkowitego i frakcji LDL różniły się one tylko między grupami z MetS i bez niego wydzielonymi na podstawie definicji AHA/NHLBI (a nie na podstawie kryteriów IDF). U mężczyzn wykazano statystycznie istotne różnice stężeń cholesterolu całkowitego HbA1c między grupami z MetS i bez niego określonym według AHA/NHLBI (ale nie według IDF). U kobiet z HTGW stwierdzono wyższe stężenia cholesterolu całkowitego i cholesterolu frakcji LDL oraz wyższe wartości ciśnienia skurczowego i rozkurczowego. U mężczyzn z HTGW odnotowano wyższe wartości stężeń cholesterolu całkowitego, rozkurczowego ciśnienia tętniczego, HbA1c, FPG i PPG. Wnioski: Rozpoznanie MetS lub HTGW pozwala zidentyfikować osoby obciążone zwiększonym ryzykiem sercowo-naczyniowym. (Endokrynol Pol 2011; 62 (4): 316&#8211;323

Ferroelectric properties of BiFeO3 ceramics with cation substitutions at Bi-site (La3+, Eu3+) and Fe-site (Nb5+, Zr4+)

BiFeO3 is one of the few multiferroic perovskites that exhibits magnetic and ferroelectric properties at room temperature. However, it is also distinguished by high leakage current, low remnant electric and magnetic polarization, and high electric coercive field. These features keep it away from any practical use in electronics. Therefore, many attempts have been made to improve the properties of BiFeO3 by Bi- or Fe-site doping or by both. Previous investigations suggest that doping with Nbat Fe-site can positively affect the magnetic behavior of BiFeO3 and decrease the leakage current. In this study, various cation substitutions at Bi-site (La3+, Eu3+) and Fe-site (Nb5+, Zr4+) were examined to investigate their possible synergism and benefit for the ferroelectric properties. The role of the cations with higher valence is to suppress the formation of structural defects during synthesis, such as oxygen and bismuth vacancies. These defects are responsible for high leakage currents and, consequently, low breakdown voltages characteristic of the pure BiFeO3. On the other hand, rare earth cations at the Bisite usually enable densification of the ceramics in a wider range of temperatures, preventing bismuth loss and forming defects and secondary phases during sintering. However, do pant concentrations above 10–15mol% may give rise to transition from polar, rhombohedral (R3c) to non-polar, orthorhombic (Pnma) symmetry. The carefully selected compositions of doped BiFeO3 were synthesized by a simple hydro-evaporation method. The ceramics samples were characterized using X-ray diffraction (XRD) analysis, scanning electron microscopy (SEM), and polarization techniques, including leakage current measurements. Although the introduction of Nb5+or Zr4+decreased the leakage current, they surprisingly deteriorated the ferroelectric properties even at concentrations as low as 1 mol%. This effect was more pronounced for the samples containing Nb. On the contrary, both La3+ and Eu3+ (incorporated at the Bi-site) improved the ferroelectric properties as their concentrations increased. The La-doped samples exhibited higher remnant electric polarizations at observed electric fields. The highest remnant electric polarization of31.9 μC/cm2at 150 kV/cm was measured for Bi0.85La0.15Fe0.998Zr0.002O3, indicating the synergetic effect of La3+ and Zr4+, which is limited to very low Zr4+concentrations