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Acute B. canis infection can lead to an acute phase reaction (APR) in dogs. The parasite invades red blood cells causinganemia through immune-mediated hemolysis and possible erythropoietic suppression. A regenerative response of theerythroid lineage during the babesiosis has not been described in extension. This research examines hematologic parametersfocusing on the absolute reticulocyte count and apolipoprotein A I (ApoA I) level on the day of admission and 14 days aftertreatment with imidocarb-dipropionate in young (n=11) and adult (n=11) dogs naturally infected with B. canis. Metabolicand inflammatory processes were characterized by analyzing protein and lipid profiles, as well as ApoA I at specified timepoints. Automated analyzers were used to determine complete blood count and biochemical parameters, while ApoA I wasassessed using radioimmunoassay. The reticulocyte count was determined using a manual method by means of supravitalstaining. Both young and adult dogs with acute B. canis infection showed non-regenerative anemia without difference.Fourteen days after successful treatment with imidocarb-dipropionate, the anemia was corrected and a high reticulocytecount was observed (p<0.05). This indicates that the erythroid regenerative response was efficient in young and adult dogs,although vital signs, leukocyte count and triglyceride concentration suggest a more intense APR in young dogs. A decreasein ApoA I in both groups 14 days after treatment (p<0.01) confirmed that this lipoprotein acts as a positive acute-phaseprotein in acute B. canis infection in dogs, but further studies are needed to connect its role in erythroid lineage regeneration.

The use of vanadium complexes for potential applications in medicine largely depends on the structural properties of the complex itself, as well as on the electronic configuration of the metal and its oxidation state. When the vanadium complex binds to biomolecules or by binding solvent molecules to the complex, there is a change in the structure but also a change in the redox properties of the complex. Using theoretical methods, especially Density Functional theory (DFT), it is possible to determine which factors influence changes in the redox properties of the complex. Furthermore, by calculating the Electron Paramagnetic Resonance (EPR) constants of hyperfine coupling, it is possible to obtain not only data on the electronic configuration, but also to predict changes in redox properties upon changes in the structure of the complex. DFT results show that the binding of pyridine or imidazole to the VO(acac)2 complex leads to a lowering of the redox potential. The largest changes in the redox potential were observed in the case when the incoming ligand binds in a cis position relative to the V==O bond.

Prisustvo radiohemijske nečistoće C u 99mTc-MIBI injekciji utiče na kvalitet skena, jer se radiofarmaceutik nedovoljno nakuplja u organu od interesa, dok je aktivnost okolnih organa i tkiva velika. Zbog toga je i doza zračenja koju prime okolni organi i tkiva iznad propisanih granica. Da bi se obezbedilo da je planirano izlaganje zračenju pacijenata svedeno na minimum, farmakopeja zahteva ispitivanje sadržaja radiohemijske nečistoće C u 99mTc-MIBI injekciji neposredno pre primene radiofarmaceutika u pacijenta. Za ova ispitivanja se koriste metode hromatografije. U radu je predstavljena brza i osetljiva ITLC metoda namenjena za rutinsko ispitivanje sadržaja radiohemijske nečistoće C u 99mTc-MIBI injekciji. ITLC metoda je validirana, a ispitivani su pogodnost sistema, tačnost, preciznost, ponovljivost, specifičnost, limit detekcije, limit kvantifikacije, linearnost, robustnost i osetljivost metode. Dobre "recovery" vrednosti i niska relativna standardna devijacija potvrđuju da je predložena ITLC metoda pogodna za rutinsko određivanje nečistoće C u 99mTc-MIBI u injekciji., The European Pharmacopoeia mandates that all radiopharmaceuticals used in nuclear medicine for diagnostic and therapeutic purposes must be of the correct radiochemical and radionuclidic purity and have the correct radioactivity present at the stated time of injection to ensure that the intended radiation exposure of patients is kept to a minimum. These factors have an effect on the overall radiation dose to the patient, as impurities of the radionuclide and/or its chemical composition may affect the biodistribution of the injected radiopharmaceutical and consequently the radiation dose to any one particular organ or the whole body dose. The presence of radiochemical impurity C in 99mTc-MIBI injection affects the quality of the image, because 99mTc-MIBI accumulates insufficiently in the organ of interest, while the activity of the surrounding organs and tissues is high. Therefore, the radiation dose received by the surrounding organs and tissues is above the permitted level. In order to avoid unnecessary irradiation of surrounding organs and tissues, the pharmacopoeia requires examination of the content of radiochemical impurity C immediately before administering of 99mTc-MIBI to the patient. Chromatographic methods are used for these tests. The paper presents a fast and sensitive ITLC method intended for routine examination of the content of radiochemical impurity C in 99mTc-MIBI injection. The ITLC method was validated, and the suitability of the system, accuracy, precision, repeatability, specificity, limit of detection, limit of quantification, linearity, robustness and sensitivity of the method were examined. Good "recovery" values and low relative standard deviation confirm that the proposed ITLC method is suitable for routine determination of impurity C in 99mTc-MIBI in injection.

Radiofarmaceutici koji se koriste za ispitivanje skeletnog sistema od neprocenjivog su značaja u nuklearnoj medicini, kako za dijagnostiku primarnih tumora koštanog tkiva, tako i metastaza. Pre primene na pacijentima, ovi radiofarmaceutici podležu različitim fizičko-hemijskim i biološkim ispitivanjima. Ispitivanje fiziološke raspodele leka in vivo je od presudnog značaja jer od akumulacije leka u odgovarajućoj meri u ciljnom organu (skeletu) zavisi kvalitet dobijenog scintigrama, kao i doza zračenja koje će primiti pojedinačni organi i tkiva. U evropskoj farmakopeji (Ph.Eur.) date su metode kontrole kvaliteta kao i parametri kvaliteta sa granicama prihvatljivosti (specifikacijske granice) za 99mTc-metilendifosfonat (99mTc-MDP). Cilj ovog rada je prikaz metode ispitivanja fiziološke raspodele 99mTc-DPD koja je razvijena u Laboratoriji za radioizotope po smernicama evropske farmakopeje za 99mTc-MDP, uz manje modifikacije. Rezultati biodistribucije na Wistar pacovima su pokazali da je 99mTc-DPD proizveden u Laboratoriji za radioizotope zadovoljio sve postavljene kriterijume, kako odmah nakon proizvodnje, tako i nakon šest i dvanaest meseci od proizvodnje., Radiopharmaceuticals used to examine the skeletal system are of invaluable importance in nuclear medicine, both for the diagnosis of primary bone tissue tumors and metastases. Before administration to patients, these radiopharmaceuticals undergo various physico-chemical and biological tests. Investigation of the physiological distribution of the drug in vivo is of crucial importance because the quality of the obtained scintigram depends on the accumulation of the drug in the target organ (skeleton), as well as the radiation dose received by individual organs and tissues. The European pharmacopoeia (Ph.Eur.) provides quality control methods and quality parameters with acceptance limits (specification limits) for 99mTc-methylenediphosphonate (99mTc-MDP). The method of testing the physiological distribution of 99mTc-DPD in the Laboratory for Radioisotopes, which is presented in this paper, is done according to the guidelines of the European Pharmacopoeia for 99mTc-MDP, with minor modifications. Results of biodistribution on Wistar rats showed that 99mTc-DPD produced in the Laboratory for Radioisotopes met all the set criteria, both immediately after the production and after six and twelve months from production.

Juglansnigraleaf is a source of health-promoting biologically active compounds and used in traditional medicine. Can we predict theradioprotective dose level of plant extracts based on modeling change biodistribution of radiopharmaceuticals by response surface methodology (RSM)? The present study aimed to the effects of J. nigra leaf extract oral intake on the biodistribution of 99mTc-radiopharmaceutical in healthy rats and to formulate a mathematical model that will associate the changes in radioactivity in organ with dose levels of extract and body mass of rats. The extract was administered daily by oral gavage to rats at dose levels of 6.9, 10.3, or 13.7 mg kg-1 body weight (bw) day-1 for 10 days. On the eleventh day, 0.1 ml (approximately 148 kBq) of the 99mTc-dimercaptosuccinic acid (DMSA) was injected into the tail vein. The organs of interest were isolated and radioactivity in each organ was counted by a gamma counter with a NaI (Tl) detector. After treatment of rats with the extract, there was a statistically significant decrease (p<0.05) in the uptake of 99mTc-DMSA (%ID/organ) in the kidneys compared to controls.The RSM model based on the second-order polynomial equation was apply to correlate changes in radioactivity in kidney with dose levels of extract and body mass of rats.The statistical significance of RSM as well as independent variables and their interactions were estimated by ANOVA (Analysis of variance). The F-value (265) and p-value (< 0,001) demonstrated that the developed model has statistical significance at the confidence level of 95%. The R2 values (0.987) proved a good fit by the second-order polynomial equation, while relatively low values of the CV (0.69) indicated the remarkable precision and reliability of the model. The low value of mean relative percent deviation (0.4) between the experimental data and the predicted radioactivity of kidney obtained by RSM showed that RSM was suitable for modeling the change biodistributionof radiophar

Laboratorija za radioizotope Instituta Vinča je jedinstven centar u regionu koji poseduje Rešenja Ministarstva zdravlja Republike Srbije i Direktorata za radijacionu i nuklearnu sigurnost i bezbednost Srbije za proizvodnju radiofarmaceutika. Radiofarmaceutik koji se proizvodi više od 40 godina u Laboratoriji za radioizotope, a primenjuje u terapiji tumora štitaste žlezde, kao i hipertireozi su kapsule natrijum-jodida (I-131). Radijacioni efekti I-131 na ćelije štitaste žlezde potiču od beta-zračenja koje emituje I-131 tokom radioaktivnog raspada u samoj štitastoj žlezdi jer se I-131 nakon oralne primene nakuplja prvenstveno u štitastoj žlezdi u kojoj ima dugu retenciju. Za efikasnu terapiju, ali u isto vreme u cilju smanjenja izloženosti nepotrebnim dozama, za svakog pacijenta određuje se odgovarajuća doza I-131 koju je neophodno da primi, odnosno primenjuje se tzv. personalizovana terapija. U radu je opisan postupak proizvodnje kapsula I-131 u Laboratoriji za radioizotope putem manuelnog punjenja kapsula rastvorom I-131, kao i osnovni zahtevi koje je neophodno da sistem za automatsku proizvodnju radiofarmaceutika ispuni, a to su pre svih, odgovarajuća zaštita operatera od zračenja, jednostavna upotreba i kompjuterska kontrola., The Laboratory for radioisotopes of the Vinča Institute is a unique center in the region with licences of the Ministry of Health of the Republic of Serbia and the Directorate for Radiation and Nuclear Safety and Security of Serbia for the production of radiopharmaceuticals. Sodium iodide (I-131) capsules are radiopharmaceuticals that have been produced for more than 40 years in the Laboratory for Radioisotopes, and are used in the treatment of tumors of thyroid gland, as well as in hyperthyroidism. The radiation effects of I-131 on thyroid cells originate from beta-radiation emitted by I-131 during radioactive decay in the thyroid gland itself because I-131 after oral administration accumulates primarily in the thyroid gland where it has a long retention. For the effective therapy, but at the same time in order to reduce exposure to unnecessary high doses, the appropriate dose of I-131 is determined for each patient, in the so-called personalized therapy. The paper describes the current procedure for the production of I-131 capsules in the Laboratory for Radioisotopes by manually filling the capsules with I-131 solution and the basic requirements for design the system for automating the production of radiopharmaceuticals, which above all must provide adequate protection for the operator from radiation, must be user friendly and computer-controlled.

As an alternative to classical brachytherapy, intratumoral injection of radionuclide-labeled nanoparticles (nanobrachytherapy, NBT) has been investigated as a superior delivery method over an intravenous route for radionuclide therapy of solid tumors. We created superparamagnetic iron oxide nanoparticles (SPIONs) coated with meso-1,2-dimercaptosuccinic acid (DMSA) and radiolabeled with Lutetium-177 (177Lu), generating 177Lu-DMSA@SPIONs as a potential antitumor agent for nanobrachytherapy. Efficient radiolabeling of DMSA@SPIONS by 177Lu resulted in a stable bond with minimal leakage in vitro. After an intratumoral injection to mouse colorectal CT-26 or breast 4T1 subcutaneous tumors, the nanoparticles remained well localized at the injection site for weeks, with limited leakage. The dose of 3.70 MBq/100 µg/50 µL of 177Lu-DMSA@SPIONs applied intratumorally resulted in a high therapeutic efficacy, without signs of general toxicity. A decreased dose of 1.85 MBq/100 µg/50 µL still retained therapeutic efficacy, while an increased dose of 9.25 MBq/100 µg/50 µL did not significantly benefit the therapy. Histopathology analysis revealed that the 177Lu-DMSA@SPIONs act within a limited range around the injection site, which explains the good therapeutic efficacy achieved by a single administration of a relatively low dose without the need for increased or repeated dosing. Overall, 177Lu-DMSA@SPIONs are safe and potent agents suitable for intra-tumoral administration for localized tumor radionuclide therapy

Asymptomatic outdoor dogs can be carriers of Babesia canis, but data describing the development of an acute phase response (APR) are not available. We hypothesised that these dogs have a moderate APR that could be detected by hematological and biochemical changes. Two groups of Babesia-exposed dogs were represented by nine B. canis PCR-positive and twenty B. canis PCR-negative, seroreactive dogs. The control group consisted of ten Babesia-naïve dogs. Serum amyloid A (SAA), paraoxonase-1 (PON-1), complete blood count, and biochemistry parameters were analysed by standard methodologies. Protein and lipoprotein fractions were separated using agarose gel electrophoresis (GE), and the dominant diameters of lipoproteins were assessed on gradient GE. Results were evaluated using non-parametric tests and the Receiver Operating Characteristic curve. SAA (median 39.0 μg/mL, range 2.2–48.8 μg/mL), total protein (median 74.7 g/L, range 57.1–98.3 g/L) and the dominant diameter of α-lipoproteins (median 13.31 nm, range 12.09–14.17 nm) in B. canis PCR-positive dogs were higher relative to dogs in the control group or dogs that were PCR-negative but seroreactive (p < 0.001 for both groups). Mild to moderate anemia (4/29), thrombocytopenia (7/29), and leukocyte counts that were close to the upper limit of the reference range were encountered in both Babesia-exposed groups. When compared to controls, Babesia-exposed dogs displayed decreased a PON-1 activity and protein GE pattern consistent with low-grade chronic inflammation (p < 0.001 for both groups). Dogs with detectable amounts of B. canis DNA in blood contain increased levels of SAA and total protein along with α-lipoproteins that display an increased diameter relative to those dogs with positive Babesia serology but undetectable levels of B. canis DNA in blood.

Two new Schiff base cobalt(III) ([Co(LH)Cl2], 1) and nickel(II) ([Ni(LH)ClO4], 2) complexes with a diimine-dioxime ligand, (4,9-diaza-3,10-diethyl-3,9-dodecadiene-2,11-dione bis oxime (LH2)), were synthesized and characterized. The compounds were obtained in MeOH from corresponding metal salts and LH2 in molar ratio 1:1 and further characterized by mass spectrometry, IR spectroscopy, electrochemistry, and elemental analysis. Previously reported copper(II) analog, ([Cu2(LH)2]·(ClO4)2, 3) was joined to 1 and 2, and the three metal analogs, 1-3, were further investigated in terms of their electrochemical behavior. The binding studies of the complexes with deoxyribonucleic acid (DNA) and human serum albumin (HSA) were carried out using both spectrophotometric and electrochemical methods. All three complexes exhibit binding affinity towards the DNA chain through intercalative interaction. The binding reaction with HSA showed for 1 and 3 complexes decrease in the peak current obtained in the case of complexes before the addition of HSA, while resulted compound obtained from Ni complex – HSA possesses the same electroactivity as starting complex. Furthermore, the cytotoxicity of LH2 as well as its metal complexes, and cisplatin were evaluated on CT-26 mouse colon carcinoma and human LS174T cancer cell lines employing MTT assay. The copper(II) complex exhibited very promising anticancer activity compared with cisplatin.

Background: Lower homocysteine (Hcy) concentraon was noced in dogs with systemic inflammatory response syndrome of various aeology, in comparison with healthy dogs. Objecve. The study had two objecves: to compare Hcy concentraons in serum between dogs naturally infected with Babesia canis and healthy dogs; to assess the relaonship between Hcy concentraon and the results of the roune laboratory tests. Materials and methods. The study enrolled twelve dogs infected with B. canis (BAB) and six healthy dogs (HD). The commercial immunoassay, spectrophotometry, and haematology kits were used. Stascal analyses included the Mann-Whitney U test and Spearman's rank correlaon analysis. Results: BAB had lower concentraons of Hcy than HD (p=0.045). When analysing the results from all studied dogs together, Hcy had a posive correlaon with erythrocyte count (r=0.771; p=0.001), haemoglobin concentraon (r=0.696; p=0.004), haematocrit (r=0.664; p=0.007), leukocyte count (r=0.554; p=0.032), and total protein concentraon (r=0.689; p=0.004), and a negave with glycaemia (r=- 0.693; p=0.004). Conclusion: The obtained results provide preliminary evidence about the associaon between acute canine babesiosis and lowered Hcy concentraon in blood. Further studies will decipher whether this finding has clinical applicability or represents just an APR epiphenomenon.

Novel methods of cancer therapy are constantly being investigated since the current approach heavily relies on the use of non-specific and toxic chemotherapy agents. Ideally, a drug used for cancer therapy would specifically target tumor sites or rather bind specifically with cancer cells. The way to achieve this is by targeting cancer cell specific receptors or receptors present in abnormally high counts at the surface. Rapid proliferation of cancer cells is fueled by large amounts of energy that is in turn produced by abnormal glucose uptake. Because of this high energy/glucose demand, cancer cells exhibit an abnormally high glucose receptor (GLUTs) count on their surface, compared to normal, healthy cells. We have utilized this glucose dependency to create glucose modified liposomes (Glucosomes) that are specifically bound by cancer cells. Glucosomes can be used to transport different substances, either hydrophilic or hydrophobic, and can therefore deliver any type of drug to cancer cells, increasing its efficiency. Another important aspect to consider is the controlled release of the drug being transported in order to maximize therapeutic efficiency. Controlled release can be achieved by utilizing different internal or external influences. In our study, we have used standard Fe3O4 magnetic nanoparticles to load glucosomes and induce their controlled opening via an external magnetic field. By applying an external magnetic field, the magnetic nanoparticles start heating up and transferring this thermal energy to the surrounding lipid bilayer, causing its perturbation and opening of the glucosome. Our study has found that controlled release can be achieved with high efficiency while the chemical stability of the Fe3O4 nanoparticles stays practically intact. Using EPR spectroscopy, we have shown that Fe3O4 nanoparticles remain trapped within the lipid bilayer and are essentially protected from oxidation that would diminish their magnetic properties. Since magnetic F

Juglans nigra L. (Black walnut) green husk contains a variety of useful chemical compounds with numerous health benefits. However, the biological effects of these compounds are not fully known. The aim of this research was to evaluate the effect of the extracts from J. nigra green husks on the biodistribution of the sodium pertechenetate (Na99mTcO4). The extract was orally administered to the healthy Wistar rats (male, 1-month-old, weighing 89.4±3.4g) at single doses of 13.7 mg/kg/day by gavage for 10 days. On the eleventh day, 0.1 ml (approximately 148 kBq) of the Na99mTcO4 was injected into the tail vein. Rats were sacrificed at different time intervals and the radioactivity in the organs of interest was measured in a gamma counter with a NaI (Tl) detector. The percentage of radioactivity per organ (%ID/organ) was calculated. The organ uptake of the Na99mTcO4 in an additional control group of animals was also studied. The results obtained showed an alteration in the organ uptake of Na99mTcO4 in rats treated with extract. The radiopharmaceutical Na99mTcO4 is generally distributed throughout the vasculature and interstitial fluid and is concentrated in the stomach, intestinal tract, thyroid and salivary glands. After treatment of rats with the extract, there was a statistically significant decrease (p<0.05) in the uptake of Na99mTcO4 (%ID/organ) in the thyroid, heart, kidneys, liver and colon, and an increase in intestinal uptake compared to controls. These results are associated with properties of the chemical compounds present in the J. nigra extract. We assume that the compounds from the extract J. nigra could promote physiological modifications in these organs and alter the biodistribution of Na99mTcO4 in the treated animals. Although these research studies were performed in animals, the findings suggest that caution should be exercised while interpreting the results of Na99mTcO4 based nuclear medicine examinations in patients using J. nigra extract from green h

Surface modification of magnetic nanoparticles with poly-L-lysine, proline, and tryptophan was used to design potential theranostic agents for the application in cancer diagnosis and radionuclide-hyperthermia therapy. Characterization of bare and functionalized magnetic nanoparticles was performed in detail. The transparency of the examined magnetic nanoparticles was measured in the non-alternating magnetic field for a complete and better understanding of hyperthermia. For the first time amino acid-functionalized magnetic nanoparticles were labeled with theranostic radionuclides 131I and 177Lu. The specific absorption rate (SAR) procured for poly-L-lysine functionalized magnetic nanoparticles (SAR values of 99.7 W/g at H0 = 15.9 kA/m and resonant frequency of 252 kHz) demonstrated their possible application in magnetic hyperthermia. Poly-L-lysine functionalized magnetic nanoparticles labeled with 177Lu showed the highest radiochemical purity (>99.00 %) and in vitro stability in saline and serum (>98.00 % up to 96 h). The in vivo analysis performed after their intravenous administration in healthy Wistar rats presented good in vivo stability for several days. Encouraging results as well as magnetic and radiochemical properties of 177Lu–PLL-MNPs (80 °C) justify their further testing toward the potential use as theranostic agents for diagnostic and combined radionuclide-hyperthermia therapeutic applications.

Two new Schiff base cobalt(III) ([Co(LH)Cl2], 1) and nickel(II) ([Ni(LH)ClO4], 2) complexes with a diimine-dioxime ligand, (4,9-diaza-3,10-diethyl-3,9-dodecadiene-2,11-dione bis oxime (LH2)), were synthesized and characterized. The compounds were obtained in MeOH from corresponding metal salts and LH2 in molar ratio 1:1 and further characterized by mass spectrometry, IR spectroscopy, electrochemistry, and elemental analysis. Previously reported copper(II) analog ([Cu2(LH)2]·(ClO4)2, 3) was joined to 1 and 2, and the three metal analogs, 1–3, were further investigated in terms of their electrochemical behavior. Binding studies of the complexes with deoxyribonucleic acid (DNA) and human serum albumin (HSA) were carried out using both spectrophotometric and electrochemical methods. All three complexes exhibit binding affinity towards the DNA chain through intercalative interactions. The binding reaction with HSA showed for 1 and 3 decrease in the peak current obtained in the case of complexes before the addition of HSA, while the Ni complex–HSA possesses the same electroactivity as starting complex. The cytotoxicity of LH2 as well as its metal complexes, and cisplatin were evaluated on CT-26 mouse colon carcinoma and human LS174T cancer cell lines employing MTT assay. The copper(II) complex exhibited very promising anticancer activity compared with cisplatin.

This work presents advanced electrochemical platform based on screen printed diamond electrode (SPDE) system for the single drop “point-of-care” testing. Proposed approach was applied for the quantification of doxorubicin hydrochloride (DOX) in biological fluids and pharmaceutical product. Using a single drop (~30 μL) of the tested solution at the electrode surface, DOX showed high electroactivity over a wide range of pHs. In these conditions, single oval shaped, well-defined and pH dependent oxidation peak was observed in the potential range from 0.5 V to 1.3 V. In the reverse scan, two cathodic peaks, were noted – around 0.3 V and – 0.5 V. Similarly, first reduction peak was pH dependent, while second one was independent in the studied range. Experimental conditions for DOX quantification were optimized and natures of the electrode reactions were investigated. Working linear range obtained for DOX detection was from 0.1 to 2.5 μM. Diffusion controlled electrode reaction reveal long life time of the proposed electrode as well high potential for practical application. Developed procedure was successfully applied for the DOX analysis in biological fluids – urine and pharmaceutical formulation. Obtained results clearly indicated that given procedure can be easily implemented for pharmaceutical control and medical analysis, in both, laboratory and field conditions.