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1.
Molecules ; 28(22)2023 Nov 19.
Article in English | MEDLINE | ID: mdl-38005390

ABSTRACT

The concept of theranostics uses radioisotopes of the same or chemically similar elements to label biological ligands in a way that allows the use of diagnostic and therapeutic radiation for a combined diagnosis and treatment regimen. For scandium, radioisotopes -43 and -44 can be used as diagnostic markers, while radioisotope scandium-47 can be used in the same configuration for targeted therapy. This work presents the latest achievements in the production and processing of radioisotopes and briefly characterizes solutions aimed at increasing the availability of these radioisotopes for research and clinical practice.


Subject(s)
Radiopharmaceuticals , Scandium , Radiopharmaceuticals/therapeutic use , Radiopharmaceuticals/chemistry , Scandium/chemistry , Radioisotopes/therapeutic use , Radioisotopes/chemistry , Precision Medicine
2.
Molecules ; 28(5)2023 Mar 03.
Article in English | MEDLINE | ID: mdl-36903596

ABSTRACT

Searching for new compounds and synthetic routes for medical applications is a great challenge for modern chemistry. Porphyrins, natural macrocycles able to tightly bind metal ions, can serve as complexing and delivering agents in nuclear medicine diagnostic imaging utilizing radioactive nuclides of copper with particular emphasis on 64Cu. This nuclide can, due to multiple decay modes, serve also as a therapeutic agent. As the complexation reaction of porphyrins suffers from relatively poor kinetics, the aim of this study was to optimize the reaction of copper ions with various water-soluble porphyrins in terms of time and chemical conditions, that would meet pharmaceutical requirements and to develop a method that can be applied for various water-soluble porphyrins. In the first method, reactions were conducted in a presence of a reducing agent (ascorbic acid). Optimal conditions, in which the reaction time was 1 min, comprised borate buffer at pH 9 with a 10-fold excess of ascorbic acid over Cu2+. The second approach involved a microwave-assisted synthesis at 140 °C for 1-2 min. The proposed method with ascorbic acid was applied for radiolabeling of porphyrin with 64Cu. The complex was then subjected to a purification procedure and the final product was identified using high-performance liquid chromatography with radiometric detection.


Subject(s)
Porphyrins , Porphyrins/chemistry , Copper/chemistry , Radiopharmaceuticals , Water , Ascorbic Acid/chemistry , Ions
3.
Molecules ; 27(10)2022 May 21.
Article in English | MEDLINE | ID: mdl-35630788

ABSTRACT

Porphyrin ligands, showing a significant affinity for cancer cells, also have the ability to chelate metallic radioisotopes to form potential diagnostic radiopharmaceuticals. They can be applied in single-photon emission computed tomography (SPECT) and positron emission tomography (PET) to evaluate metabolic changes in the human body for tumor diagnostics. The aim of this paper is to present a short overview of the main metallic radionuclides complexed by porphyrin ligands and used in these techniques. These chelation reactions are discussed in terms of the complexation conditions and kinetics and the complex stability.


Subject(s)
Nuclear Medicine , Porphyrins , Chelating Agents , Humans , Ligands , Molecular Imaging/methods , Radioisotopes
4.
Sci Rep ; 11(1): 19825, 2021 10 06.
Article in English | MEDLINE | ID: mdl-34615887

ABSTRACT

Preclinical and clinical studies have shown that stem cells can promote the regeneration of damaged tissues, but therapeutic protocols need better quality control to confirm the location and number of transplanted cells. This study describes in vivo imaging while assessing reporter gene expression by its binding to a radiolabelled molecule to the respective receptor expressed in target cells. Five mice underwent human skeletal muscle-derived stem/progenitor cell (huSkMDS/PC EF1-HSV-TK) intracardial transplantation after induction of myocardial infarction (MI). The metabolic parameters of control and post-infarction stem progenitor cell-implanted mice were monitored using 2-deoxy-18F-fluorodeoxyglucose ([18F]-FDG) before and after double promotor/reporter probe imaging with 9-(4-18F-fluoro-3-[hydroxymethyl]butyl)guanine ([18F]-FHBG) using positron emission tomography (PET) combined with computed tomography (CT). Standardized uptake values (SUVs) were then calculated based on set regions of interest (ROIs). Experimental animals were euthanized after magnetic resonance imaging (MRI). Molecular [18F]-FHBG imaging of myogenic stem/progenitor cells in control and post-infarction mice confirmed the survival and proliferation of transplanted cells, as shown by an increased or stable signal from the PET apparatus throughout the 5 weeks of monitoring. huSkMDS/PC EF1-HSV-TK transplantation improved cardiac metabolic ([18F]-FDG with PET) and haemodynamic (MRI) parameters. In vivo PET/CT and MRI revealed that the precise use of a promotor/reporter probe incorporated into stem/progenitor cells may improve non-invasive monitoring of targeted cellular therapy in the cardiovascular system.


Subject(s)
Fluorodeoxyglucose F18 , Molecular Imaging , Myoblasts, Cardiac/metabolism , Myocardial Infarction/metabolism , Myocardial Infarction/pathology , Positron Emission Tomography Computed Tomography , Adult Stem Cells/metabolism , Animals , Disease Models, Animal , Echocardiography , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Male , Mice , Mice, SCID , Molecular Imaging/methods , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/etiology , Polyesters
5.
Article in English | MEDLINE | ID: mdl-32752242

ABSTRACT

PURPOSE: Comparison of the activity of 11beta-hydroxysteroid dehydrogenase type 2 in the placenta and the umbilical cord blood cortisol level between caesarean sections with or without uterine contraction and vaginal delivery groups. Cortisol is the main stress hormone responsible for the normal adaptation of the neonate to extrauterine life. The disorders resulting from a dysfunction of the 11ß-HSD 2-cortisol system can explain the higher risk of developing diseases in children born by caesarean section. METHODS: 111 healthy, pregnant women in singular pregnancy at term of delivery were included into the study. The study comprised 11ß-HSD 2 in placental tissue from 49 pregnant women delivering by elective caesarean section and 46 pregnant women delivering by vagina. In 16 cases of the elective caesarean section, regular uterine contractions were declared. Cortisol level was estimated in umbilical cord blood directly after delivery. RESULTS: We found no statistically significant differences in the activity of 11ß-HSD 2 in placentas delivered via caesarean sections (29.61 on average in elective caesarean sections and 26.65 on average in intrapartum caesarean sections) compared to vaginal deliveries (31.94 on average, p = 0.381), while umbilical cord blood cortisol in the elective caesarean sections group was significantly lower (29.86 on average) compared to the vaginal deliveries (55.50 on average, p < 0.001) and intrapartum caesarean sections (52.27 on average, p < 0.001). CONCLUSIONS: The model of placental 11ß-HSD 2 activity and umbilical cord blood cortisol concentration seems to be significant in conditions of stress associated with natural uterine contractions in labour.


Subject(s)
11-beta-Hydroxysteroid Dehydrogenase Type 2 , Cesarean Section , Hydrocortisone , Labor, Obstetric , 11-beta-Hydroxysteroid Dehydrogenase Type 2/metabolism , Child , Female , Fetal Blood/chemistry , Humans , Hydrocortisone/analysis , Infant, Newborn , Placenta/metabolism , Pregnancy , Stress, Physiological , Uterine Contraction
6.
Bioorg Chem ; 91: 103136, 2019 10.
Article in English | MEDLINE | ID: mdl-31374521

ABSTRACT

Design, physicochemical and biological studies of novel radioconjugates for the early diagnosis of Alzheimer's disease, based on the newly synthesized tacrine derivatives were performed. Novel tacrine analogues were labeled with technetium-99m and gallium-68. For all obtained radioconjugates ([99mTc]Tc-Hynic-(tricine)2NH(CH2)ntacrine and [68Ga]Ga-DOTA-NH(CH2)9tacrine, where n = 2-9 denotes the number of methylene groups CH2) the studies of physicochemical properties (lipophilicity, stability in the presence of an excess of standard amino acids cysteine or histidine, human serum and in cerebrospinal fluid) were performed. For two selected radioconjugates [99mTc]Tc-Hynic-(tricine)2NH(CH2)9Tac and [68Ga]Ga-DOTA-NH(CH2)9tacrine (characterized with the highest lipophilicity values) the biological tests (inhibition of cholinesterases action, molecular docking and biodistribution studies) have been performed. All novel radioconjugates showed high stability in biological solutions used. Both selected radioconjugates proved to be good inhibitors of cholinesterases and be able to cross the blood-brain barrier. Radioconjugates [99mTc]Tc-Hynic-(tricine)2NH(CH2)9tacrine and [68Ga]Ga-DOTA-NH(CH2)9tacrine fulfil the conditions for application in nuclear medicine. Radiopharmaceutical [68Ga]Ga-DOTA-NH(CH2)9tacrine, due to increased accuracy and improved sensitivity in PET imaging, may be better potential diagnostic tool for early diagnosis of Alzheimer's disease.


Subject(s)
Cholinesterase Inhibitors/pharmacology , Organotechnetium Compounds/pharmacology , Radiopharmaceuticals/pharmacology , Tacrine/analogs & derivatives , Tacrine/pharmacology , Acetylcholinesterase/chemistry , Acetylcholinesterase/metabolism , Alzheimer Disease/diagnosis , Animals , Brain/metabolism , Butyrylcholinesterase/chemistry , Butyrylcholinesterase/metabolism , Catalytic Domain , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/metabolism , Drug Stability , Gallium Radioisotopes , Humans , Male , Molecular Docking Simulation , Organotechnetium Compounds/chemical synthesis , Organotechnetium Compounds/metabolism , Protein Binding , Radiopharmaceuticals/chemical synthesis , Radiopharmaceuticals/metabolism , Rats, Wistar , Tacrine/chemical synthesis , Tacrine/metabolism
7.
PLoS One ; 13(11): e0206706, 2018.
Article in English | MEDLINE | ID: mdl-30412628

ABSTRACT

The aim of this study was to evaluate hypoxia level at various tumor developmental stages and to compare various methods of hypoxia evaluation in pre-clinical CT26 tumor model. Using three methods of hypoxia determination, we evaluated hypoxia levels during CT26 tumor development in BALB/c mice from day 4 till day 19, in 2-3 days intervals. Molecular method was based on the analysis of selected genes expression related to hypoxia (HIF1A, ANGPTL4, TGFB1, VEGFA, ERBB3, CA9) or specific for inflammation in hypoxic sites (CCL2, CCL5) at various time points after CT26 cancer cells inoculation. Imaging methods of hypoxia evaluation included: positron-emission tomography (PET) imaging using [18F]fluoromisonidazole ([18F]FMISO) and a fluorescence microscope imaging of pimonidazole (PIMO)-positive tumor areas at various time points. Our results showed that tumor hypoxia at molecular level was relatively high at early stage of tumor development as reflected by initially high HIF1A and VEGFA expression levels and their subsequent decrease. However, imaging methods (both PET and fluorescence microscopy) showed that hypoxia increased till day 14 of tumor development. Additionally, necrotic regions dominated the tumor tissue at later stages of development, decreasing the number of hypoxic areas and completely eliminating normoxic regions (observed by PET). These results showed that molecular methods of hypoxia determination are more sensitive to show changes undergoing at cellular level, however in order to measure and visualize hypoxia in the whole organ, especially at later stages of tumor development, PET is the preferred tool. Furthermore we concluded, that during development of tumor, two peaks of hypoxia occur.


Subject(s)
Carcinoma/physiopathology , Colorectal Neoplasms/physiopathology , Hypoxia/physiopathology , Animals , Carcinoma/diagnostic imaging , Carcinoma/pathology , Cell Hypoxia , Cell Line, Tumor , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/pathology , Disease Progression , Female , Gene Expression Regulation, Neoplastic , Hypoxia/diagnostic imaging , Hypoxia/pathology , Mice, Inbred BALB C , Necrosis , Neoplasm Transplantation , Tumor Microenvironment
8.
Biomed Res Int ; 2018: 6793726, 2018.
Article in English | MEDLINE | ID: mdl-30140700

ABSTRACT

Uterine fibroids (UFs) are benign tumors of the reproductive tract, arising from smooth muscle cells of the uterus. Steroid hormones, estrogen, and progesterone are considered to be the most important links in the pathophysiology of UFs. Alpha-tocopherol (AT) is the most active form of vitamin E. What is important as far as UFs are concerned is that ATs contain structural determinants, which makes them possible ligands for estrogen receptors (ERs). We present a retrospective cohort study performed in a university teaching hospital. We included a total of 162 patients divided into 2 groups: with UFs and controls. The effects of age, body mass index (BMI), positive medical history, parity, and AT serum concentrations on the risk for the development of UFs were investigated. Mean AT serum concentrations were 11.66 ± 4.97 µg/ml and 7.83 ± 3.13 µg/ml (medians 10.56 µg/ml and 7.42 µg/ml) in patients with UFs confirmed on ultrasound and controls, respectively. The presented difference was statistically significant. Higher BMI, positive family history, and low parity were found to be major risk factors for UFs. In our study, we confirmed that elevated serum AT concentration might be an important risk factor for UFs in Caucasian women. Further research in this area is necessary.


Subject(s)
Leiomyoma/blood , Uterine Neoplasms/blood , alpha-Tocopherol/blood , Adult , Cohort Studies , Female , Humans , Middle Aged , Pilot Projects , Poland , Retrospective Studies
9.
Molecules ; 23(7)2018 Jul 20.
Article in English | MEDLINE | ID: mdl-30036947

ABSTRACT

The rapid increase in applications of scandium isotopes in nuclear medicine requires new efficient production routes for these radioisotopes. Recently, irradiations of calcium in cyclotrons by α, deuteron, and proton beams have been used. Therefore, effective post-irradiation separation and preconcentration of the radioactive scandium from the calcium matrix are important to obtain the pure final product in a relatively small volume. Nobias resin was used as a sorbent for effective separation of 44Sc from calcium targets. Separation was performed at pH 3 using a column containing 10 mg of resin. Scandium was eluted with 100 µL of 2 mol L-1 HCl. Particular attention was paid to the reduction of calcium concentration, presence of metallic impurities, robustness and simple automation. 44Sc was separated with 94.9 ± 2.8% yield, with results in the range of 91.7⁻99.0%. Purity of the eluate was confirmed with ICP-OES determination of metallic impurities and >99% chelation efficiency with DOTATATE, followed by >36 h radiochemical stability of the complex. A wide range of optimal conditions and robustness to target variability and suspended matter facilitates the proposed method in automatic systems for scandium isotope separation and synthesis of scandium-labeled radiopharmaceuticals.


Subject(s)
Calcium Carbonate/chemistry , Octreotide/chemical synthesis , Radioisotopes/chemistry , Scandium/chemistry , Hydrogen-Ion Concentration , Octreotide/chemistry , Organometallic Compounds/chemical synthesis , Organometallic Compounds/chemistry , Positron-Emission Tomography
10.
Article in English | MEDLINE | ID: mdl-26836453

ABSTRACT

Porphyrin based photosensitizers are useful agents for photodynamic therapy and fluorescence imaging of cancer. Additionally, porphyrins are excellent metal chelators, forming stable metalo-complexes and (64)Cu isotope can serve as a positron emitter (t1/2=12.7h). The other advantage of (64)Cu is its decay characteristics that facilitates the use of (64)Cu-porphyrin complex as a therapeutic agent. Thus, (64)Cu chelation with porphyrin photosensitizer may become a simple and versatile labeling strategy for clinical positron emission tomography. The present study reports a convenient method for the synthesis of Cu complex with tetrakis(4-carboxyphenyl)porphyrin (TCPP). The experimental conditions for labeling, such as the metal-to-ligand molar ratio, pH and time of reaction were optimized to achieve a high complexation efficiency in a short period of time as possible. In order to accelerate the metallation, the use of substitution reactions of cadmium or lead porphyrin and the presence of reducing agent, such as ascorbic acid, hydroxylamine and flavonoid - morin, were evaluated. The optimum conditions for the synthesis of the copper complex were borate buffer at pH9 with the addition of 10-fold molar excess, with respect to Cu(2+) ions and TCPP and ascorbic acid which resulted in reduction of the reaction time from 30 min to below 1 min.


Subject(s)
Coordination Complexes/chemical synthesis , Copper Radioisotopes/chemistry , Metalloporphyrins/chemical synthesis , Photosensitizing Agents/chemical synthesis , Positron-Emission Tomography , Chelating Agents/chemical synthesis , Chelating Agents/chemistry , Coordination Complexes/chemistry , Metalloporphyrins/chemistry , Oxidation-Reduction , Photosensitizing Agents/chemistry , Porphyrins/chemical synthesis , Porphyrins/chemistry
11.
Rep Pract Oncol Radiother ; 19(Suppl): S13-S21, 2014 May.
Article in English | MEDLINE | ID: mdl-28443194

ABSTRACT

The construction of the 68Ge/68Ga generator has increased application of radiopharmaceuticals labeled with this isotope in medicine. 68Ga-PET is widely employed in the management of neuroendocrine tumors but favorable chemistry with tri- and tetraaza-ring molecules has opened wide range of 68Ga application in other fields of PET imaging. This review covers the radiopharmaceuticals labeled with gallium in molecular imaging and shows perspectives on the use of gallium-68 as a substitute for technetium-99, fluorine-18 and carbon-11 in some applications.

12.
Rep Pract Oncol Radiother ; 19(Suppl): S22-S31, 2014 May.
Article in English | MEDLINE | ID: mdl-28443195

ABSTRACT

AIM: The aim of this study was to synthesize 18FDG in some consecutive runs and check the quality of manufactured radiopharmaceuticals and to determine the distribution of metallic impurities in the synthesis process. BACKGROUND: For radiopharmaceuticals the general requirements are listed in European Pharmacopeia and these parameters have to be checked before application for human use. MATERIALS AND METHODS: Standard methods for the determination of basic characteristics of radiopharmaceuticals were used. Additionally, high resolution γ spectrometry was used for the assessment of nuclidic purity and inductively coupled plasma with mass spectrometry to evaluate metallic content. RESULTS: Results showed sources and distribution of metallic and radiometallic impurities in the production process. Main part is trapped in the initial separation column of the synthesis unit and is not distributed to the final product in significant amounts. CONCLUSIONS: Produced 18FDG filled requirements of Ph.Eur. and the content of radionuclidic and metallic impurities was in the acceptable range.

13.
Water Res ; 41(13): 2839-51, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17499837

ABSTRACT

Determination of cadmium is often required in various environmental, biological and food samples as it is recognized worldwide as a toxic metal. However, these analysis with atomic spectrometry detectors are often difficult due to relatively low content of cadmium and complex matrices. Several preconcentration/separation procedures to determine cadmium have been devised, among them the methods based on sorbent extraction are the most popular. They can be easily implemented and controlled in flow injection (FI) or sequential injection (SI) systems to perform appropriate sample pretreatment. This work reviews the papers, published from 1990, concerning procedures based on sorption principles for on-line determination of cadmium. They were compared using experimental enhancement factor (EF) and concentration efficiency (CE) values.


Subject(s)
Cadmium/chemistry , Environmental Pollutants/chemistry , Spectrophotometry, Atomic , Water/chemistry
14.
Talanta ; 71(1): 406-10, 2007 Jan 15.
Article in English | MEDLINE | ID: mdl-19071319

ABSTRACT

An on-line preconcentration procedure for the determination of manganese using flow-injection approach with flame atomic absorption spectrometry as a detection method is described. The proposed method is based on the complexation between Mn(II) and 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP). Two approaches were investigated for enrichment of manganese; the formation of Mn-TCPP complex in a solution followed by its retention on a sorbent and the sorption of manganese ions onto the TCPP-modified resin. The best results was obtained for the first approach when 10(-5)M reagent was on-line mixed with an aqueous sample solution and passed through the microcolumn packed with anion-exchange resin Amberlite IRA-904 for 5min. The sorbed complexes were then eluted with 0.5ml of 2M HNO(3). A good precision (2.2-3.1% R.S.D. for 50mugl(-1) manganese) and the enrichment factor of 30 were obtained with the detection limit of 12mugl(-1) for 5min loading time. The interference of anions and cations has been studied to optimize the conditions and the method was applied for determination of manganese in natural water samples. The results obtained by FI-FAAS and ETAAS (as a reference method) were not statistically different for a significance level of 0.05.

15.
J Sep Sci ; 29(2): 282-7, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16524104

ABSTRACT

Several metallocomplexes of tetrakis-carboxyphenylporphyrin (TCPP) were separated on fused-silica capillary using CZE with UV-VIS detection. Metalloporphyrins of Co(II), Cu(II), Mn(II), Ni(II), and Zn(II) were formed directly in TCPP solution with addition of Cd(II) to increase the formation reaction rate. The composition of BGE, its concentration, and pH were optimized to ensure the stability of complexes and proper resolution. In particular, the problem of signals' shape was investigated and discussed. The presence of beta-CD in borate buffer significantly improved separation efficiency and signal shapes due to formation of inclusion complexes. Under the best separation conditions (50 mM borate running buffer at pH 9 with addition of 2 mM beta-CD, 30 kV applied voltage) a separation of metal complexes with TCPP was accomplished in 16 min.

16.
Electrophoresis ; 24(12-13): 2259-2263, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12858399

ABSTRACT

We present a method for the speciation of chromium by capillary electrophoresis. Cr(III) was complexed with diethylenetriaminepentaacetic acid (DTPA) to form a negatively charged complex. Using 20 mM phosphate buffer of pH 8 containing 0.5 mM tetradecyltrimethylammonium hydroxide (TTAOH) at a separation voltage of -15 kV, both forms of chromium CrDTPA(2-) and CrO(4) (2-) were separated in less than 6 min. Direct UV detection at 214 nm was used. The effect of the presence of interfering ions was investigated. The application of the developed method to speciation of chromium in tanning liquor is demonstrated. The obtained results have shown a good correlation with those of flame atomic absorbance spectrometry (FAAS), inductively coupled plasma-mass spectrometry (ICP-MS) and UV/VIS spectrophotometry.


Subject(s)
Chromium/chemistry , Electrophoresis, Capillary/methods , Textile Industry , Mass Spectrometry , Spectrophotometry, Atomic
17.
Talanta ; 60(4): 669-78, 2003 Jul 04.
Article in English | MEDLINE | ID: mdl-18969091

ABSTRACT

The reaction of 5,10,15,20-tetrakis(4-carboxylphenyl)porphyrin (TCPP) with Cd(II), Pb(II), Hg(II) and Zn(II) was studied spectrophotometrically and kinetics, equilibrium constants as well as photodecomposition of complexes were determined. It was verified that these metal ions with large radius accelerate the incorporation reaction of zinc into TCPP. On the basis of the mechanism and kinetics of this reaction, a sensitive method for the spectrophotometric determination of trace amounts of Zn(II) has been developed. The molar absorptivity of examined Zn-TCPP complex and Sandell's sensitivity at 423 nm were 3.5x10(5) M(-1) cm(-1) and 18.3 ng cm(-2). The detection limit for the recommended procedure was 1.4x10(-9) M (0.9 ng ml(-1)) and precision in range 20-100 ng ml(-1) not exceeds 2.7% RSD. The proposed method applied for zinc determination in natural waters and nutritional supplement was compared with AAS results and declared value.

18.
Anal Sci ; 18(5): 571-4, 2002 May.
Article in English | MEDLINE | ID: mdl-12036127

ABSTRACT

The suitability of 5,10,15,20-tetrakis(4-carboxyphenyl)porphine as a complexing agent for the on-line preconcentration of cadmium using an anion exchanger (Amberlite IRA-904) in a microcolumn has been tested. Various parameters which affect complex formation and its sorption, as well as elution into the nebulizer of flame atomic absorption spectrometry (FAAS), were optimized. A 5 x 10(-4) mol 1(-1) reagent was on-line mixed with an aqueous sample solution and flowed through the microcolumn for 2 min. The sorbed complexes were then eluted with 2 mol 1(-1) of nitric acid into the nebulizer of FAAS. A good precision (2.1% RSD for 40 microg 1(-1) cadmium) and a high enrichment factor (36) with a detection limit (3sigma) of 1.4 microg 1(-1) were obtained. The achieved analytical results for a standard reference material (SRM 1643d) were in good agreement with the certified values.

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