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Development of a Ready-to-Use PSMA-11 Kit Formulation and Biological Evaluation of Binding Affinity

Advances in Molecular Imaging 2024年第2期13卷 7-22页

作者： Maria Renata Valente Brandão Freire Natália Marchesan Bexiga Marco Antonio Stephano João Ezequiel Oliveira Carlos Roberto Jorge Soares ana Cláudia Camargo Miranda Anna Carolina de Alcântara Barbosa Marycel Figols de Barboza Laura Fernanda Garcia Luiz Felipe S. Teixeira Maria Helena Marumo Bellini Natanael Gomes da silva Luiza Mascarenhas Balieiro Joel Mendes Elaine Bortoleti de Araújo Centro de Radiofarmcia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Tecnologia Farmacutica Faculdade de Cincias Farmacuticas (USP) Cidade Universitria So Paulo Brasil Centro de Biotecnologia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Medicina Nuclear do Hospital Israelita Albert Einstein So Paulo/SP Brasil

Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.

关键词： 68Ga-PSMA-11 Prostate-Specific Membrane Antigen (PSMA) Ready-to-Use Kit GMP-Grade Generators Metastatic Prostate Cancer PET Imaging

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Bartter's syndrome:clinical findings,genetic causes and therapeutic approach

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World Journal of Pediatrics 2021年第1期17卷 31-39页

作者： Flavia Cristina Carvalho Mrad Sílvia Bouissou Morais Soares Luiz Alberto Wanderley de Menezes silva Pedro Versiani dos Anjos Menezes ana Cristina Simoes-e-silva Interdisciplinary Laboratory of Medical Investigation Faculty of MedicineFederal University of Minas Gerais(UFMG)Av.Alfredo Balena190Room#281Belo HorizonteMG 30130-100Brazil Pediatric Nephrology Unit Faculty of MedicineUFMGBelo HorizonteBrazil

Backgound Bartter's syndrome(BS)is a rare group of salt losing tubulopathies due to the impairment of transport mecha-nisms at the thick ascending limb of the Henle's *** sources Literature reviews and original research articles were collected from database,including PubMed and *** According to the time of onset and symptoms,BS can be classified into antenatal and classic *** studies have identified different subtypes of *** types Ⅰ,Ⅱ and Ⅲ are caused by mutations on genes encoding the luminal Na^(+)-K^(+)-2Cl^(-) co-transporter,the luminal K+ channel ROMK,and the basolateral chloride channel ClC-Kb(CLCNKB),***-of-function mutations of Barttin CLCNK type accessory beta subunit cause BS type Ⅳ*** mutations of CLCNKB and CLCNKA cause BS type Ⅳ*** type Ⅴ consists in a novel transient form characterized by antenatal presentation due to mutations in the MAGE family member *** gain-of-function mutations of the extracellular calcium sensing receptor gene can result in an autosomal dominant condition of *** clinical and biochemical alterations in BS include polyuria,dehydration,hypokalemia,hypochloremic metabolic alka-losis,hyperreninemia,high levels of prostaglandins,normal or low blood pressure,hypercalciuria and failure to *** focuses mainly at correcting dehydration and electrolyte disturbances and in measures to reduce polyuria,including the use of nonsteroidal anti-inflammatory medications to control excessive renal prostaglandin E2 *** Early diagnosis and treatment of BS may prevent long-term consequences such as growth failure,nephrocal-cinosis and end-stage renal disease.

关键词： Bartter's syndrome Hypercalciuria Hypokalemia Metabolic alkalosis Nephrocalcinosis

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PtRu nanoparticles supported on noble carbons for ethanol electrooxidation

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Journal of Energy Chemistry 2022年第3期31卷 168-180,I0006页

作者： Alberto Rodríguez-Gómez Enrico Lepre Luz Sánchez-silva Nieves López-Salas ana Raquel de la Osa Faculty of Chemical Sciences and Technologies University of Castilla-La ManchaEnrique Costa Novella Building.Avda.Camilo Jose Cela1213071 Ciudad RealSpain Colloid Chemistry Department Max Planck Institute of Colloids and InterfacesAm Mühlenberg 114476 PotsdamGermany

In this work,three cytosine derived nitrogen doped carbonaceous materials(noble carbons,NCs)with different atomic C/N ratios and porous networks have been synthesized and used as supports for Pt Ru electrocatalysts in the ethanol oxidation reaction(EOR)for clean hydrogen ***,the metal phase and the carbon support play critical roles in the electrocatalysts final *** NPs size distribution was obtained over supports with low atomic C/N ratios(i.e.,4 and 6)and defined porosity(i.e.,1701 m^(2)g^(-1)for Pt Ru/CNZ and 1834 m^(2)g^(-1)for Pt Ru/CLZ,respectively).In contrast,a lower C/N ratio and poor porous network(i.e.,65 m^(2)g^(-1),Pt Ru/CLK)led to the largest particle size and fostered an increase of the alloying degree between Pt and Ru NPs(i.e.,3%for C/N~6 and 28%for C/N~3).Electrochemical active surface area was found to increase with decreasing NPs size and the alloy extent,due to a higher availability of Pt active *** degradation tests showed that Pt Ru/NCs outperform similar to Pt Ru NPs on commercial carbon pointing at the stabilizing effect of *** Ru/CNZ exhibited the best electrochemical performance(i.e.,69.1 m A mgPt-1),outperforming Pt Ru/CLZ and Pt Ru/CLK by3-and 9-fold,respectively,due to a suitable compromise between particle sizes,degree of alloy,textural properties and elemental *** anodes were scaled-up to a proton exchange membrane cell and Pt Ru/CNZ was proved to provide the best electrocatalytic activity(262 m A cm^(-2)and low energy requirements),matching the values obtained by the state of the art of EOR electrocatalysts.

关键词： Noble carbon Cytosine H2 production Ethanol electrooxidation PtRu anode PEM cell

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Evaluation of Biodegradation in Aqueous Medium of Poly(Hydroxybutyrate-Co-Hydroxyvalerate)/Carbon Nanotubes Films in Respirometric System

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Journal of Renewable Materials 2019年第2期7卷 117-128页

作者： Larissa Stieven Montagna Isabela CÉSAR Oyama Rita de CÁSSIA Barbosa Camargo Lamparelli ana Paula silva THAIS Larissa do Amaral Montanheiro ana Paula Lemes Federal University of São Paulo(UNIFESP) Institute of Science and TechnologyTechnology Laboratory of Polymers and Biopolymers(TecPBio)Talim330São Josédos CamposSP12231-280BrazilSão Josédos CamposSPBrazil

Biodegradable polymers have been increasingly used for scientific and commercial applications because they are similar to some conventional thermoplastics and exhibit the ability of ***(3-hydroxybutyrate-co-3-hydroxyvalerate)(PHBV)nanocomposites films with 1 and 2 wt% of carbon nanotubes(CNT)were prepared by solution mixing,followed by solvent *** this work,PHBV/CNT nanocomposites were submitted to biodegradation in an aqueous medium for 34 days through a respirometric ***,the PHBV films were analyzed by the CO2 production and mineralization as a response of a microbial attack,which was monitored by back titration during all the *** films were also characterized by measuring the weight loss;crystallinity was evaluated by differential scanning calorimetry(DSC)and the surface morphology by scanning electron microscopy(SEM).By analyzing the weight loss of the films,it was observed that adding CNT increases the resistance to biodegradation *** obtained values of CO2 production and mineralization of the samples,as well as the values of weight loss,showed that the biodegradation of PHBV/CNT nanocomposites was minor in comparison to neat *** addition of CNT in PHBV matrix influences the surface morphology,causing the presence of cavities and an increase of roughness.

关键词： Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) carbon nanotube nanocomposites biodegradation in aqueous medium

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Ecophysiological acclimatization to cyclic water stress in Eucalyptus

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Journal of Forestry Research 2020年第3期31卷 797-806页

作者： Rogerio de Souza Noia Junior Genilda Canuto Amaral Jose Eduardo Macedo Pezzopane Mariana Duarte silva Fonseca ana Paula Camara da silva Talita Miranda Teixeira Xavier Department of Biosystems Engineering ESALQ University of Sao PauloPiracicabaSao PauloBrazil Department of Forestry Sciences NEDTEC Federal University of Espirito SantoJero nimo MonteiroEspirito SantoBrazil

Drought is considered the main environmental factor limiting productivity in eucalyptus plantations in Brazil. However, recent studies have reported that exposure to water deficit conditions enables plants to respond to subsequent stresses. Thus, this study investigates the ecophysiological acclimatization of eucalyptus clones submitted to recurrent water deficit cycles. Eucalyptus seedlings were submitted to three recurrent water deficit cycles and anatomical, morphological and physiological changes were analyzed. The results were:(1) Eucalyptus seedlings responded to water deficits by directing carbohydrates to root and stem growth;(2) Size and number of stomata were reduced;(3) Stomatal conductance decreased which allowed the plants to reduce water losses through transpiration,increasing instantaneous water use efficiency;(4) The relationship between gas exchanges and available water contents allowed the seedlings to uptake the retained soil water athigher tensions;and,(5) Physiological recovery from subsequent water deficits became faster. As a result of these changes, the eucalyptus seedlings recovered from the same degree of water stress more rapidly.

关键词： Carbon partition Drought Gas exchange Morpho-physiological changes Photosynthetic apparatus

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Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer

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Genes & Diseases 2019年第2期6卷 176-184页

作者： Fernanda S.Manoel-Caetano ana Flávia T.Rossi Gabriela Calvet de Morais Fábio Eduardo Severino ana Elizabete silva Department of Biology UNESPSāo Paulo State UniversityCampus of Sāo Josédo Rio PretoRua Cristòvāo Colombo226515.054-000Sāo Josédo Rio PretoSāo PauloBrazil Department of Surgery and Orthopedics Faculty of MedicineUNESPSāo Paulo State UniversityCampus of BotucatuAv.Prof.Mário Rubens Guimarāes Montenegros/n18.618-687BotucatuSāo PauloBrazil

Gastric cancer remains one of the leading causes of cancer-related death worldwide,and most of the cases are associated with Helicobacter pylori *** bacterium promotes the production of reactive oxygen species(ROS),which cause DNA damage in gastric epithelial *** this study,we evaluated the expression of important genes involved in the recognition of DNA damage(ATM,ATR,and H2AX)and ROS-induced damage repair(APE1)and the expression of some miRNAs(miR-15a,miR-21,miR-24,miR-421 and miR-605)that target genes involved in the DNA damage response(DDR)in 31 fresh tissues of gastric *** v3.1.1 was used to construct the postulated miRNA:mRNA interaction *** performed by real-time quantitative PCR exhibited significantly increased levels of the APE1(RQ=2.55,panalysis reinforced some of the gene:gene(ATM/ATR/H2AX)and miRNA:mRNA relationships obtained also with the interaction ***,our findings show that tumor cells from gastric cancer presents deregulation of genes and miRNAs that participate in the recognition and repair of DNA damage,which could confer an advantage to cell survival and proliferation in the tumor microenvironment.

关键词： DNA damage response DNA repair Gastric cancer Gene expression microRNA

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Renin angiotensin system in liver diseases: Friend or foe?

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World Journal of Gastroenterology 2017年第19期23卷 3396-3406页

作者： ana Cristina Simoes e silva Aline S Miranda Natália P Rocha Antonio L Teixeira Department of Pediatrics Faculty of MedicineFederal University of Minas Gerais Interdisciplinary Laboratory of Medical Investigation Faculty of MedicineUFMG Laboratory of Neurobiology Department of MorphologyInstitute of Biological SciencesUFMG Neuropsychiatry Program Department of Psychiatry and Behavioral SciencesMcGovern Medical SchoolUniversity of Texas Health Science Center at Houston

In the last three decades,the understanding of the renin angiotensin system(RAS)has been changed by the discoveries of functional local systems,novel biologically active peptides,additional specific receptors,alternative pathways of angiotensin(Ang)?Ⅱ?generation,and new roles for enzymes and precursor components other than those in Ang?Ⅱ?*** this regard,the discovery that Ang-(1-7)opposes the pressor,proliferative,pro-fibrotic,and pro-inflammatory effects mediated by Ang?Ⅱ?has contributed to the realization that the RAS is composed of two *** first axis consists of the angiotensin-converting enzyme(ACE),with Ang?Ⅱ?as the end product,and the angiotensin type 1(AT1)receptor as the main effector mediating the biological actions of Ang?Ⅱ.The second axis results from ACE2-mediated hydrolysis of Ang?Ⅱ,leading to the production of Ang-(1-7),with the Mas receptor as the main effector conveying the vasodilatory,antiproliferative,anti-fibrotic,and anti-inflammatory effects of Ang-(1-7).Experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver *** this manuscript,we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications,including hemodynamic changes and hepatorenal *** therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed.

关键词： Renin angiotensin system Angiotensin Ⅱ Angiotensin-(1-7) Hepatic cirrhosis Liver fibrosis Hepatorenal syndrome

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Palliative oral care in terminal cancer patients:Integrated review

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World Journal of Clinical Cases 2023年第13期11卷 2966-2980页

作者： ana Rute Preis silva Augusto Vanni Bodanezi Emanuely silva Chrun Mariah Luz Lisboa Alessandra R de Camargo Etiene Andrade Munhoz Department of Dentistry Federal University of Santa CatarinaFlorianopolis 88040-379Brazil Department of Pathology Federal University of Santa CatarinaFlorianopolis 88040900Brazil Professor Polydoro São Thiago Ernani Hospital Federal University of Santa CatarinaFlorianopolis 88040900Brazil Department of Dentistry Health Science CentreFederal University of Santa CatarinaFlorianopolis 88040-379Brazil

BACKGROUND Palliative care(PC)aims to improve quality of life in patients and its families against life threatening diseases,through suffering’s prevention and *** is the duty of the dental surgeon to possess the knowledge needed to treat a patient with little life span,in order to establish an adequate treatment plan for each *** To synthesize the published evidence on oral conditions,impact,management and challenges in managing oral conditions among palliative *** Articles were selected from PubMed and Scopus electronic platforms,using a research strategy with diverse descriptors related to“palliative care”,“cancer”and“oral health”.The article’s selection was done in two *** first one was performed by the main researcher through the reading of the *** the second phase two researchers selected eligible articles after reading in full those previous *** was tabulated and analyzed,obtaining information about what is found in literature related to this subject and what is necessary to be approached in future researches about *** As results,the total of 15 articles were eligible,being one a qualitative analysis,13(92.8%)clinical trials and one observational *** the 15 articles,8(53.4%)involved questionnaires,while the rest involved:one systematic review about oral care in a hospital environment,2 oral exams and oral sample collection,one investigation of terminal patient’s(TP)oral assessment records,2 collection of oral samples and their respective analysis and one treatment of the observed oral *** It can be concluded that the oral manifestations in oncologic patients in terminal stage are,oral candidiasis,dry mouth,dysphagia,dysgeusia,oral mucositis and orofacial *** a protocol for the care of these and other complications of cancer–or cancer therapy–based on scientific evidence with the latest cutting-edge research results is of fundamental importance for the multidis

关键词： Palliative care Oral lesion Terminal patients,Oral mucositis,Oral candidiasis

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Compatibility and stability studies involving polymers used in fused deposition modeling 3D printing of medicines

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Journal of Pharmaceutical analysis 2022年第3期12卷 424-435页

作者： Ihatanderson A.silva ana Luiza Lima Tais Gratieri Guilherme M.Gelfuso Livia L.Sa-Barreto Marcilio Cunha-Filho Laboratory of Food Drugand Cosmetics(LTMAC)School of Health SciencesUniversity of Brasilia70910-900BrasíliaDFBrazil Faculty of Ceilandia University of Brasilia(UnB)72220-900BrasíliaDFBrazil

One of the challenges in developing three-dimensional printed medicines is related to their stability due to the manufacturing conditions involving high *** work proposed a new protocol for preformulation studies simulating thermal processing and aging of the printed medicines,tested regarding their morphology and thermal,crystallographic,and spectroscopic ***,despite the strong drug-polymer interactions observed,the chemical stability of the model drugs was preserved under such *** fact,in the metoprolol and Soluplus®composition,the drug's solubilization in the polymer produced a delay in the drug decomposition,suggesting a protective effect of the *** and polyvinyl alcohol mixture,in turn,showed unmistakable signs of thermal instability and chemical decomposition,in addition to physical *** the presented context,establishing protocols that simulate processing and storage conditions may be decisive for obtaining stable pharmaceutical dosage forms using three-dimensional printing technology.

关键词： Three-dimensional printing Preformulation Hot-melt extrusion Thermal analysis Drug-polymer compatibility

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Targeting of Pollen Tubes to Ovules Is Dependent on Nitric Oxide （NO） Signaling

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Molecular Plant 2008年第4期1卷 703-714页

作者： ana Margarida Prado Renato Colaco Nuno Moreno ana Catarina silva Jose A. Feijo Instituto Gulbenkian de Ciencla Centro de Blologia do Desenvolvimento PT-2780-156 Oeiras Portugal Universidade de Lisboa Faculdade de Clencias Dept Biologia Vegetal Campo Grande Ed.C2. PT-1749-016 Lisboa Portugal

The guidance signals that drive pollen tube navigation inside the pistil and micropyle targeting are still, to a great extent, unknown. Previous studies in vitro showed that nitric oxide （NO） works as a negative chemotropic cue for pollen tube growth in lily （Lilium Iongiflorum）. Furthermore, Arabidopsis thaliana Atnosl mutant plants, which show de- fective NO production, have reduced fertility. Here, we focus in the role of NO in the process of pollen-pistil communication, using Arabidopsis in-vivo and lily semi-vivo assays. Cross-pollination between wild-type and Atnosl plants shows that the mutation affects the pistil tissues in a way that is compatible with abnormal pollen tube guidance. Moreover, DAF- 2DA staining for NO in kanadi floral mutants showed the presence of NO in an asymmetric restricted area around the micropyle. The pollen-pistil interaction transcriptome indicates a time-course-specific modulation of transcripts of AtNOS1 and two Nitrate Reductases （nrl and nr2）, which collectively are thought to trigger a putative NO signaling pathway. Semivivo assays with isolated ovules and lily pollen further showed that NO is necessary for micropyle targeting to occur. This evidence is supported by CPTIO treatment with subsequent formation of balloon tips in pollen tubes facing ovules. Activation of calcium influx in pollen tubes partially rescued normal pollen tube morphology, suggesting that this pathway is also dependent on Ca^2＋ signaling. A role of NO in modulating Ca^2＋ signaling was further substantiated by direct imaging the cytosolic free Ca^2＋ concentration during NO-induced re-orientation, where two peaks of Ca^2＋ occur--one during the slowdown/stop response, the second during re-orientation and growth resumption. Taken together, these results provide evidence for the participation of NO signaling events during pollen-pistil interaction. Of special relevance, NO seems to directly affect the targeting of pollen tubes to the ovule＇s micropyle by modu

关键词： pollen tubes NO fertilization guidance calcium signaling

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