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

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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

Analgesic effect of inhaled lavender essential oil for frenotomy in healthy neonates:a randomized clinical trial

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World Journal of Pediatrics 2022年第6期18卷 398-403页

作者： Silvia Maya-Enero Montserrat Fàbregas-Mitjans rosa maria Llufriu-Marquès Júlia Candel-Pau Jordi garcia-garcia MaríaÁngeles López-Vílchez Department of Neonatology Service of PediatricsHospital del MarParc de Salut MarUniversitat Pompeu FabraPasseig Marítim 25-2908003BarcelonaSpain

Background Neonatal pain may affect long-term neurodevelopment and must be *** is a painful procedure wherein a common strategy to relieve pain(sucking)cannot be used because the technique is performed on the *** essential oil(LEO)has sedative and antispasmodic properties and has been successfully used to treat pain during heel puncture and *** aim was to demonstrate if the use of inhaled LEO is effective in reducing pain during frenotomy in healthy,full-term *** We conducted a randomized clinical trial in neonates who underwent a frenotomy between August 2020 and April *** assessed pain using pre and post-procedure heart rate and oxygen saturation,crying time and Neonatal Infant Pain Scale(NIPS)*** with type 3 tongue tie were randomized into the“experimental group”and“control group”.In both groups,we performed swaddling,administered oral sucrose,and let the newborn suck for two *** the experimental group,we also placed a gauze pad with one drop of LEO under the neonate’s nose for two minutes prior to and during the *** We enrolled 142 patients(71 per group).The experimental group showed significantly lower NIPS scores(1.88 vs 2.92)and cried almost half the amount of time(14.8 vs.24.6 seconds,P=0.006).Comparing with the control group,we observed no side effects in either of the *** We observed a significant decrease in crying time and lower NIPS scores in the neonates who received inhaled LEO and underwent a frenotomy for type 3 ***,we recommend using inhaled LEO during neonatal frenotomies.

关键词： Ankyloglossia Aromatherapy Frenotomy Lavender Neonate Neonatal pain Tongue-tie

A Review on Genetically Modified Plants Designed to Phytoremediate Polluted Soils： Biochemical Responses and International Regulation

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Pedosphere 2018年第5期28卷 697-712页

作者： Edgar VAZQUEZ-NUNEZ Julian M. PENA-CASTRO Fabian FERNANDEZ-LUQUENO Eduardo CEJUDO maria G. de la rosa-ALVAREZ maria C. garcia-CASTANED Departamento de Ingenierias Quimica Electronica y Biomedica Division de Ciencias e Ingenierlas Universidad de Guanajuato (UG) Campus Leon Loma del Bosque 103 Leon Gto. 37150 (Mexico) Laboratorio de Biotecnologla Vegetal Instituto de Biotecnologia Universidad del Papaloapan Tuxtepec Oaxaca 68333 (Mexico) programa en Sustentabilidad de los Recursos Naturales y Eneryla Cinvestav Saltillo Industria Metalurgica 1062 Parque Industrial Saltillo-Ramos-Arizpe Ramos Arizpe Coahuila 25900 (Mexico) CONACYT Unidad de Ciencias del Agua (UCIA) Centro de Investigacion Cientifica de Yucatan A.C. Cancdn Quintana Roo 77500 (Mexico) Center for the Environmental Implications of Nanotechnology University of California at Los Angeles- University of Texas at El Paso 500 W University Ave El Paso 79968 (USA) CONACYT Universidad de Guanajuato Loma del Bosque 103 Leon Guanajuato 37150 (Mexico)

In recent years,there has been an increasing interest in finding sustainable strategies for the efficient removal of contaminants from *** objective of this review is to examine the biochemical principles of specific genetic modifications in plants,their applications in the field for specific contaminants as phytotechnologies,and their international *** addition,the review presents some biological aspects of rhizosphere-related phenomena,the interactions of organic and inorganic pollutants with plants,and the performance of the phytotechnologies across the *** the last few decades,at least eight genera of genetically modified plants(GMPs)have been tested and used for soil remediation with outstanding ***,Nicotiana,and Oryza are the plant genera most widely *** plant genes such as metal transporters,chelators,metallothioneins,phytochelatins,and oxygenases have been transferred to plants to improve the elimination of contaminants in *** discuss some important aspects of gene manipulation and its application for removal of diverse contaminants.A key challenge faced by phytotechnologies is the final disposal of the generated biomass,from a safety *** argue that the commercial success of phytotechnologies depends on the generation of valuable biomass on contaminated land and its use for bioenergy *** use of such technologies would promote a broader understanding of the importance of plants,especially GMPs,in the environment and their contribution to environmental sustainability.

关键词： bioenergy contaminants gene manipulation phytotechnology plant-microbe interaction regulatory policy soil pollu-tion soil remediation

Novel aspects of tRNA-derived small RNAs with potential impact in infectious diseases

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Advances in Bioscience and Biotechnology 2013年第5期4卷 17-25页

作者： maria rosa garcia-Silva Florencia Cabrera-Cabrera maria Catalina Güida Alfonso Cayota Department of Medicine Hospital de Clínicas Montevideo Uruguay Laboratory of Functional Genomics Institute Pasteur of Montevideo Montevideo Uruguay

The complete understanding of the growing catalog of regulatory non-coding RNAs is going to shed light in different aspects of a wide range of pathogenic mechanisms in human diseases. This review was aimed to highlight recent advances in the small non- coding RNA world that could have implications in the development of new strategies in medical sciences. Among the diverse group of small non-coding RNAs, we highlight the group of tRNA-derived fragments as molecules known for a long time which have recently emerged as novel regulators influencing several aspects of cell biology. We describe here recent advances in the field of tRNA-derived fragments playing key roles in the biology of some infectious agents, including E. coli, A. fumigatus, G. lamblia, Ascaris, T. cruzi, Virus, Prions and a brief overview linking them to cancer biology. Additionally, we focus on the potential implications of these molecules in future biotechnological applications in the development of new biomarkers and as new therapeutic targets.

关键词： Non-Coding RNAs Small tRNAs tRFs tRNA Halves Infectious Diseases

Beneficial effects of saffron(Crocus sativus L.) in ocular pathologies, particularly neurodegenerative retinal diseases

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Neural Regeneration Research 2020年第8期15卷 1408-1416页

作者： Jose A.Fernandez-Albarral rosa de Hoz Ana I.Ramirez Ines Lopez-Cuenca Elena Salobrar-garcia maria D.Pinazo-Duran Jose M.Ramirez Juan J.Salazar Instituto de Investigaciones Oftalmologicas Ramon Castroviejo MadridSpain Departamento de Inmunologia Oftalmologia y ORLFacultad de Optica y OptometriaMadridSpain Departamento de Inmunologia Oftalmologia y ORLFacultad de MedicinaMadridSpain Unidad de Investigacion Oftalmologica Santiago Grisolia Universidad de ValenciaValenciaSpain

Saffron(Crocus sativus L.)has been traditionally used in food preparation and as a medicinal *** currently has numerous therapeutic properties attributed to it,such as protection against ischemia,as well as anticonvulsant,antidepressant,anxiolytic,hypolipidemic,anti-atherogenic,anti-hypertensive,antidiabetic,and anti-cancer *** addition,saffron has remarkable beneficial properties,such as anti-apoptotic,anti-inflammatory and antioxidant activities,due to its main metabolites,among which crocin and crocetin stand ***,increasing evidence underwrites the possible neuroprotective role of the main bioactive saffron constituents in neurodegenerative diseases,such as Parkinson’s and Alzheimer’s diseases,both in experimental models and in clinical studies in ***,saffron supplementation is being tested for ocular neurodegenerative pathologies,such as diabetic retinopathy,retinitis pigmentosa,age-related macular degeneration and glaucoma,among others,and shows beneficial *** present article provides a comprehensive and up to date report of the investigations on the beneficial effects of saffron extracts on the main neurodegenerative ocular pathologies and other ocular *** review showed that saffron extracts could be considered promising therapeutic agents to help in the treatment of ocular neurodegenerative diseases.

关键词： AMD crocetin crocin Crocus sativus L. diabetic retinopathy glaucoma neuroprotection ocular diseases retinitis pigmentosa saffron safranal

Plasmon-induced dual-wavelength operation in a Yb^(3+) laser

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Light(Science & Applications) 2019年第1期8卷 1042-1050页

作者： Laura Sanchez-garcia Mariola O.Ramirez rosa maria Sole Joan J.Carvajal Francesc Diaz Luisa E.Bausa Deparment Fisica de Materiales Instituto Nicolas Cabrera and Condensed Matter Physics Center(IFIMAC)Universidad Autonoma de Madrid28049 MadridSpain Universitat Rovira i Virgili Departament Quimica Fisica i InorganicaFisica i Cristal·lografia de Materials i Nanomaterials(FiCMA-FiCNA)-EMaSE-43007 TarragonaSpain

Expanding the functionalities of plasmon-assisted lasers is essential for emergent applications in nanoscience and ***,we report on a novel ability of plasmonic structures to induce dual-wavelength lasing in the near-infrared region in a Yb^(3+) solid-state *** means of the effects of disordered plasmonic networks deposited on the surface of a Yb^(3+)-doped nonlinear RTP crystal,room-temperature dual-wavelength lasing,with a frequency difference between the lines in the THz range,is *** dual-wavelength laser is produced by the simultaneous activation of two lasing channels,namely,an electronic-and a phonon-terminated laser *** latter is enabled by the out-of-plane field components that are generated by the plasmonic structures,which excite specific Raman ***,multiline radiation at three different wavelengths is demonstrated in the visible spectral region via two self-frequency conversion processes,which occur in the vicinities of the plasmonic *** results demonstrate the potential of plasmonic nanostructures for inducing drastic modifications in the operational mode of a solid-state laser and hold promise for applications in a variety of fields,including multiplexing,precise spectroscopies,and THz radiation generation via a simple and cost-effective procedure.

关键词： laser lasing dual

Clinical use of estimating glomerular filtration rate equ-ations during pregnancy

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Health 2011年第1期3卷 32-36页

作者： Luiz Paulo José Marques Regina Rocco maria Helena Victor Benedita Calheiros de Novaes Ana luiza Batista de Carvalho Omar da rosa Santos 不详

Background: Kidney disease, even when mild, was once considered so major an impediment to successful pregnancy and so dangerous to the mother’s wellbeing. High-risk pregnancy mainly associated to renal impairment may occur in 10-20% of gestations and it is very important that renal function is closely monitored to prevent or minimize maternal and fetal complications. This study was designed to investigate the performance of Cockcroft-Gault CGeq and the simplified MDRDeq equations in healthy pregnant women to assess renal function. Methods: We studied 167 normal ambulatory pregnant women and kidney function was contemporaneously estimated through the CGeq and the simplified MDRDeq and calculated through the creatinine clearance (Ccr). Serum and urinary creatinine were assayed using Jaffé reaction method in the same AutoAnalyser. Results: When we compared calculated and estimated clearences for measurement of kidney function we observed that CGeq overestimated renal function (CGeq = 168.41 ± 38.80 ml/ min/1.73 m2, Ccr = 146.27 ± 30.49 ml/min / 1.73 m2, p < 0.001), MDRDeq underestimated renal function (Ccr = 146.27 ± 30.49 ml/min / 1.73 m2, MDRDeq = 129.15 ± 29.28 ml/min / 1.73m2, p < 0.001). Conclusions: Our results demonstrated that CGeq overestimated, MDRDeq underestimated significantly kidney function during gestation in healthy women and cannot be recommended to assess renal function in obstetric practice. Ccr remains a useful clinical tool in pregnant women until the development of a specific equation that considers the several important maternal renal physiological alterations and provides the measure of GFR the most unbiased and precise as possible.

关键词： Pregnancy Kidney function Glomerular Filtration Rate MDRD equation Cockcroft-Gault equation.

Tubastraea coccinea: A Non-Indigenous Coral (Cnidaria, Scleractinia) Collected at Arvoredo Island, South of Brazil with Potential MRSA and VRE Antimicrobial Activity

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Open Journal of Marine Science 2016年第2期6卷 334-340页

作者： Éverson Miguel Bianco Simone Quintana de Oliveira Tatiana da rosa Guimarães luiza Gabriela de Souza Pessoa maria Eduarda Alves Santos Felipe Dal-Pizzol Eloir Paulo Schenkel Flávio Henrique Reginatto Departamento de Ciências do Mar Universidade Federal de Sao Paulo Campus Baixada Santista Santos Brazil Programa de Pós-Graduacao em Farmácia Universidade Federal de Santa Catarina Florianópolis Brazil Molecular Invertebrate and Systematics Ecology Laboratory Department of Biology Chemistry and Marine Sciences University of the Ryukyus Nishihara Japan Departamento de Clínica Médica Universidade Federal de Santa Catarina Campus Universitário Trindade Florianópolis Brazil

Bacterial infection is considered to be one of the most critical health issues of the world. It is essential to overcome this problem by the development of new drugs. Marine organisms as corals, sponges, seaweeds, and other are an incredible source of novel pharmacologically active compounds. Herein, the antimicrobial activity (extract/fractions) of the invasive stony coralTubastraea coccinea was evaluated by the disk diffusion method against 21 microbial strains (ATCC and clinical strains). Micro broth dilution was used to determinate the MIC of the fractions that showed antimicrobial activity by the disk diffusion method. Bioautography assay was also performed. Our results showed that the n-butanol (BF) and aqueous fractions (AF) showed activity against ATCC strains Staphylococcus aureus (MIC 31.25 and 250 μg/mL),Salmonella typhimurium (MIC 125 and 500 μg/mL), Escherichia coli (MIC 62.5 and 500 μg/mL) and Pseudomonas aeruginosa (MIC 62.5 and 500 μg/mL), respectively. Moreover, BF fraction was also effective against the clinical strains S. aureus(MIC 62.5 μg/mL), Klebsiella pneumoniae Carbapenemase—KPC (MIC 125 μg/mL), Methicillin-Resistant Staphylococcus aureus—MRSA (MIC 125 μg/mL) and Vancomycin-Resistant Enterococcus faecalis—VRE (MIC 62.5 μg/mL). The ratio MBC/MIC reinforces the bactericidal profile of BF fraction. The bioautography assay of BF fraction showed the presence of antimicrobial components at Rf0.55.

关键词： Marine Natural Products Tubastraea coccinea Scleractinia Antimicrobial Activity Methicillin- Resistant Staphylococcus aureus (MRSA) Vancomycin-Resistant Enterococcus faecalis (VRE)

An opportunity for improvement with a medication reconciliation programme

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Open Journal of Internal Medicine 2013年第4期3卷 129-134页

作者： Ana Belén Jiménez-Munoz Ana Clara Zoni Esther Duran-garcia Paz Rodriguez Pérez maria Sanjurjo Saez rosa Pla-Mestre Preventive Medicine Hospital Universitario Severo OchoaMadridSpain Preventive Medicine and Quality Management Department Hospital General Universitario Gregorio MaranonC/Doctor EsquerdoMadridSpain

Medication reconciliation is priority in safety. Between 54% and 67% of hospitalized patients have at least one unintended discrepancies (UDs) between pharmacological treatment of a hospital inpatient and treatment that they were previously taking at home. Quasi-experimental pre-post study performed. The objective is to assess the impact of an intervention aimed at decreasing UDs between medication prescribed on admission and patient’s regular treatment. Patients who were hospitalised for more than 24 hours and were undergoing treatment prior to admission which involved taking three or more medicines were included. The number of patients included was 331 and 3781 medicines were reconciled. The incidence of UDs decreased significantly from 7.24% to 4.18%. Omission was the most common UD, with a significant decrease from 5.8% to 3.4%. Respect to clinical impact, we observed that error type C (error reached patient without causing harm) predominates, how- ever, experienced a statistically significant decrease from 5.3% to 2.4%.

关键词： Medication Reconciliation Admission Unintended Discrepancies