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Brassinosteroids (BRs) are vital plant steroid hormones sensed at the cell surface by a membrane signaling complex comprising the receptor kinase BRI1 and a SERK-family co-receptor kinase. Activation of this complex lead to dissociation of the inhibitor protein BKI1 from the receptor and to differential phosphorylation of BZR1/BES1 transcription factors by the glycogen synthase kinase 3 protein BIN2. Many phosphoproteins of the BR signaling pathway, including BRI1, SERKs, BKI1 and BZR1/BES1 can associate with 14-3-3 proteins. In this study, we use quantitative ligand binding assays to define the minimal 14-3-3 binding sites in the N-terminal lobe of the BRI1 kinase domain, in BKI1, and in BZR1 from Arabidopsis thaliana. All three motifs require to be phosphorylated to specifically bind 14-3-3s with mid- to low micromolar affinity. BR signaling components display minimal isoform preference within the 14-3-3 non-ε subgroup. 14-3-3λ and 14-3-3ω isoform complex crystal structures reveal that BKI1 and BZR1 bind as canonical type II 14-3-3 linear motifs. Disruption of key amino acids in the phosphopeptide binding site through mutation impairs the interaction of 14-3-3λ with all three linear motifs. Notably, quadruple loss-of-function mutants from the non-ε group exhibit gain-of-function brassinosteroid signaling phenotypes, suggesting a role for 14-3-3 proteins as overall negative regulators of the BR pathway. Collectively, our work provides further mechanistic and genetic evidence for the regulatory role of 14-3-3 proteins at various stages of the brassinosteroid signaling cascade.
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Elevated aldehyde dehydrogenase (ALDH) activity correlates with poor outcome for many solid tumors as ALDHs may regulate cell proliferation and chemoresistance of cancer stem cells (CSCs). Accordingly, potent, and selective inhibitors of key ALDH enzymes may represent a novel CSC-directed treatment paradigm for ALDH+ cancer types. Of the many ALDH isoforms, we and others have implicated the elevated expression of ALDH1A3 in mesenchymal glioma stem cells (MES GSCs) as a target for the development of novel therapeutics. To this end, our structure of human ALDH1A3 combined with in silico modeling identifies a selective, active-site inhibitor of ALDH1A3. The lead compound, MCI-INI-3, is a selective competitive inhibitor of human ALDH1A3 and shows poor inhibitory effect on the structurally related isoform ALDH1A1. Mass spectrometry-based cellular thermal shift analysis reveals that ALDH1A3 is the primary binding protein for MCI-INI-3 in MES GSC lysates. The inhibitory effect of MCI-INI-3 on retinoic acid biosynthesis is comparable with that of ALDH1A3 knockout, suggesting that effective inhibition of ALDH1A3 is achieved with MCI-INI-3. Further development is warranted to characterize the role of ALDH1A3 and retinoic acid biosynthesis in glioma stem cell growth and differentiation.
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Aldeído Oxirredutases/antagonistas & inibidores , Glioma/metabolismo , Células-Tronco Neoplásicas/metabolismo , Tretinoína/metabolismo , HumanosRESUMO
In a patient requiring pacing and defibrillation therapy, but without superior venous access, combined therapy with S-ICD and leadless pacemaker could be the best solution. An appropriate programming of both devices represents the technical challenge in order to avoid inappropriate shocks due to leadless pacing oversensing.
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OBJECTIVES AND BACKGROUND: There is conflicting evidence about the effects of drug-coated balloons (DCB) compared with drug-eluting stents (DES) in patients with native small vessel coronary artery disease (CAD). METHODS: The PubMed, Embase, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov databases and main international conference proceedings were searched for randomized controlled trials (RCT) comparing DCB versus DES in patients with native small vessel CAD. Data were pooled by meta-analysis using a random-effects model. The primary endpoint was target vessel revascularization (TVR). Secondary clinical endpoints were: myocardial infarction (MI), target lesion revascularization (TLR), all-cause death, cardiac death, and stent thrombosis or target vessel thrombosis. Secondary angiographic outcomes were: in-segment restenosis, in-segment percentage-diameter stenosis, in-segment late lumen loss, in-segment net luminal gain, and in-segment minimal lumen diameter. RESULTS: Five trials enrolling 1,459 patients were included. Mean clinical follow-up was 10.2 months. The use of DCB, compared with DES, was associated with similar risk of TVR (odds ratio [OR]: 0.97; 95% confidence interval [CI] 0.56 to 1.68; p = .92), TLR (OR: 1.74; 95% CI: 0.57 to 5.28; p = .33), all-cause death (OR: 1.03; 95% CI: 0.14 to 7.48; p = .98), with a trend toward a lower risk of MI (OR: 0.49; 95% CI: 0.23 to 1.03; p = .06), and with significant lower risk of vessel thrombosis (OR: 0.12; 95% CI: 0.01 to 0.94; p = .04). DCB use was associated with similar risk of angiographic restenosis (OR: 1.12; 95% CI 0.69 to 1.84; p = .64), comparable late luminal loss (standardized mean difference (SMD): -0.18; 95% CI: -0.39 to 0.03; p = .09), while leading to significant higher percentage diameter stenosis (SMD: 0.27; 95% CI 0.12 to 0.41; p < .01) and smaller minimal luminal diameter (SMD: -0.52; 95% CI: -0.86 to -0.18; p = .003). CONCLUSION: Compared with DES, the use of DCB for the treatment of native small vessel CAD is associated with similar TVR and restenosis and reduces the risk of vessel thrombosis, although DES implantation yields slightly better angiographic surrogate endpoints.
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Angioplastia Coronária com Balão , Doença da Artéria Coronariana , Reestenose Coronária , Stents Farmacológicos , Intervenção Coronária Percutânea , Preparações Farmacêuticas , Materiais Revestidos Biocompatíveis , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/terapia , Reestenose Coronária/diagnóstico por imagem , Reestenose Coronária/etiologia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Desenho de Prótese , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do TratamentoRESUMO
Although rare, stent thrombosis remains a severe complication after stent implantation owing to its high morbidity and mortality, and represents a challenging scenario for interventional cardiology. Sub-struts stenting could constitute a rare last-resort-bailout technique for recanalization. We present herein a case of acute coronary syndrome secondary to in-stent restenosis and very late thrombosis, successfully treated with a partial sub-struts stenting.
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Stents , Trombose , Reestenose Coronária , Tratamento de Emergência , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Levels of circulating endothelial progenitor cells (EPCs) are associated with the short-term prognosis of patients with coronary artery disease (CAD). No previous study, however, has ascertained if EPCs are related also to long-term outcome. We performed a pre-specified analysis of the PROCREATION (PROgenitor Cells role in Restenosis and progression of coronary ATherosclerosis after percutaneous coronary intervention) study in order to assess if EPCs predict the 10-year prognosis. METHODS AND RESULTS: Consecutive stable patients with CAD who were included in the PROCREATION study were evaluated. Patients underwent an extended 10-year follow-up to assess major adverse cardiac or cerebrovascular events (MACCE), i.e. death, stroke, myocardial infarction, and revascularization. During follow-up, MACCE occurred in 79 of 149 patients (53%). Most clinical and angiographic baseline variables were similar in patients with or without MACCE, apart from age, diabetes, chronic kidney disease, ejection fraction, and extent of CAD. Comparison of EPCs, conversely, showed that patients with MACCE had greater levels of CD34+/KDR+/CD45- cells (p=0.0002) and CD133+/KDR+/CD45- cells (p=0.0001). Multivariate analysis showed that factors independently associated with 10-year MACCEs were age (p=0.001), ejection fraction (p=0.018), and CD34+/KDR+/CD45- cells (p=0.024). CONCLUSION: Subpopulations of EPCs can improve long-term risk factor characterization in patients with CAD. (ClinicalTrials.gov: NCT01575431).
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Doença da Artéria Coronariana , Células Progenitoras Endoteliais , Infarto do Miocárdio , Intervenção Coronária Percutânea , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Seguimentos , HumanosRESUMO
Acute chest pain caused by aortic dissection (AD) or acute myocardial infarction (AMI) is one of the most serious medical emergencies and requires a very quick differential diagnosis to choose the best timing for treatment. AD and AMI are often manifested with similar symptoms, making it difficult to differentially diagnose these two conditions. After supracoronary aortic repair for type A AD, small intimal flap could remain in the anastomosis area. Aortic intramural hematoma could extend to the coronary ostia causing an extrinsic compression. Intravascular ultrasound is a safe and effective methodology to distinguish an atherosclerotic plaque from an extrinsic compression. We present the case of a 68-year-old man, with a recent surgical correction of a type A AD, referred to our emergency department for an acute coronary syndrome.
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Síndrome Coronariana Aguda/diagnóstico por imagem , Dissecção Aórtica/diagnóstico por imagem , Implante de Prótese de Valva Cardíaca , Ultrassonografia de Intervenção , Idoso , Dissecção Aórtica/cirurgia , Valvopatia Aórtica/cirurgia , Dor no Peito/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Infarto do Miocárdio/diagnóstico por imagemRESUMO
The synthesis of cyclohepta[b]indole derivatives through the dearomative (4 + 3) cycloaddition reaction of 2-vinylindoles or 4H-furo[3,2-b]indoles with in situ generated oxyallyl cations is reported. Oxyallyl cations are generated from α-bromoketones in the presence of a base and a perfluorinated solvent. Cyclohepta[b]indole scaffolds are obtained under mild reaction conditions, in the absence of expensive catalysts, starting from simple reagents, in good to excellent yields and with complete diasteroselectivity. Preliminary expansion of the scope to 3-vinylindoles and to aza-oxyallyl cations is reported.
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BACKGROUND: The present study aimed to better define the usefulness of F-FDG PET/CT in predicting pathological tumor response (PTR) and survival in patients with noncardia gastric cancer treated with preoperative chemotherapy. METHODS: Seventy-one patients were recruited in 6 Italian centers. The SUV of F-FDG PET/CT was measured at baseline and after treatment, and the difference (dSUV) was computed. The association between PET indexes and PTR, assessed by the Becker score, was evaluated by nonparametric regression. The discriminant power of PET indexes with respect to the absence of PTR (Becker 2/3) was studied by receiver operating characteristic (ROC) curve and synthesized by the area under the curve (ROC-AUC). RESULTS: dSUV allowed to partially discriminate between absence/presence of PTR, when expressed as either absolute value (ROC-AUC, 0.73; 95% confidence interval, 0.59-0.87) or percentage (ROC-AUC, 0.74; 95% confidence interval, 0.59-0.89). However, only extreme values of percent dSUV were really informative. All 7 patients whose F-FDG uptake had increased despite preoperative treatment showed no tumor regression at pathologic examination. Seven of the 10 patients whose metabolic response had been 70% or greater had complete or nearly complete pathologic tumor regression (Becker score 1a or 1b). The metabolic response of the remaining 54 patients, which ranged between 0% and 70%, did not permit to reliably forecast pathologic tumor regression. Survival significantly decreased with increasing Becker score but was unaffected by metabolic response. CONCLUSIONS: The present study suggests that F-FDG PET/CT has limited usefulness in predicting cancer regression. The lack of metabolic response in serial measurements indicates the probable ineffectiveness of preoperative treatment.
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Recidiva Local de Neoplasia/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Complicações Pós-Operatórias/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico por imagem , Idoso , Fluordesoxiglucose F18 , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Masculino , Glicoproteínas de Membrana , Compostos Organometálicos , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgiaRESUMO
Plants use leucine-rich repeat receptor kinases (LRR-RKs) to sense sequence diverse peptide hormones at the cell surface. A 3.0-Å crystal structure of the LRR-RK GSO1/SGN3 regulating Casparian strip formation in the endodermis reveals a large spiral-shaped ectodomain. The domain provides a binding platform for 21 amino acid CIF peptide ligands, which are tyrosine sulfated by the tyrosylprotein sulfotransferase TPST/SGN2. GSO1/SGN3 harbors a binding pocket for sulfotyrosine and makes extended backbone interactions with CIF2. Quantitative biochemical comparisons reveal that GSO1/SGN3-CIF2 represents one of the strongest receptor-ligand pairs known in plants. Multiple missense mutations are required to block CIF2 binding in vitro and GSO1/SGN3 function in vivo. Using structure-guided sequence analysis we uncover previously uncharacterized CIF peptides conserved among higher plants. Quantitative binding assays with known and novel CIFs suggest that the homologous LRR-RKs GSO1/SGN3 and GSO2 have evolved unique peptide binding properties to control different developmental processes. A quantitative biochemical interaction screen, a CIF peptide antagonist and genetic analyses together implicate SERK proteins as essential coreceptor kinases required for GSO1/SGN3 and GSO2 receptor activation. Our work provides a mechanistic framework for the recognition of sequence-divergent peptide hormones in plants.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Peptídeos/metabolismo , Proteínas Quinases/metabolismo , Sequência de Aminoácidos , Arabidopsis/química , Arabidopsis/enzimologia , Arabidopsis/genética , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Cinética , Ligantes , Peptídeos/química , Reguladores de Crescimento de Plantas/química , Reguladores de Crescimento de Plantas/metabolismo , Ligação Proteica , Proteínas Quinases/química , Proteínas Quinases/genéticaRESUMO
Calcified coronary plaque represents a challenging scenario for interventional cardiology. It is often associated with stent under-expansion during percutaneous coronary intervention. We report two cases of unexpected coronary stent under-expansion due to heavily calcified plaque, successfully treated with shockwave coronary lithoplasty.
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Doença da Artéria Coronariana , Litotripsia , Stents , Angiografia Coronária , Doença da Artéria Coronariana/terapia , Vasos Coronários , Humanos , Resultado do TratamentoRESUMO
Thrombus burden remains an important mortality risk factor during primary percutaneous coronary interventions (PCI), especially when associated with distal embolization of atheromatous debris (Sharma et al., 2016; Ibanez et al., 2018 [1,2]). Although routine thrombus aspiration during primary PCI in acute coronary syndrome (ACS) is not recommended (Sharma et al., 2016 [1]), some procedures become very challenging when thrombus removal and vessel reperfusion is not achieved with conventional dedicated devices. We describe a case of a 60-year old man with a late-comer infero-lateral ST-segment elevation myocardial infarction (STEMI) undergoing right coronary artery primary PCI. A high thrombotic burden was shown requiring an ultra-deep guide catheter intubation to perform a successful thromboaspiration and stenting.
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Angioplastia Coronária com Balão/instrumentação , Cateterismo Cardíaco/instrumentação , Cateteres Cardíacos , Trombose Coronária/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Trombectomia/instrumentação , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/fisiopatologia , Stents Farmacológicos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/fisiopatologia , Sucção/instrumentação , Resultado do TratamentoRESUMO
We performed a pilot randomised study to assess the feasibility and radiation exposure of a new computed tomography (CT) protocol that allows screening of both coronary artery disease (CAD) and lung cancer. Current or former heavy smokers at high lung cancer risk with indication to cardiac CT for suspected or known CAD were randomised to undergo concomitant CT evaluation of either cardiac or thoracic area or cardiac CT only. Out of 129 subjects deemed eligible for the study, 110 agreed to participate and were randomised to simultaneous cardiac and lung CT (Gr.A; n = 55) or cardiac CT only (Gr.B; n = 55). The feasibility (i.e. adequate visualization of coronary artery segments) was noninferior with simultaneous cardiac and lung CT compared with the standard cardiac CT (870 of 889 segments [97%] in Gr.A vs 878/890 segments [99%] in Gr.B; mean difference 2.0% [90% confidence interval: -0.3% to 4.1%]). The safety (i.e. effective radiation dose) of the concomitant cardiac and lung CT protocol was noninferior to the standard cardiac CT (1.5 [95% confidence intervals: 1.2-1.7] vs. 1.4 [95% confidence intervals: 1.1-1.6] mSv; mean difference 0.1 mSv [90% confidence interval: -0.2 to 0.3 mSv]). In the two groups, a total of 25 significant (>70%) coronary stenoses were found at cardiac CT (9/55 cases of Gr.A vs 11/55 cases of Gr.B). Pulmonary nodules >2 mm were detected in 7 of the 55 Gr.A subjects. This pilot randomised study shows that concomitant CAD and lung cancer screening by means of a new CT protocol is both feasible and safe, thus allowing a comprehensive evaluation of both cardiac and thoracic regions during one CT scanning only. (ClinicalTrials.gov Identifier: NCT03727958).
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Doença da Artéria Coronariana/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Programas de Rastreamento/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Doses de RadiaçãoRESUMO
BACKGROUND: Healthcare providers across Europe are facing an ever-growing demand in clinical PET referrals. Currently, it is estimated that the administration of the PET tracer accounts for approximately 40% of the unitary PET procedure reimbursement (uPETr). Although the cost of PET/CT is highly dependent on the radiopharmaceutical cost itself, little is known about the economic impact of the utilized administration method and the repercussions on staff radiation exposure. Our objective was to evaluate the cost-effectiveness of automatic injection/fractionation system Intego™ (Bayer HealthCare, MEDRAD Europe, Netherlands) for istaff radiation exposure reduction and to validate its use with 18F-choline (FCH). METHODS: In order to validate Intego™ use with FCH we analyzed sterility, radioactivity fractionation accuracy and radiation protection for staff. We analyzed Intego™ impact on examination costs and its impact on organization efficiency. A cost-effectiveness analysis (CEA) was estimated as the incremental cost to reduce staff radiationexposure. RESULTS: According to our data, Intego™ ensures both sterility and accuracy of FCH doses' activity, reducing, at the same time, the exposure to radiation either whole body and at the extremities (94% and 75% respectively for the technicians and complete reduction for physicians). Intego™'s variable unit costs are higher than the SA (respectively 1.8% and 0.4% of PET reimbursement), while staff costs are significantly higher with SA (respectively 0.27% and 1.57% of unitary PET reimbursement [uPETr]). In our simulation, based on a 2,450 PET yearly output, the differential costs were slightly higher by using Intego™™ (+ 14%). The incremental cost-effectiveness ratio (ICER) was equal to 1.1, i.e. the healthcare provider pays an additional cost of 0.38% of uPETr to obtain a significant reduction of staff radiation exposure (-4.5 µS). CONCLUSIONS: Intego™, for its favorable results in terms of cost effectiveness, could be a useful tool in a nuclear medicine department, limiting the staff radiation exposure.
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Análise Custo-Benefício , Tomografia por Emissão de Pósitrons/efeitos adversos , Tomografia por Emissão de Pósitrons/economia , Colina/administração & dosagem , Colina/análogos & derivados , Injeções , Exposição à Radiação/prevenção & controle , RadiometriaRESUMO
In the version of this Letter originally published, there were errors in the x axis labels of Figs 1, 2 and 4: in Fig. 1b, the label Col-0 should not have been included on the axis; in Fig. 2b BIR should have read BIR2, and DN221 should have read D122N; in Fig. 4f, pSEK3 should have read pSERK3. These figures have now been amended in all versions of the Letter.
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The leucine-rich repeat receptor kinase (LRR-RK) BRASSINOSTEROID INSENSITIVE 1 (BRI1) requires a shape-complementary SOMATIC EMBRYOGENESIS RECEPTOR KINASE (SERK) co-receptor for brassinosteroid sensing and receptor activation1. Interface mutations that weaken the interaction between receptor and co-receptor in vitro reduce brassinosteroid signalling responses2. The SERK3 elongated (elg) allele3-5 maps to the complex interface and shows enhanced brassinosteroid signalling, but surprisingly no tighter binding to the BRI1 ectodomain in vitro. Here, we report that rather than promoting the interaction with BRI1, the elg mutation disrupts the ability of the co-receptor to interact with the ectodomains of BRI1-ASSOCIATED-KINASE1 INTERACTING KINASE (BIR) receptor pseudokinases, negative regulators of LRR-RK signalling6. A conserved lateral surface patch in BIR LRR domains is required for targeting SERK co-receptors and the elg allele maps to the core of the complex interface in a 1.25 Å BIR3-SERK1 structure. Collectively, our structural, quantitative biochemical and genetic analyses suggest that brassinosteroid signalling complex formation is negatively regulated by BIR receptor ectodomains.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Brassinosteroides/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Alelos , Proteínas de Plantas/metabolismo , Conformação Proteica , Domínios e Motivos de Interação entre Proteínas , Proteínas Quinases/metabolismo , Relação Estrutura-AtividadeRESUMO
PURPOSE: The role of 18F-choline positron emission tomography/computed tomography (FCH-PET/CT) in patients with metastatic castration-resistant prostate cancer (mCRPC) has been firmly established in recent years. We analyzed the prognostic value of functional parameters such as mean standardized uptake volume (SUVmean), maximum standardized uptake volume (SUVmax), metabolic total volume (MTV; the volume of interest consisting of all spatially connected voxels within a fixed threshold of 40% of the SUVmax), and total lesion activity (TLA: the product of MTV and mean standardized uptake value) estimated with FCH-PET/CT in mCRPC patients in progression after docetaxel and treated with new antiandrogen receptor therapies, abiraterone or enzalutamide. METHODS: We retrospectively studied 94 mCRPC patients, mean age 74 years (range 42-90), previously treated with docetaxel who were treated with either abiraterone (n = 52) or enzalutamide (n = 42). An FCH-PET/CT was performed at baseline, and patients were evaluated on a monthly basis for serological PSA response and every 3 months for radiological response. We measured MTV, SUVmean, SUVmax and TLA for each lesion and analyzed the sum of MTV (SMTV), SUVmean (SSUVmean), SUVmax (SSUVmax) and TLA (STLA) values for a maximum of 20 lesions. Univariate analysis was used to correlate these data with PFS and OS. RESULTS: We observed a median SMTV of 130 cm3, median SSUVmax of 106.5 and a median STLA of 495,070. All of these parameters were significant for PFS and OS in univariate analysis, while only STLA was significant for PFS and OS in multivariate analysis after adjusting for lesion and age (p < 0.0001 and p = 0.001, respectively). Baseline PSA values maintained a certain reliability for OS (p = 0.034). CONCLUSIONS: Semiquantitative parameters of FCH-PET/CT play a prognostic role in mCRCP patients treated with abiraterone or enzalutamide.
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Androstenos/uso terapêutico , Colina/análogos & derivados , Feniltioidantoína/análogos & derivados , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Benzamidas , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Nitrilas , Feniltioidantoína/uso terapêutico , Prognóstico , Estudos Prospectivos , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
PURPOSE: Urea-based prostate-specific membrane antigen (PSMA) ligands labelled with 68Ga or 177Lu are new tracers with great potential for theranostic approaches in prostate cancer. However, clinical studies have shown that the kidneys are one of the off-target organs along with the salivary and lacrimal glands. In the kidneys, PSMA is physiologically expressed in the apical epithelium of the proximal tubules, and mannitol acts as an osmotic diuretic in these tubules. We investigated the potential of mannitol to reduce renal uptake of 68Ga-PSMA. METHODS: Kidney uptake (SUVmax) was calculated in nine patients undergoing 68Ga-PSMA PET/CT at baseline (b-PET/CT) and after intravenous infusion of 500 ml of 10% mannitol (m-PET/CT). Two different infusion schemes for mannitol were used: (1) 500 ml mannitol was infused over 40 min after 68Ga-PSMA administration (A-infusion) and (2) 250 ml mannitol was infused over 15 min before and again after 68Ga-PSMA administration (B-infusion). RESULTS: In patients receiving the A-infusion, mean SUVmax increased by 11.9% and 7.4% in the right and left kidney, respectively. In patients receiving the B-infusion, mean SUVmax decreased by 24.3% and 22.4% in the right and left kidney, respectively. CONCLUSION: Our preliminary findings indicate that mannitol may play a role in reducing off-target 68Ga-PSMA renal uptake. Administration of the osmotic diuretic should be rapid and start before 68Ga-PSMA injection. These results warrant dosimetric studies in patients treated with 177Lu-PSMA to find the best scheme for mannitol administration.
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Ácido Edético/análogos & derivados , Rim/efeitos dos fármacos , Rim/metabolismo , Manitol/administração & dosagem , Manitol/farmacologia , Oligopeptídeos/metabolismo , Idoso , Transporte Biológico/efeitos dos fármacos , Ácido Edético/efeitos adversos , Ácido Edético/metabolismo , Feminino , Isótopos de Gálio , Radioisótopos de Gálio , Humanos , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/efeitos adversos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/efeitos adversosRESUMO
We present the cases of two postmenopausal women presenting to our emergency department with acute chest discomfort soon after the Central Italy earthquake. Different diagnoses were made in the two patients. The role of the earthquake as a stressful event triggering diverse chest pain syndromes is discussed.